bluuebunny/crossref_metadata_2025 huggingface dataset:
Double-blind, randomized, placebo-controlled clinical trial with gamma-band transcranial alternating current stimulation for the treatment of schizophrenic auditory hallucinations
Authors: Liu Shuang , Wang Xiaojuan , Zhang Xiaochen , Chang Yuan , Liao Jingmeng , Ming Dong
Published: October 2023

Gamma oscillations are essential for communication between brain regions, and 40Hz neural oscillation defects in schizophrenia. Due to the impaired functional connectivity of the left frontotemporal region, the information communication and integration between the frontal lobe and the temporo-parietal region of schizophrenia are faulty, thus produce auditory hallucinations. Homophasic transcranial alternating current stimulation is thought to enhance connectivity between different brain regions by modulating brain oscillations. In this work, we applied a frontal-temporal-parietal 40Hz-tACS stimulation strategy for treating auditory hallucinations and further explored the effect of tACS on functional connectivity of brain networks. 32 schizophrenia patients with refractory auditory hallucinations received 20 daily 20-min, 40Hz, 1-mA sessions of active or sham tACS on weekdays for 4 consecutive weeks, followed by a 2-week follow-up period without stimulation.Auditory hallucination symptom scores and 64-channel electroencephalograms were measured at baseline, week2, week4 and follow-up. For clinical symptom score, we observed a significant interaction between group and time for auditory hallucinations symptoms (F(3,90) = 26.964, p༜0.001), and subsequent analysis showed that the 40Hz-tACS group had a higher symptom reduction rate than the sham group at week4 (p = 0.036) and follow-up (p = 0.047). EEG results showed that, the 40Hz-tACS group had higher functional connectivity in the right and left frontal (F (1, 30) = 4.15, p = 0.051), right frontal to parietal (F (1, 30) = 7.24, p = 0.012), right frontal to occipital (F (1, 30) = 7.98, p = 0.008) and right intrafrontal (F (1, 30) = 4.13, p = 0.051) than the sham group at week4. Further, functional brain network controllability outcomes showed that the 40Hz-tACS group had increased average controllability (F (1, 30) = 6.26, p = 0.018) and decreased modality controllability (F (1, 30) = 6.50, p = 0.016) in the right frontal lobe compared to the sham group. Our study indicates that 40Hz-tACS may be an effective treatment for targeting symptoms specific to auditory hallucinations and altering functional connectivity and controllability at the network level.
Evaluating the association between placenta DNA methylation and cognitive functions in the offspring
Authors: Cosin-Tomas Marta , Diez-Ahijado Laia , Cislleros-Portet Ariadna , Fernández-Jimenez Nora , Fernández Mariana F. , Guxens Mònica , Julvez Jordi , Llop Sabrina , Lopez-Espinosa Maria-Jose , Subiza Mikel , Lozano Manuel , Ibarluzea Jesus , Sunyer Jordi , Bustamante Mariona , Cosin-Tomas Marta
Published: October 2023

Placenta plays a crucial role protecting the foetus from environmental harm and supports the development of its brain. In fact, compromised placental function could predispose an individual to neurodevelopmental disorders. Placental epigenetic modifications, including DNA methylation, could be considered a proxy of placental function and thus plausible mediators of the association between intrauterine environmental exposures and genetics, and childhood and adult mental health. Although neurodevelopmental disorders such as autism spectrum disorder have been investigated in relation to placenta DNA methylation, no studies have addressed the association between placenta DNA methylation and child’s cognitive functions. Thus, our goal here was to investigate whether placental DNA methylation profile measured using the Illumina EPIC array is associated with three different cognitive domains (namely verbal score, perceptive performance score, and general cognitive score) assessed by the McCarthy Scales of Children’s functions in childhood at age 4. To this end, we conducted epigenome-wide association analyses including data from 255 mother-child pairs within the INMA project and performed a follow-up functional analysis to help the interpretation of the findings. After multiple-testing correction, we found that methylation at 4 CpGs (cg1548200, cg02986379, cg00866476 and cg14113931) was significantly associated with the general cognitive score, and 2 distinct differentially methylated regions (DMRs) (including 27 CpGs) were significantly associated with each cognitive dimension. Interestingly, the genes annotated to these CpGs were involved in placenta, foetal, and brain development. Moreover, functional enrichment analyses of suggestive CpGs (p < 1x10− 4) revealed gene-sets involved in placenta development, foetus formation and brain growth. These findings suggest that placental DNAm could be a mechanism contributing to the alteration of important pathways in the placenta that have a consequence on the offspring’s brain development and cognitive function. .
Inferring molecular Inhibition potency with AlphaFold predicted structures
Authors: Falcao Andre , Oliveira Pedro , Guedes Rita
Published: October 2023

Even though in silico drug ligand-based methods have been successful in predicting interactions with known target proteins, they struggle with new, unassessed targets. To address this challenge, we propose an innovative approach that integrates structural data from AlphaFold 2-predicted protein structures into machine learning models. Our method extracts 3D structural protein fingerprints and combines them with ligand structural data to train a single machine learning model. This model captures the relationship between ligand properties and the unique structural features of various target proteins, enabling predictions for novel molecules and protein targets. To assess our model, we used a dataset of 144 Human G-protein Coupled Receptors (GPCRs) with over 140,000 measured inhibition constants (Ki) values. Our results demonstrate that our approach performs as well as state-of-the-art ligand-based methods, even for previously unencountered targets. In a test set of 15 protein targets with removed Ki information from the training data, our model predicted interactions for 73% of targets, with explained variances exceeding 0.50 in 22% of cases. In conclusion, our study presents an in silico drug development approach that bridges the gap between ligand-based methods and structural data integration for predicting protein-molecule interaction even for orphan targets.
A robust penalized-regression-based method for multivariable Mendelian randomization using GWAS summary statistics
Authors: Zhao Hongyu , Jiang Wei , Song Shuang , Lyu Liangbo , Chang Changgee , Zhao Yize , Wu Baolin , Wang Lan , Girgenti Matthew
Published: October 2023

Mendelian randomization (MR) is a statistical approach to inferring the causal relationships from genome-wide association studies (GWAS) by using genetic variants as instrumental variables (IVs). As IVs, the selected genetic variants should be solely associated with the exposure of interest, and have no associations with confounders and the studied outcome except through the exposure. Sometimes the selected genetic variants have effects on the outcome through other pathways, a phenomenon known as horizontal pleiotropy, which makes the selected variants violate IV assumptions. Two different approaches have been proposed to address this issue: one is to improve robustness to pleiotropic effects, and the other one is to generalize univariate exposure to multivariate cases so that we can incorporate possible pathways into MR analysis. Compared to pleiotropy-robust methods, multivariable Mendelian randomization (MVMR) can uncover the exposures having direct effects on the outcome. However, measuring all possible pathways from genetic variants to the outcome in MVMR analysis is difficult. Although MVMR methods with robustness to unmeasured pleiotropy have been proposed recently, they are statistically inefficient as a result of ignoring correlations among exposures and distributions of effect sizes.

Given the limitations from both directions, we propose a novel method named MVMR-PRESS that can infer causal relationships between multivariate exposures and the outcome with robustness to horizontal pleiotropic effects from unconsidered pathways. MVMR-PRESS estimates causal effects by using a Penalized Regression on Summary Statistics from GWAS considering both correlations among exposures and distributions of effect sizes. One merit of MVMR-PRESS is that samples in GWAS of different exposures can have overlaps, which allows us to include GWAS summary statistics from the same cohort or consortium. Simulation experiments showed that our method achieved the smallest bias and highest power compared to existing pleiotropy-robust MR and MVMR methods while the type 1 error rate was well-controlled. Applying MVMR-PRESS to publicly available GWAS summary statistics demonstrated that body mass index (BMI), height (HT), and low-density lipoprotein cholesterol (LDL) have significant causal effects on coronary artery disease (CAD), and BMI and high-density lipoprotein cholesterol (HDL) were causally related to type 2 diabetes (T2D). On the contrary, the causal estimates of triglycerides (TG), HDL, and total cholesterol (TC) on CAD, and the estimates of HT, LDL, TG, and TC on T2D were non-significant. In addition, we found no evidence suggesting BMI, HT, and lipid levels have causal effects on inflammatory bowel disease (IBD) and schizophrenia (SCZ).
Long-term outcomes of physical activity counseling in in-patients with major depressive disorder: Results from the PACINPAT randomized controlled trial
Authors: Kreppke Jan-Niklas , Cody Robyn , Beck Johannes , Brand Serge , Donath Lars , Eckert Anne , Faude Oliver , Hatzinger Martin , Imboden Christian , Lang Undine , Ludyga Sebastian , Mans Sarah , Mikoteit Thorsten , Oswald Anja , Schweinfurt Nina , Holsboer-Trachsler Edith , Zahner Lukas , Gerber Markus
Published: October 2023

Background: Major depressive disorder (MDD) is an increasingly common psychiatric illness associated with a high risk of insufficient physical activity, which in turn is associated with negative mental and physical health outcomes. Theory-based, individually tailored, in-person and remote physical activity counseling has the potential to increase physical activity levels in various populations. Given this, the present study investigated the effect of such a physical activity intervention on the physical activity behavior of in-patients with MDD.
Methods: This was a multi-center, two-arm randomized controlled trial including initially insufficiently physically active adult in-patients with MDD from four study sites in Switzerland. The sample consisted of 220 participants (Mage = 41 ± 12.6 years, 52% women), 113 of whom were randomized to the intervention group and 107 to the control group. The main outcome, moderate-to-vigorous physical activity (MVPA), was assessed at three time points via hip-worn accelerometer.
Results: According to accelerometer measures, there was no significant difference in minutes spent in MVPA over a 12-month intervention period when comparing the intervention with the control group (β = -1.02, 95% CI = -10.68 to 8.64). Higher baseline physical activity significantly predicted physical activity at post and follow-up.
Conclusion: This study showed that it is feasible to deliver an individually tailored, theory-based physical activity counseling intervention to in-patients with MDD, however yielding no significant effects on accelerometer-based MVPA levels. Further efforts are warranted to identify efficacious approaches.
Trial registration: ISRCTN, ISRCTN10469580, registered on 3rd September 2018, https://www.isrctn.com/ISRCTN10469580
A modular framework for FAIR shallow landslide susceptibility mapping based on machine learning
Authors: Edrich Ann-Kathrin , Yildiz Anil , Roscher Ribana , Kowalski Julia
Published: October 2023

Machine learning (ML) has become increasingly popular in recent years for susceptibility and hazard mapping tasks. Necessary steps of ML-based workflows for various purposes in the context of geohazards are implemented repeatedly for new studies. To facilitate an effective, modular and extensible application of ML for susceptibility and hazard mapping, a generic framework based on a Random Forest (RF) classifier is presented herein. It supports especially data pre-processing and RF input dataset generation, as well as the susceptibility or hazard map generation adapted to an individual research question. The FAIR data principles were adopted as a guideline during the design and implementation of the framework. In addition to the reproducibility of the resulting binary maps, the implementation enables extensibility and scalability. The framework is applied to the test case of rainfall triggered shallow landslide susceptibility in canton Grisons, Switzerland. Computational experiments investigating the influence of the composition of the training dataset on the mapping result are conducted. Thereby the combination of features, sampling strategies for absence (non-landslide) locations, and transferability from local to regional scale were of interest. The results emphasise the importance of considering the composition of training data for the quality of the model and as a result also the reliability of the generated map.
Oral Health Related Quality Of Life In Head And Neck Cancer Patients Visiting A Tertiary Center In Central Nepal
Authors: Koirala Resham , shrestha ashish , bhagat tarakant , agrawal santosh kumari , rimal jyotsna , gautam dejkumar
Published: October 2023

Background: Head and Neck Cancer (HNC) cases are rising every year. It is associated with various manifestations in oral cavity and leads to a compromise in Oral Health Related Quality of Life of the pateints.
Objectives: This study was conducted to assess Oral Health Related Quality of Life (OHRQoL) in Head and Neck cancer patients and compare it with their apparently normal counterparts.
Methods: A comparative cross–sectional study was conducted among 65 cases of HNC and their apparently normal counterparts visiting a tertiary cancer center in central Nepal. Diagnosed cases of HNC who were 18 years or more, providing consent and willing to participate in the study were taken as cases and 65 apparently healthy attendants after matching of age, sex and socio-economic status were taken as controls. Terminally ill, pregnant and those not providing consent were excluded from the study. Translated and validated OHIP-14 questionnaire was used to assess the Oral Health Related Quality of Life. Stage of cancer, site of cancer and time since diagnosed was assessed from the patient’s record file. Response to OHIP-14 items were recorded on a likert scale and the mean score was calculated. The results were statistically analysed using Mann-Whitney U test and Kruskal Wallis test.
Results: Majority of the participants belonged to upper lower socio-economic class. Mean OHIP -14 score in case group and control group were 23.91±9.71 and 6.54±4.86 respectively and the difference was statistically significant (p<0.001). The highest affected domain in case group was psychological discomfort (6.10±1.49) and that in control group was physical pain (2.50±1.70). In salivary gland tumor, the highest affected domain was handicap. In all other tumors, psychological discomfort was the highest affected domain and the values were not statistically significant.
Conclusion: There is an impairment of the OHRQoL in HNC patients which is higher than their normal counterparts.
TREM2+ macrophages regulate suppressive tumor microenvironment in TNBC
Authors: Sun Xiaohu , Yu Zhihao , Wang Kenie , Yu Yue , Wang Xin , Kang Ning , Cao Xu-Chen
Published: October 2023

Triple negative breast cancer (TNBC) possesses the poorest prognosis among the major breast cancer subtypes due to the limited treatment options. Nevertheless, TNBC is more immune-activated than other subtypes due to the higher mutation load, implicating that TNBC patients might benefit from immunotherapy. Previous studies have reported that the presence of tumor infiltrating lymphocytes in TNBC might create a suppressive immune microenvironment, which is associated with worse prognosis. Therefore, our work aims to compare the tumor microenvironment (TME) differences among breast cancer subtypes and discover the targetable Achilles’ heel of TNBC. We utilized public single-cell RNA-Seq (scRNA-Seq) dataset to analyze the cell composition and cell-cell communication network differences between TNBC and other subtypes. Further differential gene analysis and enrichment analysis was performed to define the transcriptomic variation. Our data showed that TREM2+ macrophages were elevated in TNBC and centrally located in the communication network. Finally, survival analysis was conducted in large cohort data to assess the involvement of TREM2+ macrophages in the progression of TNBC. Notably, the advanced TREM2+ macrophage signature was implicated with the survival outcomes of TNBC patients but not all breast cancer patients. Accordingly, this study uncovered a highly suppressive TME in TNBC, highlighted the essential role of TREM2+ macrophages in regulating the TME in TNBC, and revealed TREM2+ macrophages as a promising target for generating more favorable therapies in TNBC treatment.
Novel Compound Heterozygous MYO15A Splicing Variants in Autosomal Recessive Non-syndromic Hearing Loss
Authors: Zheng Kaifeng , Lin Sheng , Gao Jian , Chen Shiguo , Su Jindi , Liu Zhiqiang , Duan Shan
Published: October 2023

Background:Hereditary hearing loss is ahighly heterogeneous disorder both genetically and clinically. In this study, we aimed to identify the genetic cause of a Chinese family with autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL).
Methods:Clinical information and peripheral blood samples were collected from the proband and its parents. Two-stephigh-throughput next-generation sequencing on theIon Torrent platform was applied to detect mutations as follows. First, long-range PCR was performed to amplify the entire regions of the GJB2, GJB3, SLC26A4 and MT-RNR1 genes, and the products were submitted to next-generation sequencing. Targeted exon sequencing with AmpliSeq technology was further performed to examine another 64 deafness-associated genes. The identified variants and the cosegregationwith disease phenotypes in the family were validated by Sanger sequencing. We then assessed the effect of the mutation on the splicing of the MYO15A gene by bioinformatics prediction and minigene assays.
Results:Two candidate MYO15A gene heterozygous splicing mutations, c.6177+1G>T and c.9690+1G>A, were identified in the proband, and these two variants were both annotated as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Further bioinformatic analysis predicted that thec.6177+1G>T mutation might cause exon skipping and that the c.9690+1G>A mutation might activate a cryptic splicing donor site in the downstream intronic region. An in vitro minigene assay confirmed the above predictions.
Conclusions:We identified a compound heterozygous splicing mutation in the MYO15A gene in a Han Chinese family with ARNSHL. Our results broaden the spectrum of MYO15A mutations, potentially benefiting the early diagnosis, prevention and treatment of the disease.
Heracleum sosnowskyi or Heracleum mantegazzianum? DNA-based identification of invasive hogweeds (Apiaceae) in two key regions of the species' invasion history in the territory of the former Soviet Union
Authors: Shadrin Dmitry , Dalke Igor , Zakhozhiy Ilya , Shilnikov Dmitry , Kozhin Mikhail , Chadin Ivan
Published: October 2023

Heracleum mantegazzianum Sommier & Levier and Heracleum sosnowskyi Manden. are two species that belong to the giant invasive hogweed complex. H. mantegazzianum is predominantly found in Western European countries, while H. sosnowskyi is invasive in the European part of Russia and Eastern European countries. The taxonomy of the Heracleum genus is quite complex, and identifying these species requires extensive expertise. Surprisingly, although H. mantegazzianum and H. sosnowskyi are considered separate species, their morphological and ecological-physiological properties, as well as their ontogeny and population structure, exhibit remarkable similarities, making them ecological twins. The intentional introduction of this invasive species was initially conducted in the cities of Kirovsk city (Murmansk region, Russia) and Syktyvkar city (Komi Republic, Russia). Plant materials sourced from these two regions were subsequently distributed to all regions encompassing the modern hogweed invasion range across the former USSR countries. The objective of this study was to test the hypothesis that the plants initially introduced in Kirovsk and Syktyvkar actually belong to H. mantegazzianum. To accomplish this, herbarium material was collected, and DNA barcoding was performed on 16 samples of giant invasive hogweed from the vicinity of the cities of Kirovsk and Syktyvkar, as well as on 30 H. mantegazzianum samples collected within its native range in the Western Caucasus. The results of morphological identification combined with DNA barcoding demonstrate that H. mantegazzianum and the plants growing in Kirovsk and Syktyvkar belong to the same species – H. mantegazzianum, rather than H. sosnowskyi as previously believed.
Parametric effects on the behavior of the center and wall modes in viscoelastic channel flow of FENE-P fluid
Authors: Cheng Haotian , Zhang Hongna , Wang Suming , Zhang Wenhua , Li Xiaobin , Li Fengchen
Published: October 2023

The stability analysis plays an important role in comprehending the origin of elasto-inertial turbulence (EIT) of viscoelastic fluid. Currently, there is still a debate on whether it is the center mode or the wall mode that is the origin of EIT. The present paper conducts the linear stability analysis of viscoelastic fluid channel flows with the finitely extensible non-linear elastic Peterlin (FENE-P) model and focuses on the parametric effects, especially the nonlinear extension effect, on the characteristics of the center mode and wall mode. The effects of increasing Weissenberg number (Wi) and Reynolds number (Re) on the center mode and the wall mode are completely different, and the ranges of perturbation wavenumber α inducing the center mode and the wall mode instability vary greatly. The perturbation wavenumber causing the wall mode instability is around 1, whereas the range of wavenumber for the center mode instability can extend about from 1 to tens or even hundreds under the parameters concerned in this study. Moreover, with the increase of the maximum extension length L2, the wall mode and the center mode show the evolution trends of U-shaped and inverted U-shaped, respectively, and these two non-monotonic evolution trends are linked to the effective elasticity of FENE-P fluid. Additionally, we obtained a scaling correlation corresponding to the most unstable center mode with the largest growth rate. It indicates that the combination of effective elasticity and elasticity number (E=Wi/Re) can better reflect the elasticity strength felt by viscoelastic fluid flows.
Physical, nutritional, functional and rehydration properties of palm beetle (Oryctes rhynoceros) larvae as affected by drying and roasting
Authors: Falade Kolawole , Vigbe David
Published: October 2023

The effects of sun-drying, oven-drying and roasting on physical, chemical, functional and rehydration properties of palm beetle (Oryctes rhinoceros L.) larvae were investigated. Average weight (18.64g), length (67.74mm), breadth (22.56mm), and thickness (19.12mm) of live larvae reduced to 2.85-3.86mm, 36.78-38.24mm, 20.10-21.05mm and 16.50-18.88mm, respectively, with degutting, drying and roasting. Generally, lightness (49.93) and yellowness (11.68) of live larvae reduced to 28.89 and 5.60, when sun-dried. Crude protein, ash, fat and crude fibre contents of processed larvae varied from 65.46–69.99, 9.75–10.27. 13.79–21.01 and 0.55-1.23g/100g, respectively. Potassium, magnesium and sodium contents of processed larvae varied from 212.6–379.1, 58.76–184.6, and 104.65–170.75mg/100g, respectively. Sun-dried larvae showed higher amino acids contents than oven-dried and roasted larvae. However, the processed beetle larvae were rich in leucine, lysine, phenylalanine, aspartic acid, glutamic acid, isoleucine, leucine, threonine, valine, arginine, histidine and tyrosine. The water and absorption, OAC, loose and packed bulk density and dispersibility varied between 1.77–2.03, 1.20–1.33, 0.38-0.41g/mL, 0.56-0.60g/mL, 15.15-24.67sec and 18.77-26.00sec, respectively. Moisture contents of rehydrated sun-dried larvae were higher than oven-dried and roasted larvae between 15-45oC.
The moderating effect of social participation on the relationship between health status and depressive symptoms in older adults
Authors: Ow Yvonne Su Yong , Wei Chia-Shine , Li Yang-Tzu
Published: October 2023

Background
Depression is a common mental health problem among older adults and a leading cause of disability worldwide. Health status and social participation has been found significantly associated with depression in older adults. However, the role of social participation in the relationship between health status and depression remains unclear. This study aims to investigate the relationship between health status and depressive symptoms in older adults and the moderating effect of social participation in the relationship.
Methods
A cross-sectional study with data from the National Health Interview Survey (NHIS) in 2013. Older adults aged 65 years or older were included in the study. Multiple regression analysis was performed to examine the relationship between health status and depressive symptoms and assess the moderating effect of social participation.
Results
Of the 2731 participants, higher depressive symptoms were observed among older women, older adults who were single, living alone and having lower satisfaction on financial status. Regression analyses showed that ADL and IADL disability were positively associated with higher depressive symptoms. Perceived health status, cognitive functions and social participation were found negatively associated with depressive symptoms. A significant moderating effect of social participation between perceived health status and depressive symptoms was observed in this study.
Conclusions
The findings highlight the role of social participation in moderating the effect of perceived health status on depressive symptoms and suggest that promoting social participation among older adults may be helpful for reducing depressive symptoms.
CHIP Drives Proteasomal Degradation of Nur77 to Alleviate Oxidative Stress and Intrinsic Apoptosis in Cisplatin-induced Nephropathy
Authors: Zhang Hao , Deng Zebin , Wang Yilong , Zheng Xiaoping , Zhou Lizhi , Yan Shu , Wang Yinhuai , Dai Yingbo , Kanwar Yashpal. S , Deng Fei
Published: October 2023

Carboxy-terminus of Hsc70-interacting protein (CHIP), an E3 ligase, modulates the stability of its targeted proteins to alleviate various pathological perturbations in various organ systems. Cisplatin is a widely used chemotherapeutic agent, but it is also known for its alarming renal toxicity. The role of CHIP in the pathogenesis of cisplatin-induced acute kidney injury (AKI) has not been adequately investigated. Herein, we demonstrate that CHIP is abundantly expressed in the renal proximal tubular epithelia, and its expression is downregulated in cisplatin-induced AKI. Further investigation revealed that CHIP overexpression or activation alleviated, while its gene disruption promoted, oxidative stress and apoptosis in renal proximal tubular epithelia induced by cisplatin. In terms of mechanism, CHIP interacted with and ubiquitinated Nur77 to promote its degradation, which consequently shielded Bcl2 to maintain mitochondrial permeability of renal proximal tubular cells in the presence of cisplatin. Also, we demonstrate that CHIP interacts with Nur77 via its central coiled-coil (CC) domain, a non-canonical interactive pattern. In conclusion, these findings indicate that CHIP ubiquitinates and degrades its substrate Nur77 to attenuate intrinsic apoptosis in cisplatin-treated renal proximal tubular epithelia, thus providing a novel insight for the pathogenesis of cisplatin-induced AKI.
Factors associated with unindicated discontinuation of long-acting reversible contraceptives among refugee women in Rhino Camp and Kyangwali refugee settlements, Uganda
Authors: Kirima Andrew , Tuhebwe Doreen , Bukenya Justine N.
Published: October 2023

Background:
Unindicated discontinuation of long-acting reversible contraceptives (LARCs) poses a growing concern among refugee women residing in Rhino Camp and Kyangwali refugee settlements. This practice is closely linked with unintended pregnancies, short birth intervals, unsafe abortions, and maternal mortality. This study assessed the level and factors associated with the unindicated discontinuation of LARCs among refugee women in these settlements.
Methods:
A community-based cross-sectional study was conducted from January to March 2022, involving 284 refugee women. Data were collected through structured questionnaires and key informant interviews. Qualitative and quantitative data were analyzed using thematic analysis and STATA 14, respectively. Prevalence ratios and the corresponding 95% confidence intervals were determined.
Results:
The findings revealed that 90/284 refugee women (32% CI; 22.9%-41.1%) in Rhino camp and Kyangwali refugee settlements had discontinued their LARCs without indication. Notably, users of Implant contraceptives were more prone to discontinuation without a clinical indication. Several factors were associated with unindicated discontinuation, including residing in Rhino camp (adjusted prevalence ratio aPR = = 1.5, 95% confidence interval (CI): 1.01 - 2.30), having an education level up to primary (Upper) level (aPR= 4.9, 95% CI: 2.35 - 10.19), marital status (never married, (aPR = 1.299, 95% CI: 1.088 - 3.001), South Sudanese origin (aPR = 10.2, 95%CI: 1.51 - 68.45), living with all children in one household (aPR= 4.9, 95% CI: 1.26 – 19.16) and having given birth to only one child (aPR = 3.5, 95CI: 1.19 - 10.08).
Conversely, women who experienced mild side effects (aPR = 0.24, 95% CI: 0.12 - 0.48), perceived LARC devices as 100% effective in preventing pregnancy (aPR = 0.02, 95%CI: 0.00 - 0.24), lived with their partners (aPR = 0.38, 95% CI: 0.18 - 0.78) and had the support of their spouses in using LARC devices (aPR = 0.42, 95% CI: 0.19 - 0.94) exhibited a lower prevalence of unindicated LARC discontinuation. Additionally, health workers identified domestic violence and fear of side effects as underlying causes of unindicated LARC discontinuation.
Conclusions and Recommendations:
This study highlights the common occurrence of unindicated LARC discontinuation among refugee women in Rhino camp and Kyangwali refugee settlements, with a higher prevalence in Rhino camp. To address this issue, we recommend implementing comprehensive pre-insertion counselling, particularly for implant users, and launching extensive behavioural change initiatives to combat negative cultural practices, particularly among refugee women from patriarchal communities.
Fostering biodiversity in Neotropical savannahs: fire as a diversity driver for fruit-feeding butterfly assemblages in the Brazilian Cerrado
Authors: Freire Geraldo de Brito , Elias-Paiva André , Ribeiro Danilo Bandini , Araujo Raquel , Sudta Chantchanok , Oliveira Hernani , Domingos Fabrícius , Escarlate-Tavares Fabrício
Published: October 2023

Fire has significantly shaped the dynamics of Brazilian Cerrado fauna and flora, but the interference of human activities and climate change has disrupted the natural fire regime, imperiling multiple animal and plant populations. Our study, performed at Reserva Ecológica do Roncador (RECOR) in Brasília-Brazil, examined the influence of fire frequency and post-fire intervals on diversity patterns of fruit-feeding butterflies in savannah woodlands. We sampled 1012 individuals from 16 butterfly species, in which Biblidinae and Charaxinae were the most representative clades. Sites with higher fire frequency and shorter post-fire intervals exhibited greater taxonomic, functional and phylogenetic diversity compared to sites with longer intervals. Sites with longer post-fire intervals were primarily dominated by Biblidinae, whereas charaxines and satyrines mostly occurred in sites with shorter post-fire intervals. Species with wing eyespots and temporal restrictions thrived in sites with recent fires. These findings emphasize fire's pivotal role in maintaining open vegetation, crucial for conserving butterfly assemblages, particularly charaxines and satyrines. Importantly, fire suppression leads to fuel accumulation, elevating the risk of severe wildfires in the Cerrado. In conclusion, our results underscore the adverse impact of a zero-fire policy on insect communities, including fruit-feeding butterflies, within this unique ecosystem.
Atmospheric isoprene measurements reveal larger-than-expected Southern Ocean emissions
Authors: Ferracci Valerio , Weber James , Bolas Conor , Robinson Andrew , Tummon Fiona , Rodríguez-Ros Pablo , Cortés Pau , Baccarini Andrea , Jones Rod , Galí Martí , Simó Rafel , Schmale Julia , Harris Neil
Published: October 2023

Isoprene is a key trace component of the atmosphere emitted by vegetation and other organisms. It is highly reactive and can impact atmospheric composition and climate by affecting the greenhouse gases ozone and methane and secondary organic aerosol formation. Marine emissions are poorly constrained due to the paucity of long-term measurements: this in turn limits our understanding of isoprene cycling in the ocean. Here we present the analysis of isoprene concentrations in the atmosphere measured across the Southern Ocean over 4 months in the summertime. The highest concentrations originated from the marginal ice zone (MIZ) in the Ross and Amundsen seas, indicating the MIZ is a significant source of isoprene at high latitudes. Using the global chemistry-climate model UKESM1 we show that current estimates of sea-to-air isoprene fluxes underestimate observed isoprene by a factor > 20. A daytime source of isoprene is required to reconcile models with observations. Increased isoprene emissions would lead to > 8% decrease in the hydroxyl radical in regions of the Southern Ocean, with implications for our understanding of atmospheric oxidation and composition in remote environments, often used as proxies for the pre-industrial atmosphere.
Peatlands have the potential to emerge as significant contributors to future climate warming
Authors: Chaudhary Nitin , Tuovinen Juha-Pekka , Kou Dan , Burman Pramit Kumar Deb , Lodh Abhishek , Lamba Shubhangi , Shurpali Narasinha , Schurgers Guy , Page Susan , Westermann Sebastian , Zhang Wenxin
Published: October 2023

Peatlands are huge reservoirs of carbon in the terrestrial ecosystem. They are both long-term sinks of organic carbon and a major natural source of atmospheric methane. These carbon-rich ecosystems are at risk of losing their carbon sink capacity and becoming a huge source of carbon dioxide and methane due to ongoing warming. In this study, we examined the past and future trends of peatland carbon and methane fluxes and their influence on the climate system. We found that peatlands > 25 °N will remain a carbon sink and methane source under a low-warming scenario (RCP2.6) but they would shift from being not only a source of methane but also of carbon dioxide under a high-warming scenario (RCP8.5) by the mid-21st century leading to a strong radiative forcing (0.25 W m-2) by the end of the 23rd century. This underlines the potential warming feedback in which peatland radiative forcing on the climate system would shift from negative to positive in the future.
Chorea-echinocytosis caused by two novel compound heterozygous mutations in the VPS13A gene: a case report and literature review
Authors: Li Ruozhao , Wang Qiang , Li Haiwen , Liu Yunquan , Zhao Yuanqi , Xu Haoyou
Published: October 2023

Chorea-acanthocytosis (ChAc) is a rare neurodegenerative disease caused by mutations in the VPS13A gene (vacuolar proteinsorting protein 13). Here we report a case of ChAc caused by two new compound heterozygous mutation in the VPS13A. A 36-year-old female presented with orolingual dystonia, dysarthria and mental symptom. A diagnosis of ChAc was established based on typical clinical symptoms, neuroimaging features, acanthocytosis in the peripheral blood smears. Then, whole-exome sequencing of the proband family members determined two novel mutations in VPS13A, including c.4242 + 1G > T (exon36, NM_033305) and c.9270_9274dupCAGAC (exon36, NM_033305). Two novel compound heterozygous mutations in VPS13A cause ChAc, which deepens current understanding about the pathogenesis of ChAC.
Significance of RNA N6-methyladenosine modulators and immune infiltration in the diagnosis and subtyping of ischemic stroke
Authors: Gao Zhijie , Wang Yuedong , Lu Hongji , Wang Lixin
Published: October 2023

RNA N6-methyladenosine (M6A) regulators play an important part in a variety of cellular physiological and pathological processes. However, the part of m6A modulators in ischemic stroke remains unclear.Six important m6A regulators were selected from the gene expression repertoire GSE22255, GSE16561 and GSE37587 datasets by differential gene expression analysis between healthy people and ischemic stroke patients.A two models were constructed, and the RF model was used to screen six significant m6A regulators (Methyltransferase-like 3, Leucine Rich Pentatricopeptide Repeat Containing, Cbl Proto-Oncogene Like 1, Wilm's tumor 1 -associated protein, ELAV Like RNA Binding Protein 1 and AlkB Homolog 5, RNA Demethylase) to predict the risk of ischemic stroke.Based on 6 candidate M6A modulators, a nomogram model was established to analyze the clinical benefit of ischemic patients.Using consensus clustering, ischemic stroke patients were separated among m6A-cluster subtypes (cluster A and cluster B) based on selected significant m6A regulators. A PCA algorithm was applied to compute m6A scores for each sample to quantify m6A-cluster subtypes.The m6A scores of ischemic stroke patients in group B were lower than those in group A.At the same time, this research also found that ischemic stroke patients with low gene expression of ALKBH5, ELAVL1, LRPPRC and METTL3 improved immune cell infiltration, and ischemic stroke patients with high gene expression of CBLL1 and WTAP improved immune cell infiltration.In conclusion, m6A regulators play an important part in the disease process of ischemic stroke. The study of m6A-cluster subtypes is beneficial to direct future immunotherapy tactics for ischemic stroke.
A Bidirectional Mendelian Randomization Study Revealed Genetic Evidence of Breast Cancer as a Risk Factor for Meningioma
Authors: Zhou Yao , Gong Jie , Deng Xianguang , Shen Lele , Wu Shiting , Fan Hongqiao , Liu Lifang
Published: October 2023

Background
Although preceding observational research mentioned a potential connection between meningioma and breast cancer, verifying an unambiguous causal relationship has turned out problematic. Aiming to determine if breast cancer and the risk of meningioma intersect, we utilized a bidirectional two-sample Mendelian randomization (MR) analysis in this study. Besides, we investigated the influence of various estrogen receptor (ER) phenotypes on that association.
Methods
Breast cancer data from the Breast Cancer Association Consortium (BCAC) coupled with meningioma data from the FinnGen cohort were adopted in our investigation. Total participants of European descent were divided into four groups: 228,951 individuals (122,977 cases of breast cancer and 105,974 controls), 175,475 individuals (69,501 cases of ER-positive breast cancer and 105,974 controls), 127,442 individuals (21,468 cases of ER-negative breast cancer and 105,974 controls), and 287,614 individuals (1.237 cases of meningioma and 286,377 controls). The MR research, which utilized the power of the inverse variance weighting (IVW), weighted median (WM), and MR-Egger means, used tightly opted instrumental SNPs that were profoundly connected with exposure.
Results
According to the results of our forward MR study, there was a significant causal correlation between total breast cancer on meningioma (MR-Egger: OR = 1.4, 95% CI = 1.05–1.90, P = 0.022; WM: OR = 1.3, 95% CI = 1.02–1.50, P = 0.0248; IVW: OR = 1.2, 95% CI = 1.05–1.4, P = 0.0075). Furthermore, there was a probable causative relationship among ER-positive (ER+) breast cancer on meningioma (IVW: OR = 1.20, 95% CI: 1.03–1.30, P = 0.014), whereas no apparent connection between ER-negative breast cancer on meningioma emerged. Meningioma had little impact on the risk of breast cancer and breast cancer with different ER states, as shown to the inverse MR analysis drawing on the IVW, MR-Egger, and WM tests.
Conclusion
Following what comes of our forward MR investigation, there existed an unambiguous connection between the breast cancer in the population of European descent on meningioma. Likewise, we uncovered a potential combination referring to a causative relationship among ER + breast cancer on meningioma. However, there was no confirmation that suffering ER-breast cancer increases the possibility to grow meningioma. Furthermore, there was no causal relationship between overall breast cancer and breast cancer with different ER status on meningioma by our reverse MR examination.
Apomorphine is a potent inhibitor of ferroptosis independent of dopaminergic receptors
Authors: Miyauchi Akihiko , Watanabe Chika , Yamada Naoya , Jimbo Eriko F. , Kobayashi Mizuki , Ohishi Natsumi , Nagayoshi Atsuko , Aoki Shiho , Kishita Yoshihito , Ohtake Akira , Ohno Nobuhiko , Takahashi Masafumi , Yamagata Takanori , Osaka Hitoshi
Published: October 2023

Originally, apomorphine was a broad-spectrum dopamine agonist with an affinity for all subtypes of the Dopamine D1 receptor to the D5 receptor. We previously identified apomorphine as a potential therapeutic agent for mitochondrial diseases by screening a chemical library of fibroblasts from patients with mitochondrial diseases. In this study, we showed that apomorphine prevented ferroptosis in fibroblasts from various types of mitochondrial diseases as well as in normal controls. Well-known biomarkers of ferroptosis include protein markers such as prostaglandin endoperoxide synthase 2 (PTGS2), a key gene for ferroptosis-related inflammation PTGS2, lipid peroxidation, and reactive oxygen species. Our findings that apomorphine induced significant downregulation of Ptgs2, and suppressed lipid peroxide to the same extent as other inhibitors of ferroptosis also indicate that apomorphine suppresses ferroptosis. To our knowledge, this is the first study to report that the anti-ferroptosis effect of apomorphine is not related to dopamine receptor agonist action and that apomorphine is a potent inhibitor of ferroptotic cell death independent of dopaminergic receptors.
Lung transplant list withdrawal in a liver transplant patient thanks to elexacaftor-tezacaftor-ivacaftor: a case report
Authors: Traunero Arianna , Galletti Anna , Ghirardo Sergio , Barbi Egidio , Maschio Massimo
Published: October 2023

Background Elexacaftor-tezacaftor-ivacaftor (ETI) is a transmembrane conductance regulator modulator that significantly improves lung function in patients affected by cystic fibrosis (CF). This triple drug is currently not indicated in liver transplant patients, as clinical trials including subjects with previous solid organ transplantation are lacking.Case presentation We report on a liver transplant girl with CF-related advanced pulmonary disease meeting clinical criteria for lung transplant, who started the triple modulator because she could not get on the lung transplant waiting list due to psycho-social motivations. Since initiation of ETI therapy, she has experienced a significant improvement in respiratory function and quality of life, without adverse effects.Conclusions This case shows that ETI therapy can represent a lifesaving drug for individuals without alternatives, even in liver transplant patients. The clinical benefits of the modulator overcome risks, which may be limited with a close drug monitoring of immunosuppressants serum levels and functional liver tests.
Facilitators and Barriers to Asylum Seeker and Refugee Oral Health Care Access: A Qualitative Systematic Review
Authors: Wainman Nathan , Phillips Olivia , Morling Jo
Published: October 2023

Objectives: Asylum Seekers and refugees (ASRs) encounter barriers when accessing oral health care (OHC). A qualitative systematic review was conducted to understand the perceptions, attitudes, behaviours, and experiences of ASRs regarding their OHC. Themes were extracted to identify the barriers and facilitators ASRs face when accessing OHC.
Data sources: PubMed, APA PsycInfo, Cochrane database, Web of science, and CINAHL were searched on the 4th and 5th of October 2022
Data selection: Primary studies including ASRs of any age or nationality were included. Qualitative data of ASRs lived experiences of Oral Health (OH) and accessing OHC were extracted. The CASP quality appraisal tool was used to assess methodological quality.
Data synthesis: Data findings were extracted by hand and then meta-aggregation was performed using inductive reasoning. 13 primary qualitative studies were included. Three barriers to care were identified including difficulty accessing treatments and appointments, cultural and language changes, and ASRs lack of OHC knowledge or incongruous beliefs surrounding OH. Good OHC was facilitated by good OH education, social influence and support from care providers or government.
Conclusions: Caregivers and governments should adapt current policy to facilitate access to OHC, educate ASRs on OH and offer support to fund access and maintenance of good oral health. More research is needed to understand the barriers and facilitators to OHC for other people groups who experience health inequalities.
Improving nutritional status after allogeneic stem cell transplantation: results of phase 2 ALLONUT clinical trial
Authors: Cluzeau Thomas , Estran Sophie , Loschi Michael , Benachour Sami , Soldati Alizee , Chiche Edmond , Sammut Rinzine , Robert Guillaume , Jacquel Arnaud , Chibois Jacques , Schneider Stephane
Published: October 2023

Background
Malnutrition increases the risk of non-relapse mortality after allogeneic stem cell transplantation (aHSCT). Here are the results of the ALLONUT clinical trial designed to improve the nutritional outcome of patients receiving aHSCT
Methods
ALLONUT is a prospective open label phase 2 clinical trial assessing the efficacy of a close tailored nutritional support and management with traditional and original solutions to improve patients nutritional status following aHSCT. Nutritional status evaluation was performed before transplantation, at Day 0, 30, 100 and one year after transplantation.
Results
The study involved 70 patients treated by aHSCT. 10% of patients were moderately or severely malnutrition at baseline and 26.9 were severely malnutrition at D30. Patients' nutritional status improved thanks to the cooking classes and the personalized outpatient nutrition program. At D100, 23% were still malnutrition, while only 10.8% were severely malnutrition one year after transplantation. The QLQ-C30 show that quality of life (QoL) decreased until D30, and improve to reach the pre-transplant level on D100 before exceeding it on D360
Conclusions
Our study confirmed that a close, personalized nutritional program combining traditional and original measures can improve both nutritional status and QoL for patients suffering from moderate or severe malnutrition after aHCST