bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational analysis of affinity dynamics between the variants of SARS-CoV-2 spike protein (RBD) and human ACE-2 receptor
Authors: Sultana Nishad , Nagesha S. N. , Reddy C. N. Lakshminarayana , Ramesh B. N. , Shyamalamma S. , Shashidhara K. S. , Satish K. M. , Pradeep C. , Vidyadhar G. D 
Published: April 2024

AbstractThe novel coronavirus SARS-CoV-2 resulted in a significant worldwide health emergency known as the COVID-19 pandemic. This crisis has been marked by the widespread of various variants, with certain ones causing notable apprehension. In this study, we harnessed computational techniques to scrutinize these Variants of Concern (VOCs), including various Omicron subvariants. Our approach involved the use of protein structure prediction algorithms and molecular docking techniques, we have investigated the effects of mutations within the Receptor Binding Domain (RBD) of SARS-CoV-2 and how these mutations influence its interactions with the human angiotensin-converting enzyme 2 (hACE-2) receptor. Further we have predicted the structural alterations in the RBD of naturally occurring SARS-CoV-2 variants using the tr-Rosetta algorithm. Subsequent docking and binding analysis employing HADDOCK and PRODIGY illuminated crucial interactions occurring at the Receptor-Binding Motif (RBM). Our findings revealed a hierarchy of increased binding affinity between the human ACE2 receptor and the various RBDs, in the order of wild type (Wuhan-strain) < Beta < Alpha < Gamma < Omicron-B.1.1.529 < Delta < Omicron-BA.2.12.1 < Omicron-BA.5.2.1 < Omicron-BA.1.1. Notably, Omicron-BA.1.1 demonstrated the highest binding affinity of -17.4 kcal mol−1 to the hACE2 receptor when compared to all the mutant complexes. Additionally, our examination indicated that mutations occurring in active residues of the Receptor Binding Domain (RBD) consistently improved the binding affinity and intermolecular interactions in all mutant complexes. Analysis of the differences among variants has laid a foundation for the structure-based drug design targeting the RBD region of SARS-CoV-2.
Brief interventions 2.0: a new agenda for alcohol policy, practice and research
Authors: Stewart Duncan , Madden Mary , McCambridge Jim 
Published: April 2024

Abstract
Background
Alcohol problems are increasing across the world and becoming more complex. Limitations to international evidence and practice mean that the screening and brief intervention paradigm forged in the 1980s is no longer fit for the purpose of informing how conversations about alcohol should take place in healthcare and other services. A new paradigm for brief interventions has been called for.

Brief interventions 2.0
We must start with a re-appraisal of the roles of alcohol in society now and the damage it does to individual and population health. Industry marketing and older unresolved ideas about alcohol continue to impede honest and thoughtful conversations and perpetuate stigma, stereotypes, and outright fictions. This makes it harder to think about and talk about how alcohol affects health, well-being, and other aspects of life, and how we as a society should respond. To progress, brief interventions should not be restricted only to the self-regulation of one’s own drinking. Content can be orientated to the properties of the drug itself and the overlooked problems it causes, the policy issues and the politics of a powerful globalised industry. This entails challenging and reframing stigmatising notions of alcohol problems, and incorporating wider alcohol policy measures and issues that are relevant to how people think about their own and others' drinking. We draw on recent empirical work to examine the implications of this agenda for practitioners and for changing the public conversation on alcohol.

Conclusion
Against a backdrop of continued financial pressures on health service delivery, this analysis provokes debate and invites new thinking on alcohol. We suggest that the case for advancing brief interventions version 2.0 is both compelling and urgent.
Clinical values of different specimen preparation methods for the diagnosis of lung cancer by EBUS-TBNA
Authors: Wang Hansheng , Wang Jiankun , Liu Yan , Wang Yunyun , Zhou Yanhui , Yu Dan , You Hui , Ren Tao , Tang Yijun , Wang Meifang 
Published: April 2024

Abstract
Background and objective
EBUS-TBNA has emerged as an important minimally invasive procedure for the diagnosis and staging of lung cancer. Our objective was to evaluate the effect of different specimen preparation from aspirates on the diagnosis of lung cancer.

Methods
181 consecutive patients with known or suspected lung cancer accompanied by hilar / mediastinal lymphadenopathy underwent EBUS-TBNA from January 2019 to December 2022. Specimens obtained by EBUS-TBNA were processed by three methods: Traditional smear cytology of aspirates (TSC), liquid-based cytology of aspirates (LBC) and histopathology of core biopsies.

Results
EBUS-TBNA was performed in 181 patients on 213 lymph nodes, the total positive rate of the combination of three specimen preparation methods was 80.7%. The diagnostic positive rate of histopathology was 72.3%, TSC was 68.1%, and LBC was 65.3%, no significant differences was observed (p = 0.29); however, statistically significant difference was noted between the combination of three preparation methods and any single specimen preparation methods (p = 0.002). The diagnostic sensitivity of histopathology combined with TSC and histopathology combined with LBC were 96.5 and 94.8%, the specificity was 95.0% and 97.5%, the PPV was 98.8% and 99.4%, the NPV was 86.4% and 81.2%, the diagnostic accuracy was 96.2% and 95.3%, respectively; The sensitivity and accuracy of above methods were higher than that of single specimen preparation, but lower than that of combination of three preparation methods.

Conclusion
When EBUS-TBNA is used for the diagnosis and staging of lung cancer, histopathology combined with TSC can achieve enough diagnostic efficiency and better cost-effectiveness.
Stepwise transvenous lead extraction due to pacemaker pocket infection following lactational mastitis complicated with breast abscess
Authors: Poposka Lidija , Risteski Dejan , Cvetkovski Dimitar , Pocesta Bekim , Janusevski Filip , Zimbakov Zhan , Trajkov Ivan , Stefanovski Dime , Logar Mateja , Ksela Jus 
Published: April 2024

Abstract
Background
Lactational mastitis is a common painful and debilitating inflammation of breast tissue, generally treated conservatively or with pus puncture in case of breast abscess. However, treating mastitis in patients with implantable surgical material located in the affected breast region can be extremely challenging. We present an unusual case of lactational mastitis complicated by pacemaker pocket infection in a breastfeeding mother.

Case presentation
A 35-year-old pacemaker-dependent female developed lactational mastitis seven weeks postpartum. Initially, the condition was treated conservatively with analgesics and antibiotics. After abscess formation, pus was aspirated using fine-needle aspiration technique. Four weeks after mastitis resolution, pacemaker pocket infection developed. According to current cardiovascular implantable electronic device infection treatment guidelines a complete surgical extraction of the entire electronic system, followed by targeted antibiotic treatment and reimplantation of a new device after infection resolution, was recommended. However, after thorough discussion with the young woman and her family and after detailed review of surgery-related risks, she declined a potentially high-risk surgical procedure. Thus, only the pulse generator was explanted; pacing leads positioned in the sub-pectoral pocket; new pacemaker implanted on the contralateral side and broad-spectrum antibiotic therapy continued for six weeks. After breastfeeding cessation, and with chronic fistula development at the primary pacemaker implantation site, the possibility of delayed surgical intervention including complete extraction of retained pacemaker leads was again thoroughly discussed with her. After thoughtful consideration the woman consented to the proposed treatment strategy. A surgical procedure including transvenous lead extraction through the primary implantation venous entry site, using hand-powered bidirectional rotational sheaths, was successfully performed, removing all retained leads through the left subclavian venous entry site, and leaving the fully functional and clinically uninfected pacemaker on the contralateral site intact.

Conclusion
Although patients’ decisions for delayed extraction in a case of cardiovascular implantable electronic device infection should be discouraged by attending physicians and members of interdisciplinary teams, our case shows that a stepwise treatment strategy may be successful as a bailout clinical scenario in patients with specific requests, demands and / or clinical needs.
Elevated serum B-cell activator factor levels predict rapid progressive interstitial lung disease in anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis
Authors: Shi Yumeng , You Hanxiao , Liu Chang , Qiu Yulu , Lv Chengyin , Zhu Yujing , Xu Lingxiao , Wang Fang , Zhang Miaojia , Tan Wenfeng 
Published: April 2024

Abstract
Background
Rapid progressive interstitial lung disease (RP-ILD) is the leading cause of anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) related death. Elevated serum B-cell activating factor (BAFF) levels have been implicated in connective tissue diseases associated ILD. Here, we evaluate whether BAFF could be a prognostic biomarker for predicting RP-ILD in anti-MDA5+DM patients.

Methods
Serums were collected from 39 patients with anti-MDA5+DM (20 with RP-ILD and 19 with non-RP-ILD), 20 antisynthase syndrome (ASS) patients and 20 healthy controls (HC). BAFF concentration was measured by an enzyme-linked immunosorbent assay.

Results
Serum BAFF level was higher in anti-MDA5+DM patients than those in ASS patients and HC (3882.32 ± 1880.09 vs. 2540.89 ± 1403.04 and 2486.28 ± 767.97 pg/mL, p = 0.0056 and 0.0038, respectively). Within anti-MDA5+DM groups, RP-ILD patients exhibited higher BAFF concentration than non-RP-ILD group (4549.78 ± 1839.97 vs. 3297.28 ± 1794.69 pg/mL, p = 0.04). The BAFF concentration was positively correlated with levels of C-reactive protein (CRP), dehydrogenase (LDH) and cytokeratin (CK) in anti-MDA5+DM patients (r = 0.350, p = 0.035; r = 0.393, p = 0.016; r = 0.518, p = 0.001; respectively). The best cut-off value of BAFF concentration was 2971.5 pg/mL by ROC curve (AUC area = 0.690, p = 0.045) and BAFF > 2971.5 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR = 9.389, 95% CI = 1.609—54.769; p = 0.013).

Conclusions
Serum BAFF could be a useful prognostic biomarker for early detecting RP-ILD risk in anti-MDA5+DM patients.
NR1H4 disease: rapidly progressing neonatal intrahepatic cholestasis and early death
Authors: Li Zhong-Die , Li Yu-Chuan , Jing-Zhao  , Wang Jian-She , Xie Xin-Bao 
Published: April 2024

Abstract
Background
Clinical studies on progressive familial intrahepatic cholestasis (PFIC) type 5 caused by mutations in NR1H4 are limited.

Methods
New patients with biallelic NR1H4 variants from our center and all patients from literature were retrospectively analyzed.

Results
Three new patients were identified to be carrying five new variants. Liver phenotypes of our patients manifests as low-γ-glutamyl transferase cholestasis, liver failure and related complications. One patient underwent liver transplantation (LT) and survived, and two other patients died without LT. Nine other patients were collected through literature review. Twelve out of 13 patients showed neonatal jaundice, with the median age of onset being 7 days after birth. Reported clinical manifestations included cholestasis (13/13, 100%), elevated AFP (11/11, 100%), coagulopathy (11/11, 100%), hypoglycemia (9/13, 69%), failure to thrive (8/13, 62%), splenomegaly (7/13, 54%), hyperammonemia (7/13, 54%), and hepatomegaly (6/13, 46%). Six of 13 patients received LT at a median age of 6.2 months, and only one patient died of acute infection at one year after LT. Other 7 patients had no LT and died with a median age of 5 months (range 1.2-8). There were 8 patients with homozygous genotype and 5 patients with compound heterozygous genotype. In total, 13 different variants were detected, and 5 out of 12 single or multiple nucleotides variants were located in exon 5.

Conclusions
We identified three newly-diagnosed patients and five novel mutations. NR1H4-related PFIC typically cause progressive disease and early death. LT may be the only lifesaving therapy leading to cure.
Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration
Authors: Yehia Asmaa , Abulseoud Osama A. 
Published: April 2024

AbstractThe unprecedented pandemic of COVID-19 swept millions of lives in a short period, yet its menace continues among its survivors in the form of post-COVID syndrome. An exponentially growing number of COVID-19 survivors suffer from cognitive impairment, with compelling evidence of a trajectory of accelerated aging and neurodegeneration. The novel and enigmatic nature of this yet-to-unfold pathology demands extensive research seeking answers for both the molecular underpinnings and potential therapeutic targets. Ferroptosis, an iron-dependent cell death, is a strongly proposed underlying mechanism in post-COVID-19 aging and neurodegeneration discourse. COVID-19 incites neuroinflammation, iron dysregulation, reactive oxygen species (ROS) accumulation, antioxidant system repression, renin-angiotensin system (RAS) disruption, and clock gene alteration. These events pave the way for ferroptosis, which shows its signature in COVID-19, premature aging, and neurodegenerative disorders. In the search for a treatment, melatonin shines as a promising ferroptosis inhibitor with its repeatedly reported safety and tolerability. According to various studies, melatonin has proven efficacy in attenuating the severity of certain COVID-19 manifestations, validating its reputation as an anti-viral compound. Melatonin has well-documented anti-aging properties and combating neurodegenerative-related pathologies. Melatonin can block the leading events of ferroptosis since it is an efficient anti-inflammatory, iron chelator, antioxidant, angiotensin II antagonist, and clock gene regulator. Therefore, we propose ferroptosis as the culprit behind the post-COVID-19 trajectory of aging and neurodegeneration and melatonin, a well-fitting ferroptosis inhibitor, as a potential treatment.
Unveiling the gastric microbiota: implications for gastric carcinogenesis, immune responses, and clinical prospects
Authors: Liu Zhiyi , Zhang Dachuan , Chen Siyu 
Published: April 2024

AbstractHigh-throughput sequencing has ushered in a paradigm shift in gastric microbiota, breaking the stereotype that the stomach is hostile to microorganisms beyond H. pylori. Recent attention directed toward the composition and functionality of this 'community' has shed light on its potential relevance in cancer. The microbial composition in the stomach of health displays host specificity which changes throughout a person's lifespan and is subject to both external and internal factors. Distinctive alterations in gastric microbiome signature are discernible at different stages of gastric precancerous lesions and malignancy. The robust microbes that dominate in gastric malignant tissue are intricately implicated in gastric cancer susceptibility, carcinogenesis, and the modulation of immunosurveillance and immune escape. These revelations offer fresh avenues for utilizing gastric microbiota as predictive biomarkers in clinical settings. Furthermore, inter-individual microbiota variations partially account for differential responses to cancer immunotherapy. In this review, we summarize current literature on the influence of the gastric microbiota on gastric carcinogenesis, anti-tumor immunity and immunotherapy, providing insights into potential clinical applications.
Tri-ponderal mass index and left ventricular hypertrophy in a cohort of caucasian children and adolescents with obesity
Authors: Vizzuso Sara , Torto Alberico Del , Fiore Giulia , Carugo Stefano , Zuccotti Gianvincenzo , Verduci Elvira 
Published: April 2024

Abstract
Background
Pediatric obesity is a global emerging burden for society; among its health-related consequences there are hypertension (HTN) and left ventricular hypertrophy (LVH). Several anthropometric indices have been investigated for the early identification of cardiovascular risk in children. The aim of the present study was to assess whether tri-ponderal mass index (TMI) was associated with LVH in a cohort of Caucasian children and adolescents with obesity.

Methods
In this observational study, 63 children and adolescents with obesity aged 7-to-16 years were enrolled. During outpatient visits, adiposity, and cardio-metabolic indices (BMI z-score, WHR, TMI, ABSI) were collected. All subjects underwent a 24-hour ambulatory blood pressure monitoring (ABPM) and transthoracic echocardiography.

Results
Children and adolescents with obesity with LVH had significantly higher BMI z-score (p = 0.009), WHR (p = 0.006) and TMI (p = 0.026) compared to children without LVH. WC and WHR were the only indices significantly associated with left ventricular mass index (LVMI).

Conclusion
Left ventricular remodeling is associated with the cardio-metabolic risk markers WC and WHR, but not with the adiposity index TMI among children with obesity.
A simulation training of family management for parents of children with epilepsy: a randomized clinical trial
Authors: Liu Hua-yan , Zeng Shan , Chen Yue-wei , Yi Min , Tan Xiao-yan , Xie Jian-hui , Wu Xia , Zhu Li-hui 
Published: April 2024

Abstract
Background
Epilepsy is a chronic neurological disorder that is more likely to be diagnosed in children. The main treatment involves long-term use of anti-epileptic drugs and above all, home care is of great importance. As there has not been a widely accepted home care protocols, simulating a home care environment is necessary for caregivers to develop skills of proper home care. This study aims to evaluate the effectiveness of a simulation training of family management style (STOFMS) for parents of children with epilepsy in China.

Methods
A randomized controlled trial was conducted on 463 children with epilepsy and their families. They were recruited from March 2020 to November 2022 and randomly assigned to the STOFMS group or the conventional group in a 1:1 ratio. Scores of family management measures, 8-item of Morisky Medication Adherence and epilepsy clinical symptom of both groups were collected at three points of time: within 24 h after admission (T0), 3 months after discharge (T1), and 6 months after discharge (T2). Changes due to intervention were compared across groups by repeated-measures ANOVA. The study report followed the CONSORT 2010 checklist.

Results
There were statistically significant differences between the two groups at T2. A considerable increase over the baseline was observed in the total management level score and subscale scores in the STOFMS group at T1, compared with essentially no change in the control group. In terms of medication adherence, the STOFMS group performance improved greatly at T1 and T2 compared with the control group. The same result was also found in clinical efficacy at T2 (p < 0.05).

Conclusion
STOFMS is an effective intervention to improve family management level, treatment adherence and clinical efficacy for children with epilepsy.

Trial registration
The registration number is ChiCTR2200065128. Registered at 18 October 2022, http://www.medresman.org.cn
Severe cellulitis from methicillin-resistant Staphylococcus aureus (MRSA) in a couple of preterm twins: a case report
Authors: Zampatti Noemi , Bonato Irene , Calandrino Andrea , Saffioti Carolina , Parodi Alessandro , Brigati Giorgia , Minghetti Diego , Ramenghi Luca Antonio 
Published: April 2024

Abstract
Background
Preterms are at risk of systemic infections as the barrier function of their immature skin is insufficient. The long period of hospitalization and the huge number of invasive procedures represent a risk factor for complications. Among the nosocomial infections of the skin, methicillin-resistant Staphylococcus aureus (MRSA) is associated with significant morbidity and mortality.
We report a clinical case of cellulitis and abscess in two preterm twins caused by MRSA in a tertiary level Neonatal Intensive Care Unit (NICU).

Case presentation
Two preterm female babies developed cellulitis from MRSA within the first month of extrauterine life. The first one (BW 990 g) showed signs of clinical instability 4 days before the detection of a hyperaemic and painful mass on the thorax. The second one (BW 1240 g) showed signs of clinical instability contextually to the detection of an erythematous, oedematous and painful area in the right submandibular space. In both cases the diagnosis of cellulitis was confirmed by ultrasound. A broad spectrum, multidrug antimicrobial therapy was administered till complete resolution.

Conclusions
Due to the characteristic antibiotic resistance of MRSA and the potential complications of those infections in such delicate patients, basic prevention measures still represent the key to avoid the spreading of neonatal MRSA infections in NICUs, which include hand hygiene and strict precautions, as well as screening of patients for MRSA on admission and during hospital stay, routine prophylactic topical antibiotic of patients, enhanced environmental cleaning, cohorting and isolation of positive patients, barrier precautions, avoidance of ward crowding, and, in some units, surveillance, education and decolonization of healthcare workers and visiting parents.
Measuring, visualizing, and diagnosing reference bias with biastools
Authors: Lin Mao-Jan , Iyer Sheila , Chen Nae-Chyun , Langmead Ben 
Published: April 2024

AbstractMany bioinformatics methods seek to reduce reference bias, but no methods exist to comprehensively measure it. analyzes and categorizes instances of reference bias. It works in various scenarios: when the donor’s variants are known and reads are simulated; when donor variants are known and reads are real; and when variants are unknown and reads are real. Using , we observe that more inclusive graph genomes result in fewer biased sites. We find that end-to-end alignment reduces bias at indels relative to local aligners. Finally, we use to characterize how T2T references improve large-scale bias.