bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical definition of secondary resistance to immunotherapy in non‐small cell lung cancer
Authors: Huang Dingzhi , Lin Gen , Chu Qian , Hu Yi , Wang Jun , Wang Zhijie , Yang Fan , Zhong Wenzhao , Zhou Chengzhi , Zhu Bo , Ai Xinghao , Cao Baoshan , Cao Yabing , Chen Mingqiu , Chen Xiaohui , Chu Tianqing , Duan Jianchun , Fan Yun , Fang Yong , Feng Shuitu , Feng Weineng , Guo Hui , Han Chengbo , He Yong , Hong Shaodong , Hu Jie , Huang Meijuan , Huang Yan , Jiang Da , Jiang Kan , Jiang Richeng , Jin Bo , Jin Shi , Li Jisheng , Li Min , Li Ziming , Li Chao , Lin Jie , Liu Anwen , Liu Si‐Yang Maggie , Liu Yutao , Liu Zhefeng , Liu Zhe , Liu Zhenhua , Liu Zhentian , Liu Zhigang , Lu Yuping , Lv Tangfeng , Ma Zhiyong , Miao Qian , Peng Min , Pu Xingxiang , Ren Xiu Bao , Shan Jianzhen , Shan Jinlu , Shen Peng , Shen Bo , Shi Meiqi , Song Yong , Song Zhengbo , Su ChunXia , Sun Jianguo , Tian Panwen , Wang Jinliang , Wang Feng , Wang Huijuan , Wang Jialei , Wang Qian , Wang Wenxian , Wang Yan , Wu Lin , Wu Fang , Xia Yang , Xie Congying , Xie Conghua , Xin Tao , Xiong Jianping , Xu Haipeng , Xu Song , Xu Yiquan , Xu Bin , Xu Chunwei , Yan Xiaolong , Yang Zhenzhou , Yao Wenxiu , Yu Yao , Feng Ye , Yu Zongyang , Yu Yongfeng , Yue Dongsheng , Zhang Haibo , Zhang HongMei , Zhang Li , Zhang Longfeng , Zhang Qiuyu , Zhang Tongmei , Zhang Bicheng , Zhao Jun , Zhao Mingfang , Zheng Xiaobin , Zhong Fengqiao , Zhou Jin , Zhou Penghui , Zhu Zhengfei , Zou Juntao , Zou Zihua 
Published: November 2023

AbstractImmune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.
Calorie restriction reduces biomarkers of cellular senescence in humans
Authors: Aversa Zaira , White Thomas A. , Heeren Amanda A. , Hulshizer Cassondra A. , Saul Dominik , Zhang Xu , Molina Anthony J. A. , Redman Leanne M. , Martin Corby K. , Racette Susan B. , Huffman Kim M. , Bhapkar Manjushri , Khosla Sundeep , Das Sai Krupa , Fielding Roger A. , Atkinson Elizabeth J. , LeBrasseur Nathan K. 
Published: November 2023

AbstractCalorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young‐to‐middle‐aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging‐related conditions. Using plasma specimens from the Comprehensive Assessment of Long‐term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change in HOMA‐IR and insulin sensitivity index at 12 and 24 months, and the change in resting metabolic rate residual at 12 months. Finally, using adipose tissue RNA‐sequencing data from a subset of participants, we observed a significant reduction in a senescence‐focused gene set in response to CR at both 12 and 24 months compared to baseline. Our results advance the understanding of the effects of CR in humans and further support a link between cellular senescence and metabolic health.
From threatened to threatening: Impacts of a reintroduced predator on reintroduced prey
Authors: Stepkovitch B. , Neave G. , Jensen M. A. , Tuft K. , Moseby K. E. 
Published: November 2023

AbstractDespite the recent global increase in projects utilizing conservation fencing, reintroductions of predators to fenced conservation reserves are rare. Reintroducing threatened predators into closed ecosystems raises potential issues of overabundance, population viability and inbreeding. In particular, impacts to resident prey species are not well studied across predator reintroductions worldwide, in part due to the difficulties in measuring predator impacts without adequate control areas. Over the 4 years following release, we used multiple lines of evidence and a paired treatment and control area to assess the potential impact of a reintroduced threatened predator, the western quoll, on four reintroduced threatened mammal species in a fenced reserve. Diet analysis, radio‐tracking and direct observation suggested that quolls killed and consumed all four reintroduced threatened native prey species, but two of these prey species (bettongs and bandicoots) were preferred prey. Abundance indices of these two prey species declined in parts of the reserve where quolls were present relative to control areas, yet local extinction did not occur. Quoll hunting behaviour suggested that these preferences may be driven, in part, by differences in the detectability and accessibility of similar‐sized prey. Dietary selection for threatened prey was reduced at times when native rodents, a highly preferred prey species, were in high abundance. The presence of rodents, coupled with the quoll‐exclusion control area and carcass dumps, may have protected reintroduced threatened prey from local extinction. Predator reintroductions to fenced reserves may help maintain ecosystem balance; however, predators may be incompatible with conservation of some threatened prey species unless alternative common prey are present or intensive management actions are implemented.
Regulation of ethanol‐mediated dopamine elevation by glycine receptors located on cholinergic interneurons in the nucleus accumbens
Authors: Loftén Anna , Adermark Louise , Ericson Mia , Söderpalm Bo 
Published: November 2023

AbstractAlcohol use disorder is one of the major psychiatric disorders worldwide, and there are many factors and effects contributing to the disorder, for example, the experience of ethanol reward. The rewarding and reinforcing properties of ethanol have been linked to activation of the mesolimbic dopamine system, an effect that appears to involve glycine receptors (GlyRs) in the nucleus accumbens. On which neuronal subtypes these receptors are located is, however, not known. The aim of this study was to explore the role of GlyRs on cholinergic interneurons (CIN) in sustaining extracellular dopamine levels and in ethanol‐induced dopamine release. To this end, CIN were ablated by anti‐choline acetyltransferase‐saporin administered locally in the nucleus accumbens of male Wistar rats. Changes in dopamine levels induced by ablation, ethanol and/or a GlyR antagonist were monitored using in vivo microdialysis. The GlyRs antagonist strychnine depressed extracellular dopamine in a similar manner independent on local ablation, suggesting that GlyRs on CIN are not important for sustaining the extracellular dopamine tone. However, a low concentration of strychnine hampered ethanol‐induced dopamine release in sham‐treated animals, whilst no reduction was seen in ablated animals, suggesting that GlyRs located on CIN are involved in ethanol‐induced dopamine release. Further, in ablated rats, ethanol‐induced increases of the extracellular levels of the GlyR agonists glycine and taurine were attenuated. In conclusion, this study suggests that CIN are not important for GlyR‐mediated regulation of basal dopamine output, but that CIN ablation blunts the ethanol‐induced dopamine release, putatively by reducing the release of GlyR agonists.
Extinction and reinstatement of methamphetamine‐induced conditioned place preference in zebrafish
Authors: Chen Liao‐Chen , Chan Ming‐Huan , Chen Hwei‐Hsien 
Published: November 2023

AbstractConditioned place preference (CPP) paradigm in zebrafish has been used to measure drug reward, but there is limited research on CPP reinstatement to determine relapse vulnerability. The present study aimed to investigate extinction and reinstatement of methamphetamine (MA)‐induced CPP in zebrafish and evaluate the model's predictive validity. Zebrafish received different doses of MA (0–60 mg/kg) during CPP training. The preferred dose of MA at 40 mg/kg was used for extinction via either confined or nonconfined procedures. The extinguished CPP was reinstated by administering a priming dose of MA (20 mg/kg) or various stressors. To assess persistent susceptibility to reinstatement, MA CPP and reinstatement were retested following 14 days of abstinence. In addition, the effects of SCH23390, naltrexone, and clonidine on MA CPP during acquisition, expression, or reinstatement phases were monitored. MA induced CPP in a dose‐dependent manner. Both nonconfined and confined extinction procedures time‐dependently reduced the time spent on the MA‐paired side. A priming dose of MA, chasing stress, or yohimbine reinstated the extinguished CPP. After 14 days of abstinence, the MA CPP remained extinguished and was significantly reinstated by MA priming or chasing stress. Similar to the observations in rodents, SCH23390 suppressed the acquisition of MA CPP, naltrexone reduced the expression and MA priming‐induced reinstatement, while clonidine prevented stress‐induced reinstatement of MA CPP. This work expanded the zebrafish CPP paradigm to include extinction and reinstatement phases, demonstrating predictive validity and highlighting its potential as a valuable tool for exploring drug relapse.
Effects of wetland connectivity on overwintering and movement behaviours of Australian freshwater turtles
Authors: Van Dyke James U. , McPhan Luke M. , Howard Katie , Hamilton Tracy , Ross Liticia , Watts Robyn J. 
Published: November 2023

AbstractFreshwater turtles are important consumers in Australian freshwater ecosystems. They serve as scavengers, nutrient regulators, and as food sources and Totems for Traditional Owners throughout Australia. Despite their importance, most Australian freshwater turtle species are declining. The impact of winter wetland drying on turtle populations remains unknown, and winter exposure of hibernating turtles may be an important additional source of mortality. We aimed to examine turtle responses to seasonal and episodic wetland drying in wetlands using acoustic telemetry and active trapping. Wetlands were chosen that spanned a range of hydrological connectivity to the adjacent Edward/Kolety‐Wakool River. We found that tagged Emydura macquarii typically exit wetlands disconnected from the adjacent permanent river prior to winter, and overwinter in the river. Female E. macquarii rapidly re‐entered ‘home’ wetlands (wetlands in which they were initially tagged) the following spring, whereas males tended to leave the study area, returning occasionally. Although we were not able to evaluate a winter drying event, one of the wetlands experienced partial summer drying. All three local turtle species (E. macquarii, Chelodina expansa, C. longicollis) exited the wetland long before winter drying would have become a potential threat. Our results suggest that turtles in this system may be protected from winter wetland drying because they move to the adjacent permanent river prior to winter. Spending the winter in the river channel reduces the risks of being trapped in a drying wetland as temperatures drop in winter.
Oral versus intravenous antibiotics in the treatment of uncomplicated colonic diverticulitis: results of a randomized non‐inferiority control trial
Authors: McClintock Sam , Stupart Douglas , Hoh Su Mei , Redden Ann‐Maree , Schultz Belinda , Robertson Amy , Moore Eileen , Pollard James , Guest Glenn , Watters David 
Published: November 2023

AbstractBackgroundColonic diverticular disease is common and its incidence increases with age, with uncomplicated diverticulitis being the most common acute presentation (1). This typically results in inpatient admission, placing a significant burden on healthcare services (2). We aimed to determine the safety and effectiveness of using intravenous or oral antibiotics in the treatment of uncomplicated diverticulitis on 30‐day unplanned admissions, c‐reactive protein (CRP), White Cell Count (WCC), pain resolution, cessation of pain medication, return to normal nutrition, and return to normal bowel function.MethodsThis single centre, 2‐arm, parallel, 1:1, unblinded non‐inferiority randomized controlled trial compared the safety and efficacy of oral antibiotics versus intravenous antibiotics in the outpatient treatment of uncomplicated colonic diverticulitis. Inclusion criteria were patients older than 18 years of age with CT proven acute uncomplicated colonic diverticulitis (Modified Hinchey Classification Stage 0–1a). Patients were randomly allocated receive either intravenous or oral antibiotics, both groups being treated in the outpatient setting with a Hospital in the Home (HITH) service. The primary outcome was the 30‐day unplanned admission rate, secondary outcomes were biochemical markers, time to pain resolution, time to cessation of pain medication, time to return to normal function and time to return to normal bowel function.ResultsIn total 118 patients who presented with uncomplicated colonic diverticulitis were recruited into the trial. Fifty‐eight participants were treated with IV antibiotics, and 60 were given oral antibiotics. We found there was no significant difference between groups with regards to 30‐day unplanned admissions or inflammatory markers. There was also no significant difference with regards to time to pain resolution, cessation of pain medication use, return to normal nutrition, or return to normal bowel function.ConclusionOutpatient management of uncomplicated diverticulitis with oral antibiotics proved equally as safe and efficacious as intravenous antibiotic treatment in this randomized non‐inferiority control trial.
Heterogeneity in the longitudinal courses of global functioning in children at familial risk of major psychiatric disorders: Association with trauma and familial characteristics
Authors: Bureau Alexandre , Berthelot Nicolas , Ricard Jasmin , Lafrance Camille , Jomphe Valérie , Dioni Abdoulaye , Fortin‐Fabbro Énora , Boisvert Marie‐Claude , Maziade Michel 
Published: November 2023

AbstractObjectivesThe extent to which heterogeneity in childhood risk trajectories may underlie later heterogeneity in schizophrenia (SZ), bipolar disorder (BP), and major depressive disorder (MDD) remains a chief question. Answers may optimally be found by studying the longitudinal trajectories of children born to an affected parent. We aimed to differentiate trajectories of global functioning and their sensitive periods from the age of 6 to 17 years in children at familial risk (FHRs).MethodsFirst, a latent class mixed model analysis (LCMM) was applied to yearly ratings of the Children's Global Assessment Scale (CGAS) from the age of 6 to 17 years in 170 FHRs born to a parent affected by DSM‐IV SZ (N = 37), BP (N = 82) or MDD (N = 51). Then, we compared the obtained Classes or trajectories of FHRs in terms of sex, parental diagnosis, IQ, child clinical status, childhood trauma, polygenic risk score (PRS), and outcome in transition to illness.ResultsThe LCMM on yearly CGAS trajectories identified a 4‐class solution showing markedly different childhood and adolescence dynamic courses and temporal vulnerability windows marked by a functioning decline and a degree of specificity in parental diagnosis. Moreover, IQ, trauma exposure, PRS level, and timing of later transition to illness differentiated the trajectories. Almost half (46%) of the FHRs exhibited a good and stable global functioning trajectory.ConclusionsFHRs of major psychiatric disorders show heterogeneous functional decline during development associated with parental diagnosis, polygenic risk loading, and childhood trauma.
Is intravenous valproate more efficacious than oral valproate for inpatients with bipolar I disorder with a manic or depressive episode and concomitant symptoms of opposite polarity?
Authors: Cuomo Alessandro , Barillà Giovanni , Cattolico Matteo , Carmellini Pietro , Spiti Alessandro , Pozza Andrea , Fagiolini Andrea 
Published: November 2023

AbstractIntroValproic acid (VPA) is a commonly prescribed mood stabilizer, available in both oral (OS) and intravenous (IV) formulations. However, few studies have compared their safety and efficacy. This retrospective study aimed to investigate the safety and efficacy of and IV‐VPA in patients with Bipolar Disorder.MethodsFifty patients with Bipolar Disorder experiencing a manic or depressive episode, with concomitant symptoms of opposite polarity, admitted to our inpatient unit and treated with IV‐VPA were included in a retrospective, single‐centre, non‐randomized, open‐label, parallel‐group comparative study. Fifty patients experiencing a manic or depressive episode, with concomitant symptoms of opposite polarity, treated with oral‐VPA and selected among those who were admitted to the inpatient unit prior to the introduction of IV‐VPA in our clinical practice, were included as the control group (matched based on age, gender and clinical scales score at baseline). The Clinical Global Impression (CGI), Young Mania Rating Scale (YMRS), Montgomery‐Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM‐A) scores were recorded at baseline, after 3 days of treatment and discharge from the inpatient unit. Patients were asked to respond on the basis of the symptoms present on the day the scale was administered. Response rate and the presence of adverse effects were also recorded.ResultsBoth patients treated with oral and IV‐VPA demonstrated significant improvements in all psychometric scales (p < 0.001). However, the IV group exhibited superior efficacy, with significantly lower scores on the CGI, YMRS, MADRS and HAM‐A scales on Day 3 and at discharge from the inpatient unit. The IV‐VPA treatment showed higher response rates on all psychometric scales, and no adverse effects were reported in either group.ConclusionThis retrospective study supports the use of IV‐VPA as a more efficacious treatment option for patients with Bipolar Disorder, particularly in acute settings where rapid symptom improvement is crucial. Both oral and IV‐VPA were found to be safe and well‐tolerated.
Teachers' proactive behaviour: Interactions with job characteristics and professional competence in a longitudinal study
Authors: Jörg Verena , Hartmann Ulrike , Philipp Anja , Kunter Mareike 
Published: November 2023

AbstractBackgroundIn times of accelerating changes, teachers who proactively engage in activities towards school improvement and innovation are increasingly needed. Still, studies on factors that affect teachers' proactive behaviour are rare.AimsIntegrating previous research on proactive behaviour within the Job Demand–Resources (JD‐R) Model, this paper investigates how job characteristics (time pressure, bureaucratic structures, participative climate, personal initiative of the team) and aspects of teachers' professional competence (self‐efficacy, self‐regulation skills and knowledge) contribute to and interact with their proactive behaviour.SampleA total of 130 German secondary school teachers (M(SD)age = 44.05 (11.36), 65% female) participated in this study.MethodsWe employed a full two‐wave panel design, with measurement points 5 months apart. The data were analysed with (moderated) single indicator modelling and a cross‐lagged panel model.ResultsWhile teachers' self‐efficacy in implementing change and self‐regulation skills predicted their concurrent proactive behaviour, job characteristics and teachers' knowledge had no such cross‐sectional effects. In addition, we found an interaction effect of time pressure and teachers' self‐efficacy on proactive behaviour. Including the second measurement point, data indicated no cross‐lagged effects of the job and personal factors on proactive behaviour. However, cross‐lagged analysis revealed that teachers' proactive behaviour predicted their later self‐efficacy in implementing change and the time pressure they perceive.ConclusionsExamining both cross‐sectional and longitudinal effects, this study highlights the importance of measurements over time when analysing factors that influence teachers' proactive behaviour: While aspects of professional competence appear to be trainable concurrent resources, time pressure can limit their effect. Finally, cross‐lagged effects of teachers' proactive behaviour on their later self‐efficacy and time pressure appear as influential in the long run.
Genetic defects of gamma‐secretase genes in a multiple myeloma patient with high and dysregulated BCMA surface density: A case report
Authors: Cattaneo Irene , Valgardsdottir Rut , Cavagna Roberta , Spinelli Orietta , Bartoletti‐Stella Anna , Capellari Sabina , Galli Monica , Golay Josée 
Published: November 2023

SummaryMultiple myeloma (MM) cells from 1 out of 20 patient expressed high basal levels of membrane B‐cell maturation antigen (BCMA, TNFRSF17, CD269), which was not upregulated by gamma‐secretase inhibitor, suggesting a defective BCMA shedding by gamma‐secretase. Genetic analyses of the patient's bone marrow DNA showed no mutations within the BCMA coding region, but rather partial deletion of PSEN1 and amplification of PSEN2, which encode alternative catalytic units of gamma‐secretase. Altogether the data suggest that pt#12 MM cells express high and dysregulated BCMA with no shedding, due to genetic alterations of one or more gamma‐secretase subunits.