bluuebunny/crossref_metadata_2025_split huggingface dataset:
JSKN003, A NOVEL BIPARATOPIC ANTI-HER2 ANTIBODY-DRUG CONJUGATE, EXHIBITS POTENT ANTITUMOR EFFICACY
Authors: Wang Pilin , Guo Kangping , Peng Jianjian , Sun Jie , Xu Ting 
Published: July 2023

Abstract
In human advanced solid tumors, expression of HER2 protein has been reported in various tumor tissues and a variety of cultured tumor cell lines including breast cancer, gastric cancer, pancreatic cancer, lung cancer, colorectal cancer, and ovarian cancer. Due to the critical roles of HER2 in carcinogenesis, two main targeted therapies have been developed in the past two decades to block the HER2-driven pathways, which include small molecule compounds that inhibit the tyrosine kinase activity of the intracellular domain, and mono-antibodies (mAbs) that target the extracellular domain (ECD) of the receptors. JSKN003 is an antibody-drug conjugate (ADC) comprised of a recombinant, humanized anti-human epidermal growth factor receptor 2 (HER2) bispecific antibody conjugated to a topoisomerase I inhibitor via a dibenzocyclooctyne tetrapeptide linker. The anti-HER2 component, KN026, is a recombinant, humanized bispecific antibody that targets both extra-cellular domains II (pertuzumab binding site) and IV (trastuzumab binding site) of HER2. JSKN003 showed high affinity binding to human HER2 with KDs of 2.209 E-10M, which is comparable to its parental antibody KN026 and bound to NCI-N87 and BxPC-3 cells in a concentration-dependent manner. At the same time JSKN003 showed more extensive and faster internalization than DS8201 on NCI-N87 cells. As expected, JSKN003 showed directly inhibits growth by targeting HER2 positive tumor model (NCI-N87 and BT474 cell models). The single dose and multiple dose pharmacokinetics study in cynomolgus monkey indicated that JSKN003, total antibody and DXd had general linear dynamic characteristics, and pharmacokinetics parameters showed no significant differences between males and females in the range 0.3-30 mg/kg. The HNSTD (highest non-severely toxic dose) of JSKN003 was determined as 30mg/kg in cynomolgus monkeys. These preclinical data suggest that JSKN003 could potentially benefit patients with tumors co-expressing HER2 through improved drug selectivity and efficacy. JSKN003’s safety, tolerability and preliminary anti-tumor activity are currently being evaluated in a first-in-human phase I study in advanced stage solid tumors in Australia (NCT05494918) using a BOIN design. This ADC is targeted on the subjects who has HER2 expression and/or HER2-gene mutation and may address an unmet medical need for these patients.
POTENT AND SELECTIVE A2AR MONOCLONAL ANTIBODY ANTAGONIST FOR THE TREATMENT OF CANCER
Authors: Hu Changyun , Wang Yanyan , Lan Xiqian , Zhang Jiandong , Zhao Xinyan 
Published: July 2023

Abstract

Background and significance
The presence of adenosine at abnormally high concentrations in tumor microenvironment leads to the activation of adenosine receptor 2A (A2aR) and represents one of the mechanisms for cancer patients to be resistance to immune checkpoint blockade therapies. CD39 and CD73 play an important role in converting ATP to adenosine. Currently antibodies or small molecule inhibitors (SMIs) targeting CD39 and CD73, as well as SMIs targeting adenosine receptors, are under preclinical investigation and early clinical development. However, effective biologics targeting adenosine receptors has not been reported. Here we demonstrated that humanized anti-A2aR antibodies represent promising novel therapeutic candidates for developing immunotherapy to restore anti-tumor responses in solid tumors that only partially respond or are completely resistance to ICB therapies.

Methods
Humanized anti-human A2aR monoclonal antibodies (mAbs) were generated from mouse hybridoma antibody via classic CDR grafting method. The A2aR binding and non-human primate cross-reactivity were measured by FACS using human A2aR-expressing HEK293 cells as well as human and cynomolgus monkey PBMCs. Internalizing properties were determined by FACS and immunofluorescent method. The cellular potency of these mAbs was assessed by their capability of inhibiting cAMP production induced by A2aR agonist adenosine and NECA in hA2aR-overexpressing HEK293 cells. The ability of lead candidates to reverse adenosine-mediated suppression of human effector cell function was determined using standard CD3/CD28 activation conditions in the presence of A2aR agonist NECA.

Results and Conclusion
We successfully humanized anti-A2aR antibody discovered via hybridoma technology. Humanized anti-A2aR antibodies maintain binding, cross-reactivity to human and cynomolgus monkey A2aR, as well as internalizing property and A2aR-antagonizing potency, in comparison with parental antibody. Humanized antibodies are 5~10 fold more potent than clinical stage small molecule inhibitors CPI-444 and AB928 in inhibiting cAMP production. Blockade of A2aR with humanized antibody can restore activation and cytokine production of human T and NK cells suppressed by A2aR agonist adenosine or NECA. Thus, antibody-mediated blockade of A2aR pathway represents a novel strategy to mitigate adenosine-mediated tumor resistance to immune checkpoint blockade therapies.
Exploring the natural and treatment history of vitiligo: perceptions of patients and healthcare professionals from the global VALIANT study
Authors: Hamzavi Iltefat H , Bibeau Kristen , Grimes Pearl , Harris John E , van Geel Nanja , Parsad Davinder , Tulpule Mukta , Gardner Jackie , Valle Yan , Tlhong Matewa Gaone , LaFiura Christine , Ren Haobo , Ezzedine Khaled 
Published: July 2023

Abstract

Background
Vitiligo is a chronic autoimmune disease affecting melanocytes, resulting in skin depigmentation. Patients with vitiligo often have reduced quality of life and comorbid autoimmune conditions and have reported a lack of available treatments for their vitiligo.

Objectives
The Vitiligo and Life Impact Among International Communities (VALIANT) study is the first global survey to explore the natural history and management of vitiligo from the perspectives of patients and healthcare professionals (HCPs).

Methods
The survey recruited adults (≥ 18 years) diagnosed with vitiligo and HCPs treating patients with vitiligo via an online panel in 17 countries. Patients were queried regarding clinical characteristics and vitiligo treatment. HCPs were queried regarding diagnosis and management of patients with vitiligo.

Results
Included in the analysis were 3541 patients and 1203 HCPs. Nearly half (45.2%) of the patients had &gt; 5% affected body surface area; 57.1% reported family history. Patients obtained formal diagnosis after a mean (SD) of 2.4 (4.1) years; 44.9% reported previous misdiagnosis. Many patients (56.7%) reported being told that vitiligo could not be treated; 53.9% of HCPs believed patients who never treated their vitiligo had been told that vitiligo could not be treated. One-quarter of HCPs (26.3%) did not believe that an effective therapy for vitiligo exists; 44.6% of patients reported giving up on finding an effective therapy. Top treatment goals for patients and HCPs, respectively, were reduction or cessation of spread (24.7% and 18.5%) and repigmentation (22.5% and 37.2%). Patient perception of effective care was similar for treatment by dermatologists (66.9%) and primary care HCPs (67.0%).

Conclusions
Patients with vitiligo and HCPs reported similar treatment goals and expressed frustration with the lack of effective therapies. Patients reported high rates of initial misdiagnosis; many ceased seeking healthcare because they perceived that vitiligo could not be treated. The findings highlight the need for earlier diagnosis and improved disease management for vitiligo.
Artificial intelligence-assisted publishing in five prominent dermatology journals: a quantitative study of recent publications
Authors: Heerfordt Ida M 
Published: July 2023

The potential applications of artificial intelligence (AI) in dermatology literature are discussed, and AI-generated content within abstracts of five prominent dermatology journals is investigated. Using validated AI detection software, the study categorized 57 abstracts and found none to be possibly or likely AI-generated. A highlighted limitation was the reliability of the software in detecting AI-generated content.
Temporal characteristics of gamma rhythm constrain properties of noise in an inhibition-stabilized network model
Authors: Krishnakumaran R , Ray Supratim 
Published: July 2023

Abstract
Gamma rhythm refers to oscillatory neural activity between 30 and 80 Hz, induced in visual cortex by stimuli such as iso-luminant hues or gratings. The power and peak frequency of gamma depend on the properties of the stimulus such as size and contrast. Gamma waveform is typically arch-shaped, with narrow troughs and broad peaks, and can be replicated in a self-oscillating Wilson–Cowan (WC) model operating in an appropriate regime. However, oscillations in this model are infinitely long, unlike physiological gamma that occurs in short bursts. Further, unlike the model, gamma is faster after stimulus onset and slows down over time. Here, we first characterized gamma burst duration in local field potential data recorded from two monkeys as they viewed full screen iso-luminant hues. We then added different types of noise in the inputs to the WC model and tested how that affected duration and temporal dynamics of gamma. While the model failed with the often-used Poisson noise, Ornstein–Uhlenbeck noise applied to both the excitatory and the inhibitory populations replicated the duration and slowing of gamma and replicated the shape and stimulus dependencies. Thus, the temporal dynamics of gamma oscillations put constraints on the type and properties of underlying neural noise.
Moisture and soil type are primary drivers of Helicoverpa zea (Lepidoptera: Noctuidae) pupation
Authors: Dillard DeShae , Reisig Dominic D , Schug Hayden T , Burrack Hannah J 
Published: July 2023

Abstract
Studies in the lab have demonstrated that evaluating the effect of soil moisture and other variables is essential for understanding the importance of environmental factors influencing the Heliothinae pupal stage, but simulated field studies are conducted infrequently. We compared the pupation of Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) under saturated and unsaturated conditions across 3 distinct soil types (coarse sand, high organic muck, and fine-textured clay) and observed adult emergence, as well as pupal depth and weight. The interaction between soil type and moisture had a significant effect on adult emergence. Fewer adults emerged from dry fine-textured clay soil than from dry coarse sand and high organic muck. However, there was no effect of soil type and no interaction between soil and moisture on pupal depth. Soil moisture was the primary driver of pupal depth, suggesting prepupae use moisture to mediate their position within the pupal chamber. In addition, pupal weight was unrelated to soil type, moisture, or their interaction. Our study demonstrates that soil moisture can be a greater driver of H. zea pupation than soil type, but additional observations are necessary to understand the mechanism by which moisture impacts pupation.
Maternal behavioral thermoregulation facilitated evolutionary transitions from egg laying to live birth
Authors: Pettersen Amanda K , Feiner Nathalie , Noble Daniel W A , While Geoffrey M , Uller Tobias , Cornwallis Charlie K 
Published: July 2023

Abstract
Live birth is a key innovation that has evolved from egg-laying ancestors over 100 times in reptiles. However, egg-laying lizards and snakes can have preferred body temperatures that are lethal to developing embryos, which should select against prolonged egg retention. Here, we demonstrate that thermal mismatches between mothers and offspring are widespread across the squamate phylogeny. This mismatch is resolved by gravid females adjusting their body temperature towards the thermal optimum of their embryos. We find that the same response occurs in both live-bearing and egg-laying species, despite the latter only retaining embryos during the early stages of development. Importantly, phylogenetic reconstructions suggest this thermoregulatory behavior in gravid females evolved in egg-laying species prior to the evolution of live birth. Maternal thermoregulatory behavior, therefore, bypasses the constraints imposed by a slowly evolving thermal physiology and has likely been a key facilitator in the repeated transition to live birth.
Do China’s Foreign Economic Ties Lead to Influence Abroad? New Evidence from Recent Events
Authors: Wang Guan , Pearson Margaret M , Kastner Scott L 
Published: July 2023

AbstractDo China’s growing foreign economic ties translate into political influence abroad? We identify issues about which China cares deeply, and assess whether increased economic ties correlate with greater expressed support for Chinese activities on these issues. We collect new data to measure how countries have responded to China’s implementation of a National Security Law for Hong Kong, and recent policies in Xinjiang. We find that countries with closer economic linkages to China were less likely to criticize—and in some cases more likely to support—China’s actions in Hong Kong and Xinjiang, but the strength and significance of this effect vary considerably depending on the context and type of economic ties. Interestingly, the effects of China’s foreign economic ties are substantively smaller than levels of democracy and development. The findings call into question simple assumptions about the translation of economic ties into political influence, and suggest directions for future study.
Identity-by-descent-based estimation of the X chromosome effective population size with application to sex-specific demographic history
Authors: Cai Ruoyi , Browning Brian L , Browning Sharon R 
Published: July 2023

Abstract
The effective size of a population (Ne) in the recent past can be estimated through analysis of identity-by-descent (IBD) segments. Several methods have been developed for estimating Ne from autosomal IBD segments, but no such effort has been made with X chromosome IBD segments. In this work, we propose a method to estimate the X chromosome effective population size from X chromosome IBD segments. We show how to use the estimated autosome Ne and X chromosome Ne to estimate the female and male effective population sizes. We demonstrate the accuracy of our autosome and X chromosome Ne estimation with simulated data. We find that the estimated female and male effective population sizes generally reflect the simulated sex-specific effective population sizes across the past 100 generations but that short-term differences between the estimated sex-specific Ne across tens of generations may not reliably indicate true sex-specific differences. We analyzed the effective size of populations represented by samples of sequenced UK White British and UK Indian individuals from the UK Biobank.
A graph approach for fast dense array inter-station phase delay interpretation
Authors: Lecointre A , Roux P , Bouttier P-A , Picard C , Louvet V 
Published: July 2023

SUMMARY
We present a phase-delay detection procedure adapted for seismic arrays composed of a large number of stations. We use graph formalism to introduce a direct method to compute station phase delays starting from inter-station phase differences deduced from noise cross-correlation functions. We focus this study on surface wave main arrival as phase-difference evaluation at each station requires high coherence level. Then, we perform numerical experiments with synthetic data computed as a realistic and dense network of 79 stations in a 400 by $400\, \mathrm{km^2}$ square box. For one of the 79 stations, we simulate a phase difference of 15 per cent of the signal period. Further, we evaluate the accuracy and precision of phase-delay estimation at each station with regard to the quality of the cross-correlation functions (i.e. the signal-to-noise ratio). When the inter-station coherence levels are larger than 0.6 (i.e. a high-quality signal), we show good agreement between the phase-delay estimation and its expected value of 15 per cent of the signal period. We introduce a coherence-weighted estimate of phase delay and show that applying this weighting allows us to be less vulnerable to phase-delay underestimation for intermediate-quality signals. Then, the method is applied to experimental data recorded by a high density nodal array with 923 vertical geophones with 19 d of continuous records, centred on the 600 by $600\, \mathrm{m^2}$ damage zone of the Clark branch of the San Jacinto Fault Zone, Southern California (USA). We verify that the San Jacinto network is well synchronized, as most of the estimated phase delays are less than 2 per cent of the central period of the signal, and they are associated with high levels of inter-station coherence. More surprisingly, the spatial features of the estimated phase delays show deterministic geographical patterns that are related to topography and that exhibit similarities with phase velocity maps at $4.5\, \mathrm{Hz}$ from previous 3-D velocity inversions. This suggests that the topographic effect may be accounted for to estimate accurate phase delays. Also, we note that the temporal variability of the estimated phase delays in the case of the San Jacinto data set are related to atmospheric forcing. Our direct method for estimating phase delays is applicable to structure-oriented monitoring studies, and it opens perspectives in the monitoring of seismic velocity variations.
Adherence and persistence to direct factor Xa inhibitors in the community following newly diagnosed venous thromboembolism: a retrospective pharmacy-linkage study
Authors: Dix Caroline , Bortz Hadley , da Gama Mike , Treloar Michael , Reynolds Michael , Ramanan Radha , Day Thomas , Tran Huyen 
Published: July 2023

Abstract

Objectives
To assess adherence and persistence to the direct factor Xa inhibitor oral anticoagulants in the community following newly diagnosed venous thromboembolism (VTE).

Methods
We retrospectively reviewed community pharmacy dispensing data on all patients with newly diagnosed VTE who were prescribed direct factor Xa inhibitors, apixaban or rivaroxaban, between January 2018 and December 2019 at our institution. Proportion of days covered (PDC) was used to assess adherence at 90 days, and 6- and 12 months. Persistence was measured by participants having both dispensed supply of a factor Xa inhibitor at the end of the treatment period and no significant gaps (maximum of 60 days) in supply.

Key findings
There were 225 patients identified. Overall PDC at 90 days, 6- and 12 months were 84.6%, 86.2% and 86.1%, respectively. Apixaban had a higher mean overall PDC than rivaroxaban (86.2% and 80.6%, respectively). Females demonstrated higher PDC compared with males (87.3% versus 81.2%). Overall, 133 patients (64%) were persistent with therapy.

Conclusions
In patients with newly diagnosed VTE treated with a factor Xa inhibitor, adherence rates are high at &gt;80%, with females and those prescribed apixaban exhibiting higher adherence. These findings may assist clinicians in identifying those patients with VTE at risk of poor adherence.
The Cluster Multiplication Theorem for Acyclic Quantum Cluster Algebras
Authors: Chen Xueqing , Ding Ming , Zhang Haicheng 
Published: July 2023

Abstract
Let $Q$ be a finite acyclic valued quiver. We give the cluster multiplication formulas in the quantum cluster algebra of $Q$ with arbitrary coefficients, by applying certain quotients of derived Hall subalgebras of $Q$. These formulas can be viewed as the quantum version of the cluster multiplication theorem in the classical cluster algebra proved by Caldero–Keller for finite type, Hubery for affine type, and Xiao–Xu for acyclic quivers.
Intelligent monitoring of vibration and structural-borne noise induced by rail transit
Authors: Liu Qingjie , Xu Lu , Feng Qingsong 
Published: July 2023

Abstract
The monitoring of urban rail transit vibration and structural-borne noise can well solve the problem of small amount of data and large discreteness in traditional evaluation tests. In this study, a monitoring system is utilized to collect and preprocess vibration and noise signals. By employing cellular network and cloud-based services, real-time acquisition and analysis of vibration and noise signals are achieved. In this article, it is proposed to normalize the vibration data obtained after edge computing. After treatment, the gray correlation analysis method was used to determine the correlation between each vibration data component and vibration data classification. Combining frequency domain analysis of vibration data, the data components with high correlation are used as inputs to an improved K-nearest neighbours (KNN) model. Additionally, the correlation of each data component is introduced into the distance calculation formula. The improved KNN model shows improvements in recall rate, precision rate, F-measure, and accuracy compared to the original KNN model, with increases of 0.76 per cent, 2.76 per cent, 1.81 per cent, and 1.61 per cent respectively. Through practical measurements, it is found that different vehicles cause significant variations in vibration, with differences of up to 11 dB in tunnel wall vibration. The differences in tunnel wall vibration caused by the same vehicle at different passenger loads do not exceed 5 dB. Combining practical application cases, the rail transit environmental noise monitoring system established in this study demonstrates its applicability in monitoring vibration and noise-sensitive areas, as well as analysing the effectiveness of vibration reduction and noise control measures.
LC–MS-MS-MS3 for the determination and quantification of ∆9-tetrahydrocannabinol and metabolites in blood samples
Authors: Proença Paula , Teixeira Helena M , Martinho Beatriz , Monteiro Carla , Franco João , Corte-Real Francisco 
Published: July 2023

Abstract
Due to the high prevalence of cannabinoids in forensic toxicology analysis, it is crucial to have an efficient method that allows the use of a small sample amount and that requires a minimal sample preparation for the determination and quantification of low concentrations. A simple, highly selective and high throughput liquid chromatography–tandem mass spectrometry methodology (LC–MS-MS-MS3) was developed for the determination and quantification of ∆9-tetrahydrocannabinol (THC), 11-hydroxy-∆9- tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THC-COOH) in blood samples. Chromatographic analysis of THC, THC-OH and THC-COOH and their deuterated internal standards was preceded by protein precipitation (PPT) of 0.1 mL of blood samples with acetonitrile. Chromatographic separation was achieved by use of an Acquity UPLC® HHS T3 (100 mm × 2.1 mm i.d., 1.8 μm) reversed-phase column, using a gradient elution of 2 mM aqueous ammonium formate, 0.1% formic acid and methanol at a flow rate of 0.4 mL/min, with a run time of 10 min. For the MS-MS-MS3 analysis, a SCIEX QTRAP® 6500+ triple quadrupole linear ion trap mass spectrometer was used via electrospray ionization (ESI), operated in multiple reaction monitoring (MRM) and linear ion trap mode (MS3). The method was validated in accordance with internationally accepted criteria and guidelines, and proved to be selective and linear between 0.5 and 100 ng/mL (r2 &gt; 0.995). The lower limits of quantification (LLOQ) corresponded to the lowest concentrations used for the calibration curves. The coefficients of variation obtained for accuracy and precision were &lt;15%. The mean recoveries were between 88.0% and 117.2% for the studied concentration levels (1 ng/mL, 5 ng/mL and 50 ng/mL). No significant interfering compounds, matrix effects or carryover were observed. The validated method provides a sensitive, efficient and robust procedure for the quantification of cannabinoids in blood, using LC–MS-MS-MS3 and a sample volume of 0.1 mL. This work is also a proof of concept for using LC–MS3 technique to determine drugs in biological samples.