bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dexamethasone Upregulates the Expression of the Human SLC26A3 (DRA, Down-Regulated in Adenoma) Transporter (an IBD Susceptibility Gene) in Intestinal Epithelial Cells and Attenuates Gut Inflammation
Authors: Kumar Anoop , Husain Nazim , Anbazhagan Arivarasu N , Jayawardena Dulari , Priyamvada Shubha , Singhal Megha , Jain Charu , Kaur Prabhdeep , Guzman Grace , Saksena Seema , Dudeja Pradeep K 
Published: December 2024

Abstract

Background
Down-Regulated in Adenoma (DRA) plays a critical role in intestinal chloride absorption and a decrease in its expression is a key event in diarrheal disorders. Recently, DRA has emerged as an Inflammatory Bowel Disease (IBD) susceptibility gene. Therefore, the strategies to upregulate DRA expression are potentially novel approaches to not only treat IBD-associated diarrhea but also gut inflammation. In this study, the effect of dexamethasone (DEX), an anti-inflammatory corticosteroid on DRA expression was investigated.

Methods
GR (glucocorticoid receptor) overexpressed Caco-2 cells and C57BL/6/J mice and anti-αIL-10R mAb model of IBD were used. Protein expression was assessed by immunoblotting and immunofluorescence. Transcript levels were assessed by quantative-real-time polymerase chain reaction (qRT-PCR) and promoter activity was measured by luciferase assays.

Results
Our results showed that DEX significantly increased DRA mRNA and protein expression in GR overexpressing Caco-2 cells. DEX-induced upregulation of DRA was GR dependent and appeared at least in part to occur via a transcriptional mechanism, as promoter activity of the DRA construct (−1183/+114 bp) was significantly increased in response to DEX. The increase in DRA mRNA was abrogated in the presence of MKP-1 inhibitor, triptolide. Administration of DEX (2 mg/kg body weight) to mice for 24 and 48 hours significantly increased the DRA expression in mouse colon. DEX treatment to mice for 7 days in the αIL-10R mAb model of colitis was able to significantly attenuate the gut inflammation and associated decrease in DRA expression.

Conclusions
We demonstrate that DEX stimulates DRA expression via transcriptional mechanisms and suggest that upregulation of DRA may contribute to both anti-inflammatory and pro-absorptive effects of DEX.
Community pharmacists’ readiness for minor ailment services in Saudi Arabia: a cross-sectional study of perceptions, barriers, and facilitators
Authors: Alzahrani Fahad , Khairi Nosaiba B , Alattas Baraah O , Alrehaili Toqa H , Aljehani Ghadeer S , Alahmadi Renad B , Refi Dalia Mohammed , Aljohani Lama S , Fadil Haifa Abdulrahman , Alnezary Faris S , Al Thaqfan Sultan S 
Published: December 2024

Abstract

Objectives
Minor ailments are a significant burden on primary care services globally. In Saudi Arabia’s evolving healthcare landscape, pharmacists play a crucial informal role, but no coordinated national approach exists. Understanding pharmacists’ preparedness is thus vital to optimize successful integration. This study evaluated Saudi community pharmacists’ perceptions, barriers, and facilitators related to minor ailment services (MAS) for capacity-building strategies.

Methods
A cross-sectional survey was conducted from April to July 2023. Data were collected from participants using a self-administered, anonymous questionnaire with 48 questions. The data were analyzed using descriptive and inferential statistics in SPSS v.27.

Key findings
Of the 720 pharmacists invited to participate, 442 completed the questionnaire, yielding an overall response rate of 61.4% (442/720). Most pharmacists recognized the value of accessible self-care support using their skills (92.6%), but 26.9% feared misdiagnosis risks. Most (93.9%) emphasized prudent triage and history-taking, and yet 22.2% were ambivalent on referrals. Key barriers that were identified included the lack of patient information (71.5%), lack of reimbursement for MAS (61.8%), lack of a private/counseling area (59.5%), and lack of knowledge for minor ailment management (48.2%). Pharmacists who work in rural areas, work part-time, and have not attended any training or education programs also tend to display a more uncertain attitude toward delivering services for minor ailments.

Conclusions
Pharmacists in Saudi Arabia can play a significant role in managing minor ailments, but the identified barriers must be addressed to integrate their services thoroughly. That can be done through comprehensive training, allocating resources, and establishing structured communication and referral pathways. This integration can improve healthcare accessibility, reduce costs, and better utilize pharmacists’ expertise for delivering patient care.
Rational Weighted Projective Hypersurfaces
Authors: Esser Louis 
Published: December 2024

Abstract
A very general hypersurface of dimension $n$ and degree $d$ in complex projective space is rational if $d \leq 2$, but is expected to be irrational for all $n, d \geq 3$. Hypersurfaces in weighted projective space with degree small relative to the weights are likewise rational. In this paper, we introduce rationality constructions for weighted hypersurfaces of higher degree that provide many new rational examples over any field. We answer in the affirmative a question of Okada about the existence of very general terminal Fano rational weighted hypersurfaces in all dimensions $n \geq 6$.
Evaluation of joint external evaluation to COVID-19 and other infectious diseases mortality outcomes in 96 countries
Authors: Lee Yuri , Kim Siwoo , Lee Sieun , Kim Min Kyung , Gostin Lawrence O , Oh Juhwan 
Published: December 2024

Abstract

Background
This study evaluated the effectiveness of Joint External Evaluation (JEE) scores with regard to coronavirus disease 2019 (COVID-19) and other infectious diseases performance in 96 countries. To propose a revised JEE tool, potential JEE indicators were also examined.

Methods
JEE data from 2016–2019 were linked with outcomes such as COVID-19 fatality rates and infections, as well as mortality rates for other infectious diseases. We also examined potential indicators such as the Sustainable Development Goals (SDGs) and Universal Health Coverage index to propose enhancements to the JEE tool. Multiple regression analysis was used to assess these associations.

Results
The average JEE score was 2.70 (SD=0.92) in 96 countries. Detection capabilities received the highest average score (3.23), while the other areas (2.30) section received the lowest scores. However, the analysis revealed that the JEE tool had limited predictive accuracy for COVID-19 outcomes. By contrast, the JEE scores showed a negative association with the performance of other infectious diseases. Notably, SDGs 2 (zero hunger), 4 (quality education) and 8 (decent work and economic growth) were strongly associated with better COVID-19 outcomes.

Conclusion
The JEE scores showed limited predictive value for COVID-19 mortality outcomes in 96 countries. The tool offers insights into health security, but needs revision to better handle future pandemics.
Virophage infection mode determines ecological and evolutionary changes in a host-virus-virophage system
Authors: del Arco Ana , Becks Lutz 
Published: December 2024

Abstract
Giant viruses can control their eukaryotic host populations, shaping the ecology and evolution of aquatic microbial communities. Understanding the impact of the viruses’ own parasites, the virophages, on the control of microbial communities remains a challenge. Most virophages have two modes of infection. They can exist as free particles coinfecting host cells together with the virus, where they replicate while inhibiting viral replication. Virophages can also integrate into the host genome, replicate through host cell division and remain dormant until the host is infected with a virus, leading to virophage reactivation and replication without inhibiting viral replication. Both infection modes (reactivation vs. coinfection) occur within host-virus-virophage communities, and their relative contributions are expected to be dynamic and context dependent. The consequences of this dynamic regime for ecological and evolutionary dynamics remain unexplored. Here, we test whether and how the relative contribution of virophage infection modes influences the ecological dynamics of an experimental host-virus-virophage system and the evolutionary responses of the virophage. We indirectly manipulated the level of virophage (Mavirus) integration into the host (Cafeteria burkhardae) in the presence of the giant Cafeteria roenbergensis virus. Communities with higher virophage integration were characterized by lower population densities and reduced fluctuations in host and virus populations, whereas virophage fluctuations were increased. The virophage evolved toward lower inhibition and higher replication, but the evolution of these traits was weaker with higher virophage integration. Our study shows that differences in the virophage infection modes contributes to the complex interplay between virophages, viruses and hosts.
Ceftolozane/tazobactam disrupts Pseudomonas aeruginosa biofilms under static and dynamic conditions
Authors: Kostoulias Xenia , Fu Ying , Morris Faye C , Yu Crystal , Qu Yue , Chang Christina C , Blakeway Luke , Landersdorfer Cornelia B , Abbott Iain J , Wang Lynn , Wisniewski Jessica , Yu Yunsong , Li Jian , Peleg Anton Y 
Published: December 2024

Abstract

Background
Pseudomonas aeruginosa biofilms limit the efficacy of currently available antibacterial therapies and pose significant clinical challenges. Pseudomonal biofilms are complicated further when other markers of persistence such as mucoid and hypermutable phenotypes are present. There is currently a paucity of data regarding the activity of the newer β-lactam/β-lactamase inhibitor combination ceftolozane/tazobactam against P. aeruginosa biofilms.

Methods
We evaluated the efficacy of ceftolozane/tazobactam against clinical P. aeruginosa isolates, the laboratory isolate PAO1 and its isogenic mutS-deficient hypermutator derivative (PAOMS) grown under static and dynamic biofilm conditions. The clinical isolate collection included strains with mucoid and hypermutable phenotypes.

Results
Ceftolozane/tazobactam exposure led to a bactericidal (≥3 log cfu/cm2) biofilm reduction in 15/18 (83%) clinical isolates grown under static conditions, irrespective of carbapenem susceptibility or mucoid phenotype, with greater activity compared with colistin (P &lt; 0.05). Dynamically grown biofilms were less susceptible to ceftolozane/tazobactam with active biofilm reduction (≥1 log cfu/cm2) observed in 2/3 isolates. Hypermutability did not affect the antibiofilm efficacy of ceftolozane/tazobactam in either static or dynamic conditions when comparing PAO1 and PAOMS. Consistent with the activity of ceftolozane/tazobactam as a potent inhibitor of PBP3, dramatic impacts on P. aeruginosa morphology were observed.

Conclusions
Our data demonstrate that ceftolozane/tazobactam has encouraging properties in the treatment of P. aeruginosa biofilm infections, and its activity is not diminished against mucoid or hypermutable variants at the timepoints examined.
Threshold and Spatial Effects of Fiscal Policy on Business Cycle Synchronisation in the Economic Community of West African States
Authors: Diendere Louis-Joel B , Diendere Achille A , Eggoh Jude 
Published: December 2024

Abstract
This research analyses the threshold effects of fiscal policy on business cycle synchronisation in the Economic Community of West African States (ECOWAS). The main contribution is the analysis of the effects of respecting versus not respecting deficit and debt thresholds on the synchronisation of business cycles through the creation of binary variables. The study covers the period 1990–2020 and fourteen ECOWAS countries. The results show that the optimal pro-growth thresholds for the budget deficit and debt are 5.559% and 45.61% of GDP, respectively. Furthermore, spatial analysis reveals significant positive spatial spillover effects of respecting these thresholds on synchronising business cycles within ECOWAS. The current convergence criterion of −3% for the budget balance is favourable for growth and business cycle convergence. In addition, the current debt convergence criterion of 70% of GDP could be adjusted. Our results suggest the need to strengthen revenue mobilisation, harmonise taxation and improve the monitoring of fiscal standards.
Soybean isoflavone promotes milk yield and milk fat yield through the ERα-mediated Akt/mTOR pathway in dairy goats
Authors: Shao Yuexin , Huang Jiangtao , Wei Manhong , Fan Liaoyu , Shi Huaiping , Shi Hengbo 
Published: December 2024

Abstract
Soybean isoflavone (SIF) in soybeans are natural phytoestrogens, which is functioned as an estrogen agonistic or antagonistic. SIF regulates the capacity of animals to synthesize triacylglycerols by directly utilizing long-chain fatty acids. However, few studies have focused on its regulatory lipid metabolism in lactating dairy goats. The objective of this study was to investigate the influence of SIF on milk yield and composition using Saanen dairy goats as a model, employing both in vivo and in vitro approaches. In the in vivo phase, a total of 20 goats were randomly divided into 2 groups: the control group fed a basal diet, and the experimental group fed a basal diet supplemented with SIF at a dosage of 100 mg/d. The results underscored a significant elevation in serum estrogen and prolactin levels in the SIF-supplemented group (P &lt; 0.05). Notably, SIF supplementation also displayed a higher milk fat percentage (P = 0.03). Transitioning to in vitro experimentation, the addition of SIF (75 µM) to goat mammary epithelial cells exhibited a pronounced effect on cell proliferation. It spurred cell proliferation and led to an increase in triacylglycerol levels (P &lt; 0.05). Consistently, SIF showcased an enhancement in the expression of key genes associated with milk fat de novo synthesis. SIF demonstrated a rescuing effect on the suppressive impact of MK2206 on Akt protein phosphorylation. Importantly, the study observed that the knockdown of estrogen receptor alpha (ERα) expression completely counteracted the effect of SIF on lipid droplet accumulation. Collectively, the current study establishes the critical role of SIF in process of fatty acid de novo in the goat mammary gland. This regulation is notably mediated through the ERα-Akt axis, thus enriching our understanding of this intricate biological process. This research sheds light on the potential benefits of SIF supplementation in dairy goat farming, ultimately contributing to improved milk production and quality.
Management of multiple vertebral fractures during lactation in a patient with osteogenesis imperfecta type I following twin delivery
Authors: Ng Chrislyn , Trinh Anne , Zebaze Roger , Shore-Lorenti Cat , Ebeling Peter R , Milat Frances 
Published: December 2024

Abstract
Osteogenesis imperfecta (OI) is an uncommon bone disorder caused by mutations in type I collagen involved in bone matrix leading to increased fracture risk. There are several sub-categories within OI, with OI type I being the most common and mildest form. Women with OI considering pregnancy need to be aware of bone loss and fracture risk, particularly with lactation. We report the first case of a female with twin pregnancy and OI type I who presented with multiple vertebral fractures following delivery and postpartum lactation. Following endocrine review, she weaned breast-feeding but represented within weeks with further pain and magnetic resonance imaging (MRI) demonstrating new T12 and L1 fractures. Even after receiving intravenous zoledronic acid, she experienced further thoracic pain after lifting, and MRI demonstrated a further T7 fracture. Following modification of her treatment regimen to daily teriparatide injections for 12 months, repeat dual-energy X-ray absorptiometry scan showed a significant improvement in bone mineral density at the lumbar spine and left hip. Bone loss with lactation is an important consideration for women with OI considering pregnancy. Women with OI should be assessed by an endocrinologist prior to conception to optimize bone health and have an individualized plan to mitigate bone loss and fracture risk during pregnancy and the postpartum period.
Establishing Neurorights: New Rights versus Derived Rights
Authors: Istace Timo 
Published: December 2024

Abstract
The way in which neurotechnology interferes with the human mind by enabling reverse inferences of mental states and alterations of mental processes, is a source of significant concern. Both human rights scholars and international and regional human rights institutions are actively examining which human rights safeguards are needed to address these concerns and protect the human mind. Central to this exploration is the question of how human rights law should formally establish these safeguards: through the introduction of neurorights as new stand-alone human rights, or by deriving neurorights form existing rights? This article seeks to contrast arguments in favour and against both strategies, to inform a substantiated choice for the preferable option. To this end, the article will first outline the origins of the neurorights debate. Subsequently, it will elaborate on the two identified approaches to establishing neurorights. Thereafter, both approaches will be assessed on their merits, focussing on the general criteria of ‘need’ and ‘feasibility’. Based on this evaluation, the article identifies the Derivation Approach as the preferable path forward. The need for new, stand-alone rights is insufficiently established, whereas deriving neurorights from existing rights provides clearer and more coherent safeguards, and encounters fewer political challenges.
The value of a nomogram based on 18F-FDG PET/CT metabolic parameters and metabolic heterogeneity in predicting distant metastasis in gastric cancer
Authors: Zhang Guanjie , Shi Aiqi , Ding Xiaofang , Wang Jianlin 
Published: December 2024

Abstract

Objective
To investigate the value of metabolic parameters and metabolic heterogeneity from pretreatment deoxy-2-[fluorine-18]-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting distant metastasis in gastric cancer.

Methods
Eighty-six patients with pathologically confirmed gastric adenocarcinoma were included in this study. All patients underwent a whole-body 18F-FDG PET/CT scan before treatment. Clinicopathologic and imaging data were collected, including metabolic parameters such as maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary gastric cancer lesions. Heterogeneity index (HI)-1 was expressed as the absolute value of the linear regression slopes between the MTVs at different SUVmax thresholds (40% × SUVmax, 80% × SUVmax), while HI-2 was expressed as the difference between SUVmax and SUVmean. Patients were randomly divided into training and validation cohorts at a 7:3 ratio. The correlation between the above parameters and distant metastasis in gastric cancer was analyzed using the training cohort. A nomogram prediction model was then established and later verified with the validation cohort. Finally, decision curve analysis was used to evaluate the clinical utility of the model.

Results
This study included 86 patients with gastric cancer, with 60 (69.8%) in the training cohort and 26 (30.2%) in the validation cohort. There was no significant difference in the balanced comparison between both cohorts (all P &gt; .05). Among all patients, 31 (36.0%) developed distant metastasis, while 55 (64.0%) did not. In patients who developed distant tumor metastasis, carcinoembryonic antigen, carbohydrate antigen (CA)12–5, CA19–9, CA72–4, MTV, TLG, and HI-1 were significantly higher than in patients without distant metastasis (all P &lt; .05). Multivariate logistic regression analysis identified CA72–4 (OR: 1.151, 95% CI: 1.020–1.300, P = .023) and HI-1 (OR: 1.647, 95% CI: 1.063–2.553, P = .026) as independent risk factors for predicting distant metastasis in gastric cancer. The nomogram constructed from this analysis exhibited high predictive efficacy in the training (AUC: 0.874, 95% CI: 0.766–0.983) and validation (AUC: 0.915, 95% CI: 0.790–1.000) cohorts, providing a net clinical benefit for patients.

Conclusion
HI-1 is an independent risk factor for predicting distant metastasis in gastric cancer. A comprehensive prediction model combining HI-1 with the tumor marker CA72–4 can increase the net clinical benefit for patients.
Protection From COVID-19 Vaccination and Prior SARS-CoV-2 Infection Among Children Aged 6 Months–4 Years, United States, September 2022–April 2023
Authors: Feldstein Leora R , Ruffin Jasmine , Wiegand Ryan , Grant Lauren , Babu Tara M , Briggs-Hagen Melissa , Burgess Jefferey L , Caban-Martinez Alberto J , Chu Helen Y , Ellingson Katherine D , Englund Janet A , Hegmann Kurt T , Jeddy Zuha , Kuntz Jennifer , Lauring Adam S , Lutrick Karen , Martin Emily T , Mathenge Clare , Meece Jennifer , Midgley Claire M , Monto Arnold S , Naleway Allison L , Newes-Adeyi Gabriella , Odame-Bamfo Leah , Olsho Lauren E W , Phillips Andrew L , Rai Ramona P , Saydah Sharon , Smith Ning , Tyner Harmony , Vaughan Molly , Weil Ana A , Yoon Sarang K , Britton Amadea , Gaglani Manjusha 
Published: December 2024

Abstract
To understand how coronavirus disease 2019 vaccines impact infection risk in children &lt;5 years, we assessed risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from September 2022 to April 2023 in 3 cohort studies. There was no difference in risk by vaccination status. While vaccines reduce severe disease, they may not reduce SARS-CoV-2 infections in naïve young children.
It’s about time: revisiting reciprocity and triadicity in relational event analysis
Authors: Juozaitienė Rūta , Wit Ernst C 
Published: December 2024

Abstract
Societies are intricate systems comprising interdependent social actors interconnected through diverse relationships. It has long been recognized that reciprocity and triadic closure are two fundamental components of this interdependence, and have as such been included in social network models. However, computational limitations and modelling complexity have meant that reciprodicity and triadic closure statistics included in such models have necessarily been simplified. Using novel computational and modelling approaches in relational event analysis, the aim of this paper is to explore a spectrum of endogenous network effect definitions, ranging from straightforward binary variables to complex, temporal functions accounting for the diminishing relevance of past events. Through simulation studies and real-world dataset analyses, it highlights the importance of comprehensively considering temporal dynamics and subtle assumptions in defining network effects. Neglecting these aspects can lead to significant pitfalls in the analysis. Fundamentally, the paper highlights the time-varying nature of reciprocity and triadic closure effects evident in empirical datasets. While exponential decay functions sometimes capture their temporal structure, more complex continuous functions of time often describe the intricate structure of both effects more precisely.