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de novo lipogenesis is essential for platelet production in humans.acetyl-coa carboxylase (acc) catalyses the first step of de novo lipogenesis (dnl). pharmacologic inhibition of acc has been of interest for therapeutic intervention in a wide range of diseases. we demonstrate here that acc and dnl are essential for platelet production in humans and monkeys, but in not rodents or dogs. during clinical evaluation of a systemically distributed acc inhibitor, unexpected dose-dependent reductions in platelet count were observed. while platelet count reductions were ...202032929234
argx-117, a therapeutic complement inhibiting antibody targeting c2.activation of the classical and lectin pathway of complement may contribute to tissue damage and organ dysfunction of antibody-mediated diseases and ischemia-reperfusion conditions. complement factors are being considered as targets for therapeutic intervention objective: we here characterize argx-117, a humanized inhibitory monoclonal antibody against complement c2.202032926878
experimental techniques for the development of a uterus transplantation model in cynomolgus macaques.uterus transplantation (utx) is now a treatment for women with uterine factor infertility to have a child. however, utx is still largely at the experimental stage, and many medical issues remain unsolved. therefore, adequate studies in large animals including non-human primates are required for validation of these issues. utx research, especially in non-human primates, can provide important information for its full establishment in humans due to the anatomical and physiological similarities betw ...202032924267
topical nanoparticles interfering with the dna-ll37 complex to alleviate psoriatic inflammation in mice and monkeys.cell-free dna (cfdna) released from damaged or dead cells combines with ll37 and is converted into an immune response activator to exacerbate psoriasis. here, we show that cationic nanoparticles (cnps) efficiently compete for dna from the dna-ll37 immunocomplex and inhibit dna-ll37-induced cell activation. using phenotypical images, psoriasis area and severity index scoring, histology, and immunohistochemical analysis, we demonstrate that topical application of cnps on psoriasiform skin of a mou ...202032923608
assessment of hand motor function in a non-human primate model of ischemic stroke.ischemic stroke results from arterial occlusion and can cause irreversible brain injury. a non-human primate (nhp) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. we evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. endovascular transient middle cerebral artery occlusion (mcao) with an angiographic microcatheter ind ...202032921642
highly improved aqueous lubrication of polymer surface by noncovalently bonding hyaluronic acid-based hydration layer for endotracheal intubation.hydration lubrication is the key responsible for the exceptionally low boundary friction between biosurfaces. however, it is a challenge to settle a hydration layer on a polymer surface via a noncovalent manner. herein, we develop a highly lubricated coating absorbed onto the polymer surface via intermolecular association of hyaluronic acid (ha)-based micelles. a poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymer (pluronic, f127) is recruited to complex with h ...202032920428
review: other helicobacter species.this review covers the most important, accessible, and relevant literature published between april 2019 and april 2020 in the field of non-helicobacter pylori helicobacter species (nhph). the initial part of the review covers new insights regarding the presence of gastric and enterohepatic nhph in humans and animals, while the subsequent section focuses on the progress in our understanding of animal models, the pathogenicity and omics of these species. over the last year, the clinical relevance ...202032918348
amg 701 induces cytotoxicity of multiple myeloma cells and depletes plasma cells in cynomolgus monkeys.multiple myeloma (mm) is a hematologic malignancy that is characterized by the accumulation of abnormal plasma cells (pcs) in the bone marrow (bm). patient outcome may be improved with bite (bispecific t-cell engager) molecules, which redirect t cells to lyse tumor cells. b-cell maturation antigen (bcma) supports pc survival and is highly expressed on mm cells. a half-life extended anti-bcma bite molecule (amg 701) induced selective cytotoxicity against bcma-expressing mm cells (average half-max ...202032886754
proline protects boar sperm against oxidative stress through proline dehydrogenase-mediated metabolism and the amine structure of pyrrolidine.proline was reported to improve sperm quality in rams, stallions, cynomolgus monkeys, donkeys, and canines during cryopreservation. however, the underlying mechanism remains unclear. the aim of this study was to investigate the effect of proline on boar semen during liquid storage at 17 °c and explore the underlying mechanism. freshly ejaculated boar semen was supplemented with different concentrations of proline (0, 25, 50, 75, 100, 125 mm) and stored at 17 °c for nine days. sperm motility patt ...202032883027
ds-7080a, a selective anti-robo4 antibody, shows anti-angiogenic efficacy with distinctly different profiles from anti-vegf agents.neovascular age-related macular degeneration (namd) results from choroidal neovascularization (cnv) and causes severe vision loss. intravitreal anti-vascular endothelial growth factor (vegf) therapies have significantly improved therapeutic outcomes; however, a substantial number of patients experience disease progression. roundabout 4 (robo4) has been reported to be a vascular-specific protein that stabilizes vasculature in ocular pathological angiogenesis. to explore robo4 targeting as a novel ...202032879763
pharmacokinetics of sustained-release, oral, and subcutaneous meloxicam over 72 hours in male beagle dogs.in cynomolgus macaques, plasma levels of sustained-release formulations of meloxicam meet or exceed efficaciousconcentrations for 48 to 72 h, thereby allowing less animal handling and providing more consistent efficacy than standardformulations of meloxicam. the goal of this study was to compare the pharmacokinetics of a single subcutaneous dose of asustained-release formulation of meloxicam (melox-sr) with those of oral (melox-po) and standard subcutaneous (melox-sc)formulations dosed every 24 ...202032878683
cryopreservation of mauritian cynomolgus macaque (macaca fascicularis) sperm in chemically defined medium.the objective of this study was to optimize cryopreservation of sperm from mauritian cynomolgus macaques (mcm) in defined conditions. sperm viability and motility were compared between sperm cryopreserved in chemically-defined freezing media with variable osmolarity and the presence of either ethylene glycol or glycerol. the highest percentage viability (after freeze-thaw) was seen in sperm samples that were cryopreserved in medium with an osmolarity of 310 mosm, while higher osmolarities marked ...202032878681
interspecies embryo transfer between rhesus and cynomolgus monkeys. 202032873535
impact of p-glycoprotein-mediated active efflux on drug distribution into lumbar cerebrospinal fluid in nonhuman primates.estimation of unbound drug concentration in the brain (cu,brain) is an essential part of central nervous system (cns) drug development. as a surrogate for cu,brain in humans and nonhuman primates, drug concentration in cerebrospinal fluid (ccsf) collected by lumbar puncture is often used; however, the predictability of cu,brain by lumbar ccsf is unclear, particularly for substrates of the active efflux transporter p-glycoprotein (p-gp). here, we measured lumbar ccsf in cynomolgus monkey after si ...202032862147
understanding the half-life extension of intravitreally administered antibodies binding to ocular albumin.the burden associated with frequent injections of current intravitreal (ivt) therapeutics may be reduced by long-acting delivery strategies. binding to serum albumin has been shown to extend the ocular half-life in rabbits, however, the underlying molecular mechanisms and translational relevance remain unclear. the aim of this work was to characterize the in vitro and in vivo formation of complexes between human serum albumin (hsa) and an antigen-binding fragment of a rabbit antibody linked to a ...202032858986
inflammation of a posterior ciliary artery in a naive cynomolgus macaque.this brief communication describes a previously unreported background lesion in the eye of a naive cynomolgus macaque. inflammation of a posterior ciliary artery was, in this case, morphologically similar to vascular inflammation of other tissues described in naive cynomolgus macaques. however, the available literature does not describe this lesion at this anatomical site. the affected animal did not present with any abnormal clinical signs and ophthalmological examinations were within normal li ...202032856568
save your maximum tolerated dose: how to diagnose procedure-related spinal cord lesions after lumbar intrathecal bolus administration of oligonucleotides in cynomolgus monkeys.many potential drugs for treatment of neurodegenerative diseases, particularly antisense oligonucleotides (asos), are administered via lumbar intrathecal injection, because these drugs do not cross the blood-brain barrier. intrathecal injection is a well-established method in cynomolgus monkeys, a species that is used in preclinical safety assessment when other nonrodent species cannot be used. the authors completed intrathecal aso administration in over 30 preclinical safety studies (>1000 anim ...202032856507
differences in xanthotoxin metabolites in seven mammalian liver microsomes.xanthotoxin, abundantly occurring in fruits, vegetables, grapefruit juice and oils, is widely used in medicine for the treatment of psoriasis and vitiligo. xanthotoxin possesses the ability to inhibit mechanism-based cytochrome p450 (cyp450)-mediated activities in rats and mice. furthermore, it time-dependently obstructs a number of cyp450-mediated functions in humans. cyp450 enzymes are most abundant in the liver and induce metabolic activation of numerous xenobiotic compounds. the present stud ...202032855735
vaccine targeting sivmac251 protease cleavage sites protects macaques against vaginal infection.after over 3 decades of research, an effective anti-hiv vaccine remains elusive. the recently halted hvtn702 clinical trial not only further stresses the challenge to develop an effective hiv vaccine but also emphasizes that unconventional and novel vaccine strategies are urgently needed. here, we report that a vaccine focusing the immune response on the sequences surrounding the 12 viral protease cleavage sites (pcss) provided greater than 80% protection to mauritian cynomolgus macaques against ...202032853182
antimicrobial resistance profiles in bacterial species isolated from fecal samples of free-ranging long-tailed macaques (macaca fascicularis) living in lopburi old town, thailand.at present, increasing in long-tailed macaques (macaca fascicularis) population in lopburi old town caused several problems in its community, in particular with sanitation problem. the present study aimed to explore species distribution and antimicrobial resistance patterns in bacteria isolated from feces of the free-ranging long-tailed macaques (macaca fascicularis) in lopburi old town, thailand.202032848316
pharmacologic properties and preclinical activity of sasanlimab, a high-affinity engineered anti-human pd-1 antibody.development of antagonistic mabs that specifically target the immune checkpoint receptor, programmed cell death protein-1 (pd-1), is of great interest for cancer immunotherapy. here, we report the biophysical characteristics and nonclinical antagonistic activities of sasanlimab (pf-06801591), a humanized anti-pd-1 antibody of igg4 isotype. we show that sasanlimab binds selectively and with similar high potency to human and cynomolgus monkey pd-1 receptor and blocks its interaction with pd-l1 and ...202032847983
antibody to cd137 activated by extracellular adenosine triphosphate is tumor selective and broadly effective in vivo without systemic immune activation.agonistic antibodies targeting cd137 have been clinically unsuccessful due to systemic toxicity. since conferring tumor selectivity through tumor-associated antigen limits its clinical use to cancers that highly express such antigen, we exploited extracellular adenosine triphosphate (exatp), which is a hallmark of the tumor microenvironment and highly elevated in solid tumors, as a broadly tumor selective switch. we generated a novel anti-cd137 switch antibody, sta551, which exerts agonistic act ...202032847940
the selective 5-ht1a receptor agonist, nlx-112, exerts anti-dyskinetic effects in mptp-treated macaques.long-term treatment of parkinson's disease (pd) with l-dopa typically leads to development of l-dopa induced dyskinesia (lid). amantadine, an nmda antagonist, attenuates lid, but with limited efficacy and considerable side-effects. nlx-112 (also known as befiradol or f13640), a highly selective and efficacious 5-ht1a receptor agonist, reduced lid when tested in rodent and marmoset models of pd.202032846366
normative analysis of individual brain differences based on a population mri-based atlas of cynomolgus macaques.the developmental trajectory of the primate brain varies substantially with aging across subjects. however, this ubiquitous variability between individuals in brain structure is difficult to quantify and has thus essentially been ignored. based on a large-scale structural magnetic resonance imaging dataset acquired from 162 cynomolgus macaques, we create a species-specific 3d template atlas of the macaque brain, and deploy normative modeling to characterize individual variations of cortical thic ...202032844170
simultaneous quantification and pharmacokinetic evaluation of roflumilast and its n-oxide in cynomolgus monkey plasma by lc-ms/ms method.roflumilast (rof), a nonsteroidal anti-inflammatory drug, has successfully been used to treat systemic and pulmonary inflammation associated with chronic obstructive pulmonary disease. to evaluate its pharmacokinetics in monkeys, a sensitive, rapid and reliable liquid chromatography with tandem mass spectrometry (lc-ms/ms) method was developed for the simultaneous determination of rof and its n-oxide metabolite (rno). the mobile phase contained 0.1% formic acid aqueous solution (a) and 0.1% form ...202032840886
embryonal carcinoma and glioblastoma cell lines derived from monkey induced pluripotent stem cells.induced pluripotent stem cells (ipscs) are useful for the development of therapies in regenerative medicine, analysis of pathogenesis, and exploration of candidate drugs. we developed an alternative usage of ipscs of which the mhc haplotype is matched to transplantable recipients in a cynomolgus macaque model. we established two cancer cell lines, embryonal carcinoma, and glioblastoma cell lines from cynomolgus monkey ipscs. here, we describe a method to induce the cancer cell lines including a ...202032833131
systematic characterization of the biodistribution of the oncolytic virus m1.oncolytic viruses are emerging as important tools for immunotherapy for cancer treatment; however, most of the clinically tested oncolytic candidates are still administered by intratumoral injection, and new viruses capable of intravenous injection are urgently needed. the m1 virus is a positive-sense single-stranded rna virus that belongs to the alphavirus family, and it was identified as an oncolytic virus that can selectively replicate in and kill tumor cells after intravenous injection. to f ...202032829653
as3288802, a highly selective antibody to active plasminogen activator inhibitor-1 (pai-1), exhibits long efficacy duration in cynomolgus monkeys.antibodies have strong affinity to their target molecules, a characteristic that is utilized in antibody drugs. for antibody drugs, target molecule specificity and long duration pharmacokinetics, along with strong affinity to the target molecule are important characteristics. plasminogen activator inhibitor-1 (pai-1) is one of the key regulators of the fibrinolysis system, and the benefits of pai-1 activity inhibition have been widely reported for multiple thrombosis and fibrosis-related disease ...202032828642
a 3d model to evaluate retinal nerve fiber layer thickness deviations caused by the displacement of optical coherence tomography circular scans in cynomolgus monkeys (macaca fascicularis).the main objective of the study was to analyze deviations in retinal nerve fiber layer (rnfl) thickness measurements caused by the displacement of circular optic disc optical coherence tomography scans. high-density radial scans of the optic nerve heads of cynomolgus monkeys were acquired. the retinal nerve fiber layer was manually segmented, and a surface plot of the discrete coordinates was generated. from this plot, the rnfl thicknesses were calculated and compared between accurately centered ...202032822382
congenital unilateral renal aplasia in a cynomolgus monkey (macaca fascicularis) with investigation into potential pathogenesis.we describe and characterize unilateral renal aplasia in a cynomolgus monkey (macaca fascicularis) from a chronic toxicology study adding to the limited histopathology reports of congenital renal anomalies in macaques. in the current case, the affected kidney was macroscopically small and characterized microscopically by a thin cortex with an underdeveloped medulla and an absent papilla. the remnant medulla lacked a corticomedullary junction and contained only a few irregular collecting duct-lik ...202032815469
nonclinical safety assessment of an inhaled formulation of serelaxin: a recombinant human protein in rats and cynomolgus monkeys (macaca fascicularis).serelaxin is a recombinant human relaxin-2 intended for cardiovascular indications. inhalation was chosen as alternative route to intravenous to allow daily administration for chronic applications and home treatment. a total of 4 short-term studies were conducted in rats and cynomolgus monkeys with inhaled formulation of serelaxin at dose up to 10 mg/kg/d. all rats and cynomolgus macaques receiving serelaxin were exposed to the test item. one rat and approximately 50% of macaques developed immun ...202032815455
genetic variants of udp-glucuronosyltransferases 1a1, 1a6, and 1a9 in cynomolgus and rhesus macaques.1. in the cynomolgus macaque, udp-glucuronosyltransferases (ugts) 1as have similar molecular and enzymatic characteristics to those of their human orthologs. however, genetic polymorphisms in major cynomolgus ugt1a1/6/9 have not been investigated. 2. we re-sequenced ugt1a1, ugt1a6, and ugt1a9 in 186 cynomolgus macaques (bred in cambodia, china, or indonesia) and 54 rhesus macaques and found 15, 13, and 26 non-synonymous variants, respectively. 3. of these ugt1a1, ugt1a6, and ugt1a9 variants, res ...202032811258
clinical features of irreversible rejection after allogeneic uterus transplantation in cynomolgus macaques.uterus transplantation (utx) is a potential option for women with uterine factor infertility to have a child. the clinical features indicating irreversible rejection of the uterus are unknown. in our experimental series of allogeneic utx in cynomolgus macaques, six female macaques were retrospectively examined, which were unresponsive to treatment with immunosuppressants (i.e. irreversible rejection). clinical features including general condition, hematology, uterine size, indocyanine green (icg ...202032807830
ontogenetic changes in magnitudes of integration in the macaque skull.magnitudes of morphological integration may constrain or facilitate craniofacial shape variation. the aim of this study was to analyze how the magnitude of integration in the skull of macaca fascicularis changes throughout ontogeny in relation to developmental and/or functional modules.202032803773
single-cell rna sequencing of the cynomolgus macaque testis reveals conserved transcriptional profiles during mammalian spermatogenesis.spermatogenesis is highly orchestrated and involves the differentiation of diploid spermatogonia into haploid sperm. the process is driven by spermatogonial stem cells (sscs). sscs undergo mitotic self-renewal, whereas sub-populations undergo differentiation and later gain competence to initiate meiosis. here, we describe a high-resolution single-cell rna-seq atlas of cells derived from cynomolgus macaque testis. we identify gene signatures that define spermatogonial populations and explore self ...202032795394
range of neurological signs in cynomolgus monkeys after intrathecal bolus administration of antisense oligonucleotides.intrathecal (it) dosing (ie, injection into the subarachnoidal space at the lumbar region) is a common route of administration in cynomolgus monkey preclinical safety studies conducted for antisense oligonucleotides (aso) that target central nervous system diseases. herein we report on neurological signs that have been observed in 28 it studies conducted in 1,016 cynomolgus monkeys. neurological signs were classified into 5 groups: (1) a nonadverse transient absence of lower spinal reflexes. thi ...202032794413
immunogenicity and toxicokinetics assessment of the mono-pegylated recombinant human interleukin-11 in cynomolgus monkeys.protein therapeutics have potential to elicit immune responses resulting in undesirable anti-drug antibodies (ada) that might affect product efficacy and patient safety, and should be assessed in animals before applying the treatment to humans. in this paper, we aim to assess the immunogenicity and toxicokinetics of the mono-pegylated recombinant human interleukin-11 (rhil-11), a novel protein therapeutic for the treatment of chemotherapy-induced thrombocytopenia, in repeated administration to c ...202032791145
crimean-congo hemorrhagic fever virus strains hoti and afghanistan cause viremia and mild clinical disease in cynomolgus monkeys.development of vaccines and therapies against crimean-congo hemorrhagic fever virus (cchfv) have been hindered by the lack of immunocompetent animal models. recently, a lethal nonhuman primate model based on the cchfv hoti strain was reported. cchfv hoti caused severe disease in cynomolgus monkeys with 75% lethality when given by the intravenous (i.v.) route.202032790668
immunological response in cynomolgus macaques to porcine α-1,3 galactosyltransferase knockout viable skin xenotransplants-a pre-clinical study.allogeneic skin recovered from human deceased donors (hdd) has been a mainstay interim treatment for severe burns, but unfortunately risk of infectious disease and availability limitations exist. genetically engineered ɑ-1,3 galactosyltransferase knockout (galt-ko) porcine source animals for viable skin xenotransplants may provide a promising clinical alternative.202032781479
mitogenomics of macaques (macaca) across wallace's line in the context of modern human dispersals.wallace's line demarcates a biogeographical boundary between the indomalaya and australasian ecoregions. most placental mammalian genera, for example, occur to the west of this line, whereas most marsupial genera occur to the east. however, macaque monkeys are unusual because they naturally occur on both western and eastern sides. to further explore this anomalous distribution, we analyzed 222 mitochondrial genomes from ∼20 macaque species, including new genomes from 60 specimens. these comprise ...202032781349
simple approach to accurately predict pharmacokinetics of therapeutic monoclonal antibodies after subcutaneous injection in humans.the subcutaneous injection of therapeutic monoclonal antibodies is increasingly used in the treatment of several diseases because of its convenience. thus, a simple and accurate method of predicting the pharmacokinetics of monoclonal antibodies after a subcutaneous injection in humans would be a valuable tool for preclinical/clinical development. in this study, we investigated whether the pharmacokinetics of monoclonal antibodies after a subcutaneous injection in humans can be predicted using on ...202032779124
development of an inactivated vaccine candidate, bbibp-corv, with potent protection against sars-cov-2.the coronavirus disease 2019 (covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) threatens global public health. the development of a vaccine is urgently needed for the prevention and control of covid-19. here, we report the pilot-scale production of an inactivated sars-cov-2 vaccine candidate (bbibp-corv) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus maca ...202032778225
the design, synthesis and evaluation of 2-aminobenzoxazole analogues as potent and orally efficacious chemr23 inhibitors.we previously reported 2-aminobenzoxazole analogue 1 as a potent chemr23 inhibitor. the compound showed inhibitory activity against chemerin-induced calcium signaling through chemr23 internalization in cal-1 cells, which are cell lines of plasmacytoid dendric cells (pdcs). furthermore, compound 2 inhibited chemotaxis of cal-1 triggered by chemerin in vitro. however, we noted a difference in the chemr23 response to our inhibitor between rodents and non-rodents in a previous study. to address this ...202032773087
convective forces increase rostral delivery of intrathecal radiotracers and antisense oligonucleotides in the cynomolgus monkey nervous system.the intrathecal (it) dosing route introduces drugs directly into the csf to bypass the blood-brain barrier and gain direct access to the cns. we evaluated the use of convective forces acting on the cerebrospinal fluid as a means for increasing rostral delivery of it dosed radioactive tracer molecules and antisense oligonucleotides (aso) in the monkey cns. we also measured the cerebral spinal fluid (csf) volume in a group of cynomolgus monkeys.202032771027
macaque gaze responses to the primatar: a virtual macaque head for social cognition research.following the expanding use and applications of virtual reality in everyday life, realistic virtual stimuli are of increasing interest in cognitive studies. they allow for control of features such as gaze, expression, appearance, and movement, which may help to overcome limitations of using photographs or video recordings to study social responses. in using virtual stimuli however, one must be careful to avoid the uncanny valley effect, where realistic stimuli can be perceived as eerie, and indu ...202032765373
well-balanced immune response and protective efficacy induced by a single dose of live attenuated tetravalent dengue vaccine (kd-382) in monkeys.one of the challenges developing a live attenuated tetravalent dengue vaccine (tdv) is to overcome the presumed viral interference that may be preventing the induction of a balanced immune response to all 4 serotypes of the dengue virus (denv1-4). our live attenuated tdv candidate was developed from wild-type (wt) parental strains (denv1/03135, denv2/99345, denv3/16562, and denv4/1036, respectively) using a classical host range mutation strategy: the same strategy used for the approved live atte ...202032760828
oral pretreatment with galantamine effectively mitigates the acute toxicity of a supralethal dose of soman in cynomolgus monkeys posttreated with conventional antidotes.earlier reports suggested that galantamine, a drug approved to treat mild-to-moderate alzheimer's disease (ad), and other centrally acting reversible acetylcholinesterase (ache) inhibitors can serve as adjunct pretreatments against poisoning by organophosphorus compounds, including the nerve agent soman. the present study was designed to determine whether pretreatment with a clinically relevant oral dose of galantamine hbr mitigates the acute toxicity of 4.0×ld50 soman (15.08 µg/kg) in macaca fa ...202032759369
comparative pathology study of venezuelan, eastern, and western equine encephalitis viruses in non-human primates.venezuelan, eastern, and western equine encephalitis viruses (veev, eeev, and weev) are mosquito-borne viruses in the americas that cause central nervous system (cns) disease in humans and equids. in this study, we directly characterized the pathogenesis of veev, eeev, and weev in cynomolgus macaques following subcutaneous exposure because this route more closely mimics natural infection via mosquito transmission or by an accidental needle stick. our results highlight how eeev is significantly m ...202032755661
levodopa partially rescues microglial numerical, morphological, and phagolysosomal alterations in a monkey model of parkinson's disease.parkinson's disease (pd) is the most common neurodegenerative motor disorder. the mechanisms underlying the onset and progression of levodopa (l-dopa)-induced dyskinesia (lid) during pd treatment remain elusive. emerging evidence implicates functional modification of microglia in the development of lid. thus, understanding the link between microglia and the development of lid may provide the knowledge required to preserve or promote beneficial microglial functions, even during a prolonged l-dopa ...202032755645
restorative functions of autologous stem leydig cell transplantation in a testosterone-deficient non-human primate model.rationale: stem leydig cells (slcs) transplantation can restore testosterone production in rodent models and is thus a potential solution for treating testosterone deficiency (td). however, it remains unknown whether these favorable effects will be reproduced in more clinically relevant large-animal models. therefore, we assessed the feasibility, safety and efficacy of autologous slcs transplantation in a testosterone-deficient non-human primate (nhp) model. methods: cynomolgus monkey slcs (cm-s ...202032754273
blood clearance kinetics and organ delivery of medium-chain triglyceride and fish oil-containing lipid emulsions: comparing different animal species.medium-chain triglycerides (tg) (mct) and fish oil (fo) tg are incorporated as the core tg component into intravenous (iv) lipid emulsions for infusion in parenteral nutrition. bolus injections of iv emulsions, on the other hand, have emerged as a novel therapeutic approach to treat various acute disorders. however, intravascular metabolism and organ delivery of acute iv injection of emulsions containing both mct and fo are not fully defined, nor have they been characterized across common experi ...202032753350
immune outcomes of zika virus infection in nonhuman primates.although the zika virus (zikv) epidemic is subsiding, immune responses that are important for controlling acute infection have not been definitively characterized. nonhuman primate (nhp) models were rapidly developed to understand the disease and to test vaccines, and these models have since provided an understanding of the immune responses that correlate with protection during natural infection and vaccination. here, we infected a small group of male rhesus (macaca mulatta) and cynomolgus (maca ...202032747639
a zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission.arboviruses maintain high mutation rates due to lack of proofreading ability of their viral polymerases, in some cases facilitating adaptive evolution and emergence. here we show that, just before its 2013 spread to the americas, zika virus (zikv) underwent an envelope protein v473m substitution (e-v473m) that increased neurovirulence, maternal-to-fetal transmission, and viremia to facilitate urban transmission. a preepidemic asian zikv strain (fss13025 isolated in cambodia in 2010) engineered w ...202032747564
conjugation of a peptide to an antibody engineered with free cysteines dramatically improves half-life and activity.the long circulating half-life and inherently bivalent architecture of iggs provide an ideal vehicle for presenting otherwise short-lived g-protein-coupled receptor agonists in a format that enables avidity-driven enhancement of potency. here, we describe the site-specific conjugation of a dual agonist peptide (an oxyntomodulin variant engineered for potency and in vivo stability) to the complementarity-determining regions (cdrs) of an immunologically silent igg4. a cysteine-containing heavy cha ...202032744157
10-hydroxydecanoic acid potentially elicits antigen-specific iga responses.the effective antigen (ag) uptake by microfold cells (m-cells) is important for the induction of an efficient mucosal immune responses. here, we show that 10-hydroxydecanoic acid (10-hdaa) from royal jelly (rj) potentially supports m-cell differentiation and induces effective antigen-specific mucosal immune responses in cynomolgus macaques. 10-hdaa increases the expression level of receptor activator of nuclear factor-kappab (nf-κb) (rank) in caco-2 cells, which suggests that 10-hdaa potentially ...202032741940
distribution of 14c-latanoprost following a single intracameral administration versus repeated topical administration.to qualitatively evaluate the ocular and periocular distribution of 14c-latanoprost following a single intracameral administration or repeated topical ocular administration in beagle dogs and cynomolgus monkeys.202032740740
preclinical characterization of radioimmunoconjugate 111in/90y-ff-21101 against p-cadherin expressing tumor in mouse xenograft model and non-human primate.p-cadherin is overexpressed in various cancers and can be a target for radioimmunotherapy. we investigated the preclinical pharmacokinetics and pharmacology of ff-21101, an indium-111 (111in)- or yttrium-90 (90y)-conjugated monoclonal antibody against p-cadherin, to evaluate its clinical applications. methods: the radiochemical purity, binding affinity, and in vitro serum stability of 111in/90y-labeled ff-21101 were evaluated. the pharmacokinetics of 111in/90y-ff-21101 were compared in normal mi ...202032737245
immunoaffinity lc-ms/ms is more suitable than elisa to quantify a pegylated molecule in cynomolgus monkey serum.background: polyethylene glycolylation (pegylation) technology is a long-acting delivery platform used to increase the half-life of protein therapeutics. quantitation of pegylated anti-factor d fab (peg-afd) poses bioanalytical challenges. results: an elisa was developed to determine total fab concentration in cynomolgus monkey serum following intravitreal administration of peg-afd. however, assay characterization showed a low recovery of about 25% for free unconjugated fab whereas recovery for ...202032735119
transient-mixed chimerism with nonmyeloablative conditioning does not induce liver allograft tolerance in nonhuman primates.although short-term outcomes for liver transplantation have improved, patient and graft survival are limited by infection, cancer, and other complications of immunosuppression. rapid induction of tolerance after liver transplantation would decrease these complications, improving survival and quality of life. tolerance to kidneys, but not thoracic organs or islets, has been achieved in nonhuman primates and humans through the induction of transient donor chimerism. since the liver is considered t ...202032732835
siv and mycobacterium tuberculosis synergy within the granuloma accelerates the reactivation pattern of latent tuberculosis.human immunodeficiency virus infection is the most common risk factor for severe forms of tuberculosis (tb), regardless of cd4 t cell count. using a well-characterized cynomolgus macaque model of human tb, we compared radiographic, immunologic and microbiologic characteristics of early (subclinical) reactivation of latent m. tuberculosis (mtb) infection among animals subsequently infected with simian immunodeficiency virus (siv) or who underwent anti-cd4 depletion by a depletion antibody. cd4 de ...202032730321
a dedicated eight-channel receive rf coil array for monkey brain mri at 9.4 t.the neuroimaging of nonhuman primates (nhps) realised with magnetic resonance imaging (mri) plays an important role in understanding brain structures and functions, as well as neurodegenerative diseases and pathological disorders. theoretically, an ultrahigh field mri (≥7 t) is capable of providing a higher signal-to-noise ratio (snr) for better resolution; however, the lack of appropriate radiofrequency (rf) coils for 9.4 t monkey mri undermines the benefits provided by a higher field strength. ...202032729642
analysis of conserved mirnas in cynomolgus macaque genome using small rna sequencing and homology searching.micrornas (mirnas) are important regulators that fine-tune diverse cellular activities. cynomolgus macaques (macaca fascicularis) are used extensively in biomedical and pharmaceutical research; however, substantially fewer mirnas have been identified in this species than in humans. consequently, we investigated conserved mirna profiles in cynomolgus macaques by homology searching and small rna sequencing. in total, 1,455 high-confidence mirna gene loci were identified, 408 of which were also con ...202032728489
hsp90 inhibitor hsp990 in very low dose upregulates eaat2 and exerts potent antiepileptic activity.rationale: dysfunction or reduced levels of eaat2 have been documented in epilepsy. we previously demonstrated the antiepileptic effects of hsp90 inhibitor 17aag in temporal lobe epilepsy by preventing eaat2 degradation. because of the potential toxicities of 17aag, this study aimed to identify an alternative hsp90 inhibitor with better performance on hsp90 inhibition, improved blood-brain barrier penetration and minimal toxicity. methods: we used cell-based screening and animal models of epilep ...202032724478
jp1 suppresses proliferation and metastasis of melanoma through mek1/2 mediated nedd4l-sp1-integrin αvβ3 signaling.background: jwa gene is known to down-regulate sp1 and reduces the expression level of integrin αvβ3. here, we identified a functional polypeptide (jp1) based on the active fragment of the jwa protein to suppress melanoma growth and metastasis by inhibiting the integrin αvβ3. methods: we conducted a series of melanoma growth and metastasis mouse models to evaluate anti-melanoma effect of jp1 peptide. 18f-labeled jp1 (18f-nfp-jp1) was detected by micro-pet assay to demonstrate drug biodistributio ...202032724456
absence of oatp1b (organic anion-transporting polypeptide) induction by rifampin in cynomolgus monkeys: determination using the endogenous oatp1b marker coproporphyrin and tissue gene expression.organic anion-transporting polypeptide (oatp) 1b induction is an evolving mechanism of drug disposition and interaction. however, there are contradictory reports describing oatp1b expression in hepatocytes and liver biopsies after administration of an inducer. this study investigated the in vivo effects of the common inducer rifampin (rif) on the activity and expression of cynomolgus monkey oatp1b1 and oatp1b3 transporters, which are structurally and functionally similar their human oatp1b count ...202032719071
design, synthesis, and optimization of a series of 2-azaspiro[3.3]heptane derivatives as orally bioavailable fetal hemoglobin inducers.pharmacological reactivation of the γ-globin gene for the production of fetal hemoglobin (hbf) is a promising approach for the management of β-thalassemia and sickle cell disease (scd). we conducted a phenotypic screen in human erythroid progenitor cells to identify molecules that could induce hbf, which resulted in identification of the hit compound 1. exploration of structure-activity relationships and optimization of adme properties led to 2-azaspiro[3.3]heptane derivative 18, which is more r ...202032717372
power spectrum analysis of eeg in a translational nonhuman primate model after chronic exposure to low levels of the common marine neurotoxin, domoic acid.domoic acid (da), the focus of this research, is a marine algal neurotoxin and epileptogen produced by species in the genus pseudo-nitzschia. da is found in finfish and shellfish across the globe. the current regulatory limit for da consumption (20 ppm in shellfish) was set to protect humans from acute toxic effects, but there is a growing body of evidence suggesting that regular consumption of da contaminated seafood at or below the regulatory limit may lead to subtle neurological effects in ad ...202032717199
the natural history of spontaneously occurred endometriosis in cynomolgus monkeys by monthly follow-up laparoscopy for two years.endometriosis, a disease in which endometrial tissue proliferates outside the uterus, is a progressive disease that affects women in reproductive age. it causes abdominal pain and infertility that severely affects the quality of life in young women. the mechanism of the onset and development of endometriosis has not been fully elucidated because of the complex mechanism involved in the disease. nonhuman primates have been used to study the pathogenesis of spontaneous endometriosis because of the ...202032713879
alu master copies serve as the drivers of differential sine transposition in recent primate genomes.alu elements, averaging ~300bp in length, are a family of primate-specific short intersperse nuclear elements (sines) with more than one million copies and contributing to ~11% of primate genomes. despite mostly being shared among primates, our recent study revealed highly differential recent alu transposition among the genomes of primates from hominidae and cercopithecidae families. to understand the underlying mechanism, we analyzed six primate genomes and revealed species- and lineage-specifi ...202032712063
development of a novel gripping test for the evaluation of the finger fine motor ability in mptp-treated monkeys.assessing the finger fine motor ability is extremely important. however, conventional behavioral tests in monkeys are complicated and costly. we attempted to develop a new task to assess the precise finger grip in parkinson's disease monkeys based on the principles of objectification, multipurpose, and simplification. this study involved seven adult male cynomolgus monkeys. a gripping test based on the previous food reaching test was developed. parallel experiments of food reaching test and grip ...202032706185
large granular lymphocytosis in a cynomolgus macaque (macaca fascicularis) with a subclinical trypanosoma cruzi infection.a 5.25-year-old cynomolgus macaque (macaca fascicularis) was found to have a marked leukocytosis due to a lymphocytosis on routine quarantine laboratory data prior to inclusion in a preclinical research study. the majority of lymphocytes were characterized as intermediate to large with round to convoluted nuclei, coarse to clumped chromatin, rare prominent nucleoli, and moderate amounts of lightly basophilic cytoplasm that frequently contained small magenta granules and/or clear vacuoles. the an ...202032686179
axonal extensions along corticospinal tracts from transplanted human cerebral organoids.the reconstruction of lost neural circuits by cell replacement is a possible treatment for neurological deficits after cerebral cortex injury. cerebral organoids can be a novel source for cell transplantation, but because the cellular composition of the organoids changes along the time course of the development, it remains unclear which developmental stage of the organoids is most suitable for reconstructing the corticospinal tract. here, we transplanted human embryonic stem cell-derived cerebra ...202032679062
a novel semi-mechanistic tumor growth fraction model for translation of preclinical efficacy of anti-glypican 3 antibody drug conjugate to human.the growing fraction (gf) of tumor has been reported as one of the predictive markers of the efficacy of chemotherapeutics. therefore, a semi-mechanistic model has been developed that describes tumor growth on the basis of cell cycle, allowing the incorporation of the gf of a tumor in pharmacokinetic/pharmacodynamic (pk/pd) modeling. efficacy data of anti-glypican 3 (gpc3) antibody drug conjugate (adc) in a hepatocellular carcinoma (hcc) patient derived xenograft (pdx) model was used for evaluat ...202032678919
cochlear implantation with a dexamethasone eluting electrode array: functional and anatomical changes in non-human primates.the aim of this study was to determine whether the dexamethasone-eluting electrode (dexel) has a protective anti-inflammatory effect in a normal hearing implanted cochlea, as well as its performance and safety.202032658397
aav-mediated gene delivery to foveal cones.adeno-associated virus (aav) has emerged as the vector of choice for delivering genes to the mammalian retina. from the first gene therapy to receive fda approval for the inherited retinal disease (luxturna™) to more recent clinical trials using microbial opsins to regain light sensitivity, therapeutic transgenes rely on aav vectors for safe and efficient gene delivery to retinal cells. such vectors are administered to the retina via subretinal (sr) injection or intravitreal (ivt) injection rout ...202032651912
a novel her2-targeted antibody-drug conjugate offers the possibility of clinical dosing at trastuzumab-equivalent exposure levels.trastuzumab and the related adc, ado-trastuzumab emtansine (t-dm1), both target her2-overexpressing cells. together, these drugs have treatment indications in both early-stage and metastatic settings for her2+ breast cancer. t-dm1 retains the antibody functionalities of trastuzumab and adds the potency of a cytotoxic maytansine payload. interestingly, in the clinic, t-dm1 cannot always replace the use of trastuzumab plus chemotherapy administered together as single agents. we hypothesize that th ...202032651200
regional distributions of udp-glucuronosyltransferase activities toward estradiol and serotonin in the liver and small intestine of cynomolgus macaques.the cynomolgus macaque is a nonhuman primate species that is often used in drug metabolism studies during drug development. however, the localization of udp-glucuronosyltransferases (ugts), essential drug-metabolizing enzymes, has not been fully investigated in the liver and small intestine of cynomolgus macaques. in this study, ugt activities were analyzed in liver (five lobes) and small intestine (the duodenum and six sections from the proximal jejunum to the distal ileum) using typical probe ...202032651149
chromosome-level de novo assembly of the pig-tailed macaque genome using linked-read sequencing and hic proximity scaffolding.macaque species share >93% genome homology with humans and develop many disease phenotypes similar to those of humans, making them valuable animal models for the study of human diseases (e.g., hiv and neurodegenerative diseases). however, the quality of genome assembly and annotation for several macaque species lags behind the human genome effort.202032649757
molecular characterization of udp-glucuronosyltransferases 3a and 8a in cynomolgus macaques.udp-glucuronosyltransferases (ugts) are drug-metabolizing enzymes essential for the metabolism of endogenous substrates and xenobiotics. the cynomolgus macaque is a nonhuman primate species widely used in drug metabolism studies. the molecular characteristics of ugts have been extensively investigated in humans, but they remain to be elucidated in cynomolgus macaques. in this study, cynomolgus macaque ugt3a1, ugt3a2, and ugt8a1 cdnas were isolated and characterized. amino acid sequences deduced ...202032646660
efficacy of favipiravir (t-705) against crimean-congo hemorrhagic fever virus infection in cynomolgus macaques.crimean-congo hemorrhagic fever virus (cchfv) is a widely distributed hemorrhagic fever virus found throughout eastern europe, africa, the middle east and asia. it is spread through bites from infected ticks, animal husbandry and can also be acquired in the healthcare setting during care of infected patients. in humans, cchfv can cause a sudden onset of a non-specific febrile illness that can rapidly progress to severe hemorrhagic manifestations. currently, there is no widely available vaccine a ...202032645335
population genetics of wild macaca fascicularis with low-coverage shotgun sequencing of museum specimens.long-tailed macaques (macaca fascicularis) are widely distributed throughout the mainland and islands of southeast asia, making them a useful model for understanding the complex biogeographical history resulting from drastic changes in sea levels throughout the pleistocene. past studies based on mitochondrial genomes (mitogenomes) of long-tailed macaque museum specimens have traced their colonization patterns throughout the archipelago, but mitogenomes trace only the maternal history. here, our ...202032643146
in vitro pharmacological profile of a new small molecule bradykinin b2 receptor antagonist.we here report the discovery and early characterization of compound 3, a representative of a novel class of small molecule bradykinin (bk) b2 receptor antagonists, and its superior profile to the prior art b2 receptor antagonists compound 1 and compound 2. compound 3, compound 2, and compound 1 are highly potent antagonists of the human recombinant b2 receptor (kb values 0.24, 0.95, and 1.24 nm, respectively, calcium mobilization assay). compound 3 is more potent than the prior art compounds and ...202032636746
effects of the α-2 adrenergic receptor agonists lofexidine and guanfacine on food-cocaine choice in socially housed cynomolgus monkeys.although norepinephrine (ne) does not appear to play a prominent role in mediating the abuse-related effects of cocaine, studies have indicated that ne α-2 receptor agonists can attenuate reinstatement of extinguished cocaine self-administration in rats and monkeys and can decrease cocaine craving in humans. in the present studies, we examined the effects of two α-2 receptor agonists, lofexidine and guanfacine, on choice between food and cocaine (0.0-0.1 mg/kg per injection) in cynomolgus monkey ...202032636208
selective chemonucleolysis with condoliase in cynomolgus monkeys.selective chemonucleolytic effects of condoliase, a glycosaminoglycan degrading enzyme, was investigated histopathologically in cynomolgus monkeys. condoliase was administered once into the lumber intervertebral disc (ivd), and as a comparative control, chymopapain, a proteolytic enzyme, was administered in a similar manner. histopathological changes of the ivd and the adjacent vertebral body (vb) were examined at 1 to 26 weeks after administration. major changes induced by condoliase in the ivd ...202032633701
rptmdetermine: a fully automated methodology for endogenous tyrosine nitration validation, site-localization, and beyond.we present herein rptmdetermine, an adaptive and fully automated methodology for validation of the identification of rarely occurring post-translational modifications (ptms), using a semisupervised approach with a linear discriminant analysis (lda) algorithm. with this strategy, verification is enhanced through similarity scoring of tandem mass spectrometry (ms/ms) comparisons between modified peptides and their unmodified analogues. we applied rptmdetermine to (1) perform fully automated valida ...202032628467
prevalence and characterization of clostridium perfringens isolated from feces of captive cynomolgus monkeys (macaca fascicularis).clostridium perfringens is ubiquitous in the environment and the gastrointestinal tract of warm-blooded animals. while part of the gut microbiome, abnormal growth of c. perfringens causes histotoxic, neurologic, and enteric diseases in a variety of animal species, including humans, due to the production of toxins. there is extremely limited information on c. perfringens infection in non-human primates. presently, 10 strains were successfully isolated from 126 monkeys and confirmed by molecular a ...202032623046
broadly neutralizing antibodies potently inhibit cell-to-cell transmission of semen leukocyte-derived shiv162p3.hiv-1 sexual transmission occurs mostly through infected semen, which contains both free virions and infected leukocytes. transmission initiated by infected cells has been shown by several in vitro and in vivo studies and a reduced capacity of broadly neutralizing antibodies (bnabs) to inhibit cell-to-cell transmission has also been reported. however, due to limitations of available experimental models, there is yet no clarity to which extend bnabs can prevent transmission mediated by semen leuk ...202032619962
[pharmacological characteristics and clinical study results of romosozumab (evenity®; genetical recombination), a drug with novel mechanism of action to treat osteoporosis at high risk of fracture].romosozumab (evenity®) is a humanized monoclonal antibody designed to target sclerostin. sclerostin is a glycoprotein that is secreted by osteocytes and that inhibits wnt signaling in osteoblast lineage cells, leading to decreased bone formation by osteoblasts and increased bone resorption by osteoclasts. romosozumab, by binding and inhibiting sclerostin, increases bone formation and decreases bone resorption. romosozumab is known to mainly enable increase in modeling-based bone formation. in st ...202032612041
the establishment of a rheumatoid arthritis primate model in macaca fascicularis.rheumatoid arthritis (ra) is a long-term autoimmune disorder that mostly affects the joints and leads to the destruction of cartilage. an ra model in non-human primates is especially useful because of their close phylogenetic relationship to humans in terms of cross-reactivity to compounds developed using modern drug technologies.202032605610
increased plasma concentrations of an antidyslipidemic drug pemafibrate co-administered with rifampicin or cyclosporine a in cynomolgus monkeys genotyped for the organic anion transporting polypeptide 1b1.in vitro permeability and in vivo pharmacokinetics of pemafibrate were investigated in human intestinal and animal models untreated or pretreated with cyclosporine a or rifampicin to evaluate any drug interactions. ratios of basal to apical apparent permeability (papp) over apical to basal papp in the presence of ph gradients decreased from 0.37 to 0.080 on rifampicin co-incubation, suggesting active transport of pemafibrate from basal to apical sides in intestinal models. plasma concentrations ...202032601018
structural integrity of the alveolar-capillary barrier in cynomolgus monkeys challenged with fully virulent and toxin-deficient strains of bacillus anthracis.inhalational anthrax, a disease caused by inhaling bacillus anthracis spores, leads to respiratory distress, vascular leakage, high-level bacteremia, and often death within days. anthrax lethal toxin and edema toxin, which are composed of protective antigen (pa) plus either lethal factor (lf) or edema factor (ef), respectively, play an important yet incompletely defined role in the pulmonary pathophysiology. to better understand their contribution, we examined the structural integrity of the alv ...202032598882
expression of cannabinoid cb1 r-gpr55 heteromers in neuronal subtypes of the macaca fascicularis striatum.the cannabinoid cb1 receptor (cb1 r) is the most abundant g protein-coupled receptor in the central nervous system, consistent with the important role of endocannabinoids as neuromodulators. cannabinoids also modulate the function of g protein-coupled receptor 55 (gpr55), which forms heteroreceptor complexes with the cb1 r in the striatum. the aim was to characterize cannabinoid cb1 r-gpr55 heteromers (cb1 r/gpr55hets) in the basal ganglia input nuclei of nonhuman primates, macaca fascicularis, ...202032594556
the relative efficacy of the cranium and os coxa for taxonomic assessment in macaques.the cranium is generally considered more reliable than the postcranium for assessing primate taxonomy, although recent research suggests that pelvic shape may be equally reliable. however, little research has focused on intrageneric taxonomic discrimination. here, we test the relative taxonomic efficacy of the cranium and os coxa for differentiating two macaque species, with and without considering sexual dimorphism.202032594518
nonclinical safety assessment of amg 553, an investigational chimeric antigen receptor t-cell therapy for the treatment of acute myeloid leukemia.feline mcdonough sarcoma-like tyrosine kinase 3 (flt3), a tyrosine-protein kinase involved in hematopoiesis, is detectable on the cell surface of approximately 80% of leukemia isolates from adult patients with acute myeloid leukemia (aml). amg 553 is an investigational chimeric antigen receptor (car) t-cell immunotherapy for the treatment of aml. flt3 expression analysis and in vitro and in vivo studies were leveraged to evaluate the nonclinical safety of amg 553. cynomolgus monkeys administered ...202032589753
applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.alphaviruses such as venezuelan equine encephalitis virus (veev) and eastern equine encephalitis virus (eeev) are arboviruses that can cause severe zoonotic disease in humans. both veev and eeev are highly infectious when aerosolized and can be used as biological weapons. vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. the cynomolgus macaque (macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or ...202032584818
raav8 and raav9-mediated long-term muscle transduction with tacrolimus (fk506) in non-human primates.to establish an efficient, safe immunosuppressive regimen of adeno-associated vector (aav)-mediated gene therapy for duchenne muscular dystrophy (dmd), we evaluated the effect of tacrolimus (fk506) on skeletal muscle transduction with aav8 and aav9 vectors expressing the lacz and microdystrophin (m3) genes labeled by flag. we utilized 3- to 4-year-old macaca fascicularis, screened for neutralizing antibodies against aav. 3 days before aav injection and throughout the experiment, 0.06 mg/kg tacro ...202032577431
a comparative evaluation of thermal camera and visual counting methods for primate census in a riparian forest at the lower kinabatangan wildlife sanctuary (lkws), malaysian borneo.a number of primate census techniques have been developed over the past half-century, each of which have advantages and disadvantages in terms of resources required by researchers (e.g., time and costs), availability of technologies, and effectiveness in different habitat types. this study aims to explore the effectiveness of a thermal imaging technique to estimate the group size of different primate species populations in a degraded riparian forest in the lower kinabatangan wildlife sanctuary ( ...202032572697
prediction of human pharmacokinetics and clinical effective dose of si-b001, an egfr/her3 bi-specific monoclonal antibody.si-b001 is a new egfr/her3 bi-specific antibody showing encouraging anti-tumor efficacy in the preclinical studies and was ready for further clinical research. to help with the dose design, human pharmacokinetics (pk) and clinical effective doses of si-b001 were predicted by pk and pk/pd modeling and simulation. a michaels-menten (m-m) pk model was first used to describe the pk of si-b001 in cynomolgus monkeys, whose parameters were allometrically scaled to humans for the simulation of human pk ...202032565357
preclinical efficacy and safety of an anti-human vegfa and anti-human nrp1 dual-targeting bispecific antibody (idb0076).although bevacizumab (avastin®) has been approved as an antiangiogenic agent against some cancers, the efficacy is transient and unsatisfactory in other cancers most likely owing to the presence of alternative proangiogenic factors. therefore, simultaneous blocking of several proangiogenic factors may be a promising strategy for antiangiogenic cancer therapeutics. accordingly, neuropilin-1 (nrp1) is an attractive target because it serves as a multifunctional receptor for the vascular endothelial ...202032560565
variability in the number of infraorbital foramina in rhesus macaques (macaca mulatta) and cynomolgus macaques (macaca fascicularis).this study aimed to determine the number of infraorbital foramina in monkeys of the papionini tribe. the authors performed a μct analysis of the morphology of the infraorbital foramina. a total number of 52 simian skulls belonged to two macaque species: macaca mulatta and macaca fascicularis were used in the study. the number of infraorbital foramina was counted macroscopically and with the use of a magnifying glass. next, the skull representing the most common morphological type was selected an ...202032558307
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