bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin Lesions as a Presenting Feature of Dimorphic T-Lymphoblastic Leukemia in an Adolescent Male
Authors: Chapman Stacy , Almiski Muhamad , Marko Daniel , Sekiguchi Debora , Dawson AJ , Keijzer Richard , Fromm Jonathan , Israels Sara J.
Published: April 2023

Cutaneous involvement is rare in acute lymphoblastic leukemia/lymphoma, particularly within the T-cell lineage. Review of the literature for cutaneous involvement in T-cell lymphoblastic lymphoma/leukemia identifies mostly case reports, with the majority of cases involving adults. We describe an adolescent male presenting with cervical lymphadenopathy and skin lesions leading to a diagnosis of early T-cell precursor lymphoblastic leukemia. Unique to this case is the age of the patient, presence of a dimorphic blast population, and the skin lesions preceding other signs of disease by at least 1 month.
Metastatic Melanoma in Young Child
Authors: Min Victoria , Petit Audrey , Rome Angélique , Andre Nicolas
Published: April 2023

Pediatric melanoma is a rare cancer, especially in young children, and it remains a diagnostic challenge. We report a case of massively metastatic melanoma in young patient with an atypical clinical and biological presentation and with no risk factors.
A Study of Factors Influencing Delayed Diagnosis in Pediatric Cancers: A Step Towards Better Outcomes—A Cross-sectional Study
Authors: Sampagar Abhilasha , Keerthana Sarapu , Dias Merle Casia , Reddy Nalla Anuraag , Patil Neha
Published: April 2023

Annually, India contributes to one-fifth of newly diagnosed pediatric cancers worldwide. Poor outcome in India as compared with developed nations is mainly attributed to delayed diagnosis and study of factors influencing delay in diagnosis holds paramount importance in formulating strategies and counter-measures to improve survival. It was a cross-sectional study conducted on children diagnosed with malignancy at a tertiary care hospital. Diagnosis delay was defined and further divided into patient delay and physician delay. Various patient-related factors and socioeconomic factors that could affect diagnosis were studied. Statistical analysis included descriptive analysis, Mann-Whitney U test, Kruskal-Wallis test, and multivariate linear regression. Of 185 patients enrolled, median diagnosis delay, patient delay, and physician delays were 59, 30, and 7 days respectively. Median diagnosis delay was significantly higher in younger children, children of illiterate parents, and low income. Median diagnosis delay in children presenting to a general practitioner (9 [4 to 29] days) was higher than those presenting to a pediatrician (5.5 [2 to 18] days). Sex, occupation of parents, and distance from oncology center did not affect time for diagnosis. We concluded that augmentation of the parent’s attitudes, increased awareness, and decentralization of specialized pediatric care to rural areas can significantly reduce mortality from, otherwise, curable malignancies.
Neonatal Thrombocytopenia: Differing Characteristics of NAIT Versus Non-NAIT
Authors: Zemer Vered S. , Mousa Katherin , Herscovici Tina , Steinberg-Shemer Orna , Bonstein Lilach , Yacobovich Joanne
Published: April 2023

While neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe neonatal thrombocytopenia good clinical predictors are lacking. We analyzed cases of neonatal thrombocytopenia in Schneider Children’s Medical Center of Israel to pinpoint qualifiers of NAIT (NAIT+) in comparison to non-NAIT (NAIT−) thrombocytopenia. Patient and maternal data were retrospectively collected on all thrombocytopenic newborns undergoing a workup for NAIT in our tertiary center between 2001 and 2016. Among 26 thrombocytopenic neonates, the mean nadir in NAIT+ patients (25×109/L) was significantly lower than NAIT− patients (64×109/L) (P<0.001). 61.5% of NAIT+ infants required treatment compared with 23% of non-NAIT (P=0.015). NAIT+ patients also required more therapeutic modalities than infants with NAIT− thrombocytopenia. Human platelet antigen (HPA)-1a and HPA-5b alloantibodies most frequently caused NAIT. In summary, thrombocytopenia in NAIT+ was significantly more severe compared with NAIT− and more likely to require treatment. In addition, despite the varied ethnic population in Israel, the HPA alloantibodies found in our population were most similar to those common in Western countries. In the absence of rigorous prenatal screening options, we suggest platelet counts below 40 to 50×109/L in a healthy newborn be considered most suggestive for NAIT and warrant urgent NAIT-specific analysis.
CD43-positive, EWSR1::FLI1-rearranged Soft Tissue Sarcoma in a Pediatric Patient With History of B-Cell Acute Lymphoblastic Leukemia
Authors: Ohlsen Timothy J.D. , Rudzinski Erin R. , Bohling Sandra D. , Liu Yajuan J. , Maloney Ezekiel J. , Lindberg Antoinette W. , Albert Catherine M. , Lamble Adam J. , Taylor Mallory R.
Published: April 2023

Ewing sarcoma is a small round blue cell tumor typically characterized by an EWSR1 rearrangement and expression of CD99 and NKX2.2, without expression of hematopoietic markers such as CD45. CD43 is an alternative hematopoietic immunohistochemical marker often utilized in the workup of these tumors and its expression typically argues against Ewing sarcoma. We report a 10-year-old with history of B-cell acute lymphoblastic leukemia presenting with an unusual malignant shoulder mass with variable CD43 positivity, but with an EWSR1::FLI1 fusion detected by RNA sequencing. Her challenging workup highlights the utility of next-generation DNA-based and RNA-based sequencing methods in cases with unclear or conflicting immunohistochemical results.
A Qualitative Descriptive Study of Nurse-Patient Relationships Near End of Life
Authors: Walker Suzanne , Zinck Lindsey , Sherry Victoria , Shea Kimberly
Published: April 2023

Background

The end of life (EOL) period represents a challenging time for patients with cancer as they face disruptions in their relationships with their oncology healthcare providers (HCPs) when moving toward hospice care. Poor communication and severed or altered relationships in physician-patient relationships have been shown to occur near EOL, leading to perceptions of abandonment and other negative consequences for quality EOL care. Little is known, however, about nurse-patient relationships near EOL in the cancer setting.

Objective

The purpose of this qualitative descriptive study was to describe the relationships between patients with cancer and their cancer nurses near EOL.

Methods

A qualitative descriptive methodology was used via semistructured interviews. A total of 9 participants with advanced cancer were enrolled in and completed the study. Data analysis occurred through qualitative content analysis.

Results

The overarching theme woven throughout the narratives was “Good Communication Fosters Nurse-Patient Relationships.” Three additional themes emerged from this main theme: 1) “Valuing Professionalism in the Relationship,” 2) “Embracing Personhood in the Relationship,” and 3) “An Unimaginable Termination.”

Conclusion

Patients with cancer continued to perceive good communication and strong relationships with their cancer nurses even as EOL approached. Themes consistent with negative alterations in these relationships or perceptions of abandonment were not identified.

Implication for Practice

Cancer nurses can foster nurse-patient relationships through patient-centered communication techniques. Spending adequate time engaging with patients as individuals is also recommended. Perhaps most importantly, nurse-patient relationships should continue to be supported as EOL approaches.
Systematic Review of the Effectiveness of Complementary and Alternative Medicine on Nausea and Vomiting in Children With Cancer
Authors: Ho Ka Yan , Lam Katherine Ka Wai , Xia Wei , Liu Qi , Chiu Sau Ying , Chan Godfrey Chi Fung , Li William Ho Cheung
Published: April 2023

Background

Nausea and vomiting are distressing symptoms reported by pediatric oncology patients during cancer treatment. More than 40% of them experience these symptoms even after receiving antiemetics.

Objective

Given the limitations of pharmacological interventions, this systematic review synthesized the evidence for the effectiveness of complementary and alternative medicine in controlling nausea and vomiting among pediatric oncology patients.

Methods

Ten databases were searched to identify relevant randomized controlled trials. The risk of bias of selected studies was graded using the Cochrane risk-of-bias tool for randomized trials. The primary outcomes were nausea and vomiting. The secondary outcomes were intervention adherence and number of adverse events.

Results

Nineteen papers met the inclusion criteria and were included in the review. Sixteen studies showed high risk of bias. The tested interventions were acupuncture, acupressure, aromatherapy, hypnosis, massage, active cognitive distraction/relaxation techniques, creative arts therapy, psychoeducation, and combined massage and acupressure. Acupuncture, hypnosis, and massage interventions improved nausea and vomiting. Fifteen trials reported intervention adherence; only 7 monitored adverse events. The most common reason for dropout was refusal from patients and/or their guardians. A total of 34 adverse events were noted.

Conclusions

There is insufficient evidence that complementary and alternative medicine is effective, feasible, or safe in controlling nausea and vomiting among pediatric oncology patients due to high risk of bias.

Implications for Practice

Acupuncture, hypnosis, and massage appear to have therapeutic benefits. However, more robust studies are needed to address the identified methodological issues and determine the real value of these 3 interventions.
Use of Complementary Pain Management Strategies in Postoperative Cardiac Surgical Patients
Authors: Grady Kimberly , Vital Cidalia , Crisafi Cheryl
Published: April 2023

Background:

Complementary pain management strategies are effective at reducing pain in postsurgical patients.

Local Problem:

Cardiac nurses at a large academic hospital reported inconsistent awareness of patient opioid utilization and poor implementation of complementary pain management strategies.

Methods:

A pre/post–quality improvement project was conducted on 2 inpatient cardiac units. Outcomes included nursing staff's perceived knowledge, confidence, and use of complementary pain management strategies and knowledge of patient postsurgical opioid utilization through calculation of morphine milligram equivalence (MME).

Interventions:

A comprehensive education program was implemented that included increased patient access to pain management resources, nurse education about complementary pain management strategies, and nurse education and access to MME calculations using a custom electronic health record application.

Results:

Nursing staff's perceived knowledge, confidence, and use of complementary pain techniques increased. Patient opioid utilization findings were inconclusive.

Conclusions:

Educational programs about complementary pain management offer promise to improve cardiac postsurgical patient care.
In-Hospital Aspirin Dose as a Risk Factor for Hemorrhagic Transformation in Patients Not Treated With Thrombolysis
Authors: Clares de Andrade Joao Brainer , Mohr Jay P. , Lima Fabricio Oliveira , de Carvalho Joao José Freitas , Maia Barros Levi Coelho , Pontes-Neto Octavio Marques , de Abreu Gabriel Queiroz , Silva Gisele Sampaio
Published: April 2023

Background:

Aspirin is widely used as secondary prophylaxis for acute ischemic stroke. However, its influence on the risk of spontaneous hemorrhagic transformation (HT) is still unclear. Predictive scores of HT have been proposed. We hypothesized that an increased aspirin dose might be harmful in patients at a high risk of HT. This study aimed to analyze the relationship between in-hospital daily aspirin dose (IAD) and HT in patients with acute ischemic stroke.

Methods:

We conducted a retrospective cohort study of patients admitted to our comprehensive stroke center between 2015 and 2017. The attending team defined IAD. All included patients underwent either computed tomography or magnetic resonance imaging within 7 days of admission. The risk of HT was assessed using the predictive score of HT in patients not undergoing reperfusion therapies. Regression models were used to evaluate the correlations between HT and IAD.

Results:

A total of 986 patients were included in the final analysis. The prevalence of HT was 19.2%, and parenchymatous hematomas type-2 (PH-2) represented 10% (n=19) of these cases. IAD was not associated with HT (P=0.09) or PH-2 (P=0.06) among all patients. However, in patients at a higher risk for HT (patients not undergoing reperfusion therapies ≥3), IAD was associated with PH-2 (odds ratio 1.01,95% CI 1.001-1.023,P=0.03) in an adjusted analysis. Taking 200 versus 300 mg aspirin was protective against PH-2 (odds ratio 0.102, 95% CI 0.018-0.563, P=0.009).

Conclusion:

An increased in-hospital aspirin dose is associated with intracerebral hematoma in patients at a high risk of HT. Stratifying the risk of HT may lead to individualized daily aspirin dose choices. However, clinical trials on this topic are required.
Systemic Inflammation Response Index Predicts Clinical Outcomes in Patients With Acute Ischemic Stroke (AIS) After the Treatment of Intravenous Thrombolysis
Authors: Chen Yan-Fang , Qi Shuo , Yu Zi-Jian , Li Jiang-Tao , Qian Ting-Ting , Zeng Ying , Cao Peng
Published: April 2023

Background:

Intravenous thrombolysis (IVT) is one of the most important means of therapy for patients with acute ischemic stroke (AIS). After cerebral infarction, the inflammatory response fulfills an essential role in the pathobiology of stroke, affecting the process of recanalization. Hence, we evaluated the usefulness of the systemic inflammatory response index (SIRI) for the prognosis of patients with AIS.

Methods:

A total of 161 patients suffering from AIS were retrospectively analyzed. SIRI was introduced and calculated using the absolute neutrophil, monocyte, and lymphocyte numbers from the admission blood work. The study outcomes were determined using a modified Rankin Scale (mRS) at the 3-month timepoint, and a favorable clinical outcome was calculated in the mRS score range of 0 to 2. The analysis of receiver operating characteristic (ROC) curves was performed to determine the values of the optimal cutoff of SIRI for the prediction of clinical outcomes. In addition, multivariate analyses were performed to investigate the association between clinical outcomes and SIRI.

Results:

The ROC curve analysis revealed that the ideal SIRI cutoff was at 2.54 [area under the curve, 78.85%; 95% CI, 71.70% to 86.00%; sensitivity, 70.89%; and specificity, 84.14%]. Multivariate analysis indicated that SIRI ≤2.54 (odds ratio, 1.557, 95% CI, 1.269 to 1.840; P=0.021) was an independent predictor of favorable clinical outcomes in patients suffering from AIS after treatment with IVT.

Conclusions:

We preliminary speculate that SIRI may serve as an independent predictor of clinical outcomes with AIS following IVT.
When a Hypersomnolent Hemodialyzed Patient Actually Has a Rare Stroke
Authors: Oliveira Pinheiro Filipe , Reis Maia Ruben , Duarte Delfim , Monteiro Ana , Almeida Jorge
Published: April 2023

Introduction:

Artery of Percheron (AOP) is an uncommon anatomic variant of the arterial supply of the medial thalami. Owing to variable clinical presentation, challenging imaging diagnosis, and its rarity, it is difficult to diagnose AOP infarctions. We present a clinical case of a unique presentation of AOP infarction associated with paradoxical embolism and highlight the atypical clinical manifestations and challenging diagnosis of this stroke syndrome.

Case report:

A 58-year-old White female with chronic renal insufficiency on hemodialysis was admitted to our center with a 10-hour course of hypersomnolence and right-sided ataxia. She had normal body temperature, blood pressure, peripheral oxygen saturation, and heart rate and scored 11 points in the Glasgow Coma Scale and 12 points in National Institutes of Health Stroke Scale. Initial brain computerized tomography scan, electrocardiogram, and thoracic radiography were normal; transcranial Doppler ultrasound showed >50% stenosis at the P2 segment of the right posterior cerebral artery, and transthoracic echocardiogram, a patent foramen ovale and thrombus adherent to the hemodialysis catheter. On day 3, she underwent brain magnetic resonance that showed acute ischemic lesions at the paramedian thalami and the superior cerebral peduncles. AOP infarction due to a paradoxical embolism from a patent foramen ovale with a right atrial thrombus was the final diagnosis.

Conclusions:

AOP infarctions are a rare type of stroke with elusive clinical presentations and frequently, initial imaging assessment is normal. Early recognition is crucial, and a high index of suspicion is needed to suspect this diagnosis.
High-Resolution Magnetic Resonance Imaging in Endovascular Treatment of Vertebrobasilar Junction Stenosis
Authors: Huang Rui , Gao Feng , Mo Dapeng , Yang Ming , Hou Zhikai , Liu Yifan , Cui Rongrong , Kang Kaijiang , Gu Weibin , Miao Zhongrong , Ma Ning
Published: April 2023

Introduction:

Vertebrobasilar junction (VBJ) stenosis is a challenge in endovascular treatment due to structural variants and complexities. The role of high-resolution magnetic resonance imaging (HRMRI) in endovascular treatment for patients with severe VBJ stenosis is uncertain.

Case Report:

Four patients with symptomatic VBJ stenosis underwent HRMRI of the vessel wall before endovascular treatment. In 3 patients, the VBJ could not be visualized on luminal imaging. One of them had a hypoplastic artery and 2 of them had severe stenotic arteries on HRMRI. HRMRI showed an artery with a negative remodeling in a patient with a hypoplastic vertebral artery. One patient had intraplaque hemorrhage and calcification, and 2 patients had calcification in VBJ lesions. Endovascular treatment was performed utilizing HRMRI findings to guide the decision-making process.

Conclusion:

HRMRI provides additional information about the structure and angle of the VBJ, the characteristics and vulnerability of the plaques, and the lesion size, thus helping to improve the operation process and reduce the risk of complications.
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

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

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

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

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

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.
Waste not, want not: upcycling research data from chronic pain trials
Authors: Woodbury Anna
Published: April 2023

Commentary on:

Jacobsen SM, Moore T, Douglas A, Lester D, Johnson AL, Vassar M. Discontinuation and nonpublication analysis of chronic pain randomized controlled trials. PAIN Rep 2023;8:e1069.
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

Background

Atrial 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.

Objective

We sought to determine whether deep learning evaluation of echocardiograms of patients in sinus rhythm could identify occult AF.

Methods

We 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.

Results

Our 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).

Conclusion

A 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

The 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

Human 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

The 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

Under 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

There 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.

It 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.
Characterization of walking locomotion in aged C57BL/10 mice: a comprehensive gait analysis
Authors: Rizzi Joyce Santana , de Barros Almeida Caique , Requena Lorraine Silva , de Almeida Vitoria Duarte , Mininel Thiago Vinícius , da Silva Gabriela Larissa Lima , de Oliveira Patrícia Fidelis , Castro e Horta Júnior José de Anchieta de , Matsumura Cintia Yuri , Ferretti Renato
Published: April 2023

Rodent gait analysis is crucial for modeling human aging, but the lack of comprehensive research on gait in elderly mice limits our ability to translate findings from animal models to human populations. Age-related changes in C57BL/10 strain remain unknown. The state of art protocol for gait analysis uses the CatWalk ™ XT system that allows an understanding of the locomotion pattern by a variety of parameters. We aim to provide relevant information for experimental designs, presenting benchmark data on the performance of locomotion using healthy wild-type mice for future preclinical investigations of neurological and neuromuscular gait patterns. In this study, characterization of walking locomotion was demonstrated from complete gait analysis in aged C57BL/10ScCr/PasUnib mice using open-field, CatWalk, and treadmill tests. Mice were divided into the adult group (6 months; n = 9) and the aged group (20 months; n = 9). Aged mice demonstrated decreased mobility, distance traveled, and general speed in the open-field test. The spatiotemporal and kinetic parameters were altered in aged mice, with lower speed, higher stand time and stride length, and increased base of support and duty cycle in comparison with adult mice. Interlimb coordination has changed in elderly mice. To test whether speed alters the temporal parameters, we used a treadmill test and we demonstrated higher stand time in 20-month-old mice. We demonstrated that changes in gait parameters and mobility represent direct age-related singularities in the wild-type C57BL/10 mice. Overall, aged mice took more time in contact with the ground independently of the speed. These baseline gait results shed light on measures that allow the potential investigation of therapeutics and interventions in gerontology or neuromuscular diseases.
Estimating the reproduction number and transmission heterogeneity from the size distribution of clusters of identical pathogen sequences
Authors: Tran-Kiem Cécile , Bedford Trevor
Published: April 2023

Quantifying transmission intensity and heterogeneity is crucial to ascertain the threat posed by infectious diseases and inform the design of interventions. Methods that jointly estimate the reproduction numberRand the dispersion parameterkhave however mainly remained limited to the analysis of epidemiological clusters or contact tracing data, whose collection often proves difficult. Here, we show that clusters of identical sequences are imprinted by the pathogen offspring distribution, and we derive an analytical formula for the distribution of the size of these clusters. We develop and evaluate a novel inference framework to jointly estimate the reproduction number and the dispersion parameter from the size distribution of clusters of identical sequences. We then illustrate its application across a range of epidemiological situations. Finally, we develop a hypothesis testing framework relying on clusters of identical sequences to determine whether a given pathogen genetic subpopulation is associated with increased or reduced transmissibility. Our work provides new tools to estimate the reproduction number and transmission heterogeneity from pathogen sequences without building a phylogenetic tree, thus making it easily scalable to large pathogen genome datasets.

Significance statement

For many infectious diseases, a small fraction of individuals has been documented to disproportionately contribute to onward spread. Characterizing the extent of superspreading is a crucial step towards the implementation of efficient interventions. Despite its epidemiological relevance, it remains difficult to quantify transmission heterogeneity. Here, we present a novel inference framework harnessing the size of clusters of identical pathogen sequences to estimate the reproduction number and the dispersion parameter. We also show that the size of these clusters can be used to estimate the transmission advantage of a pathogen genetic variant. This work provides crucial new tools to better characterize the spread of pathogens and evaluate their control.