bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ascorbic acid 6-palmitate modulates microglia M1/M2 polarization in lipopolysaccharide-stimulated BV-2 cells via PERK/elF2α mediated endoplasmic reticulum stress
Authors: Li Qian , Wu Yao , Chen Xue-shen , Zeng Tao , Liu Lin-ling , Feng Zi-qi , Liu Dan-yang , Zhu Ling , Wan Li-hong 
Published: November 2022

Abstract
Background
Neuroinflammation-mediated microglia polarization is a major process in various central nervous system (CNS) diseases. Endoplasmic reticulum (ER) stress contributes to the inflammatory signals as well as to microglia polarization in lipopolysaccharide (LPS) induced neuroinflammation. Ascorbic acid 6-palmitate (L-AP) has been broadly used as a dietary antioxidant in foods and demonstrated a strong inhibitory effect on 5-LOX; however, the specific anti-inflammation mechanisms remain unclear. In this study, we investigated the effects and possible mechanisms of L-AP on LPS-induced neuroinflammation in BV-2 cells.

Methods
Immortalized murine microglia cell line BV-2 cells were employed to assess the effect of L-AP to modulate microglia M1/M2 polarization in vivo, and the molecular mechanism was evaluated by qRT-PCR and Western blotting analysis. Molecular docking was used to predict the binding activity of L-AP with protein kinase R-like ER kinase (PERK).

Results
L-AP at 62.5 µM significantly modulated LPS-induced microglia M1/M2 polarization (increases of interleukin (IL)-10 and arginase-1 (Arg-1) transcriptions) independent of cell growth. Besides, L-AP at 62.5 µM significantly down-regulated glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding homologous protein (CHOP) mRNA levels. Similar data were shown in the tunicamycin (TM) induced ER stress cells model. Moreover, the protective effect of L-AP on TM-induced microglia M1/M2 polarization was similar to that of 4-phenyl butyric acid (4-PBA), the ER stress inhibitor. Molecular docking results indicated L-AP might directly bind with PERK, with a binding affinity of -7.7 kcal/mol. A further study unveiled that L-AP notably inhibited LPS-induced PERK/ eukaryotic initiation factor 2α (elf2α) activation.

Conclusion
Together, this study revealed that L-AP possessed its effect on the reconstruction of microglia M1/M2 polarization balance in LPS-stimulated BV-2 cells via modulating PERK/elF2α mediated ER stress.
Consumption of coffee and tea with all-cause and cause-specific mortality: a prospective cohort study
Authors: Chen Yanchun , Zhang Yuan , Zhang Mengnan , Yang Hongxi , Wang Yaogang 
Published: November 2022

Abstract
Background
Previous studies suggested that moderate coffee and tea consumption are associated with lower risk of mortality. However, the association between the combination of coffee and tea consumption with the risk of mortality remains unclear. This study aimed to evaluate the separate and combined associations of coffee and tea consumption with all-cause and cause-specific mortality.

Methods
This prospective cohort study included 498,158 participants (37–73 years) from the UK Biobank between 2006 and 2010. Coffee and tea consumption were assessed at baseline using a self-reported questionnaire. All-cause and cause-specific mortalities, including cardiovascular disease (CVD), respiratory disease, and digestive disease mortality, were obtained from the national death registries. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
After a median follow-up of 12.1 years, 34,699 deaths were identified. The associations of coffee and tea consumption with all-cause and cause-specific mortality attributable to CVD, respiratory disease, and digestive disease were nonlinear (all P nonlinear < 0.001). The association between separate coffee consumption and the risk of all-cause mortality was J-shaped, whereas that of separate tea consumption was reverse J-shaped. Drinking one cup of coffee or three cups of tea per day seemed to link with the lowest risk of mortality. In joint analyses, compared to neither coffee nor tea consumption, the combination of < 1–2 cups/day of coffee and 2–4 cups/day of tea had lower mortality risks for all-cause (HR, 0.78; 95% CI: 0.73–0.85), CVD (HR, 0.76; 95% CI: 0.64–0.91), and respiratory disease (HR, 0.69; 95% CI: 0.57–0.83) mortality. Nevertheless, the lowest HR (95% CI) of drinking both < 1–2 cup/day of coffee and ≥ 5 cups/day of tea for digestive disease mortality was 0.42 (0.34–0.53).

Conclusions
In this large prospective study, separate and combined coffee and tea consumption were inversely associated with all-cause and cause-specific mortality.
The use of routine health facility data for micro-stratification of malaria risk in mainland Tanzania
Authors: Thawer Sumaiyya G. , Golumbeanu Monica , Munisi Khalifa , Aaron Sijenunu , Chacky Frank , Lazaro Samwel , Mohamed Ally , Kisoka Noela , Lengeler Christian , Molteni Fabrizio , Ross Amanda , Snow Robert W. , Pothin Emilie 
Published: November 2022

Abstract
Background
Current efforts to estimate the spatially diverse malaria burden in malaria-endemic countries largely involve the use of epidemiological modelling methods for describing temporal and spatial heterogeneity using sparse interpolated prevalence data from periodic cross-sectional surveys. However, more malaria-endemic countries are beginning to consider local routine data for this purpose. Nevertheless, routine information from health facilities (HFs) remains widely under-utilized despite improved data quality, including increased access to diagnostic testing and the adoption of the electronic District Health Information System (DHIS2). This paper describes the process undertaken in mainland Tanzania using routine data to develop a high-resolution, micro-stratification risk map to guide future malaria control efforts.

Methods
Combinations of various routine malariometric indicators collected from 7098 HFs were assembled across 3065 wards of mainland Tanzania for the period 2017–2019. The reported council-level prevalence classification in school children aged 5–16 years (PfPR5–16) was used as a benchmark to define four malaria risk groups. These groups were subsequently used to derive cut-offs for the routine indicators by minimizing misclassifications and maximizing overall agreement. The derived-cutoffs were converted into numbered scores and summed across the three indicators to allocate wards into their overall risk stratum.

Results
Of 3065 wards, 353 were assigned to the very low strata (10.5% of the total ward population), 717 to the low strata (28.6% of the population), 525 to the moderate strata (16.2% of the population), and 1470 to the high strata (39.8% of the population). The resulting micro-stratification revealed malaria risk heterogeneity within 80 councils and identified wards that would benefit from community-level focal interventions, such as community-case management, indoor residual spraying and larviciding.

Conclusion
The micro-stratification approach employed is simple and pragmatic, with potential to be easily adopted by the malaria programme in Tanzania. It makes use of available routine data that are rich in spatial resolution and that can be readily accessed allowing for a stratification of malaria risk below the council level. Such a framework is optimal for supporting evidence-based, decentralized malaria control planning, thereby improving the effectiveness and allocation efficiency of malaria control interventions.
Protein arginine deiminase 2 (PAD2) modulates the polarization of THP-1 macrophages to the anti-inflammatory M2 phenotype
Authors: Stachowicz Aneta , Pandey Rakhi , Sundararaman Niveda , Venkatraman Vidya , Van Eyk Jennifer E. , Fert-Bober Justyna 
Published: November 2022

Abstract
Background
Macrophages are effector cells of the innate immune system that undergo phenotypical changes in response to organ injury and repair. These cells are most often classified as proinflammatory M1 and anti-inflammatory M2 macrophages. Protein arginine deiminase (PAD), which catalyses the irreversible conversion of protein-bound arginine into citrulline, is expressed in macrophages. However, the substrates of PAD and its role in immune cells remain unclear. This study aimed to investigate the role of PAD in THP-1 macrophage polarization to the M1 and M2 phenotypes and identify the citrullinated proteins and modified arginines that are associated with this biological switch using mass spectrometry.

Results
Our study showed that PAD2 and, to a lesser extent, PAD1 and PAD4 were predominantly expressed in M1 macrophages. We showed that inhibiting PAD expression with BB-Cl-amidine decreased macrophage polarization to the M1 phenotype (TNF-α, IL-6) and increased macrophage polarization to the M2 phenotype (MRC1, ALOX15). This process was mediated by the downregulation of proteins involved in the NF-κβ pathway. Silencing PAD2 confirmed the activation of M2 macrophages by increasing the antiviral innate immune response and interferon signalling. A total of 192 novel citrullination sites associated with inflammation, cell death and DNA/RNA processing pathways were identified in M1 and M2 macrophages.

Conclusions
We showed that inhibiting PAD activity using a pharmacological inhibitor or silencing PAD2 with PAD2 siRNA shifted the activation of macrophages towards the M2 phenotype, which can be crucial for designing novel macrophage-mediated therapeutic strategies. We revealed a major citrullinated proteome and its rearrangement following macrophage polarization, which after further validation could lead to significant clinical benefits for the treatment of inflammation and autoimmune diseases.
Identification of a novel ESR1 mutation in a Chinese PCOS woman with estrogen insensitivity in IVF treatment
Authors: Liu Faying , Tian Lifeng , Tan Jun , Li Zengming , Qin Haiyan , Xu Dingfei , Huang Zhihui , Wu Xingwu , Chen Ge , Wu Qiongfang , Zou Yang 
Published: November 2022

Abstract
Background
Polycystic ovary syndrome (PCOS) is a complex reproductive disorder, that affects approximately 5–10% of women of reproductive age. The disease is complex because its evolution may be impacted by genetic, lifestyle and environmental factors. Previous studies have emphasized the important roles of estrogen receptors in the pathogenesis of PCOS.

Objective
To use whole exome sequencing (WES) to assess possible pathogenic factors in a PCOS patient who exhibited estrogen insensitivity during hormone replacement therapy (HRT) treatment.

Methods
Genome sequencing and variant filtering via WES were performed in a patient with PCOS. DNA extraction from 364 unrelated female controls without PCOS was followed by PCR amplification, Sanger sequencing and sequence alignment. Evolutionary conservation analysis, protein structural modelling and in silico prediction were applied to analyse the potential pathogenicity of the novel ESR1 mutation.

Result(s)
During the controlled ovarian hyperstimulation (COH) period of an IVF cycle, the patient experienced markedly prolonged ovarian stimulation due to a poor response to gonadotropins (Gn) and elevated serum FSH. A novel heterozygous ESR1 mutation, c.619G > A/p.A207T, leading to the replacement of a highly conserved alanine with a threonine, was identified in this patient, via WES analysis. This novel variant was not identified in 364 unrelated female controls without PCOS, or in the Exome Aggregation Consortium (ExAC) or 1000 Genome Project.

Conclusion(s)
We identified a novel heterozygous ESR1 mutation in a Han Chinese PCOS woman exhibiting clinical signs of estrogen insensitivity. This study may provide new strategies for IVF therapy, especially for patients who exhibit estrogen insensitivity during IVF cycle.
Integration of CRISPR/Cas9 with artificial intelligence for improved cancer therapeutics
Authors: Bhat Ajaz A. , Nisar Sabah , Mukherjee Soumi , Saha Nirmalya , Yarravarapu Nageswari , Lone Saife N. , Masoodi Tariq , Chauhan Ravi , Maacha Selma , Bagga Puneet , Dhawan Punita , Akil Ammira Al-Shabeeb , El-Rifai Wael , Uddin Shahab , Reddy Ravinder , Singh Mayank , Macha Muzafar A. , Haris Mohammad 
Published: November 2022

AbstractGene editing has great potential in treating diseases caused by well-characterized molecular alterations. The introduction of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)–based gene-editing tools has substantially improved the precision and efficiency of gene editing. The CRISPR/Cas9 system offers several advantages over the existing gene-editing approaches, such as its ability to target practically any genomic sequence, enabling the rapid development and deployment of novel CRISPR-mediated knock-out/knock-in methods. CRISPR/Cas9 has been widely used to develop cancer models, validate essential genes as druggable targets, study drug-resistance mechanisms, explore gene non-coding areas, and develop biomarkers. CRISPR gene editing can create more-effective chimeric antigen receptor (CAR)-T cells that are durable, cost-effective, and more readily available. However, further research is needed to define the CRISPR/Cas9 system’s pros and cons, establish best practices, and determine social and ethical implications. This review summarizes recent CRISPR/Cas9 developments, particularly in cancer research and immunotherapy, and the potential of CRISPR/Cas9-based screening in developing cancer precision medicine and engineering models for targeted cancer therapy, highlighting the existing challenges and future directions. Lastly, we highlight the role of artificial intelligence in refining the CRISPR system's on-target and off-target effects, a critical factor for the broader application in cancer therapeutics.
Clinical electives in China: trends, experiences, barriers
Authors: Storz Maximilian Andreas 
Published: November 2022

AbstractIn recent decades, China has quickly transformed itself into a modern, urban, technological and economic powerhouse. China’s medical education system is internationalizing and attracting a considerable number of foreign students seeking medical degrees and other clinical experience, such as observerships, in China. Although the majority of international students in China come from low- and middle income countries, China’s rise towards the world’s largest medical education system also offers new opportunities for stronger cooperation with European countries. Both sides maintain tight economic ties, and China’s rise is also attracting more and more medial students for short-term clinical electives from the German-speaking countries. Such clinical electives are pertinent to global health education in a globalized world, and allow students to immerse in foreign healthcare systems for a short period. Notably, reasons for (and barriers to) electives in China are largely unexplored. To address this gap, we reviewed 4 popular German elective report databases and extrapolated key characteristics of electives in China undertaken by German-speaking medical student. N = 40 elective testimonies were analyzed with regard to students’ elective experience, elective barriers and organizational aspects. The vast majority of students reported an elective in Shanghai (n = 29, 72.50%). More than 70% of students applied directly to an elective program for foreign students, whereas less than 25% applied through a bilateral exchange program. Frequently cited positive aspects of electives in China included the Chinese hospitality and the regular high-quality teaching in English for international students. Notably, almost half of student reported some kind of difficulties during their elective (n = 18, 45%), including language barriers (n = 6), administrative issues (n = 5) and visa problems (n = 2). Our data suggest that international electives in China were overall well-rated by German-speaking students. The combination of structured clinical elective programs with English supervision and the opportunity to learn more about the Chinese culture apparently attracted said students in the past 2 decades.
Glaucoma-TrEl: A web-based interactive database to build evidence-based hypotheses on the role of trace elements in glaucoma
Authors: Choudhari Jyoti Kant , Eberhardt Martin , Chatterjee Tanushree , Hohberger Bettina , Vera Julio 
Published: November 2022

Abstract
Objective
Glaucoma is a chronic neurological disease that is associated with high intraocular pressure (IOP), causes gradual damage to retinal ganglion cells, and often culminates in vision loss. Recent research suggests that glaucoma is a complex multifactorial disease in which multiple interlinked genes and pathways play a role during onset and development. Also, differential availability of trace elements seems to play a role in glaucoma pathophysiology, although their mechanism of action is unknown. The aim of this work is to disseminate a web-based repository on interactions between trace elements and protein-coding genes linked to glaucoma pathophysiology.

Results
In this study, we present Glaucoma-TrEl, a web database containing information about interactions between trace elements and protein-coding genes that are linked to glaucoma. In the database, we include interactions between 437 unique genes and eight trace elements. Our analysis found a large number of interactions between trace elements and protein-coding genes mutated or linked to the pathophysiology of glaucoma. We associated genes interacting with multiple trace elements to pathways known to play a role in glaucoma. The web-based platform provides an easy-to-use and interactive tool, which serves as an information hub facilitating future research work on trace elements in glaucoma.
Do regulatory tools instigate measures to prevent work-related psychosocial and ergonomic risk factors? A process evaluation of a Labour inspection authority trial in the Norwegian home-care services
Authors: Johannessen Håkon A. , Knardahl Stein , Emberland Jan S. , Skare Øivind , Finnanger Garshol Bjørnar 
Published: November 2022

Abstract
Objective
There is a research gap regarding the way managers and employee representatives respond to Labour Authority interventions targeting work-related psychosocial and ergonomic risk factors. The present study aimed to determine if (I) labour inspections and (II) guidance-through-workshops led by inspectors were perceived by the target audience as equally useful and educational; and to determine if utility and enhanced knowledge were associated with the implementation of measures to prevent work-related risk factors. Finally, it aimed to determine if the managers in the intervention groups to a greater extent than the controls reported implementing such measures.

Results
Managers and employee representatives in both intervention groups reported a high level of perceived utility as well as a high level of enhanced knowledge. Both utility (p < 0.05) and enhanced knowledge (p < 0.05) were significantly associated with the implementation of, or plans to soon implement, measures to improve working conditions. When compared to controls, implemented measures, or plans to implement measures, were reported significantly more frequently by managers in the inspection group (p < 0.05).
Trial Registration ClinicalTrials.gov ID: NCT03855163 Registered on February 26, 2019.
Strategic sectors and the diffusion of the effect of a shock in Mexico for 2008 and 2012
Authors: Alatriste-Contreras Martha G. , Lugo Igor 
Published: November 2022

AbstractWe combine input–output analysis with a diffusion measure and complex network measures of centrality to propose a method to identify strategic or key sectors in an economy. We then apply our method to the case of Mexico for the years 2008 and 2012. Results for Mexico show that the ranking sectors according to the diffusion measure allows identifying strategic sectors with desirable properties such as high centrality and a high correlation to the aggregate effect of a shock. Furthermore, these sectors also have a good performance according to macroeconomic variables, such as exports and value-added. The disaggregation of the aggregate effect of a shock, together with our results on diffusion, suggests that one should focus on sectors with good diffusion to design policy recommendations.
Heat stress in pigs and broilers: role of gut dysbiosis in the impairment of the gut-liver axis and restoration of these effects by probiotics, prebiotics and synbiotics
Authors: Ringseis Robert , Eder Klaus 
Published: November 2022

AbstractHeat stress is one of the most challenging stressors for animal production due to high economic losses resulting from impaired animal’s productivity, health and welfare. Despite the fact that all farm animal species are susceptible to heat stress, birds and pigs are particularly sensitive to heat stress due to either lacking or non-functional sweat glands. Convincing evidence in the literature exists that gut dysbiosis, a term used to describe a perturbation of commensal gut microbiota, develops in broilers and pigs under heat stress. Owing to the protective role of commensal bacteria for the gut barrier, gut dysbiosis causes a disruption of the gut barrier leading to endotoxemia, which contributes to the typical characteristics of heat stressed broilers and growing and growing-finishing pigs, such as reduced feed intake, decreased growth and reduced lean carcass weight. A substantial number of studies have shown that feeding of probiotics, prebiotics and synbiotics is an efficacious strategy to protect broilers from heat stress-induced gut barrier disruption through altering the gut microbiota and promoting all decisive structural, biochemical, and immunological elements of the intestinal barrier. In most of the available studies in heat stressed broilers, the alterations of gut microbiota and improvements of gut barrier function induced by feeding of either probiotics, prebiotics or synbiotics were accompanied by an improved productivity, health and/or welfare when compared to non-supplemented broilers exposed to heat stress. These findings indicate that the restoration of gut homeostasis and function is a key target for dietary interventions aiming to provide at least partial protection of broilers from the detrimental impact of heat stress conditions. Despite the fact that the number of studies dealing with the same feeding strategy in heat stressed pigs is limited, the available few studies suggest that feeding of probiotics might also be a suitable approach to enhance productivity, health and welfare in pigs kept under heat stress conditions.
Analysis of the risk of theft from vehicle crime in Kyoto, Japan using environmental indicators of streetscapes
Authors: Adachi Hiroki M. , Nakaya Tomoki 
Published: November 2022

AbstractWith the advent of spatial analysis, the importance of analyzing crime patterns based on location has become more apparent. Previous studies have advanced our understanding of the factors associated with crime concentration in street networks. However, it has recently become possible to assess the factors associated with crime at even finer spatial scales of streetscapes, such as the existence of greenery or walls, owing to the availability of streetscape image data and progress in machine learning-based image analysis. Such place-scale environments can be both crime-producing and crime-preventing, depending on the composition of the streetscape environment. In this study, we attempted to assess the risk of crime occurrence through place-scale indicators using streetscape images and their interaction terms through binomial logistic regression modeling of the place-scale crime risk of theft from vehicles in the central part of Kyoto City, Japan. The results suggest that the effects of specific streetscape components on the risk of crime occurrence are certainly dependent on other components. For example, the association of the crime occurrence risk with the occupancy rate of vegetation in a streetscape image is positive when there are few buildings and walls, and vice versa. The findings of this study show the importance of considering the complex composition of visible streetscape components in assessing the place-scale risk of crime occurrence.