bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenibut: Review and Pharmacologic Approaches to Treating Withdrawal
Authors: Penzak Scott R. , Bulloch Marilyn 
Published: February 2024

Abstractβ‐Phenyl‐γ‐aminobutyric acid (phenibut) is an analog of the inhibitory neurotransmitter γ‐aminobutyric acid (GABA) that was first synthesized in Russia in the early 1960s. It is marketed as a nootropic (smart drug) to improve cognitive performance, and to treat generalized and social anxiety, insomnia, and alcohol withdrawal. The use of phenibut is legal in the USA and it is widely available online without a prescription. Increased public awareness of phenibut has led to a growing number of reports of acute intoxication and withdrawal. In this review, we describe the pharmacology of phenibut, the presentation and management of acute intoxication, and regulatory issues, placing particular emphasis on the treatment of acute withdrawal, for which there are no comparative studies. Among 29 cases of phenibut withdrawal, patients were successfully treated with baclofen, benzodiazepines, and phenobarbital, as individual agents or in various combinations. Ancillary medications included antipsychotics, dexmedetomidine, gabapentin, and pregabalin. After stabilization, a number of patients did well on baclofen tapers, whereas others were weaned off benzodiazepines or phenobarbital. Phenobarbital may be preferred over baclofen, or used as an added agent, in patients at risk for seizures. As long as phenibut remains legal, cases of phenibut intoxication and withdrawal are likely to increase. As urine or plasma drug screening for phenibut is not widely available, it is vital that clinicians obtain a detailed medication history in patients presenting to the emergency department with nonspecific symptoms that may represent phenibut intoxication or withdrawal. Further, clinicians may wish to consult an addiction specialist or toxicologist in these situations.
Manure nutrient cycling in US animal agriculture basins—North Carolina case study
Authors: Huezo Luis , Jones Daniela , Edwards Eric , Sharara Mahmoud 
Published: February 2024

AbstractNutrient cycling in crop–animal production is impacted by changes in both systems, with imbalance hotspots in concentrated animal production regions severely impacting water quality. This study assesses manure–crop nutrient balances in five river basins in North Carolina and demonstrates a new approach for partial nutrient balances along hydrological boundaries. County‐level crop production data were combined with crop‐type spatial distribution data to derive spatially referenced nutrient uptake and removal. Similarly, spatially referred animal production inventory data were used to derive excreted and recovered manure nutrients. Partial nutrient balances were developed for both N and P in basins and hydrologic units. Excreted manure N and P were 139% and 159% of respective plant N and P removal at harvest across the five basins. Finer geographical scales revealed hotspots for manure surplus, particularly within the Cape Fear basin (up to 96% N and 97% P). Despite N hotspots, plant‐available manure N met only 38% of crop N demand due to significant losses during storage. Plant‐available manure P exceeded crop P removal by 54% over the entire area. Cape Fear showed the greatest P excess, 76% greater than crop removal. This study contributes to nutrient cycling improvements by connecting crop–animal nutrient budgets to hydrologic resources. Furthermore, we show the value of finer spatial scales to identify hotspots that play a significant role in nutrient losses. We conclude that nutrient‐surplus basins require, in addition to manure nutrient conservation, a basin‐wide redistribution and export strategies to address nutrient excesses and water quality impacts.
Bioengineered small extracellular vesicles deliver multiple SARS‐CoV‐2 antigenic fragments and drive a broad immunological response
Authors: Jackson Hannah K. , Long Heather M. , Yam‐Puc Juan Carlos , Palmulli Roberta , Haigh Tracey A. , Gerber Pehuén Pereyra , Lee Jin S. , Matheson Nicholas J. , Young Lesley , Trowsdale John , Lo Mathew , Taylor Graham S. , Thaventhiran James E. , Edgar James R. 
Published: February 2024

AbstractThe COVID‐19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. The scientific community responded by developing several efficacious vaccines which were expedited by the global need for vaccines. The emergence of SARS‐CoV‐2 breakthrough infections highlights the need for additional vaccine modalities to provide stronger, long‐lived protective immunity. Here we report the design and preclinical testing of small extracellular vesicles (sEVs) as a multi‐subunit vaccine. Cell lines were engineered to produce sEVs containing either the SARS‐CoV‐2 Spike receptor‐binding domain, or an antigenic region from SARS‐CoV‐2 Nucleocapsid, or both in combination, and we tested their ability to evoke immune responses in vitro and in vivo. B cells incubated with bioengineered sEVs were potent activators of antigen‐specific T cell clones. Mice immunised with sEVs containing both sRBD and Nucleocapsid antigens generated sRBD‐specific IgGs, nucleocapsid‐specific IgGs, which neutralised SARS‐CoV‐2 infection. sEV‐based vaccines allow multiple antigens to be delivered simultaneously resulting in potent, broad immunity, and provide a quick, cheap, and reliable method to test vaccine candidates.
Clinical and prognostic significance analysis of glycolysis‐related genes in HNSCC
Authors: Yuan Qiuyun , Mao Mengqian , Xia Xiaoqiang , Yang Wanchun 
Published: February 2024

AbstractBackgroundHead and neck squamous cell carcinoma (HNSCC) represents one of the most malignant cancers worldwide, with poor survival. Experimental evidence implies that glycolysis/hypoxia is associated with HNSCC. In this study, we aimed to construct a novel glycolysis‐/hypoxia‐related gene (GHRG) signature for survival prediction of HNSCC.MethodsA multistage screening strategy was used to establish the GHRG prognostic model by univariate/least absolute shrinkage and selection operator (LASSO)/step multivariate Cox regressions from The Cancer Genome Atlas cohort. A nomogram was constructed to quantify the survival probability. Correlations between risk score and immune infiltration and chemotherapy sensitivity were explored.ResultsWe established a 12‐GHRG mRNA signature to predict the prognosis in HNSCC patients. Patients in the high‐risk score group had a much worse prognosis. The predictive power of the model was validated by external HNSCC cohorts, and the model was identified as an independent factor for survival prediction. Immune infiltration analysis showed that the high‐risk score group had an immunosuppressive microenvironment. Finally, the model was effective in predicting chemotherapeutic sensitivity.ConclusionsOur study demonstrated that the GHRG model is a robust prognostic tool for survival prediction of HNSCC. Findings of this work provide novel insights for immune infiltration and chemotherapy of HNSCC, and may be applied clinically to guide therapeutic strategies.
Impact of mental health boarding on clinicians at a children's hospital: A qualitative analysis
Authors: Worsley Diana , Bowden Cadence , Keating Cameron , Cassidy Kyla , Doupnik Stephanie K. 
Published: February 2024

AbstractBackgroundThe child and adolescent mental health boarding crisis (i.e., prolonged stays in acute care hospitals for patients awaiting mental health treatment) continues to challenge acute care hospital staff and resources. We sought to understand clinician's experiences while caring for patients experiencing mental health boarding.MethodsWe conducted semistructured qualitative interviews with clinicians who care for patients experiencing mental health boarding in an acute care freestanding children's hospital with no inpatient psychiatric unit. We used an inductive approach to determine interview themes and major findings.ResultsThe study included 48 clinician participants from diverse specialties, including 13 social workers, 11 nurses, five psychiatric technicians, six pediatric residents, four attending pediatric hospitalists, four attending psychiatrists, one psychologist, and four other mental health specialists. We identified emergent themes in five domains: (1) frustrations with the mental healthcare system, (2) lack of training in mental healthcare skills, (3) feelings of helplessness, (4) ineffectiveness of medical model of care during mental health boarding, and (5) resilience and support factors.ConclusionsCaring for patients with mental health boarding has negative effects on clinicians, and health system efforts to prevent boarding could improve workforce retention and reduce burnout.
Functional MRI of the Brainstem for Assessing Its Autonomic Functions: From Imaging Parameters and Analysis to Functional Atlas
Authors: Mohamed Abdalla Z. , Kwiatek Richard , Del Fante Peter , Calhoun Vince D. , Lagopoulos Jim , Shan Zack Y. 
Published: February 2024

BackgroundThe brainstem is a crucial component of the central autonomic nervous (CAN) system. Functional MRI (fMRI) of the brainstem remains challenging due to a range of factors, including diverse imaging protocols, analysis, and interpretation.PurposeTo develop an fMRI protocol for establishing a functional atlas in the brainstem.Study TypeProspective cross‐sectional study.SubjectsTen healthy subjects (four males, six females).Field Strength/SequenceUsing a 3.0 Tesla MR scanner, we acquired T1‐weighted images and three different fMRI scans using fMRI protocols of the optimized functional Imaging of Brainstem (FIBS), the Human Connectome Project (HCP), and the Adolescent Brain Cognitive Development (ABCD) project.AssessmentThe temporal signal‐to‐noise‐ratio (TSNR) of fMRI data was compared between the FIBS, HCP, and ABCD protocols. Additionally, the main normalization algorithms (i.e., FSL‐FNIRT, SPM‐DARTEL, and ANTS‐SyN) were compared to identify the best approach to normalize brainstem data using root‐mean‐square (RMS) error computed based on manually defined reference points. Finally, a functional autonomic brainstem atlas that maps brainstem regions involved in the CAN system was defined using meta‐analysis and data‐driven approaches.Statistical TestsANOVA was used to compare the performance of different imaging and preprocessing pipelines with multiple comparison corrections (P ≤ 0.05). Dice coefficient estimated ROI overlap, with 50% overlap between ROIs identified in each approach considered significant.ResultsThe optimized FIBS protocol showed significantly higher brainstem TSNR than the HCP and ABCD protocols (P ≤ 0.05). Furthermore, FSL‐FNIRT RMS error (2.1 ± 1.22 mm; P ≤ 0.001) exceeded SPM (1.5 ± 0.75 mm; P ≤ 0.01) and ANTs (1.1 ± 0.54 mm). Finally, a set of 12 final brainstem ROIs with dice coefficient ≥0.50, as a step toward the development of a functional brainstem atlas.Data ConclusionThe FIBS protocol yielded more robust brainstem CAN results and outperformed both the HCP and ABCD protocols.Evidence Level2Technical EfficacyStage 1
First report of ATP2A2 somatic mosaicism occurring during embryogenesis in transient acantholytic dermatosis
Authors: Hiromatsu Emi , Abe Toshifumi , Teye Kwesi , Koga Hiroshi , Ishii Norito , Hamada Takahiro , Nakama Takekuni 
Published: February 2024

AbstractTransient acantholytic dermatosis (TAD) is a relatively common skin disease that typically affects older individuals, which shows clinical and histologic similarities to autosomal dominant Darier disease. TAD was recently shown to be caused by somatic ATP2A2 damaging variants. In this study, we performed Sanger sequencing and droplet digital PCR (ddPCR) in a Japanese elderly male with TAD to identify ATP2A2 somatic mosaicism occurring during embryogenesis for the first time and mutant allelic fraction (MAF). Sanger sequencing revealed a known heterozygous substitution c.1645C>T, p.Arg549* in ATP2A2 from blood and the affected skin containing the epidermis and dermis, whereas the signals of the mutated allele were weaker, suggesting that discrepancy of signal intensities demonstrates the presence of somatic mosaicism. By ddPCR, the normal and mutant allele were identified in genomic DNAs and the MAFs were 20.1% (affected skin) and 14.7% (blood), respectively. In the present case, somatic mosaicisms observed in ectodermal (epidermis) and mesodermal (dermis and blood) origin DNA can be explained by a mutational event during the early‐stage differentiation of embryonic epiblast in embryogenesis, and mutant embryonic cells somewhat preferentially differentiate to form the epidermis, rather than the dermis and blood. Disrupted intracellular Ca2+ homoeostasis through clinical deterioration together with ATP2A2 somatic mosaicism in this patient might result in transient skin eruptions.
Hyperbranched Polymer Induced Antibacterial Tree‐Like Nanofibrous Membrane for High Effective Air Filtration
Authors: Zhao Weitao , Wang Mengxuan , Yao Ying , Cheng Zhongqiu , Shen Yaxinru , Zhang Yufan , Tao Jin , Xiong Jiaqing , Cao Hongmei , Zhang Desuo 
Published: February 2024

AbstractThe air filtration materials with high efficiency, low resistance, and extra antibacterial property are crucial for personal health protection. Herein, a tree‐like polyvinylidene fluoride (PVDF) nanofibrous membrane with hierarchical structure (trunk fiber of 447 nm, branched fiber of 24.7 nm) and high filtration capacity is demonstrated. Specifically, 2‐hydroxypropyl trimethyl ammonium chloride terminated hyperbranched polymer (HBP‐HTC) with near‐spherical three‐dimensional molecular structure and adjustable terminal positive groups is synthesized as an additive for PVDF electrospinning to enhance the jet splitting and promote the formation of branched ultrafine nanofibers, achieving a coverage rate of branched nanofibers over 90% that is superior than small molecular quaternary ammonium salts. The branched nanofibers network enhances mechanical properties and filtration efficiency (99.995% for 0.26 µm sodium chloride particles) of the PVDF/HBP‐HTC membrane, which demonstrates reduced pressure drop (122.4 Pa) and a quality factor up to 0.083 Pa−1 on a 40 µm‐thick sample. More importantly, the numerous quaternary ammonium salt groups of HBP‐HTC deliver excellent antibacterial properties to the PVDF membranes. Bacterial inhibitive rate of 99.9% against both S. aureus and E. coli is demonstrated in a membrane with 3.0 wt% HBP‐HTC. This work provides a new strategy for development of high‐efficiency and antibacterial protection products.
Associations of genetic variants within TYK2 with pulmonary tuberculosis among Chinese population
Authors: Zhang Mingwu , Liu Zhengwei , Zhu Yelei , Wu Kunyang , Zhou Lin , Peng Ying , Pan Junhang , Chen Bin , Wang Xiaomeng , Chen Songhua 
Published: February 2024

AbstractBackgroundPulmonary tuberculosis (PTB) is a common infectious disease caused by mycobacterium tuberculosis (MTB) and the present study aims to explore the associations of genetic variants within tyrosine kinases 2 (TYK2) with PTB incidence.MethodsA population‐based case control study including 168 smear‐positive PTB cases and 251 controls was conducted. Five single nucleotide polymorphisms (SNPs) including rs280520, rs91755, rs2304256, rs12720270, rs280519 located within TYK2 gene were selected and MassARRAY® MALDI‐TOF system was employed for genotyping. SPSS 19.0 was adopted for statistical analysis, non‐conditional logistic regression was conducted. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed to estimate their contributions to PTB incidence.ResultsIn the overall study population, rs91755 TT and rs280519 AA genotypes were found to be associated with reduced PTB risk (OR = 0.34, 95% CI: 0.16–0.72; OR = 0.38, 95% CI: 0.18–0.79, respectively). After stratification for sex, we found that among the male population, rs91755TG/TT, rs12720270AG/GG and rs280519AG/AA genotypes were associated with reduced PTB risk (OR = 0.41, 95% CI: 0.21–0.80; OR = 0.44, 95% CI: 0.21–0.94; OR = 0.42, 95% CI: 0.21–0.82, respectively). After stratification for age, we found that among those aged <60 years, rs91755TT and rs280519AA genotype were associated with reduced PTB risk (OR = 0.29, 95% CI: 0.09–0.90; OR = 0.34, 95% CI: 0.11–1.08, respectively); while rs2304256AC/AA genotype was associated with increased PTB risk (OR = 2.68, 95% CI: 1.05–6.85). Haplotype analysis revealed that AGAAG and ATCGA (Combined with rs280520, rs91755, rs2304256, rs12720270 and rs280519) were associated with increased (OR = 1.54, 95% CI: 1.01–2.37) and decreased PTB risk (OR = 0.70, 95% CI: 0.52–0.94), respectively.ConclusionsThe genetic variants located within TYK2 including rs91755, rs12720270 and rs280519 were found to be associated with modified PTB risk and the SNPs had potential to be the biomarkers to predict PTB incidence risk.
Real‐world data of Brazilian adults with X‐linked hypophosphatemia (XLH) treated with burosumab and comparison with other worldwide cohorts
Authors: Vaisbich Maria Helena , de Cillo Antônio César Paulillo , Silva Bárbara Campolina C. , DÁlva Catarina Brasil , de Carvalho Érico Higino , de Almeida Juliana M. C. M. , Marques Larissa L. M. , Ribeiro Marcia , da Silva Mauro Borghi M. , de Medeiros Paula Frassinetti V. , Mendes Pedro Henrique 
Published: February 2024

AbstractBackgroundDisease‐related variants in PHEX cause XLH by an increase of fibroblast growth factor 23 (FGF23) circulating levels, resulting in hypophosphatemia and 1,25(OH)2 vitamin D deficiency. XLH manifests in early life with rickets and persists in adulthood with osseous and extraosseous manifestations. Conventional therapy (oral phosphate and calcitriol) improves some symptoms, but evidence show that it is not completely effective, and it can lead to nephrocalcinosis (NC) and hyperparathyroidism (HPT). Burosumab (anti‐FGF23 antibody) has shown to be effective and safety in the clinical trials.MethodsThe current real‐world collaborative study evaluated genetic, clinical and laboratory data of XLH Brazilian adult patients treated with burosumab.ResultsNineteen unrelated patients were studied. Patients reported pain, limb deformities and claudication, before burosumab initiation. 78% of them were previously treated with conventional therapy. The severity of the disease was moderate to severe (15 patients with score >5). At the baseline, 3 patients presented NC (16.7%) and 12 HPT (63%). After 16 ± 8.4 months under burosumab, we observed a significant: increase in stature (p = 0.02), in serum phosphate from 1.90 ± 0.43 to 2.67 ± 0.52 mg/dL (p = 0.02); in TmP/GFR from 1.30 ± 0.46 to 2.27 ± 0.64 mg/dL (p = 0.0001), in 1,25 (OH)2 D from 50.5 ± 23.3 to 71.1 ± 19.1 pg/mL (p = 0.03), and a decrease in iPTH from 86.8 ± 37.4 pg/mL to 66.5 ± 31.1 (p = 0.002). Nineteen variants were found (10 novel). HPT tended to develop in patients with truncated PHEX variants (p = 0.06).ConclusionsThis study confirms the efficacy and safety of burosumab on XLH adult patients observed in clinical trials. Additionally, we observed a decrease in iPTH levels in patients with moderate to severe HPT at the baseline.
Hemizygous splicing variant in CNKSR2 results in X‐linked intellectual developmental disorder
Authors: Lou Yuting , Shi Xinglei , Su Guofa , Guo Yufan , Gao Liuyan , Wang Ye , Miao Pu , Feng Jianhua 
Published: February 2024

AbstractBackgroundIntellectual disability (ID) refers to a childhood‐onset neurodevelopmental disorder with a prevalence of approximately 1%–3%.MethodsWe performed whole exome sequencing for the patient with ID. And the splicing variant we found was validated by minigene assay.ResultsHere, we report a boy with ID caused by a variant of CNKSR2. His neurological examination revealed hypsarrhythmia via electroencephalography and a right temporal polar arachnoid cyst via brain magnetic resonance imaging. A novel splicing variant in the CNKSR2 gene (NM_014927.5, c.1657+1G>A) was discovered by exome sequencing. The variant caused a 166 bp intron retention between exons 14 and 15, which was validated by a minigene assay. The variant was not reported in public databases such as gnomAD and the Exome Aggregation Consortium.ConclusionsThe variant was predicted to be damaging to correct the translation of the CNKRS2 protein and was classified as likely pathogenic according to the ACMG guidelines.
Initial investigations into the production of triploid sunshine bass using temperature shock
Authors: Straus David L. , Abernathy Jason W. , Kelly Anita M. , Quintero Herbert E. , Freeze T. Mike , Williams Ric S. 
Published: February 2024

Abstract

Objective
The sunshine bass (female White Bass Morone chrysops × male Striped Bass M. saxatilis) is an important food fish raised in U.S. aquaculture. Spawning is performed by manually stripping and fertilizing White Bass eggs with Striped Bass sperm. Embryos hatch in approximately 48 h. Mature sunshine bass females can become fertile and produce viable eggs, which is problematic in commercial food-fish production; therefore, triploid fish are desired.

Methods
The present nonreplicated study incorporated three warm and three cold temperature shocks, along with three postfertilization initiation times and three exposure times for each temperature, during initial stages of incubation to induce triploidy. After exposure to temperature shocks, fertilized eggs were incubated in experimental hatching systems. The best performing cold and warm temperatures and times (and an ambient diploid control) were then used to incubate fertilized eggs in a commercial-scale trial using standard industry practices with a single batch of eggs. Larvae were stocked at about 185,000 larvae/ha (75,000 larvae/acre) in newly filled and fertilized ponds. Fry were sampled weekly and harvested at 30 days.

Result
There were 15 survivors from the pond containing fish derived from cold-shocked fertilized eggs; these individuals were tested via Coulter Counter, and no triploids were detected. Testing of 50 survivors from the pond containing fish derived from warm-shocked fertilized eggs indicated that 14% were triploid.

Conclusion
Therefore, initial trials indicate that warm temperature shock is preferable to cold shock for inducing a greater percentage of triploid sunshine bass.
Exploring the reinforcement and conductivity mechanism of K2FeO4‐modified multiwalled carbon nanotubes in carbon black/natural rubber composites
Authors: Xue Junxiu , Hao Yingjie , Qu Shengqi , Wang Chuansheng , Li Li 
Published: February 2024

AbstractThis study employs potassium ferrate (K2FeO4) for the oxidation treatment of multi‐walled carbon nanotubes (MWNTs) under neutral and acidic conditions. A wet flash evaporation process is utilized to prepare natural rubber/MWNTs/carbon black composites, enhancing the performance of rubber composites. The increased oxidation level of MWNTs enhances their hydrophilicity, increases the quantity of oxygen‐containing hydroxyl groups on the surface, promotes dispersion within the natural rubber matrix, and ultimately improves the performance of the rubber products. The effective dispersion of MWNTs reduces electron transport resistance, forming a favorable electron transport channel in natural rubber. Experimental results indicate that K2FeO4 achieves the highest oxidation degree and optimal performance in an acidic environment. Compared to untreated MWNTs rubber composites, the oxidized MWNTs rubber composites exhibit a 34.9% reduction in the Payne effect, a 15.7% decrease in wear, a 12.7% reduction in rolling resistance, and a two‐order‐of‐magnitude increase in conductivity. This study provides a novel approach for preparing water‐dispersible MWNTs and high‐performance rubber composites, holding potential applications in premium rubber products and conductive rubber fields.Highlights
The wet flash refining process improved the dispersion of MWNTs.
K2FeO4 oxidation of MWNTs was enhanced under acidic conditions.
Oxidized MWNTs combined with CB to form a CB‐MWNTs‐CB filler network.
Oxidized MWNTs and CB increased the “ball‐chain” arrangement in NR.