bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the fibroblast in Barrett's esophagus and esophageal adenocarcinoma
Authors: Zhu Huili , Jin Ramon U. 
Published: April 2024

Purpose of review
Barrett's esophagus (BE) is the number one risk factor for developing esophageal adenocarcinoma (EAC), a deadly cancer with limited treatment options that has been increasing in incidence in the US. In this report, we discuss current studies on the role of mesenchyme and cancer-associated fibroblasts (CAFs) in BE and EAC, and we highlight translational prospects of targeting these cells.

Recent findings
New insights through studies using single-cell RNA sequencing (sc-RNA seq) have revealed an important emerging role of the mesenchyme in developmental signaling and cancer initiation. BE and EAC share similar stromal gene expression, as functional classifications of nonepithelial cells in BE show a remarkable similarity to EAC CAFs. Several recent sc-RNA seq studies and novel organoid fibroblast co-culture systems have characterized the subgroups of fibroblasts in BE and EAC, and have shown that these cells can directly influence the epithelium to induce BE development and cancer progression. Targeting the CAFs in EAC with may be a promising novel therapeutic strategy.

Summary
The fibroblasts in the surrounding mesenchyme may have a direct role in influencing altered epithelial plasticity during BE development and progression to EAC.
A systematic review and meta-analysis of extra-intestinal manifestation of inflammatory bowel disease in the Eastern Mediterranean Region (EMRO) countries
Authors: Momayez Sanat Zahra , Vahedi Homayoon , Malekzadeh Reza , Fanni Zeinab 
Published: April 2024

Background:
Inflammatory bowel disease which is subgrouped mainly to ulcerative colitis and Crohn’s disease is thought to be a multi-organ disease. Most organs can be involved in the disease course in addition to gastrointestinal tract involvement. In this systematic review we aimed to assess the prevalence of these manifestations in Eastern Mediterranean Regional Office (EMRO) countries.

Method:
The present systematic review and meta-analysis study was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline. Joanna Briggs Institute (JBI) Critical Appraisal Checklist was admired for the quality evaluation of the included studies. For determining the heterogeneity, we used Cochran test and I2 statistics.

Result:
Finally, 12 studies were included in our study. Based on the results of our study the prevalence of arthritis in ulcerative colitis and Crohn’s disease patients was 7.1% (95% CI: 2.6–18.2%) and 13.5% (95% CI: 2.6–47.3%), respectively. Prevalence of arthralgia in ulcerative colitis patients was 18.4% (95% CI: 14.3–23.3%). skin involvement prevalence was 9.9% (95% CI 4.7–19.6%) in inflammatory bowel disease (IBD) patients. ocular involvement prevalence was 7.2% (95% CI 17–25.8%) in IBD patients. PSC prevalence in ulcerative colitis and Crohn’s disease patients was 3.5% (95% CI: 1.7–7.3%) and 2.7% (95% CI: 1.3–5.5%), respectively.

Conclusion:
Based on the results of this study arthralgia and arthritis were the most common extra-intestinal manifestation of IBD followed by dermatologic and ocular involvements. This extra-intestinal manifestation can challenge the patients’ management and identifying their pattern is important during the disease course.
Systemic sclerosis (positive anti-Ro 52 and anti-centromere antibodies) in a patient after COVID-19 infection: a rare case report
Authors: Oli Paras , Poudel Prabhat , KC Shradha , KC Aastha , Sah Anil Kumar , Yadav Pankaj 
Published: April 2024

Introduction and importance:
The SARS-CoV-2 is the source of COVID-19, a respiratory disease. It typically manifests as restricted pulmonary symptoms, but autoimmune dysfunction might occasionally show up. A COVID-19 infection may cause a multi-system connective tissue disease known as systemic sclerosis (SSc). In patients who recovered from COVID-19, autoimmunity may have multiple underlying causes.

Case presentation:
The authors report the case of a 68-year-old female who, 1 month after contracting COVID-19, complained of dyspnoea and muscle exhaustion. The patient was treated for post-COVID syndrome. She developed symptoms of chronic dyspnoea, pale fingers, pursed lips, trouble chewing and swallowing, and muscle weakness after 7 weeks. A chest high-resolution computerised tomography (HRCT) scan suggested interstitial lung disease. Clinical characteristics and an autoantibody profile containing anti-Ro 52 and anti-centromere antibodies pointed towards SSc. She was treated with azathioprine and prednisolone at a reduced dosage, and she is now stable with monthly follow-ups.

Clinical discussion:
COVID-19 might induce cytokine storms and immunological dysregulation, ultimately culminating in autoimmune manifestations. Several autoantibodies are observed in autoimmune illnesses in post-COVID-19 infection patients. Our situation is distinct because SSc following a COVID-19 infection is not commonly seen as an autoimmune illness.

Conclusion:
The number of patients with rare autoimmune diseases, like SSc, following COVID-19 has been rising. Therefore, we should consider the possibility of autoimmune disease when looking into a patient who presents strangely or has developed new symptoms after COVID and should contact the patient’s management immediately.
Hematological parameters to predict post-COVID-19 immune response among vaccinated and nonvaccinated individuals: a retrospective cross-sectional study
Authors: Khan Qaisar A. , Atta Tahira , Tango Tamara , Mumtaz Arif , Saravanan Priyadharshini , Vallabhaneni Sree H. , Shinwari Ismail K. , Vattikuti Bhavana , Jan Rukhsar , Verma Ravina , Sami Nayab , Farrukh Ameer M. , Levin-Carrion Yaxel 
Published: April 2024

Background:
This study finds the changes in the hematological parameters of healthy individuals to predict the immune status against coronavirus disease 2019 (COVID-19) among COVID -19 vaccinated and nonvaccinated individuals.

Methods:
A comparative cross-sectional study among 210 healthy individuals was conducted. All individuals were divided into three groups, that is, IgG positive, IgG negative, and IgG and IgM positive, based on ELISA. Data analysis was done using SPSS version 25 for Windows.

Results:
A statistically significant effect was found among the three groups in terms of mean levels of hemoglobin (Hb), hematocrit (Hct), mean corpuscular hemoglobin concentration (MCHC), red blood cells (RBC), RDW-CV, lymphocyte, neutrophil, eosinophils, and basophil count. The study also showed that 52.8% (n=74) had neither taken vaccination nor had any history of previous COVID-19 infection but were IgG antibody positive.

Conclusion:
There was a statistically significant difference among hematological parameters between immune and nonimmune groups, and it can predict the COVID-19 immune status.
Tailoring epilepsy treatment: personalized micro-physiological systems illuminate individual drug responses
Authors: Shariff Sanobar , Kantawala Burhan , Xochitun Gopar Franco William , Dejene Ayele Nitsuh , Munyangaju Isabelle , Esam Alzain Fatima , Nazir Abubakar , Wojtara Madga , Uwishema Olivier 
Published: April 2024

Introduction:
Approximately 50 million people worldwide have epilepsy, with many not achieving seizure freedom. Organ-on-chip technology, which mimics organ-level physiology, could revolutionize drug development for epilepsy by replacing animal models in preclinical studies. The authors’ goal is to determine if customized micro-physiological systems can lead to tailored drug treatments for epileptic patients.

Materials and methods:
A comprehensive literature search was conducted utilizing various databases, including PubMed, Ebscohost, Medline, and the National Library of Medicine, using a predetermined search strategy. The authors focused on articles that addressed the role of personalized micro-physiological systems in individual drug responses and articles that discussed different types of epilepsy, diagnosis, and current treatment options. Additionally, articles that explored the components and design considerations of micro-physiological systems were reviewed to identify challenges and opportunities in drug development for challenging epilepsy cases.

Results:
The micro-physiological system offers a more accurate and cost-effective alternative to traditional models for assessing drug effects, toxicities, and disease mechanisms. Nevertheless, designing patient-specific models presents critical considerations, including the integration of analytical biosensors and patient-derived cells, while addressing regulatory, material, and biological complexities. Material selection, standardization, integration of vascular systems, cost efficiency, real-time monitoring, and ethical considerations are also crucial to the successful use of this technology in drug development.

Conclusion:
The future of organ-on-chip technology holds great promise, with the potential to integrate artificial intelligence and machine learning for personalized treatment of epileptic patients.
Antibiotic Duration and UTI Outcomes in Recurrent UTI Patients
Authors: Shinnick Julia , Josephs Isabel , Suskin Johanna A. , Kurchena Kathryn , Pileika Lindsey , Darveau Spencer , Scarpaci Matthew M. , Carberry Cassandra 
Published: April 2024

Importance
Little evidence is available to inform management of acute urinary tract infections (UTIs) in women with recurrent urinary tract infection (rUTI).

Objective
This study aimed to compare the proportion of acute UTIs with persistence/relapse or recurrence based on duration of treatment antibiotics (acute UTI guideline-consistent versus extended).

Study Design
A retrospective noninferiority study of women with rUTI was performed at an academic tertiary referral center from January 2016 to December 2020. Exposure was UTI treatment with acute UTI guideline-consistent versus extended antibiotics. Outcomes were persistent/relapsed UTI (subsequent culture with the same pathogen requiring additional antibiotics within 4 weeks), recurrent UTI (culture with different pathogen), or resolution. Sample size was calculated under the null hypothesis that the proportion of acute UTIs with persistence/relapse or recurrence after acute UTI guideline-consistent antibiotics would be within a 10% noninferiority margin of extended duration (α = 0.05, β = 0.20, 2-sided tests, P < 0.05 significant).

Results
We included 219 patients with 553 acute UTIs. The mean ± SD number of UTIs per patient was 2.53 ± 1.88, the mean ± SD age was 68.60 ± 16.29 years, and the mean ± SD body mass index was 29.73 ± 7 (calculated as weight in kilograms divided by height in meters squared). There were no differences in prior surgical procedures postvoid residual volume, pelvic floor disorders, or preventive treatments between groups. Two-hundred sixty UTIs (260 of 553 [47%]) were treated with acute UTI guideline-consistent antibiotics. Overall, 86 of 553 UTIs (15.6%) persisted/relapsed, and 29 of 553 (5.2%) recurred. The difference in the proportions of UTIs with persistence/relapse or recurrence excluded the noninferiority margin (4.4%; 95% confidence interval, −0.04 to 6.80%). In total, 115 of 553 UTIs (20.8%) had persistence/relapse or recurrence.

Conclusion
In this cohort of patients with rUTI experiencing acute UTIs, acute UTI guideline-consistent duration of antibiotics was noninferior.
Nocturnal Urinary Symptoms as Screening Tools for Obstructive Sleep Apnea
Authors: Burr Eliza F. , Myer Emily N.B. , Kikuchi Jacqueline Y. , Chen Chi Chiung Grace 
Published: April 2024

Importance
Nocturnal lower urinary tract symptoms are part of obstructive sleep apnea (OSA), and urogynecology clinics may serve as OSA screening sites.

Objective
This study’s aim was to determine the accuracy of nocturia and nocturnal enuresis (NE) as screening tools for OSA in new patients at a urogynecology clinic.

Study Design
Using a retrospective study design, we gathered information regarding diagnostic OSA testing, continuous positive airflow pressure use, and lower urinary tract symptoms improvement from women in a urogynecology clinic who were previously screened for OSA using validated questionnaires. Nocturia and NE were tested for sensitivity and specificity using positive OSA diagnosis by polysomnography as the gold standard.

Results
Nocturia with a cutoff of ≥2 episodes per night had the best test characteristics—86.4% sensitivity (95% confidence interval [CI], 65.1–97.1) and 58.5% specificity (95% CI, 44.1–71.9) for an overall accuracy of 78.4% (95% CI, 67.0–89.8). Nocturnal enuresis with a cutoff of ≥1 episode per week had the best NE characteristics with 31.8% sensitivity (95% CI, 13.9–54.9) and 79.3% specificity (95% CI, 65.9–89.2) for an overall accuracy of 56.1% (95% CI, 41.2–71).

Conclusions
Lower urinary tract symptoms such as nocturia and NE are routinely assessed in urogynecology clinics, making them useful for OSA screening and referral. The present study found nocturia symptoms with ≥2 episodes per night to retain acceptable test characteristics in screening for OSA, whereas NE was found to have less acceptable test characteristics for OSA screening. Urogynecology clinics may utilize nocturia symptoms in clinical decision making for OSA referral.
Francis James Macdonald Farley. 13 October 1920—16 July 2018
Authors: Crease Robert P. 
Published: April 2024

Francis Farley was a British experimental physicist who worked for much of his career at CERN. He was a clever designer and builder of particle beams, and a team leader and player who inspired, advised, amused and regaled others. In the middle of his career he worked on the first four experiments to measure
g
− 2, one of the most important numbers in particle physics. Three of these were conducted while he was at CERN, and one at Brookhaven National Laboratory in New York. Later he studied the problem of extracting energy from water waves, attempting to build proof of concept models as well as to study the problems that might stand in the way of commercial application. Farley had the rare ability to synthesize both theoretical and experimental knowledge of a subject, to collaborate in solving problems and to pass on what he knew to others. He was also articulate about the wonder and awe that he found in science.
Surviving under Ice: Insights into gene expression changes during ice encasement in timothy (Phleum pratenseL.)
Authors: Pashapu Akhil Reddy , Dalmannsdottir Sigridur , Jørgensen Marit , Rognli Odd Arne , Kovi Mallikarjuna Rao 
Published: April 2024

AbstractThe predicted increase in frequency and duration of winter warming episodes (WWEs) at the higher northern latitudes is expected to negatively impact the forage production in this region. The formation of non-permeable ice cover due to WWEs creates hypoxic or anoxic conditions for plants leading to severe winter damages. Knowledge about molecular mechanisms underlying various winter stresses is crucial to develop cultivars with better winter survival under changing climatic conditions. In the current study, we aimed at identifying genes involved in ice encasement stress responses by RNAseq in the perennial forage grass timothy (Phleum pratenseL.) and study gene expression differentiation due to field survival using cultivars with diverse genetic backgrounds. The LD50estimates varied across cultivars and material. The expression of ethylene-responsive transcription factors, alcohol dehydrogenase, pyruvate decarboxylase, sucrose synthase, dehydrins, and heat shock proteins were highly upregulated under ice encasement conditions. Functional analysis of differentially expressed genes revealed that the upregulated genes were involved in glycolysis, pyruvate metabolism, carbon metabolism, and biosynthesis of amino acids while genes involved in photosynthesis, phenylpropanoid biosynthesis and flavonoid biosynthesis pathways were downregulated. The results from the current study indicate a substantial overlap of ice encasement stress responses with those of hypoxia and freezing stresses. In addition, the potential strategies leading to higher ice encasement tolerance of timothy are outlined. Furthermore, differences in gene expression between field survivors and the original plant material, and differences between ice encasement responses of northern-adapted and southern-adapted cultivars are briefly discussed.
Exploring the Spatial Distribution of Persistent SARS-CoV-2 Mutations - Leveraging mobility data for targeted sampling
Authors: Spott Riccardo , Pletz Mathias W. , Fleischmann-Struzek Carolin , Kimmig Aurelia , Hadlich Christiane , Hauert Mathias , Lohde Mara , Jundzill Mateusz , Marquet Mike , Dickmann Petra , Schüchner Ruben , Hölzer Martin , Kühnert Denise , Brandt Christian 
Published: April 2024

AbstractGiven the rapid cross-country spread of SARS-CoV-2 and the resulting difficulty in tracking lineage spread, we investigated the potential of combining mobile service data and fine-granular metadata (such as postal codes and genomic data) to advance integrated genomic surveillance of the pandemic in the federal state of Thuringia, Germany. We sequenced over 6,500 SARS-CoV-2 Alpha genomes (B.1.1.7) across seven months within Thuringia while collecting patients’ isolation dates and postal codes. Our dataset is complemented by over 66,000 publicly available German Alpha genomes and mobile service data for Thuringia. We identified the existence and spread of nine persistent mutation variants within the Alpha lineage, seven of which formed separate phylogenetic clusters with different spreading patterns in Thuringia. The remaining two are sub-clusters. Mobile service data can indicate these clusters’ spread and highlight a potential sampling bias, especially of low-prevalence variants. Thereby, mobile service data can be used either retrospectively to assess surveillance coverage and efficiency from already collected data or to actively guide part of a surveillance sampling process to districts where these variants are expected to emerge. The latter concept was successfully implemented as a proof-of-concept for a mobility-guided sampling strategy in response to the surveillance of Omicron sublineage BQ.1.1. The combination of mobile service data and SARS-CoV-2 surveillance by genome sequencing is a valuable tool for more targeted and responsive surveillance.
Bridge Capture permits cost-efficient, rapid and sensitive molecular precision diagnostics
Authors: Adamusová Simona , Korkiakoski Anttoni , Laine Nea , Musku Anna , Rantasalo Tuula , Kim Jorma , Blomster Juuso , Laine Jukka , Hirvonen Tatu , Pursiheimo Juha-Pekka , Tamminen Manu 
Published: April 2024

AbstractLiquid biopsies are a less invasive alternative to tissue biopsies that have been the mainstay of cancer diagnostics to date. Recently, the quantification of mutations in circulating tumor DNA (ctDNA) by targeted next-generation sequencing (NGS) has been gaining popularity. Targeted NGS can be achieved through various library preparation methods, each with distinct advantages and limitations. Here we introduce Bridge Capture, a novel technology that goes beyond the advantages of market-leading liquid biopsy technologies, eliminating the need to compromise between scalability, cost-efficiency, sensitivity, or panel size. We compared Bridge Capture to leading commercial technologies currently available in cancer diagnostics; Archer™ LIQUIDPlex™ and AmpliSeq™ Cancer HotSpot Panel v2 for Illumina®. Of all methods, Bridge Capture detected the lowest mutant allele frequency (MAF) on matched contrived colorectal biospecimens mimicking ctDNA. Next, we demonstrated the capability of Bridge Capture to effectively utilize the sequencing capacity, permitting affordable and sensitive variant detection in smaller laboratories, while delivering significant cost savings for central laboratories. Additionally, we demonstrated the reproducibility of Bridge Capture by a high correlation between the results from two independent laboratories. These results highlight the method’s portability and suitability for kit use in entirely new settings. Moreover, we presented ease of automation and minimal hands-on time of Bridge Capture. Owing to its unique design, the Bridge Capture is compatible with the most commonly used NGS platforms. Taken together, Bridge Capture is cost efficient, simple, rapid and sensitive cancer diagnostics tool that significantly improves the detection of mutations in liquid biopsies.
CHAPAS-4 trial: second-line anchor drugs for children with HIV in Africa
Authors: Bwakura-Dangarembizi Mutsa , Szubert Alexander J , Mumbiro Vivian , Kityo Cissy M , Lugemwa Abbas , Doerholt Katja , Chabala Chishala , Nyathi Mary , Nduna Bwendo , Burger David , Shakeshaft Clare , Nathoo Kusum , Musiime Victor , Yawe Ibrahim , South Annabelle , Lungu Joyce , Ndebele Wedu , Mwamabazi Mwate , Griffiths Anna , Nazzinda Rashidah , Zimba Kevin , Zhang Yingying , Walker Simon , Turkova Anna , Walker A Sarah , Bamford Alasdair , Gibb Diana M ,   CHAPAS-4 Trial Team
Published: April 2024

AbstractBackgroundChildren living with HIV requiring second-line antiretroviral therapy (ART) have limited options, an unmet need considering children require life-long ART.MethodsChildren from Uganda, Zambia, Zimbabwe were randomised to one of four second-line anchor drugs: dolutegravir(DTG), ritonavir-boosted darunavir(DRV/r), atazanavir(ATV/r), or lopinavir(LPV/r) in the factorial CHAPAS-4 trial (second randomisation to tenofovir alafenamide fumarate(TAF) or standard-of-care(SOC) backbone, reported elsewhere). Dosing followed WHO weight-bands. The primary endpoint was viral load(VL) <400copies/mL at week-96, analysed using logistic regression, hypothesising that DTG and DRV/r would be superior (threshold p=0.03) to LPV/r and ATV/r arms combined and ATV/r would be non-inferior to LPV/r(12% margin). Secondary endpoints included immunology and safety. Analyses were intention-to-treat.Results919 children, median(IQR) age 10(8-13) years, 54% male, baseline VL 17,573(5549,55700) copies/mL, CD4 669(413, 971) cells/mm3, weight-for-age Z-score -1.6(-2.4,-0.9), had spent median(IQR) 5.6(3.3,7.8) years on first-line ART. At week-96, DTG was superior (by 9.7%(95% CI 4.8%, 14.5%); p<0.0001) and DRV/r showed a trend to superiority(by 5.6%(0.3%, 11.0%); p=0.04) compared to LPV/r and ATV/r arms combined. ATV/r was non-inferior to LPV/r(+3.4%(-3.4%,+10.2%); p=0.33). CD4 counts increased with no differences between arms. Toxicity was lowest with DTG. All arms except LPV/r showed age-appropriate weight/height gains at week-96. DTG was not associated with excess absolute weight-gain(<1kg) vs. DRV/r or ATZ/r, irrespective of backbone randomisation.ConclusionsDTG-based regimens are safe and cost-effective for second-line ART. DRV/r and ATV/r are also good options. Fixed-dose combinations of DTG, DRV/r or ATV/r with nucleoside/nucleotide-reverse-transcriptase-inhibitors(NRTIs) would increase access to robust, essential second-line options for children.(ISRCTN22964075)