bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Genome-Wide Association Studies of COVID-19 Susceptibility and Hospitalization Reveal Risk Loci for Long COVID
Authors: Cheng Zhongshan
Published: February 2025

Long COVID presents a significant public health challenge, characterized by over 200 reported symptoms spanning multiple organ systems. Despite its complexity, genome-wide association studies (GWAS) offer a pathway to uncovering genetic risk factors, though progress has been hindered by the disorder’s symptom heterogeneity and the limited power of available datasets. Recent long COVID GWASs have highlighted key genetic associations, such as variants close toFOXP4,ABO, andHLA-DQA1, while underscoring the limitations posed by small sample sizes, restricted diversity, and misclassification biases. Here, an integrative analysis using COVID-19 GWAS data from the Host Genetics Initiative (HGI, release 7) was performed by leveraging proxy phenotypes to overcome the challenges of limited sample size or heterogeneity of long COVID cohorts, resulting in 62 independent single nucleotide polymorphisms (SNPs) prioritized as potentially associated with long COVID. These SNPs were categorized into three groups: (1) severe COVID-19-specific SNPs, such as SNPs mapped to two well-known loci involved in SARS-CoV2 entry (ACE2[rs190509934] andTMPRSS2[rs12329760]), as well as variants ofDPP9(rs7251000),FOXP4(rs12660421) andHLA-DQA1(rs17219281), exhibiting associations with severe COVID-19 but displaying weaker signals in non-hospitalized COVID-19 cases; (2) SNPs associated with both severe and mild COVID-19, including the SNP close toABO(rs505922), representing a catalog of SNPs predispose to both acute COVID-19 and chronic long COVID; and (3) non-hospitalization-specific SNPs, such as variants inKCTD16(rs62401842) andWASF3(rs56143829), highlighting genetic contributors specific to mild COVID-19 cases that might also contribute to long COVID. Further transcriptome-wide association studies (TWASs) across 48 GTEx tissues, leveraging GWAS data on COVID-19 hospitalization, susceptibility, and long COVID from the HGI consortium, revealed distinct tissue-specific patterns of association. Compared to the acute COVID-19 phenotypes, long COVID exhibited weaker association signals across heart, brain, and muscle-related tissues, as determined by correlations between gene expression of adjacent genes of candidate SNPs (43 out of 62 SNPs) and different COVID phenotypes. Notable TWAS hits includedDPP9(rs7251000),CCR1(rs17078348), andTHBS3(rs41264915). Phenome-wide TWASs also identified additional significant associations with long COVID related phenotypes, such asHLA-DQA1(rs17219281),HLA-A(rs9260038), andHLA-C(rs1634761) associated with immune-related diseases,GSDMB(rs9916158) associated with asthma,FOXP4(rs12660421) linked with sleep duration, highlighting their potential roles in long COVID pathophysiology. Therefore, current integrative approach offers a scalable framework for long COVID research by maximizing the statistical power of existing large-scale COVID-19 GWASs and provides novel insights into the genetic underpinnings of long COVID.
Neurodevelopmental Delay and Associated Factors among Preterm Infants Aged 6 to 24 months Adjusted Gestation Age in Two Urban Hospitals in Uganda
Authors: Nalwoga Joyce , Nakibuuka Victoria , Manirakiza Leonard , Namata Tracy Tushabe , Sebunya Robert
Published: February 2025

Introduction

Neurodevelopmental delay has been reported among preterm infants who survive beyond the neonatal period. However, there is paucity of data regarding neurodevelopmental outcomes in preterm infants in Africa, including Uganda.

Objectives

This study aimed at determining the prevalence and factors associated with neurodevelopment delay (NDD) in preterm infants aged 6 to 24 months of adjusted gestation age.

Methods

A cross-sectional study was conducted among 206 preterm infants, aged between 6 and 24 months of adjusted gestation age in the preterm follow up clinics at St. Francis Hospital Nsambya and Mulago Specialized Women and Neonatal Hospital in Kampala-Uganda from 1stJanuary 2021 to 1stJanuary 2022.

Results

The prevalence of NDD was 13.6% (28/206), with social delay comprising 12.1% (25/206), fine motor delay 11.7% (24/206), language delay 10.7% (22/206) and gross motor delay 7.8% (16/206). Factors associated with NDD included microcephaly [aPR=6.2, CI: 2.6-33.5, P=0.0002], severe acute malnutrition (SAM) [aPR=4.6, CI: 1.87-12.56, P=0.021], incomplete immunization [aPR=2.8, CI: 1.23-4.76, P=0.013], neonatal sepsis [aPR=3.8, CI: 1.1-9.3, P=0.026], neonatal hypoglycemia [aPR=6.2, CI: 1.8-16.4, P=0.002], lack of caretaker social support [aPR=8.3, CI: 2.43-37.9, P=0.002] and families with more than 5 children [aPR=6.8, CI: 2.24-22.7, P=0.002]

Conclusions

The 13.6% prevalence of NDD is noteworthy, with the social and fine motor domains affected most. Modifiable factors like malnutrition, lack of caretaker social support and incomplete immunization should be screened and addressed to reduce NDD among preterm infants in Uganda.
Trends in the Distribution ofP Valuesin Epidemiology Journals: DecreasedPHacking or Increased Power?
Authors: Ackley Sarah F. , Andrews Ryan M. , Seaman Christopher , Flanders Michael , Chen Ruijia , Wang Jingxuan , Lopes Grissel , Sims Kendra D. , Buto Peter , Ferguson Erin , Allen Isabel Elaine , Glymour M. Maria
Published: February 2025

Epidemiologists have advocated for reporting confidence intervals and deemphasizingPvalues to address long-standing concerns about null-hypothesis statistical-significance testing,Phacking, and reproducibility. It is unknown if efforts to reduce reliance onPvalues have altered the distribution ofPvalues. For 21,377 abstracts published 2000-2024 in 4 major epidemiology journals, two-sidedPvalues (N=25,360) were calculated from estimates and confidence intervals scraped using ChatGPT’s 4o model. We evaluated trends over time to determine whether the empirical distribution ofPvalues changed. We fitted to expectedPvalue distributions and simulated these distributions with and without assuming changes in statistical power over time. AveragePvalues decreased from 2000 to 2024, as did the fraction just below the 0.05 threshold. Fits to models indicate that statistical power increased. Increasing power would reduce averagePvalue while also decreasingPvalues near the 0.05 threshold—precisely the trends observed in epidemiology journals. Although the frequency ofPvalues near the 0.05 threshold has declined modestly, this likely reflects increases in statistical power rather than decreases inPhacking.
PregMedNet: Multifaceted Maternal Medication Impacts on Neonatal Complications
Authors: Kim Yeasul , Marić Ivana , Kashiwagi Chloe M. , Han Lichy , Chung Philip , Reiss Jonathan D , Butcher Lindsay D. , Caoili Kaitlin J. , Berson Eloïse , Xue Lei , Espinosa Camilo , James Tomin , Shome Sayane , Xie Feng , Ghanem Marc , Seong David , Chang Alan L , Reincke S Momsen , Mataraso Samson , Shu Chi-Hung , Francesco Davide De , Becker Martin , Kumar Wasan M , Wong Ron , Gaudilliere Brice , Angst Martin S , Shaw Gary M , Bateman Brian T , Stevenson David K , Prince Lance S , Aghaeepour Nima
Published: February 2025

While medication intake is common among pregnant women, medication safety remains underexplored, leading to unclear guidance for patients and healthcare professionals. PregMedNet addresses this gap by providing a multifaceted maternal medication safety framework based on systematic analysis of 1.19 million mother-baby dyads from U.S. claims databases. A novel confounding adjustment pipeline was applied to systematically control confounders for multiple medication-disease pairs, robustly identifying both known and novel maternal medication effects.

Notably, one of the newly discovered associations was experimentally validated, demonstrating the reliability of claims data and machine learning for perinatal medication safety studies. Additionally, potential biological mechanisms of newly identified associations were generated using a graph learning method. These findings highlight PregMedNet’s value in promoting safer medication use during pregnancy and maternal-neonatal outcomes.
Unraveling the Co-Morbidity between COVID-19 and Neurodegenerative Diseases Through Multi-scale Graph Analysis: A Systematic Investigation of Biological Databases and Text Mining
Authors: Babaiha Negin Sadat , Geissler Stefan , Nibart Vincent , Güvenilir Heval Atas , Bharadhwaj Vinay Srinivas , Kodamullil Alpha Tom , Klein Juergen , Jacobs Marc , Hofmann-Apitius Martin
Published: February 2025

The COVID-19 pandemic has produced an overwhelming volume of research, yet much of it remains focused on individual diseases, largely ignoring the complex relationships between comorbidities. Although extensive literature exists on both neurodegenerative diseases (NDDs), namely Alzheimer’s and Parkinson’s, and COVID-19, their intersection remains underexplored. Co-morbidity modeling is essential, as patients, particularly those hospitalized, often present with multiple conditions. This study addresses this gap by investigating the crosstalk between COVID-19 and NDDs using a combination of knowledge graphs built from curated biomedical datasets and text mining tools. We conducted comprehensive graph analyses, including path analysis, phenotype coverage assessment, and mapping of cellular and genetic factors, to examine how various Knowledge Graphs (KGs)—such as PrimeKG, DrugBank, OpenTargets, and those generated from natural language processing (NLP) methodologies—illuminate molecular and phenotypic relationships between these diseases. Our findings reveal significant variability in graph density and connectivity across datasets, each offering unique insights into the landscape of COVID-19 and NDD co-morbidities. By integrating structured biological data with unstructured textual data, this study aimed to optimize co-morbidity modeling, maximize recall for identifying potential co-morbidity mechanisms, and consolidate this information in a dedicated co-morbidity hypothesis database. Key genetic and inflammatory markers, particularly immune response genes, emerged as consistent features across multiple KGs, reinforcing their potential role in COVID-19–NDD interactions. This integrative approach advances our understanding of the underlying mechanisms linking these diseases and facilitates the identification of potential therapeutic targets.

All data, methodologies, and detailed instructions for accessing the co-morbidity hypothesis database are publicly available and thoroughly documented at:https://github.com/SCAI-BIO/covid-NDD-comorbidity-NLP.
Comprehensive Metagenomic Profiling of Diverse Microbiomes
Authors: Kakuk Balázs , Dörmő Ákos , Taifi Ahmed , Járay Tamás , Kurucsai Gábor , Gulyás Gábor , Prazsák István , Boldogkői Zsolt , Tombácz Dóra
Published: February 2025

The canine gut microbiome serves as a key model for veterinary and human health research, but inconsistent findings arise due to methodological variations. This study presents a three-part dataset to clarify how DNA extraction, primer selection, and sequencing platforms influence microbial profiling. First, we performed ultra-deep sequencing of a single dog fecal sample using five DNA isolation kits, multiple library protocols, and four sequencing platforms (Illumina MiSeq/NovaSeq, ONT MinION, PacBio Sequel IIe), enabling direct comparisons of 16S rRNA and shotgun sequencing techniques. Second, we analyzed 40 fecal samples from eight co-housed dogs using Zymo High-Molecular-Weight (ZHMW) and Zymo MagBead (ZMB) extraction kits to assess longitudinal extraction-kit effects. Third, we evaluated three 16S primer systems (standard ONT, PacBio, and modified ONT with degenerate bases) using synthetic mock communities and human/canine fecal samples to quantify primer biases. By integrating synthetic and biological replicates, this dataset provides a standardized resource for benchmarking bioinformatics pipelines and improving cross-study comparability. The study generated 75.31GB of new sequencing data: 43.451GB from ZHMW-ZMB comparisons, 22.611GB for primer evaluations, and 9.191GB from the single-sample analysis. Combined with 31.51GB of prior data, the total dataset exceeds 1061GB, including all analytical outputs. These resources enhance methodological transparency and accuracy in canine gut microbiome research across diverse laboratory workflows.
From Archaea to the atmosphere: remotely sensing Arctic methane
Authors: Varner Ruth K. , Cronin Dylan R. , Crill Patrick , Palace Michael , McCalley Carmody K. , Deng Jia , Herrick Christina , Kuhn McKenzie , Hodgkins Suzanne B. , McArthur Kellen , Singer Jessica DelGreco , Bolduc Benjamin , Li Yueh-Fen ,   The Archaea to Atmosphere (A2A) Project Team,   EMERGE Institute Coordinators, Li Changsheng , Tyson Gene , Frolking Steve , Chanton Jeffrey P. , Persson Andreas , Saleska Scott R. , Rich Virginia I.
Published: February 2025

Global atmospheric methane concentrations are rapidly rising and becoming isotopically more depleted, implying an unresolved microbial contribution. Rising Arctic temperatures are variably altering soil methane cycling, causing consequential uncertainty in the atmospheric methane budget. We demonstrated in an Arctic wetland that below-ground microbiota and methane-cycling features parallelled above-ground plant communities. To upscale emissions, we applied machine learning to remote sensing data to identify habitats, which were assigned average emissions. To upscale dynamically, we incorporated climate data, remotely-sensed water table variation, and habitat classes into a temporally-resolved biogeochemical model, to predict methane flux and isotope dynamics. This accurately estimated more depleted 13C-methane than previously used for Arctic habitats in global source partitioning. Remote-sensing of these rapidly changing inaccessible landscapes can thus help constrain the role of the Arctic in ongoing changes in global methane emissions.
Repurposing AZD-5991 for inhibiting growth and biofilm formation ofStaphylococcus aureusby disrupting the cell membrane and targeting FabI
Authors: Tang Yuanyuan , Deng Han , Xu Zhichao , Yu Zhijian , Xiang Yong , Wen Zewen , Han Shiqing , Chen Zhong , Hou Tieying
Published: February 2025

Staphylococcus aureusinfections have already become a major threat to public health worldwide. Drug resistance and biofilm formation are two critical factors that significantly affect the efficacy of the antimicrobial treatment ofS. aureusinfections using conventional antibiotics. Therefore, the discovery of novel antimicrobial agents with potent antibacterial and antibiofilm activity has become a hotspot in recent years. Here, we first demonstrated the remarkable inhibitory activity of AZD-5991, a selective Mcl-1 inhibitor, againstS. aureus. The MIC50and MIC90of AZD-5991 againstS. aureuswere 12.5 μM, and AZD-5991 significantly inhibited the growth ofS. aureusat a subinhibitory concentration of 1/2 × MIC. Besides, AZD-5991 displayed bactericidal activity and a robust capacity for inhibiting biofilm formation againstS. aureuswith very low drug toxicity against host cell lines. Our data demonstrated the disruption ofS.aureuscell integrity by AZD-5991 through membrane permeability assays and the ingredients of the bacterial phospholipids could neutralize the antibacterial activity of AZD-5991. Moreover, whole-genome sequencing and proteomic analysis were also applied to gain insights into the possible impact of AZD-5991 on the fatty metabolism ofS. aureus. Furthermore, the antibacterial activity of AZD-5991 was significantly elevated by exogenous fatty acids linoleic acid (C18:2 Δ 9,12) and arachidonic acid (C20:4 Δ 5,8,11,14). Lastly, the biolayer interferometry assay supported the direct interaction of AZD-5991 with FabI, a necessary protein related closely to bacterial growth and fatty acid metabolism. Conclusively, this study suggests that AZD-5991 could inhibit the planktonic growth and biofilm formation ofS. aureusby disrupting the cell membrane and targeting FabI. AZD-5991 might be a promising new antibiotic candidate for the antimicrobial treatment ofS. aureusinfections resistant to traditional clinical drugs.

Graphical Abstract
Aggregate sales decline and cost stickiness: a multinational study
Authors: Wang Weiwei , Zheng Kenneth
Published: February 2025

Purpose

This study investigates the implications of country-level aggregate sales decline on firms’ cost stickiness and explores how legal systems and cultural dimensions moderate this relationship.

Design/methodology/approach

We analyze an international sample of firms from 39 countries over the 2003–2022 period using regression analysis to examine the relationship between aggregate sales decline and firms’ cost behavior.

Findings

Our findings reveal that country-level aggregate sales decline reduces firms’ cost stickiness, in contrast to the extensively documented positive association between firm-level sales decline and cost stickiness. This reduction in cost stickiness is statistically and economically significant, regardless of whether firms individually experience consecutive sales declines. Moreover, the impact is significantly stronger for firms in common-law countries, countries with long-term orientation and countries with higher levels of individualism.

Originality/value

The study is the first multinational study to examine the effect of aggregate sales decline on cost stickiness. The study also offers insights into the role of legal systems and cultural dimensions in moderating this relationship.
A novel self-adaptive multivariate grey model with external intervention for port cargo throughput prediction
Authors: Li Xuemei , Sun Yuyu , Shi Yansong , Zhao Yufeng , Zhou Shiwei
Published: February 2025

Purpose

Accurate prediction of port cargo throughput within Free Trade Zones (FTZs) can optimize resource allocation, reduce environmental pollution, enhance economic benefits and promote sustainable transportation development.

Design/methodology/approach

This paper introduces a novel self-adaptive grey multivariate prediction modeling framework (FARDCGM(1,N)) to forecast port cargo throughput in China, addressing the challenges posed by mutations and time lag characteristics of time series data. The model explores policy-driven mechanisms and autoregressive time lag terms, incorporating policy dummy variables to capture deviations in system development trends. The inclusion of autoregressive time lag terms enhances the model’s ability to describe the evolving system complexity. Additionally, the fractional-order accumulative generation operation effectively captures data features, while the Grey Wolf Optimization algorithm determines optimal nonlinear parameters, enhancing the model’s robustness.

Findings

Verification using port cargo throughput forecasts for FTZs in Shanghai, Guangdong and Zhejiang provinces demonstrates the FARDCGM(1,N) model’s remarkable accuracy and stability. This innovative model proves to be an excellent forecasting tool for systematically analyzing port cargo throughput under external interventions and time lag effects.

Originality/value

A novel self-adaptive grey multivariate modeling framework, FARDCGM(1,N), is introduced for accurately predicting port cargo throughput, considering policy-driven impacts and autoregressive time-lag effects. The model incorporates the GWO algorithm for optimal parameter selection, enhancing adaptability to sudden changes. It explores the dual role of policy variables in influencing system trends and the impact of time lag on dynamic response rates, improving the model’s complexity handling.
Rethinking process improvement: from diffusion to translation
Authors: Al Hasan Rima , Micheli Pietro
Published: February 2025

Purpose

Despite firms’ growing investments, process improvement (PI) programs often fail to deliver the expected benefits. In this paper, we argue that the widespread adoption in PI research of a paradigm founded in positivism plays a primary role in deriving these conclusions and limits the development of PI theory and practice.

Design/methodology/approach

We examine the main characteristics of the dominant paradigm in PI research and then propose an alternative perspective drawing on research in management innovation and complexity. Findings from two empirical case studies in a pharmaceutical and an automotive firm are reported to support our theoretical argument.

Findings

The proposed perspective highlights the interaction between various PI approaches – such as lean, Six Sigma and total quality management (TQM) – and the context-dependence and experiential aspects of PI. We argue that this perspective can better account for where, by whom and how PI approaches are shaped and used and, ultimately, can more effectively advance both theory and practice.

Originality/value

This study suggests that PI approaches should be considered as adaptable rather than static, in combination rather than as single entities and as continuously interpreted and translated by organizational actors rather than homogeneously diffused across companies and business units. In this paper, we discuss the substantial conceptual, methodological and practical implications of adopting this perspective.
“How does workplace spirituality influence organizational citizenship behavior in the hospitality industry?”: a person-organization fit perspective
Authors: Srivastava Shalini , Dhamija Pavitra , Madan Poornima
Published: February 2025

Purpose

Using the person-organization (P-O) fit perspective, the present study explores the interlinkages between workplace spirituality (WPS) and organizational citizenship behavior (OCB). It further attempts to understand the mediating effects of psychological ownership and innovative work behavior (IWB) for the association.

Design/methodology/approach

Data was collected in three waves from 283 frontline hotel employees in the Delhi NCR region of India. Partial least square (PLS-structural equation modeling) was used to test the hypothesized model.

Findings

A significant association was found between WPS and OCB. Psychological ownership and IWB had a significant serial mediation effect on WPS and OCB relationship.

Practical implications

The involvement of spirituality in the workplace is one of the significant factors contributing to positive organizational performance from the perspective of perishable services. Hence, understanding and implementing best practices to encourage WPS and strengthening psychological ownership for favorable behavioral outcomes must be one of the significant priorities for human resource managers in the hospitality industry.

Originality/value

WPS is an under-explored area in the hospitality industry. The present study will be novel and critical in bridging the research gap wherein psychological ownership and IWBs mediate the relationship between WPS and OCB in the hospitality sector. Furthermore, the present study notably contributes to using person organizational fit theory for the hypothesized relationships between study variables for the hospitality sector employees in India.
Commercial real property instalment land contracts
Authors: Larsen James E. , Akhbari Marlena L. , Morris Brandon C.L.
Published: February 2025

Purpose

This paper reports the results of an investigation of the use of instalment land contracts (ILCs) in the Montgomery County, Ohio commercial real property market.

Design/methodology/approach

Generalised spatial two-stage least squares regression is used to analyse data from 164 ILC financed commercial property transactions and 918 traditionally financed commercial property transactions, all of which were initiated between January 1, 2016 and December 31, 2023.

Findings

In our sample, the use of ILCs for the acquisition of commercial real estate is concentrated on relatively low-value properties. A bargaining power imbalance was discovered; the price ILC vendees promised to pay was more than buyers using traditional financing paid for similar property.

Practical implications

The results suggest that some commercial property investors use ILCs because they cannot qualify for a loan from an institutional lender, and some may benefit from the additional regulations that ILC critics have proposed.

Originality/value

This is the first published empirical study of ILC use in a local commercial property market.
Mitigating bias in long‐term terrestrial ecoacoustic studies
Authors: Jarrett David , Barnett Ross , Bradfer‐Lawrence Tom , Froidevaux Jérémy S. P. , Gibb Kieran , Guinet Pauline , Greenhalgh Jack , Heath Becky , Johnston Alison , Monfort José Joaquín Lahoz , Rogers Alex , Willis Stephen G. , Metcalf Oliver
Published: February 2025

Long‐term biodiversity monitoring is needed to track progress towards ambitious global targets to reduce species loss and restore ecosystems. The recent development of cheap and robust acoustic recording devices offers a cost‐effective means of gathering standardised long‐term datasets.

Accounting for sources of bias in ecological monitoring and research is a fundamental part of the study design process. To highlight this issue in the context of long‐term terrestrial ecoacoustic monitoring, here we collate and discuss sources of bias arising from (i) hardware devices, (ii) firmware, software and analysis tools and (iii) the deployment environment.

One important source of bias is unavoidable changes in recording hardware—to demonstrate how this potentially introduces bias, we present two case studies comparing the output from simultaneous recordings from different recorders.

To mitigate biases, we recommend effective documentation of environmental and hardware‐related variables, as well as a long‐term data storage strategy that facilitates reanalysis. Additionally, the use of regular calibration tests to measure variation in the acoustic detection space will facilitate analytical approaches or post‐hoc AI solutions that remove unwanted biases.

Synthesis and applications: The sources of bias and suggested mitigations described here will be of relevance to hardware manufacturers, ecological researchers and conservation practitioners. Researchers and conservation practitioners must be fully aware of relevant biases when designing long‐term ecoacoustic studies and should incorporate appropriate mitigations into their study design.
Serving her Sentence: Gender and the Segregation of Carceral Space in Nineteenth‐Century America
Authors: Turner Felicity M.
Published: February 2025

Drawing on court cases, newspaper reports and pardon records from nineteenth‐century North Carolina in relation to infant murder and infanticide, this article complicates historical ideas about gender and incarceration by positing that in some circumstances, segregation in carceral spaces by virtue of gender served to benefit some women. Using the example of North Carolina – singular because of its lack of a centralised state prison in the years prior to the US Civil War – the article argues that segregation by gender advantaged white women, in particular, no matter how poor. Local communities accepted that such women, no matter the severity of their crime, could not be incarcerated with men. The absence of carceral spaces for white women then provided pathways to executive pardons for convicted women as there was nowhere to incarcerate them.
The Synergistic Impact of Digital Technology and Financial Systems on Sustainable Environment
Authors: Tahir Safdar Husain , Wang Xiaohui , Zulfiqar Muhammad , Ullah Muhammad Rizwan , Sajid Mushtaq A.
Published: February 2025

This paper exclusively adds value to the state‐of‐the‐art literature, offering the combined impact of various conditions (variables) on environmental sustainability in the context of complexity theory. Unlike the conventional regression‐based research methods, the fuzzy set qualitative comparative analysis applies a novel configuration approach for analysing the data of 63 countries around the globe covering the period from 1990 to 2020. In addition, analytical induction is also used to diagnose existing patterns of solutions in the dataset. The input conditions are digital transformation, financial innovation, financial inclusion, foreign direct investment, and financial openness, while the outcome condition (variable) is an environmental sustainability. The necessary condition analysis shows no individual conditions indispensable for the outcome. However, sufficiency condition analysis discovers eight alternative solutions/ pathways, sufficient for the outcome. This study makes notable contributions to the existing body of knowledge that offers unique long‐term insights and practical solutions for academicians and policymakers working on sustainable environments worldwide, in particular.
Peanut skin polyphenols inhibit proliferation of leukemia cells in vitro, and its A‐type procyanidins selectively pass through a Caco‐2 intestinal barrier
Authors: Jantip Pornpat (Aom) , Singh Chandra K. , Klu Yaa Asantewaa Kafui , Ahmad Nihal , Bolling Bradley W.
Published: February 2025

Increased consumption of nuts is associated with reduced risk of some forms of cancer, including leukemia. Peanut skins are not typically retained during food processing but are a potential source of anticarcinogenic polyphenols. There are limited data about the antileukemic activity and bioavailability of peanut skin polyphenols. This study determined the polyphenol profile of raw peanut skin extract (PSE), its antiproliferative activity toward Jurkat cells, and intestinal bioavailability and metabolism using a Caco‐2 intestinal monolayer model. High‐resolution mass spectrometry (UHPLC–Q‐Orbitrap) was used to analyze PSE and extracts of PSE‐treated Jurkat cells to determine PSE polyphenols associated with antiproliferative activity. PSE reduced Jurkat cell viability, indicating its antiproliferative activity. PSE contained at least 63 polyphenols, including phenolic acids, proanthocyanidins, and prenylated flavonoids, among others. Multiple PSE polyphenols, particularly proanthocyanidins with A‐type bonds, interacted with Jurkat cells. In Caco‐2 cells, PSE intestinal bioavailability was limited to (+)‐catechin, quercetin, procyanidin A2, and tentatively procyanidin A1. Caco‐2 cells metabolized PSE polyphenols, including the methylation of A‐type procyanidin dimer. Thus, these cell‐based studies demonstrate that raw peanut skins contain intestinal bioavailable polyphenols with potential antileukemic properties. PSE polyphenols, including A‐type proanthocyanidins, were metabolized by intestinal cells. Thus, the antileukemic activity of PSE polyphenols is modulated by the bioavailability and metabolism of A‐type proanthocyanidins.

Practical Application

Raw peanut skins are rich in polyphenols, including A‐type proanthocyanidins. Extracts of peanut skins inhibit the growth of cultured leukemia cells, and peanut A‐type proanthocyanidins are associated with this effect. Peanut skins are not typically retained in food processing, so further research and development are needed to recover or retain these compounds and document their health‐promoting activities in human research studies.
Role of IL‐34 in Tumors and Its Application to Regulate Inflammation
Authors: Igarashi Yuichi , Seino Ken‐ichiro
Published: February 2025

Interleukin (IL)‐34 is a relatively recently discovered cytokine which binds to colony‐stimulating factor‐1 receptor (CSF‐1R). So far, there has been no clear explanation as to why CSF‐1R requires two ligands. While CSF‐1 is ubiquitously expressed, the expression of IL‐34 is relatively restricted. However, it has been revealed that IL‐34 expression increases in various diseases and is associated with their pathology. Naturally, both IL‐34 and CSF‐1 stimulate CSF‐1R, thereby contributing to the differentiation of monocytes into macrophages. In many cases, the induced macrophages significantly influence the disease pathology. In particular, we have demonstrated that IL‐34 expression in cancer is deeply involved in tumor progression and therapeutic resistance. We have shown that the blockade of IL‐34 significantly improved therapeutic efficacy such as chemotherapy, radiotherapy, and immune checkpoint blockade against IL‐34‐expressing cancers. Recently, since macrophages induced by IL‐34 exhibit immunosuppressive properties, whereas IL‐34 can enhance inflammation, there is growing interest in actively regulating inflammation utilizing IL‐34. In this review article, we provide an overview of the characteristics and roles of IL‐34 and discuss how it could be applied to future diagnostics and therapeutics.
Single‐Nucleus RNA Sequencing and Spatial Transcriptomics for Squamous Cell Carcinoma Arising From Ovarian Mature Teratoma
Authors: Yoshida Kosuke , Yokoi Akira , Suzuki Hironori , Tamauchi Satoshi , Kitagawa Masami , Inami Eri , Nakayama Jun , Mori Yutaro , Okamoto Koji , Suzuki Yutaka , Yoshida Hiroshi , Kato Tomoyasu , Kajiyama Hiroaki , Yamamoto Yusuke
Published: February 2025

Squamous cell carcinoma arising from mature teratoma (SCC‐MT) is a rare ovarian malignancy. The detailed molecular pathology of SCC‐MT is not well understood. Moreover, the prognosis of the patients remains poor because no standard treatment has been established. In this study, we performed single‐nucleus RNA sequencing and spatial transcriptomics using clinical SCC‐MT samples to identify novel therapeutic candidates. snRNA‐seq revealed three epithelial cell clusters, of which one was significantly associated with epidermis and keratinocyte development. Moreover, spatial transcriptomics revealed that the epithelial‐mesenchymal transition was significantly inhibited, and the MYC and E2F targets were significantly activated in cancer spots on specimen sections. We focused on KLF5, which was one of the upregulated genes in cancer cells, and performed a functional analysis using NOSCC‐1, a cell line derived from an SCC‐MT. KLF5 downregulation significantly decreased cell proliferation and increased apoptosis. Furthermore, we previously identified miR‐145‐5p as a downregulated miRNA in SCC‐MT. We demonstrated that miR‐145‐5p overexpression attenuated cell proliferation and decreased KLF5 expression. In conclusion, through multi‐omics analyses, we identified unique gene expression profiles of SCC‐MT and determined a role for KLF5 in SCC‐MT development. Therefore, KLF5‐related factors may be novel therapeutic targets, and further studies are needed to improve the diagnosis and treatment of SCC‐MT.
Anti‐Inflammatory Compounds From Roots of Heracleum sphondylium subsp. cyclocarpum
Authors: Kurtul Ekin , Acıkara Özlem Bahadır , Ağören Büşra Karpuz , Akkol Esra Küpeli
Published: February 2025

Heracleum sphondylium subsp. cyclocarpum (K. Koch) P.H. Davis from Heracleum L. genus, which is one of the widest genera of the Apiaceae family and known as “Hogweed or Tavşancılotu”. This genus has a variety of traditional uses, including treating gastrointestinal, cardiovascular, gynecological, and cognitive disorders, skin problems, rheumatism, and inflammation. In particular, these plants are commonly used for inflammatory diseases. This research aimed to examine in detail the anti‐inflammatory properties of Heracleum sphondylium subsp. cyclocarpum roots. Bioactivity‐guided fractionation was used to isolate the active compounds. Carrageenan‐ and prostaglandin E2‐induced inflammation models were employed to test the activity. Dichloromethane and methanolic extracts of the plant material were tested for activity and found to be effective in inhibiting inflammation. The subfractions obtained by column chromatography were further evaluated for their activities. The active fractions were used to obtain responsible compounds by using semipreparative HPLC. Five coumarin derivatives were isolated and identified as heraclenol (1), byakangelicin (2), heraclenol‐3″‐O‐β‐glucoside (3), byakangelicin‐3″‐O‐β‐glucoside (4), and meranzin hydrate III (5). The isolated compounds were investigated for their anti‐inflammatory activities, and heraclenol‐3″‐O‐β‐glucoside was found to inhibit the carrageenan and prostaglandin E2‐induced edema significantly compared to the control group and have higher activity than the extracts.
Needs and Expectations of Nurse‐Led Digital Support Among Parents of Children in Child Health Care
Authors: Valan Lotha , Isaksson Ulf , Hörnsten Åsa
Published: February 2025

Introduction

Sweden has an extensive national child health care programme (CHCP) implying that all parents are offered support to raise their children and support them for healthy development. The programme is today built on personal physical contacts and digital components unusual. Although the digital world could be frightening and insecure, it also has benefits, because it is not dependent on face‐to face meetings and is accessible more hours. In order to develop a digital channel to complement the CHPC, for the support of parents of children within child health care (CHC), parents' perspectives must be investigated. The aim of the study was therefore to describe parents' needs and expectations of digital support in the context of child health care.

Methods

The study had a qualitative approach using workshop discussions with parents as data. The interview data were analysed using qualitative content analysis.

Results

The main theme highlights that parents expected that a digital support channel would be something that might strengthen them towards independence concerning the care of their children, in a positive way. However, they also felt that they needed personal support and that relationships with other parents and the child health care nurse were significant and meaningful. Another parental desire that emerged was that a future digital channel would facilitate and simplify access to care and they suggested having both planned and urgent times available for parents to book. The digital channel was expected to make this possible and be a good complement to the physical contacts the traditional child health care currently offers.

Discussion/Conclusions

The parents in this study believed that digital solutions could increase their parental power in relation to the care of their children. Examples were given as digital nurse‐led parent groups where parents with similar problems and experiences around their children could support each other and were expected to strengthen them over time. The parents stressed that a planned digital support channel also needs satisfactory solutions for both contact and response and have bookable digital meetings for both planned and urgent needs.
The impact of surgeon speciality on surgical outcomes following colorectal resection for endometriosis
Authors: Nasseri Yosef , Ma Rachel , Fani Negin , La Kristina , Solis‐Pazmino Paola , Xu Vincent , Siedhoff Matthew T. , Wright Kelly N. , Schneyer Rebecca , Hamilton Kacey M. , Barnajian Moshe , Meyer Raanan
Published: February 2025

Aim

An estimated 5%–25% of women with endometriosis have colorectal involvement. Colorectal resection is the most suitable surgical management for cases with large bowel infiltration. However, this method is also associated with the highest rate of postoperative complications. Data focusing on surgeon speciality and surgical outcomes are currently limited. The aim of this work was to evaluate the surgical characteristics and short‐term postoperative outcomes following colorectal resection for endometriosis according to surgeon speciality.

Method

Using the National Surgical Quality Improvement Program (NSQIP) database, we included women who underwent colorectal resection for endometriosis between 2012 and 2020. Surgeries by general/colorectal surgeons were compared with those by gynaecological surgeons. The primary outcome was major complications according to the Clavien–Dindo classification.

Results

Among 745 colorectal resections, 82.3% were performed by general/colorectal surgeons and 17.7% by gynaecologists. Racial and ethnic characteristics differed between groups, but other baseline characteristics were comparable. General/colorectal surgeons performed fewer minimally invasive surgeries (29.9% vs. 58.3%, p < 0.001). General/colorectal surgery cases had lower rates of any postoperative complications and minor complications (14.8% vs. 29.5%, p < 0.001; 10.1% vs. 23.5%, p < 0.001), while major complication rates were similar. Multivariable regression showed no association between major complications and surgical speciality. In a propensity score‐matched analysis, no significant differences were found between the two cohorts.

Conclusion

Most colorectal resections are performed by general/colorectal surgeons while a minimally invasive approach is more common among gynaecologists. There were no significant differences in outcomes between the two groups after adjusting for confounding variables. This suggests considering a multidisciplinary or dual surgery team approach to deep infiltrative endometriosis requiring bowel resection.
Efficacy of inferior vesical vessels preservation in lateral lymph node dissection for rectal cancer: Short‐ and long‐term outcomes
Authors: Arai Sodai , Kagawa Hiroyasu , Shiomi Akio , Manabe Shoichi , Yamaoka Yusuke , Maeda Chikara , Tanaka Yusuke , Kasai Shunsuke , Notsu Akifumi , Kinugasa Yusuke
Published: February 2025

Aim

Lateral lymph node dissection (LLD) is performed for rectal cancer, with some cases requiring resection of the inferior vesical vessels (IVV). However, whether preservation or resection of the IVV affects urinary dysfunction (UD) as a major complication or local recurrence (LR) is unclear. Thus, we assessed the effect of IVV resection on the short‐ and long‐term outcomes of rectal cancer.

Method

This retrospective cohort study included patients who underwent robotic mesorectal excision with LLD between December 2011 and April 2021. The patients were divided into two groups based on preserved and resected IVV. Postoperative complications, including UD, and long‐term outcomes, including cumulative LR and cumulative lateral local recurrence (LLR), were evaluated.

Results

Among 340 patients, 298 (87.6%) and 42 (12.4%) were included in the IVV preservation and resection groups, respectively. UD was more frequent (50% vs. 16.8%) in the IVV resection group than in the IVV preservation group (p < 0.01). In the multivariate analysis, IVV and autonomic nervous system resections were significantly associated with UD. The 3‐year LR was 4.0% and 5.7% in the IVV preservation and resection groups, respectively (p = 0.99). The 3‐year LLR was 2.1% and 0% in the IVV preservation and resection groups, respectively (p = 0.27).

Conclusion

IVV resection and autonomic nervous system resection were independent risk factors for UD in robotic LLD. IVV preservation, except in cases of necessity, improves patients’ quality of life and has favourable oncological outcomes.
Balancing ecotourism and wildlife management through a conservation behavior approach
Authors: Chock Rachel Y. , Bessa Eduardo , Arteaga‐Torres Josue David , Baker Liv , Buchholz Richard , Clucas Barbara , Nuñez Cassandra , Pinho Gabriela M. , Schulte Bruce A. , Blumstein Daniel T. , Kitheka Bernard , Allison Alexander G. , Arevalo J. Edgardo , Hamilton Debra A. , Monteza‐Moreno Claudio M. , Nute Laney H. , Rodríguez‐Fonseca Javier , Sandoval Luis , Stamn Jessica , Verdolin Jennifer L. , Von Hagen Lynn , Wehsener Jimmy W. , Seymoure Brett M.
Published: February 2025

Ecotourism promises to reconcile wildlife conservation and human development if negative impacts of human visitation and associated infrastructure can be minimized. Animal behavior studies can be used to identify individual and population responses to anthropogenic impacts before other fitness consequences are documented. With input from professionals in animal behavior and ecotourism, we identified key questions needed to better understand the impact of ecotourism on wildlife. Activity budgets, foraging, movement, stress, habituation, and reproduction were themes that emerged from our survey. We highlight promising research on these themes and identify remaining behavioral research questions about conserving wildlife in the context of ecotourism. Although ecotourism activities often have detrimental effects on animal behavior, we highlight research needs that can inform management and ecotourist education to improve human behavior to be more compatible with sustainable use of nature.
Gross Motor Function Measure‐66 Item Sets for use with infants and toddlers at high risk for cerebral palsy: Construct validity and responsiveness
Authors: Koziol Natalie A. , Butera Christiana D. , Hsu Lin‐Ya , Pereira Silvana Alves , Dusing Stacey C.
Published: February 2025

Aim

To evaluate the construct validity and responsiveness of the Gross Motor Function Measure‐66 Item Set (GMFM‐66‐IS), a standardized criterion‐referenced observational measure, for use with children younger than 24 months with or at high risk for cerebral palsy (CP).

Method

Non‐experimental integrative data analysis was performed on secondary data from three clinical trials involving children with or at high risk for CP (n = 79, 42 males, mean corrected age = 11.3 months [SD = 4.9]), and one observational study of typically developing children (n = 32, 14 males, mean age = 5.7 months [SD = 0.8]). The GMFM‐66‐IS and comparator instrument (gross motor subtest from the Bayley Scales of Infant and Toddler Development, Third Edition [Bayley‐III] or Bayley Scales of Infant and Toddler Development, Fourth Edition [Bayley‐4], depending on the study) were administered at baseline and 3 months later. Comparator groups were based on neurological impairment, clinical rating of gross motor change, and CP status. Correlations (r) and regression‐adjusted standardized mean differences (Hedges' g) were computed.

Results

GMFM‐66‐IS and Bayley scores were correlated at baseline (r = 0.83), 3 months later (r = 0.88), and across time (r = 0.83). Children with mild impairment had higher mean GMFM‐66‐IS scores at baseline (g = 0.87) and 3 months later (g = 0.95). Children rated as demonstrating greater than expected gross motor change had larger mean GMFM‐66‐IS change scores than children demonstrating less than expected change (g = 0.62). Typically developing children had larger mean GMFM‐66‐IS change scores (g = 1.00).

Interpretation

GMFM‐66‐IS scores were supported by evidence of strong construct validity and moderate responsiveness.
Exploring healthcare professionals' attitudes to screening for disordered eating in type 1 diabetes
Authors: Fitzgerald Katie , Jones Christina , Partridge Helen , Rouse Lindsey , Satherley Rose‐Marie
Published: February 2025

Aims

Eating disorders and disordered eating behaviours are prevalent among adults with type 1 diabetes, making early identification essential for improving health outcomes. Although screening tools exist to detect disordered eating in type 1 diabetes (T1DE), their application in clinical practice remains limited. This study investigates healthcare professionals' perspectives and attitudes towards screening for disordered eating in adult diabetes services.

Methodology

This qualitative study employed semi‐structured interviews with 13 healthcare professionals from adult diabetes services. Purposive sampling was used to ensure a broad range of healthcare professional viewpoints. The interviews centred on their perceptions of screening for disordered eating in type 1 diabetes.

Results

Reflexive thematic analysis was used to identify four themes: (1) Uncertainty and Inevitabiltiy of T1DE: ‘A bit of a black hole’, (2) Asking about T1DE: ‘My fear is…am I overstepping the line’, (3) Patient‐provider relationships: ‘A backward step’, and (4) Lack of support for T1DE: ‘Where do you go?’. While healthcare professionals recognised the link between diabetes management and disordered eating, they lacked confidence in screening for these challenges due to limited time and the scarcity of specialist disordered eating resources for type 1 diabetes.

Conclusion

This study highlights the challenges healthcare professionals face in screening for disordered eating in type 1 diabetes. By highlighting the need for enhanced training and clear clinical guidelines, this research suggests pathways to improve healthcare professional confidence in addressing these critical conversations with patients, ultimately supporting better health outcomes.