bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of in vitro activities of newer triazoles and classic antifungal agents against dermatophyte species isolated from Iranian University Hospitals: a multi-central study
Authors: Badiee Parisa , Shokohi Tahereh , Hashemi Jamal , Mohammadi Rasoul , Najafzadeh Mohammad Javad , Amin Shahidi Maneli , Ghasemi Fatemeh , Jafarian Hadis 
Published: February 2023

Abstract
Background
Dermatophytes have the ability to invade the keratin layer of humans and cause infections. The aims of this study were the accurate identification of dermatophytes by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method and sequencing and comparison between the in vitro activities of newer and established antifungal agents against them.

Methods
Clinical specimens of patients from five Iranian university laboratories were entered in this study. Samples were cultured on sabouraud dextrose agar medium. For molecular identification, extracted DNAs were amplified by the universal fungal primers ITS1 and ITS4, and digested with MvaI enzymes. The antifungal susceptibility test for each isolate to terbinafine, griseofulvin, caspofungin, fluconazole, itraconazole, luliconazole, and isavuconazole was performed, according to the microdilution CLSI M38-A2 and CLSI M61 standard methods.

Results
Two hundred and seven fungi species similar to dermatophytes were isolated of which 198 (95.6%) were dermatophytes by molecular assay. The most commonly isolated were Trichophyton mentagrophytes (76/198), followed by Trichophyton interdigitale (57/198), Trichophyton rubrum (34/198), Trichophyton tonsurans (12/198), Microsporum canis (10/198), Trichophyton simii (3/198), Epidermophyton floccosum (3/198), Trichophyton violaceum (2/198), and Trichophyton benhamiae (1/198). The GM MIC and MIC90 values for all the isolates were as follows: terbinafine (0.091 and 1 μg/ml), griseofulvin (1.01 and 4 μg/ml), caspofungin (0.06 and 4 μg/ml), fluconazole (16.52 and 32 μg/ml), itraconazole (0.861 and 8 μg/ml), isavuconazole (0.074 and 2 μg/ml), and luliconazole (0.018 and 0.25 μg/ml).

Conclusion
Trichophyton mentagrophytes, Trichophyton interdigitale, and Trichophyton rubrum were the most common fungal species isolated from the patients. luliconazole, terbinafine, and isavuconazole in vitro were revealed to be the most effective antifungal agents against all dermatophyte isolates.
Genetic determinants of macrolide and tetracycline resistance in penicillin non-susceptible Streptococcus pneumoniae isolates from people living with HIV in Dar es Salaam, Tanzania
Authors: Manyahi Joel , Moyo Sabrina J. , Langeland Nina , Blomberg Bjørn 
Published: February 2023

Abstract
Background
Over one million yearly deaths are attributable to Streptococcus pneumoniae and people living with HIV are particularly vulnerable. Emerging penicillin non-susceptible Streptococcus pneumoniae (PNSP) challenges therapy of pneumococcal disease. The aim of this study was to determine the mechanisms of antibiotic resistance among PNSP isolates by next generation sequencing.

Methods
We assessed 26 PNSP isolates obtained from the nasopharynx from 537 healthy human immunodeficiency virus (HIV) infected adults in Dar es Salaam, Tanzania, participating in the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890, registered on 23rd March, 2017). Next generation whole genome sequencing on the Illumina platform was used to identify mechanisms of resistance to antibiotics among PNSP.

Results
Fifty percent (13/26) of PNSP were resistant to erythromycin, of these 54% (7/13) and 46% (6/13) had MLSB phenotype and M phenotype respectively. All erythromycin resistant PNSP carried macrolide resistance genes; six isolates had mef(A)-msr(D), five isolates had both erm(B) and mef(A)-msr(D) while two isolates carried erm(B) alone. Isolates harboring the erm(B) gene had increased MIC (> 256 µg/mL) towards macrolides, compared to isolates without erm(B) gene (MIC 4-12 µg/mL) p < 0.001. Using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, the prevalence of azithromycin resistance was overestimated compared to genetic correlates. Tetracycline resistance was detected in 13/26 (50%) of PNSP and all the 13 isolates harbored the tet(M) gene. All isolates carrying the tet(M) gene and 11/13 isolates with macrolide resistance genes were associated with the mobile genetic element Tn6009 transposon family. Of 26 PNSP isolates, serotype 3 was the most common (6/26), and sequence type ST271 accounted for 15% (4/26). Serotypes 3 and 19 displayed high-level macrolide resistance and frequently carried both macrolide and tetracycline resistance genes.

Conclusion
The erm(B) and mef(A)-msr(D) were common genes conferring resistance to MLSB in PNSP. Resistance to tetracycline was conferred by the tet(M) gene. Resistance genes were associated with the Tn6009 transposon.
Parental stress and physical violence against children during the second year of the COVID-19 pandemic: results of a population-based survey in Germany
Authors: Geprägs Alina , Bürgin David , Fegert Jörg M. , Brähler Elmar , Clemens Vera 
Published: February 2023

Abstract
Background
Parents and caregivers belonged to those with the highest burdens during the COVID-pandemic. Considering the close link between parental stress and child maltreatment, identifying families with high parental stress is of utmost importance to prevent violence against children. Within this study, we thus aimed to investigate the interplay of parental stress, changes in parental stress, and physical violence against children during the second year of the COVID-pandemic on an exploratory level.

Methods
We conducted a cross-sectional, observational study in Germany from July to October 2021. By using different sampling steps, a representative probability sample of the German population was generated. A subsample of these participants with children under the age of 18 was included for analysis within this study (N = 453, 60.3% females, Mage = 40.08; SD = 8.53).

Results
Higher parental stress levels were associated with more physical violence against children, higher levels of own experiences of child maltreatment, and mental health symptoms. An increase in parental stress during the pandemic was associated with female sex, the use of physical violence against children, and parental experience of child maltreatment. Parents who have ever used physical violence against their children have been characterized by higher parental stress levels, a stronger increase in parental stress during the pandemic, own experience of child maltreatment, mental health symptoms and sociodemographic characteristics. Higher parental stress levels, a stronger increase of parental stress during the pandemic, having pre-existing psychiatric disorders, and parental experience of child maltreatment predicted an increased use of physical violence against children during the pandemic.

Conclusions
Our results underscore the importance of parental stress for the risk of physical violence against children, more so in times of overall increased stress due to the pandemic and underline the need for low threshold support for families at risk in times of crises.
The gut microbiota and metabolite profiles are altered in patients with spinal cord injury
Authors: Kong Ganggang , Zhang Wenwu , Zhang Siyun , Chen Jiewen , He kejun , Zhang Changming , Yuan Xi , Xie Baoshu 
Published: February 2023

Abstract
Background
Metabolites secreted by the gut microbiota may play an essential role in microbiota–gut–central nervous system crosstalk. In this study, we explored the changes occurring in the gut microbiota and their metabolites in patients with spinal cord injury (SCI) and analyzed the correlations among them.

Methods
The structure and composition of the gut microbiota derived from fecal samples collected from patients with SCI (n = 11) and matched control individuals (n = 10) were evaluated using 16S rRNA gene sequencing. Additionally, an untargeted metabolomics approach was used to compare the serum metabolite profiles of both groups. Meanwhile, the association among serum metabolites, the gut microbiota, and clinical parameters (including injury duration and neurological grade) was also analyzed. Finally, metabolites with the potential for use in the treatment of SCI were identified based on the differential metabolite abundance analysis.

Results
The composition of the gut microbiota was different between patients with SCI and healthy controls. At the genus level, compared with the control group, the abundance of UBA1819, Anaerostignum, Eggerthella, and Enterococcus was significantly increased in the SCI group, whereas that of Faecalibacterium, Blautia, Escherichia–Shigella, Agathobacter, Collinsella, Dorea, Ruminococcus, Fusicatenibacter, and Eubacterium was decreased. Forty-one named metabolites displayed significant differential abundance between SCI patients and healthy controls, including 18 that were upregulated and 23 that were downregulated. Correlation analysis further indicated that the variation in gut microbiota abundance was associated with changes in serum metabolite levels, suggesting that gut dysbiosis is an important cause of metabolic disorders in SCI. Finally, gut dysbiosis and serum metabolite dysregulation was found to be associated with injury duration and severity of motor dysfunction after SCI.

Conclusions
We present a comprehensive landscape of the gut microbiota and metabolite profiles in patients with SCI and provide evidence that their interaction plays a role in the pathogenesis of SCI. Furthermore, our findings suggested that uridine, hypoxanthine, PC(18:2/0:0), and kojic acid may be important therapeutic targets for the treatment of this condition.
Diagnostic accuracy of a three-protein signature in women with suspicious breast lesions: a multicenter prospective trial
Authors: Lee Eun-Shin , Kim Yumi , Shin Hee-Chul , Hwang Ki-Tae , Min Junwon , Kim Min Kyoon , Ahn SooKyung , Jung So-Youn , Shin Hyukjai , Chung MinSung , Yoo Tae-Kyung , Jung Seungpil , Woo Sang Uk , Kim Ju-Yeon , Noh Dong-Young , Moon Hyeong-Gon 
Published: February 2023

Abstract
Background
Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions.

Findings
This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants.

Conclusions
The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials.
This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 (https://cris.nih.go.kr).
siVAE: interpretable deep generative models for single-cell transcriptomes
Authors: Choi Yongin , Li Ruoxin , Quon Gerald 
Published: February 2023

AbstractNeural networks such as variational autoencoders (VAE) perform dimensionality reduction for the visualization and analysis of genomic data, but are limited in their interpretability: it is unknown which data features are represented by each embedding dimension. We present siVAE, a VAE that is interpretable by design, thereby enhancing downstream analysis tasks. Through interpretation, siVAE also identifies gene modules and hubs without explicit gene network inference. We use siVAE to identify gene modules whose connectivity is associated with diverse phenotypes such as iPSC neuronal differentiation efficiency and dementia, showcasing the wide applicability of interpretable generative models for genomic data analysis.
Effect of vitamin D supplementation versus placebo on recovery delay among COVID-19 Tunisian patients: a randomized-controlled clinical trial
Authors: Abroug Hela , Maatouk Amani , Bennasrallah Cyrine , Dhouib Wafa , Ben Fredj Manel , Zemni Imen , Kacem Meriem , Mhalla Salma , Nouira Sarra , Ben Belgacem Manel , Nasri Aymen , Klii Rim , Loussaief Chawki , Ben Alya Nissaf , Bouanene Ines , Belguith Sriha Asma 
Published: February 2023

Abstract

Introduction
The present study aimed to determine the impact of vitamin D supplementation (VDs) on recovery delay among COVID-19 patients.

Methods
We performed a randomized controlled clinical trial at the national COVID-19 containment center in Monastir (Tunisia), from May to August 2020. Simple randomization was done in a 1:1 allocation ratio. We included patients aged more than 18 years who had confirmed reverse transcription-polymerase chain reaction (RT-PCR) and who remained positive on the 14th day. The intervention group received VDs (200,000 IU/1 ml of cholecalciferol); the control group received a placebo treatment (physiological saline (1 ml)). We measured the recovery delay and the cycle threshold (Ct) values in RT-PCR for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The log-rank test and hazard ratios (HR) were calculated.

Results
A total of 117 patients were enrolled. The mean age was 42.7 years (SD 14). Males represented 55.6%. The median duration of viral RNA conversion was 37 days (95% confidence interval (CI): 29–45.50) in the intervention group and 28 days (95% CI: 23–39) in the placebo group (p=0.010). HR was 1.58 (95% CI: 1.09–2.29, p=0.015). Ct values revealed a stable trend over time in both groups.

Conclusion
VDs was not associated with a shortened recovery delay when given to patients for whom the RT-PCR remained positive on the 14th day.

Trial registration

This study was approved by the Human Subjects Protection Tunisia center (TN2020-NAT-INS-40) on April 28, 2020, and by ClinicalTrial.gov on May 12, 2021 with approval number ClinicalTrials.gov ID: NCT04883203.
Effectiveness of four deconstructive meditative practices on well-being and self-deconstruction: study protocol for an exploratory randomized controlled trial
Authors: García-Campayo Javier , Hijar-Aguinaga Rinchen , López-Del-Hoyo Yolanda , Magallón-Botaya Rosa , Fernández-Martínez Selene , Barceló-Soler Alberto , Soler-Ribaudi Joaquim , Montero-Marin Jesus 
Published: February 2023

Abstract
Introduction
The efficacy of interventions based on mindfulness and compassion has been demonstrated in both clinical and general population, and in different social contexts. These interventions include so-called attentional and constructive meditation practices, respectively. However, there is a third group, known as deconstructive meditation practices, which has not been scientifically studied. Deconstructive practices aim to undo maladaptive cognitive patterns and generate knowledge about internal models of oneself, others and the world. Although there are theoretical and philosophical studies on the origin of addiction to the self or on the mechanisms of action associated with the deconstruction of the self, there are no randomized controlled trials evaluating these techniques in either a healthy population or clinical samples. This study aims to evaluate the effect of three deconstructive techniques by comparing them to mindfulness in the general population.

Methods and analysis
A randomized controlled clinical trial will be conducted with about 240 participants allocated to four groups: (a) mindful breathing, (b) prostrations, according to Tibetan Buddhist tradition; (c) the Koan Mu, according to Zen Buddhist tradition; and (d) the mirror exercise, according to Toltec tradition. The primary outcome will be the qualities of the non-dual experience and spiritual awakening, measured by the Nondual Embodiment Thematic Inventory, assessed at pre- and post-treatment and at 3- and 6-month follow-ups. Other outcomes will be mindfulness, happiness, compassion, affectivity and altered state of consciousness. Quantitative data will be compared using mixed-effects linear regression models, and qualitative data will be analysed through thematic analysis and using the constant comparative method from grounded theory.

Ethics and dissemination
Approval was obtained from the Research Ethics Committee of Aragon, Spain. The results will be submitted to peer-reviewed specialized journals, and brief reports will be sent to participants on request.

Trial registration
ClinicalTrials.gov NCT05317754. Registered on August 2,2022.
Synthesis, DFT investigations, antioxidant, antibacterial activity and SAR-study of novel thiophene-2-carboxamide derivatives
Authors: Metwally Heba M. , Khalaf Norhan A. , Abdel-Latif Ehab , Ismail Mohamed A. 
Published: February 2023

AbstractSynthetic strategy for the synthesis of thiophene 2-carboxamide derivatives substituted with hydroxyl, methyl and amino groups at position-3 was proposed. The strategy includes the cyclization of the precursor ethyl 2-arylazo-3-mercapto-3-(phenylamino)acrylate derivatives, 2-acetyl-2-arylazo-thioacetanilide derivatives and N-aryl-2-cyano-3-mercapto-3-(phenylamino)acrylamide derivatives with N-(4-acetylphenyl)-2-chloroacetamide in alcoholic sodium ethoxide. IR, 1H NMR, and mass spectroscopic analyses were used to characterize the synthesized derivatives. In addition, molecular, electronic properties of the synthesized products were studied by the density functional theory (DFT) where they exhibited close HOMO–LUMO energy gap (ΔEH-L) in which the amino derivatives 7a-c have the highest while the methyl derivatives 5a-c were the lowest. Using the ABTS method, the antioxidant properties of the produced compounds were evaluated, where amino thiophene-2-carboxamide 7a exhibit significant inhibition activity 62.0% compared to ascorbic acid The antibacterial activity against two pathogenic Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two of pathogenic Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) revealed that 7b records the highest activity index compared to ampicillin 83.3, 82.6, 64.0, 86.9%, respectively. Furthermore, the thiophene-2-carboxamide derivatives were docked with five different proteins with the use molecular docking tools and the results explained interactions between amino acid residue of enzyme and compounds. Compounds 3b and 3c showed the highest binding score with 2AS1 protein.
Graphical Abstract
Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder
Authors: Cardo Lucia F. , de la Fuente Daniel C. , Li Meng 
Published: February 2023

Abstract
Background
Disruptions of SETBP1 (SET binding protein 1) on 18q12.3 by heterozygous gene deletion or loss-of-function variants cause SETBP1 disorder. Clinical features are frequently associated with moderate to severe intellectual disability, autistic traits and speech and motor delays. Despite the association of SETBP1 with neurodevelopmental disorders, little is known about its role in brain development.

Methods
Using CRISPR/Cas9 genome editing technology, we generated a SETBP1 deletion model in human embryonic stem cells (hESCs) and examined the effects of SETBP1-deficiency in neural progenitors (NPCs) and neurons derived from these stem cells using a battery of cellular assays, genome-wide transcriptomic profiling and drug-based phenotypic rescue.

Results
Neural induction occurred efficiently in all SETBP1 deletion models as indicated by uniform transition into neural rosettes. However, SETBP1-deficient NPCs exhibited an extended proliferative window and a decrease in neurogenesis coupled with a deficiency in their ability to acquire ventral forebrain fate. Genome-wide transcriptome profiling and protein biochemical analysis revealed enhanced activation of Wnt/β-catenin signaling in SETBP1 deleted cells. Crucially, treatment of the SETBP1-deficient NPCs with a small molecule Wnt inhibitor XAV939 restored hyper canonical β-catenin activity and restored both cortical and MGE neuronal differentiation.

Limitations
The current study is based on analysis of isogenic hESC lines with genome-edited SETBP1 deletion and further studies would benefit from the use of patient-derived iPSC lines that may harbor additional genetic risk that aggravate brain pathology of SETBP1 disorder.

Conclusions
We identified an important role for SETBP1 in controlling forebrain progenitor expansion and neurogenic differentiation. Our study establishes a novel regulatory link between SETBP1 and Wnt/β-catenin signaling during human cortical neurogenesis and provides mechanistic insights into structural abnormalities and potential therapeutic avenues for SETBP1 disorder.
Single cell and lineage tracing studies reveal the impact of CD34+ cells on myocardial fibrosis during heart failure
Authors: Du Luping , Sun Xiaotong , Gong Hui , Wang Ting , Jiang Liujun , Huang Chengchen , Xu Xiaodong , Li Zhoubin , Xu Hongfei , Ma Liang , Li Weidong , Chen Ting , Xu Qingbo 
Published: February 2023

Abstract
Background
CD34+ cells have been used to treat the patients with heart failure, but the outcome is variable. It is of great significance to scrutinize the fate and the mechanism of CD34+ cell differentiation in vivo during heart failure and explore its intervention strategy.

Methods
We performed single-cell RNA sequencing (scRNA-seq) of the total non-cardiomyocytes and enriched Cd34-tdTomato+ lineage cells in the murine (male Cd34-CreERT2; Rosa26-tdTomato mice) pressure overload model (transverse aortic constriction, TAC), and total non-cardiomyocytes from human adult hearts. Then, in order to determine the origin of CD34+ cell that plays a role in myocardial fibrosis, bone marrow transplantation model was performed. Furthermore, to further clarify the role of CD34 + cells in myocardial remodeling in response to TAC injury, we generated Cd34-CreERT2; Rosa26-eGFP-DTA (Cre/DTA) mice.

Results
By analyzing the transcriptomes of 59,505 single cells from the mouse heart and 22,537 single cells from the human heart, we illustrated the dynamics of cell landscape during the progression of heart hypertrophy, including CD34+ cells, fibroblasts, endothelial and immune cells. By combining genetic lineage tracing and bone marrow transplantation models, we demonstrated that non-bone-marrow-derived CD34+ cells give rise to fibroblasts and endothelial cells, while bone-marrow-derived CD34+ cell turned into immune cells only in response to pressure overload. Interestingly, partial depletion of CD34+ cells alleviated the severity of myocardial fibrosis with a significant improvement of cardiac function in Cd34-CreERT2; Rosa26-eGFP-DTA model. Similar changes of non-cardiomyocyte composition and cellular heterogeneity of heart failure were also observed in human patient with heart failure. Furthermore, immunostaining showed a double labeling of CD34 and fibroblast markers in human heart tissue. Mechanistically, our single-cell pseudotime analysis of scRNA-seq data and in vitro cell culture study revealed that Wnt-β-catenin and TGFβ1/Smad pathways are critical in regulating CD34+ cell differentiation toward fibroblasts.

Conclusions
Our study provides a cellular landscape of CD34+ cell-derived cells in the hypertrophy heart of human and animal models, indicating that non-bone-marrow-derived CD34+ cells differentiating into fibroblasts largely account for cardiac fibrosis. These findings may provide novel insights for the pathogenesis of cardiac fibrosis and have further potential therapeutic implications for the heart failure.