bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep behavioural phenotyping of the Q175 Huntington disease mouse model: effects of age, sex, and weight
Authors: Koch Ellen T. , Cheng Judy , Ramandi Daniel , Sepers Marja D. , Hsu Alex , Fong Tony , Murphy Timothy H. , Yttri Eric , Raymond Lynn A. 
Published: May 2024

Abstract
Background
Huntington disease (HD) is a neurodegenerative disorder with complex motor and behavioural manifestations. The Q175 knock-in mouse model of HD has gained recent popularity as a genetically accurate model of the human disease. However, behavioural phenotypes are often subtle and progress slowly in this model. Here, we have implemented machine-learning algorithms to investigate behaviour in the Q175 model and compare differences between sexes and disease stages. We explore distinct behavioural patterns and motor functions in open field, rotarod, water T-maze, and home cage lever-pulling tasks.

Results
In the open field, we observed habituation deficits in two versions of the Q175 model (zQ175dn and Q175FDN, on two different background strains), and using B-SOiD, an advanced machine learning approach, we found altered performance of rearing in male manifest zQ175dn mice. Notably, we found that weight had a considerable effect on performance of accelerating rotarod and water T-maze tasks and controlled for this by normalizing for weight. Manifest zQ175dn mice displayed a deficit in accelerating rotarod (after weight normalization), as well as changes to paw kinematics specific to males. Our water T-maze experiments revealed response learning deficits in manifest zQ175dn mice and reversal learning deficits in premanifest male zQ175dn mice; further analysis using PyMouseTracks software allowed us to characterize new behavioural features in this task, including time at decision point and number of accelerations. In a home cage-based lever-pulling assessment, we found significant learning deficits in male manifest zQ175dn mice. A subset of mice also underwent electrophysiology slice experiments, revealing a reduced spontaneous excitatory event frequency in male manifest zQ175dn mice.

Conclusions
Our study uncovered several behavioural changes in Q175 mice that differed by sex, age, and strain. Our results highlight the impact of weight and experimental protocol on behavioural results, and the utility of machine learning tools to examine behaviour in more detailed ways than was previously possible. Specifically, this work provides the field with an updated overview of behavioural impairments in this model of HD, as well as novel techniques for dissecting behaviour in the open field, accelerating rotarod, and T-maze tasks.
Role of LsrR in the regulation of biofilm formation in mammary pathogenic Escherichia coli
Authors: Xu Li , Wang Wei , Zhang Xin , Ma Kai , Wang Hui , Xue Ting 
Published: May 2024

Abstract
Background
Mammary Pathogenic Escherichia coli (MPEC) is an important pathogen that can escape the attack of the host immune system through biofilm formation and proliferate in the mammary gland continuously, resulting in mastitis in cows and causing enormous economic losses. As an effector of AI-2 quorum sensing, LsrR extensively affects the expression levels of hundreds of genes related to multiple biological processes in model E. coli strain. However, the regulatory role of LsrR in MPEC and whether it is involved in pathogenesis has been seldom reported.

Results
In this study, the function of LsrR in strain MPEC5, obtained from a milk sample in dairy cows with mastitis, was investigated by performing high-throughput sequencing (RNA-seq) assays. The results revealed that LsrR down-regulated the transcript levels of fimAICDFGH (encoding Type 1 pili), which have been reported to be associated with biofilm formation process. Biofilm assays confirmed that deletion of lsrR resulted in a significant increase in biofilm formation in vitro. In addition, electrophoretic mobility shift assay (EMSA) provided evidence that LsrR protein could directly bind to the promoter regions of fimAICDFGH in a dose-dependent manner.

Conclusions
These results indicate that LsrR protein inhibits the biofilm formation ability of MPEC5 by directly binding to the fimAICDFGH promoter region. This study presents a novel clue for further exploration of the prevention and treatment of MPEC.
The Interleukin-6 gene variants may protect against SARS-CoV-2 infection and the severity of COVID-19: a case-control study in a Moroccan population
Authors: Noureddine Rachid , Baba Hanâ , Aqillouch Safaa , Abounouh Karima , Laazaazia Oumaima , Elmessaoudi-Idrissi Mohcine , Bahmani Fatima Zohra , Tanouti Ikram Allah , Ouladlahsen Ahd , Sarih M’hammed , Dehbi Hind , Ezzikouri Sayeh 
Published: May 2024

AbstractThe symptoms of SARS-CoV-2 infection vary widely, ranging from asymptomatic cases to severe forms marked by acute respiratory distress syndrome, multi-organ damage, and fatalities. Studies indicate a correlation between specific genes and susceptibility to SARS-CoV-2 infection and disease severity, particularly involving variants in genes linked to inflammation and immune responses. The objective of this study is to investigate the association between rs1800795 (− 174 G > C) and rs1800797 (− 597 A > G) variants in the interleukin-6 (IL-6) promoter region and susceptibility to SARS-CoV-2 infection. Additionally, we aim to explore their correlation with COVID-19 severity in a Moroccan population. In this case-control study, we enrolled 270 unvaccinated COVID-19 patients, consisting of 132 with severe COVID-19 and 138 with asymptomatic-moderate COVID-19. Additionally, we included 339 SARS-CoV-2-negative group. Genotyping of rs1800795 and rs1800797 polymorphisms of the IL-6 gene was performed using predesigned TaqMan SNP genotyping. The median age of SARS-CoV-2-negative controls was 50 years, while severe COVID-19 cases exhibited a median age of 61 years. Additionally, individuals with asymptomatic to moderate COVID-19 had a median age of 36 years. We observed a significant age difference between severe and mild COVID-19 patients (p < 0.0001), and an association was noted between gender and the severity of COVID-19 (p = 0.011). The allele and genotype frequencies of the IL-6 − 597G > A and − 174G > C variants did not show significant associations with susceptibility to SARS-CoV-2 infection (p > 0.05). However, further analysis revealed that the linkage disequilibrium between rs1800797 and rs1800795 indicated that individuals with the GC* haplotype (OR = 0.04, 95% CI 0.01–0.30, p = 0.001) and AG* haplotype (OR = 0.11, 95% CI 0.03–0.46, p = 0.002) were significantly associated with protection against SARS-CoV-2 infection. Moreover, in the overdominant model, the IL-6 − 174 G/C genotype was found to be protective against the development of severe disease compared to those with the G/G-C/C genotypes (p = 0.03; OR = 0.41, 95% CI 0.18–0.96). However, correlations between complete blood count markers, hematological markers, D-dimer, C-reactive protein, and ferritin levels according to − 597 A > G and − 174G > C genotypes showed no significant differences (all p > 0.05). Our findings provide valuable insights into the pathogenesis of COVID-19, suggesting that genetic variations at the IL-6 gene may contribute to the susceptibility to severe SARS-CoV-2 infection within the Moroccan population.
A novel functionalized CuTi hybrid nanocomposites: facile one-pot mycosynthesis, characterization, antimicrobial, antibiofilm, antifouling and wastewater disinfection performance
Authors: Almahdy Asmaa G. , El-Sayed Ahmed , Eltarahony Marwa 
Published: May 2024

Abstract
Background
The continuous progress in nanotechnology is rapid and extensive with overwhelming futuristic aspects. Through modernizing inventive synthesis protocols, a paradigm leapfrogging in novelties and findings are channeled toward fostering human health and sustaining the surrounding environment. Owing to the overpricing and jeopardy of physicochemical synthesizing approaches, the quest for ecologically adequate schemes is incontestable. By developing environmentally friendly strategies, mycosynthesis of nanocomposites has been alluring.

Results
Herein, a novel architecture of binary CuO and TiO2 in nanocomposites form was fabricated using bionanofactory Candida sp., for the first time. For accentuating the structural properties of CuTi nanocomposites (CuTiNCs), various characterization techniques were employed. UV-Vis spectroscopy detected SPR at 350 nm, and XRD ascertained the crystalline nature of a hybrid system. However, absorption peaks at 8, 4.5, and 0.5 keV confirmed the presence of Cu, Ti and oxygen, respectively, in an undefined assemblage of polygonal-spheres of 15–75 nm aggregated in the fungal matrix of biomolecules as revealed by EDX, SEM and TEM. However, FTIR, ζ-potential and TGA reflected long-term stability (− 27.7 mV) of self-functionalized CuTiNCs. Interestingly, a considerable and significant biocide performance was detected at 50 µg/mL of CuTiNCs against some human and plant pathogens, compared to monometallic counterparts. Further, CuTiNCs (200 µg/mL) ceased significantly the development of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans biofilms by 80.3 ± 1.4, 68.7 ± 3.0 and 55.7 ± 3.0%, respectively. Whereas, 64.63 ± 3.5 and 89.82 ± 4.3% antimicrofouling potentiality was recorded for 100 and 200 µg/ml of CuTiNCs, respectively; highlighting their destructive effect against marine microfoulers cells and decaying of their extracellular polymeric skeleton as visualized by SEM. Moreover, CuTiNCs (100 and 200 µg/ml) exerted significantly outstanding disinfection potency within 2 h by reducing the microbial load (i.e., total plate count, mold & yeast, total coliforms and faecal Streptococcus) in domestic and agricultural effluents reached >50%.

Conclusion
The synergistic efficiency provided by CuNPs and TiNPs in mycofunctionalized CuTiNCs boosted its recruitment as antiphytopathogenic, antibiofilm, antimicrofouling and disinfectant agent in various realms.
Towards malaria elimination: a reflection about digital notification modules to improve malaria cases notification speed and follow-up in the Brazilian Amazon region
Authors: Garcia Klauss Kleydmann Sabino , Rodovalho Sheila Rodrigues , Siqueira André M. 
Published: May 2024

Abstract
Background
Health information systems (HIS) are a pivotal element in epidemiological surveillance. In Brazil, malaria persists as a public health challenge, with 99% of its occurrences concentrated in the Amazon region, where cases are reported through the HIS Sivep-Malaria. Recent technological advancements indicate that case notifications can be expedited through more efficient systems with broader coverage. The objective of this study is to analyse opportunities for notification within Sivep-Malaria and explore the implementation of mobile electronic devices and applications to enhance the performance of malaria case notifications and use.

Methods
This descriptive study analyses data on malaria-positive cases in the Brazilian Amazon from 2004 to 2022. Malaria Epidemiological Surveillance System (Sivep-Malaria) data were used. The Brazilian Amazon region area is approximately 5 million km2 across nine different states in Brazil. Data entry opportunities were assessed by considering the time difference between the 'date of data entry' and the 'date of notification.' Descriptive statistics, including analyses of means and medians, were conducted across the entire Amazon region, and for indigenous population villages and gold mining areas.

Results
Between 2004 and 2022, 6,176,878 new malaria cases were recorded in Brazil. The average data entry opportunity throughout the period was 17.9 days, with a median of 8 days. The most frequently occurring value was 1 day, and 99% of all notifications were entered within 138 days, with 75.0% entered within 20 days after notification. The states with the poorest data entry opportunities were Roraima and Tocantins, with averages of 31.3 and 31.0 days, respectively. For indigenous population villages and gold mining areas, the median data entry opportunities were 23 and 15 days, respectively.

Conclusions
In malaria elimination, where surveillance is a primary strategy for evaluating each reported case, reducing notification time, enhancing data quality and being able to follow-up cases through computerized reports offer significant benefits for cases investigation. Technological improvements in Sivep-Malaria could yield substantial benefits for malaria control in Brazil, aiding the country in achieving disease elimination and fulfilling the Sustainable Development Goals.
Discrimination, disadvantage and disempowerment during COVID-19: a qualitative intrasectional analysis of the lived experiences of an ethnically diverse healthcare workforce in the United Kingdom
Authors: Gogoi Mayuri , Qureshi Irtiza , Chaloner Jonathan , Al-Oraibi Amani , Reilly Holly , Wobi Fatimah , Agbonmwandolor Joy Oghogho , Ekezie Winifred , Hassan Osama , Lal Zainab , Kapilashrami Anuj , Nellums Laura , Pareek Manish ,   on behalf of the UK-REACH Study Collaborative Group Members, Gray Laura , Guyatt Anna L , Johns Catherine , McManus Chris I , Woolf Katherine , Abubakar Ibrahim , Gupta Amit , Abrams Keith R , Tobin Martin D , Wain Louise , Carr Sue , Dove Edward , Khunti Kamlesh , Ford David , Free Robert 
Published: May 2024

Abstract
Background
Healthcare workers (HCWs) in the United Kingdom (UK) have faced many challenges during the COVID-19 pandemic, some of these arising out of their social positions. Existing literature explicating these challenges (e.g., lack of appropriate PPE, redeployment, understaffing) have highlighted inequities in how these have been experienced by HCWs based on ethnicity, gender or, job role. In this paper, we move a step ahead and examine how the intersection of these social positions have impacted HCWs’ experiences of challenges during the pandemic.

Methods
We collected qualitative data, using interviews and focus groups, from 164 HCWs from different ethnicities, gender, job roles, migration statuses, and regions in the United Kingdom (UK) between December 2020 and July 2021. Interviews and focus groups were conducted online or by telephone, and recorded with participants’ permission. Recordings were transcribed and a hybrid thematic analytical approach integrating inductive data-driven codes with deductive ones informed by an intersectional framework was adopted to analyse the transcripts.

Results
Thematic analysis of transcripts identified disempowerment, disadvantage and, discrimination as the three main themes around which HCWs’ experiences of challenges were centred, based on their intersecting identities (e.g., ethnicity gender, and/or migration status). Our analysis also acknowledges that disadvantages faced by HCWs were linked to systemic and structural factors at the micro, meso and macro ecosystemic levels. This merging of analysis which is grounded in intersectionality and considers the ecosystemic levels has been termed as ‘intrasectionalism’.

Discussion
Our research demonstrates how an intrasectional lens can help better understand how different forms of mutually reinforcing inequities exist at all levels within the healthcare workforce and how these impact HCWs from certain backgrounds who face greater disadvantage, discrimination and disempowerment, particularly during times of crisis like the COVID-19 pandemic.
Navigating the nexus between British Columbia’s public consumption and decriminalization policies of illegal drugs
Authors: Ali Farihah , Law Justine , Russell Cayley , Crépault Jean-Francois , Goulão João Castel-Branco , Lock Kurt , Rehm Jürgen 
Published: May 2024

AbstractIn January 2023, the province of British Columbia (BC) decriminalized the possession of certain illegal drugs for personal use. The province’s primary intent was to reduce the stigma associated with drug use, as well as barriers for people who use drugs (PWUD) to access treatment and supports. However, less than ten months into the decriminalization policy, due to growing concerns about public safety voiced by municipal governments and communities, the provincial government made amendments to the policy to ban the public consumption of illicit drugs in additional locations, and subsequently introduced additional legislation, Bill 34, aimed at regulating public consumption of drugs in public spaces. Some communities have also implemented local bylaws similarly regulating public drug use. Bill 34 and local bylaws may serve as tools to promote community health and safety and minimize direct and indirect harms associated with public drug use. However, such legislation may re-criminalize PWUD and reinforce negative perceptions surrounding drug use, especially if these policies are not paired with strategies to expand the availability and accessibility of critical harm reduction and housing services. Without ample access to these services, limitations on public drug use can potentially displace individuals to areas where they are more likely to use alone, further exposing them to substance use-related harms, and undermining the goals of decriminalization. The potential effects of these restrictions may also disproportionately impact marginalized populations. As of April 2024, Bill 34 remains on hold. Moving forward, it will be important to monitor this bill, as well as other public consumption bylaws and legislation, and their impact on BC’s overall decriminalization initiative. Decision-makers are urged to increase engagement with PWUD and relevant stakeholders in the design and implementation of policies pertaining to public consumption to ensure that they effectively address the evolving needs and realities of PWUD, and align with decriminalization goals.
An association between elevated telomerase reverse transcriptase expression and the immune tolerance disruption of dendritic cells
Authors: Xu Xuejie , Mo Lihua , Liao Yun , Zhang Kaitlyn Song , Zhang Hanqing , Liu Le , Liu Yu , Tang Aifa , Yang Pingchang , Liu Xiaoyu 
Published: May 2024

Abstract
Background
To elucidate the mechanism of dysfunction of tolerogenic dendritic cells (DCs) is of significance. Telomerase involves the regulation of the cell fate and activities. The objective of this study is to investigate the role of telomerase reverse transcriptase (TERT) in regulating the tolerogenic feature of DCs.

Methods
The telomerase was assessed in DCs, which were collected from patients with allergic rhinitis (AR), healthy control (HC) subjects, and mice. RNAs were extracted from DCs, and analyzed by RNA sequencing (RNAseq), real-time quantitative RT-PCR, and Western blotting.

Results
The results showed that expression of TERT was higher in peripheral DCs of AR patients. The expression of IL10 in DCs was negatively correlated with the levels of TERT expression. Importantly, the levels of TERT mRNA in DCs were associated with the AR response in patients with AR. Endoplasmic reticulum (ER) stress promoted the expression of Tert in DCs. Sensitization with the ovalbumin-aluminum hydroxide protocol increased the expression of Tert in DCs by exacerbating ER stress. TERT interacting with c-Maf (the transcription factor of IL-10) inducing protein (CMIP) in DCs resulted in CMIP ubiquitination and degradation, and thus, suppressed the production of IL-10. Inhibition of Tert in DCs mitigated experimental AR.

Conclusions
Elevated amounts of TERT were detected in DCs of patients with AR. The tolerogenic feature of DCs was impacted by TERT. Inhibited TERT attenuated experimental AR.
APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition
Authors: Zhao Huihui , Cheng Xinxin , Yan Liping , Mi Fang , Wang Wenqing , Hu Yuying , Liu Xingyang , Fan Yuyan , Min Qingjie , Wang Yan , Zhang Weimin , Wu Qingnan , Zhan Qimin 
Published: May 2024

Abstract
Background
In addition to functioning as a precise monitoring mechanism in cell cycle, the anaphase-promoting complex/cyclosome (APC/C) is reported to be involved in regulating multiple metabolic processes by facilitating the ubiquitin-mediated degradation of key enzymes. Fatty acid oxidation is a metabolic pathway utilized by tumor cells that is crucial for malignant progression; however, its association with APC/C remains to be explored.

Methods
Cell cycle synchronization, immunoblotting, and propidium iodide staining were performed to investigate the carnitine palmitoyltransferase 1 C (CPT1C) expression manner. Proximity ligation assay and co-immunoprecipitation were performed to detect interactions between CPT1C and APC/C. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium, inner salt (MTS) assays, cell-scratch assays, and transwell assays and xenograft transplantation assays were performed to investigate the role of CPT1C in tumor progression in vitro and in vivo. Immunohistochemistry was performed on tumor tissue microarray to evaluate the expression levels of CPT1C and explore its potential clinical value.

Results
We identified CPT1C as a novel APC/C substrate. CPT1C protein levels exhibited cell cycle-dependent fluctuations, peaking at the G1/S boundary. Elevated CPT1C accelerated the G1/S transition, facilitating tumor cell proliferation in vitro and in vivo. Furthermore, CPT1C enhanced fatty acid utilization, upregulated ATP levels, and decreased reactive oxygen species levels, thereby favoring cell survival in a harsh metabolic environment. Clinically, high CPT1C expression correlated with poor survival in patients with esophageal squamous cell carcinoma.

Conclusions
Overall, our results revealed a novel interplay between fatty acid utilization and cell cycle machinery in tumor cells. Additionally, CPT1C promoted tumor cell proliferation and survival by augmenting cellular ATP levels and preserving redox homeostasis, particularly under metabolic stress. Therefore, CPT1C could be an independent prognostic indicator in esophageal squamous cell carcinoma.