bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic association between ankylosing spondylitis and major depressive disorders: Shared pathways, protein networks and the key gene
Authors: Dong Tiantian , Lu Shiyou , Li Xuhao , Yang Jiguo , Liu Yuanxiang
Published: June 2023

The prevalence of ankylosing spondylitis (AS) and major depressive disorders (MDD) becomes increasingly pronounced, exerting a significant impact on the life quality of contemporary people. Although there is mounting evidence of a link between AS and major depression disorders, the specific interactions between the two have not been thoroughly investigated. To this end, this study aimed to check whether the gene expression profiles of patients with AS and major depression disorders overlapped, and whether there were any functional links between the identified genes via protein–protein interactions. Herein, the relationship between the 4 datasets (GSE73754, GSE98793, GSE25101, and GSE54564) chosen from the Gene Expression Omnibus for evaluation and validation was investigated using gene characterization and functional enrichment. Then, following Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes that explore the biological processes of common genes and demonstrate the interrelationships between common genes, hub genes were obtained using the STRING database and the application cytoHubba plugin of Cytoscape software. The correlation between the gene and 22 types of immuno-infiltrating cells was explored, and the key gene as well as the diagnostic efficiency of the key gene was obtained through verification. A total of 204 shared genes were discovered, the majority of which were functionally enriched in Ribosome, Coronavirus disease COVID19, Starch and sucrose metabolism, and Galactose metabolism. Then, efforts were made to go through STRING. Immuno-infiltration studies revealed that Neutrophils, T cells CD8, T cells CD4 naive, T cells CD4 memory resting, T cells CD4 memory activated, and T cells regulatory were associated with the pathogenesis of AS and MDD. Additionally, the receiver operating characteristic curve revealed that the key gene MRPL13 played diagnostic roles in AS and MDD after intersecting 10 hub genes with 37 differential expression genes from the 2 validation datasets. The obtained results suggest an overlapping genetic structure between AS and major depression disorders. MRPL13 may provide key insights into the relationship between AS and MDD.
Distal radial artery access is a safe and feasible technique in the anatomical snuffbox for visceral intervention
Authors: Jiang Feng , Fan Wen-Long , Zheng Weiliang , Wu Xia , Hu Hongjie
Published: June 2023

Regarding the site of arterial access during the intervention, transracial intervention can reduce the risk of bleeding and vessel-related complications as well as improve patient comfort. Importantly, the distal radial artery (DRA) approach may reduce the incidence of radial artery occlusion and digital ischemia, but the feasibility and safety of DRA in performing subdiaphragmatic vascular interventions remain unclear. From January 2018 to December 2019, 106 patients were admitted to our department for visceral angiography and intervention by left distal radial artery accessing in an anatomical snuffbox. In total, 152 times of vascular interventions were performed during this period. Patients demographics, procedure details, technical success, and access site-related complications were recorded and evaluated. The mean age was 58.9 (range 22-86) years. Males accounted for 80.2%. Thirty-five patients (33%) had 2 or more procedures via the DRA approach. Technical success was achieved for 96.1% of procedures (146 cases) and 3.9% of cases failed to perform the intended procedure via the DRA approach (6 cases). The 4-Fr sheath was used in 86.8% of cases, and the 5 Fr sheath was used in the rest of the 13.2% of procedures. The rate of asymptomatic radial artery occlusion was 5.7% (6 of 106 patients). No patient suffered from distal limb ischemia after a long-time follow-up. Eight patients suffered postoperative local pain, transient numbness, or local bruised in the anatomical snuffbox without major complications. Patients with postoperative complications recovered quickly by using nonsteroidal anti-inflammatory drugs or without further treatment. Left distal radial artery access is safe and feasible as a new technique for visceral angiography and intervention.
Prevalence of type 2 diabetes mellitus and related factors among the general adult population in Saudi Arabia between 2016–2022: A systematic review and meta-analysis of the cross-sectional studies
Authors: Alwadeai Khalid S. , Alhammad Saad A.
Published: June 2023

Background:

Health officials need current knowledge of type 2 diabetes mellitus (T2DM) and related risk factors to prioritize prevention and control measures due to lifestyle changes, population structure, and the high incidence of diabetes in Saudi Arabia. The present systematic review aims to estimate the current pooled prevalence of T2DM and related risk factors among the general adult population in Saudi Arabia between 2016 and 2022.

Methods:

PubMed, Web of Science, and Google Scholar databases were searched for cross-sectional studies that reported T2DM among adults in Saudi Arabia and were published between December 31, 2016, and December 31, 2022. The PRISMA guidelines and the AXIS tool were employed to report and evaluate study quality and bias risk.

Results:

The meta-analysis with a fixed effect model included 10 studies comprising 8457 general men and women adults aged 18 or older. The prevalence of T2DM was 28% (95% CI = 27–28, P < .001), and risks of T2DM in persons over 40 were nearly twice as high (OR = 1.74, 95% CI = 1.34–2.27) than in age under 40 among general adult population in Saudi Arabia between 2016–2022. This difference was statistically significant (P < .0001).

Conclusion:

The evidence from this review provided alarming and highlighted points about the prevalence of T2DM between 2016 and 2022, but there was high heterogeneity between the studies. Individuals aged 40 or older had a high risk of T2DM among the general adult population in Saudi Arabia.
Cerebellar infarction caused by vertebral artery dissection: A case report
Authors: Zhao Jing , Luo Bin , Yao Xinlu , Zhang Xiaoyun , He Daquan , Cai Lina , Xu Yahui , Li Qin , Wan Zhirong
Published: June 2023

Rationale:

Vertebral artery dissection is an important cause of posterior circulation ischemic stroke in young and middle-aged people. We reported a young man with cerebellar infarction caused by dissection of the right vertebral artery.

Patient concerns:

A 34-year-old man presented with intermittent dizziness, blurred vision, nausea, and transient tinnitus 10 days before admission. All these symptoms were gradually aggravated and followed by vomiting and unfavorable movement of the right limbs. All these symptoms gradually aggravated.

Diagnosis:

Neurological examination on admission showed ataxia of the right limbs. Magnetic resonance imaging of the head revealed a right cerebellar infarction. High-resolution vessel wall magnetic resonance imaging showed dissection of the right vertebral artery. Whole-brain CT digital subtraction angiography revealed occlusion of the third segment (V3) of the right vertebral artery. This supports the diagnosis of vertebral artery dissection.

Interventions:

The patient received anticoagulant treatment with warfarin.

Outcomes:

After 2 weeks of treatment, the patient showed remarkably alleviated dizziness and unfavorable movement of the right limbs. After 3 months of treatment, the modified Rankin Scale score was 0. MRI of the head revealed that the original right cerebellar focus was softened, and there were no newly formed infarct foci.

Lessons:

When young and middle-aged patients without atherosclerotic risk factors encounter sudden dizziness, tinnitus, and unfavorable limb movement, vertebral artery dissection may be considered. Careful inquiry into the medical history may help make a final diagnosis. Further high-resolution vessel wall magnetic resonance imaging is an effective means to find arterial dissection. Early diagnosis and treatment for vertebral artery dissection has a favorable prognosis.
Insights into adeno-associated virus-based ocular gene therapy: A bibliometric and visual analysis
Authors: Chen Xi , Yu Yang , Nie Huiling , Qin Xun , Bai Wen , Ren Junsong , Yao Jin , Li Juxue , Jiang Qin
Published: June 2023

Background:

Adeno-associated virus (AAV) plays a vital role in ocular gene therapy and has been widely studied since 1996. This study summarizes and explores the publication outputs and future research trends of AAV-based ocular gene therapy.

Methods:

Publications and data about AAV-based ocular gene therapy were downloaded from the Web of Science Core Collection or ClinicalTrials.gov database. The publications and data were analyzed by Microsoft Excel, CiteSpace, VOS viewer, and a free online platform (http://bibliometric.com).

Results:

Totally 832 publications from the Web of Science Core Collection relevant to AAV-based ocular gene therapy were published from 1996 to 2022. These publications were contributed by research institutes from 42 countries or regions. The US contributed the most publications among these countries or regions, notably the University of Florida. Hauswirth WW was the most productive author. “Efficacy” and “safety” are the main focus areas for future research according to the references and keywords analysis. Eighty clinical trials examined AAV-based ocular gene therapy were registered on ClinicalTrials.Gov. Institutes from the US and European did the dominant number or the large proportion of the trials.

Conclusions:

The research focus of the AAV-based ocular gene therapy has transitioned from the study in biological theory to clinical trialing. The AAV-based gene therapy is not limited to inherited retinal diseases but various ocular diseases.
Artificial intelligence in orthopedics: A qualitative exploration of the surgeon perspective
Authors: Kamal Ahmed Hassan , Zakaria Ossama Mohammed , Majzoub Rabab Abbas , Nasir El Walid Fadul
Published: June 2023

Artificial intelligence (AI) is currently integrated into many medical services. AI is utilized in many aspects of orthopedic surgery. The scope ranges from diagnosis to complex surgery. To evaluate the perceptions, attitudes, and interests of Sudanese orthopedic surgeons regarding the different applications of AI in orthopedic surgery. This qualitative questionnaire-based study was conducted through an anonymous electronic survey using Google Forms distributed among Sudanese orthopedic surgeons. The questionnaire entailed 4 sections. The first section included the participants’ demographic data. The remaining 3 sections included questions for the assessment of the perception, attitude, and interest of surgeons toward (AI). The validity and reliability of the questionnaire were tested and piloted before the final dissemination. One hundred twenty-nine surgeons responded to the questionnaires. Most respondents needed to be more aware of the basic concepts of AI. However, most respondents were aware of its use in spinal and joint replacement surgeries. Most respondents had doubts regarding the safety of (AI). However, they were highly interested in utilizing (AI) in many orthopedic surgical aspects. Orthopedic surgery is a rapidly evolving branch of surgery that involves adoption of new technologies. Therefore, orthopedic surgeons should be encouraged to enroll in research activities to generate more studies and reviews to assess the usefulness and safety of emerging technologies.
Current State of Dor Yeshorim, Expanded Carrier, and Newborn Screening
Authors: Anderson Sharon
Published: June 2023

Availability and accessibility of preconception and prenatal genetic carrier and newborn biochemical and genetic screening have grown exponentially over the past 2 decades and as such, it is challenging for clinicians to keep pace. Although genetic counseling or genetic consultation should be offered to all expectant and new parents for prenatal screening decisions and positive results, benefits and limitations of these tests and results must be known and familiar to perinatal and pediatric clinicians. A brief historical overview of Dor Yeshorim, preconception and prenatal expanded carrier, and newborn screening is presented, followed by discussion about the conditions screened and considerations surrounding the benefits and limitations of these tests in the practice setting.
Exploring Clinical Nurse Specialist Impact in Primary Health Care: Exemplars From a Student’s Clinical Practice
Authors: Bostelman Chelsea , Passwater Chelsea , Urton Michael
Published: June 2023

Purpose/Objectives

Primary healthcare (PHC) is a clinical frontier full of opportunities for clinical nurse specialists (CNSs) to improve population outcomes, facilitate smooth care transitions, and overcome challenges through a unique lens. Clinical nurse specialist practice in primary care is exceedingly rare, and there is a paucity of literature on the topic. This article provides exemplary projects implemented by a CNS student in a primary care clinic.

Description of the Project/Program

Primary healthcare has been described as the “front door” of the health system. It has increasingly relied on nursing to deliver health services, yet PHC and nursing practice in this setting remain poorly defined. Clinical nurse specialists are well-positioned to define these concepts, standardize processes used to deliver services, and impact patient outcomes in PHC. The CNS student successfully supported a primary care clinic in these activities.

Outcome

Reviewing the impact of the CNS student’s experience offers a better understanding of CNS practice in PHC.

Conclusion

Gaps exist in the literature regarding best practices and care delivery in PHC. Clinical nurse specialists are educationally prepared to address these gaps and improve patient outcomes at the health system’s “front door.” Utilizing a CNS’s unique skill set achieves cost-effective and efficient healthcare delivery in a new way that bolsters the strategy of utilizing nurse practitioners to meet the challenge of provider shortages.
Evaluating the Accuracy and Reliability of Blowout Fracture Area Measurement Methods: A Review and the Potential Role of Artificial Intelligence
Authors: Kang Daihun
Published: June 2023

Blowout fractures are a common type of facial injury that requires accurate measurement of the fracture area for proper treatment planning. This systematic review aimed to summarize and evaluate the current methods for measuring blowout fracture areas and explore the potential role of artificial intelligence (AI) in enhancing accuracy and reliability. A comprehensive search of the PubMed database was conducted, focusing on studies published since 2000 that investigated methods for measuring blowout fracture area using computed tomography scans. The review included 20 studies, and the results showed that automatic methods, such as computer-aided measurements and computed tomography-based volumetric analysis, provide higher accuracy and reliability compared with manual and semiautomatic techniques. Standardizing the method for measuring blowout fracture areas can improve clinical decision-making and facilitate outcome comparison across studies. Future research should focus on developing AI models that can account for multiple factors, including fracture area and herniated tissue volume, to enhance their accuracy and reliability. Integration of AI models has the potential to improve clinical decision-making and patient outcomes in the assessment and management of blowout fractures.
Recurrent Deeply Invasive Basal Cell Carcinoma
Authors: Milvydaitė Greta , Ivanauskas Andrius , Keizeris Tadas , Ryškienė Silvija , Rokicki Jan Pavel , Janužis Gintaras , Razukevičius Dainius
Published: June 2023

Introduction:

Basal cell carcinoma (BCC) is the most frequent skin malignancy worldwide. The majority of BCCs grow slowly and have a low metastatic potential. However, they can be destructive to surrounding tissues since they are locally invasive.

Methods:

This case report was conducted on a 78-year-old woman complaining of a solid lump on the left side of the neck and nonhealing lesion. Three years earlier, she had BCC on the same site. Clinical and radiographic examinations were made. The biopsy specimens revealed that it is a recurrent BCC. In operating room, during blunt tissue dissection, the arterial wall was damaged. Tumor was overgrown left internal carotid artery near the bifurcation. Infiltrated part of arteria wall was resected, and a synthetic arterial prosthesis was placed.

Results:

Follow-up after 4 months showed that the wound was healing well. No complications regarding cardiovascular and other organ systems were seen.
The Histone Methyltransferase Setdb2 Modulates TIMP-MMP Activity During Abdominal Aortic Aneurysm Development
Authors: Davis Frank M. , Melvin William J. , Mangum Kevin , Tsoi Lam C. , Joshi Amrita D. , Cai Qing , Henke Peter K. , Gudjonsson Johann E. , Gallagher Katherine A.
Published: June 2023

Objective:

To determine macrophage-specific alterations in epigenetic enzyme function contributing to development of abdominal aortic aneurysms (AAAs).

Summary Background Data:

AAA are a life-threatening disease, characterized by pathological vascular remodeling driven by an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Identifying mechanisms regulating macrophage-mediated extracellular matrix degradation is of critical importance to developing novel therapies.

Methods:

The role of SETDB2 in AAA formation was examined in human aortic tissue samples by single-cell RNA sequencing and in a myeloid-specific SETDB2 deficient murine model induced by challenging mice with a combination of a high-fat diet and angiotensin II.

Results:

Single-cell RNA sequencing of human AAA tissues, identified SETDB2 was upregulated in aortic monocyte/macrophages and murine AAA models compared to controls. Mechanistically, interferon-β regulatesSetdb2expression via JAK/STAT signaling which trimethylates histone 3 lysine 9 (H3K9) on the TIMP1-3 gene promoters thereby suppressingTimp1-3transcription and leading to unregulated MMP activity. Macrophage-specific knockout of SETDB2 (Setdb2f/fLyz2Cre+) protected mice from AAA formation with suppression of vascular inflammation, macrophage infiltration, and elastin fragmentation. Genetic depletion of SETDB2 prevented AAA development due to removal of the repressive H3K9-trimethylation mark on theTimp1-3gene promoter resulting in increased TIMP expression, decreased protease activity, and preserved aortic architecture. Lastly, inhibition of the JAK/STAT pathway with an FDA approved inhibitor, Tofacitinib, limitedSetdb2expression in aortic macrophages.

Conclusions:

These findings identify SETDB2 as a critical regulator of macrophage-mediated protease activity in AAAs and identify SETDB2 as a mechanistic target for the management of AAAs.
Breast Conservation Surgery and Mastectomy have Similar Locoregional Recurrence Following Neoadjuvant Chemotherapy
Authors: Mukhtar Rita A. , Chau Harrison , Woriax Hannah , Piltin Mara , Ahrendt Gretchen , Tchou Julia , Yu Hongmei , Ding Qian , Dugan Catherine Lu , Sheade Jori , Crown Angelena , Carr Michael , Wong Jasmine , Son Jennifer , Yang Rachel , Chan Theresa , Terando Alicia , Alvarado Michael , Ewing Cheryl , Tonneson Jennifer , Tamirisa Nina , Gould Rebekah , Singh Puneet , Godellas Constantine , Larson Kelsey , Chiba Akiko , Rao Roshni , Sauder Candice , Postlewait Lauren , Lee Marie Catherine , Symmans William Fraser , Esserman Laura J. ,   ISPY-2 Locoregional Working Group, Boughey Judy C.
Published: June 2023

Neoadjuvant chemotherapy (NAC) increases rates of successful breast conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II-III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs. mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and Residual Cancer Burden (RCB). In 1,462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analyses. The unadjusted incidence of LRR was 5.4% after BCS, and 7.0% after mastectomy, at median follow up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having significantly higher hazard ratio for LRR compared to RCB 0 on multivariate analysis. Triple negative receptor subtype was also associated with increased risk of LRR (HR 2.91, 95% CI 1.8-4.6, P<0.0001), regardless of type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS following BCS compared to mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.
Risk Factors for De Novo Overactive Bladder After Midurethral Sling
Authors: Serna-Gallegos Tasha , Dutta Sonia , Crowder Carly , Wadensweiler Paul , Whitcomb Emily L. , Guaderrama Noelani M.
Published: June 2023

Importance

The low incidence of de novo overactive bladder (OAB) symptoms after a midurethral sling (MUS) procedure better informs preoperative counseling.

Objective

The study aimed to measure the incidence and risk factors for de novo OAB after MUS.

Study Design

This was a retrospective cohort study of de novo OAB symptoms in patients who underwent MUS surgery in a health maintenance organization between January 1, 2008, and September 30, 2016. Patients were identified using Current Procedural Terminology codes for MUS and International Classification of Diseases, Tenth Revision codes for urinary urgency, frequency, nocturia, OAB, and urgency urinary incontinence (UUI). The cohort of patients was identified by the absence of these International Classification of Diseases, Tenth Revision codes 12 months preoperatively and the presence of these codes within 6 months after surgery. This cohort was used to calculate the rate of de novo OAB after MUS surgery. Clinical and demographic factors were abstracted. Statistical analysis was performed using descriptive, χ
2, simple logistic, and multiple logistic regression.

Results

During the study period, 13,893 patients underwent MUS surgery and 6,634 met the inclusion criteria. The mean age was 56.9 years, mean parity was 2.76, and mean body mass index was 28.9 (calculated as weight in kilograms divided by height in meters squared). Of these, 410 (6.1%) developed de novo OAB within 12 months. The most common symptoms were urgency (65.4%), UUI (42.2%), and frequency (19.8%). On multivariable regression modeling, de novo urgency and UUI were not associated with concurrent surgery (P < 0.05). Increasing age and body mass index were associated with an increased risk of nocturia (P < 0.05).

Conclusions

The incidence of de novo OAB after MUS surgery was 6.1%. This aligns with current literature and critically informs preoperative counseling for MUS surgery.
Performance and Advancement of the Kidney Solid Organ Response Test
Authors: Lee Joshua , Barbachan e Silva Mariel , Bao Yi , Whitmarsh Ryan , Banerjee Sukanta , O’Connor Jeannine , Holbert Jeffery , Bratton Tiffany K. , Broin Pilib Ó. , Akalin Enver
Published: June 2023

Background.

The kidney solid organ response test (kSORT) has been investigated for the prediction of acute rejection in kidney transplant recipients with conflicting results. We aimed to investigate if the kSORT assay score is associated with rejection or immune quiescence.

Methods.

The blinded association between rejection and kSORT > 9 were investigated. Optimization of kSORT prediction was evaluated after unblinding to determine the optimal prediction cutoff value of kSORT score. Additionally, the predictive capability of the kSORT gene set was assessed using blinded normalized gene expression data from microarray (Affymetrix) and qPCR assays.

Results.

Of the 95 blood samples analyzed, 18 patients had blood samples before transplant, 77 patients after transplant and 71 had clinically indicated biopsies of which 15 biopsies showed acute rejection and 16 showed chronic active antibody-mediated rejection. When 31 patients with rejection were compared to the remaining 64 patients, positive predictive value (PPV) was 54.29% and negative predictive value (NPV) was 75% when stratified using a kSORT score > 9, and PPV was 57.89% and NPV was 78.95% when stratified using a kSORT score > 5. Using the kSORT assay for detection of rejection showed an area under the curve value of 0.71. Microarray data improved prediction accuracy with PPV of 53% and NPV of 84% compared to qPCR results (PPV and NPV were 36% and 66%), respectively.

Conclusions.

The kSORT assay has the potential to be used as a predictive tool for active rejection and/or immune quiescence, but additional studies will be useful in improving and refining the kSORT assay, in particular the prediction algorithm.
Detecting heterogeneous seizures in newborn infants using triple correlation
Authors: Smith Graham A , Henry Julia , van Drongelen Wim
Published: June 2023

We detect seizures in newborn infants using a novel method derived from triple correlation, which integrates spatial and temporal structure in neonatal electroencephalograms (EEGs). Triple correlation natively encompasses analogues to a variety of lower-order approaches (auto-correlation, cross-correlation) in addition to introducing higher-order signals, so we hypothesized that our approach would both effectively detect and differentiate notoriously difficult-to-detect and heterogeneous neonatal seizures. Indeed, our method in its simplest form performs comparably well to a current standard of care, amplitude-integrated EEG (aEEG), and by some measures outperforms aEEG, suggesting at a minimum that a combination of triple correlation and aEEG could produce a more effective first-line bedside detector. Moreover, we find that the triple correlation seizure-signal varies between patients, with 1) differences in dominance of either within or between channel correlations and 2) differing levels of higher order structure. We hope that our approach will provide a fertile field for future work in distinguishing and detecting seizures.
Determinants of Post-acute COVID-19 Syndrome among hospitalized severe COVID-19 patients: a 2-year follow up study
Authors: Elias Tamrat P. , Gebreamlak Tsegaye W. , Gebremeskel Tigist T. , Adde Binyam L. , Elias Bitaniya P. , Argaw Abel M. , Tenaw Addis A.
Published: June 2023

Background

Coronavirus disease-19 (COVID-19), emerged as a public health threat in December 2019. The number of COVID-19 cases worldwide is now more than 765 million with more than 6.9 million dead. During follow-up visits following discharge, a large percentage of patients were discovered to still be suffering from health issues that lower their quality of life and ability to return to work. This study assessed the prevalence and associated risk factors of post-acute COVID-19 syndrome (PACS) among severe COVID-19 patients who were discharged from Millennium COVID-19 care center, Addis Ababa, Ethiopia.

Methods

A cross-sectional study using data collected from patient charts and a follow-up telephone interview after two years of discharge. Systematic random samplingwas used to select a total of 400 patients. A structured questionnaire developed from the case report form for PACS of WHO was used. Frequency and cross-tabulation were used for descriptive statistics. Predictor variables with a p-value <0.25 in bivariate analyses were included in the logistic regression.

Result

Out of the 400 patients, 20 patients were dead, 14 patients refused to give consent, and 26 patients couldn’t be reached because their phone wasn’t working. Finally, 340 were included in the study. The majority (68.5%) were males and the mean age was 53.9 (±13.3 SD) years. Most of the patients (60%) has one or more comorbidity. The most common symptom at presentation was cough (93.5%), followed by shortness of breath (82.1%) and fatigue (69.7%). The mean duration of hospital admission was 12.3 (±6.5 SD) days. More than a third (38.1%) of the patients reported the persistence of at least one symptom after hospital discharge. The most common symptoms were fatigue (27.5%) and Cough (15.3%). older age (AOR 1.04, 95% CI 1.02 – 1.07), female sex (AOR 1.82, 95% CI 1.00 – 3.29), presence of comorbidity (AOR 2.38, 95% CI 1.35 – 4.19), alcohol use (AOR 3.05, 95% CI 1.49 – 6.26), fatigue at presentation (AOR 2.18, 95% CI 1.21 – 3.95), and longer hospital stay (AOR 1.06, 95% CI 1.02 – 1.10) were found to increase the odds of developing post-acute COVID-19 syndrome. Higher hemoglobin level was found to decrease the risk of subsequent post-acute COVID-19 syndrome (AOR 0.84, 95% CI 0.71 – 0.99).

Conclusion

establishing a dedicated PACS follow-up clinic, especially for those with a higher risk can help to provide comprehensive care for the patients and improve their quality of life.
Loss-of-function variants inCUL3cause a syndromic neurodevelopmental disorder
Authors: Blackburn Patrick R. , Ebstein Frédéric , Hsieh Tzung-Chien , Motta Marialetizia , Radio Francesca Clementina , Herkert Johanna C. , Rinne Tuula , Thiffault Isabelle , Rapp Michele , Alders Mariel , Maas Saskia , Gerard Bénédicte , Smol Thomas , Vincent-Delorme Catherine , Cogné Benjamin , Isidor Bertrand , Vincent Marie , Bachmann-Gagescu Ruxandra , Rauch Anita , Joset Pascal , Ferrero Giovanni Battista , Ciolfi Andrea , Husson Thomas , Guerrot Anne-Marie , Bacino Carlos , Macmurdo Colleen , Thompson Stephanie S. , Rosenfeld Jill A. , Faivre Laurence , Mau-Them Frederic Tran , Deb Wallid , Vignard Virginie , Agrawal Pankaj B. , Madden Jill A. , Goldenberg Alice , Lecoquierre François , Zech Michael , Prokisch Holger , Necpál Ján , Jech Robert , Winkelmann Juliane , Koprušáková Monika Turčanová , Konstantopoulou Vassiliki , Younce John R. , Shinawi Marwan , Mighton Chloe , Fung Charlotte , Morel Chantal , Ellis Jordan Lerner- , DiTroia Stephanie , Barth Magalie , Bonneau Dominique , Krapels Ingrid , Stegmann Sander , Schoot Vyne van der , Brunet Theresa , Bußmann Cornelia , Mignot Cyril , Courtin Thomas , Ravelli Claudia , Keren Boris , Ziegler Alban , Hasadsri Linda , Pichurin Pavel N. , Klee Eric W. , Grand Katheryn , Sanchez-Lara Pedro A. , Krüger Elke , Bézieau Stéphane , Klinkhammer Hannah , Krawitz Peter Michael , Eichler Evan E. , Tartaglia Marco , Küry Sébastien , Wang Tianyun
Published: June 2023

Purpose

De novovariants inCUL3(Cullin-3 ubiquitin ligase) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here we aimed to collect sporadic cases carrying rare variants inCUL3,describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism.

Methods

Genetic data and detailed clinical records were collected via multi-center collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient-derived T-cells.

Results

We assembled a cohort of 35 individuals with heterozygousCUL3variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 33 have loss-of-function (LoF) and two have missense variants.CUL3LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin-protein conjugatesin vitro. Specifically, we show that cyclin E1 (CCNE1) and 4E-BP1 (EIF4EBP1), two prominent substrates of CUL3, fail to be targeted for proteasomal degradation in patient-derived cells.

Conclusion

Our study further refines the clinical and mutational spectrum ofCUL3-associated NDDs, expands the spectrum of cullin RING E3 ligase-associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism.
Diagnostic accuracy of chest ultrasound scan in the diagnosis of childhood tuberculosis
Authors: Erem Geoffrey , Otike Caroline , Okuja Maxwell , Ameda Faith , Nalyweyiso Dorothy Irene , Mubuuke Aloysius Gonzaga , Kakinda Michael
Published: June 2023

Chest Ultrasound Scan (CUS) has been utilized in place of CXR in the diagnosis of adult pneumonia with similar or higher sensitivity and specificity to CXR. However, there is a paucity of data on the use of CUS for the diagnosis of childhood TB. This study aimed to determine the diagnostic accuracy of CUS for childhood TB.

This cross-sectional study was conducted at the Mulago National Referral Hospital in Uganda. Eighty children up to 14 years of age with presumptive TB were enrolled. They all had CUS and CXR performed and interpreted independently by radiologists. The radiologist who performed the CXR was blinded to the CUS findings, and vice versa. Radiologists noted whether TB was likely or unlikely. A two-by-two table was developed to compare the absolute number of children as either TB likely or TB unlikely on CXR or CUS. This was used to calculate the sensitivity and specificity of CUS when screening for TB in children, with a correction to accommodate the use of CXR as a reference test.

The sensitivity of CUS was 64% (95% CI 48.5%-77.3%), while its specificity was 42.7% (95% CI 25.5%-60.8%). Both the CUS and CXR found 29 children with a likelihood of TB, and 27 children unlikely to have TB.

CUS met the sensitivity target set by the WHO TPP for Triage, and it had a sensitivity and specificity comparable to that of CXR.
Admission biomarkers may not have an association with cardiovascular involvement in Latin American patients with Multisystem Inflammatory Syndrome in Children (MIS-C)
Authors: Galindo-Hayashi Jose M , González-Moctezuma Karen , Tamez-Rivera Oscar , Villarreal-Treviño Ana Victoria
Published: June 2023

Objectives

The aim of the study is to determine if there is an association between altered biomarkers and cardiovascular involvement in Latin American patients with MIS-C.

Design

The researchers of this study conducted a retrospective cohort study.

Setting

Secondary care maternal unit hospital in Monterrey, NL, Mexico.

Participants

Any register of a Latin-American pediatric patient with MIS-C within the database from March 2019 to February 2022.

Primary and secondary outcome measures

Cut, mean, odds ratio (OR), relative ratio (RR), 95% confidence interval (CI) andpvalues of inflammatory markers associated with cardiovascular affection in MIS-C. As a secondary outcome we measure being male as an independent risk factor.

Results

None of the biomarkers and gender variables taken were significant (Table 1).

Conclusions

The researchers’ analysis suggests there is no evidence of cause-effect association between admission biomarkers and the presence of cardiovascular affection in MIS-C. Remarkably, neutrophilia and ESR had a high odds ratio and a nearly significant p-value, which makes them ideal for further analysis with a bigger sample. Additionally, gender was included as a risk factor and was analyzed independently, nonetheless, it was not associated with a higher risk of presenting cardiovascular affection.

Article summary

Strengths and limitations of this study

First study measuring the association of a series of available and economical biomarkers with a higher incidence of cardiovascular involvement in MIS-C in a Latin-American population.

Set ground for further research regarding the current treatment of MIS-C

Sample size non-representative.

Since this is an observational study we can’t fully control confounding and bias (e.j. reporting bias)
Single-exon deletions ofZNRF3exon 2 cause congenital adrenal hypoplasia
Authors: Amano Naoko , Narumi Satoshi , Aizu Katsuya , Miyazawa Mari , Okamura Kohji , Ohashi Hirofumi , Katsumata Noriyuki , Ishii Tomohiro , Hasegawa Tomonobu
Published: June 2023

Primary adrenal insufficiency (PAI) is a life-threatening condition characterized by the inability of the adrenal cortex to produce sufficient steroid hormones. E3 ubiquitin protein ligase zinc and ring finger 3 (ZNRF3) is a negative regulator of Wnt/β-catenin signaling. R-spondin 1 (RSPO1) enhances Wnt/β-catenin signaling via binding and removal of ZNRF3 from the cell surface. To explore a novel genetic form of PAI, we analyzed nine childhood-onset patients with PAI of biochemically and genetically unknown etiology using array comparative genomic hybridization. We identified various-sized single-exon deletions encompassing ofZNRF3exon 2 in three patients, who showed neonatal-onset adrenal hypoplasia with glucocorticoid and mineralocorticoid deficiencies. RT-PCR analysis showed that the three distinct single exon deletions were commonly transcribed into a 126-nucleotide deleted mRNA and translated into 42-amino acid deleted protein (ΔEx2-ZNRF3). Three-dimensional structure modeling predicted that interaction between ZNRF3 and RSPO1 was disturbed in ΔEx2-ZNRF3, suggesting loss of RSPO1-dependent activation of Wnt/β-catenin signaling. Cell-based functional assays with the TCF-LEF reporter showed that RSPO1-dependent activation of Wnt/β-catenin signaling was attenuated in cells expressing ΔEx2-ZNRF3 as compared with those expressing wild-type ZNRF3. In summary, we provided genetic evidence linking deletions encompassing ZNRF3 exon 2 and congenital adrenal hypoplasia, which might be related to constitutive inactivation of Wnt/β-catenin signaling by ΔEx2-ZNRF3.
Protein-truncating variants inBSNare associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease
Authors: Zhao Yajie , Chukanova Maria , Kentistou Katherine A , Fairhurst-Hunter Zammy , Siegert Anna Maria , Jia Raina , Dowsett Georgina , Gardner Eugene J , Day Felix R , Kaisinger Lena R , Tung Yi-Chun Loraine , Hong Lam Brian Yee , Chen Hsiao-Jou Cortina , Wang Quanli , Berumen-Campos Jaime , Kuri-Morales Pablo , Tapia-Conyer Roberto , Alegre-Diaz Jesus , Emberson Jonathan , Torres Jason M , Collins Rory , Saleheen Danish , Smith Katherine R , Paul Dirk S , Merkle Florian , Wareham Nick J , Petrovski Slavé , O’Rahilly Steve , Ong Ken K , Yeo Giles S H , Perry John R B
Published: June 2023

Obesity is a major risk factor for many common diseases and has a significant heritable component. While clinical and large-scale population studies have identified several genes harbouring rare alleles with large effects on obesity risk, there are likely many unknown genes with highly penetrant effects remaining. To this end, we performed whole exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare, loss of function variants in two genes –BSNandAPBA1– with effects on BMI substantially larger than well-established obesity genes such asMC4R. One in ∼6500 individuals carry a heterozygous protein truncating variant (PTV) inBSN, which confers a 6.6, 3.7 and 3-fold higher risk of severe obesity (BMI >40kg/m2), non-alcoholic fatty liver disease and type 2 diabetes, respectively. In contrast to most other obesity-related genes, rare variants inBSNandAPBA1had no apparent effect on childhood adiposity. Furthermore,BSNPTVs magnified the influence of common genetic variants associated with BMI, with a common polygenic score exhibiting an effect on BMI twice as large inBSNPTV carriers than non-carriers. Finally, we explored the plasma proteomic signatures ofBSNPTV carriers as well as the functional consequences ofBSNdeletion in human iPSC-derived hypothalamic neurons. These approaches highlighted a network of differentially expressed genes that were collectively enriched for genomic regions associated with BMI, and suggest a role for degenerative neuronal synaptic function and neurotransmitter release in the etiology of obesity.
The relative effectiveness of a high-dose quadrivalent influenza vaccine vs standard-dose quadrivalent influenza vaccines in older adults in France: a retrospective cohort study during the 2021-22 influenza season
Authors: Hélène Bricout , Marie-Cécile Levant , Nada Assi , Pascal Crépey , Alexandre Descamps , Karine Mari , Jacques Gaillat , Gaétan Gavazzi , Benjamin Grenier , Odile Launay , Anne Mosnier , Fanny Raguideau , Laurence Watier , Harris Rebecca C , Ayman Chit
Published: June 2023

Background

High-dose quadrivalent influenza vaccine (HD-QIV) was introduced during the 2021/22 influenza season in France for adults aged ≥65 years as an alternative to standard-dose quadrivalent influenza vaccines (SD-QIV). This is the first study to estimate the relative vaccine effectiveness (rVE) of HD-QIV versus SD-QIV against influenza-related hospitalizations in France.

Methods

Community-dwelling individuals aged ≥65 years with reimbursed influenza vaccine claims during the 2021/22 influenza season were included from the French national health insurance database. Individuals were followed up from vaccination day to 30 June 2022, nursing home admission or death date. Baseline socio-demographic and health characteristics were identified from medical records over the 5 previous years. Hospitalizations due to influenza and other causes were recorded from 14 days after vaccination to end of follow-up. HD-QIV and SD-QIV vaccinees were matched using 1:4 propensity score matching with an exact constraint on age group, sex, week of vaccination and region. Incidence rate ratios (IRR) were estimated using zero-inflated Poisson or zero-inflated negative binomial regression models.

Results

We matched 405,385 (99.9%) HD-QIV to 1,621,540 SD-QIV vaccinees. HD-QIV was associated with a 23.3% (95%CI: 8.4–35.8) lower rate of influenza hospitalizations compared to SD-QIV. Post-matching, we observed higher rates in the HD-QIV group for hospitalizations non-specific to influenza and for negative control outcomes, suggesting residual confounding by indication.

Conclusions

HD-QIV was associated with lower influenza-related hospitalization rates versus SD-QIV, consistent with existing evidence, in the context of high SARS-CoV-2 circulation in France and likely prioritization of HD-QIV for older/more comorbid individuals.
Metabolic signature and proteasome activity controls synovial migration ofCDC42hiCD14+cells in rheumatoid arthritis
Authors: Malmhäll-Bah Eric , Andersson Karin M.E. , Erlandsson Malin C. , Silfverswärd Sofia T. , Pullerits Rille , Bokarewa Maria I.
Published: June 2023

Objective

Activation of Rho-GTPases in macrophages causes inflammation and severe arthritis in mice. In this study, we explore if Rho-GTPases define the joint destination of pathogenic leukocytes in rheumatoid arthritis (RA) and how JAK inhibition mitigates these effects.

Methods

CD14+cells of 136 RA patients were characterized by RNA-sequencing, and cytokine measurement to identify biological processes and transcriptional regulators specific forCDC42hiCD14+cells, which were summarized in a metabolic signature. Effect of hypoxia, and IFN-γ signaling on the metabolic signature of CD14+cells was assessed experimentally. To investigate its connection with joint inflammation, the signature was translated into the single cell characteristics ofCDC42hisynovial tissue macrophages. Sensitivity of the metabolic signature to the RA disease activity and treatment effect was assessed experimentally and clinically.

Results

CDC42hiCD14+cells carried the metabolic signature of genes functional in the oxidative phosphorylation and proteasome-dependent cell remodeling, which correlated with the cytokine-rich migratory phenotype and antigen presenting capacity of these cells. Integration ofCDC42hiCD14+and synovial macrophages marked with the metabolic signature revealed the important role of the interferon-rich environment and immunoproteasome expression in homeostasis of these pathogenic macrophages. TheCDC42hiCD14+cells were targeted by JAK-inhibitors and responded with downregulation of immunoproteasome and MHC-II molecules, which disintegrated the immunological synapse, reduced cytokine production and alleviated arthritis.

Conclusion

This study shows that the CDC42-related metabolic signature identifies the antigen-presenting CD14+cells that migrate to joints to coordinate autoimmunity. Accumulation ofCDC42hiCD14+cells disclose patients perceptive to JAKi treatment.
Personalising Alzheimer’s Disease progression using brain atrophy markers
Authors: Verdi Serena , Rutherford Saige , Fraza Charlotte , Tosun Duygu , Altmann Andre , Raket Lars Lau , Schott Jonathan M. , Marquand Andre F. , Cole James H.
Published: June 2023

INTRODUCTION: Neuroanatomical normative modelling can capture individual variability in Alzheimer’s Disease (AD). We used neuroanatomical normative modelling to track individuals’ disease progression in people with mild cognitive impairment (MCI) and patients with AD.

METHODS: Cortical thickness and subcortical volume neuroanatomical normative models were generated using healthy controls (n∼58k). These models were used to calculate regional Z-scores in 4361 T1-weighted MRI time-series scans. Regions with Z-scores <-1.96 were classified as outliers and mapped on the brain, and also summarised by total outlier count (tOC).

RESULTS: Rate of change in tOC increased in AD and in people with MCI who converted to AD and correlated with multiple non-imaging markers. Moreover, a higher annual rate of change in tOC increased the risk of MCI progression to AD. Brain Z-score maps showed that the hippocampus had the highest rate of atrophy change.

CONCLUSIONS: Individual-level atrophy rates can be tracked by using regional outlier maps and tOC.