bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficiency of copy number variation sequencing combined with karyotyping in fetuses with congenital heart disease and the following outcomes
Authors: Wang Xuezhen , Sha Jing , Han Yu , Pang Min , Liu Min , Liu Mengna , Zhang Bei , Zhai Jingfang 
Published: May 2024

Abstract
Background
Both copy number variant-sequencing (CNV-seq) and karyotype analysis have been used as powerful tools in the genetic aetiology of fetuses with congenital heart diseases (CHD). However, CNV-seq brings clinicians more confusions to interpret the detection results related to CHD with or without extracardiac abnormalities. Hence, we conducted this study to investigate the clinical value of CNV-seq in fetuses with CHD.

Results
A total of 167 patients with fetal CHD including 36 single CHD (sCHD), 41 compound CHD (cCHD) and 90 non-isolated CHD (niCHD) were recruited into the study. 28 cases (16.77%, 28/167) were revealed with chromosomal abnormalities at the level of karyotype. The pathogenic detection rate (DR) of CNV-seq (23.17%, 19/82) was higher than that of karyotyping (15.85%, 13/82) in 82 cases by CNV-seq and karyotyping simultaneously. The DR of pathogenic copy number variations (PCNVs) (31.43%) was higher in niCHD subgroup than that in sCHD and cCHD (9.52% and 23.08%). Conotruncal defect (CTD) was one of the most common heart malformations with the highest DR of PCNVs (50%) in 7 categories of CHD. In terms of all the pregnancy outcomes, 67 (40.12%) cases were terminated and 100 (59.88%) cases were live neonates. Only two among 34 cases with a pathogenic genetic result chose to continue the pregnancy.

Conclusions
CNV-seq combined with karyotyping is a reliable and accurate prenatal technique for identifying pathogenic chromosomal abnormalities associated with fetal CHD with or without extracardiac abnormalities, which can assist clinicians to perform detailed genetic counselling with regard to the etiology and related outcomes of CHD.
The risk of skin cancer in women who carry BRCA1 or BRCA2 mutations
Authors: Narod Steven A. , Metcalfe Kelly , Finch Amy , Chan An-Wen , Armel Susan Randall , Aeilts Amber , Eisen Andrea , Karlan Beth , Bordeleau Louise , Tung Nadine , Foulkes William D. , Neuhausen Susan L. , Eng Charis , Olopade Olufunmilayo , Zakalik Dana , Couch Fergus , Cullinane Carey , Pal Tuya , Sun Ping , Kotsopoulos Joanne ,   the Hereditary Breast Cancer Clinical Research Group, Poll Aletta , Kim Raymond , Fruscio Robert , Lemire Edmond , Serfas Kim , Sweet Kevin , Senter Leigha , Panchal Seema , Elser Christine , Blum Joanne L. , Rayson Daniel , Isaacs Claudine , Dungan Jeffrey , Cohen Stephanie 
Published: May 2024

Abstract
Background
It has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations.

Methods
We report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations. Women were followed from the date of baseline questionnaire to the diagnosis of skin cancer, to age 80 years, death from any cause, or the date of last follow-up.

Results
During the mean follow-up period of eight years, 3.7% of women with a BRCA1 mutation (133 of 3,623) and 3.8% of women with a BRCA2 mutation (99 of 2,584) reported a diagnosis of skin cancer (including both keratinocyte carcinomas and melanoma). The cumulative risk of all types of skin cancer from age 20 to 80 years was 14.1% for BRCA1 carriers and 10.7% for BRCA2 carriers. The cumulative risk of melanoma was 2.5% for BRCA1 carriers and 2.3% for BRCA2 carriers, compared to 1.5% for women in the general population in the United States. The strongest risk factor for skin cancer was a prior diagnosis of skin cancer.

Conclusion
The risk of non-melanoma skin cancer in women who carry a mutation in BRCA1 or BRCA2 is similar to that of non-carrier women. The risk of melanoma appears to be slightly elevated. We suggest that a referral to a dermatologist or primary care provider for BRCA mutation carriers for annual skin examination and counselling regarding limiting UV exposure, the use of sunscreen and recognizing the early signs of melanoma might be warranted, but further studies are necessary.
EmptyDropsMultiome discriminates real cells from background in single-cell multiomics assays
Authors: Megas Stathis , Lorenzi Valentina , Marioni John C. 
Published: May 2024

AbstractMultiomic droplet-based technologies allow different molecular modalities, such as chromatin accessibility and gene expression (scATAC-seq and scRNA-seq), to be probed in the same nucleus. We develop EmptyDropsMultiome, an approach that distinguishes true nuclei-containing droplets from background. Using simulations, we show that EmptyDropsMultiome has higher statistical power and accuracy than existing approaches, including CellRanger-arc and EmptyDrops. On real datasets, we observe that CellRanger-arc misses more than half of the nuclei identified by EmptyDropsMultiome and, moreover, is biased against certain cell types, some of which have a retrieval rate lower than 20%.
SCIPAC: quantitative estimation of cell-phenotype associations
Authors: Gan Dailin , Zhu Yini , Lu Xin , Li Jun 
Published: May 2024

AbstractNumerous algorithms have been proposed to identify cell types in single-cell RNA sequencing data, yet a fundamental problem remains: determining associations between cells and phenotypes such as cancer. We develop SCIPAC, the first algorithm that quantitatively estimates the association between each cell in single-cell data and a phenotype. SCIPAC also provides a p-value for each association and applies to data with virtually any type of phenotype. We demonstrate SCIPAC’s accuracy in simulated data. On four real cancerous or noncancerous datasets, insights from SCIPAC help interpret the data and generate new hypotheses. SCIPAC requires minimum tuning and is computationally very fast.
Targeting strategies for balanced energy and protein (BEP) supplementation in pregnancy: study protocol for the TARGET-BEP cluster-randomized controlled trial in rural Bangladesh
Authors: Zavala Eleonor , Mohan Diwakar , Ali Hasmot , Siddiqua Towfida J. , Haque Rezwanul , Ayesha Kaniz , Ahsan Khalid Bin , Sujan Hasan Mahmud , Khaled Nazrana , Rahman Atiya , Chakraborty Barnali , Dyer Brian , Wu Lee S. F. , Kalbarczyk Anna , Erchick Daniel J. , Thorne-Lyman Andrew L. , Tumilowicz Alison , Afsana Kaosar , Christian Parul 
Published: May 2024

Abstract
Background
The World Health Organization (WHO) recommends balanced energy and protein (BEP) supplementation be provided to all pregnant women living in undernourished populations, usually defined as having a prevalence > 20% of underweight women, to reduce the risk of stillbirths and small-for-gestational-age neonates. Few geographies meet this threshold, however, and a large proportion of undernourished women and those with inadequate gestational weight gain could miss benefiting from BEP. This study compares the effectiveness of individual targeting approaches for supplementation with micronutrient-fortified BEP vs. multiple micronutrient supplements (MMS) alone as control in pregnancy in improving birth outcomes.

Methods
The TARGET-BEP study is a four-arm, cluster-randomized controlled trial conducted in rural northwestern Bangladesh. Eligible participants are married women aged 15–35 years old identified early in pregnancy using a community-wide, monthly, urine-test-based pregnancy detection system. Beginning at 12–14 weeks of gestation, women in the study area comprising 240 predefined sectors are randomly assigned to one of four intervention arms, with sector serving as the unit of randomization. The interventions involving daily supplementation through end of pregnancy are as follows: (1) MMS (control); (2) BEP; (3) targeted BEP for those with pre-pregnancy body mass index (BMI) < 18.5 kg/m2 and MMS for others; (4) targeted BEP for those with pre-pregnancy BMI < 18.5 kg/m2, MMS for others, and women with inadequate gestational weight gain switched from MMS to BEP until the end of pregnancy. Primary outcomes include birth weight, low birth weight (< 2500 g), and small for gestational age, defined using the 10th percentile of the INTERGROWTH-21st reference, for live-born infants measured within 72 h of birth. Project-hired local female staff visit pregnant women monthly to deliver the assigned supplements, monitor adherence biweekly, and assess weight regularly during pregnancy. Trained data collectors conduct pregnancy outcome assessment and measure newborn anthropometry in the facility or home depending on the place of birth.

Discussion
This study will assess the effectiveness of targeted balanced energy and protein supplementation to improve birth outcomes among pregnant women in rural Bangladesh and similar settings.

Trial registration
ClinicalTrials.gov NCT05576207. Registered on October 5th, 2022.
Efficacy of ganglion impar block combined with pudendal nerve pulsed radiofrequency for pudendal neuralgia management—a randomized clinical trial
Authors: Ran Jiao , Lu Fan , Xu Le , Du Yu , Liu Li , Qi Tao , Zhou Xiaoli , Zhang Yulin , Liu Dong , Wang Rurong , Li Xuehan 
Published: May 2024

Abstract
Background
Pudendal neuralgia is a chronic and debilitating condition. Its prevalence ranges from 5 to 26%. Currently, therapeutic approaches to treat pudendal neuralgia include patient education, medication management, psychological and physical therapy, and procedural interventions, such as nerve block, trigger point injections, and surgery. Drug therapy has a limited effect on pain relief. A pudendal nerve block may cause a significant decrease in pain scores for a short time; however, its efficacy significantly decreases over time. In contrast, pudendal nerve pulsed radiofrequency can provide pain relief for 3 months, and ganglion impar block has been widely used for treating chronic perineal pain and chronic coccygodynia. This study aimed to determine the efficacy and safety of monotherapy (pudendal nerve pulsed radiofrequency) and combination therapy (pudendal nerve pulsed radiofrequency plus ganglion impar block) in patients with pudendal neuralgia.

Methods
This randomized, controlled clinical trial will include 84 patients with pudendal neuralgia who failed to respond to drug or physical therapy. Patients will be randomly assigned into one of the two groups: mono or combined treatment groups. The primary outcome will be a change in pain intensity measured using the visual analog scale. The secondary outcomes will include a Self-Rating Anxiety Scale score, Self-Rating Depression Scale score, the use of oral analgesics, the Medical Outcomes Study Health Survey Short Form-36 Item score, and the occurrence of adverse effects. The study results will be analyzed using intention-to-treat and per-protocol analyses. Primary and secondary outcomes will be evaluated between the mono and combined treatment groups. Subgroup analyses will be conducted based on the initial ailment, age, and baseline pain intensity. The safety of the treatment will be assessed by monitoring adverse events, which will be compared between the two groups.

Discussion
This study protocol describes a randomized, controlled clinical trial to determine the efficacy and safety of mono and combination therapies in patients with pudendal neuralgia. The study results will provide valuable information on the potential benefits of this combination therapy and contribute to the development of more effective and safer treatments for patients with pudendal neuralgia.

Trial registration
Chinese Clinical Trial Registry (ChiCTR2200061800).
Vector competence of Swedish Culex pipiens mosquitoes for Japanese encephalitis virus
Authors: Krambrich Janina , Akaberi Dario , Lindahl Johanna F. , Lundkvist Åke , Hesson Jenny C. 
Published: May 2024

AbstractBackgroundJapanese encephalitis virus (JEV) is an emerging mosquito-borne Orthoflavivirus that poses a significant public health risk in many temperate and tropical regions in Asia. Since the climate in some endemic countries is similar to temperate climates observed in Europe, understanding the role of specific mosquito species in the transmission of JEV is essential for predicting and effectively controlling the potential for the introduction and establishment of JEV in Europe.MethodsThis study aimed to investigate the vector competence of colonized Culex pipiens biotype molestus mosquitoes for JEV. The mosquitoes were initially collected from the field in southern Sweden. The mosquitoes were offered a blood meal containing the Nakayama strain of JEV (genotype III), and infection rates, dissemination rates, and transmission rates were evaluated at 14, 21, and 28 days post-feeding.ResultsThe study revealed that colonized Swedish Cx. pipiens are susceptible to JEV infection, with a stable infection rate of around 10% at all timepoints. However, the virus was only detected in the legs of one mosquito at 21 days post-feeding, and no mosquito saliva contained JEV.ConclusionsOverall, this research shows that Swedish Cx. pipiens can become infected with JEV, and emphasizes the importance of further understanding of the thresholds and barriers for JEV dissemination in mosquitoes.Graphical Abstract
Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states
Authors: Wang Frank Qingyun , Shao Li , Dang Xiao , Wang Yong-Fei , Chen Shuxiong , Liu Zhongyi , Mao Yujing , Jiang Yuping , Hou Fei , Guo Xianghua , Li Jian , Zhang Lili , Sang Yuting , Zhao Xuan , Ma Ruirui , Zhang Kai , Zhang Yanfang , Yang Jing , Wen Xiwu , Liu Jiong , Wei Wei , Zhang Chuanpeng , Li Weiyang , Qin Xiao , Lei Yao , Feng Hong , Yang Xingtian , She Chun Hing , Zhang Caicai , Su Huidong , Chen Xinxin , Yang Jing , Lau Yu Lung , Wu Qingjun , Ban Bo , Song Qin , Yang Wanling 
Published: May 2024

Abstract
Objectives
This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission.

Methods
We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks.

Results
Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse.

Conclusion
Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.
Identification and verification of a novel signature that combines cuproptosis-related genes with ferroptosis-related genes in osteoarthritis using bioinformatics analysis and experimental validation
Authors: He Baoqiang , Liao Yehui , Tian Minghao , Tang Chao , Tang Qiang , Ma Fei , Zhou Wenyang , Leng Yebo , Zhong Dejun 
Published: May 2024

Abstract
Background
Exploring the pathogenesis of osteoarthritis (OA) is important for its prevention, diagnosis, and treatment. Therefore, we aimed to construct novel signature genes (c-FRGs) combining cuproptosis-related genes (CRGs) with ferroptosis-related genes (FRGs) to explore the pathogenesis of OA and aid in its treatment.

Materials and methods
Differentially expressed c-FRGs (c-FDEGs) were obtained using R software. Enrichment analysis was performed and a protein–protein interaction (PPI) network was constructed based on these c-FDEGs. Then, seven hub genes were screened. Three machine learning methods and verification experiments were used to identify four signature biomarkers from c-FDEGs, after which gene set enrichment analysis, gene set variation analysis, single-sample gene set enrichment analysis, immune function analysis, drug prediction, and ceRNA network analysis were performed based on these signature biomarkers. Subsequently, a disease model of OA was constructed using these biomarkers and validated on the GSE82107 dataset. Finally, we analyzed the distribution of the expression of these c-FDEGs in various cell populations.

Results
A total of 63 FRGs were found to be closely associated with 11 CRGs, and 40 c-FDEGs were identified. Bioenrichment analysis showed that they were mainly associated with inflammation, external cellular stimulation, and autophagy. CDKN1A, FZD7, GABARAPL2, and SLC39A14 were identified as OA signature biomarkers, and their corresponding miRNAs and lncRNAs were predicted. Finally, scRNA-seq data analysis showed that the differentially expressed c-FRGs had significantly different expression distributions across the cell populations.

Conclusion
Four genes, namely CDKN1A, FZD7, GABARAPL2, and SLC39A14, are excellent biomarkers and prospective therapeutic targets for OA.
Peridynamic numerical investigation of asymmetric strain-controlled fatigue behaviour using the kinetic theory of fracture
Authors: Vaitkunas Tomas , Griskevicius Paulius , Dundulis Gintautas , Courtin Stephan 
Published: May 2024

AbstractNumerical fatigue process modelling is complex and still an open task. Discontinuity caused by fatigue cracks requires special finite element techniques based on additional parameters, the selection of which has a strong effect on the simulation results. Moreover, the calculation of fatigue life according to empirical material coefficients (e.g., Paris law) does not explain the process, and coefficients should be set from experimental testing, which is not always possible. A new nonlocal continuum mechanics formulation without spatial derivative of coordinates, namely, peridynamics (PD), which was created 20 y ago, provides new opportunities for modelling discontinuities, such as fatigue cracks. The fatigue process can be better described by using the atomistic approach-based kinetic theory of fracture (KTF), which includes the process temperature, maximum and minimum stresses, and loading frequency in its differential fatigue damage equation. Standard 316L stainless steel specimens are tested, and then the KTF-PD fatigue simulation is run in this study. In-house MATLAB code, calibrated from the material S‒N curve, is used for the KTF-PD simulation. A novel KTF equation based on the cycle stress‒strain hysteresis loop is proposed and applied to predict fatigue life. The simulation results are compared with the experimental results, and good agreement is observed for both symmetric and asymmetric cyclic loading.
Patient-reported outcomes during accelerating the en-masse retraction of the upper anterior teeth using low-intensity electrical stimulation: a randomized controlled trial
Authors: Shaadouh Rashad I. , Hajeer Mohammad Y. , Mahmoud Ghiath A. , Almasri Imad Addin , Jaber Samer T. , Alam Mohammad Khursheed 
Published: May 2024

Abstract
Background
Low-intensity electrical stimulation (LIES) is considered a relatively recent technology that has received little attention in orthodontics as a method of acceleration. This study aimed to evaluate patient-reported outcome measures when LIES is used to accelerate the en-masse retraction of the upper anterior teeth.

Materials and methods
The sample consisted of 40 patients (8 males, 32 females; mean age 21.1 ± 2.3 years), with Class II division I malocclusion who required extraction of the first premolars to retract upper anterior teeth. They were randomly assigned to the LIES group (n = 20) and the conventional en-masse retraction group (CER; n = 20). Patient responses regarding pain, discomfort, burning sensation, swelling, chewing difficulty, speech difficulty, and painkillers’ consumption were recorded at these nine assessment times: 24 h (T1), 3 days (T2), and 7 days (T3) after force application, then in the second month after 24 h (T4), 3 days (T5), and 7 days (T6) of force re-activation, and finally after 24 h (T7), 3 days (T8), and 7 days (T9) of force re-activation in the third month.

Results
The mean values of pain perception were smaller in the LIES group than those in the CER group at all assessment times with no statistically significant differences between the two groups except during the second and third months (T5, T6, T8, and T9; P < 0.005). However, discomfort mean values were greater in the LIES group with significant differences compared to CER group during the first week of the follow-up only (T1, T2, and T3; P < 0.005). Burning sensation levels were very mild in the LIES group, with significant differences between the two groups at T1 and T2 only (P < 0.001). Speech difficulty was significantly greater in the LIES group compared to CER group at all studied times (P < 0.001). High levels of satisfaction and acceptance were reported in both groups, without any significant difference.

Conclusion
Both the LIES-based acceleration of en-masse retraction of upper anterior teeth and the conventional retraction were accompanied by mild to moderate pain, discomfort, and chewing difficulty on the first day of retraction. These sensations gradually decreased and almost disappeared over a week after force application or re-activation.

Trial registration
ClinicalTrials.gov, ClinicalTrials.gov, NCT05920525. Registered 17 June 2023 - retrospectively registered, http://clinicaltrials.gov/study/NCT05920525?term=NCT05920525&rank=1.