bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunotherapy Improves the Survival of Stage 4 Non–Small Cell Lung Cancer Patients at the US Population Level: The Real‐World Evidence
Authors: Wei Yuxuan , Zhang Rui , Yin Ruikang , Wang Shijie , Han Jianglong , Chen Ruyan , Fu Zhenming 
Published: September 2024

ABSTRACTIntroductionImmunotherapy has revolutionized the management of lung cancer and improved lung cancer survival in trials, but its real‐world impact at the population level remains unclear.MethodsUsing data obtained from eight Surveillance, Epidemiology, and End Results (SEER) registries from 2004 through 2019, we addressed the long‐term trends in the incidence, incidence‐based mortality (IBM), and survival of lung cancer patients in the United States.ResultsThe incidence and IBM of both non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) all significantly decreased steadily from 2004 to 2019. The 1‐year survival (1‐YS) of both NSCLC and SCLC improved over time, with the best improvement observed for Stage 4 NSCLC. Two significant turning points of Stage 4 NSCLC 1‐YS were observed over the years: 0.63% (95% confidence interval [CI]: 0.33%–0.93%) from 2004 to 2010, 0.81% (95% CI: 0.41%–1.21%) from 2010 to 2014 and a striking 2.09% (95% CI: 1.70%–2.47%) from 2014 to 2019. The same two turning points in 1‐YS were pronounced for Stage 4 NSCLC in women, which were coincident with the introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) and immunotherapy. However, for Stage 4 NSCLC in men, only one significant turning point in the 1‐YS starting in 2014 was found, which might only correspond to immunotherapy. Significant period effects in reduced IBM were also observed for both Stage 4 AD and Stage 4 SQCC during the period.ConclusionThis SEER analysis found that immunotherapy improved the survival of Stage 4 NSCLC patients at the population level in the United States. This real‐world evidence confirms that immunotherapy has truly revolutionized the management of lung cancer.
Monetary policy communication shocks and the macroeconomy
Authors: Goodhead Robert , Kolb Benedikt 
Published: September 2024

AbstractUsing high‐frequency identification, we provide evidence that Fed communication surprises have larger macroeconomic effects than surprise actions. Three ingredients are central to show this: structurally distinguishing between Fed actions and communication, controlling for the Fed information effect, and including the surprise measures directly in a vector autoregression (VAR) system instead of using them as instruments. We also compare the macroeconomic effects of Fed communication surprises relating to varying horizons into the future. Fed communication with a two‐year horizon appears most powerful during the effective lower‐bound period, consistent with theoretical predictions regarding Fed forward guidance.
Impact of UK's social stock exchange trading scheme on the performance of social enterprises
Authors: Bhargava Akshat , Mukherjee Subhadip , Rani Neelam 
Published: September 2024

AbstractUsing a difference‐in‐differences (DID) framework, we evaluate the effect of UKSSE Trading scheme 2015—launch of stock trading by UK social stock exchange (UKSSE) for social enterprises (SEs) that became its members, on the productivity of UKSSE member‐firms (treated group) as compared to nonmembers (control group) for the 2008–2014 and the 2015–2018 periods, before and post the implementation of the UKSSE trading scheme 2015. Our findings suggest significant positive impact of UKSSE trading scheme opening on the productivity of all SEs (treated group) for 2 years and SEs‐SMEs (treated group) for 3 years, respectively, following the launch of this trading scheme, compared to the control groups. Thus, the UKSSE, through its trading scheme 2015, accomplished its role as a means to improve the performance of its members, measured by productivity.
Molecular cloning, functional characterization and differential expression of two novel GABAAR‐like subunits from red swamp crayfish Procambarus clarkii
Authors: Valladares‐Hernández Iván Uriel , Hernández‐Martínez Juan Manuel , Cuaxospa José Miguel , Jiménez‐Vázquez Eric Nahum , Sánchez‐Jaramillo Edith , Arias Juan Manuel , García Ubaldo 
Published: September 2024

AbstractIn this work, we cloned and functionally expressed two novel GABAA receptor subunits from Procambarus clarkii crayfish. These two new subunits, PcGABAA‐α and PcGABAA‐β2, revealed significant sequence homology with the PcGABAA‐β subunit, previously identified in our laboratory. In addition, PcGABAA‐α subunit also shared a significant degree of identity with the Drosophila melanogaster genes DmGRD (GABA and glycine‐like receptor subunits of Drosophila) as well as PcGABAA‐β2 subunit with DmLCCH3 (ligand‐gated chloride channel homolog 3). Electrophysiological recordings showed that the expression in HEK cells of the novel subunits, either alone or in combination, failed to form functional homo‐ or heteromeric receptors. However, the co‐expression of PcGABAA‐α with PcGABAA‐β evoked sodium‐ or chloride‐dependent currents that accurately reproduced the time course of the GABA‐evoked currents in the X‐organ neurons from crayfish, suggesting that these GABA subunits combine to form two types of GABA receptors, one with cationic selectivity filter and the other preferentially permeates anions. On the other hand, PcGABAA‐β2 and PcGABAA‐β co‐expression generated a chloride current that does not show desensitization. Muscimol reproduced the time course of GABA‐evoked currents in all functional receptors, and picrotoxin blocked these currents; bicuculline did not block any of the recorded currents. Reverse transcription polymerae chain reaction (RT‐PCR) amplifications and FISH revealed that PcGABAA‐α and PcGABAA‐β2 are predominantly expressed in the crayfish nervous system. Altogether, these findings provide the first evidence of a neural GABA‐gated cationic channel in the crayfish, increasing our understanding of the role of these new GABAA receptor subunits in native heteromeric receptors.
The impact of restricted grazing systems on the behaviour and welfare of ponies
Authors: Kirton Roxane , Sandford Imogen , Raffan Eleanor , Hallsworth Sarah , Burman Oliver H. P. , Morgan Ruth 
Published: September 2024

AbstractBackgroundEquine obesity is a growing concern. Much of the current management advice centres on dietary restrictions, including the removal or limitation of grazing. Little is known about the impact of these approaches on the welfare of the horse.ObjectiveThis study investigates the effect of two commonly used grazing systems advocated for the control of weight—the ‘strip‐grazing’ and the ‘track’ systems—on the behaviour and welfare of outdoor‐living ponies.Study designA within‐subject cross‐over experimental design with four groups of pasture‐kept ponies experiencing each system for 4 weeks in a random order.MethodsTime budgets and behavioural indicators of welfare were measured using 24‐h electronic surveillance, morphometric parameters including weight, body condition score and cresty neck score were measured weekly and activity levels were tracked. The effect of grazing system on movement and behaviour was tested using a general linear model.ResultsPonies moved more [median (IQR) % time spent moving, track: 3.23% (2.08%), strip: 2.02% (0.90%); p = 0.001] and travelled a greater distance [median (IQR) metres/24 h, track: 7013.47 m (1761.49 m), strip: 5331.91 m (494.16 m); p < 0.001] and engaged in less overt agonistic behaviour on the track system compared with the strip system [median (IQR) prevalence per hour; track: 0.14 (0.30), strip: 0.21 (0.37) p = 0.02].Main limitationsA relatively short time period of exposure to each grazing system.ConclusionsPonies on strip systems moved less and exhibited increased agonistic interactions compared with the track system, maybe as a result of a perceived reduction in space or concentration of resources, although the accessible areas were matched. These results suggest that there may be physical as well as psychological health benefits to the track system.
“They're not my daughter, and yet…they're also not my son”: Parents negotiating their adult child's nonbinary gender identity
Authors: Allen Samuel H. , Leslie Leigh A. 
Published: September 2024

AbstractScholars are increasingly recognizing that substantial gender heterogeneity exists among transgender populations; that is, gender identities that defy the ubiquitous binary categories of male and female. However, the developing research base on the families of transgender adults focuses almost exclusively on the family members of transgender persons with binary gender identities, a noteworthy shortcoming considering the prevalence of nonbinary gender identities among transgender populations and the pervasive assumption that only two genders exist. To address this gap, the current study sought to uncover how the parents of transgender adults with nonbinary gender identities come to understand, make sense of, and negotiate nonbinary gender identities in their families. Fourteen parents—12 mothers and 2 fathers—completed in‐depth, semi‐structured interviews, and the collected data were analyzed using reflexive thematic analysis. Analyses generated three broad themes that best‐described these parents' experience with their child's gender, which was heavily shaped by the pervasiveness of cisnormativity: (a) varied attempts to understand nonbinary gender; (b) a nonbinary “double‐edged sword”; and (c) familial resilience. Directions for future research, clinical practice, and policy change are discussed, including the therapeutic benefit of dialectical thinking and the need for legislation that legally affirms and protects nonbinary persons.
‘Prison officer pains’: How and why coloniality shapes the job of a prison officer in Guyana today
Authors: Kerrigan Dylan , Ayres Tammy , Moss Kellie 
Published: September 2024

AbstractIn this exploratory article, we look at the understudied area of prison officer's lives in the Global South and the pains of their jobs. We provide a novel and decolonial perspective on these phenomena by documenting and discussing first‐hand prison officer accounts and first‐person observations of the different dimensions of their experiences of work and home today. We understand how they see and understand their jobs, including what the pains of imprisonment for officers in Guyana look and feel like from the bottom up. We learn about what prison officers perceive as the pains of their employment in Guyana – working conditions; psychological pains; prison infrastructure; intimate relations; prison within prison; social pains; and insecurity – and how such issues include echoes of the colonial past and impact officers not just in their everyday lives but how these pains also impact those closest to them. In this way, we show how, and why, the legacies of colonialism continue to haunt contemporary prison officers in Guyana.
From the Gorgon's blood to Behring's Blutserumtherapie: A long path towards serum therapy
Authors: Lahaie Yves‐Marie , Watier Hervé 
Published: September 2024

SummaryAt the end of the 19th century medicine was turned upside down by the development of serum therapy, a great therapeutic revolution as was vaccination a few years earlier. Many serums were developed, the most famous being the German doctor Emil von Behring's diphtheria serum, which saved countless children's lives from this dreadful disease. The discovery of the serum therapy principle, allowed by the progressive understanding of humoral immunity, occurred both in Germany and France, almost at the same time. Interestingly, this principle arose from two different intellectual paths, reviving the age‐old opposition between mechanism and vitalism: while Behring came to this discovery reasoning as a chemist, French researchers Charles Richet and Jules Héricourt behaved as physiologists, focusing on the role of the host in the host‐pathogen interaction. However, we should maybe consider that serum therapy history begins much earlier. Great forerunners must not be forgotten, especially researchers who investigated the field of immunity as soon as in the very beginning of the microbiological revolution; but also many people throughout centuries who tried to cure diseases with blood: as a transfer of blood serum, serum therapy also lies in the tradition of blood transfusion.
How does audit quality affect firm innovation? Evidence from China
Authors: Hsu Charles , Wu Chaopeng , Yan Zehao , Zhu Ruichao 
Published: September 2024

AbstractExisting research based on the US setting suggests that high‐quality audits impede firm innovation by inducing managerial myopia that leads managers to sacrifice innovative activities. We extend this literature by examining the impact of audit quality on firm innovation in a major emerging market, China. Given the weak institutional environments in China, we posit that increases in audit quality enhance firm innovation by facilitating firms’ external financing abilities and promoting managers’ innovation efforts. Consistent with our predictions, we find that increased audit quality due to “switching” to BigN auditors after auditor mergers significantly improves firms’ innovation quantity and quality. We further find that increases in audit quality impact firm innovation by increasing external financing and motivating both internal and external investment in innovation. Overall, our results indicate that audit quality has a positive governance effect on firms’ real decisions in a major economy with weak legal environments.
Galileo's ship and the relativity principle
Authors: Murgueitio Ramírez Sebastián 
Published: September 2024

AbstractIt is widely acknowledged that the Galilean Relativity Principle, according to which the laws of classical systems are the same in all inertial frames in relative motion, has played an important role in the development of modern physics. It is also commonly believed that this principle holds the key to answering why, for example, we do not notice the orbital velocity of the Earth as we go about our day. And yet, I argue in this paper that the precise content of this principle is ambiguous: standard presentations, in both physics and philosophy, fail to distinguish between two principles that are ultimately inequivalent, the “External Galilean Relativity Principle” (EGRP) and the “Internal Galilean Relativity Principle” (IGRP). I demonstrate that EGRP and IGRP play distinct roles in physics practice (e.g., EGRP is connected to the concept of Galilean invariance, but IGRP is not) and that many classical systems that satisfy IGRP fail to satisfy EGRP. I further show that the Relativity Principle famously discussed by Einstein in 1905—which is not restricted to classical systems—also leads to two inequivalent principles, an external one analogous to EGRP, and an internal one analogous to IGRP. I conclude by highlighting that the phenomenon originally captured by Galileo's famous ship passage is much more general than contemporary discussions in the philosophy of symmetries suggest.
Interventions for the prevention of weight gain during festive and holiday periods in children and adults: A systematic review
Authors: Guerrero‐Magaña Diego E. , Urquijo‐Ruiz Lucía G. , Ruelas‐Yanes Alma L. , Martínez‐Contreras Teresita de J. , Díaz‐Zavala Rolando G. , Candia‐Plata Maria del Carmen , Esparza‐Romero Julián , Haby Michelle M. 
Published: September 2024

SummarySome periods during the year, such as festive and summer holiday periods, have been associated with weight gain. We aimed to assess the effect of interventions for the prevention of body weight gain during festive and holiday periods in children and adults. A systematic search was conducted in six databases and supplementary sources until January 4, 2023. We included randomized controlled trials (RCTs), cluster‐RCTs, and non‐RCTs. Our primary outcome measure was the change in body weight in adults or the change in BMI z‐score or BMI percentile in children and adolescents. From 4216 records, 12 primary studies (from 22 reports) met the inclusion criteria—10 from the United States, one from the United Kingdom, and one from Chile. Two studies had a low risk of bias, two moderate, seven high, and one critical risk of bias. The meta‐analysis in children included four of seven studies during the summer holidays (six interventions) and showed a mean difference in BMI z‐score favoring the intervention group (−0.06 [95% CI −0.10, −0.01], p = 0.01, I2 = 0%, very low certainty evidence). The meta‐analysis in adults included five studies during festive periods with a mean difference in weight favoring the intervention group (−0.99 kg [95% CI −2.15, 0.18], p = 0.10, I2 = 89%, very low certainty evidence). This review has highlighted potential interventions to prevent the increase in body weight during holiday periods. More work is needed to improve the quality of the evidence and to extend it to countries outside of the United States and United Kingdom and to the adolescent population.
A gain‐of‐function mutation at the C‐terminus of FT‐D1 promotes heading by interacting with 14‐3‐3A and FDL6 in wheat
Authors: Li Yuting , Xiong Hongchun , Guo Huijun , Xie Yongdun , Zhao Linshu , Gu Jiayu , Li Huiyuan , Zhao Shirong , Ding Yuping , Zhou Chunyun , Fang Zhengwu , Liu Luxiang 
Published: September 2024

SummaryVernalization and photoperiod pathways converging at FT1 control the transition to flowering in wheat. Here, we identified a gain‐of‐function mutation in FT‐D1 that results in earlier heading date (HD), and shorter plant height and spike length in the gamma ray‐induced eh1 wheat mutant. Knockout of the wild‐type and overexpression of the mutated FT‐D1 indicate that both alleles are functional to affect HD and plant height. Protein interaction assays demonstrated that the frameshift mutation in FT‐D1eh1 exon 3 led to gain‐of‐function interactions with 14‐3‐3A and FDL6, thereby enabling the formation of florigen activation complex (FAC) and consequently activating a flowering‐related transcriptomic programme. This mutation did not affect FT‐D1eh1 interactions with TaNaKR5 or TaFTIP7, both of which could modulate HD, potentially via mediating FT‐D1 translocation to the shoot apical meristem. Furthermore, the ‘Segment B’ external loop is essential for FT‐D1 interaction with FDL6, while residue Y85 is required for interactions with TaNaKR5 and TaFTIP7. Finally, the flowering regulatory hub gene, ELF5, was identified as the FT‐D1 regulatory target. This study illustrates FT‐D1 function in determining wheat HD with a suite of interaction partners and provides genetic resources for tuning HD in elite wheat lines.
Neural Sensing: Toward a New Approach to Understanding Emotional Responses to Place
Authors: Zhao Bo , Feng Jiaxin , Sun Yuzhi , Chang Xiaohui , Shaw Shih‐Lung 
Published: September 2024

ABSTRACTAs GIS progressively permeates our everyday lives, it becomes increasingly significant to incorporate emotional factors into the design and use of GIS technologies. While existing methods such as self‐report and AI‐enhanced techniques prevail in collecting emotional factors, they often miss real‐time emotional nuances and synchronization with geographically referenced and other accompanying data. To bridge this gap, we introduce “Neural Sensing,” a novel approach that combines Electroencephalogram (EEG) with GIS technologies to quantitatively measure emotional responses to places. This approach offers a unique lens to understand human dynamics in a hybrid physical–virtual realm, especially by delving into our mental worlds. To demonstrate the utility of Neural Sensing, we have designed a pilot empirical study to analyze emotional reactions to geographical environments. This approach broadens the domain of GIS methodologies from remote sensing and social sensing to a neural sensing approach. Through this study, we underscore the importance of the mental dimension of the hybrid physical–virtual world and encourage GIScientists to emphasize human experiences and feelings in GIS analyses.
Arabidopsis trigalactosyldiacylglycerol1 mutants reveal a critical role for phosphtidylcholine remodeling in lipid homeostasis
Authors: Fan Jilian , Sah Saroj Kumar , Lemes Jorge Gabriel , Blanford Jantana , Xie Dongling , Yu Linhui , Thelen Jay , Shanklin John , Xu Changcheng 
Published: September 2024

SUMMARYLipid remodeling plays a critical role in plant response to abiotic stress and metabolic perturbations. Key steps in this process involve modifications of phosphatidylcholine (PC) acyl chains mediated by lysophosphatidylcholine: acyl‐CoA acyltransferases (LPCATs) and phosphatidylcholine: diacylglycerol cholinephosphotransferase (ROD1). To assess their importance in lipid homeostasis, we took advantage of the trigalactosyldiacylglycerol1 (tgd1) mutant that exhibits marked increases in fatty acid synthesis and fatty acid flux through PC due to a block in inter‐organelle lipid trafficking. Here, we showed that the increased fatty acid synthesis in tgd1 is due to posttranslational activation of the plastidic acetyl‐coenzyme A carboxylase. Genetic analysis showed that knockout of LPCAT1 and 2 resulted in a lethal phenotype in tgd1. In addition, plants homozygous for lpcat2 and heterozygous for lpcat1 in the tgd1 background showed reduced levels of PC and triacylglycerols (TAG) and alterations in their fatty acid profiles. We further showed that disruption of ROD1 in tgd1 resulted in changes in fatty acid composition of PC and TAG, decreased leaf TAG content and reduced seedling growth. Together, our results reveal a critical role of LPCATs and ROD1 in maintaining cellular lipid homeostasis under conditions, in which fatty acid production largely exceeds the cellular demand for membrane lipid synthesis.
CYP76BK1 orthologs catalyze furan and lactone ring formation in clerodane diterpenoids across the mint family
Authors: Schlecht Nicholas J. , Lanier Emily R. , Andersen Trine B. , Brose Julia , Holmes Daniel , Hamberger Björn R. 
Published: September 2024

SUMMARYThe Lamiaceae (mint family) is the largest known source of furanoclerodanes, a subset of clerodane diterpenoids with broad bioactivities including insect antifeedant properties. The Ajugoideae subfamily, in particular, accumulates significant numbers of structurally related furanoclerodanes. The biosynthetic capacity for formation of these diterpenoids is retained across most Lamiaceae subfamilies, including the early‐diverging Callicarpoideae which forms a sister clade to the rest of Lamiaceae. VacCYP76BK1, a cytochrome P450 monooxygenase from Vitex agnus‐castus, was previously found to catalyze the formation of the proposed precursor to furan and lactone‐containing labdane diterpenoids. Through transcriptome‐guided pathway exploration, we identified orthologs of VacCYP76BK1 in Ajuga reptans and Callicarpa americana. Functional characterization demonstrated that both could catalyze the oxidative cyclization of clerodane backbones to yield a furan ring. Subsequent investigation revealed a total of 10 CYP76BK1 orthologs across six Lamiaceae subfamilies. Through analysis of available chromosome‐scale genomes, we identified four CYP76BK1 members as syntelogs within a conserved syntenic block across divergent subfamilies. This suggests an evolutionary lineage that predates the speciation of the Lamiaceae. Functional characterization of the CYP76BK1 orthologs affirmed conservation of function, as all catalyzed furan ring formation. Additionally, some orthologs yielded two novel lactone ring moieties. The presence of the CYP76BK1 orthologs across Lamiaceae subfamilies closely overlaps with the distribution of reported furanoclerodanes. Together, the activities and distribution of the CYP76BK1 orthologs identified here support their central role in furanoclerodane biosynthesis within the Lamiaceae family. Our findings lay the groundwork for biotechnological applications to harness the economic potential of this promising class of compounds.