bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association analysis explores the genetic loci of amino acid content in duck’s breast muscle
Authors: Wang Rui , Lu Yinjuan , Qi Jingjing , Xi Yang , Shen Zhenyang , Twumasi Grace , Bai Lili , Hu Jiwei , Wang Jiwen , Li Liang , Liu Hehe
Published: May 2024

Background

Amino acids are the basic components of protein and an important index to evaluate meat quality. With the rapid development of genomics, candidate regions and genes affecting amino acid content in livestock and poultry have been gradually revealed. Hence, genome-wide association study (GWAS) can be used to screen candidate loci associated with amino acid content in duck meat.

Result

In the current study, the content of 16 amino acids was detected in 358 duck breast muscles. The proportion of Glu to the total amino acid content was relatively high, and the proportion was 0.14. However, the proportion of Met content was relatively low, at just 0.03. By comparative analysis, significant differences were found between males and females in 3 amino acids, including Ser, Met, and Phe. In addition, 12 SNPs were significantly correlated with Pro content by GWAS analysis, and these SNPs were annotated by 7 protein-coding genes; 8 significant SNPs were associated with Tyr content, and these SNPs were annotated by 6 protein-coding genes. At the same time, linkage disequilibrium (LD) analysis was performed on these regions with significant signals. The results showed that three SNPs in the 55–56 Mbp region of chromosome 3 were highly correlated with the leader SNP (chr3:55526954) that affected Pro content (r2 > 0.6). Similarly, LD analysis showed that there were three SNPs in the 21.2–21.6 Mbp region of chromosome 13, which were highly correlated with leader SNP (chr13:21421661) (r2 > 0.6). Moreover, Through functional enrichment analysis of all candidate genes. The results of GO enrichment analysis showed that several significant GO items were associated with amino acid transport function, including amino acid transmembrane transport and glutamine transport. The results further indicate that these candidate genes are closely associated with amino acid transport. Among them, key candidate genes include SLC38A1. For KEGG enrichment analysis, CACNA2D3 and CACNA1D genes were covered by significant pathways.

Conclusion

In this study, GWAS analysis found a total of 28 significant SNPs affecting amino acid content. Through gene annotation, a total of 20 candidate genes were screened. In addition, Through LD analysis and enrichment analysis, we considered that SERAC1, CACNA2D3 and SLC38A1 genes are important candidate genes affecting amino acid content in duck breast muscle.
Genome-wide detections for runs of homozygosity and selective signatures reveal novel candidate genes under domestication in chickens
Authors: Tan Xiaodong , Liu Lu , Dong Jie , Huang Minjie , Zhang Jiawen , Li Qinghai , Wang Huanhuan , Bai Lijuan , Cui Ming , Zhou Zhenzhen , Wu De , Xiang Yun , Li Weifen , Wang Deqian
Published: May 2024

Background

Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding.

Results

To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima’s D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively.

Conclusion

Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies.
Enhancer selectivity across cell types delineates three functionally distinct enhancer-promoter regulation patterns
Authors: Wu Chengyi , Huang Jialiang
Published: May 2024

Background

Multiple enhancers co-regulating the same gene is prevalent and plays a crucial role during development and disease. However, how multiple enhancers coordinate the same gene expression across various cell types remains largely unexplored at genome scale.

Results

We develop a computational approach that enables the quantitative assessment of enhancer specificity and selectivity across diverse cell types, leveraging enhancer-promoter (E-P) interactions data. We observe two well-known gene regulation patterns controlled by enhancer clusters, which regulate the same gene either in a limited number of cell types (Specific pattern, Spe) or in the majority of cell types (Conserved pattern, Con), both of which are enriched for super-enhancers (SEs). We identify a previously overlooked pattern (Variable pattern, Var) that multiple enhancers link to the same gene, but rarely coexist in the same cell type. These three patterns control the genes associating with distinct biological function and exhibit unique epigenetic features. Specifically, we discover a subset of Var patterns contains Shared enhancers with stable enhancer-promoter interactions in the majority of cell types, which might contribute to maintaining gene expression by recruiting abundant CTCF.

Conclusions

Together, our findings reveal three distinct E-P regulation patterns across different cell types, providing insights into deciphering the complexity of gene transcriptional regulation.
A novel family of defensin-like peptides from Hermetia illucens with antibacterial properties
Authors: Fahmy Leila , Generalovic Tomas , Ali Youssif M. , Seilly David , Sivanesan Kesavan , Kalmar Lajos , Pipan Miha , Christie Graham , Grant Andrew J
Published: May 2024

Background

The world faces a major infectious disease challenge. Interest in the discovery, design, or development of antimicrobial peptides (AMPs) as an alternative approach for the treatment of bacterial infections has increased. Insects are a good source of AMPs which are the main effector molecules of their innate immune system. Black Soldier Fly Larvae (BSFL) are being developed for large-scale rearing for food sustainability, waste reduction and as sustainable animal and fish feed. Bioinformatic studies have suggested that BSFL have the largest number of AMPs identified in insects. However, most AMPs identified in BSF have not yet undergone antimicrobial evaluation but are promising leads to treat critical infections.

Results

Jg7197.t1, Jg7902.t1 and Jg7904.t1 were expressed into the haemolymph of larvae following infection with Salmonella enterica serovar Typhimurium and were predicted to be AMPs using the computational tool ampir. The genes encoding these proteins were within 2 distinct clusters in chromosome 1 of the BSF genome. Following removal of signal peptides, predicted structures of the mature proteins were superimposed, highlighting a high degree of structural conservation. The 3 AMPs share primary sequences with proteins that contain a Kunitz-binding domain; characterised for inhibitory action against proteases, and antimicrobial activities. An in vitro antimicrobial screen indicated that heterologously expressed SUMO-Jg7197.t1 and SUMO-Jg7902.t1 did not show activity against 12 bacterial strains. While recombinant SUMO-Jg7904.t1 had antimicrobial activity against a range of Gram-negative and Gram-positive bacteria, including the serious pathogen Pseudomonas aeruginosa.

Conclusions

We have cloned and purified putative AMPs from BSFL and performed initial in vitro experiments to evaluate their antimicrobial activity. In doing so, we have identified a putative novel defensin-like AMP, Jg7904.t1, encoded in a paralogous gene cluster, with antimicrobial activity against P. aeruginosa.
Epicardial fat volume is associated with primary coronary slow-flow phenomenon in patients with severe aortic stenosis undergoing transcatheter valve implantation
Authors: Weferling Maren , Rolf Andreas , Treiber Julia , Fischer-Rasokat Ulrich , Liebetrau Christoph , Hamm Christian W. , Dey Damini , Kim Won-Keun
Published: May 2024

Background

Primary coronary slow flow (CSF) is defined as delayed opacification of the distal epicardial vasculature during coronary angiography in the absence of relevant coronary artery stenoses. Microvascular disease is thought to be the underlying cause of this pathology. Epicardial fat tissue (EFT) is an active endocrine organ directly surrounding the coronary arteries that provides pro-inflammatory factors to the adjacent tissue by paracrine and vasocrine mechanisms. The aim of the present study was to investigate a potential association between EFT and primary CSF and whether EFT can predict the presence of primary CSF.

Methods

Between 2016 and 2017,n = 88 patients with high-grade aortic stenosis who were planned for transcatheter aortic valve implantation (TAVI) were included in this retrospective study. EFT volume was measured by pre-TAVI computed tomography (CT) using dedicated software. The presence of primary CSF was defined based on the TIMI frame count from the pre-TAVI coronary angiograms.

Results

Thirty-nine of 88 TAVI patients had CSF (44.3%). EFT volume was markedly higher in patients with CSF (142 ml [IQR 107–180] vs. 113 ml [IQR 89–147];p = 0.009) and was strongly associated with the presence of CSF (OR 1.012 [95%CI 1.002–1.021];p = 0.014). After adjustment, EFT volume was still an independent predictor of CSF (OR 1.016 [95%CI 1.004–1.026];p = 0.009).

Conclusion

Primary CSF was independently associated with increased EFT volume. Further studies are needed to validate this finding and elucidate whether a causal relationship exists.
The long-term effects of blood urea nitrogen levels on cardiovascular disease and all-cause mortality in diabetes: a prospective cohort study
Authors: Liu Hongfang , Xin Xiaoqin , Gan Jinghui , Huang Jungao
Published: May 2024

Background

The long-term effects of blood urea nitrogen(BUN) in patients with diabetes remain unknown. Current studies reporting the target BUN level in patients with diabetes are also limited. Hence, this prospective study aimed to explore the relationship of BUN with all-cause and cardiovascular mortalities in patients with diabetes.

Methods

In total, 10,507 participants with diabetes from the National Health and Nutrition Examination Survey (1999–2018) were enrolled. The causes and numbers of deaths were determined based on the National Death Index mortality data from the date of NHANES interview until follow-up (December 31, 2019). Multivariate Cox proportional hazard regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs) of mortality.

Results

Of the adult participants with diabetes, 4963 (47.2%) were female. The median (interquartile range) BUN level of participants was 5 (3.93–6.43) mmol/L. After 86,601 person-years of follow-up, 2,441 deaths were documented. After adjusting for variables, the HRs of cardiovascular disease (CVD) and all-cause mortality in the highest BUN level group were 1.52 and 1.35, respectively, compared with those in the lowest BUN level group. With a one-unit increment in BUN levels, the HRs of all-cause and CVD mortality rates were 1.07 and 1.08, respectively. The results remained robust when several sensitivity and stratified analyses were performed. Moreover, BUN showed a nonlinear association with all-cause and CVD mortality. Their curves all showed that the inflection points were close to the BUN level of 5 mmol/L.

Conclusion

BUN had a nonlinear association with all-cause and CVD mortality in patients with diabetes. The inflection point was at 5 mmol/L.
Association between migraine and pre-eclampsia among pregnant women: a single hospital-based case–control study in India
Authors: Biswas Shyamashree , Singh Ranjana , Radhika A. G.
Published: May 2024

Background

Pre-eclampsia and migraine share some similar aspects of pathophysiology such as vascular function, platelet activation, and enhanced clotting. A few observational studies from different demographics showed that pregnant women with a history of migraine were at higher risk of developing pre-eclampsia. However, there is no such evidence available from the Indian context. Hence, a hospital-based case–control study was conducted among Indian women to determine the association between migraine and pre-eclampsia.

Method

It was a single-centre case-control study in a tertiary care hospital in India. Cases were pregnant women with clinically diagnosed pre-eclampsia, and controls were normotensive pregnant women. Migraine was diagnosed with a questionnaire adapted from the “International Classification of Headache Disorders (ICHD), 3rd Edition” by the International Headache Society, (IHS). We performed logistic regression to explore the association between migraine and pre-eclampsia.

Result

One hundred sixty-four women (82 women per group) were enrolled. The mean age among the cases (24.5 years, standard deviation of 2.4 years) was slightly higher than the mean age of the controls (23.5 years, standard deviation of 2.5 years) with ap-value of 0.006. We found that women with a history of migraine were more likely to develop pre-eclampsia (Adjusted Odds Ratio 6.17;p-value < 0.001, 95% Confidence Interval of 2.85 to 13.62).

Conclusion

The current findings suggest a significant association between migraine and pre-eclampsia aligning with previous study findings; nevertheless, larger follow-up studies including women from different states in India are needed.
Liver cancer in China: the analysis of mortality and burden of disease trends from 2008 to 2021
Authors: Qin Yajun , Tang Changlin , Li Jinhao , Gong Jianping
Published: May 2024

Background

Liver cancer is one of the most common cancers in China. To understand the basic death situation and disease burden change trend, we analyze the death information of liver cancer among Chinese residents from 2008 to 2021.

Methods

Data was collected from the Cause-of-Death Surveillance dataset of the National Cause-of-Death Surveillance System from 2008 to 2021. Excel 2016 was used for data entry and to calculate the Crude Mortality Rate (CMR), Age-Standardized Mortality Rate (ASMR), Potential Years of Life Lost (PYLL), and Potential Years of Life Lost Rate (PYLLR). SPSS 25.0 was used to statistically analyze CMR, ASMR, PYLL, and other indicators. Annual percent change (APC) and average APC(AAPC) was used for trend analysis and tested by t tests. Joinpoint 4.9.1.0 was used to calculate APC and AAPC. Age-Period-Cohort model was used to assess the effects of age, period, and birth cohort on liver cancer mortality.

Results

From 2008 to 2021, 491,701 liver cancer deaths were reported in the National Disease Surveillance Points System. The ASMR of liver cancer in Chinese residents decreased from 27.58/100,000 in 2008 to 17.95/100,000 in 2021 at an average annual rate of 3.40% (t = -5.10, P < 0.001). The mortality rate was higher in males than in females (all P < 0.001) and higher in rural areas than in urban areas (all P < 0.001). The mortality rate of liver cancer varied significantly among eastern, central, and western China (all P < 0.001). The PYLLR of liver cancer in Chinese residents decreased from 2.89‰ in 2008 to 2.06‰ in 2021 at an average annual rate of 2.40% (t = -5.10, P < 0.001). Males had a lower PYLLR than females, decreasing at average annual rates of 2.20% (t = -5.40, P < 0.001) and 2.90% (t = -8.40, P < 0.001), respectively. Urban areas had a lower PYLLR than rural areas, decreasing at average annual rate of 3.30% (t = -4.00, P < 0.001) and 2.50% (t = -11.60, P < 0.001), respectively. Eastern, central, and western China decreased at average annual rates of 3.40%, 2.30%, and 2.10%, respectively (t = -7.80, -3.60, -7.10, P < 0.001 for all). The risk of China liver cancer mortality increased with age, decreased with birth cohort.

Conclusions

The mortality and disease burdens of liver cancer in China decreased yearly and were higher in males and in people living in rural areas, with significant differences among those living in eastern, central, and western China.
Prediction of esophageal cancer risk based on genetic variants and environmental risk factors in Chinese population
Authors: Liu Haiyan , Li Keming , Xia Junfen , Zhu Jicun , Cheng Yifan , Zhang Xiaoyue , Ye Hua , Wang Peng
Published: May 2024

Background

Results regarding whether it is essential to incorporate genetic variants into risk prediction models for esophageal cancer (EC) are inconsistent due to the different genetic backgrounds of the populations studied. We aimed to identify single-nucleotide polymorphisms (SNPs) associated with EC among the Chinese population and to evaluate the performance of genetic and non-genetic factors in a risk model for developing EC.

Methods

A meta-analysis was performed to systematically identify potential SNPs, which were further verified by a case-control study. Three risk models were developed: a genetic model with weighted genetic risk score (wGRS) based on promising SNPs, a non-genetic model with environmental risk factors, and a combined model including both genetic and non-genetic factors. The discrimination ability of the models was compared using the area under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI). The Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to assess the goodness-of-fit of the models.

Results

Five promising SNPs were ultimately utilized to calculate the wGRS. Individuals in the highest quartile of the wGRS had a 4.93-fold (95% confidence interval [CI]: 2.59 to 9.38) increased risk of EC compared with those in the lowest quartile. The genetic or non-genetic model identified EC patients with AUCs ranging from 0.618 to 0.650. The combined model had an AUC of 0.707 (95% CI: 0.669 to 0.743) and was the best-fitting model (AIC = 750.55, BIC = 759.34). The NRI improved when the wGRS was added to the risk model with non-genetic factors only (NRI = 0.082, P = 0.037).

Conclusions

Among the three risk models for EC, the combined model showed optimal predictive performance and can help to identify individuals at risk of EC for tailored preventive measures.
Identification of shared gene signatures in major depressive disorder and triple-negative breast cancer
Authors: Xie Hua , Ding Chenxiang , Li Qianwen , Sheng Wei , Xu Jie , Feng Renjian , Cheng Huaidong
Published: May 2024

Background

Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD.

Methods

Public datasets GSE65194 and GSE98793 were analyzed to identify differentially expressed genes (DEGs) shared by both datasets. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify key PPI genes using cytoHubba. Hub DEGs were obtained from the intersection of hub genes from a PPI network with genes in the disease associated modules of the Weighed Gene Co-expression Network Analysis (WGCNA). Independent datasets (TCGA and GSE76826) and RT-qPCR validated hub gene expression.

Results

A total of 113 overlapping DEGs were identified between TNBC and MDD. The PPI network was constructed, and 35 hub DEGs were identified. Through WGCNA, the blue, brown, and turquoise modules were recognized as highly correlated with TNBC, while the brown, turquoise, and yellow modules were similarly correlated with MDD. Notably, G3BP1, MAF, NCEH1, and TMEM45A emerged as hub DEGs as they appeared both in modules and PPI hub DEGs. Within the GSE65194 and GSE98793 datasets, G3BP1 and MAF exhibited a significant downregulation in TNBC and MDD groups compared to the control, whereas NCEH1 and TMEM45A demonstrated a significant upregulation. These findings were further substantiated by TCGA and GSE76826, as well as through RT-qPCR validation.

Conclusions

This study identified G3BP1, MAF, NCEH1 and TMEM45A as key pathological genes in both TNBC and MDD.
Temporal change in prevalence of BMI categories in India: patterns across States and Union territories of India, 1999–2021
Authors: Sung Meekang , Kumar Akhil , Mishra Raman , Kulkarni Bharati , Kim Rockli , Subramanian S. V.
Published: May 2024

Background

The problem of overweight/obesity often coexists with the burden of undernutrition in most low- and middle-income countries. BMI change in India incorporating the most recent trends has been under-researched.

Methods

This repeated cross-sectional study of 1,477,885 adults in India analyzed the prevalence of different categories of BMI among adults (age 20–54) in 4 rounds of National Family Health Surveys (1998–1999, 2005–2006, 2015–2016, and 2019–2021) for 36 states/UTs. State differences across time were harmonized for accurate analysis. The categories were Severely/Moderately Thin (BMI < 17.0), Mildly Thin (17.0-18.4), Normal (18.5–24.9), Overweight (25.0-29.9), and Obese (≥ 30.0). We also estimated change in Standardized Absolute Change (SAC), ranking of states, and headcount burden to quantify the trend of BMI distribution across time periods for all-India, urban/rural residence, and by states/UTs.

Results

The prevalence of thinness declined from 31.7% in 1999 to 14.2% in 2021 for women, and from 23.4% in 2006 to 10.0% in 2021 for men. Obesity prevalence increased from 2.9% (1999) to 6.3% (2021) for women, and from 2.0% (2006) to 4.2% (2021) for men. In 2021, the states with the highest obesity prevalence were Puducherry, Chandigarh, and Delhi. These states also had a high prevalence of overweight. Dadra and Nagar Haveli and Diu, Gujarat, Jharkhand, and Bihar had the highest prevalence of severe/moderately thin. Prevalence of extreme categories (severely/moderately thin and obese) was larger in the case of women than men. While States/UTs with a higher prevalence of thin populations tend to have a larger absolute burden of severe or moderate thinness, the relationship between headcount burden and prevalence for overweight and obese is unclear.

Conclusions

We found persistent interstate inequalities of undernutrition. Tailored efforts at state levels are required to further strengthen existing policies and develop new interventions to target both forms of malnutrition.
Unlocking the potential: exploring the impact of dolutegravir treatment on body mass index improvement in underweight adults with HIV in Malawi
Authors: Maphosa Thulani , Dunga Shalom , Makonokaya Lucky , Woelk Godfrey , Maida Alice , Wang Alice , Ahimbisibwe Allan , Chamanga Rachel K. , Zimba Suzgo B. , Kayira Dumbani , Machekano Rhoderick
Published: May 2024

Background

The introduction of dolutegravir (DTG) in treating HIV has shown enhanced efficacy and tolerability. This study examined changes in weight gain and body mass index (BMI) at 6- and 12-months after post-initiating antiretroviral therapy (ART), comparing people living with HIV (PLHIV) on DTG-based regimens with those on non-DTG-based regimens in Malawi.

Methods

Retrospective cohort data from 40 public health facilities in Malawi were used, including adult ART patients (aged ≥ 15 years) from January 2017 to March 2020. The primary outcomes were BMI changes/transitions, with secondary outcomes focused on estimating the proportion of mean weight gain > 10% post-ART initiation and BMI category transitions. Descriptive statistics and binomial regression were used to estimate the unadjusted and adjusted relative risks (RR) of weight gain of more than ( >) 10%.

Results

The study included 3,520 adult ART patients with baseline weight after ART initiation, predominantly female (62.7%) and aged 25–49 (61.1%), with a median age of 33 years (interquartile range (IQR), 23–42 years). These findings highlight the influence of age, ART history, and current regimen on weight gain. After 12months follow up, compared to those aged 15–24 years, individuals aged 25–49 had an Adjusted RR (ARR) of 0.5 (95% Confidence Interval (CI): 0.35–0.70), suggesting a 50% reduced likelihood of > 10% weight gain after post-ART initiation. Similarly, those aged 50 + had an ARR of 0.33 (95% CI: 0.20–0.58), indicating a 67% decreased likelihood compared to the youngest age group 15–24 years. This study highlights the positive impact of DTG-based regimens, revealing significant transitions from underweight to normal BMI categories at 6- and 12-months post-initiation.

Conclusion

This study provides insights into weight gain patterns in patients on DTG-based regimens compared with those on non-DTG regimens. Younger individuals (15–24 years) exhibited higher odds of weight gain, suggesting a need for increased surveillance in this age group. These findings contribute to the understanding DTG's potential effects on weight gain, aiding clinical decision making. Further research is required to comprehensively understand the underlying mechanisms and long-term implications of weight gain in patients receiving DTG-based regimens.
No genetic causal associations between periodontitis and brain atrophy or cognitive impairment: evidence from a comprehensive bidirectional Mendelian randomization study
Authors: Deng Zhixing , Li Jiaming , Zhang Yuhao , Zhang Yinian
Published: May 2024

Background

Observational studies have explored the relationships of periodontitis with brain atrophy and cognitive impairment, but these findings are limited by reverse causation, confounders and have reported conflicting results. Our study aimed to investigate the causal associations of periodontitis with brain atrophy and cognitive impairment through a comprehensive bidirectional Mendelian randomization (MR) research.

Methods

We incorporated two distinct genome-wide association study (GWAS) summary datasets as an exploration cohort and a replication cohort for periodontitis. Four and eight metrics were selected for the insightful evaluation of brain atrophy and cognitive impairment, respectively. The former involved cortical thickness and surface area, left and right hippocampal volumes, with the latter covering assessments of cognitive performance, fluid intelligence scores, prospective memory, and reaction time for mild cognitive impairment to Alzheimer's disease (AD), Lewy body dementia, vascular dementia and frontotemporal dementia for severe situations. Furthermore, supplementary analyses were conducted to examine the associations between the longitudinal rates of change in brain atrophy and cognitive function metrics with periodontitis. The main analysis utilized the inverse variance weighting (IVW) method and evaluated the robustness of the results through a series of sensitivity analyses. For multiple tests, associations with p-values < 0.0021 were considered statistically significant, while p-values ≥ 0.0021 and < 0.05 were regarded as suggestive of significance.

Results

In the exploration cohort, forward and reverse MR results revealed no causal associations between periodontitis and brain atrophy or cognitive impairment, and only a potential causal association was found between AD and periodontitis (IVW: OR = 0.917, 95% CI from 0.845 to 0.995, P = 0.038). Results from the replication cohort similarly corroborated the absence of a causal relationship. In the supplementary analyses, the longitudinal rates of change in brain atrophy and cognitive function were also not found to have causal relationships with periodontitis.

Conclusions

The MR analyses indicated a lack of substantial evidence for a causal connection between periodontitis and both brain atrophy and cognitive impairment.
Non-technical skills training for Nigerian interprofessional surgical teams: a cross-sectional survey
Authors: Alayande Barnabas Tobi , Forbes Callum , Kingpriest Paul , Adejumo Adeyinka , Williams Wendy , Wina Felix , Agbo Christian Agbo , Omolabake Bamidele , Bekele Abebe , Ismaila Bashiru O , Kerray Fiona , Sule Augustine , Abahuje Egide , Robertson Jamie M. ,   The Non-technical Skills for Surgery Nigeria Group, Abah Tosin , Shattah Akims , Homoweto Linus Hapiyati , Onyeji John , Okoko Joseph , Sule Joshua , Yule Steven , Riviello Robert , Isichei Mercy
Published: May 2024

Introduction

Non-technical skills (NTS) including communication, teamwork, leadership, situational awareness, and decision making, are essential for enhancing surgical safety. Often perceived as tangential soft skills, NTS are many times not included in formal medical education curricula or continuing medical professional development. We aimed to explore exposure of interprofessional teams in North-Central Nigeria to NTS and ascertain perceived facilitators and barriers to interprofessional training in these skills to enhance surgical safety and inform design of a relevant contextualized curriculum.

Methods

Six health facilities characterised by high surgical volumes in Nigeria’s North-Central geopolitical zone were purposively identified. Federal, state, and private university teaching hospitals, non-teaching public and private hospitals, and a not-for-profit health facility were included. A nineteen-item, web-based, cross-sectional survey was distributed to 71 surgical providers, operating room nurses, and anaesthesia providers by snowball sampling through interprofessional surgical team leads from August to November 2021. Data were analysed using Fisher’s exact test, proportions, and constant comparative methods for free text responses.

Results

Respondents included 17 anaesthesia providers, 21 perioperative nurses, and 29 surgeons and surgical trainees, with a 95.7% survey completion rate. Over 96% had never heard of any NTS for surgery framework useful for variable resource contexts and only 8% had ever received any form of NTS training. Interprofessional teams identified communication and teamwork as the most deficient personal skills (38, 57%), and as the most needed for surgical team improvement (45, 67%). There was a very high demand for NTS training by all surgical team members (64, 96%). The main motivations for training were expectations of resultant improved patient safety and improved interprofessional team dynamics. Week-long, hybrid training courses (with combined in-person and online components) were the preferred format for delivery of NTS education. Factors that would facilitate attendance included a desire for patient safety and self-improvement, while barriers to attendance were conflicts of time, and training costs.

Conclusions

Interprofessional surgical teams in the Nigerian context have a high degree of interest in NTS training, and believe it can improve team dynamics, personal performance, and ultimately patient safety. Implementation of NTS training programs should emphasize interprofessional communication and teamworking.
Ethical considerations and concerns in the implementation of AI in pharmacy practice: a cross-sectional study
Authors: Hasan Hisham E. , Jaber Deema , Khabour Omar F. , Alzoubi Karem H.
Published: May 2024

Background

Integrating artificial intelligence (AI) into healthcare has raised significant ethical concerns. In pharmacy practice, AI offers promising advances but also poses ethical challenges.

Methods

A cross-sectional study was conducted in countries from the Middle East and North Africa (MENA) region on 501 pharmacy professionals. A 12-item online questionnaire assessed ethical concerns related to the adoption of AI in pharmacy practice. Demographic factors associated with ethical concerns were analyzed via SPSS v.27 software using appropriate statistical tests.

Results

Participants expressed concerns about patient data privacy (58.9%), cybersecurity threats (58.9%), potential job displacement (62.9%), and lack of legal regulation (67.0%). Tech-savviness and basic AI understanding were correlated with higher concern scores (p < 0.001). Ethical implications include the need for informed consent, beneficence, justice, and transparency in the use of AI.

Conclusion

The findings emphasize the importance of ethical guidelines, education, and patient autonomy in adopting AI. Collaboration, data privacy, and equitable access are crucial to the responsible use of AI in pharmacy practice.
Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma
Authors: Liu Yun , He Mingwei , Tang Haijun , Xie Tianyu , Lin Yunhua , Liu Shangyu , Liang Jiming , Li Feicui , Luo Kai , Yang Mingxiu , Teng Hongcai , Luo Xiaoting , He Juliang , Liao Shijie , Huang Qian , Feng Wenyu , Zhan Xinli , Wei Qingjun
Published: May 2024

Background

Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear.

Methods

Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics.

Results

From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells.

Conclusions

Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.
Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda
Authors: Schreidah Cecile , Giesbrecht David , Gashema Pierre , Young Neeva Wernsman , Munyaneza Tharcisse , Muvunyi Claude Mambo , Thwai Kyaw , Mazarati Jean-Baptiste , Bailey Jeffrey A. , Juliano Jonathan J. , Karema Corine
Published: May 2024

Background

Emerging artemisinin partial resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (k13) propeller-domain mutations that confer artemisinin partial resistance have emerged in Africa. k13-561H was initially described at a frequency of 7.4% from Masaka in 2014–2015, but not present in nearby Rukara. By 2018, 19.6% of isolates in Masaka and 22% of isolates in Rukara contained the mutation. Longitudinal monitoring is essential to inform control efforts. In Rukara, an assessment was conducted to evaluate recent k13-561H prevalence changes, as well as other key mutations. Prevalence of hrp2/3 deletions was also assessed.

Methods

Samples collected in Rukara in 2021 were genotyped for key artemisinin and partner drug resistance mutations using molecular inversion probe assays and for hrp2/3 deletions using qPCR.

Results

Clinically validated k13 artemisinin partial resistance mutations continue to increase in prevalence with the overall level of mutant infections reaching 32% in Rwanda. The increase appears to be due to the rapid emergence of k13-675V (6.4%, 6/94 infections), previously not observed, rather than continued expansion of 561H (23.5% 20/85). Mutations to partner drugs and other anti-malarials were variable, with high levels of multidrug resistance 1 (mdr1) N86 (95.5%) associated with lumefantrine decreased susceptibility and dihydrofolate reductase (dhfr) 164L (24.7%) associated with a high level of antifolate resistance, but low levels of amodiaquine resistance polymorphisms with chloroquine resistance transporter (crt) 76T: at 6.1% prevalence. No hrp2 or hrp3 gene deletions associated with diagnostic resistance were found.

Conclusions

Increasing prevalence of artemisinin partial resistance due to k13-561H and the rapid expansion of k13-675V is concerning for the longevity of artemisinin effectiveness in the region. False negative RDT results do not appear to be an issue with no hrp2 or hpr3 deletions detected. Continued molecular surveillance in this region and surrounding areas is needed to follow artemisinin partial resistance and provide early detection of partner drug resistance, which would likely compromise control and increase malaria morbidity and mortality in East Africa.
NEMO/NF-κB signaling functions as a double-edged sword in PanIN formation versus progression to pancreatic cancer
Authors: Tsesmelis Miltiadis , Büttner Ulrike F. G. , Gerstenlauer Melanie , Manfras Uta , Tsesmelis Konstantinos , Du Ziwei , Sperb Nadine , Weissinger Stephanie Ellen , Möller Peter , Barth Thomas F. E. , Maier Harald J. , Chan Lap Kwan , Wirth Thomas
Published: May 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) is marked by a dismal survival rate, lacking effective therapeutics due to its aggressive growth, late-stage diagnosis, and chemotherapy resistance. Despite debates on NF-κB targeting for PDAC treatment, no successful approach has emerged.

Methods

To elucidate the role of NF-κB, we ablated NF-κB essential modulator (NEMO), critical for conventional NF-κB signaling, in the pancreata of mice that develop precancerous lesions (KC mouse model). Secretagogue-induced pancreatitis by cerulein injections was utilized to promote inflammation and accelerate PDAC development.

Results

NEMO deletion reduced fibrosis and inflammation in young KC mice, resulting in fewer pancreatic intraepithelial neoplasias (PanINs) at later stages. Paradoxically, however, NEMO deletion accelerated the progression of these fewer PanINs to PDAC and reduced median lifespan. Further, analysis of tissue microarrays from human PDAC sections highlighted the correlation between reduced NEMO expression in neoplastic cells and poorer prognosis, supporting our observation in mice. Mechanistically, NEMO deletion impeded oncogene-induced senescence (OIS), which is normally active in low-grade PanINs. This blockage resulted in fewer senescence-associated secretory phenotype (SASP) factors, reducing inflammation. However, blocked OIS fostered replication stress and DNA damage accumulation which accelerated PanIN progression to PDAC. Finally, treatment with the DNA damage-inducing reagent etoposide resulted in elevated cell death in NEMO-ablated PDAC cells compared to their NEMO-competent counterparts, indicative of a synthetic lethality paradigm.

Conclusions

NEMO exhibited both oncogenic and tumor-suppressive properties during PDAC development. Caution is suggested in therapeutic interventions targeting NF-κB, which may be detrimental during PanIN progression but beneficial post-PDAC development.

Graphical Abstract
Synergistic activity of gold nanoparticles with amphotericin B on persister cells of Candida tropicalis biofilms
Authors: Dasilva M. A. , Andrada K. F. Crespo , Torales M. Maldonado , Hughes I. Manrrique , Pez P. , García-Martínez J. C. , Paraje María Gabriela
Published: May 2024

Aim

The antifungal activity was studied on sessile and persister cells (PCs) of Candida tropicalis biofilms of gold nanoparticles (AuNPs) stabilized with cetyltrimethylammonium bromide (CTAB-AuNPs) and those conjugated with cysteine, in combination with Amphotericin B (AmB).

Materials/methods

The PC model was used and synergistic activity was tested by the checkerboard assay. Biofilms were studied by crystal violet and scanning electron microscopy.

Results/Conclusions

After the combination of both AuNPs and AmB the biofilm biomass was reduced, with significant differences in architecture being observed with a reduced biofilm matrix. In addition, the CTAB-AuNPs-AmB combination significantly reduced PCs. Understanding how these AuNPs aid in the fight against biofilms and the development of new approaches to eradicate PCs has relevance for chronic infection treatment.
Natural products in the management of neurodegenerative diseases
Authors: Goyal Rajat , Mittal Pooja , Gautam Rupesh K. , Kamal Mohammad Amjad , Perveen Asma , Garg Vandana , Alexiou Athanasios , Saboor Muhammad , Haque Shafiul , Farhana Aisha , Papadakis Marios , Ashraf Ghulam Md
Published: May 2024

Neurodegenerative diseases represent one of the utmost imperative well-being health issues and apprehensions due to their escalating incidence of mortality. Natural derivatives are more efficacious in various preclinical models of neurodegenerative illnesses. These natural compounds include phytoconstituents in herbs, vegetables, fruits, nuts, and marine and freshwater flora, with remarkable efficacy in mitigating neurodegeneration and enhancing cognitive abilities in preclinical models. According to the latest research, the therapeutic activity of natural substances can be increased by adding phytoconstituents in nanocarriers such as nanoparticles, nanogels, and nanostructured lipid carriers. They can enhance the stability and specificity of the bioactive compounds to a more considerable extent. Nanotechnology can also provide targeting, enhancing their specificity to the respective site of action. In light of these findings, this article discusses the biological and therapeutic potential of natural products and their bioactive derivatives to exert neuroprotective effects and some clinical studies assessing their translational potential to treat neurodegenerative disorders.

Graphical Abstract

Common mechanisms, therapeutic targets, and molecular pathogenesis of neurodegeneration. It is focused on the biological and therapeutic potential of natural products and their bioactive derivatives to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.
A novel MT-ATP6 variant associated with complicated ataxia in two unrelated Italian patients: case report and functional studies
Authors: Sala Daniele , Marchet Silvia , Nanetti Lorenzo , Legati Andrea , Mariotti Caterina , Lamantea Eleonora , Ghezzi Daniele , Catania Alessia , Lamperti Costanza
Published: May 2024

Background

MT-ATP6 is a mitochondrial gene which encodes for the intramembrane subunit 6 (or A) of the mitochondrial ATP synthase, also known asl complex V, which is involved in the last step of oxidative phosphorylation to produce cellular ATP through aerobic metabolism. Although classically associated with the NARP syndrome, recent evidence highlights an important role of MT-ATP6 pathogenic variants in complicated adult-onset ataxias.

Methods

We describe two unrelated patients with adult-onset cerebellar ataxia associated with severe optic atrophy and mild cognitive impairment. Whole mitochondrial DNA sequencing was performed in both patients. We employed patients’ primary fibroblasts and cytoplasmic hybrids (cybrids), generated from patients-derived cells, to assess the activity of respiratory chain complexes, oxygen consumption rate (OCR), ATP production and mitochondrial membrane potential.

Results

In both patients, we identified the same novel m.8777 T > C variant in MT-ATP6 with variable heteroplasmy level in different tissues. We identifed an additional heteroplasmic novel variant in MT-ATP6, m.8879G > T, in the patients with the most severe phenotype. A significant reduction in complex V activity, OCR and ATP production was observed in cybrid clones homoplasmic for the m.8777 T > C variant, while no functional defect was detected in m.8879G > T homoplasmic clones. In addition, fibroblasts with high heteroplasmic levelsof m.8777 T > C variant showed hyperpolarization of mitochondrial membranes.

Conclusions

We describe a novel pathogenic mtDNA variant in MT-ATP6 associated with adult-onset ataxia, reinforcing the value of mtDNA screening within the diagnostic workflow of selected patients with late onset ataxias.
3D molecular structural modeling and characterization of indium phosphide via irregularity topological indices
Authors: Salman Muhammad , Ullah Asad , Zaman Shahid , Mahmoud Emad E. , Belay Melaku Berhe
Published: May 2024

Indium phosphide (InP) is a binary semiconductor composed of indium and phosphorus. It has a zinc blende crystal structure, which is a type of cubic lattice structure. This lattice is composed of indium and phosphorus atoms arranged in a lattice of cube-shaped cells, with each cell containing four indium atoms and four phosphorus atoms. This lattice structure is the same for all materials with a zinc blende crystal structure and is the most common type of lattice structure in semiconductors. Indium phosphide (InP) has several chemical applications. It is commonly used as a dopant in the production of semiconductors, where it helps control the electrical properties of the material. InP is also utilized in the synthesis various indium-containing compounds, which can have applications in catalysts and chemical reactions. Additionally, InP nanoparticles have been investigated for their potential use in biomedical imaging and drug delivery systems. The topological characterization of 3D molecular structures can be performed via graph theory. In graph theory, the connections between atoms are represented as edges and the atoms themselves are represented as nodes. Furthermore, graph theory can be used to calculate the topological descriptors of the molecule such as the degree-based and reverse degree-based irregularity toplogical indices. These descriptors can be used to compare the topology of different molecules. This paper deals with the modeling and topological characterization of indium phosphide $$({\text{InP}})$$

(
InP
)

via degree-based and reverse irregularity indices. The 3D crystal structure of the InP is topologically modeled via partition of the edges, and derived closed form expressions for its irregularity indices. Our obtained results will be surely be helpful in investigating the QSPR/QSAR analysis as well as understanding the deep irregular behavior of the indium phosphide $$({\text{InP}})$$

(
InP
)

.