bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in the NUP93, NUP107 and NUP160 genes cause steroid-resistant nephrotic syndrome in Chinese children
Authors: Han Yanxinli , Sha Hongyu , Yang Yuan , Yu Zhuowei , Zhou Lanqi , Wang Yi , Yang Fengjie , Qiu Liru , Zhang Yu , Zhou Jianhua 
Published: April 2024

Abstract
Background
The variants of nucleoporins are extremely rare in hereditary steroid-resistant nephrotic syndrome (SRNS). Most of the patients carrying such variants progress to end stage kidney disease (ESKD) in their childhood. More clinical and genetic data from these patients are needed to characterize their genotype–phenotype relationships and elucidate the role of nucleoporins in SRNS.

Methods
Four patients of SRNS carrying biallelic variants in the NUP93, NUP107 and NUP160 genes were presented. The clinical and molecular genetic characteristics of these patients were summarized, and relevant literature was reviewed.

Results
All four patients in this study were female and initially presented with SRNS. The median age at the onset of the disease was 5.08 years, ranging from 1 to 10.5 years. Among the four patients, three progressed to ESKD at a median age of 7 years, ranging from 1.5 to 10.5 years, while one patient reached stage 3 chronic kidney disease (CKD3). Kidney biopsies revealed focal segmental glomerulosclerosis in three patients. Biallelic variants were detected in NUP93 in one patient, NUP107 in two patients, as well as NUP160 in one patient respectively. Among these variants, five yielded single amino acid substitutions, one led to nonsense mutation causing premature termination of NUP107 translation, one caused a single nucleotide deletion resulting in frameshift and truncation of NUP107. Furthermore, one splicing donor mutation was observed in NUP160. None of these variants had been reported previously.

Conclusion
This report indicates that biallelic variants in NUP93, NUP107 and NUP160 can cause severe early-onset SRNS, which rapidly progresses to ESKD. Moreover, these findings expand the spectrum of phenotypes and genotypes and highlight the importance of next-generation sequencing in elucidating the molecular basis of SRNS and allowing rational treatment for affected individuals.
The translocator protein 18kDa ligand etifoxine in the treatment of depressive disorders—a double-blind, randomized, placebo-controlled proof-of-concept study
Authors: Brunner Lisa-Marie , Riebel Marco , Wein Simon , Koller Michael , Zeman Florian , Huppertz Gunnar , Emmer Tanja , Eberhardt Yvonne , Schwarzbach Jens , Rupprecht Rainer , Nothdurfter Caroline 
Published: April 2024

Abstract
Background
Recent developments suggest that neurosteroids may achieve rapid antidepressant effects. As such, neurosteroidogenesis mediated by the translocator protein 18 kDa (TSPO) might constitute a promising option for the treatment of depression. Therefore, the current clinical trial aims to get the first evidence of whether TPSO ligands promote rapid antidepressant effects. Furthermore, we study which mechanisms of action, e.g., modulation of distinct neuronal networks, neurosteroidogenesis, endocrinological mechanisms, TSPO expression or microbiome composition, contribute to their putative antidepressant effects.

Methods
This is a randomized, placebo-controlled, double-blind single-center trial of 2-week treatment with the TSPO ligand etifoxine versus placebo in depressive patients. Main eligibility criteria: male or female individuals aged 18 to 65 years with unipolar/bipolar depressive disorder with no other psychiatric main diagnosis or acute neurological/somatic disorder or drug/alcohol dependence during their lifetime.
The primary endpoint is the time point at which 50% of the maximal effect has occurred (ET50) estimated by the scores of the Hamilton Depression Scale (HAMD-21). A total of 20 patients per group are needed to detect changes of therapeutic efficacy about 5% and changes of ET50 about 10% with a power of 70%. Assuming a drop-out rate of 10–20%, 50 patients will be randomized in total. The study will be conducted at the Department of Psychiatry and Psychotherapy of the University of Regensburg.

Discussion
This study will provide a first proof-of-concept on the potential of the TSPO ligand etifoxine in the treatment of depressive disorders.

Trial registration
Clinical Trials Register (EudraCT number: 2021-006773-38, registration date: 14 September 2022) and German Register of Clinical Studies (DRKS number: DRKS00031099, registration date: 23 January 2023).
Impact of the COVID-19 pandemic on utilization and cost for care of pediatric and young adult ALL
Authors: Hoover Alex , Watson Dave , Reimche Paige , Tanner Lynn , Gilchrist Laura , Finch Mike , Messinger Yoav H , Turcotte Lucie M. 
Published: April 2024

Abstract
Objective
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and among the most common malignancies in young adults and requires a unique pattern of healthcare utilization including an acute/emergent presentation and an intensive initial 8 months of therapy followed by two years of outpatient treatment. The COVID-19 pandemic caused massive global disruptions in healthcare use and delivery. This report aims to examine the effects of the COVID-19 pandemic on the presentation, diagnosis and continued management of childhood and young adult ALL in regard to utilization and cost of care among commercially insured individuals in the United States.

Results
Utilizing a commercial insurance claims database, 529 pediatric and young adult patients were identified who were diagnosed with ALL between January 2016 and March 2021. New diagnoses were evaluated by era and demographics. Utilization was measured by COVID-related era as number of inpatient and outpatient encounters, inpatient days, and cumulative cost during the initial 8 months of therapy. None of these cost or utilization factors changed significantly during or shortly after the pandemic. These findings reinforce that the necessary care for pediatric and young adult ALL was unwavering despite the massive shifts in the healthcare system caused by the COVID-19 pandemic. This provides a valuable benchmark as we further examine the factors that influence the pandemic’s impact on health equity and access to care, especially in vulnerable pediatric and young adult populations. This is the first investigation of the effect of the COVID-19 pandemic on utilization and cost of care in pediatric and young adult cancer.
Fixed point results for Geraghty–Ćirić-type contraction mappings in b-metric space with applications
Authors: Kalo Albray Gebremariam , Tola Kidane Koyas , Yesuf Haider Ebrahim 
Published: April 2024

AbstractIn this study, we manifest a new class of mappings that satisfy Geraghty–Ćirić-type contractive conditions in the context of b-metric spaces and prove a theorem on the existence and uniqueness of fixed points. Our results unify and generalize the results of Geraghty; Ćirić; Dukic, Kadelburg, and Radenović; and Shu-fang Li, Fei Hi, and Ning Lu in the setting of b-metric spaces. Furthermore, we provide examples to verify the correctness and applicability of our results. We also utilize our findings to show the existence of a unique solution for a nonlinear integral equation.
Unveilling genetic profiles and correlations of biofilm-associated genes, quorum sensing, and antibiotic resistance in Staphylococcus aureus isolated from a Malaysian Teaching Hospital
Authors: Chan Yun Li , Chee Chin Fei , Tang Soo Nee , Tay Sun Tee 
Published: April 2024

Abstract
Background
Staphylococcus aureus is a notorious multidrug resistant pathogen prevalent in healthcare facilities worldwide. Unveiling the mechanisms underlying biofilm formation, quorum sensing and antibiotic resistance can help in developing more effective therapy for S. aureus infection. There is a scarcity of literature addressing the genetic profiles and correlations of biofilm-associated genes, quorum sensing, and antibiotic resistance among S. aureus isolates from Malaysia.

Methods
Biofilm and slime production of 68 methicillin-susceptible S. aureus (MSSA) and 54 methicillin-resistant (MRSA) isolates were determined using a a plate-based crystal violet assay and Congo Red agar method, respectively. The minimum inhibitory concentration values against 14 antibiotics were determined using VITEK® AST-GP67 cards and interpreted according to CLSI-M100 guidelines. Genetic profiling of 11 S. aureus biofilm-associated genes and agr/sar quorum sensing genes was performed using single or multiplex polymerase chain reaction (PCR) assays.

Results
In this study, 75.9% (n = 41) of MRSA and 83.8% (n = 57) of MSSA isolates showed strong biofilm-forming capabilities. Intermediate slime production was detected in approximately 70% of the isolates. Compared to MSSA, significantly higher resistance of clindamycin, erythromycin, and fluoroquinolones was noted among the MRSA isolates. The presence of intracellular adhesion A (icaA) gene was detected in all S. aureus isolates. All MSSA isolates harbored the laminin-binding protein (eno) gene, while all MRSA isolates harbored intracellular adhesion D (icaD), clumping factors A and B (clfA and clfB) genes. The presence of agrI and elastin-binding protein (ebpS) genes was significantly associated with biofilm production in MSSA and MRSA isolates, respectively. In addition, agrI gene was also significantly correlated with oxacillin, cefoxitin, and fluoroquinolone resistance.

Conclusions
The high prevalence of biofilm and slime production among MSSA and MRSA isolates correlates well with the detection of a high prevalence of biofilm-associated genes and agr quorum sensing system. A significant association of agrI gene was found with cefoxitin, oxacillin, and fluoroquinolone resistance. A more focused approach targeting biofilm-associated and quorum sensing genes is important in developing new surveillance and treatment strategies against S. aureus biofilm infection.
Blocking group 2 innate lymphoid cell activation and macrophage M2 polarization: potential therapeutic mechanisms in ovalbumin-induced allergic asthma by calycosin
Authors: Tian Chunyan , Liu Qi , Zhang Xiaoyu , Li Zhuying 
Published: April 2024

Abstract
Background
Calycosin, a flavonoid compound extracted from Astragalus membranaceus, has shown anti-asthma benefits in house dust mite-induced asthma. Recent studies have suggested that innate-type cells, including group 2 innate lymphoid cells (ILC2s) and macrophages, serve as incentives for type 2 immunity and targets for drug development in asthma. This work focuses on the effects of calycosin on the dysregulated ILC2s and macrophages in allergic asthma.

Methods
In vivo, the asthmatic mouse model was established with ovalbumin (OVA) sensitization and challenge, and calycosin was intraperitoneally administered at doses of 20 and 40 mg/kg. In vivo, mouse primary ILC2s were stimulated with interleukin (IL)-33 and mouse RAW264.7 macrophages were stimulated with IL-4 and IL-13 to establish the cell models. Cells were treated with calycosin at doses of 5 and 10 µM.

Results
In vivo, we observed significantly reduced numbers of eosinophils, neutrophils, monocyte macrophages and lymphocytes in the bronchoalveolar lavage fluid (BALF) of OVA-exposed mice with 40 mg/kg calycosin. Histopathological assessment showed that calycosin inhibited the airway inflammation and remodeling caused by OVA. Calycosin markedly decreased the up-regulated IL-4, IL-5, IL-13, IL-33, and suppression tumorigenicity 2 (ST2) induced by OVA in BALF and/or lung tissues of asthmatic mice. Calycosin repressed the augment of arginase 1 (ARG1), IL-10, chitinase-like 3 (YM1) and mannose receptor C-type 1 (MRC1) levels in the lung tissues of asthmatic mice. In vivo, calycosin inhibited the IL-33-induced activation as well as the increase of IL-4, IL-5, IL-13 and ST2 in ILC2s. Calycosin also repressed the increase of ARG1, IL-10, YM1 and MRC1 induced by IL-4 and IL-13 in RAW264.7 macrophages. In addition, we found that these changes were more significant in 40 mg/kg calycosin treatment than 20 mg/kg calycosin.

Conclusions
Collectively, this study showed that calycosin might attenuate OVA-induced airway inflammation and remodeling in asthmatic mice via preventing ILC2 activation and macrophage M2 polarization. Our study might contribute to further study of asthmatic therapy.
Knowledge, attitudes, and practices related to dietary salt among older adults in Abha, Saudi Arabia
Authors: Alhazmi Amani , Hawash Manal Mohammed , Ali Haroon , Narapureddy Bayapa Reddy , Aziz Farah 
Published: April 2024

AbstractThe need to foster successful aging has intensified with the aging of the global population. This study aimed to assess the knowledge, attitudes, and practices (KAP) concerning dietary salt consumption and to investigate the correlations between sociodemographic variables and salt-related KAP. A structured interview was administered to a cohort of 200 older adults in Abha City, Saudi Arabia, recruited through a convenience sampling approach. The evaluation of salt-related KAP revealed widespread low knowledge (91.5%) as participants scored less than 3, negative attitudes (85.5%) scored less than 12, and predominantly unsatisfactory practices (69.5%) with scores less than 26. Noteworthy differences emerged between participants with poor overall KAP (81.5%) and those with good KAP (18.5%). Significantly weak negative correlations were found between age (r=-0.212), marital status (-0.236), and body mass index (-0.243) with overall KAP. Further examination revealed a significantly weak positive correlation between attitude and practice (r = 0.141). KAP scores show a highly significant positive correlation with overall KAP scores (r = 0.169, 0.352, 0.969). The uncovered correlations contribute to a valuable understanding of the complex dynamics surrounding salt-related KAP. This understanding guides the design of targeted interventions, such as health education programs, promoting successful aging and public health outcomes.
Comparison of canine colostrum and milk using a multi-omics approach
Authors: Cohen Alisa , Turjeman Sondra , Levin Rachel , Tal Smadar , Koren Omry 
Published: April 2024

Abstract
Background
A mother’s milk is considered the gold standard of nutrition in neonates and is a source of cytokines, immunoglobulins, growth factors, and other important components, yet little is known about the components of canine milk, specifically colostrum, and the knowledge related to its microbial and metabolic profiles is particularly underwhelming. In this study, we characterized canine colostrum and milk microbiota and metabolome for several breeds of dogs and examined profile shifts as milk matures in the first 8 days post-whelping.

Results
Through untargeted metabolomics, we identified 63 named metabolites that were significantly differentially abundant between days 1 and 8 of lactation. Surprisingly, the microbial compositions of the colostrum and milk, characterized using 16S rRNA gene sequencing, were largely similar, with only two differentiating genera. The shifts observed, mainly increases in several sugars and amino sugars over time and shifts in amino acid metabolites, align with shifts observed in human milk samples and track with puppy development.

Conclusion
Like human milk, canine milk composition is dynamic, and shifts are well correlated with developing puppies’ needs. Such a study of the metabolic profile of canine milk, and its relation to the microbial community, provides insights into the changing needs of the neonate, as well as the ideal nutrition profile for optimal functionality. This information will add to the existing knowledge base of canine milk composition with the prospect of creating a quality, tailored milk substitute or supplement for puppies.
Cloning, heterologous expression and purification of the novel thermo-alkalistable cellulase from Geobacillus sp. TP-3 and its molecular characterisation
Authors: Arya Meghna , Chauhan Garima , Verma Utsav , Sharma Monica 
Published: April 2024

Abstract
Background
Thermophilic cellulases are essential for effectively degrading cellulose, which is a significant part of lignocellulosic waste. In this study, we focused on a cellulase gene (~ 1.2 kb) obtained from Geobacillus sp. TP-3, a thermo-alkalophilic bacterium isolated from the hot springs of Tapovan (Uttarakhand, India). Cellulase gene (~ 1.2 kb) was amplified via PCR, cloned into pET-28a (+) vector, transferred to Escherichia coli DH5α cells and expressed in Escherichia coli BL21 (DE3). The recombinant cellulase (rCel_TP) was purified using Ni2+-NTA affinity chromatography.

Results
The purified rCel_TP enzyme exhibited optimal activity at 50 ºC and pH 8, displaying stability even after 3 h of incubation at 50 ºC. The molecular weight of the purified 6 × His-tagged rCel_TP was determined to be ~ 40.2 kDa. Under conditions of 50 ºC and pH 8, the kinetic parameters of the purified enzyme were determined, with Km and Vmax values of 116.78 mg/mL and 44.05 µmolmg−1 min−1, respectively. The activity of the rCel_TP cellulase was significantly improved by Hg2+, Cu2+ and Co2+. However, it was suppressed by dithiothreitol and β-mercaptoethanol. Ethylenediaminetetraacetic acid and solvents also had a slight inhibitory effect.

Conclusion
These results suggest the potential applications of the recombinant cellulase in biomass conversion processes for the production of fuels and other industrial operations. The study contributes valuable insights into the properties and applicability of cellulases derived from extremophilic microorganisms.

Graphical abstract
Use of Sodium Thiosulfate as an Otoprotectant in Patients With Cancer Treated With Platinum Compounds: A Review of the Literature
Authors: Meijer Annelot J.M. , Diepstraten Franciscus A. , Ansari Marc , Bouffet Eric , Bleyer Archie , Fresneau Brice , Geller James I. , Huitema Alwin D.R. , Kogner Per , Maibach Rudolf , O'Neill Allison F. , Papadakis Vassilios , Rajput Kaukab M. , Veal Gareth J. , Sullivan Michael , van den Heuvel-Eibrink Marry M. , Brock Penelope R. 
Published: April 2024

PURPOSE Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL). DESIGN A comprehensive narrative review is presented. RESULTS Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting. CONCLUSION Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss.
Identification of Eukaryotic Translation Initiation Factor 4B as a Novel Candidate Gene for Congenital Hypothyroidism
Authors: Sun Feng , Zhang Rui-Jia , Fang Ya , Yan Cheng-Yan , Zhang Chang-Run , Wu Feng-Yao , Yang Rui-Meng , Han Bing , Song Huai-Dong , Zhao Shuang-Xia 
Published: April 2024

Abstract

Context
Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates, but its etiology is still poorly understood.

Objective
We performed whole exome sequencing to identify a novel causative gene for CH and functional studies to validate its role in the occurrence of CH.

Methods
Whole exome sequencing in 98 CH patients not harboring known CH candidate genes and bioinformatic analysis were performed. Functional analysis was performed using morpholino, a synthetic short antisense oligonucleotide that contains 25 DNA bases on a methylene morpholine backbone, in zebrafish and CRISPR-Cas9-mediated gene knockout in mice.

Results
Eukaryotic translation initiation factor 4B (EIF4B) was identified as the most promising candidate gene. The EIF4B gene was inherited in an autosomal recessive model, and 1 patient with thyroid dysgenesis carried EIF4B biallelic variants (p.S430F/p.P328L). In zebrafish, the knockdown of eif4ba/b expression caused thyroid dysgenesis and growth retardation. Thyroid hormone levels were significantly decreased in morphants compared with controls. Thyroxine treatment in morphants partially rescued growth retardation. In mice, the homozygous conceptuses of Eif4b+/− parents did not survive. Eif4b knockout embryos showed severe growth retardation, including thyroid dysgenesis and embryonic lethality before E18.5.

Conclusion
These experimental data support a role for EIF4B function in the pathogenesis of the hypothyroid phenotype seen in CH patients. Our work indicates that EIF4B was identified as a novel candidate gene in CH. EIF4B is essential for animal survival, but further studies are needed to validate its role in the pathogenesis of CH.
Molecular Assessment of Proadipogenic Effects for Common-Use Contraceptives and Their Mixtures
Authors: Chiang Yu-Ting Tiffany , Kassotis Christopher D 
Published: April 2024

Abstract
Hormonal contraceptives are widely prescribed due to their effectiveness and convenience and have become an integral part of family planning strategies worldwide. In the United States, approximately 65% of reproductive-aged women are estimated to be using contraceptive options, with approximately 33% using one or a combination of hormonal contraceptives. While these methods have undeniably contributed to improved reproductive health, recent studies have raised concerns regarding their potential effect on metabolic health. Despite widespread anecdotal reports, epidemiological research has been mixed as to whether hormonal contraceptives contribute to metabolic health effects. As such, the goals of this study were to assess the adipogenic activity of common hormonal contraceptive chemicals and their mixtures. Five different models of adipogenesis were used to provide a rigorous assessment of metabolism-disrupting effects. Interestingly, every individual contraceptive (both estrogens and progestins) and each mixture promoted significant adipogenesis (eg, triglyceride accumulation and/or preadipocyte proliferation). These effects appeared to be mediated in part through estrogen receptor signaling, particularly for the contraceptive mixtures, as cotreatment with fulvestrant acted to inhibit contraceptive-mediated proadipogenic effects on triglyceride accumulation. In conclusion, this research provides valuable insights into the complex interactions between hormonal contraceptives and adipocyte development. The results suggest that both progestins and estrogens within these contraceptives can influence adipogenesis, and the specific effects may vary based on the receptor disruption profiles. Further research is warranted to establish translation of these findings to in vivo models and to further assess causal mechanisms underlying these effects.