bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential genetic association between coffee/caffeine consumption and erectile dysfunction: a Mendelian randomization study and meta-analysis
Authors: Xiang Nana , Hu Yanhua , Peng Wenchun , Luo Mei , Chen Hong , Zhang Qiuhua 
Published: October 2024

BackgroundCoffee is a widely consumed beverage with potential benefits for various chronic diseases. Its effect on reducing erectile dysfunction (ED) risk is unclear. This Mendelian randomization (MR) study investigates the impact of coffee/caffeine consumption on ED.MethodsTwo sets of coffee consumption-associated genetic variants at the genome-wide significance level were obtained from recent studies of coffee consumption. Taking into account other sources of caffeine, genetic variants associated with caffeine consumption from tea were also obtained. The inverse variance weighted (IVW) method was utilized as the primary analysis. Sensitivity analysis methods and meta-analysis methods were performed to confirm the robustness of the results, while the genetic variants associated with confounders, e.g., diabetes and hypertension, were excluded.ResultsGenetically predicted coffee/caffeine consumption was unlikely to be associated with the risk of ED in the Bovijn datasets, with similar directional associations observed in the FinnGen datasets. The combined odds ratio for ED was 1.011 (95% CI 0.841–1.216, p=0.906) for coffee consumption from the genome-wide meta-analysis, 1.049 (95% CI 0.487–2.260, p=0.903) for coffee consumption from the genome-wide association study, and 1.061 (95% CI 0.682–1.651, p=0.793) for caffeine from tea.ConclusionUsing genetic data, this study found no association between coffee/caffeine consumption and the risk of ED.
Shallow drainage of agricultural peatlands without land-use change: have your peat and eat it too
Authors: Heuts T. S. , Giersbergen Q. van , Nouta R. , Nijman T. P. A. , Aben R. C. H. , Scheer O. van der , Heuts P. G. M. , Skovsholt L. J. , Quadra G. R. , Smolders A. J. P. , Fritz C. 
Published: October 2024

IntroductionDrainage for agricultural purposes is one of the main drivers of peatland degradation, leading to significant greenhouse gas (GHG) emissions, biodiversity loss, and soil eutrophication. Rewetting is a potential solution to restore peatlands, but it generally requires a land-use shift to paludiculture or nature areas.MethodsThis study explored whether three different water level management techniques (subsoil irrigation, furrow irrigation, and dynamic ditch water level regulation) could be implemented on dairy grasslands to yield increases in essential ecosystem services (vegetation diversity and soil biogeochemistry) without the need to change the current land use or intensity. We investigated vegetation diversity, soil biogeochemistry, and CO2 emission reduction in fourteen agricultural livestock pastures on drained peat soils in Friesland (Netherlands).ResultsAcross all pastures, Shannon-Wiener diversity was below 1, and the species richness was below 5. The plant-available phosphorus (P) was consistently higher than 3 mmol L−1. None of the water level management (WLM) techniques enhanced vegetation diversity or changed soil biogeochemistry despite a notable increase in water table levels. The potential for CO2 emission reduction remained small or even absent. Indicators of land-use intensity (i.e., grass harvest and fertilization intensity), however, showed a strong negative correlation with vegetation diversity. Furthermore, all sites’ total and plant-available P and nitrate exceeded the upper threshold for species-rich grassland communities.DiscussionIn conclusion, our research suggests that incomplete rewetting (i.e., higher water tables while maintaining drainage) while continuing the current land use does neither effectively mitigate GHG emissions nor benefit vegetation diversity. Therefore, we conclude that combining WLM and reducing land-use intensity is essential to limit the degradation of peat soils and restore more biodiverse vegetation.
The evolution of flexibility and function in the Fc domains of IgM, IgY, and IgE
Authors: Calvert Rosaleen A. , Nyamboya Rosemary A. , Beavil Andrew J. , Sutton Brian J. 
Published: October 2024

IntroductionAntibody Fc regions harbour the binding sites for receptors that mediate effector functions following antigen engagement by the Fab regions. An extended “hinge” region in IgG allows flexibility between Fab and Fc, but in both the most primitive antibody, IgM, and in the evolutionarily more recent IgE, the hinge is replaced by an additional domain pair in the homodimeric six-domain Fc region. This permits additional flexibility within the Fc region, which has been exploited by nature to modulate antibody effector functions. Thus, in pentameric or hexameric IgM, the Fc regions appear to adopt a planar conformation in solution until antigen binding causes a conformational change and exposes the complement binding sites. In contrast, IgE-Fc principally adopts an acutely bent conformation in solution, but the binding of different receptors is controlled by the degree of bending, and there is allosteric communication between receptor binding sites.MethodsWe sought to trace the evolution of Fc conformational diversity from IgM to IgE via the intermediate avian IgY by studying the solution conformations of their Fc regions by small-angle X-ray scattering. We compared four extant proteins: human IgM-Fc homodimer, chicken IgY-Fc, platypus IgE-Fc, and human IgE-Fc. These are examples of proteins that first appeared in the jawed fish [425 million years ago (mya)], tetrapod (310 mya), monotreme (166 mya), and hominid (2.5 mya) clades, respectively.Results and discussionWe analysed the scattering curves in terms of contributions from a pool of variously bent models chosen by a non-negative linear least-squares algorithm and found that the four proteins form a series in which the proportion of acutely bent material increases: IgM-Fc &lt; IgY-Fc &lt; plIgE-Fc &lt; huIgE-Fc. This follows their order of appearance in evolution. For the huIgM-Fc homodimer, although none are acutely bent, and a significant fraction of the protein is sufficiently bent to expose the C1q-binding site, it predominantly adopts a fully extended conformation. In contrast, huIgE-Fc is found principally to be acutely bent, as expected from earlier studies. IgY-Fc, in this first structural analysis of the complete Fc region, exhibits an ensemble of conformations from acutely bent to fully extended, reflecting IgY’s position as an evolutionary intermediate between IgM and IgE.
Grip strength and depressive symptoms in Chinese middle-aged and older adults: the mediating effects of cognitive function
Authors: Wang Xinzheng , Wu Lifei , Zhou Huifen , He Jiandong 
Published: October 2024

ObjectiveThis study investigates the associations and mediating pathways between grip strength, cognitive function, and depression in middle-aged and elderly individuals in China.MethodsUtilizing data from the 2011 China Health and Retirement Longitudinal Study (CHARLS), we employed logistic regression and mediation analysis to examine the relationships and mediating factors between grip strength, cognitive function, and depression, while adjusting for potential confounders.ResultsThe study included 6,841 participants, of whom 1,734 (25.35%) exhibited symptoms of depression. Our findings indicate that weak grip strength is significantly associated with an increased risk of depression (OR: 1.57, 95% CI: 1.32–1.87) among the middle-aged and elderly population. Conversely, good cognitive function was found to be protective against depression (OR: 0.94, 95% CI: 0.93–0.95). Grip strength indirectly affected depression through cognitive function, accounting for 9.4% of the total effect (β = −0.008, 95% CI [−0.013, −0.004]). This mediating effect was 23.8% in men (β = −0.013, 95% CI [−0.020, −0.007]); and 23.2% in those aged 60 years and over (β = −0.015, 95% CI [−0.022, −0.009]).ConclusionThis study highlights that weak grip strength increases risk of depressive symptoms, and adequate cognitive function can mitigate the association between weak grip strength and an increased risk of depression among middle-aged and elderly individuals in China. Psychological care for elder adults with weak grip strength and poor cognitive function should be strengthened.
Transthyretin amyloidosis in patients with spinal stenosis who underwent spinal surgery: a systematic review and meta-analysis
Authors: Tamasauskas Domantas , Tamasauskiene Laura 
Published: October 2024

BackgroundAccumulation of transthyretin amyloids (ATTR) is detected in ligamentum flavum in about 1/3 of patients underwent surgery for spinal stenosis. However, the significance of this finding is not known. The aim of this systematic review and meta-analysis is to analyze the incidence and importance of ATTR in patients with spinal stenosis who underwent spinal surgery.MethodsThe primary outcome measure was incidence of ATTR in patients with spinal stenosis. English language observational studies published within 10 years period were searched in Pubmed and Taylor and Francis databases.ResultsNine articles were included in the systematic review. The incidence of positive ATTR among patients who underwent lumbar spinal surgery was 48% (95%CI 38–58%). ATTR deposits were found in the lumbar region the most frequently. Seven studies showed that patients with positive ATTR were older than those with negative. Five studies investigated and found a significant relationship between the ligamentum flavum thickness and positive ATTR. Five studies investigated cardiac involvement among patients with positive ATTR.ConclusionATTR deposits are frequently found in older patients with spinal stenosis, especially in the lumbar region. The presence of ATTR deposits is related to ligamentum flavum thickness.
Natural resources used in the traditional medicine of the Marinaú community, Caxiuanã forest, Brazil
Authors: de Oliveira Paula Maria Correa , Sousa João Paulo Barreto , Albernaz Lorena C. , Salmen Espindola Laila , Coelho-Ferreira Márlia 
Published: October 2024

BackgroundThe diversity of Conservation Units in Brazil, ranging from Strict Protection areas like National Parks to Sustainable Use areas such as National Forests, supports the coexistence of human populations with extensive traditional knowledge of local natural resources. This traditional and local knowledge plays a crucial role in their subsistence and has significant potential to contribute to bioprospecting initiatives, as well as to enhance research and strategies for biological conservation. The São Sebastião de Marinaú community, situated within the Caxiuanã National Forest, offers valuable opportunities for ethnobiological studies.MethodsThe field study was carried out with 48 informants from the São Sebastião de Marinaú Community, Caxiuanã National Forest (CNF), Brazil, a Sustainable Use Conservation Unit. It involved participant observation, semi-structured interviews, and guided tours. Indices of Use Value (UV), Fidelity Level (FL), and Consensus Factor (ICF) indicated plant species with therapeutic potential.ResultsA total of 944 uses associated with 154 plants and 21 animals were reported. Statistical tests pointed out that factors such as gender and age are not determinants in the richness of known plants among the residents. The plants are distributed among 59 botanical families and 126 genera. They predominantly use species native to Brazil (69%), among which 47 are endemic to the Amazon. The medicines are prepared mainly by decoction of leaves and bark. According to UV, veronica (Dalbergia monetaria L.f.) was the most important. The animals used are all vertebrates, and paca (Cuniculus paca Linnaeus, 1766,) was the most cited. Bile and lard are the parts most used in the recipes. They mentioned 116 diseases, especially those of the digestive system. The ceruzeiro (Allantoma lineata (Mart. ex O.Berg) Miers) had a high consensus of local use, and no additional studies on this species exist.ConclusionThis study underscores the vital role of traditional communities in sustainable conservation units, as their involvement is crucial for preserving plant and animal species essential to local traditional medicine. Such research also promotes the recognition of non-timber products as valuable raw materials with potential applications in the chemical and pharmaceutical industries. Additionally, mapping the occurrence and use of species in vulnerable conditions aids in developing effective conservation strategies for these resources.
Psychological wellbeing among carers of children and adolescents with physical disabilities in North-Eastern Tanzania—a cross-sectional survey study
Authors: Swai Elia Asanterabi , Moshi Haleluya Imanueli , Msuya Sia Emmanueli , Sörlin Ann , Sahlen Klas-Göran , Lindkvist Marie 
Published: October 2024

IntroductionCaring for physically disabled children, particularly in contexts where resources are often insufficient or absent, exposes primary carers to significant psychological strain. The lack of structured mechanisms to address this psychological burden poses a considerable threat to the wellbeing of both carers and the children with disabilities under their care. However, research on the psychological wellbeing of carers in Tanzania is scarce. This study aimed to evaluate the psychological wellbeing and symptoms of anxiety and depression, along with associated factors, of carers of children, and adolescents with physical disabilities in the Kilimanjaro region.MethodsA cross-sectional survey was conducted from November 2020 to June 2021 in the Kilimanjaro region, involving 212 carers. The Swahili versions of the WHO-5 Wellbeing Index and Hopkins Symptoms Check List-25 were used to assess psychological wellbeing and symptoms of anxiety and depression. Data were analysed using IBM SPSS Statistics V.28. Multivariable linear and binary logistic regression were used to assess the associations.ResultsMore than four fifths (81%) of the carers were parents, and most of these parents were mothers (92%). Of the 212 carers, more than half (51%) exhibited poor psychological wellbeing, 42% had symptoms of anxiety, and 38% symptoms of depression. Notably, poor psychological wellbeing was significantly associated with symptoms of anxiety and depression. Results of a multivariable regression analysis indicated that extended family support was associated with better psychological wellbeing and lower odds of symptoms of anxiety and depression. A higher estimated monthly income was associated with better psychological wellbeing, and lower odds of symptoms of depression. Access to rehabilitation for the child was associated with improved psychological wellbeing and decreased likelihood of symptoms of anxiety.ConclusionMany carers of children, and adolescents with physical disabilities in Tanzania are at high risk of having poor psychological wellbeing, and symptoms of anxiety and depression. Support from extended-family networks is crucial in promoting good psychological wellbeing. The government in Tanzania should improve rehabilitation services, especially in disadvantaged rural areas, and integrate mental-health screening for carers in both rehabilitation programmes and primary healthcare.
Global A-to-I RNA editing during myogenic differentiation of goat MuSCs
Authors: Xu Xiaoli , Zhang Mancheng , Zhan Siyuan , Chen Yuan , Wei Chengqi , Cao Jiaxue , Guo Jiazhong , Dai Dinghui , Wang Linjie , Zhong Tao , Zhang Hongping , Li Li 
Published: October 2024

BackgroundRNA editing, especially A-to-I editing sites, is a common RNA modification critical for stem cell differentiation, muscle development, and disease occurrence. Unveiling comprehensive RNA A-to-I editing events associated with myogenesis of the skeletal muscle satellite cells (MuSCs) is essential for extending our knowledge of the mechanism underpinning muscle development.ResultsA total of 9,632 RNA editing sites (RESs) were screened in the myoblasts (GM), myocytes (DM1), and myotubes (DM5) samples. Among these sites, 4,559 A-to-I edits were classified and further analyzed. There were 3,266 A-to-I sites in the protein-coding region, out of which 113 missense sites recoded protein. Notably, five A-to-I sites in the 3′ UTR of four genes (TRAF6, NALF1, SLC38A1, ENSCHIG00000019092) altered their targeted miRNAs. Furthermore, a total of 370 A-to-I sites with different editing levels were detected, including FBN1, MYH10, GSK3B, CSNK1D, and PRKACB genes. These genes were predominantly enriched in the cytoskeleton in muscle cells, the hippo signaling pathway, and the tight junction. Furthermore, we identified 14 hub genes (TUFM, GSK3B, JAK2, RPSA, YARS1, CDH2, PRKACB, RUNX1, NOTCH2, CDC23, VCP, FBN1, RARS1, MEF2C) that potentially related to muscle development. Additionally, 123 stage-specific A-to-I editing sites were identified, with 43 sites in GM, 25 in DM1, and 55 in DM5 samples. These stage-specific edited genes significantly enriched essential biological pathways, including the cell cycle, oocyte meiosis, motor proteins, and hedgehog signaling pathway.ConclusionWe systematically identified the RNA editing events in proliferating and differentiating goat MuSCs, which was crucial for expanding our understanding of the regulatory mechanisms of muscle development.
Identification of multiple novel viruses in bar-headed goose feces from Tibet of China
Authors: Sun Yijie , Wang Yan , Ji Li , Pei Yifei , Sun Xiaoyi , Ji Likai , Shen Quan , Wang Xiaochun , Liu Yuwei , Yang Shixing , Zhang Wen 
Published: October 2024

IntroductionThe bar-headed goose is a typical high-altitude bird that primarily inhabits alpine lakes and wetlands in Central Asia, with a remarkable ability to adapt to high elevations. Previous studies have shown that they can be infected with parasites such as Cryptosporidium spp. At present, there were few reports on its infection with the virus.MethodsIn this study, we utilized viral metagenomics to conduct a detailed analysis of the viral components in the fecal samples of bar-headed geese (Anser indicus) from the Tibet region of China.ResultsMultiple novel viruses were identified including four novel astroviruses, four novel caliciviruses, ten novel circoviruses, and nineteen novel parvoviruses. Among them, four astroviruses shared the highest amino acid sequence identities of 63.45–99.47% with different avastrovirus strains. Four caliciviruses and ten circoviruses were identified as unclassified caliciviruses and unclassified circoviruses, separately. Nineteen parvoviruses clustering into four groups maybe four different novel species of the genus Chaphamaparvovirus.ConclusionThese newly discovered viruses have potential implications for the health of avian species, particularly bar-headed geese. This study not only helps us understand the health status of bar-headed geese, but also offers crucial genomic information for future disease prevention and treatment strategies.
Vector Competence of Aedes aegypti from São Tomé and Príncipe for West Nile Virus Transmission
Authors: Marmé Rafael , Tomaz Filipe , Sousa Carla A. , Pinto João , Lanzaro Gregory C. , Parreira Ricardo , Seixas Gonçalo 
Published: October 2024

The global distribution of Aedes aegypti mosquitoes, particularly in tropical regions, poses a significant public health risk due to their apparent ability to transmit arboviruses such as West Nile virus (WNV). This study aimed to evaluate the vector competence of Ae. aegypti from São Tomé and Príncipe (STP) for the transmission of the WNV PT6.39 strain, considering its potential role as a bridge vector in a region where Culex quinquefasciatus would be the main vector. Aedes aegypti mosquitoes were collected, reared, and experimentally infected with WNV, with viral dissemination and transmission potential assessed 7, 14, and 21 days post infection (dpi). The results showed an increasing trend in infection rates, from 5% at 7 dpi to 35% at 21 dpi, with corresponding dissemination rates of 0%, 100%, and 43%. The transmission rates also increased from 0% at 7 dpi to 67% at 21 dpi, with a maximum transmission efficiency of 10% observed at the final time point. Although Ae. aegypti from STP demonstrated the potential to transmit WNV, the overall transmission efficiency remained relatively low. These findings provide necessary insights into the vector competence of Ae. aegypti in this region, highlighting the importance of continued monitoring and targeted vector control measures to mitigate the risk of potential WNV outbreaks.
Efficacy and Safety of Nefecon in Patients with IgA Nephropathy from Mainland China: 2-Year NefIgArd Trial Results
Authors: Zhang Hong , Lafayette Richard , Wang Bei , Ying Lisa , Zhu Zhengying , Stone Andrew , Kristensen Jens , Barratt Jonathan 
Published: October 2024

Key Points

In the NefIgArd trial China cohort, 9 months of nefecon treatment led to clinically relevant preservation of kidney function over 2 years.Durable proteinuria reduction was also observed over 2 years with 9 months of nefecon treatment.These results were consistent with those of the global study population and support the disease-modifying effects of nefecon.

Background
IgA nephropathy (IgAN), an immune-mediated kidney disease, is particularly prevalent among individuals of East Asian ancestry. Nefecon is a novel, oral, targeted-release budesonide formulation designed to inhibit galactose-deficient IgA1 formation underlying IgAN pathophysiology. We present findings in patients with IgAN from mainland China participating in the 2-year, multicenter, randomized, double-blind, phase 3 NefIgArd trial of nefecon.

Methods
Patients (aged 18 years and older) with primary IgAN (eGFR 35–90 ml/min per 1.73 m2, persistent proteinuria [urine protein–creatinine ratio ≥0.8 g/g or proteinuria ≥1 g/24 hours] despite optimized renin-angiotensin system blockade) received nefecon or placebo over 9 months, followed by a 15-month follow-up phase on supportive care alone. The primary efficacy end point was time-weighted average of eGFR over 2 years.

Results
Sixty-two patients from mainland China were included in this prespecified analysis. The primary efficacy end point was 9.6 ml/min per 1.73 m2 (95% confidence interval, 2.0 to 19.8) in favor of nefecon versus placebo. This was consistent with (and numerically greater than) that of the global study population. Time to confirmed 30% eGFR reduction or kidney failure from baseline was substantially delayed with nefecon (patients with an event: 9%) versus placebo (30%; hazard ratio, 0.21; 95% confidence interval, 0.04 to 0.73). No deaths were reported in the China cohort. In the nefecon group, treatment-emergent serious adverse events were reported by one patient during treatment and two patients during follow-up (versus no patients and seven patients, respectively, in the placebo group). No severe infections requiring hospitalization were reported.

Conclusions
Nefecon treatment for 9 months showed greater preservation of eGFR over 2 years compared with placebo. The efficacy outcomes were consistent with global study results, with a numerically greater treatment benefit observed in patients from China. Nefecon was well tolerated, with no unexpected safety signals.

Clinical Trial registry name and registration number:
Efficacy and Safety of Nefecon in Patients With Primary IgAN, NCT03643965.