bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence rate in patients with stage IV breast cancer: a retrospective cohort study
Authors: Grobler Leanda , Orchard Ané , Moodley Shun D. , Pypers Ion , Khan Razeeya 
Published: April 2023

Abstract

Introduction:
Metastatic breast cancer (mBC) remains incurable, with a median overall survival (OS) of approximately 3 years and a 5-year survival rate of approximately 25%, irrespective of the economic classification of the country where treatment is received. Cyclin-dependent kinase (CDK) inhibitors increase overall survival in both first and second-line settings in the treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative mBC. This retrospective cohort study investigated the progression-free survival in women with mBC receiving combination therapy with abemaciclib (CDK4/CDK6 inhibitor) and letrozole or fulvestrant as opposed to abemaciclib only.

Methods:
The study included all eligible women with stage IV breast cancer treated with abemaciclib at a private oncology facility in Johannesburg over the study period. Data were collected from medical records from April 1, 2019 to March 31, 2021. Analyses were conducted to assess the overall survival rate, progression-free survival probability, and safety of abemaciclib in women with stage IV breast cancer.

Results:
Thirty-two patients were eligible for inclusion in this study. The progression-free survival probability was 60% after a period of 17 months, irrespective of treatment options. After 17 months, the OS of women on a combination of abemaciclib and letrozole was 80%, on a combination of abemaciclib and fulvestrant was 80%, and on abemaciclib monotherapy was 70%. The most noted adverse effects were diarrhea (92.0%), neutropenia (92.0%), fatigue (48.0%), and hepatotoxicity (16.0%).

Discussion:
Abemaciclib with endocrine therapy or an aromatase inhibitor provided an improvement in the OS compared with abemaciclib monotherapy. These findings are representative of the use of abemaciclib in a local population and are similar to those of larger studies conducted internationally.
Ossifying Fibromyxoid Tumor of the Genitourinary Tract
Authors: Argani Pedram , Dickson Brendan C. , Gross John M. , Matoso Andres , Baraban Ezra , Antonescu Cristina R. 
Published: April 2023

Ossifying fibromyxoid tumors (OFMTs) are rare mesenchymal neoplasms which typically present in the superficial subcutaneous tissues and have not been reported to arise in visceral organs. We now report 4 molecularly confirmed cases of OFMT involving the genitourinary tract. All patients were males, ranging in age from 20 to 66 years (mean: 43 y). One case each arose in the kidney, ureter, perirenal soft tissue, and penis. All neoplasms demonstrated bland epithelioid to spindled cells set in a variably fibrous to fibromyxoid stroma, and only 1 had a peripheral shell of lamellar bone. All cases appeared well-circumscribed on gross/radiologic examination, though the primary renal neoplasm permeated between native renal tubules. By immunohistochemistry, S100 protein was negative in all 4 cases, while desmin was positive in 2 cases. In 2 cases, the Illumina TruSight RNA Fusion Panel demonstrated a PHF1::TFE3 and EP400::PHF1 fusion, respectively. In the remaining 2 cases, PHF1 gene rearrangement was confirmed by fluorescence in situ hybridization analysis. Due to unusual clinical presentation, lack of S100 positivity, and only occasional bone formation, the correct diagnosis was challenging in the absence of molecular testing. In summary, OFMT may rarely present primarily in the genitourinary tract. Given their nonspecific morphology and immunophenotype, molecular analysis is crucial to establish the correct diagnosis.
Unplanned Extubations Requiring Reintubation in Pediatric Critical Care: An Epidemiological Study
Authors: Wollny Krista , McNeil Deborah , Moss Stephana J. , Sajobi Tolulope , Parsons Simon J. , Benzies Karen , Metcalfe Amy 
Published: April 2023

OBJECTIVES:
Unplanned extubations are an infrequent but life-threatening adverse event in pediatric critical care. Due to the rarity of these events, previous studies have been small, limiting the generalizability of findings and the ability to detect associations. Our objectives were to describe unplanned extubations and explore predictors of unplanned extubation requiring reintubation in PICUs.

DESIGN:
Retrospective observational study and multilevel regression model.

SETTING:
PICUs participating in Virtual Pediatric Systems (LLC).

PATIENTS:
Patients (≤ 18 yr) who had an unplanned extubation in PICU (2012–2020).

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
We developed and trained a multilevel least absolute shrinkage and selection operator (LASSO) logistic regression model in the 2012–2016 sample that accounted for between-PICU variations as a random effect to predict reintubation after unplanned extubation. The remaining sample (2017–2020) was used to externally validate the model. Predictors included age, weight, sex, primary diagnosis, admission type, and readmission status. Model calibration and discriminatory performance were evaluated using Hosmer-Lemeshow goodness-of-fit (HL-GOF) and area under the receiver operating characteristic curve (AUROC), respectively. Of the 5,703 patients included, 1,661 (29.1%) required reintubation. Variables associated with increased risk of reintubation were age (< 2 yr; odds ratio [OR], 1.5; 95% CI, 1.1–1.9) and diagnosis (respiratory; OR, 1.3; 95% CI, 1.1–1.6). Scheduled admission was associated with decreased risk of reintubation (OR, 0.7; 95% CI, 0.6–0.9). With LASSO (lambda = 0.011), remaining variables were age, weight, diagnosis, and scheduled admission. The predictors resulted in AUROC of 0.59 (95% CI, 0.57–0.61); HL-GOF showed the model was well calibrated (p = 0.88). The model performed similarly in external validation (AUROC, 0.58; 95% CI, 0.56–0.61).

CONCLUSIONS:
Predictors associated with increased risk of reintubation included age and respiratory primary diagnosis. Including clinical factors (e.g., oxygen and ventilatory requirements at the time of unplanned extubation) in the model may increase predictive ability.
Comparison of Functional Outcomes following Acute Inpatient Rehabilitation after Acquired Brain Injury before and during the COVID-19 Pandemic
Authors: Wang Christine Yunjae , Petriello Marla , Chou Jiling , Zorowitz Richard David 
Published: April 2023

ABSTRACT

Objective
The objective of this study was to characterize and compare functional outcomes of acquired brain injury (ABI) patients in an inpatient rehabilitation facility in the year before (April 2019 - March 2020) and during the first year (April 2020 – March 2021) of the COVID-19 pandemic, when the most drastic changes in the delivery of healthcare occurred.

Design
In this retrospective single-center chart review study, functional outcomes, based on the Center for Medicare and Medicaid Services (CMS) Inpatient Rehabilitation Facility - Patient Assessment Instrument (IRF-PAI), were obtained and analyzed for patients in acute inpatient rehabilitation with acquired brain injury.

Results
Data from 1330 patients were included for analysis. Functional outcomes of average Self-Care, Bed Mobility, and Transfer scores were statistically, but not clinically, different between groups. More patients in the pandemic group were discharged home (pre-pandemic n = 454 (65.4%); pandemic n = 461 (72.6%); p = 0.011), although they had significantly longer lengths of stay (pre-pandemic median 14.0 [IQR 9.0, 23.0]; pandemic 16.0 [10.0, 23.0]; p = 0.037).

Conclusion
Despite the impact of hospital policies due to the COVID-19 pandemic, similar functional outcomes were obtained for those with ABI after inpatient rehabilitation.
Association of Osteoarthritis Prevalence with Age and Obesity Factors in OECD Countries: Panel Regression Model
Authors: KUŞ Gamze , YASACI Zeynal , BOZ Canser , TÜRKMEN Ezgi 
Published: April 2023

ABSTRACT

Introduction
According to cross-sectional analysis studies supported by microdata, incidence of Osteoarthritis (OA) increases in parallel with ageing and obesity, which are common predictors of the disease. The aim of this study is to reveal whether ageing and obesity have an effect on the increase in OA prevalence by analyzing cross-country data from Organization for Economic Cooperation and Development (OECD) countries.

Methods
We used static panel data regression analysis for 36 countries for the period between 2000 and 2017. Along with OA prevalence, we used a group of people with a BMI ≤ 30 within the population as obesity indicator and those aged +65 within the population as ageing indicator. We calculated the effect of ageing and obesity on OA prevalence using STATA 13 software.

Results
Both variable coefficients, age, and obesity, respectively, were found to be positive and statistically significant at the 1% level. This study shows that both ageing, and obesity contribute to an increase in the OA prevalence based on macro data from 36 OECD countries.

Conclusions
These findings have significant implications that can be used by both the public and policymakers for preventing the OA. Adopting the preventive measures could contribute to decrease in health expenditures.
Complete Resolution of Refractory Axial Low Back Pain Following Myomectomy: A Case Report
Authors: Haber Daniel , Kitei Paul M. , Oboudiyat Sahba , Surrey David E. 
Published: April 2023

Abstract
We present a case of a 39-year-old female with a three-month history of axial low back pain who was found to have a 3.8 cm uterine fibroid, which was initially thought to be an incidental finding. Her low back pain failed to respond to conservative management, and she was eventually referred to gynecology. Her pain subsequently resolved following myomectomy. To the best of our knowledge, complete resolution of low back pain following myomectomy has not been previously described in the literature. Although uterine fibroids are commonly noted on imaging, they are often ignored. We encourage clinicians to consider fibroids as pain generators, especially when treating patients with refractory axial low back pain.
Engagement in an mHealth guided exercise therapy program is associated with reductions in chronic musculoskeletal pain
Authors: Delgado Andrew Dean , Salazar Sophia Isela , Rozaieski Kendal , Putrino David , Tabacof Laura 
Published: April 2023

Abstract

Context
Chronic musculoskeletal (MSK) pain costs the US $980 billion annually. Conservative treatments are the gold standard, but scalable methods of treatment remain to be evaluated.

Objective
To determine the effects of pain reduction and the perceived benefits of an mHealth exercise therapy program.

Design
This is a retrospective observational study on data from 3109 people, (18-98, 49% female) with MSK pain in an mHealth exercise program. Pre-session pain was measured via 11-point NRS and non-standardized single-item questions for work and quality of Life (QoL); all were analyzed using mixed-effects models.

Results
By 11 sessions, there was an estimated a 2.09-point decrease in average NRS pain levels. There was an average percent increase of ~0.7-points for Work-Life and QoL (t????=6,632 = 12.06; p < 0.001). User engagement was high; 46% of participants were performing more than one session per day, and 88% were engaging within a week, indicating the feasibility of the deployment of an mHealth exercise app.

Conclusion
An mHealth exercise program was associated with significant decrease in pain and increased perceived benefits in a large population. These findings serve as preliminary findings of the feasibility for mHealth exercise interventions as scalable tools to improve chronic MSK pain outcomes.
Deep Learning Evaluation of Echocardiograms to Identify Occult Atrial Fibrillation
Authors: Stein Nathan R. , Duffy Grant , Sandhu Roopinder K. , Chugh Sumeet S. , Albert Christine M. , Cheng Susan , Ouyang David , Yuan Neal 
Published: April 2023

ABSTRACTBackgroundAtrial fibrillation (AF) can often be missed by intermittent screening given its frequently paroxysmal and asymptomatic presentation. Deep learning algorithms have been developed to identify patients with paroxysmal AF from electrocardiograms (ECGs) in sinus rhythm. Transthoracic echocardiograms (TTEs) may provide additional structural information complementary to ECGs that could also be used to help identify occult AF.ObjectiveWe sought to determine whether deep learning evaluation of echocardiograms of patients in sinus rhythm could identify occult AF.MethodsWe identified patients who had TTEs performed between 2004 and 2021. We created a two-stage model that (1) distinguished which TTEs were in sinus rhythm and which were in AF and then (2) predicted which of the TTEs in sinus rhythm were in patients with paroxysmal AF. Models were trained from video-based convolutional neural networks using TTE parasternal long axis (PLAX) videos. The AF prediction performance was compared to prediction using clinical variables, CHADSVASc score, and left atrial (LA) size.ResultsOur model trained on 111,319 TTE videos distinguished TTEs in AF from those in sinus rhythm with high accuracy (AUC 0.96, 0.95-0.96). A total of 72,181 TTE videos were in sinus rhythm. When tested on a held-out sample, the model predicted the occurrence of concurrent AF with an AUC of 0.71 (0.69-0.73). Using the max F1 threshold, the PPV was 0.20 and the NPV was 0.95. The model performed better than predicting concurrent AF using clinical risk factors (AUC 0.67, 0.65-0.69), LA area (AUC 0.63, 0.62-0.64), and CHADSVASc (AUC 0.61, 0.60-0.62).ConclusionA deep learning model distinguished AF from sinus rhythm TTEs with high accuracy and predicted the presence of AF within 90 days of sinus rhythm TTEs moderately well, better than clinical variables or LA size alone. TTEs may help inform automated opportunistic AF screening efforts.
The role ofN-glycosylation in spike antigenicity for the SARS-CoV-2 Gamma variant
Authors: Pegg Cassandra L. , Modhiran Naphak , Parry Rhys , Liang Benjamin , Amarilla Alberto A. , Khromykh Alexander A. , Burr Lucy , Young Paul R. , Chappell Keith , Schulz Benjamin L. , Watterson Daniel 
Published: April 2023

AbstractThe emergence of SARS-CoV-2 variants alters the efficacy of existing immunity towards the viral spike protein, whether acquired from infection or vaccination. Mutations that impactN-glycosylation of spike may be particularly important in influencing antigenicity, but their consequences are difficult to predict. Here, we compare the glycosylation profiles and antigenicity of recombinant viral spike of ancestral Wu-1 and the Gamma strain, which has two additionalN-glycosylation sites due to amino acid substitutions in the N-terminal domain (NTD). We found that a mutation at residue 20 from threonine to asparagine within the NTD caused the loss of NTD-specific antibody binding. Glycan site-occupancy analyses revealed that the mutation resulted inN-glycosylation switching to the new sequon at N20 from the native N17 site. Site-specific glycosylation profiles demonstrated distinct glycoform differences between Wu-1, Gamma, and selected NTD variant spike proteins, but these did not affect antibody binding. Finally, we evaluated the specificity of spike proteins against convalescent COVID-19 sera and found reduced cross-reactivity against some mutants, but not Gamma spike compared to Wuhan spike. Our results illustrate the impact of viral divergence on spike glycosylation and SARS-CoV-2 antibody binding profiles.
Novel structural insights on full-length human RAD52: Cryo-EM and beyond
Authors: Balboni Beatrice , Marotta Roberto , Rinaldi Francesco , Girotto Stefania , Cavalli Andrea 
Published: April 2023

AbstractHuman RAD52 is a DNA-binding protein involved in many DNA repair mechanisms and genomic stability maintenance. In the last few years, this protein was discovered to be a promising novel pharmacological target for anticancer synthetic lethality strategies since its inhibition or modulation, under specific genetic conditions, was proved to enhance therapies efficacy in various cancer cell types. Although the interest in RAD52 has exponentially grown in the last decade, most information about its structure and mechanism of action is still missing. This work provides novel insights into full-length RAD52 (RAD52 FL) protein, focusing on its structural and functional characterization. The Cryo-Electron Microscopy (Cryo-EM) structure of RAD52 FL, here presented at a resolution (2.16 Å) higher than the one currently available for RAD52 N-terminal X-ray structure, allows hypothesizing the role of individual amino acid residues. While the N-terminal region of RAD52 FL is structured in an undecameric ring, the C-terminal part is intrinsically disordered as fully characterized through SAXS and biophysical analyses. These detailed (atomic level) structural analyses will substantially impact future characterizations of RAD52 mechanisms of action and inhibitors development, particularly in the context of novel approaches to synthetic lethality.
HCV E1 influences the fitness landscape of E2 and may enhance escape from E2-specific antibodies
Authors: Zhang Hang , Bull Rowena A. , Quadeer Ahmed A. , McKay Matthew R. 
Published: April 2023

AbstractThe Hepatitis C virus (HCV) envelope glycoprotein E1 forms a noncovalent heterodimer with E2, the main target of neutralizing antibodies. How E1-E2 interactions influence viral fitness and contribute to resistance to E2-specific antibodies remains largely unknown. We investigate this problem using a combination of fitness landscape and evolutionary modelling. Our analysis indicates that E1 and E2 proteins collectively mediate viral fitness, and suggests that fitness-compensating E1 mutations may accelerate escape from E2-targeting antibodies. Our analysis also identifies a set of E2-specific human monoclonal antibodies that are predicted to be especially resilient to escape via genetic variation in both E1 and E2, providing directions for robust HCV vaccine development.
Evaluating the use of a novel low-cost measurement insole to characterise plantar foot strain during gait loading regimes
Authors: Crossland Sarah R , Siddle Heidi J , Brockett Claire L , Culmer Peter 
Published: April 2023

ABSTRACTUnder plantar loading regimes, it is accepted that both pressure and shear strain biomechanically contribute to formation and deterioration of diabetic foot ulceration (DFU). Plantar foot strain characteristics in the at-risk diabetic foot are little researched due to lack of measurement devices. Plantar pressure comparatively, is widely quantified and used in the characterisation of diabetic foot ulceration risk, with a range of clinically implemented pressure measurement devices on the market. With the development of novel strain quantification methods in its infancy, feasibility testing and validation of these measurement devices for use is required. Initial studies centre on normal walking speed, reflecting common activities of daily living, but evaluating response to differing gait loading regimes is needed to support the use of such technologies for potential clinical translation. This study evaluates the effects of speed and inclination on stance time, strain location and strain response using a low-cost novel strain measurement insole. The STrain Analysis and Mapping of the Plantar Aspect (STAMPS) insole has been developed, and feasibility tested under self-selected normal walking speeds to characterise plantar foot strain, with testing beyond this limited regime required. A treadmill was implemented to standardise speed and inclination for a range of daily plantar loading conditions. A small cohort, comprising of five non-diabetic participants, were examined at slow (0.75 m/s), normal (1.25 m/s) and brisk (2 m/s) walking speeds and normal speed at inclination (10% gradient). Plantar strain active regions were seen to increase with increasing speed across all participants. With inclination, it was seen that strain active regions reduce in the hindfoot and show a tendency to forefoot with discretionary changes to strain seen. Stance time decreases with increasing speed, as expected, with reduced stance time with inclination. Comparison of the strain response and stance time should be considered when evaluating foot biomechanics in diabetic populations to assess strain time interval effects. This study supports the evaluation of the STAMPS insole to successfully track strain changes under differing plantar loading conditions and warrants further investigation of healthy and diabetic cohorts to assess the implications for use as a risk assessment tool for DFU.
Binary classification machine-learning Unveils Sex-Dependent mutated gene Signatures in Melanoma
Authors: Elkoshi Nadav , Parikh Shivang , Mahameed Sajeda , Meidan Abraham , Rubin Eitan , Levy Carmit 
Published: April 2023

AbstractThere are significant differences in the prevalence of cancer type, primary tumor body site, and mutation load between men and women, but the mechanisms underlying these sex-dependent differences is mostly unknown. Here we used binary classification machine-learning methodology to study sex-correlated somatic mutations signatures in cutaneous melanoma. We identified a number of genes that are more frequently mutated in females compared to males. Mutations in two genes,LAMA2andTPTE, together with a set of specific genes that are not mutated, can predict sex of melanoma patients. Over representation analysis of genes clustered withLAMA2revealed significant enrichment in androgen and estrogen biosynthesis and metabolism pathways, suggesting that mutation ofLAMA2might be involved in biased sex hormone synthesis in melanoma. Taken together, our analysis shows that gender can be predicted based on mutation status of genes in melanoma and that certain mutations are predictive of survival beyond sex differences. Our results will lead to better diagnosis and more effective personalized treatment of melanoma.SummaryIt was observed that between men and women there is a significant difference in the prevalence of cancer type, the primary tumor body site, and the number of mutations found in a given tumor type. However, the mechanisms behind these gender differences are mostly unknown. To investigate sex corelated somatic mutation signatures in cutaneous melanoma we used binary classification machine-learning methodology. We identified specific genes that are more frequently mutated in females compared to males, includingLAMA2andTPTE, which are predictive of gender. We also found a significant enrichment in androgen and estrogen biosynthesis and metabolism pathways clustered withLAMA2, suggesting that mutation ofLAMA2might be involved in biased sex hormone synthesis in melanoma. We showed that gender can be predicted based on mutation status of genes in melanoma and that certain mutations are predictive of survival. Our findings could lead to better diagnosis and more effective personalized treatment of melanoma.