bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of a machine learning method based on structural and locational information from AlphaFold2 for predicting the pathogenicity of TARDBP and FUS gene variants in ALS
Authors: Hatano Yuya , Ishihara Tomohiko , Onodera Osamu 
Published: May 2023

Abstract
Background
In the sporadic form of amyotrophic lateral sclerosis (ALS), the pathogenicity of rare variants in the causative genes characterizing the familial form remains largely unknown. To predict the pathogenicity of such variants, in silico analysis is commonly used. In some ALS causative genes, the pathogenic variants are concentrated in specific regions, and the resulting alterations in protein structure are thought to significantly affect pathogenicity. However, existing methods have not taken this issue into account. To address this, we have developed a technique termed MOVA (method for evaluating the pathogenicity of missense variants using AlphaFold2), which applies positional information for structural variants predicted by AlphaFold2. Here we examined the utility of MOVA for analysis of several causative genes of ALS.

Methods
We analyzed variants of 12 ALS-related genes (TARDBP, FUS, SETX, TBK1, OPTN, SOD1, VCP, SQSTM1, ANG, UBQLN2, DCTN1, and CCNF) and classified them as pathogenic or neutral. For each gene, the features of the variants, consisting of their positions in the 3D structure predicted by AlphaFold2, pLDDT score, and BLOSUM62 were trained into a random forest and evaluated by the stratified fivefold cross validation method. We compared how accurately MOVA predicted mutant pathogenicity with other in silico prediction methods and evaluated the prediction accuracy at TARDBP and FUS hotspots. We also examined which of the MOVA features had the greatest impact on pathogenicity discrimination.

Results
MOVA yielded useful results (AUC ≥ 0.70) for TARDBP, FUS, SOD1, VCP, and UBQLN2 of 12 ALS causative genes. In addition, when comparing the prediction accuracy with other in silico prediction methods, MOVA obtained the best results among those compared for TARDBP, VCP, UBQLN2, and CCNF. MOVA demonstrated superior predictive accuracy for the pathogenicity of mutations at hotspots of TARDBP and FUS. Moreover, higher accuracy was achieved by combining MOVA with REVEL or CADD. Among the features of MOVA, the x, y, and z coordinates performed the best and were highly correlated with MOVA.

Conclusions
MOVA is useful for predicting the virulence of rare variants in which they are concentrated at specific structural sites, and for use in combination with other prediction methods.
Effect of bacillus subtilis strain Z15 secondary metabolites on immune function in mice
Authors: Cao Xi-Yuan , Aimaier Reyihanguli , Yang Jun , Yang Jing , Chen Zhong-Yi , Zhao Jing-Jing , Yin Li , Zhang Qi , You Jia , Zhang Hui , Li Hao-Ran , Chen Jia-Yi , Mao Qing-Chen , Yang Li-Ping , Yu Fei , Zhao He-Ping , Zhao Hui-Xin 
Published: May 2023

Abstract
Background
Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis.

Results
The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5).

Conclusions
BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.
Restriction site-associated DNA sequencing technologies as an alternative to low-density SNP chips for genomic selection: a simulation study in layer chickens
Authors: Herry Florian , Hérault Frédéric , Lecerf Frédéric , Lagoutte Laëtitia , Doublet Mathilde , Picard-Druet David , Bardou Philippe , Varenne Amandine , Burlot Thierry , Le Roy Pascale , Allais Sophie 
Published: May 2023

Abstract
Background
To reduce the cost of genomic selection, a low-density (LD) single nucleotide polymorphism (SNP) chip can be used in combination with imputation for genotyping selection candidates instead of using a high-density (HD) SNP chip. Next-generation sequencing (NGS) techniques have been increasingly used in livestock species but remain expensive for routine use for genomic selection. An alternative and cost-efficient solution is to use restriction site-associated DNA sequencing (RADseq) techniques to sequence only a fraction of the genome using restriction enzymes. From this perspective, use of RADseq techniques followed by an imputation step on HD chip as alternatives to LD chips for genomic selection was studied in a pure layer line.

Results
Genome reduction and sequencing fragments were identified on reference genome using four restriction enzymes (EcoRI, TaqI, AvaII and PstI) and a double-digest RADseq (ddRADseq) method (TaqI-PstI). The SNPs contained in these fragments were detected from the 20X sequence data of the individuals in our population. Imputation accuracy on HD chip with these genotypes was assessed as the mean correlation between true and imputed genotypes. Several production traits were evaluated using single-step GBLUP methodology. The impact of imputation errors on the ranking of the selection candidates was assessed by comparing a genomic evaluation based on ancestry using true HD or imputed HD genotyping. The relative accuracy of genomic estimated breeding values (GEBVs) was investigated by considering the GEBVs estimated on offspring as a reference. With AvaII or PstI and ddRADseq with TaqI and PstI, more than 10 K SNPs were detected in common with the HD SNP chip, resulting in an imputation accuracy greater than 0.97. The impact of imputation errors on genomic evaluation of the breeders was reduced, with a Spearman correlation greater than 0.99. Finally, the relative accuracy of GEBVs was equivalent.

Conclusions
RADseq approaches can be interesting alternatives to low-density SNP chips for genomic selection. With more than 10 K SNPs in common with the SNPs of the HD SNP chip, good imputation and genomic evaluation results can be obtained. However, with real data, heterogeneity between individuals with missing data must be considered.
A first insight into the genomic background of Ilex pubescens (Aquifoliaceae) by flow cytometry and genome survey sequencing
Authors: Zhou Peng , Zhang Qiang , Li Jiao , Li Fei , Huang Jing , Zhang Min 
Published: May 2023

Abstract
Background
Ilex pubescens is an important traditional Chinese medicinal plant with many naturally occurring compounds and multiple pharmacological effects. However, the lack of reference genomic information has led to tardiness in molecular biology research and breeding programs of this plant.

Results
To obtain knowledge on the genomic information of I. pubescens, a genome survey was performed for the first time by next generation sequencing (NGS) together with genome size estimation using flow cytometry. The whole genome survey of I. pubescens generated 46.472 Gb of sequence data with approximately 82.2 × coverage. K-mer analysis indicated that I. pubescens has a small genome of approximately 553 Mb with 1.93% heterozygosity rate and 39.1% repeat rate. Meanwhile, the genome size was estimated to be 722 Mb using flow cytometry, which was possibly more precise for assessment of genome size than k-mer analysis. A total of 45.842 Gb clean reads were assembled into 808,938 scaffolds with a relatively short N50 of 760 bp. The average guanine and cytosine (GC) content was 37.52%. In total, 197,429 microsatellite motifs were detected with a frequency of 2.8 kb, among which mononucleotide motifs were the most abundant (up to 62.47% of the total microsatellite motifs), followed by dinucleotide and trinucleotide motifs.

Conclusion
In summary, the genome of I. pubescens is small but complex with a high level of heterozygosity. Even though not successfully applied for estimation of genome size due to its complex genome, the survey sequences will help to design whole genome sequencing strategies and provide genetic information support for resource protection, genetic diversity analysis, genetic improvement and artificial breeding of I. pubescens.
Metabolomic analysis reveals the influence of HMBOX1 on RAW264.7 cells proliferation based on UPLC-MS/MS
Authors: Jiang Wen , Jiang Yu , Zhang Xinghai , Mu Hongli , Song Yuanming , Zhao Hengli 
Published: May 2023

AbstractMacrophages are important effector cells in tumor progression and immune regulation. Previously, we demonstrated that the transcription suppressor homeobox containing 1(HMBOX1) exhibits immunosuppressive activity in LPS-induced acute liver injury by impeding macrophage infiltration and activation. We also observed a lower proliferation in HMBOX1-overexpressed RAW264.7 cells. However, the specific mechanism was unclear. Here, a work was performed to characterize HMBOX1 function related to cell proliferation from a metabolomics standpoint by comparing the metabolic profiles of HMBOX1-overexpressed RAW264.7 cells to those of the controls. Firstly, we assessed HMBOX1 anti-proliferation activity in RAW264.7 cells with CCK8 assay and clone formation. Then, we performed metabolomic analyses by ultra-liquid chromatography coupled with mass spectrometry to explore the potential mechanisms. Our results indicated that HMBOX1 inhibited the macrophage growth curve and clone formation ability. Metabolomic analyses showed significant changes in HMBOX1-overexpressed RAW264.7 metabolites. A total of 1312 metabolites were detected, and 185 differential metabolites were identified based on the criterion of OPLS-DA VIP > 1 and p value < 0.05. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the elevated HMBOX1 in RAW264.7 inhibited the pathways of amino acid and nucleotide metabolism. Glutamine concentrations decreased significantly in HMBOX1-overexpressed macrophages, and glutamine-related transporter SLC1A5 was also downregulated. Furthermore, SLC1A5 overexpression reversed HMBOX1 inhibition of macrophage proliferation. This study demonstrated the potential mechanism of the HMBOX1/SLC1A5 pathway in cell proliferation by regulating glutamine transportation. The results may help provide a new direction for therapeutic interventions in macrophage-related inflammatory diseases.
Severe combined immunodeficiency: improved survival leading to detection of underlying liver disease
Authors: Vittal Anusha , Abdul Majeed Nehna , Garabedian Elizabeth , Marko Jamie , Kleiner David E , Sokolic Rob , Candotti Fabio , Malech Harry , Heller Theo , Koh Christopher 
Published: May 2023

Abstract
Background
Adenosine deaminase deficiency (ADA) is an autosomal recessive disorder leading to severe combined immunodeficiency (SCID). It is characterized patho-physiologically by intracellular accumulation of toxic products affecting lymphocytes. Other organ systems are known to be affected causing non-immune abnormalities. We aimed to conduct a cross sectional study to describe liver disease in autosomal recessive ADA-SCID.

Methods
Single center retrospective analysis of genetically confirmed autosomal recessive ADA-SCID was performed. Liver disease was defined as ≥1.5x the gender specific upper limit of normal (ULN; 33 IU/L for males and 25 IU/L for females) alanine aminotransferase (ALT) or moderate and severe increase in liver echogenicity on ultrasound.

Results
The cohort included 18 patients with 11 males. The median age was 11.5 (3.5–30.0 years) and median BMI percentile was 75.5 [36.75, 89.5]. All patients received enzyme replacement therapy at the time of evaluation. Seven (38%) and five (27%) patients had gene therapy (GT) and hematopoietic stem cell transplant (HSCT) in the past. Five patients had 1.5x ALT level more than 1.5x the U. Liver echogenicity was mild in 6 (33%), moderate in 2 (11%) and severe in 2 (11%) patients. All patients had normal Fibrosis-4 Index and Non-alcoholic fatty liver disease fibrosis biomarker scores indicating absence of advanced fibrosis in our cohort. Of 5 patients who had liver biopsies, steatohepatitis was noted in 3 patients (NAS score of 3,3,4).

Discussion
Non-immunologic manifestations of ADA-SCID have become more apparent in recent years as survival improved. We concluded that steatosis is the most common finding noted in our ADA-SCID cohort.
Changes in the salivary metabolome in patients with chronic erosive gastritis
Authors: Liu Shaowei , Zhang Shixiong , Chen Haoyu , Zhou Pingping , Yang Tianxiao , Lv Jingjing , Li Huixia , Wang Yangang 
Published: May 2023

Abstract
Introduction
Chronic erosive gastritis (CEG) is closely related to gastric cancer, which requires early diagnosis and intervention. The invasiveness and discomfort of electronic gastroscope have limited its application in the large-scale screening of CEG. Therefore, a simple and noninvasive screening method is needed in the clinic.

Objectives
The aim of this study is to screen potential biomarkers that can identify diseases from the saliva samples of CEG patients using metabolomics.

Methods
Saliva samples from 64 CEG patients and 30 healthy volunteers were collected, and metabolomic analysis was performed using UHPLC-Q-TOF/MS in the positive and negative ion modes. Statistical analysis was performed using both univariate (Student’s t-test) and multivariate (orthogonal partial least squares discriminant analysis) tests. Receiver operating characteristic (ROC) analysis was conducted to determine significant predictors in the saliva of CEG patients.

Results
By comparing the saliva samples from CEG patients and healthy volunteers, 45 differentially expressed metabolites were identified, of which 37 were up-regulated and 8 were down-regulated. These differential metabolites were related to amino acid, lipid, phenylalanine metabolism, protein digestion and absorption, and mTOR signaling pathway. In the ROC analysis, the AUC values of 7 metabolites were greater than 0.8, among which the AUC values of 1,2-dioleoyl-sn-glycoro-3-phosphodylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phospholine (SOPC) were greater than 0.9.

Conclusions
In summary, a total of 45 metabolites were identified in the saliva of CEG patients. Among them, 1,2-dioleoyl-sn-glycoro-3-phosphorylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phosphorine (SOPC) might have potential clinical application value.
Post-discharge light physical activity indicates recovery in acutely hospitalized older adults – the Hospital-ADL study
Authors: Terbraak Michel , Kolk Daisy , Vroomen Janet L. MacNeil , Twisk Jos W. R. , Buurman Bianca M. , van der Schaaf Marike 
Published: May 2023

Abstract
Background
Physical activity (PA) levels might be a simple overall physical function indicator of recovery in acutely hospitalized older adults; however it is unknown which amount and level of PA is associated with recovery. Our objective was to evaluate the amount and level of post discharge PA and its optimum cut-off values associated with recovery among acutely hospitalized older adults and stratified for frailty.

Methods
We performed a prospective observational cohort study including acutely hospitalized older adults (≥ 70 years). Frailty was assessed using Fried’s criteria. PA was assessed using Fitbit up to one week post discharge and quantified in steps and minutes light, moderate or higher intensity. The primary outcome was recovery at 3-months post discharge. ROC-curve analyses were used to determine cut-off values and area under the curve (AUC), and logistic regression analyses to calculate odds ratios (ORs).

Results
The analytic sample included 174 participants with a mean (standard deviation) age of 79.2 (6.7) years of whom 84/174 (48%) were frail. At 3-months, 109/174 participants (63%) had recovered of whom 48 were frail. In all participants, determined cut-off values were 1369 steps/day (OR: 2.7, 95% confidence interval [CI]: 1.3–5.9, AUC 0.7) and 76 min/day of light intensity PA (OR: 3.9, 95% CI: 1.8–8.5, AUC 0.73). In frail participants, cut-off values were 1043 steps/day (OR: 5.0, 95% CI: 1.7–14.8, AUC 0.72) and 72 min/day of light intensity PA (OR: 7.2, 95% CI: 2.2–23.1, AUC 0,74). Determined cut-off values were not significantly associated with recovery in non-frail participants.

Conclusions
Post-discharge PA cut-offs indicate the odds of recovery in older adults, especially in frail individuals, however are not equipped for use as a diagnostic test in daily practice. This is a first step in providing a direction for setting rehabilitation goals in older adults after hospitalization.
Fascioliasis associated with chronic cholecystitis in a woman from Sistan and Baluchestan province, a non-endemic region in Southeastern Iran
Authors: Shafiee Mohammad , Nasibi Saeid , Lashkarizadeh Mohammad Reza , Fasihi Harandi Majid 
Published: May 2023

Abstract
Background
Fascioliasis, caused by Fasciola hepatica, is a neglected zoonotic food-borne trematodiasis. The Caspian littoral in northern Iran is endemic for the disease, and human fascioliasis is well-known in that region. In the present study, we report the diagnosis, identification, and clinical management of a human case of fascioliasis associated with common bile duct (CBD) obstruction from a non-endemic remote area in southeastern Iran.

Case presentation
A 42-year-old female was admitted to Afzalipour Medical Center hepatobiliary surgery ward in Kerman with abdominal pain for the past three months. Dilated biliary tract and an ill-defined mass in CBD were reported in abdominal ultrasonography and magnetic resonance cholangiopancreatography, respectively. During distal CBD operation, nine leaf-like motile flatworms were isolated. A morphological study confirmed all the isolates as Fasciola, and further molecular investigations, identified the flukes as F. hepatica using both pepck multiplex PCR and cox1 sequencing.

Conclusion
Molecular and morphological findings of the study indicated the presence of human fascioliasis in the southeastern province of Sistan and Baluchestan in Iran. Fascioliasis is among the etiologies of chronic cholecystitis, and physicians should consider chronic cholecystitis associated with fascioliasis in the differential diagnosis. In the present report, endoscopic ultrasound was usefully applied for the accurate diagnosis of biliary fasciolosis.
Healthcare utilization and adverse outcomes stratified by sex, age and long-term care residency using the Alberta COVID-19 Analytics and Research Database (ACARD): a population-based descriptive study
Authors: Rennert-May Elissa , Crocker Alysha , D’Souza Adam G. , Zhang Zuying , Chew Derek , Beall Reed , Vickers David M. , Leal Jenine 
Published: May 2023

Abstract
Background
Understanding the epidemiology of Coronavirus Disease of 2019 (COVID-19) in a local context is valuable for both future pandemic preparedness and potential increases in COVID-19 case volume, particularly due to variant strains.

Methods
Our work allowed us to complete a population-based study on patients who tested positive for COVID-19 in Alberta from March 1, 2020 to December 15, 2021. We completed a multi-centre, retrospective population-based descriptive study using secondary data sources in Alberta, Canada. We identified all adult patients (≥ 18 years of age) tested and subsequently positive for COVID-19 (including only the first incident case of COVID-19) on a laboratory test. We determined positive COVID-19 tests, gender, age, comorbidities, residency in a long-term care (LTC) facility, time to hospitalization, length of stay (LOS) in hospital, and mortality. Patients were followed for 60 days from a COVID-19 positive test.

Results
Between March 1, 2020 and December 15, 2021, 255,037 adults were identified with COVID-19 in Alberta. Most confirmed cases occurred among those less than 60 years of age (84.3%); however, most deaths (89.3%) occurred among those older than 60 years. Overall hospitalization rate among those who tested positive was 5.9%. Being a resident of LTC was associated with substantial mortality of 24.6% within 60 days of a positive COVID-19 test. The most common comorbidity among those with COVID-19 was depression. Across all patients 17.3% of males and 18.6% of females had an unplanned ambulatory visit subsequent to their positive COVID-19 test.

Conclusions
COVID-19 is associated with extensive healthcare utilization. Residents of LTC were substantially impacted during the COVID-19 pandemic with high associated mortality. Further work should be done to better understand the economic burden associated with related healthcare utilization following a COVID-19 infection to inform healthcare system resource allocation, planning, and forecasting.
Maternal, obstetric and gynecological factors associated with preterm birth in Rwanda: findings from a national longitudinal study
Authors: Rutayisire Erigene , Mochama Monica , Ntihabose Corneille Killy , Utumatwishima Jean Nepo , Habtu Michael 
Published: May 2023

Abstract
Background
Preterm birth is one of the key causes of morbidity and mortality among neonates in low-income countries. In Rwanda, at least 35,000 babies are born prematurely each year, and 2600 children under the age of five die due to direct complications of prematurity each year. A limited number of studies have been conducted locally, many of which are not nationally representative. Thus, this study determined the prevalence as well as the maternal, obstetric, and gynecological factors associated with preterm birth in Rwanda at the national level.

Methods
A longitudinal cohort study was conducted from July 2020 to July 2021 among first-trimester pregnant women. A total of 817 women from 30 health facilities in 10 districts were included in the analysis. A pre-tested questionnaire was used to collect data. In addition, medical records were reviewed to extract relevant data. Ultrasound examination was used to assess and confirm gestational age on recruitment. A multivariable logistic regression analysis was performed to determine the independent maternal, obstetric, and gynecological factors associated with preterm birth.

Results
The prevalence of preterm births was 13.8%. Older maternal age- 35 to 49 years [Adjusted odds ratio (AOR) = 2.00; 95% Confidence Interval (CI) = 1.13–3.53)], secondhand smoke exposure during pregnancy (AOR = 1.91; 95% CI = 1.04–3.51), a history of abortion (AOR = 1.89; 95% CI = 1.13–3.15), premature membrane rupture (AOR = 9.30; 95% CI = 3.18–27.16), and hypertension during pregnancy (AOR = 4.40; 95% CI = 1.18–16.42) were identified as independent risk factors for preterm birth.

Conclusion
Preterm birth remains a significant public health issue in Rwanda. The associated risk factors for preterm birth were advanced maternal age, secondhand smoke, hypertension, history of abortion, and preterm membrane rupture. This study therefore recommends routine antenatal screening to identify and closely follow-up of those high-risk groups, in order to avoid the short- and long-term effects of preterm birth.