bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foundational model aided automatic high-throughput drug screening using self-controlled cohort study
Authors: Xu Shenbo , Cobzaru Raluca , Finkelstein Stan N. , Welsch Roy E. , Ng Kenney , Middleton Lefkos 
Published: August 2024

AbstractBackgroundDeveloping medicine from scratch to governmental authorization and detecting adverse drug reactions (ADR) have barely been economical, expeditious, and risk-averse investments. The availability of large-scale observational healthcare databases and the popularity of large language models offer an unparalleled opportunity to enable automatic high-throughput drug screening for both repurposing and pharmacovigilance.ObjectivesTo demonstrate a general workflow for automatic high-throughput drug screening with the following advantages: (i) the association of various exposure on diseases can be estimated; (ii) both repurposing and pharmacovigilance are integrated; (iii) accurate exposure length for each prescription is parsed from clinical texts; (iv) intrinsic relationship between drugs and diseases are removed jointly by bioinformatic mapping and large language model - ChatGPT; (v) causal-wise interpretations for incidence rate contrasts are provided.MethodsUsing a self-controlled cohort study design where subjects serve as their own control group, we tested the intention-to-treat association between medications on the incidence of diseases. Exposure length for each prescription is determined by parsing common dosages in English free text into a structured format. Exposure period starts from initial prescription to treatment discontinuation. A same exposure length preceding initial treatment is the control period. Clinical outcomes and categories are identified using existing phenotyping algorithms. Incident rate ratios (IRR) are tested using uniformly most powerful (UMP) unbiased tests.ResultsWe assessed 3,444 medications on 276 diseases on 6,613,198 patients from the Clinical Practice Research Datalink (CPRD), an UK primary care electronic health records (EHR) spanning from 1987 to 2018. Due to the built-in selection bias of self-controlled cohort studies, ingredients-disease pairs confounded by deterministic medical relationships are removed by existing map from RxNorm and nonexistent maps by calling ChatGPT. A total of 16,901 drug-disease pairs reveals significant risk reduction, which can be considered as candidates for repurposing, while a total of 11,089 pairs showed significant risk increase, where drug safety might be of a concern instead.ConclusionsThis work developed a data-driven, nonparametric, hypothesis generating, and automatic high-throughput workflow, which reveals the potential of natural language processing in pharmacoepidemiology. We demonstrate the paradigm to a large observational health dataset to help discover potential novel therapies and adverse drug effects. The framework of this study can be extended to other observational medical databases.
Design and Biophysical Characterization of Second-Generation Cyclic Peptide LAG-3 Inhibitors for Cancer Immunotherapy
Authors: Calvo-Barreiro Laura , Zhang Longfei , Ali Yaser , Rehman Ashfaq Ur , Gabr Moustafa 
Published: August 2024

AbstractLymphocyte activation gene 3 (LAG-3) is an inhibitory immune checkpoint crucial for suppressing the immune response against cancer. Blocking LAG-3 interactions enables T cells to recover their cytotoxic capabilities and diminishes the immunosuppressive effects of regulatory T cells. A cyclic peptide (Cys-Val-Pro-Met-Thr-Tyr-Arg-Ala-Cys, disulfide bridge: 1-9) was recently reported as a LAG-3 inhibitor. Based on this peptide, we designed 19 derivatives by substituting tyrosine residue to maximize LAG-3 inhibition. Screening via TR-FRET assay identified 8 outperforming derivatives, with cyclic peptides 12 [Tyr6(L-3-CN-Phe)], 13 [Tyr6(L-4-NH2-Phe)], and 17 [Tyr6(L-3,5-DiF-Phe)] as top candidates. Cyclic peptide 12 exhibited the highest inhibition (IC50= 4.45 ± 1.36 µM). MST analysis showed cyclic peptides 12 and 13 bound LAG-3 withKDvalues of 2.66 ± 2.06 µM and 1.81 ± 1.42 µM, respectively, surpassing the original peptide (9.94 ± 4.13 µM). Docking simulations indicated enhanced binding for cyclic peptide 12, with a docking score of -7.236 kcal/mol compared to -5.236 kcal/mol for the original peptide.
Random Sanitization in DNA information storage using CRISPR-Cas12a
Authors: Shen Hongyu , Weng Zhi , Zhao Haipei , Song Haitao , Wang Fei , Fan Chunhai , Song Ping 
Published: August 2024

AbstractDNA information storage provides an excellent solution for metadata storage due to its high density, programmability, and long-term stability. However, current research in DNA storage primarily focuses on the processes of storing and reading data, lacking comprehensive solutions for the secure metadata wiping. Herein, we present a method of random sanitization in DNA information storage using CRISPR-Cas12a (RSDISC) based on precise control of the thermodynamic energy of primer-template hybridization. We utilize the collateral cleavage (trans-activity) of single-stranded DNA (ssDNA) by CRISPR-Cas12a to achieve selective sanitization of files in metadata. This method enables ssDNA degradation with different GC content, lengths, and secondary structures to achieve a sanitization efficiency up to 99.9% for 28,258 oligonucleotides in DNA storage within one round. We demonstrate that the number of erasable files could reach 1011.7based on a model of primer-template hybridization efficiency. Overall, RSDISC provides a random sanitization approach to set the foundation of information encryption, file classification, memory deallocation and accurate reading in DNA data storage.
The Interaction Effects of Sex, Age, APOE and Common Health Risk Factors on Human Brain Functions
Authors: Li Tengfei , Chen Jie , Zhao Bingxin , Garden Gwenn A. , Giovanello Kelly S. , Wu Guorong , Zhu Hongtu 
Published: August 2024

ABSTRACTImportanceNonlinear changes in brain function during aging are shaped by a complex interplay of factors, including sex, age, genetics, and modifiable health risk factors. However, the combined effects and underlying mechanisms of these factors on brain functional connectivity remain poorly understood.ObjectiveTo comprehensively investigate the combined associations of sex, age,APOEgenotypes, and ten common modifiable health risk factors with brain functional connectivities during aging.Design, Setting, and ParticipantsThis analysis used data from 36,630 UK Biobank participants, aged 44–81, who were assessed for sex, age,APOEgenotypes, 10 health risk factors, and brain functional connectivities through resting-state functional magnetic resonance imaging.Main Outcomes and MeasuresBrain functional connectivities were evaluated through within- and between-network functional connectivities and connectivity strength. Associations between risk factors and brain functional connectivities, including their interaction effects, were analyzed.ResultsHypertension, BMI, and education were the top three influential factors. Sex-specific effects were also observed in interactions involving APOE4 gene, smoking, alcohol consumption, diabetes, BMI, and education. Notably, a negative sex-excessive alcohol interaction showed a stronger negative effect on functional connectivities in males, particularly between the dorsal attention network and the language network, while moderate alcohol consumption appeared to have protective effects. A significant negative interaction between sex andAPOE4revealed a greater reduction in functional connectivity between the cingulo-opercular network and the posterior multimodal network in maleAPOE4carriers. Additional findings included a negative age-BMI interaction between the visual and dorsal attention networks, and a positive age-hypertension interaction between the frontoparietal and default mode networks.Conclusions and RelevanceThe findings highlight significant sex disparities in the associations between age, theAPOE-ε4 gene, modifiable health risk factors, and brain functional connectivity, emphasizing the necessity of jointly considering these factors to gain a deeper understanding of the complex processes underlying brain aging.
Improvements in Patient-Reported Functioning after Lung Transplant is Associated with Improved Quality of Life and Survival
Authors: Seijo Leslie , Gao Ying , Betancourt Legna , Venado Aida , Hays Steven R. , Kukreja Jasleen , Calabrese Danny R. , Greenland John R. , Singer Jonathan P. 
Published: August 2024

AbstractLung transplantation aims to improve health-related quality of life (HRQL) and survival. While lung function improvements are associated with these outcomes, the association between physical functioning and these outcomes is less clear. We investigated the association between changes in patient-reported physical functioning and HRQL, chronic lung allograft dysfunction (CLAD), and survival after lung transplantation.This single-center prospective cohort study analyzed 220 lung transplant recipients who completed the 15-item Lung Transplant Valued Life Activities (LT-VLA) before and repeatedly after transplant. HRQL was assessed using generic, respiratory disease-specific, and utility measures. Associations between 0.3-point changes (the minimally important difference) in LT-VLA as a time-varying predictor on HRQL, CLAD, and mortality were tested using linear regression and Cox proportional hazard models. Models were adjusted for demographics, disease diagnosis, and post-operative lung function as a time-varying covariate.Participants were 45% female and 75% White, with a mean age of 56 (±12) years. Each 0.3-point improvement in LT-VLA was associated with substantially improved HRQL across all measures (adjusted p-values <0.01). Each 0.3-point improvement in LT-VLA was associated with a 13% reduced hazard of CLAD (adjusted HR: 0.87, 95% CI: 0.76–0.99, p=0.03) and a 19% reduced hazard of mortality (adjusted HR: 0.81, 95% CI: 0.67–0.95, p=0.01).Improvements in patient-reported physical functioning after lung transplantation are associated with improved HRQL and reduced risk of CLAD and death, independent of allograft function. The simplicity of the LT-VLA suggests it could be a valuable monitoring or outcome measure in both clinical and research settings.
Multi-species cryoEM calibration and workflow verification standard
Authors: Bobe Daija , Kopylov Mykhailo , Miller Jessalyn , Owji Aaron P. , Eng Edward T. 
Published: August 2024

AbstractCryogenic electron microscopy (cryoEM) is a rapidly growing structural biology modality that has been successful in revealing molecular details of biological systems. However, unlike established biophysical and analytical techniques with calibration standards, cryoEM has lacked comprehensive biological test samples. We introduce a cryoEM calibration sample that is a mixture of compatible macromolecules that can be used not only for resolution optimization but also provides multiple reference points for evaluating instrument performance, data quality, and image processing workflows in a single experiment. This combined test specimen provides researchers a reference point for validating their cryoEM pipeline, benchmarking their methodologies, and testing new algorithms.
Investigating cocaine- and abstinence-induced effects on astrocyte gene expression in the nucleus accumbens
Authors: Franklin Janay P. , Testen Anze , Mieczkowski Piotr A. , Hepperla Austin , Crynen Gogce , Simon Jeremy M. , Wood Jonathan D. , Harder Eden V. , Bellinger Tania J. , Witt Emily A. , Powell N. LaShae , Reissner Kathryn J. 
Published: August 2024

ABSTRACTIn recent years, astrocytes have been increasingly implicated in cellular mechanisms of substance use disorders (SUD). Astrocytes are structurally altered following exposure to drugs of abuse; specifically, astrocytes within the nucleus accumbens (NAc) exhibit significantly decreased surface area, volume, and synaptic colocalization after operant self-administration of cocaine and extinction or protracted abstinence (45 days). However, the mechanisms that elicit these morphological modifications are unknown. The current study aims to elucidate the molecular modifications that lead to observed astrocyte structural changes in rats across cocaine abstinence using astrocyte-specific RiboTag and RNA-seq, as an unbiased, comprehensive approach to identify genes whose transcription or translation change within NAc astrocytes following cocaine self- administration and extended abstinence. Using this method, our data reveal cellular processes including cholesterol biosynthesis that are altered specifically by cocaine self-administration and abstinence, suggesting that astrocyte involvement in these processes is changed in cocaine-abstinent rats. Overall, the results of this study provide insight into astrocyte functional adaptations that occur due to cocaine exposure or during cocaine withdrawal, which may pinpoint further mechanisms that contribute to cocaine-seeking behavior.
Unpacking the black box between market culture and innovation performance: the role of absorptive capacity and resistance to change
Authors: Kara Gizem , Turkcan Hulya , Imamoglu Salih Zeki , Ince Huseyin 
Published: August 2024

PurposeThis study aims to investigate the relationship between market culture and innovation performance and to reveal the role of absorptive capacity and resistance to change by building on the resource-based view.Design/methodology/approachData was gathered from 222 firm managers of manufacturing firms by using the survey method. Structural equation modeling and PROCESS macro were used to analyze the data.FindingsThe results indicate that market culture is positively related to innovation performance and absorptive capacity mediates this relationship. It is also found that resistance to change negatively moderates the relationship between market culture and innovation performance, but it has no moderating effect on the relationship between absorptive capacity and innovation performance.Originality/valuePrevious research examining the association between market culture and innovation performance is scarce and provides contradictory findings. This indicates that there is an underlying mechanism of this association neglected before. This study is an attempt to reconcile contradictory findings and enlighten the fuzzy areas of this relationship. Accordingly, this study focuses on absorptive capacity as a mediator and proves its role empirically. Moreover, this study is the first to examine the role of resistance to change and demonstrates its buffer role in the market culture-innovation performance link. It is also revealed that resistance to change does not moderate the relationship between absorptive capacity and innovation performance. The findings elucidate the underlying mechanism of the relationship between market culture and innovation performance, reconcile contradictory findings of extant research, expand the current knowledge, and provide practical implications.
Structural change and employment growth in India: reinterpreting “Manufacturing as an Engine of Growth”
Authors: Padhi Satya Prasad 
Published: August 2024

PurposeThe present paper aims to highlight how manufacturing expansions under conditions of increasing returns, which involve the growth of intermediate goods specializations, support advanced service employment. In addition, the increasing use of manufacturing products in services highlights additional, new service sector employment opportunities.Design/methodology/approachThis paper investigates (1) the manufacturing and service interactions and (2) the investment behaviour in manufacturing using Auto-Regressive Distributed lags (ARDL) and Vector Autoregressive (VAR) models. The models allow for different specifications to study whether investment behaviour in manufacturing supports dynamic manufacturing and service interactions.FindingsThe results underpin how Kaldorian manufacturing as an engine of growth is still relevant in Indian growth and is key to achieving higher advanced employment, export-orientation and services and manufacturing nexus outcomes. What matters, though, is that manufacturing investments are to be guided mainly by intermediate goods specializations. The slowdown of these specializations, explaining the slowdown of manufacturing investment, is therefore, a concern.Originality/valueA reinterpretation of manufacturing as an engine of growth in which primacy is given to investment behaviour in technical progress functions that can support the growth of specializations in manufacturing and such specialized service employment.
First Peoples economic landscape: analysis of the ecosystem
Authors: Jones Mark , Stanton Pauline , Rose Mark 
Published: August 2024

PurposeThis paper focuses on First Peoples Founders of for-profit entities in Australia and the role of the Indigenous Economic Development Agencies (IEDAs). We explore the challenges facing First Peoples enterprises, influenced by historical exclusion from white settler society, and the practices of the IEDAs from the perspectives of Founders and agencies.Design/methodology/approachA qualitative study utilising Indigenous Standpoint Theory and Indigenous research methods, elevating Founder perspectives, in the Yaruwu language - the Nilangany Ngarrungunil, owners of knowledge, to that of research collaborators.FindingsThe First Peoples economic landscape is continually evolving with IEDAs contributing to that evolution despite contentious identity ownership definitions. Founders secure in their own identity, are focused on self-determination and opportunities provided by IEDAs, government and corporate sector policies. However, opportunities are undermined by ongoing racism, discrimination and prevailing stereotypes leading to homogeneity, invisibility and exclusion. Founders question organisational commitments to overcoming systemic exclusion in particular their commitment to building respectful relationships and understanding First Peoples ways of working. Instead, Founders focus on building a sustainable First Peoples economic ecosystem through relationship-based practices rather than transactional reconciliation which ignores the reality of the lived experience of everyday racism.Originality/valueThis study extends the scholarly discourse on First Peoples for-profit enterprise success written with an Indigenous voice. We demonstrate how this Founder generation are strengthened by culture with identity infused in organisational practices underpinning their aspirations of economic self-determination.
Reproductive health rights: a bibliometric analysis of childbirth
Authors: Farizi Sofia Al 
Published: August 2024

Purpose
Reproductive health rights became an issue of interest long before the 1990s. Several policies were created to guarantee reproductive health rights, including birth rights. Women have the right to give birth in a way that is respectful and free from obstetric violence. Policymaking must, of course, be based on empirical evidence, so it is necessary to map studies on human rights in the context of childbirth. This study aims to investigate the viewpoint on human rights during childbirth across time by using a bibliometric methodology.

Design/methodology/approach
Bibliometric analysis was conducted using the VOSviewer application. The analysis was sourced from 301 articles on human rights during delivery for the 1976–2023 period from the Scopus database.

Findings
The studies concerning reproductive health rights encompass various topics, including reproductive health policy, human rights during childbirth, child marriage and human rights, pandemics and health care related to human rights.

Research limitations/implications
Studies related to human rights in reproductive health (especially childbirth) must be increased. Remember, policymaking must be based on the evidence found. Apart from that, empirical information about harmful actions during childbirth must be revealed so that it becomes a concern. While there has been a significant increase in the establishment of human rights during childbirth, there is a lack of research on this topic specifically in the Asian context. Researchers might consider this to be a matter of concern, given the implications for human rights. Two themes that have citations but a small number relate to obstetric violence and respectful maternity care during childbirth, so this could be a concern for other researchers for further studies.

Originality/value
This paper provides an overview of the most cited topics of human rights during childbirth, contributions by the distribution of studies throughout time, distribution of studies by country, the highest number of publications and citations.
How and when does perceived organizational politics undermine employee performance? Examination through the lens of opportunistic silence in Indian HPDOs
Authors: Randev Kadumbri Kriti , Jha Jatinder Kumar , Shukla Keerti 
Published: August 2024

PurposeThe main aim of this paper is to explore the influence mechanisms of perceived organizational politics (POP) on employee performance (EP). Drawing on the job demands-resources theory (JD-R), this paper investigates opportunistic silence (OS) as a mediating factor and job level as a moderating effect in the POP-OS-performance relationship.Design/methodology/approachThis study’s data were collected from 203 employees working in Indian high-power distance organizations (HPDOs), such as the military, police and security forces. Mediation and moderation analysis were conducted using PLS-SEM, and the moderated mediation index was calculated using Hayes PROCESS Macro.FindingsThe results indicate that OS fully mediates the POP-performance relationship – specifically, POP as a job demand activates OS, which acts as an energy/resource depleting mechanism and further deteriorates task performance. Interestingly, the overall negative influence of POP and OS on EP was stronger for employees at lower job levels than those at senior job levels.Originality/valueThis paper offers a unique set of findings that enrich the understanding of factors responsible for employees’ performance in the highly political environments of HPDOs. By using the lens of JD-R theory, this paper draws attention towards the tendency of employees to indulge in self-serving behaviours like OS in politically charged contexts which is detrimental to their performance and may also undermine overall organization’s productivity. Furthermore, this paper also highlights the conditional effects exerted by job level in the unique nexus of POP, OS and EP.