bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust preimplantation genetic testing of the common F8 Inv22 pathogenic variant of severe hemophilia A using a highly polymorphic multi-marker panel encompassing the paracentric inversion
Authors: Nguyen Minh Tam , Nguyen Thanh Tung , Nguyen Duy Bac , Nguyen Thi Mai , Nguyen Kim Ngan , Ngo Van Nhat Minh , Nguyen Van Dieu , Tran Ngoc Anh , Lian Mulias , Tan Arnold S. C. , Chong Samuel S. , Dang Tien Truong 
Published: October 2023

Abstract
Background
Hemophilia A (HEMA) is an X-linked bleeding disorder caused by reduced/absent coagulation factor VIII expression, as a result of pathogenic variants in the F8 gene. Preimplantation prevention of HEMA should ideally include direct pathogenic F8 variant detection, complemented by linkage analysis of flanking markers to identify the high-risk F8 allele. Linkage analysis is particularly indispensable when the pathogenic variant cannot be detected directly or identified. This study evaluated the suitability of a panel of F8 intragenic and extragenic short tandem repeat markers for standalone linkage-based preimplantation genetic testing for monogenic disorder (PGT-M) of the Inv22 pathogenic variant, an almost 600 kb paracentric inversion responsible for almost half of all severe HEMA globally, for which direct detection is challenging.

Methods
Thirteen markers spanning 1 Mb and encompassing both F8 and the Inv22 inversion interval were genotyped in 153 unrelated females of Viet Kinh ethnicity.

Results
All individuals were heterozygous for ≥ 1 marker, ~ 90% were heterozygous for ≥ 1 of the five F8 intragenic markers, and almost 98% were heterozygous for ≥ 1 upstream (telomeric) and ≥ 1 downstream (centromeric) markers. A prospective PGT-M couple at risk of transmitting F8 Inv22 were fully informative at four marker loci (2 intra-inversion, 1 centromeric, 1 telomeric) and partially informative at another five (2 intra-inversion, 3 centromeric), allowing robust phasing of low- and high-risk haplotypes. In vitro fertilization produced three embryos, all of which clearly inherited the low-risk maternal allele, enabling reliable unaffected diagnoses. A single embryo transfer produced a clinical pregnancy, which was confirmed as unaffected by amniocentesis and long-range PCR, and a healthy baby girl was delivered at term.

Conclusion
Robust and reliable PGT-M of HEMA, including the common F8 Inv22 pathogenic variant, can be achieved with sufficient informative intragenic and flanking markers.
A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials
Authors: Kelly Sharmony B. , Tran Nhi T. , Polglase Graeme R. , Hunt Rodney W. , Nold Marcel F. , Nold-Petry Claudia A. , Olson David M. , Chemtob Sylvain , Lodygensky Gregory A. , Robertson Sarah A. , Gunn Alistair J. , Galinsky Robert 
Published: October 2023

Abstract
Background
Perinatal infection/inflammation is associated with a high risk for neurological injury and neurodevelopmental impairment after birth. Despite a growing preclinical evidence base, anti-inflammatory interventions have not been established in clinical practice, partly because of the range of potential targets. We therefore systematically reviewed preclinical studies of immunomodulation to improve neurological outcomes in the perinatal brain and assessed their therapeutic potential.

Methods
We reviewed relevant studies published from January 2012 to July 2023 using PubMed, Medline (OvidSP) and EMBASE databases. Studies were assessed for risk of bias using the SYRCLE risk of bias assessment tool (PROSPERO; registration number CRD42023395690).

Results
Forty preclinical publications using 12 models of perinatal neuroinflammation were identified and divided into 59 individual studies. Twenty-seven anti-inflammatory agents in 19 categories were investigated. Forty-five (76%) of 59 studies reported neuroprotection, from all 19 categories of therapeutics. Notably, 10/10 (100%) studies investigating anti-interleukin (IL)-1 therapies reported improved outcome, whereas half of the studies using corticosteroids (5/10; 50%) reported no improvement or worse outcomes with treatment. Most studies (49/59, 83%) did not control core body temperature (a known potential confounder), and 25 of 59 studies (42%) did not report the sex of subjects. Many studies did not clearly state whether they controlled for potential study bias.

Conclusion
Anti-inflammatory therapies are promising candidates for treatment or even prevention of perinatal brain injury. Our analysis highlights key knowledge gaps and opportunities to improve preclinical study design that must be addressed to support clinical translation.
Measuring cell-to-cell expression variability in single-cell RNA-sequencing data: a comparative analysis and applications to B cell aging
Authors: Zheng Huiwen , Vijg Jan , Fard Atefeh Taherian , Mar Jessica Cara 
Published: October 2023

Abstract
Background
Single-cell RNA-sequencing (scRNA-seq) technologies enable the capture of gene expression heterogeneity and consequently facilitate the study of cell-to-cell variability at the cell type level. Although different methods have been proposed to quantify cell-to-cell variability, it is unclear what the optimal statistical approach is, especially in light of challenging data structures that are unique to scRNA-seq data like zero inflation.

Results
We systematically evaluate the performance of 14 different variability metrics that are commonly applied to transcriptomic data for measuring cell-to-cell variability. Leveraging simulations and real datasets, we benchmark the metric performance based on data-specific features, sparsity and sequencing platform, biological properties, and the ability to recapitulate true levels of biological variability based on known gene sets. Next, we use scran, the metric with the strongest all-round performance, to investigate changes in cell-to-cell variability that occur during B cell differentiation and the aging processes. The analysis of primary cell types from hematopoietic stem cells (HSCs) and B lymphopoiesis reveals unique gene signatures with consistent patterns of variable and stable expression profiles during B cell differentiation which highlights the significance of these methods. Identifying differentially variable genes between young and old cells elucidates the regulatory changes that may be overlooked by solely focusing on mean expression changes and we investigate this in the context of regulatory networks.

Conclusions
We highlight the importance of capturing cell-to-cell gene expression variability in a complex biological process like differentiation and aging and emphasize the value of these findings at the level of individual cell types.
SPIRAL: integrating and aligning spatially resolved transcriptomics data across different experiments, conditions, and technologies
Authors: Guo Tiantian , Yuan Zhiyuan , Pan Yan , Wang Jiakang , Chen Fengling , Zhang Michael Q. , Li Xiangyu 
Published: October 2023

AbstractProperly integrating spatially resolved transcriptomics (SRT) generated from different batches into a unified gene-spatial coordinate system could enable the construction of a comprehensive spatial transcriptome atlas. Here, we propose SPIRAL, consisting of two consecutive modules: SPIRAL-integration, with graph domain adaptation-based data integration, and SPIRAL-alignment, with cluster-aware optimal transport-based coordination alignment. We verify SPIRAL with both synthetic and real SRT datasets. By encoding spatial correlations to gene expressions, SPIRAL-integration surpasses state-of-the-art methods in both batch effect removal and joint spatial domain identification. By aligning spots cluster-wise, SPIRAL-alignment achieves more accurate coordinate alignments than existing methods.
Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity
Authors: Ruyssen-Witrand Adeline , Guernec Gregory , Dupont Julia , Lapuyade Diane , Lioté Frédéric , Vittecoq Olivier , Degboé Yannick , Constantin Arnaud 
Published: October 2023

Abstract
Background
To compare the 10-year structural and functional prognosis between patients in sustained remission versus patients in sustained low disease activity (LDA) in early rheumatoid arthritis (RA).

Methods
We included 256 patients from the ESPOIR cohort who fulfilled the 2010 ACR/EULAR criteria for RA and who were in sustained remission using the Simple Disease Activity Index (SDAI) score (n = 48), in sustained LDA (n = 139) or in sustained moderate to high disease activity (MDA or HDA, n = 69) over 10 years. The mTSSs progression over 10 years and the 10-year HAQ-DI scores were compared between the 3 groups. A longitudinal latent process mixed model was used to assess the independent effect of SDAI status over time on 10-year mTSS progression and HAQ-DI at 10 years.

Results
Patients in sustained remission group were younger, had lower baseline HAQ-DI and mTSS scores and were less exposed to glucocorticoids, methotrexate or biologic disease-modifying anti-rheumatic drugs over 10 years. Patients in sustained remission had lower 10-year structural progression (variation of mTSS in the remission group: 4.06 (± 4.75) versus 14.59 (± 19.76) in the LDA group and 21.04 (± 24.08), p < 0.001 in the MDA or HDA groups) and lower 10-year HAQ-DI scores (10-year HAQ-DI in the remission group: 0.14 (± 0.33) versus 0.53 (± 0.49) in the LDA group and 1.20 (± 0.62) in the MDA or HDA groups, p < 0.001). The incidence of serious adverse events over 10 years was low, about 3.34/100 patient years, without any difference between the three groups.

Conclusion
RA patients in sustained SDAI remission have better long-term structural and functional outcomes in comparison to patients in sustained LDA.
Misdiagnosed metabolic bone abnormality: a case report
Authors: Alsabri Mohammed , Street Hannah , Sircy Aaron , Labib Bahaaeldin 
Published: October 2023

Abstract
Background
Metabolic bone disease causes significant morbidity and mortality, especially when misdiagnosed. With genetic testing, multiple disease pathologies can be analyzed.

Case presentation
A 5-year and 9-month-old otherwise healthy Yemeni girl presented to her Yemen physician for evaluation of inward bending of her right knee and short stature. After extensive medical testing, she was given a diagnosis of hypophosphatemic rickets and growth hormone deficiency and started on treatment. Despite appropriate treatment, however, her condition continued to progress, prompting her family to pursue additional workup including genetic testing outside of Yemen. Genetic testing ultimately revealed a variation of unknown significance associated with amelogenesis imperfecta.

Conclusions
Hypophosphatemic rickets secondary to renal tubular acidosis was the working diagnosis. However, the patient’s condition did not improve. Further genetic testing revealed a variation of unknown significance associated with amelogenesis imperfecta. We aim to present this case, provide an overview of the causes, and diagnostic metabolic bone health evaluation.
Treatment of severe metformin-associated lactic acidosis with renal replacement therapy and tris-hydroxymethyl aminomethane: a case report
Authors: Yusim Diana , Tiru Bogdan , Abdullin Marat , Landry Daniel L. , Hodgins Spencer , Braden Gregory L. 
Published: October 2023

Abstract
Background
Type B lactic acidosis is a rare but serious side effect of metformin use. The risk of metformin-associated lactic acidosis is elevated in renal or liver impairment, heart failure and in metformin overdose. Metformin-associated lactic acidosis is treated with renal replacement therapy although this can be limited by metformin’s large volume of distribution and a patient’s hemodynamic instability. Tris-hydroxymethyl aminomethane is a buffer that rapidly equilibrates in liver cells and increases the intracellular pH of hepatocytes. Intracellular alkalosis increases lactate uptake by the liver and can promote gluconeogenesis which results in increased lactate metabolism and decreased lactate production. Unlike intravenous bicarbonate which can worsen acidosis due to carbon dioxide retention and hypocalcemia, tris-hydroxymethyl aminomethane does not generate large amounts of carbon dioxide and can improve cardiac contractility in experimental models.

Case presentation
We present a case of a 43-year-old African American male who intentionally ingested 480,000 g of metformin. He developed severe metformin-associated lactic acidosis that was refractory to 21 hours of high flux hemodialysis. This was followed by an additional 12 hours of high flux hemodialysis augmented by continuous intravenous infusion of tris-hydroxymethyl aminomethane. After initiating tris-hydroxymethyl aminomethane, the patient had rapid reversal of lactic acidosis and was weaned off vasopressors and mechanical ventilation.

Conclusions
While metformin-associated lactic acidosis can be treated with renal replacement therapy, severe cases of lactic acidosis may not be amenable to renal replacement therapy alone. Through its unique buffer mechanisms, tris-hydroxymethyl aminomethane can be used in conjunction with dialysis to rapidly improve acidosis associated with metformin.
Efficacy and safety of mesenchymal stem cell therapy in liver cirrhosis: a systematic review and meta-analysis
Authors: Lu Wenming , Qu Jiayang , Yan Longxiang , Tang Xingkun , Wang Xuesong , Ye Anqi , Zou Zhengwei , Li Lincai , Ye Junsong , Zhou Lin 
Published: October 2023

Abstract
Aim
Although the efficacy and safety of mesenchymal stem cell therapy for liver cirrhosis have been demonstrated in several studies. Clinical cases of mesenchymal stem cell therapy for patients with liver cirrhosis are limited and these studies lack the consistency of treatment effects. This article aimed to systematically investigate the efficacy and safety of mesenchymal stem cells in the treatment of liver cirrhosis.

Method
The data source included PubMed/Medline, Web of Science, EMBASE, and Cochrane Library, from inception to May 2023. Literature was screened by the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Outcome indicators of the assessment included liver functions and adverse events. Statistical analysis was performed using Review Manager 5.4.

Results
A total of 11 clinical trials met the selection criteria. The pooled analysis' findings demonstrated that both primary and secondary indicators had improved. Compared to the control group, infusion of mesenchymal stem cells significantly increased ALB levels in 2 weeks, 1 month, 3 months, and 6 months, and significantly decreased MELD score in 1 month, 2 months, and 6 months, according to a subgroup analysis using a random-effects model. Additionally, the hepatic arterial injection favored improvements in MELD score and ALB levels. Importantly, none of the included studies indicated any severe adverse effects.

Conclusion
The results showed that mesenchymal stem cell was effective and safe in the treatment of liver cirrhosis, improving liver function (such as a decrease in MELD score and an increase in ALB levels) in patients with liver cirrhosis and exerting protective effects on complications of liver cirrhosis and the incidence of hepatocellular carcinoma. Although the results of the subgroup analysis were informative for the selection of mesenchymal stem cells for clinical treatment, a large number of high-quality randomized controlled trials validations are still needed.
The historical evolution of the Greek retail trade: a first overview of its organisational-functional and spatial restructuring
Authors: Manioudis Manolis , Meramveliotakis Giorgos 
Published: October 2023

AbstractThe history of retailing has become an area of growing scholarly interest over the last few decades, with publications mainly concerning the national historiography of retail and wholesaling. On the other hand, although the retail sector is considered to be one of the most historically significant sectors of the Greek economy, the economic history of the Greek retail industry remains a notoriously underdeveloped area of inquiry and, as such, is on the margins of economic and social studies in Greek historiography. In this paper, we, attempt to provide a first concise (and certainly not exhaustive) analysis of the historical development of the Greek retail sector from the nineteenth century to the present (in circa) day. Specifically, we aim to analyse the evolution of the Greek retail trade to assess the spatial and social impacts associated with establishing and operating “new forms” of commerce. The focus is on the sectoral and organisational restructuring of the retail trade with the changes in the standards of the spatial location, which relate to the establishment and operation of retail businesses. Students and scholars of the history of retailing would benefit from this worthwhile exercise which for the first time provides a first overview of the historical development of the Greek retail sector.
The relationship between positive and negative stress and posttraumatic growth in university students: the mediating role of resilience
Authors: Serpa-Barrientos Antonio , Calvet María Luisa Matalinares , Acosta Ana Gloria Díaz , Fernández Ana Cecilia Pareja , Rivas Díaz Luisa Hortensia , Albites Flor María Ayala , Saintila Jacksaint 
Published: October 2023

Abstract
Background
Information on understanding the mediating role of resilience in the relationship between posttraumatic growth (PTG) and positive and negative stress among students is limited. The objective of this research was to evaluate the mediating role of resilience in the relationship between positive and negative stress and PTG in university students.

Methods
The research was carried out using an associative strategy with an empirical approach and explanatory design, with a sample of 507 participants whose average age was 22.38 years ($${\text{S}\text{D}}_{\text{a}\text{g}\text{e}}$$= 3.758), the sample was mostly composed of women (70.4%).

Results
The results allow us to describe that resilience plays a complete mediating role in the relationship between negative stress and PTG. On the other hand, mediation was partial when resilience mediated the relationship between positive stress and PTG. In addition, multigroup invariance analyses according to gender and geographic context show that there is no difference in males, females, and the region where they reside.

Conclusion
In conclusion, the hypothesis that resilience fulfills the mediating function is ratified.
A novel risk score for venous thromboembolism in lung cancer patients: a retrospective cohort study
Authors: Rouis Houda , Moussa Chirine , mejri Islem , Debbiche Soumaya , Khalfallah Nourchene , Ben Hmida Lenda , Khattab Amel , Moetamri Zied , Megdiche Mohamed Lamine , Kamoun Hela , Maâlej Sonia 
Published: October 2023

Background: Venous thromboembolism (VTE) is a common and potentially fatal complication in patients with lung cancer. This study aimed to develop and validate a risk score for early prediction of VTE in these patients. Methods: Four hundred and one patients with lung cancer from three pulmonology departments hospitalized between January 2011 and December 2021 were retrospectively assessed. The population was divided into two groups: a Development Group (182 patients) and a validation group (199 patients). In the development group, the risk score system was developed, via univariate and multivariate analyses, based on demographic and clinicopathological variables; it was then validated in the validation group. Results: The incidence of VTE was 26.8% in the development group. It was 25.8%, and 27.6% in the internal and external validation groups, respectively. Hemoglobin level <10g/l, metastasis, histological type poorly or undifferentiated non-small cell carcinoma, and active smoking were the items of the risk score system. This score allowed proper stratification of patients with either high or low risk of VTE in the development group (c statistic =0.703). The patients in the development group were classified into 3 risk groups: low risk (scores 0-1), moderate risk (scores 2-3), and high risk (scores 4-5). When validated in the validation group, there was a moderate loss of predictive power of the score (c statistic=0.641), but the categorization of the patients by the score remained clinically useful. Conclusions: This risk score requires prospective validation studies on a nationwide scale in order to use it as a valid tool for the prevention of VTE in lung cancer.
Living with bronchial asthma: A qualitative study among patients in a hill village in Nepal
Authors: Paudel Sabita , Shankar Pathiyil Ravi , Subedi Nuwadatta , Palaian Subish 
Published: October 2023

Introduction
Bronchial asthma continues to be a problem in the Himalayan country of Nepal. This study explored the impact of bronchial asthma on patients’ lives in a hill village in Syangja district, Nepal, and obtained information about the perceived impact of the illness, knowledge of the disease, self-care behaviors and treatment among patients.

Material and methods
The study site is the village of Jyamire (located at an elevation between 900 to 1200 m) Syangja district. Individuals suffering from asthma residing in the village aged 18 years or above were included. Semi-structured interviews were conducted face-to-face with the respondents at their homes using an interview guide. The interviews were audio recorded, transcribed in the Nepali language, and then translated into English for further analysis.

Results
Most participants were female, between 18 to 60 years of age, and housewives. Most houses were built of mud and poorly ventilated. Gas was used for cooking though firewood was also used. Most used to get an average of three serious attacks a year both during winter and summer. The themes that emerged were the number and seasonal variation in attacks, the perceived effect of asthma on their lives and social interactions, the knowledge of the interviewee about the disease, the impact of asthma on their socioeconomic status, and treatment and self-care behaviors. Residing in a hill village required them to walk up and down several times a day and the disease seriously impacted their lives. The smoke produced during different ceremonies and during cooking also worsened their asthma.

Conclusion
Findings suggest, the existence of multiple factors, a few unique to Nepal contributing to poor asthma control. Though the recent socioeconomic improvement has led to improved prevention and treatment options, asthma seriously affected the patients.