bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of Psychiatric Pharmacogenomic Testing by Primary Care Physicians and Advanced Practice Providers: Confidence and Implementation Barriers
Authors: Griggs Ryan B. , Albers Renee E. , Maheshwari Priya , Kartikeyan Ramya , Kasten Chelsea R. , Bahra Sukhbir , Lubarda Jovana , Guevara Natalie , Parikh Sagar V. , Johnson Holly L. 
Published: January 2025

IntroductionPharmacogenomic (PGx) testing identifies individual genetic variation that may inform medication treatment. Sentiment and barriers may limit PGx testing. Here we compare confidence in utilizing PGx testing and barriers to implementation by type of provider and treatment condition as identified in a survey.MethodsHealthcare providers in the primary care setting were targeted between November 2022 and February 2023 via the Medscape Members paid market research program. The survey included 5 demographic, 5 multiple-choice, and 4 multi-component five-point Likert scale questions to assess PGx sentiments, use, and education in mental health (e.g., depression) and primary care (e.g., cardiovascular disease) conditions. Responses were descriptively compared.ResultsOf 305 U.S. provider respondents [40% nurse practitioners (NPs), 33% frontline MDs/DOs, 3% physician assistants (PAs), 24% other], 32% of NPs/PAs and 29% of MDs/DOs had used PGx testing for mental health conditions. The major barriers to adopt PGx testing were similar for mental health and primary care conditions yet differed by provider type. NPs/PAs (72-77%) were more concerned with patient cost than MDs/DOs (46-55%), whereas MDs/DOs were more concerned with evidence of clinical utility (54-59%) than NPs/PAs (40-42%). In respondents who use PGx testing, MDs/DOs reported slightly more confidence utilizing PGx than NPs/PAs. For both groups, confidence in using PGx for mental health conditions was somewhat greater than for non-mental health conditions.ConclusionsThese data illuminate the implementation barriers and confidence levels of clinicians utilizing PGx testing. Increasing awareness around patient cost and evidence of clinical utility for PGx testing may improve utilization.FundingMyriad Genetics, Inc.
Reforming ESG: a European and Global South perspective
Authors: Borghesi Simone , Costantini Valeria , D'Amato Alessio , Dibattista Ilaria , Koundouri Phoebe , Li Qinci , Mazzarano Matteo , Sterner Thomas , Tiwari Mira Manini , Vis Peter , Xepapadeas Anastasios 
Published: January 2025

Abstract
The EU's non-financial reporting (NFR) regulations have significant impacts on Global South stakeholders, firms that must report, actors lower in the value chain, and organisations seeking investment from NFR-compliant firms or institutions. This paper sets forth six proposals to improve the global equity and sustainability implications of the EU's NFR from a Global South perspective. The proposals involve (1) developing regulation cooperatively with the Global South; (2) streamlining reporting to enable the regulations to have real effects and limit incorrect accounting; (3) digitalising reporting through accessible technologies for greater accountability and lower administrative burdens; (4) mandating scope 3 emissions accounting and incentivising related investment; (5) anchoring financial institutions' role in ethical investment and bridging Northern and Southern actors; and (6) strengthening citizen data and sustainability literacy to close the circle of incentives, implementation, and impact.
Unraveling the enigma: decomposing China’s output and productivity growth in the new era—insights from listed companies
Authors: Huang Minjie , Zhao Shunan , Xie Mengjun 
Published: January 2025

Abstract
Building upon recent developments in production function identification and decomposition methods, this paper investigates the sources of output and productivity growth among China’s listed manufacturing companies from 2000 to 2022. While previous studies on China’s manufacturing have predominantly focused on the period preceding 2007, our study extends the analysis to a broader timeframe and divide it into four sub-periods to accommodate diverse economic conditions and varying growth rates. We provide new insights into the Chinese economy during a period marked by gradual economic transformation. Specifically, we first decompose industry output growth into factor deepening and firm productivity progress within each sub-period. To account for heterogeneity across firms in terms of production technology and sources of growth, we employ a nonparametric production function and decompose firm output growth at both the mean and different quantiles of the output distribution. We find that increased materials usage and productivity growth are primary growth drivers. However, the contribution of productivity experiences a significant decline, particularly in recent years and among median-sized and large firms. Furthermore, we examine China’s industry aggregate productivity growth and its origins among state-invested, foreign-invested, and domestic private firms. Our findings suggest that reforms among state firms are the largest contributor to industry productivity growth before the 2008 financial crisis, whereas productivity progress of domestic private firms emerges as the sole significant driver in recent years. Additionally, there is no evidence of improvements in output reallocation efficiency within China’s manufacturing sector throughout our sample period.
NONLINEAR MODULATION OF RANDOM WAVE SPECTRA FOR SURFACE-GRAVITY WAVES WITH LINEAR SHEAR CURRENTS
Authors: MUKHERJEE SUMAN , HALDER SOURAV , DHAR A. K. 
Published: January 2025

AbstractWe first derive Alber’s equation for the Wigner distribution function using the fourth-order nonlinear Schrödinger equation, and on the basis of this equation we next analyse the stability of the narrowband approximation of the Joint North Sea Wave Project spectrum. Therefore, one interesting result of this study concerns the effect of modulational instability obtained from the fourth-order nonlinear Schrödinger equation. The analysis is restricted to one horizontal direction, parallel to the direction of wave motion, to take advantage of potential flow theory. We find that shear currents considerably modify the instability behaviours of weakly nonlinear waves. The key point of this study is that the present fourth-order analysis shows considerable deviations in the modulational instability properties from the third-order analysis and reduces the growth rate of instability. Moreover, we present here a connection between the random and deterministic properties of a random wavetrain for vanishing spectrum bandwidth.
The pseudo-kindness of wartime lawbreakers
Authors: Hayashi Nobuo 
Published: January 2025

Abstract
It is sometimes said that cruel yet short wars are better for humanity than restrained yet lengthy ones. The idea finds sympathy among Francis Lieber and his Prussian contemporaries, as well as some modern writers who back selective non-compliance with international humanitarian law (IHL) on act-utilitarian grounds. This article refutes three underlying claims and reaffirms that IHL progressively narrows room for crude interest-balancing by its duty-bearers. First, it is claimed that toughening wars quickens them, whereas moderating wars prolongs them. This empirical claim overlooks how actions of the party resorting to brutality – the “brutalizer”, for short – interact with the intention of its adversary. Although the brutalizer clearly controls the amount of violence that it chooses to inflict on its opponent, it does not control the opponent's will to resist and, consequently, the length of the war it fights. History abounds with instances where adding cruelty has stiffened the enemy's resolve rather than accelerating surrender. Second, it is claimed that ruthless but swift wars lessen net inhumanity. On this act-utilitarian view, it is normatively superior to hasten wars through barbarity than to lengthen them through moderation; it is therefore the brutalizer's responsibility to toughen fighting and the brutalized party's responsibility to refrain from resisting the brutalizer. Problematically, the brutalizer usurps authority by imposing its own utilitarian considerations upon the brutalized party. Moreover, the brutalizer blames its disobliging adversary for the extra bloodshed to which it resorts in the name of maximum utility. Third, it is claimed that IHL does or should permit non-conformity when non-conformity stands a reasonable chance of increasing net humanity. This position is inconsistent with IHL's functions, however. IHL does aim to reduce net wartime harm, but it would be a mistake to assume that utilitarian ends necessarily justify, let alone require, utilitarian means. When IHL enacts unqualified rules, it predetermines their conformity or non-conformity through processes that are distinctly not act-utilitarian. Nowhere in these processes do lesser-evil justifications naturally belong.
Stream Discharge Determinations Using Slug Additions and Specific Conductance
Authors: McCleskey R. Blaine , Runkel Robert L. , Murphy Sheila F. , Roth David A. 
Published: January 2025

AbstractStream discharge is often determined by wading the stream and measuring the point velocity at fixed widths and depths. However, there are conditions when wading measurements are not safe or the measurements are poor because of high turbulence, rocky streambeds, non‐standard velocity distributions, shallow or sheet flow, aquatic plants, or inaccessibility due to ice. Under these conditions, it is often preferable to determine discharge using salt slug addition and downstream measurement of salt concentration with time. A new method for determining stream discharge using specific conductance as a surrogate for salt concentrations is presented. The method adapts an approach that accurately calculates the specific conductance by utilizing ionic molal conductivities to determine the concentration of salt. The method was applied at four mountainous stream sites where a total of twenty‐nine slug‐additions were performed. The discharge determined from the new method was compared to four alternative methods including discharge from continuous injection, slug addition with discrete sample calibration, wading measurements with velocity measurement, and a stream gage. The discharge ranged from 21.5 to 778 L/s and the median difference between the new method and the traditional methods was −0.01%. Additionally, the p‐value (0.75) determined from a paired t‐test indicates that there is no significant difference between the discharge determined from the new and alternative discharge methods. The primary advantage of the new method is that it obviates the need to collect and analyze discrete samples to accurately quantify the specific conductance‐salt surrogate relationship, allowing for rapid, low‐cost determination of discharge.
Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome
Authors: Mondéjar-Parreño Gema , Moreno-Manuel Ana I. , Ruiz-Robles Juan Manuel , Jalife José 
Published: January 2025

AbstractA well-balanced ion channel trafficking machinery is paramount for the normal electromechanical function of the heart. Ion channel variants and many drugs can alter the cardiac action potential and lead to arrhythmias by interfering with mechanisms like ion channel synthesis, trafficking, gating, permeation, and recycling. A case in point is the Long QT syndrome (LQTS), a highly arrhythmogenic disease characterized by an abnormally prolonged QT interval on ECG produced by variants and drugs that interfere with the action potential. Disruption of ion channel trafficking is one of the main sources of LQTS. We review some molecular pathways and mechanisms involved in cardiac ion channel trafficking. We highlight the importance of channelosomes and other macromolecular complexes in helping to maintain normal cardiac electrical function, and the defects that prolong the QT interval as a consequence of variants or the effect of drugs. We examine the concept of “interactome mapping” and illustrate by example the multiple protein–protein interactions an ion channel may undergo throughout its lifetime. We also comment on how mapping the interactomes of the different cardiac ion channels may help advance research into LQTS and other cardiac diseases. Finally, we discuss how using human induced pluripotent stem cell technology to model ion channel trafficking and its defects may help accelerate drug discovery toward preventing life-threatening arrhythmias. Advancements in understanding ion channel trafficking and channelosome complexities are needed to find novel therapeutic targets, predict drug interactions, and enhance the overall management and treatment of LQTS patients.
Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia
Authors: Abdel Wadood Noran , Hollenhorst Monika I. , Elhawy Mohamed Ibrahem , Zhao Na , Englisch Clara , Evers Saskia B. , Sabachvili Mahana , Maxeiner Stephan , Wyatt Amanda , Herr Christian , Burkhart Ann-Kathrin , Krause Elmar , Yildiz Daniela , Beckmann Anja , Kusumakshi Soumya , Riethmacher Dieter , Bischoff Markus , Iden Sandra , Becker Sören L. , Canning Brendan J. , Flockerzi Veit , Gudermann Thomas , Chubanov Vladimir , Bals Robert , Meier Carola , Boehm Ulrich , Krasteva-Christ Gabriela 
Published: January 2025

AbstractTracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels. Taste signaling through the Trpm5 channel is essential for bacterial tuft cell activation and ATP release. We demonstrate that activated tuft cells recruit dendritic cells to the trachea and lung. ATP released by tuft cells initiates dendritic cell activation, phagocytosis and migration. Tuft cell stimulation also involves an adaptive immune response through recruitment of IL-17A secreting T helper cells. Collectively, the results provide a molecular framework defining tuft cell dependent regulation of both innate and adaptive immune responses in the airways to combat bacterial infection.
A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection
Authors: Liu Jun , Wang Li , Kurtesi Alexandra , Budylowski Patrick , Potts Kyle G. , Menon Haritha , Tan Yilin , Samaan Philip , Liu Xinan , Wang Yisen , Hu Queenie , Samson Reuben , Qi Freda , Evseev Danyel , John Cini , Ellestad Kristofor K. , Fan Yue , Budiman Frans , Tohan Ellaine Riczly , Udayakumar Suji , Yang Jennifer , Marcusson Eric G. , Gingras Anne-Claude , Mahoney Douglas J. , Ostrowski Mario A. , Martin-Orozco Natalia 
Published: January 2025

AbstractContinuously emerging SARS-CoV-2 Omicron subvariants pose a threat thwarting the effectiveness of approved COVID-19 vaccines. Especially, the protection breadth and degree of these vaccines against antigenically distant Omicron subvariants is unclear. Here, we report the immunogenicity and efficacy of a bivalent mRNA vaccine, PTX-COVID19-M1.2 (M1.2), which encodes native spike proteins from Wuhan-Hu-1 (D614G) and Omicron BA.2.12.1, in mouse and hamster models. Both primary series and booster vaccination using M1.2 elicited potent and broad nAbs against Wuhan-Hu-1 (D614G) and some Omicron subvariants. Strong spike-specific T cell responses against Wuhan-Hu-1 and Omicron subvariants, including JN.1, were also induced. Vaccination with M1.2 protected animals from Wuhan-Hu-1 and multiple Omicron subvariants challenges. Interestingly, protection against XBB.1.5 lung infection did not correlate with nAb levels. These results indicate that M1.2 generated a broadly protective immune response against antigenically distant Omicron subvariants, and spike-specific T cells probably contributed to the breadth of the protection.
Metabolic and transcriptional analysis of tuber expansion in Curcuma kwangsiensis
Authors: Zhou Yunyi , Yao Lixiang , Xie Yueying , Huang Baoyou , Li Ying , Huang Xueyan , Yu Liying , Pan Chunliu 
Published: January 2025

AbstractThe tubers of Curcuma kwangsiensis are regarded as an important medicinal material in China. In C. kwangsiensis cultivation, tuber expansion is key to yield and quality, but the regulatory mechanisms are not well understood. In this study, metabolomic and transcriptomic analyses were conducted to elucidate the mechanism underlying tuber expansion development. The results showed that auxin (IAA), jasmonic acid (JA), gibberellin (GA3), ethylene (ETH), and brassinolide (BR) levels increased during tuber expansion development. Metabolomic analysis showed that 197 differentially accumulated metabolites (DAMs) accumulated during tuber expansion development and these also play important roles in the accumulation of carbohydrates and secondary metabolites. 6962 differentially expressed genes (DEGs) were enriched in plant hormone signal transduction, starch and sucrose metabolism, linoleic acid metabolism, MAPK signaling pathway as well as sesquiterpenoid and triterpenoid biosynthesis. Comprehensive analysis revealed that DEGs and DAMs of plant hormone signal transduction, ABC transporters and biosynthesis of phenylpropanoids and terpenoids are critical pathways in regulating tuber expansion. In addition, some transcription factors (ARF, C2H2, C3H, NAC, bHLH, GRAS and WRKY) as well as hub genes (HDS, HMGR, ARF7, PP2CA, PAL and CCOMT) are also involved in this process. This study lays a theoretical basis for the molecular mechanism of tuber expansion in C. kwangsiensis.
Exploring the comorbidity mechanisms between atherosclerosis and hashimoto’s thyroiditis based on microarray and single-cell sequencing analysis
Authors: Ma Yirong , Wu Shuguang , Lai Junyu , Wan Qiang , Hu Jingxuan , Liu Yanhong , Zhou Ziyi , Wu Jianguang 
Published: January 2025

Abstract
Atherosclerosis (AS) is a chronic vascular disease characterized by inflammation of the arterial wall and the formation of cholesterol plaques. Hashimoto’s thyroiditis (HT) is an autoimmune disorder marked by chronic inflammation and destruction of thyroid tissue. Although previous studies have identified common risk factors between AS and HT, the specific etiology and pathogenic mechanisms underlying these associations remain unclear. We obtained relevant datasets for AS and HT from the Gene Expression Omnibus (GEO). By employing the Limma package, we pinpointed common differentially expressed genes (DEGs) and discerned co-expression modules linked to AS and HT via Weighted Gene Co-expression Network Analysis (WGCNA). We elucidated gene functions and regulatory networks across various biological scenarios through enrichment and pathway analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Core genes were identified using Cytoscape software and further validated with external datasets. We also conducted immune infiltration analysis on these core genes utilizing the CIBERSORT method. Lastly, Single-cell analysis was instrumental in uncovering common diagnostic markers. Based on differential analysis and WGCNA, we identified 119 candidate genes within the cohorts for AS and HT. KEGG and GO enrichment analyses indicate that these genes are significantly involved in antigen processing and presentation, along with various immune-inflammatory pathways. Two pivotal genes, PTPRC and TYROBP, were identified using five algorithms from the cytoHubba plugin. Validation through external datasets confirmed their substantial diagnostic value for AS and HT. Moreover, the results of Gene Set Enrichment Analysis (GSEA) indicated that these core genes are significantly enriched in various receptor interactions and signaling pathways. Immune infiltration analysis revealed a strong association of lymphocytes and macrophages with the pathogenesis of AS and HT. Single-cell analysis demonstrated predominant expression of the core genes in macrophages, monocytes, T cells and Common Myeloid Progenitor (CMP). This study proposes that an aberrant immune response might represent a shared pathogenic mechanism in AS and HT. The genes PTPRC and TYROBP are identified as critical potential biomarkers and therapeutic targets for these comorbid conditions. Furthermore, the core genes and their interactions with immune cells could serve as promising targets for future diagnostic and therapeutic strategies.
High Ano1 expression as key driver of resistance to radiation and cisplatin in HPV-negative head and neck squamous cell carcinoma
Authors: Bourdier Solenne , Fisch Anne-Sophie , Alp Keziban Merve , Das Ridhima , Mertins Philipp , Tinhofer Ingeborg 
Published: January 2025

AbstractHuman papilloma virus-negative head and neck squamous cell carcinoma (HNSCC) frequently harbors 11q13 amplifications. Among the oncogenes at this locus, CCND1 and ANO1 are linked to poor prognosis; however, their individual roles in treatment resistance remain unclear. The impact of Cyclin D1 and Ano1 overexpression on survival was analyzed using the TCGA HNSCC dataset and a Charité cohort treated with cisplatin (CDDP)-based radiochemotherapy. High Ano1 expression was primarily associated with poor overall survival in both datasets. The effects of CCND1 and ANO1 knockdown (KD) on radio- and drug sensitivity, along with changes in global protein expression, cell viability, growth, and DNA repair, were studied in an 11q13-amplified HNSCC cell line model of primary cisplatin resistance. Unique pathway alterations– VEGF in CCND1 KD and the Rho GTPase cycle in ANO1 KD– were observed, along with shared changes like DNA damage and cell cycle dysregulation. Silencing CCND1 or ANO1 increased CDDP sensitivity, while only ANO1 silencing increased radiosensitivity. Copanlisib and afatinib were identified as promising candidates for combination therapy of 11q13-amplified HNSCC tumors. We demonstrated a predominant role for Ano1 in treatment resistance in Cyclin D1highAno1high HNSCC tumors and identified novel potential treatment combinations for this high-risk patient group.
Highly viable gastrointestinal Chlamydia trachomatis in women abstaining from receptive anal intercourse
Authors: Karlsson Philip A. , Wänn Mimmi , Wang Helen , Falk Lars , Herrmann Björn 
Published: January 2025

AbstractChlamydia trachomatis (CT) may employ persistence to evade antimicrobial clearance, possibly residing in the gastrointestinal tract. This study assessed the reliability of droplet digital PCR (ddPCR) in CT detection, its functionality in viability assessment, and predictions on CT transmission dynamics by combining viability PCR (vPCR) and clinical data from 52 infected women. The ddPCR showed 94% positive and 100% negative agreement with Abbott Alinity STI-M for endocervical samples, and 92% positive and 87% negative agreement in rectal samples. Viability was higher in endocervical samples (89.1%) than in rectal samples (69.4%). Samples from participants not engaging in anal intercourse, and with non-concordant multi-locus sequence typing between rectum and endocervix, had on average the highest viability in rectum, indicating a persistent population residing in the gastrointestinal tract. This study demonstrates the effectiveness of ddPCR in detecting CT, especially in samples with high inhibition or low bacterial load, suggesting its superiority over quantitative real-time PCR. These findings support that rectal CT infection can occur independently of anal intercourse, possibly through vaginorectal contamination or oral routes. High rectal CT viability, independent of endocervical infection, indicates potential gastrointestinal establishment. Understanding CT dynamics in various infection sites can provide insights into the epidemiology and pathogenesis of CT.