bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast-enhanced ultrasound for assessing tissue perfusion and predicting functional recovery following acute traumatic spinal injury: translation from rat model to humans
Authors: Khaing Zin Z. , Leyendecker Jannik , Harmon Jennifer N. , Sivakanthan Sananthan , Cates Lindsay N. , Hyde Jeffrey E. , Krueger Melissa , Glenny Robb W. , Bruce Matthew , Hofstetter Christoph P.
Published: January 2024

Traumatic spinal cord injury (tSCI) leads to an immediate loss of neurological function, with its recovery being difficult to predict in the acute phase. Here, we developed a contrast-enhanced ultrasound (CEUS) imaging biomarker to quantify the intraspinal vascular disruption after tSCI. In rodent thoracic tSCI, CEUS revealed a perfusion area deficit (PAD) which increased with injury severity (p = 0.001). The PAD size significantly correlated with hindlimb locomotor function at 8 weeks post injury (R2= 0.82, p < 0.001). Additionally, we calculated a spinal perfusion index (SPI) comparing the amount of perfused tissue at the injury center to that in injury periphery. Our experiments demonstrated that SPI decreased in more severe injuries and correlated significantly with hindlimb locomotor function at 8 weeks post injury (R2= 0.83, p < 0.001). Subsequently, we demonstrated the feasibility of intraoperative CEUS imaging in 20 patients with acute tSCI. A hyper-perfusion pattern was commonly seen in cervical motor-incomplete tSCI, while necrosis penumbra pattern was associated with motor-complete cervical or thoracic tSCI. We measured both PAD and SPI and detected statistically significant differences between motor-complete and motor-incomplete patients. In our patient cohort, SPI exhibited a strong predictive capacity for functional recovery at 6 months (R2= 0.79, p < .001) compared to PAD. In conclusion, our study suggests that an intraoperative CEUS-derived biomarker holds promise for predicting injury severity and chronic functional outcome after tSCI. Larger clinical studies are needed to better assess the reliability of the proposed CEUS-derived biomarker and its prognostic capacity.

One Sentence Summary

This paper introduces a novel biomarker utilizing contrast-enhanced ultrasound in humans and rats that accurately predicts injury severity after traumatic spinal cord injury based on tissue perfusion.
Comparing Adverse Maternal And Neonatal Outcomes in Adolescent versus Adult Mothers in Sub-Saharan Africa
Authors: Onuzo Chibuikem N. , Sefogah Promise E. , Damale Nelson K. , Boafor Theodore K. , Swarray-Deen Alim , Mumuni Kareem
Published: January 2024

Objective

Adolescent pregnancy is a major social and public health problem that burdens affected families, the communities and societies globally. It has been associated with a higher prevalence of adverse pregnancy outcomes compared to pregnancy in adults. To compare adverse pregnancy outcomes in adolescents (13-19 years) and those in adults (20 to 35 years) at the Korle-Bu Teaching Hospital in Accra, Ghana and investigate the associated factors among adolescents.

Methods

This comparative cross-sectional study involved 110 adolescents (13-19 years) and 220 adults (20 to 35 years) who delivered at the Maternity Unit of the Korle-Bu Teaching Hospital between November 2016 and February 2017. Participants were recruited using the convenience sampling method. After study protocol was explained to the parturient, informed voluntary consent and assent were obtained. Participants who met the inclusion criteria were recruited in the study. Sociodemographic characteristics, antenatal and delivery records; and maternal and perinatal outcomes were collected using an interviewer administered questionnaire and the participants’ records. Data analysis was done using SPSS version 16.0.

Results

The incidence of adolescent pregnancies during the study period was 5.1%. Compared to adults, adolescents were about 3 times more likely to have eclampsia although preeclampsia occurred more in adults. Adolescents that resided in sub-urban dwellings were more likely to have an adverse perinatal outcome compared to their adult counterparts.

Conclusion

Our study found that, in addition to their socioeconomic and biophysical disadvantages, adolescents were likely to have exceptionally high risk of eclampsia.
A comparison of self-triage tools to nurse driven triage in the emergency department
Authors: Trivedi Sachin V , Batta Rachit , Henao – Romero Nicolas , Mondal Prosanta , Wilson Tracy , Stempien James
Published: January 2024

INTRODUCTION

Canadian patients presenting to the emergency department (ED) typically undergo a triage process where they are assessed by a specially trained nurse and assigned a Canadian Triage and Acuity Scale (CTAS) score, indicating their level of acuity and urgency of assessment. We sought to assess the ability of patients to self-triage themselves through use of one of two of our proprietary self-triage tools, and how this would compare with the standard nurse-driven triage process.

METHODS

We enrolled a convenience sample of ambulatory ED patients aged 17 years or older who presented with chief complaints of chest pain, abdominal pain, breathing problems, or musculoskeletal pain. Participants completed one, or both, of an algorithm generated self-triage (AGST) survey, or visual acuity scale (VAS) based self-triage tool which subsequently generated a CTAS score. Our primary outcome was to assess the accuracy of these tools to the CTAS score generated through the nurse-driven triage process.

RESULTS

A total of 223 patients were included in our analysis. Of these, 32 (14.3%) presented with chest pain, 25 (11.2%) with shortness of breath, 75 (33.6%) with abdominal pain, and 91 (40.8%) with musculoskeletal pain. Of the total number of patients, 142 (47.2%) completed the AGST tool, 159 (52.8%) completed the VAS tool and 78 (25.9%) completed both tools. When compared to the nurse-driven triage standard, both the AGST and VAS tools had poor levels of agreement for each of the four presenting complaints.

CONCLUSIONS

Self-triage through use of an AGST or VAS tool is inaccurate and does not appear to be a viable option to enhance the current triage process. Further study is required to show if self-triage can be used in the ED to optimize the triage process.
Vitamin D for glycemic control following an acute pulmonary exacerbation: A secondary analysis of a multicenter, double-blind, randomized, placebo-controlled trial in adults with cystic fibrosis
Authors: Sivapiromrat Alisa K. , Hunt William R. , Alvarez Jessica A. , Ziegler Thomas R. , Tangpricha Vin
Published: January 2024

Individuals with cystic fibrosis (CF) often incur damage to pancreatic tissue due to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, leading to altered chloride transport on epithelial surfaces and subsequent development of cystic fibrosis-related diabetes (CFRD). Vitamin D deficiency has been associated with the development of CFRD. This was a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study in adults with CF hospitalized for an acute pulmonary exacerbation (APE), known as the Vitamin D for the Immune System in Cystic Fibrosis (DISC) trial (NCT01426256). This was a pre-planned secondary analysis to examine if a high-dose bolus of cholecalciferol (vitamin D3) can mitigate declined glucose tolerance commonly associated with an acute pulmonary exacerbation (APE). Glycemic control was assessed by hemoglobin A1c (HbA1c) and fasting blood glucose levels before and 12 months after the study intervention. Within 72 hours of hospital admission, participants were randomly assigned to a single dose of oral vitamin D3(250,000 IU) or placebo, and subsequently, received 50,000 IU of vitamin D3or placebo every other week, beginning at month 3 and ending on month 12. Forty-nine of the 91 participants in the parent study were eligible for the secondary analysis. There were no differences in 12-month changes in HbA1c or fasting blood glucose in participants randomized to vitamin D or placebo. A high-dose bolus of vitamin D3followed by maintenance vitamin D3supplementation did not improve glycemic control in patients with CF after an APE.
Coronary perforation occurring during percutaneous coronary intervention is associated with persistent high inpatient mortality and complications
Authors: Movahed Mohammad Reza , Satapathy Nishant , Hashemzadeh Mehrtash
Published: January 2024

Background

Coronary perforation is one of the major complications of percutaneous coronary intervention (PCI). The goal of this study was to evaluate adverse outcomes and mortality in patients suffering from coronary perforation during PCI above the age of 30.

Methods

The National Inpatient Sample (NIS) database, years 2016-2020, was studied using ICD 10 codes. Patients suffering from perforation were compared to patients without perforation during PCI.

Results

PCI was performed in a weighted total of 10,059,269 patients. Coronary perforation occurred in 11,725 (0.12 %) of all PCI performed. The mortality rate of patients with perforations was very high in comparison to patients without perforations. (12.9% vs 2.5%, OR: 5.6, CI:5-6.3 p<0.001). Furthermore, patients with coronary perforations had much higher rates of urgent coronary bypass surgery, tamponade, cardiac arrest, and major cardiovascular outcomes. Mortality remained high and over 10% in the 5-year study period.

Conclusion

Using a large national inpatient database, all-cause inpatient mortality in patients with coronary perforation is very high (over 10%) with persistently high mortality rates over the years study suggesting that treatment of perforations needs further improvement.
Rivaroxaban for patients with coronary dissection after drug-coated balloon angioplasty : A Randomized Controlled Trial
Authors: Liu Kaiyuan , Guo Quan , Qingbo Shi , Nie Ming , Yu Haosen , Zhang Zhiwen , Li Muwei
Published: January 2024

Background

After drug-coated balloon (DCB) angioplasty in patients with de novo coronary lesions, coronary dissections can result in the continuous presence of thrombi within the vessel wall, potentially leading to late luminal loss. Rivaroxaban, a novel oral anticoagulant, may mitigate lumen loss attributable to coronary dissection.

Objectives

This study was conducted to evaluate the effectiveness and safety of low-dose rivaroxaban in improving outcomes for patients with dissections following DCB intervention.

Methods

This trial was a prospective, randomized, controlled study including patients with acute coronary syndrome (ACS) who exhibited non-flow-limiting dissections after DCB angioplasty for de novo coronary lesions. The rivaroxaban group received a standard dual antiplatelet therapy (DAPT) regimen along with 2.5 mg of rivaroxaban twice daily for one month, reverting to DAPT thereafter. The control group was treated with standard DAPT for 6 months. All patients underwent coronary angiography at the 6-month mark. The primary endpoint involved late lumen loss in the target vessel at 6 months, and the primary safety endpoint consisted of bleeding events, as classified according to BARC criteria (types 1-3 or 5). This study has been registered with ClinicalTrials.gov, numberNCT05750758.

Results

Out of 140 randomized patients, 137 (69 in the rivaroxaban group, 68 in the control group) completed the study. Low-dose rivaroxaban was associated with a significant reduction in late lumen loss compared to controls (−0.12 ± 0.56 mm versus 0.14 ± 0.37 mm, P = 0.002). The rivaroxaban group experienced more minor bleeding events (BARC 1-2), though this was not statistically significant (P = 0.059). Clinical outcomes were similar between groups (P = 0.354).

Conclusions

This study demonstrates that the combination of rivaroxaban with dual antiplatelet therapy shows promise in reducing stenosis and enhancing late lumen expansion in lesions with dissections post-DCB intervention.
Post-Market Surveillance of Six COVID-19 Point-of-Care Tests Using Pre-Omicron and Omicron SARS-CoV-2 Variants
Authors: Exner Hannah M. , Gregorchuk Branden S. J. , Castor AC-Green , Crisostomo Leandro , Kolsun Kurt , Giesbrecht Shayna , Dust Kerry , Alexander David , Bolaji Ayooluwa , Quill Zoe , Head Breanne M. , Meyers Adrienne F. A. , Sandstrom Paul , Becker Michael G.
Published: January 2024

Post-market surveillance of test performance is a critical function of public health agencies and clinical researchers that ensures diagnostics maintain performance characteristics following their regulatory approval. Changes in product quality, manufacturing processes over time, or the evolution of new variants may impact product quality. During the COVID-19 pandemic, a plethora of point-of-care tests (POCTs) were released onto the Canadian market. This study evaluated the performance characteristics of several of the most widely-distributed POCTs in Canada, including four rapid antigen tests (Abbott Panbio, BTNX Rapid Response, SD Biosensor, Quidel QuickVue) and two molecular tests (Abbott ID NOW, Lucira Check IT). All tests were challenged with 149 SARS-CoV-2 clinical positives, including multiple variants up to and including Omicron XBB.1.5, as well as 29 clinical negatives. Results were stratified based on whether the isolate was Omicron or pre-Omicron as well as by RT-qPCR Ct value. The test performance of each POCT was consistent with the manufacturers’ claims and showed no significant decline in clinical performance against any of the variants tested. These findings provide continued confidence in the results of these POCTs as they continue to be used to support decentralized COVID-19 testing. This work demonstrates the essential role of post-market surveillance in ensuring reliability in diagnostic tools.
Are aortic biomechanical properties early markers of dilatation in patients with Marfan Syndrome? – A Systematic Review and Meta-Analysis
Authors: Rosnel Claire , Sivera Raphael , Cervi Elena , Danton Mark , Schievano Silvia , Capelli Claudio , Aggarwal Ankush
Published: January 2024

Background

Although the stiffness of tissue is known to play an important role in aortic dilatation, the current guidelines for offering a preventative aortic surgery in patients with Marfan syndrome rely solely on the aortic diameter. In this systematic review and meta-analysis, we analyze and compare literature on in-vivo aortic stiffness measurements in Marfan patients. Our aim is to assess the potential of these measurements as early indicators of aortic dilatation.

Methods

Following the PRISMA guidelines, we collected literature on diameter and three in-vivo stiffness measures: Pulse Wave Velocity (PWV),β-stiffness index and Distensibility, at five different aortic locations in patients with Marfan syndrome. Reported results were reviewed and compared against each other. For meta-analysis, an augmented dataset was created by combining extracted data from the reviewed literature. Regression with respect to age and statistical comparison were performed on the augmented dataset for all three measures at five different locations.

Results

30 articles reporting data from 1925 patients with Marfan and 836 patients without Marfan were reviewed. PWV was found to be statistically higher in Marfan at most aortic locations, but only when the aorta is already dilated. Distensibility was found to be lower at all aortic locations even in non-dilated aortas, and its decrease has been associated with higher chances of developing aortic dilatation.β-stiffness index was higher in Marfan patients and was positively correlated with the rate of aortic dilatation, emphasizing its role as a valuable indicator. In our meta-analysis based on a total 1197 datapoints, diameter was found to be higher only at the root (p <0.001). All stiffness measures showed a significant variation with age. PWV at the root and carotid-femoral region was not statistically different (p= 0.62 andp= 0.14 respectively), but was positively correlated with age at all locations. Distensibility andβ-stiffness index were different in Marfan patients at all locations, and the difference was more pronounced after accounting for age-related variation.

Conclusion

Based on the results in the literature,β-stiffness index and distensibility emerge as the best predictors of future aortic dilatation. Our meta-analysis quantifies age-related changes in aortic stiffness and highlights the importance of accounting for age in comparing these measurements. Missing diameter values in the literature limited our analysis. Further analysis based on combined aortic stiffness and diameter criteria is recommended to evaluate aortic disease in a comprehensive way and assist clinical decisions for prophylactic surgery.
Bridging the gap: improving correspondence between low-field and high-field magnetic resonance images in young people
Authors: Cooper Rebecca , Hayes Rebecca , Corcoran Mary , Sheth Kevin N , Arnold Thomas Campbell , Stein Joel , Glahn David C. , Jalbrzikowski Maria
Published: January 2024

Background

Portable low-field-strength magnetic resonance imaging (MRI) systems represent a promising alternative to traditional high-field-strength systems with the potential to make MR technology available at scale in low-resource settings. However, lower image quality and resolution may limit the research and clinical potential of these devices. We tested two super-resolution methods to enhance image quality in a low-field MR system and compared their correspondence with images acquired from a high-field system in a sample of young people.

Methods

T1- and T2-weighted structural MR images were obtained from a low-field (64mT) Hyperfine and high-field (3T) Siemens system in N = 70 individuals (mean age=20.39 years, range 9-26 years). We tested two super-resolution approaches to improve image correspondence between images acquired at high- and low-field: 1) processing via a convolutional neural network (‘SynthSR’), and 2) multi-orientation image averaging. We extracted brain region volumes, cortical thickness, and cortical surface area estimates. We used Pearson correlations to test the correspondence between these measures, and Steiger Z tests to compare the difference in correspondence between standard imaging and super-resolution approaches.

Results

Single pairs of T1- and T2-weighted images acquired at low field showed high correspondence to high-field-strength images for estimates of total intracranial volume, surface area cortical volume, subcortical volume, and total brain volume (rrange=0.60-0.88). Correspondence was lower for cerebral white matter volume (r=0.32,p=.007,q=.009) and non-significant for mean cortical thickness (r=-0.05,p=.664,q =.664). Processing images with SynthSR yielded significant improvements in correspondence for total brain volume, white matter volume, total surface area, subcortical volume, cortical volume, and total intracranial volume (rrange=0.85-0.97), with the exception of global mean cortical thickness (r=0.14). An alternative multi-orientation image averaging approach improved correspondence for cerebral white matter and total brain volume.

Processing with SynthSR also significantly improved correspondence across widespread regions for estimates of cortical volume, surface area and subcortical volume, as well as within isolated prefrontal and temporal regions for estimates of cortical thickness.

Conclusions

Applying super-resolution approaches to low-field imaging improves regional brain volume and surface area accuracy in young people. Finer-scale brain measurements, such as cortical thickness, remain challenging with the limited resolution of low-field systems.
The diabetic myocardial transcriptome reveals Erbb3 as a novel biomarker of incident heart failure
Authors: Conning-Rowland Marcella S , Giannoudi Marilena , Drozd Michael , Brown Oliver I , Yuldasheva Nadira Y , Cheng Chew W , Meakin Paul J , Straw Sam , Gierula John , Ajjan Ramzi A , Kearney Mark T , Levelt Eylem , Roberts Lee D , Griffin Kathryn J , Cubbon Richard M
Published: January 2024

Aims

Diabetes mellitus (DM) increases heart failure incidence and worsens prognosis, but the molecular basis of diabetic heart disease is poorly defined in humans. We aimed to define the diabetic myocardial transcriptome and validate hits in their circulating protein form to define disease mechanisms and biomarkers.

Methods and Results

RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project was used to define differentially expressed genes (DEGs) in right atrial (RA) and left ventricular (LV) myocardium from people with versus without DM (type 1 or 2). DEGs were validated in their circulating protein form in the UK Biobank cohort, searching for directionally concordant differential expression. Validated plasma proteins were characterized in UK Biobank participants, irrespective of diabetes status, using cardiac magnetic resonance imaging, incident heart failure and cardiovascular mortality.

We found 32 and 32 DEGs associated with DM in the RA and LV, respectively, with no overlap between these. Plasma proteomic data was available for 6 hits, with only ERBB3 (LV hit) exhibiting directional concordance, being lower in myocardium and blood of people with DM. Irrespective of DM status, lower circulating ERBB3 was associated with impaired left ventricular contractility and higher LV mass. Participants in the lowest quartile of circulating ERBB3 had increased incident heart failure and cardiovascular death vs. participants in all other quartiles. Similar associations were noted for ERBB2 and ERBB4.

Conclusions

DM is characterized by lower ERBB3 expression in the myocardium and lower plasma protein concentration. This is associated with left ventricular dysfunction, incident heart failure and cardiovascular mortality.
Availability and prescribing of extended release buprenorphine injection for Medicaid beneficiaries, 2018-2022
Authors: Ross Rachael K. , Rudolph Kara E. , Shover Chelsea
Published: January 2024

Background and aims

Extended release buprenorphine injection (INJ-BUP) has been available in the United States since 2018. INJ-BUP has the potential to positively impact OUD treatment outcomes by providing additional treatment options and patient choice. We aimed to describe the availability and prescribing of INJ-BUP for Medicaid beneficiaries since its availability, nationwide and by state.

Methods

To assess availability, we measured the number of substance use disorder (SUD) facilities that offered INJ-BUP and accepted Medicaid insurance in 2018-2021 and calculated the percentage of all facilities offering medications of OUD. To assess prescribing, we measured the number of prescriptions for INJ-BUP paid by Medicaid 2018-2022 and calculated the percentage of all buprenorphine prescriptions paid by Medicaid. Data sources were publicly available.

Results

The number of facilities that offered INJ-BUP and accepted Medicaid insurance increased from 360 (2.5% of all SUD facilities offering medication) in 2018 to 2,257 (13.3%) in 2021. The number of prescriptions for INJ-BUP paid by Medicaid increased from 4,322 (0.1% of all buprenorphine prescriptions) in 2018 to 186,861 (2.0%) in 2022. There was notable variability in the number of facilities and prescriptions by state.

Conclusions

There has been exponential increase in the number of INJ-BUP prescriptions but uptake is much less than observed in other countries in shorter time periods. Limited availability at SUD treatment facilities that accept Medicaid may be one barrier to access.
TP53Variant Clusters Stratify the Li-Fraumeni Spectrum and Reveal an Osteosarcoma-Prone Subgroup
Authors: Fischer Nicholas W , Laverty Brianne , Alon Noa , Montellier Emilie , Maxwell Kara N , Kratz Christian P , Hainaut Pierre , Kafri Ran , Malkin David
Published: January 2024

Li-Fraumeni syndrome (LFS) has recently been redefined as a ‘spectrum’ cancer predisposition disorder to reflect its broad phenotypic heterogeneity. The wide functional gradient associated with differentTP53variants is thought to contribute to LFS heterogeneity, although it is still poorly understood and there is an unmet clinical need for risk stratification strategies. Leveraging p53 mutagenesis dataset, we performed an unsupervised cluster analysis that revealed fiveTP53variant clusters with unique structural and functional consequences. Classifying variant carriers according to these clusters stratified cancer onset and survival using discovery and validation cohorts, and exposed important clinical characteristics to consider for patient management. In particular, we identified a subgroup of monomericTP53variant carriers prone to osteosarcoma, along with a cluster associated with less “LFS-like” phenotypes enriched in carriers with no history of cancer. Our classification ofTP53variants demonstrates the existence of a wideTP53-heritable cancer susceptibility spectrum and provides a new framework to delineate carriers toward personalized patient care.
Public Support for Tobacco Endgame Policies: A Systematic Review and Meta-analysis
Authors: Kim Hana , Gartner Coral , Edwards Richard , Puljević Cheneal , Morphett Kylie , Kim Dong Ha , Chun Hae-Ryoung , Ekdahl Martin , Kang Heewon
Published: January 2024

Introductions

An increasing number of countries are adopting the tobacco endgame goal. High levels of public support can accelerate momentum towards implementing tobacco endgame policies. We aimed to conduct a systematic review on the level of public support for tobacco endgame policies and to examine the geographical distribution of studies, support among key populations (adolescents and young adults, people who smoke), and the association between survey design and support.

Methods

We searched Embase, PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2013 onwards. Google was used to search the grey literature. The reference lists of included articles were hand-searched. Studies were included if they reported the proportions of people supporting one or more endgame policies. Risk of bias was assessed using the JBI checklist for prevalence studies.

Results

Forty-seven articles were included. New Zealand and the United States were the countries with the most studies (n=11, respectively). Three-level meta-analyses showed the highest support for mandating a very low nicotine content in tobacco products (76%, 95% CI 61–87%). Meta-regressions were performed to assess the associations of population subgroup and survey design with support levels. The level of support was lower among people who smoke compared to the general population (β range: −1.59 to −0.51). Support for some policies was lower whenneutralordon’t knowresponse options were included.

Conclusions

Public support for most tobacco endgame policies was high.

Implications

Assessing public support can assist with progressing tobacco endgame policies. Policies that are widely supported by the public may be more politically feasible to implement. Qualitative studies and trial studies can further inform communication and implementation strategies for tobacco endgame policies.
Prenatal glycolysis restoration can rescue myocardial hypoplasia caused by platelet isoform of phosphofructokinase 1(PFKP) deficiency
Authors: Zhang Siyao , Sun Hairui , Hao Xiaoyan , Zhi Xu , Liu Ruimin , Yi Tong , Zhang Ye , Gu Xiaoyan , Han Jiancheng , Li Xiaowei , Fan Jiaqi , Yan LiYing , Liu Hankui , Lan Feng , Zhang Hongjia , Qiao Jie , He Yihua
Published: January 2024

Background

Congenital myocardial hypoplasia affects heart function in congenital heart diseases, but its causes and mechanisms are unclear.Methods:Fetuses with myocardial hypoplasia were examined using echocardiography imaging and genetic testing. The identified pathogenic genes were genetically targeted to validate mechanistic findings. We used stem cells and transgenic mice to understand molecular mechanisms and applied Preimplantation Genetic Testing for monogenic defects to obtain healthy offspring. In addition, 1,300 genetic sequencing records were screened to understand the prevalence of the disease and deepen our understanding of myocardial hypoplasia treatment.

Results

This is the first study to link PFKP pathogenic variant to human myocardial hypoplasia. We found that PFKP deficiency decreased embryonic heart glycolysis, resulting in a thinning myocardial wall and impaired cardiac function, attributable to a decline in cardiomyocyte proliferation. The intrauterine supplement with Fructose 1,6-bisphosphate, a direct product of PFKP catalysis, can rescue the main myocardial phenotype of fetal mice. Assisted reproductive technology was used to prevent PFKP pathogenic variant transmission to offspring. Finally, one of the family lines (family 1) obtained a healthy offspring with a normal heart.ConclusionsPFKP plays a key role in regulating glycolysis during embryonic cardiac development. Addressing glycolytic defects is crucial for myocardial hypoplasia. We provide new insights that have implications for genetic interventions, prenatal screening, and targeted intervention strategies.
Association of the rs1042522 SNP with prostate cancer risk: a study of cancer tissues, primary tumor cultures and serum samples from a European Caucasian population
Authors: Toscano-Guerra Emily , Maggio Valentina , García Javier , Semidey Maria Eugenia , Celma Ana , Morote Juan , Torres Inés de , Giralt Marina , Ferrer Roser , Paciucci Rosanna
Published: January 2024

Prostate cancer (PCa) is the most common cancer in men and the third leading cause of cancer death in Europe. TheTP53gene, the most frequently mutated gene in human cancer, is a tumor suppressor gene with crucial functions in preventing tumor development. The single nucleotide polymorphism rs1042522, characterized by the substitution of a proline (PRO) for an arginine (ARG) at the position 72 of the p53 protein (P72R SNP), was studied in 12 primary tumor cultures from prostate biopsies of untreated hormone-naïve patients (hnPCs) with aggressive-metastatic cancer (Gleason ≥8), 11 radical prostatectomies, and a cohort of 94 serums from patient with aggressive prostate cancer using DNA sequencing and melting curve analysis. The results identified a high frequency of the P72R SNP in prostate cancer samples compared to the general European (non-cancer) population, suggesting a very significant association (p<0.0001) between this SNP and the risk of prostate cancer with an odds ratio of 7.937 (IC 95% 5.37-11.00). The G allele (R72) was more frequent in patients with high Gleason scores (≥8) suggesting its association to more undifferentiated-malignant PCa lesions.
Effectiveness and Safety of Type- and Energy-based Extracorporeal Shockwave Therapy in Clinical Practice: Umbrella Review and Evidence Mapping
Authors: Mo Qingcong , Zheng Jialing , Hu Fangfei , Gao Peng , Wu Tong , Wei Simeng , Zhang Jiaqi , Tang Chun-Zhi , Zou Jihua , Zheng Xiaoyan
Published: January 2024

Background

The role of distinct type- and energy-based extracorporeal shockwave therapy (ESWT) in clinical practice is unclear.

Objectives

To appraise meta-analytically determined effectiveness and safety of type- and energy-based ESWT for diseases or conditions, and visualize evidence maps of findings.

Methods

Nine online databases and reference lists were systematically searched for systematic reviews (SRs) of randomized controlled trials (RCTs) evaluating the effectiveness or safety of ESWT from inception to September 2023. SRs were then updated if up-to-date RCTs were eligible. Overall effects were re-estimated using random-effects model and reported as relative risk or standardized mean difference with 95% confidence intervals. Methodological quality, certainty of evidence, and safety were assessed with AMSTAR 2, GRADE tool, and MedDRA, respectively.

Results

Our research identified 210 relevant SRs encompassing 636 RCTs and 41649 participants across 7 therapeutic areas and 37 diseases and conditions. Methodological quality of most published SRs was low or critically low. Four treatment statuses of type- and energy-based ESWT were identified, including potential dominant efficacy (plantar fasciitis, erectile dysfunction, lateral epicondylitis, knee osteoarthritis, frozen shoulder, cerebral palsy spasticity, post-stroke lower limb spasticity; GRADE moderate), potential positive efficacy (chronic prostatitis/chronic pelvic pain syndrome, myofascial pain syndrome, patellar tendinopathy, achilles tendinopathy, stenosing tenosynovitis, frozen shoulder, rotator cuff tear, cerebral palsy spasticity, post-stroke upper limb spasticity, cervical spondylotic radiculopathy; GRADE low or very low), potential similar efficacy (osteonecrosis of the femoral head, plantar heel pain, patellar tendinopathy; GRADE low or very low), and potential adverse efficacy (patellar tendinopathy; GRADE very low). Along with courses of ESWT treatment, pain, flushing, and swelling were the most prevalent side effects and serious adverse reactions were limited.

Conclusion

Variable type- and energy-based ESWT is probably effective and safe in clinical practice. Due to lack of available data and high certainty in current evidence, future research should prioritize large-scale and well-designed studies.

Registration

PROSPERO number CRD42023477234
The Prevalence of Imposter Phenomenon in (Post)graduate Medical Education
Authors: Cheung Jessica , Sibbald Matthew , Ruan Brandon , Sherbino Jonathan
Published: January 2024

Phenomenon

Imposter phenomenon (IP) is the feeling of inadequacy despite demonstrating external standards of success. Few studies have broadly examined the prevalence of IP in resident-physicians. This study assessed the prevalence of self-reported IP in resident-physicians, exploring the correlation of demographic risk factors and feelings of IP.

Approach

All residents, across all years of training and programs at McMaster University during the 2019-2020 academic year were recruited to complete a self-report survey. Survey items gathered demographic information and measured self-reported feelings of IP and Clance Imposter Phenomenon Scale (CIPS) scores.

Findings

519 out of 977 (53.1%) individuals completed the survey. Measured by the CIPS, clinically significant IP occurred in 59.2% (n=307) of participants. After completing the CIPS, participants self-reported feelings of low (25.0%, n=130), medium (41.9%, n=218), high (19.0%, n=99), and intense (3.7%, n= 19) IP. 64.9% (n=337) of respondents felt they hid feelings of IP during residency. 62.4% (n=324) of respondents were unaware of resources available to them as they struggled with feelings of IP. Only female gender was associated with IP (p <0.001).

Insights

IP is highly prevalent across a broad range of residents, independent of clinical discipline and most demographics. Educators and administrators should attend to IP by normalizing the discussion of IP and ensuring adequate access to resources for support.
Applying Multimodal Data Fusion based on Deep Learning Methods for the Diagnoses of Neglected Tropical Diseases: A Systematic Review
Authors: Minyilu Yohannes , Abebe Mohammed , Meshesha Million
Published: January 2024

Neglected tropical diseases (NTDs) are the most prevalent diseases worldwide affecting one-tenth of the world population. Although there are multiple approaches to diagnosing these diseases, using skin manifestations and lesions caused as a result of these diseases along with other medical records is the preferred method. This fact triggers the need to explore and implement a deep learning-based diagnostic model using multimodal data fusion (MMDF) techniques to enhance the diagnostic process. This paper, thus, endeavored to present a thorough systematic review of studies regarding the implementation of MMDF techniques for the diagnoses of skin-related NTDs. To achieve its objective, the study used the PRISMA method based on predefined questions and collected 427 articles from seven major and reputed sources and critically appraised each article. Since no previous studies were found regarding the implementation of MMDF for the diagnoses of skin related NTDs, similar studies using MMDF for the diagnoses of other skin diseases, such as skin cancer, were collected and analyzed in this review to extract information about the implementation of these methods. In doing so, various studies are analyzed using six different parameters including research approaches, disease selected for diagnosis, dataset, algorithms, performance achievements and future directions. Accordingly, although all the studies used diverse research methods and datasets based on their problem, deep learning-based convolutional neural networks (CNN) algorithms are found to be the most frequently used and best performing models in all studies reviewed.
A retrospective investigation of the population structure and geospatial distribution ofSalmonellaParatyphi A in Kathmandu, Nepal
Authors: Mylona Elli , Duy Pham Thanh , Keane Jacqueline , Dongol Sabina , Basnyat Buddha , Dolecek Christiane , Voong Vinh Phat , Tran Vu Thieu Nga , Nguyen Thi Nguyen To , Karkey Abhilasha , Baker Stephen
Published: January 2024

SalmonellaParatyphi A, one of the major etiologic agents of enteric fever, has been on the rise over the last decades in certain endemic regions compared toS.Typhi, the most prevalent cause of enteric fever. Despite this, data on the prevalence and molecular epidemiology ofS.Paratyphi A remain scarce. Here, we analysed the whole genome sequences of a total of 216S. Paratyphi A isolates originating in Nepal between 2005 and 2014, of which 200 were from acute patients and 16 from chronic carriers of enteric fever. By using the recently developed genotyping framework forS. Paratyphi A (paratype), we identified several genotypes circulating in Kathmandu. Importantly, we observed an unusual clonal expansion of genotype 2.4.3 over a four-year period that spread geographically and replaced other genotypes. This rapid genotype replacement is hypothesised to have been driven by both reduced sensitivity to fluoroquinolones and genetic changes to virulence factors, such as functional and structural genes of type 3 secretion systems. Finally, we show that person to person is likely the most common mode of transmission and chronic carriers play a limited role in maintaining disease circulation.
The Evolutionary History of Metastatic Pancreatic Neuroendocrine Tumours Reveals a Therapy Driven Route to High-Grade Transformation
Authors: Backman Samuel , Botling Johan , Nord Helena , Ghosal Suman , Stålberg Peter , Juhlin C. Christofer , Almlöf Jonas , Sundin Anders , Zhang Liang , Moens Lotte , Eriksson Barbro , Welin Staffan , Hellman Per , Skogseid Britt , Pacak Karel , Mollazadegan Kazhan , Åkerström Tobias , Crona Joakim
Published: January 2024

Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular, show frequent progression from a low/intermediate to a high-grade disease. To understand the molecular mechanisms underlying this phenomenon, we performed multi-omics analysis of 32 longitudinal samples from six metastatic PanNET patients. Following MEN1 inactivation, PanNETs exhibit genetic heterogeneity on both spatial and temporal dimensions with parallel and convergent tumuor evolution involving theATRX/DAXXand mTOR pathways. Following alkylating chemotherapy treatment, some PanNETs develop mismatch repair deficiency and acquire a hypermutator phenotype. This DNA hypermutation phenotype was only found in cases that also showed transformation into a high-grade PanNET. Overall, our findings contribute to broaden the understanding of metastatic PanNET, and suggests that therapy driven disease evolution is an important hallmark of this disease.
Biases in the Willingness to Download a mHealth App: A Discrete Choices Experimental Study Among Nigerian Healthcare App Subscribers
Authors: Ogbaga Ignatius Nwoyibe
Published: January 2024

Background

Although there has been an increase in the availability of mobile health (mHealth) tools globally and their potential benefits for both healthcare providers and patients, the adoption of mHealth is still relatively low. Additionally, only a limited number of studies have investigated the intention of individuals to download mHealth apps.

Objective

We conducted a study to explore people’s inclination towards using a health app.

Methods

We conducted the study in Nigeria using a discrete choice experiment. The study had a sample size of 2800 participants who were presented with two different attributes and levels. These attributes were price ($20 = N 17932.80 [at a currency exchange rate of $1= N896.64], and free subscription option) and data protection (with options of data protection vs no data protection). The participants were randomly assigned to the different attribute and level options. For the analysis, we used the conditional logistic model.

Results

According to the results of the study, the likelihood of downloading a mHealth app is significantly higher when the app is offered for free. The study also found that users tend to ignore data protection specifications, and instead prioritize free subscription offers while showing reluctance towards apps that come with a price tag.

Conclusions

The use of mobile health (mHealth) tools has a high potential in reducing healthcare costs and enhancing the efficacy of traditional health interventions and therapies. The major driving forces behind the increasing adoption of mHealth apps in the future are cost reduction and the establishment of sound business models. It is crucial to establish reliable standards for mHealth apps, which can include information about pricing and legislation regarding data protection, to ensure that potential consumers can make informed decisions.
Relationship of subjective and objective cognition with post-stroke mood differs between early and long-term stroke
Authors: Kusec Andrea ,   the OX-CHRONIC Team, Demeyere Nele
Published: January 2024

Background

Depression and anxiety affects 1 in 3 stroke survivors. Performance on standardized objective cognitive tests and self-reported subjective cognitive complaints are associated with concurrent depression and anxiety, but it is unknown whether and how objective and subjective cognition relate to longer-term emotional outcomes.

Method

N =99 stroke survivors (Mage = 68.9,SD= 13.1; Median NIHSS = 5) from the OX-CHRONIC cohort completed measures of depression and anxiety (Hospital Anxiety and Depression Scale; HADS), objective cognition (Oxford Cognitive Screen) and subjective cognitive complaints (Cognitive Failures Questionnaire) at 6-months (Time 1), at ∼4.5 years (Time 2) and ∼5.5 years (Time 3) post-stroke. The contribution of objective and subjective cognition to depression and anxiety was determined via mixed-effects models.

Results

We found no evidence that age, stroke severity, years of education, and participant sex related to changes in HADS-Depression or HADS-Anxiety scores. Objective cognitive impairments at Time 1 (b =-0.79,p< .05) and increases in subjective cognitive complaints at Time 3 (b =0.77,p <.05) related to increased HADS-Depression scores (Marginal R2= 0.22). Only increases in subjective cognitive complaints at Time 3 (b =0.96,p <.05) related to increased HADS-Anxiety scores (Marginal R2= 0.20). When conducting models in reverse, HADS-Depression and HADS-Anxiety scores did not reciprocally explain changes in subjective cognitive complaints.

Conclusions

Objective cognitive abilities are more strongly associated with depression at 6-months post-stroke, while subjective cognitive complaints are more relevant to both long-term post-stroke depression and anxiety.
Human versus Artificial Intelligence: ChatGPT-4 Outperforming Bing, Bard, ChatGPT-3.5, and Humans in Clinical Chemistry Multiple-Choice Questions
Authors: Sallam Malik , Al-Salahat Khaled , Eid Huda , Egger Jan , Puladi Behrus
Published: January 2024

The advances in large language models (LLMs) are evolving rapidly. Artificial intelligence (AI) chatbots based on LLMs excel in language understanding and generation, with potential utility to transform healthcare education and practice. However, it is important to assess the performance of such AI models in various topics to highlight its strengths and possible limitations. Therefore, this study aimed to evaluate the performance of ChatGPT (GPT-3.5 and GPT-4), Bing, and Bard compared to human students at a postgraduate master’s (MSc) level in Medical Laboratory Sciences. The study design was based on the METRICS checklist for the design and reporting of AI-based studies in healthcare. The study utilized a dataset of 60 Clinical Chemistry multiple-choice questions (MCQs) initially conceived for assessment of 20 MSc students. The revised Bloom’s taxonomy was used as the framework for classifying the MCQs into four cognitive categories: Remember, Understand, Analyze, and Apply. A modified version of the CLEAR tool was used for assessment of the quality of AI-generated content, with Cohen’s κ for inter-rater agreement. Compared to the mean students’ score which was 40/60 (66.8%), GPT-4 scored 54/60 (90.0%), followed by Bing (46/60, 76.7%), GPT-3.5 (44/60, 73.3%), and Bard (40/60, 66.7%). Statistically significant better performance was noted in lower cognitive domains (Remember and Understand) in GPT-3.5, GPT-4, and Bard. The CLEAR scores indicated that ChatGPT-4 performance was “Excellent” compared to “Above average” performance of ChatGPT-3.5, Bing, and Bard. The findings indicated that ChatGPT-4 excelled in the Clinical Chemistry exam, while ChatGPT-3.5, Bing, and Bard were above-average. Given that the MCQs were directed to postgraduate students with a high degree of specialization, the performance of these AI chatbots was remarkable. Due to the risks of academic dishonesty and possible dependence on these AI models, the appropriateness of MCQs as an assessment tool in higher education should be re-evaluated.
Sex Differences in the Role of Sleep on Cognition in Older Adults
Authors: Wiranto Yumiko , Siengsukon Catherine , Mazzotti Diego R. , Burns Jeffrey M. , Watts Amber
Published: January 2024

Study Objectives

The study aimed to investigate sex differences in the relationship between sleep quality (self-report and objective) and cognitive function across three domains (executive function, verbal memory, and attention) in older adults.

Methods

We analyzed cross-sectional data from 207 participants with normal cognition or mild cognitive impairment (89 males and 118 females) aged over 60. The relationship between sleep quality and cognitive performance was estimated using generalized additive models. Objective sleep was measured with the GT9X Link Actigraph, and self-reported sleep was measured with the Pittsburgh Sleep Quality Index.

Results

We found that females exhibited stable performance of executive function with up to about 400 minutes of total sleep time, with significant declines in performance (p= 0.02) when total sleep time was longer. Additionally, a longer total sleep time contributed to lower verbal memory in a slightly non-linear manner (p= 0.03). Higher self-reported sleep complaints were associated with poorer executive function in females with normal cognition (p= 0.02). In males, a positive linear relationship emerged between sleep efficiency and executive function (p= 0.04), while self-reported sleep was not associated with cognitive performance in males with normal cognition.

Conclusions

Our findings suggest that the relationships between sleep quality and cognition differ between older males and females, with executive function being the most influenced by objective and self-reported sleep. Interventions targeting sleep quality to mitigate cognitive decline in older adults may need to be tailored according to sex, with distinct approaches for males and females.

Statement of Significance

This research is significant as it addresses the gap in a previously underexplored area of sex differences in the interplay between sleep quality and cognitive function in older populations. By examining both objective and self-reported sleep measures across three cognitive domains, the study provides valuable insights into how sleep impacts various cognitive domains differently in older males and females. Notably, the findings suggest that interventions to improve sleep quality and potentially mitigate cognitive decline may need to be sex-specific.