bluuebunny/crossref_metadata_2025_split huggingface dataset:
Final Analysis of Post‐Marketing Surveillance for Avelumab + Axitinib in Patients With Renal Cell Carcinoma in Japan
Authors: Nonomura Norio , Ito Taito , Sato Masashi , Morita Makiko , Ogi Mie , Kajita Masahiro , Oya Mototsugu 
Published: January 2025

ABSTRACTIntroductionAvelumab, an anti‐programmed death ligand 1 antibody, was approved in combination with axitinib for curatively unresectable or metastatic renal cell carcinoma (RCC) in Japan in December 2019. Because the pivotal JAVELIN Renal 101 study included a limited number of Japanese patients, post‐marketing surveillance (PMS) was required to evaluate outcomes (safety and effectiveness) in patients with RCC who received avelumab + axitinib treatment in clinical practice in Japan.Materials and MethodsWe report data from prospective, noncomparative, multicenter, observational PMS in patients with RCC who received ≥ 1 dose of avelumab. Patients were enrolled between December 2019 (date of regulatory approval) and May 2021. The primary objective was to evaluate safety, defined as adverse drug reactions (ADRs) of safety specifications occurring during an observation period of ≤ 52 weeks for each patient. The secondary objective was to evaluate effectiveness, including best overall response and overall survival (OS).ResultsIn total, 328 patients were included in the safety and effectiveness analysis sets. Overall, 173 patients (52.7%) had ADRs of safety specifications of any grade, most commonly thyroid dysfunction (n = 69 [21.0%]), infusion reaction (n = 65 [19.8%]), and hepatic disorders (n = 45 [13.7%]). Objective responses occurred in 118 patients (36.0%), including complete or partial responses in 13 (4.0%) and 105 (32.0%), respectively; the disease control rate was 75.6%. The 12‐month OS rate was 83.7% (95% CI, 78.9%–87.4%).DiscussionThis PMS confirmed the safety, tolerability, and effectiveness of avelumab + axitinib in patients with RCC in clinical practice in Japan, with a benefit–risk profile comparable to that observed in clinical trials.
Therapeutic Levels of Acetaminophen Causing AKI: A Case Report and Literature Review
Authors: Tayyab Hamnah , Dhondapati Lavanya , Ullah Ashraf , Marsool Mohammed Dheyaa Marsool , Jagmeet Singh , Ahmed Khabab Abbasher Hussien Mohamed 
Published: January 2025

ABSTRACTOur case highlights the importance of being aware of the potential renal complications that can occur with acetaminophen, even when used at dosages slightly above the recommended therapeutic dose.
Relationship Between Short‐Term Outcomes and PD‐L1 Expression Based on Combined Positive Score and Tumor Proportion Score in Recurrent or Metastatic Head and Neck Cancers Treated With Anti‐PD‐1 Antibody Monotherapy
Authors: Ohara Akihiro , Mori Taisuke , Itoyama Mai , Yokoyama Kazuki , Yamamoto Shun , Kato Ken , Honma Yoshitaka 
Published: January 2025

ABSTRACTBackgroundPD‐L1 expression in tumors and immune cells is a biomarker for the efficacy of anti‐PD‐1 antibody (APA) therapy across diverse cancers. Based on the results from the KEYNOTE‐048 trial, pembrolizumab monotherapy is indicated for platinum‐sensitive recurrent/metastatic head and neck squamous cell carcinoma (R/M‐HNSCC) with a positive combined positive score (CPS). Conversely, nivolumab is utilized for platinum‐pretreated R/M‐HNSCC regardless of the positive tumor proportion score (TPS) following the results of the CheckMate‐141; however, its subgroup analysis indicated that TPS‐positive population tended to have a relatively high overall response rate and progression‐free survival (PFS). Although, the superior PD‐L1 evaluation method for predicting APA therapy efficacy in R/M‐HNSCC and the appropriate cut‐off value remain undetermined. This study aims to elucidate the relationship between short‐term outcomes and PD‐L1 expression based on CPS and TPS in R/M‐HNSCC patients undergoing APA monotherapy.MethodsR/M‐HNSCC patients receiving APA monotherapy from 2018 to 2021 with available samples were enrolled. An experienced pathologist evaluated CPS and TPS utilizing the PD‐L1 IHC 22C3 pharmDx assay. Short‐term outcomes were assessed by clinical benefit rate (CBR), objective response rate (ORR), and PFS.ResultsFifty‐three R/M‐HNSCC patients received APA monotherapy. Forty‐seven had CPS ≥ 1, and 44 had TPS ≥ 1%. By receiver‐operating characteristic curve analysis, the CPS cut‐off value for predicting better CBR was determined to be 50. The ORR/CBR tended to be higher when CPS was positive. Although differences in PFS were not observed for a cut‐off value of 1 or 20, they were observed for 50 (3.2 vs. 8.4 months; hazard ratio 0.44, p = 0.02). ORR and CBR were respectively 12.5% and 12.5% in the TPS < 1% group and 33.3% and 48.9% in the ≥ 1% group. The TPS < 1% group showed significantly poorer PFS (1.9 vs. 4.5 months, hazard ratio 0.40, p = 0.01).ConclusionThe short‐term efficacy of APA monotherapy in R/M‐HNSCC patients tended to be better when CPS was positive. TPS helps predict the population that does not benefit from APA monotherapy.
Plasmid Library Construction From Genomic DNA
Authors: Florez‐Cardona Valeria , Khani Jessica , McNutt Emily , Manta Bruno , Berkmen Mehmet 
Published: January 2025

AbstractFunctional genomic approaches have been effective at uncovering the function of uncharacterized genes and identifying new functions for known genes. Often these approaches rely on an in vivo screen or selection to associate genes with a phenotype of interest. These selections and screens are dependent upon the expression of proteins encoded in genomic DNA from an expression vector, such as a plasmid. Despite the utility of genomic DNA plasmid libraries, the protocols for their construction have remained unchanged in the past 40 years. Here, we present a procedure for constructing plasmid libraries from genomic DNA. This procedure is scalable and relies on simple techniques and common laboratory equipment and reagents. Briefly, the genomic DNA is extracted and then physically fragmented with a g‐TUBE, overhangs are repaired, and fragments are selectively purified with magnetic beads to obtain an average fragment size of 2.5 kb. Blunted fragments are ligated into a blunt‐end‐digested and dephosphorylated vector. Finally, the library is amplified by electroporating the ligation into a high‐transformation‐efficiency Escherichia coli strain and extracting the plasmid DNA from the transformants. As a proof of concept, we built and sequenced three genomic libraries from different genomes and calculated their coverage using a next‐generation sequencing (NGS) workflow. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC.Basic Protocol: Plasmid library constructionAlternate Protocol: Selection of gDNA fragments using SageELF gel fractionatorSupport Protocol 1: Extraction of gDNA with phenol/chloroformSupport Protocol 2: Vector preparation
A 37‐Color Spectral Flow Cytometric Panel to Assess Transcription Factors and Chemokine Receptors in Human Intestinal Lymphoid Cells
Authors: Jiang Qinyue , Lindelauf Ciska , van Unen Vincent , van der Meulen‐de Jong Andrea E. , Koning Frits , Pascutti M. Fernanda 
Published: January 2025

ABSTRACTWe have developed a 37‐color spectral flow cytometry panel to assess the phenotypical differentiation of innate and adaptive immune lymphoid subsets within human intestinal tissue. In addition to lineage markers for identifying innate lymphoid cells (ILC), TCRγδ, MAIT (mucosal‐associated invariant T), natural killer (NK), CD4+ and CD8+ T cells, we incorporated markers of differentiation and activation (CD45RA, CD45RO, CD25, CD27, CD38, CD39, CD69, CD103, CD127, CD161, HLA‐DR, CTLA‐4 [CD152]), alongside transcription factors (Bcl‐6, FoxP3, GATA‐3, Helios, T‐bet, PU.1 and RORγt) and chemokine receptors (CCR4, CCR6, CCR7, CXCR3, and CXCR5). Additionally, Granzyme B and Ki‐67 were included to assess cytotoxicity and proliferation potential of the different subsets. This panel is currently used for in‐depth immunophenotyping in endoscopic biopsies and peripheral blood mononuclear cells (PBMC) from inflammatory bowel disease (IBD) patients. Distinguished from other OMIP papers, the comprehensive detection of both transcription factors and chemokine receptors facilitates the efficient assessment of several subsets, particularly CD4+ T helper cells, and its potential application extends to both tissue and circulation.
Retrospective Evaluation of Novel Synthetic Opioids and Xylazine Chronic Intake by Post‐Mortem Hair Testing
Authors: Ballotari Marco , Pigaiani Nicola , Bacci Anna , Scott Karen S. , Davis Gregory G. , Gottardo Rossella , Bortolotti Federica 
Published: January 2025

ABSTRACTFentanyl and its derivatives (nonpharmaceutical fentanyl, NPFs) represent the largest group among synthetic opioids. Fentanyl‐related deaths and fatalities from tampering with pharmaceutical products have been reported. Furthermore, in the United States, adulterants such as xylazine and other substances, including the nitazenes class of opioids, have been found in an increasing number of unintentional overdose deaths, drug seizures, and reports of use by recreational drug users. Monitoring the diffusion of fentanyl, NPFs, nitazenes, and adulterants among the population is a fundamental pursuit in forensic toxicology. The use of hair analysis is perfect for this purpose, providing essential information regarding previous intake or exposure to xenobiotics. The present study focused on the development and validation of a UPLC‐MS/MS method for the detection and quantification of fentanyl, NPFs, and xylazine, as well as the semiquantitative detection of nitazenes in hair samples from post‐mortem cases collected under the jurisdiction of the Jefferson County Coroner/Medical Examiner's Office (Birmingham, AL, USA). The method was validated according to international guidelines and applied to the analysis of n = 250 post‐mortem hair samples. In 52% of the analyzed hair samples, fentanyl, its main metabolites, and related analogs were detected, showing significant exposure to these substances in the population. Moreover, xylazine was detected in n = 48 hair samples (19.2%). The developed UPLC‐MS/MS method proved suitable for rapid chromatographic separation and sensitive detection of the studied compounds. In addition, this is the first time that xylazine and protonitazene have been measured in hair samples of subjects exposed to synthetic opioids.
Life stage hypothesis modeling determines insect vulnerability during developmental life stages to climate extremes
Authors: Durney J. Simone , Debinski Diane M. , Matter Stephen F. 
Published: January 2025

AbstractButterflies are important bioindicators that can be used to monitor the effects of climate change, particularly in montane environments. Changes in butterfly population size over time, reflective of indicator life stages, can signal changes that have occurred or are occurring in their environment indicating ecosystem health. From the perspective of understanding butterflies as bioindicators in these systems, it is essential to identify influential environmental variables at each life stage that have the greatest effect on population dynamics. Life stage hypothesis modeling was used to assess the effects of multiple temperature and precipitation metrics on the population growth rate of a Parnassius clodius butterfly population from 2009 to 2018. Extreme maximum temperatures during the larval‐pupal life stages were identified to have a significant negative effect on population growth rate. We speculate that higher temperatures during the spring ephemeral host plant's flowering, and P. clodius' larval stage, may lead to earlier plant senescence and lower P. clodius growth. Because Parnassius butterflies are well studied from a global perspective, results may aid in understanding the potential indicator life stages of other insect species in montane environments to climatic changes. Findings from this study demonstrate the value in assessing a butterfly species' response to short‐term weather variation or long‐term climatic changes at each life stage in order to protect and conserve insects and their interactions with other organisms.
Environmental influences on chorusing patterns in an Australian tropical savanna frog community
Authors: Brodie Sheryn , Allen‐Ankins Slade , Schwarzkopf Lin 
Published: January 2025

AbstractEcoacoustic methods provide opportunities for ecological studies of vocalizing species within the context of the natural habitats and communities in which they occur. Continuous acoustic monitoring of species assemblages can reveal patterns in breeding phenology, behavior, and interactions. We used long‐duration false‐color spectrograms derived from acoustic indices to detect the nightly chorusing of a community of anurans in a tropical savanna in north Queensland. We described the chorusing patterns of each species over two wet seasons at three breeding sites, and used conditional random forest analysis to investigate the influence of various environmental factors. Frogs in these habitats form multispecies aggregations at water bodies during breeding periods when males form large choruses to attract females. The chorusing patterns revealed the species have different breeding periods, which could be broadly categorized as explosive or prolonged. While rain events were often a trigger for the commencement of the breeding period, species responded differently to environmental conditions. Choruses of explosive breeding species occurred only on the night of, or night after, the first high rainfall event of the wet season. The prolonged breeding species showed idiosyncratic patterns of chorusing, which were generally consistent across sites. Fine‐grained nightly data on patterns of chorusing and the relationship with environmental conditions allow us to understand the detectability of the presence, or absence, of the frog species in these habitats, and provide baseline data for monitoring and management programs.
A P‐nucleophile Interrupted Seyferth‐Gilbert Reaction
Authors: Wei Yuan‐Jie , Zhou Fei‐Long , Tian Yan , Cheng Yong‐Feng 
Published: January 2025

AbstractHerein, we report an interrupted Seyferth–Gilbert reaction of ortho‐phosphanylbenzaldehydes with Seyferth–Gilbert reagent yielding vinylphosphonates. The transformation features remarkable chemoselectivity, mild reaction condition and good functional group tolerance.
Renewable Energy in Sudan: Current Status and Future Prospects
Authors: Al‐Rikabi Ihab Jabbar , Omara Adil A. M. , Abuelnour Mohamed Ali , Abuelnuor Abuelnuor A. A. , Mohamed Ahmed Elbashir , Ismail Najib Aminu 
Published: January 2025

ABSTRACTSudan relies heavily on refined petroleum products for electricity generation, excluding hydropower, contributing to environmental degradation through petroleum combustion. This challenge underscores the need to expand renewable energy utilization. This paper reviews the current status and future potential of renewable energy in Sudan. While hydropower generates approximately 54.6% of Sudan's electricity, other renewable sources contribute only 0.78% to the national grid. Sudan's hydropower capacity stands at 1907 MW, with plans to add 2197 MW. As a Sunbelt country, Sudan has immense solar energy potential, yet it has only constructed a 10‐MW solar PV plant (5 MW on‐grid). Two additional 10‐MW solar projects are under construction, and the government aims to install 2190 MW of grid‐connected solar PV and 50 MW of solar thermal energy by 2035. Wind energy remains underutilized, with a single 0.8‐MW wind turbine connected to the grid, although a 100‐MW wind power plant is under construction. The government envisions 1550 MW of wind capacity by 2035. Bioenergy capacity, predominantly from sugar industry co‐generation, totals 199 MW, with less than 20 MW on‐grid. Plans aim to install 270 MW of grid‐connected bioenergy by 2032. Despite possessing geothermal potential in the Red Sea region, no geothermal plants have been installed. However, 54 MW of geothermal projects are planned by 2030. Additionally, Sudan's nuclear energy program targets two 600‐MW reactors by 2030, while tidal energy projects could contribute 1.2 TWh annually to the grid. These initiatives aim to diversify Sudan's energy mix and enhance the country's sustainability.
Glacier thickness modelling and monitoring with geophysical data constraints: A case study on the Indren Glacier (NW Italy)
Authors: Strallo Valeria , Colombero Chiara , Troilo Fabrizio , Mondardini Luca , Godio Alberto 
Published: January 2025

AbstractThe ongoing global temperature increase has accelerated the mass loss of glaciers worldwide, with Italian alpine glaciers being particularly vulnerable due to their small size, complex geometries and exposition that implies a fast reaction to thermal and hydrological modifications. In such a frame, the Indren Glacier (Aosta Valley, north‐western Italian Alps) provides a valid test site to check the thickness evolution over the last two decades (1999–2020), through an integrated approach combining historical data, on‐site geophysical measurements, remote sensing surveys, modelling and temperature analysis. Using a 2018 helicopter‐based photogrammetric survey and Ground Penetrating Radar (GPR) survey campaigns of 2020, we obtained new input data and constraints to build up an updated thickness model for the whole glacier through the Glacier Thickness Estimation algorithm (GlaTE). Ice thickness is indeed a key parameter to estimate the ice volume and use it as further input in evolutionary models forecasting future scenarios. As a part of this integrated approach, we also analysed remote sensing and temperature data, finding a major modification in the glacier conditions over the last decade. Further comparing these results with previous studies, we identified a significant decrease in ice thickness, and we confirmed the presence of an over‐deepening in the glacier central widest part. This integrated methodology enhances our understanding of glacier dynamics and improves predictions of future changes, offering crucial insights for managing water resources and mitigating natural hazards in the alpine region.
Disintegration characteristics of undisturbed loess in response to train vibration frequency
Authors: Li Shan , Wang Jiading , Zhang Dengfei , Wang Li , Qi Lirong , Xiao Tao , Han Kai , Wang Qinghua 
Published: January 2025

AbstractDisintegration fragments the loess body, causing erosion and the emergence of significant geohazards. The impact of vibrations on soil disintegration has been slightly documented; however, the contribution and mechanism of train vibration frequency in the disintegration of undisturbed loess remain unclear. In this study, train vibrations were monitored in situ, and the resulting vibrational parameters were used in loess disintegration tests using a customised vibration‐disintegration apparatus. The changes in the meso‐parameters of the disintegrated loess and aqueous solutions were quantified, and the microstructural differences in the residual loess after disintegration were compared under non‐vibrating and vibrating conditions. The results revealed that train vibrations in the loess progressively diminished with increasing distance from the track, with dominant vibration frequencies ranging from 17 to 49 Hz. Increasing the vibration frequency accelerated loess disintegration and enhanced the dispersion of the disintegrated fragments. Notably, the acceleration effect of disintegration was particularly pronounced in the early stages of increasing vibration frequency, and it tended to plateau above 15 Hz. The relationship between the vibration frequency and disintegration velocity (DV) of loess influenced by the initial water content can be expressed as a power function with variables. Vibrations accelerate loess disintegration primarily attributed to repetitive particle displacement and the vibrations of free water in the pores which lead to frictional damage to the weakly cemented structure and pore expansion. Higher vibration frequencies generate greater inertial forces and facilitate more frequent particle jumps, allowing the loess to reach the disintegration threshold conditions more readily than at lower frequencies. These findings provide theoretical value for the prevention and mitigation of water‐induced loess geohazards and land degradation in vibrating environments.
Lycopene Alleviates Depression‐Like Behavior in Chronic Social Defeat Stress‐Induced Mice by Promoting Synaptic Plasticity via the BDNF–TrkB Pathway
Authors: Xu Heyan , Wang Yuna , Geng Dandan , Chen Fengming , Chen Yujia , Niwenahisemo Lisa Cynthia , Shi Lei , Du Ning , He Ziqiang , Xu Xiaoming , Kuang Li 
Published: January 2025

ABSTRACTLycopene is a natural plant extract widely studied for its powerful antioxidant and neuroprotective effects. Emerging evidence suggests that it also possesses potential antidepressant properties. Compared to commonly used clinical antidepressants, lycopene offers higher safety; however, its underlying mechanisms remain unclear. Therefore, this study aims to explore the mechanisms through which lycopene exerts its antidepressant effects. We employed the chronic social defeat stress (CSDS) model to induce depressive‐like behaviors in mice, followed by lycopene treatment (20 mg/kg). Based on previous research, we focused on synaptic plasticity by examining the expression of synaptic proteins in the hippocampus to uncover potential mechanisms. The results showed that CSDS induced synaptic plasticity impairments in the hippocampus but lycopene treatment significantly improved these synaptic deficits and reversed the depressive‐like behaviors induced by CSDS. Moreover, lycopene treatment upregulated the expression of brain‐derived neurotrophic factor (BDNF) and reduced the activity of BDNF–TrkB/pTrkB pathway in the hippocampus. These molecular changes were consistent with changes in synaptic‐related proteins, suggesting that lycopene may enhance synaptic plasticity via the BDNF–TrkB/pTrkB signaling pathway. This study explored the mechanisms underlying depressive‐like behaviors induced by CSDS in mice and provided preclinical evidence that lycopene may serve as a potential antidepressant. It offers an effective avenue for the development of novel antidepressant therapies.
Early Cretaceous Tuffs From the Southwestern Ordos Basin, North China Craton: Geochronology, Geochemistry and Geological Significance
Authors: Chen Yin , Li Jianguo , Chen Lulu , Zhang Bo , Zhao Hualei 
Published: January 2025

ABSTRACTTuffs are the significant medium to figure out volcanic activities, explore regional tectonic evolution and constrain the depositional ages in basins. Tuff intervals are found in the Early Cretaceous successions from the southwestern Ordos Basin, southwestern part of the North China Craton, which supplies new geochronological and geochemical evidence to understand the Early Cretaceous tectonic setting. In this work, whole‐rock and zircon geochemistry, zircon U–Pb dating and Hf isotopic analyses were conducted. Zircon U–Pb dating results yielded ages of 125.32, 121.71 and 118.20 Ma, which have recorded the erupting of rhyolites and constrained the depositional age precisely to belong to the Aptian. Two groups of zircons Hf isotopic data are εHf(t) of 8 with TDM2 of 693–570 Ma and εHf(t) of −11.7 with TDM2 of 1908 Ma. Westerlies or southwesterlies were prevailing in the Early Cretaceous and can bring cinerites from the western or southwestern part of China. Comparative analysis of geochemistry and zircon Hf isotopes exhibited that the volcanoes from the Qiangtang Block and the Qingling Orogen were the most potential sources for the tuffs. These Early Cretaceous volcanic eruptions were triggered by the subduction of the Bangong‐Nujiang Ocean and the Paleo‐Pacific Ocean with plate roll‐back and lithospheric destruction.