bluuebunny/crossref_metadata_2025 huggingface dataset:
The burden of caring for adults with depression and suicidal ideation in five large European countries: analysis from the 2020 National Health and Wellness Survey
Authors: Jaffe D. H. , Balkaran B. L. , Yue L. , Mulhern-Haughey S. , Anjo J.
Published: November 2021

Background

Suicidal ideation (SI) affects approximately 30–40% of those with major depressive disorder (MDD). To date, studies have examined the substantial humanistic and economic burden to caregivers of persons with MDD, however little is known of the impact of caring for persons with MDD when SI is present. This study examined the additional burden imposed on caregivers for persons with unipolar depression and SI in five major European countries.

Methods

A retrospective, cross-sectional analysis was conducted in five European countries using 2020 Europe National Health Wellness Survey (France, Germany, Italy, Spain and the United Kingdom) to compare differences in health and economic outcomes between caregivers of adults with unipolar depression and SI (CAUD-SI) and caregivers of adults with unipolar depression without SI (CAUD-nSI). The outcomes assessed included health-related quality of life (HRQoL; Medical Outcomes Study Short Form [SF-12v2]), health status (Short-Form 6 Dimension [SF-6D], EuroQol 5-Dimension 5-Level [EQ-5D-5L]), Work productivity and activity impairment (WPAI) and healthcare resource utilization (HRU). Linear mixed models and generalized linear mixed models adjusted for covariates were used to compare the two groups on outcomes of interest.

Results

Of 62,319 respondents, 0.89% (n = 554) were CAUD-SI and 1.34% (n = 837) were CAUD-nSI. In adjusted models, CAUD-SI reported greater humanistic burden than CAUD-nSI, with lower HRQoL (PCS: 42.7 vs. 45.0, p < 0.001 and MCS: 37.5 vs. 38.9, p = 0.007) and health status (SF-6D: 0.57 vs 0.60, p < 0.001 and EQ-5D-5L: 0.58 vs 0.66, p < 001). CAUD-SI respondents reported significantly higher economic burden than CAUD-nSI respondents for WPAI (percent activity impairment: 64.9% vs. 52.5%, p = 0.026) and HRU (provider visits: 10.0 vs. 7.9, p < 0.001, emergency room visits: 1.49 vs. 0.73, p < 0.001 and hospitalizations: 1.03 vs. 0.52, p < 0.001).

Conclusion

In five European countries, caregivers of adults with depression and SI experience additional humanistic and economic burden than caregivers of adults with depression and no SI. Distinguishing caregiver groupings and their unique burden provide important insights for providing targeted support and interventions for both the patient and caregiver.
Optimal movement behaviors: correlates and associations with anxiety symptoms among Chinese university students
Authors: Bu He , He Ai , Gong Na , Huang Liuyue , Liang Kaixin , Kastelic Kaja , Ma Jiani , Liu Yang , Chen Si-Tong , Chi Xinli
Published: November 2021

Background

The Canadian 24-Hour Movement Guidelines for Adults was released in 2020. There is a dearth of evidence on the association between adherence to the 24 h movement guidelines and health indicators. This study aims to (a) explore the associations between potential correlates and meeting the 24 h movement guidelines using a sample of Chinese university students; and (b) examine if meeting 24 h movement guidelines is associated with the severity of anxiety symptoms.

Methods

Cross-sectional findings are based on 1846 Chinese university students (mean age = 20.7 years, 64.0% female). Movement behaviors (physical activity, sedentary behavior, and sleep duration), possible correlates, and anxiety symptoms were measured through self-reported online questionnaires. Logistic regression models were performed to examine the associations.

Results

We found that male students and those who had a mother with a master’s degree or above, more close friends and higher perceived family affluence were more likely to meet the overall 24 h guidelines. Meeting all 24 h movement guidelines presented the lower odds for severe anxiety symptoms than those meeting fewer recommendations in the 24 h movement guidelines.

Conclusions

As one of the first to examine the correlates of adherence to the 24 h movement guidelines and the relationship between anxiety symptoms and meeting the guidelines among Chinese university students, our findings contribute to the growing body of evidence linking movement behaviors, psychosocial correlates, and heath indicators. Schools and health providers can encourage movement behaviors that follow the guidelines on campus.
ICD-11: an international classification of diseases for the twenty-first century
Authors: Harrison James E. , Weber Stefanie , Jakob Robert , Chute Christopher G.
Published: November 2021

Background

The International Classification of Diseases (ICD) has long been the main basis for comparability of statistics on causes of mortality and morbidity between places and over time. This paper provides an overview of the recently completed 11th revision of the ICD, focusing on the main innovations and their implications.

Main text

Changes in content reflect knowledge and perspectives on diseases and their causes that have emerged since ICD-10 was developed about 30 years ago. Changes in design and structure reflect the arrival of the networked digital era, for which ICD-11 has been prepared. ICD-11’s information framework comprises a semantic knowledge base (the Foundation), a biomedical ontology linked to the Foundation and classifications derived from the Foundation. ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS) is the primary derived classification and the main successor to ICD-10. Innovations enabled by the new architecture include an online coding tool (replacing the index and providing additional functions), an application program interface to enable remote access to ICD-11 content and services, enhanced capability to capture and combine clinically relevant characteristics of cases and integrated support for multiple languages.

Conclusions

ICD-11 was adopted by the World Health Assembly in May 2019. Transition to implementation is in progress. ICD-11 can be accessed at icd.who.int.
Identification of missing concepts in biomedical terminologies using sequence-based formal concept analysis
Authors: Zheng Fengbo , Abeysinghe Rashmie , Cui Licong
Published: November 2021

Background

As biomedical knowledge is rapidly evolving, concept enrichment of biomedical terminologies is an active research area involving automatic identification of missing or new concepts. Previously, we prototyped a lexical-based formal concept analysis (FCA) approach in which concepts were derived by intersecting bags of words, to identify potentially missing concepts in the National Cancer Institute (NCI) Thesaurus. However, this prototype did not handle concept naming and positioning. In this paper, we introduce a sequenced-based FCA approach to identify potentially missing concepts, supporting concept naming and positioning.

Methods

We consider the concept name sequences as FCA attributes to construct the formal context. The concept-forming process is performed by computing the longest common substrings of concept name sequences. After new concepts are formalized, we further predict their potential positions in the original hierarchy by identifying their supertypes and subtypes from original concepts. Automated validation via external terminologies in the Unified Medical Language System (UMLS) and biomedical literature in PubMed is performed to evaluate the effectiveness of our approach.

Results

We applied our sequenced-based FCA approach to all the sub-hierarchies under Disease or Disorder in the NCI Thesaurus (19.08d version) and five sub-hierarchies under Clinical Finding and Procedure in the SNOMED CT (US Edition, March 2020 release). In total, 1397 potentially missing concepts were identified in the NCI Thesaurus and 7223 in the SNOMED CT. For NCI Thesaurus, 85 potentially missing concepts were found in external terminologies and 315 of the remaining 1312 appeared in biomedical literature. For SNOMED CT, 576 were found in external terminologies and 1159 out of the remaining 6647 were found in biomedical literature.

Conclusion

Our sequence-based FCA approach has shown the promise for identifying potentially missing concepts in biomedical terminologies.
Identification of asthma control factor in clinical notes using a hybrid deep learning model
Authors: Agnikula Kshatriya Bhavani Singh , Sagheb Elham , Wi Chung-Il , Yoon Jungwon , Seol Hee Yun , Juhn Young , Sohn Sunghwan
Published: November 2021

Background

There are significant variabilities in guideline-concordant documentation in asthma care. However, assessing clinician’s documentation is not feasible using only structured data but requires labor-intensive chart review of electronic health records (EHRs). A certain guideline element in asthma control factors, such as review inhaler techniques, requires context understanding to correctly capture from EHR free text.

Methods

The study data consist of two sets: (1) manual chart reviewed data—1039 clinical notes of 300 patients with asthma diagnosis, and (2) weakly labeled data (distant supervision)—27,363 clinical notes from 800 patients with asthma diagnosis. A context-aware language model, Bidirectional Encoder Representations from Transformers (BERT) was developed to identify inhaler techniques in EHR free text. Both original BERT and clinical BioBERT (cBERT) were applied with a cost-sensitivity to deal with imbalanced data. The distant supervision using weak labels by rules was also incorporated to augment the training set and alleviate a costly manual labeling process in the development of a deep learning algorithm. A hybrid approach using post-hoc rules was also explored to fix BERT model errors. The performance of BERT with/without distant supervision, hybrid, and rule-based models were compared in precision, recall, F-score, and accuracy.

Results

The BERT models on the original data performed similar to a rule-based model in F1-score (0.837, 0.845, and 0.838 for rules, BERT, and cBERT, respectively). The BERT models with distant supervision produced higher performance (0.853 and 0.880 for BERT and cBERT, respectively) than without distant supervision and a rule-based model. The hybrid models performed best in F1-score of 0.877 and 0.904 over the distant supervision on BERT and cBERT.

Conclusions

The proposed BERT models with distant supervision demonstrated its capability to identify inhaler techniques in EHR free text, and outperformed both the rule-based model and BERT models trained on the original data. With a distant supervision approach, we may alleviate costly manual chart review to generate the large training data required in most deep learning-based models. A hybrid model was able to fix BERT model errors and further improve the performance.
2D-echocardiography vs cardiac MRI strain: a prospective cohort study in patients with HER2-positive breast cancer undergoing trastuzumab
Authors: Bouwer Nathalie I. , Liesting Crista , Kofflard Marcel J. M. , Brugts Jasper J. , Kock Marc C. J. , Kitzen Jos J. E. M. , Levin Mark-David , Boersma Eric
Published: November 2021

Background

We aimed to study the predictive value of early two-dimensional echocardiography (2DE) speckle tracking (ST) for left ventricular ejection fraction (LVEF) changes during trastuzumab treatment for HER2-positive breast cancer.

Methods

HER2-positive breast cancer patients receiving trastuzumab, with or without anthracycline, underwent 2DE-ST at baseline and after 3 and 6 months (m) trastuzumab. Cardiac magnetic resonance (CMR) imaging (with ST) was performed at baseline and 6 m. We studied the correlation between 2DE-ST- and CMR-derived global longitudinal strain (GLS) and global radial strain (GRS) measured at the same time. Additionally, we associated baseline and 3 m 2DE-ST measurements with later CMR-LVEF, and with cardiotoxicity, defined as CMR-LVEF < 45% and/or absolute decline > 10% during trastuzumab.

Results

Forty-seven patients were included. Median baseline LVEF was 60.4%. GLS measurements based on 2DE-ST and CMR showed weak correlation (Pearson’s r = 0.33; p = 0.041); GRS measurements were uncorrelated (r = 0.09; p = 0.979). 2DE-LVEF at baseline and 3 m, and 2DE-ST-GLS at 3 m were predictive of CMR-LVEF at 6 m. In contrast, the change in 2DE-ST-GLS at 3 m was predictive of the change in CMR-LVEF at 6 m, whereas the change in 2DE-LVEF was not. Importantly, the 11 patients who developed cardiotoxicity (28%) had larger 2DE-ST-GLS change at 3 m than those who did not (median 5.2%-points versus 1.7%-points; odds ratio for 1% difference change 1.81, 95% confidence interval 1.11–2.93; p = 0.016; explained variance 0.34).

Conclusions

Correlations between 2DE-ST and CMR-derived measurements are weak. Nevertheless, ST-measurements appeared useful to improve the performance of 2DE in predicting LVEF changes after 6 m of trastuzumab treatment.
BH3-mimetics: recent developments in cancer therapy
Authors: Townsend Paul A. , Kozhevnikova Maria V. , Cexus Olivier N. F. , Zamyatnin Andrey A. , Soond Surinder M.
Published: November 2021

The hopeful outcomes from 30 years of research in BH3-mimetics have indeed served a number of solid paradigms for targeting intermediates from the apoptosis pathway in a variety of diseased states. Not only have such rational approaches in drug design yielded several key therapeutics, such outputs have also offered insights into the integrated mechanistic aspects of basic and clinical research at the genetics level for the future. In no other area of medical research have the effects of such work been felt, than in cancer research, through targeting the BAX-Bcl-2 protein-protein interactions. With these promising outputs in mind, several mimetics, and their potential therapeutic applications, have also been developed for several other pathological conditions, such as cardiovascular disease and tissue fibrosis, thus highlighting the universal importance of the intrinsic arm of the apoptosis pathway and its input to general tissue homeostasis. Considering such recent developments, and in a field that has generated so much scientific interest, we take stock of how the broadening area of BH3-mimetics has developed and diversified, with a focus on their uses in single and combined cancer treatment regimens and recently explored therapeutic delivery methods that may aid the development of future therapeutics of this nature.
The genetic case for cardiorespiratory fitness as a clinical vital sign and the routine prescription of physical activity in healthcare
Authors: Hanscombe Ken B. , Persyn Elodie , Traylor Matthew , Glanville Kylie P. , Hamer Mark , Coleman Jonathan R. I. , Lewis Cathryn M.
Published: November 2021

Background

Cardiorespiratory fitness (CRF) and physical activity (PA) are well-established predictors of morbidity and all-cause mortality. However, CRF is not routinely measured and PA not routinely prescribed as part of standard healthcare. The American Heart Association (AHA) recently presented a scientific case for the inclusion of CRF as a clinical vital sign based on epidemiological and clinical observation. Here, we leverage genetic data in the UK Biobank (UKB) to strengthen the case for CRF as a vital sign and make a case for the prescription of PA.

Methods

We derived two CRF measures from the heart rate data collected during a submaximal cycle ramp test: CRF-vo2max, an estimate of the participants' maximum volume of oxygen uptake, per kilogram of body weight, per minute; and CRF-slope, an estimate of the rate of increase of heart rate during exercise. Average PA over a 7-day period was derived from a wrist-worn activity tracker. After quality control, 70,783 participants had data on the two derived CRF measures, and 89,683 had PA data. We performed genome-wide association study (GWAS) analyses by sex, and post-GWAS techniques to understand genetic architecture of the traits and prioritise functional genes for follow-up.

Results

We found strong evidence that genetic variants associated with CRF and PA influenced genetic expression in a relatively small set of genes in the heart, artery, lung, skeletal muscle and adipose tissue. These functionally relevant genes were enriched among genes known to be associated with coronary artery disease (CAD), type 2 diabetes (T2D) and Alzheimer’s disease (three of the top 10 causes of death in high-income countries) as well as Parkinson’s disease, pulmonary fibrosis, and blood pressure, heart rate, and respiratory phenotypes. Genetic variation associated with lower CRF and PA was also correlated with several disease risk factors (including greater body mass index, body fat and multiple obesity phenotypes); a typical T2D profile (including higher insulin resistance, higher fasting glucose, impaired beta-cell function, hyperglycaemia, hypertriglyceridemia); increased risk for CAD and T2D; and a shorter lifespan.

Conclusions

Genetics supports three decades of evidence for the inclusion of CRF as a clinical vital sign. Given the genetic, clinical and epidemiological evidence linking CRF and PA to increased morbidity and mortality, regular measurement of CRF as a marker of health and routine prescription of PA could be a prudent strategy to support public health.
Health disparities in chronic back pain and associated mortality seen in ischemic cardiac disease: a commentary
Authors: Patel Ashruta
Published: November 2021

Prescription opioid use for nonmalignant chronic pain has grown in the US over the last decade. Those with chronic back pain have a higher risk of mortality from ischemic heart disease than those without. Studies have demonstrated a higher prevalence of cardiac disease in adults who report chronic pain. In addition, there is research that supports some association with pain sites and cardiovascular morbidity. Studies have also shown a high-grade chronic neck pain to be more associated with cardiovascular conditions when compared to moderate or low-grade chronic pain. Given this information, it is important to assess pain medication burden present in those who have a diagnosis of coronary artery disease and chronic lower back pain.
A robust and stable gene selection algorithm based on graph theory and machine learning
Authors: Saha Subrata , Soliman Ahmed , Rajasekaran Sanguthevar
Published: November 2021

Background

Nowadays we are observing an explosion of gene expression data with phenotypes. It enables us to accurately identify genes responsible for certain medical condition as well as classify them for drug target. Like any other phenotype data in medical domain, gene expression data with phenotypes also suffer from being a very underdetermined system. In a very large set of features but a very small sample size domain (e.g. DNA microarray, RNA-seq data, GWAS data, etc.), it is often reported that several contrasting feature subsets may yield near equally optimal results. This phenomenon is known as instability. Considering these facts, we have developed a robust and stable supervised gene selection algorithm to select a set of robust and stable genes having a better prediction ability from the gene expression datasets with phenotypes. Stability and robustness is ensured by class and instance level perturbations, respectively.

Results

We have performed rigorous experimental evaluations using 10 real gene expression microarray datasets with phenotypes. They reveal that our algorithm outperforms the state-of-the-art algorithms with respect to stability and classification accuracy. We have also performed biological enrichment analysis based on gene ontology-biological processes (GO-BP) terms, disease ontology (DO) terms, and biological pathways.

Conclusions

It is indisputable from the results of the performance evaluations that our proposed method is indeed an effective and efficient supervised gene selection algorithm.
Unicompartmental knee arthroplasty: A PearlDiver study evaluating complications rates, opioid use and utilization in the Medicare population
Authors: Morris Brandon L. , Ayres Jack M. , Reinhardt Daniel , Tarakemeh Armin , Mullen Scott , Schroeppel J. Paul , Vopat Bryan G.
Published: November 2021

Purpose

Despite increased utilization of unicompartmental knee arthroplasty (UKA) for unicompartmental knee osteoarthritis, outcomes in Medicare patients are not well-reported. The purpose of this study is to analyze practice patterns and outcome differences between UKA and TKA in the Medicare population. It is hypothesized that UKA utilization will have increased over the course of the study period and that UKA will be associated with reduced opioid use and lower complication rates compared to TKA.

Methods

Using PearlDiver, the Humana Claims dataset and the Medicare Standard Analytic File (SAF) were analyzed. Patients who underwent UKA and TKA were identified by CPT codes. Postoperative complications were identified by ICD-9/ICD-10 codes. Opioid use was analyzed by the number of days patients were prescribed opioids postoperatively. Survivorship was defined as conversion to TKA.

Results

In the Humana dataset, 7,808 UKA and 150,680 TKA patients were identified. 8-year survivorship was 87.7% (95% CI [0.861,0.894]). Postoperative opioid use was significantly higher after TKA (186.1 days) compared to UKA (144.7 days) (p < 0.01, Δ = 41.1, 95% CI = [30.41, 52.39]). In the SAF dataset, 20,592 UKA patients and 110,562 TKA patients were identified. Survivorship was highest in patients > 80 years old and lowest in patients < 70 years old. In both datasets, postoperative complication rates were higher in TKA patients compared to UKA patients in nearly all categories.

Conclusions

UKA represents an increasingly utilized treatment for osteoarthritis in the Medicare population and may be comparatively advantageous to TKA due to reduced opioid use and complication rates after surgery.

Level of evidence

Level III
Clinical evaluation of an authorized medical equipment based on high performance liquid chromatography for measurement of serum voriconazole concentration
Authors: Oda Kazutaka , Uchino Shota , Kurogi Kayo , Horikawa Mai , Matsumoto Naoya , Yonemaru Kou , Arakaki Hitomi , Katsume Taiki , Matsuyama Kaho , Katanoda Tomomi , Narita Yuki , Iwamura Koji , Jono Hirofumi , Saito Hideyuki
Published: November 2021

Background

Therapeutic drug monitoring for voriconazole is recommended for its optimum pharmacotherapy. Although the feedback of the measurement result of serum voriconazole concentration by outsourcing needs a certain time (days within a 1 week), there was no medical equipment for the measurement available in clinical practice. Recently, a medical equipment based on high performance liquid chromatography, named LM1010, has been developed and authorized for clinical use. In this study, to validate the clinical performance of LM1010, we compared the measured serum voriconazole concentrations by LM1010 with those by outsourcing measurement using liquid chromatography-tandem mass spectrometry.

Methods

We conducted the observational study approved by the institutional review board of Kumamoto University Hospital (No. 1786). Residual serum samples harvested for therapeutic drug monitoring were separated. Measured concentrations by LM1010 by the standard filter method (needs serum volume of > 400 μL) or the dilute method (needs serum volume of 150 μL) were compared with those by outsourcing, respectively. Acceptable measurement error range of 0.72–1.33 was considered. There were 69 serum samples, where the 35 or 34 samples were employed for evaluation of the standard filter method or the dilute method, respectively.

Results

The measured concentration using the standard filter method/outsourcing was 2.22/2.10 μg/mL as the median, 1.57–3.40/1.53–3.62 as the interquartile range, < 0.2–10.76/< 0.2–11.46 μg/mL as the range, while those using the dilute method/outsourcing was 2.36/2.29 μg/mL as the median, 1.08–2.94/1.03–3.06 as the interquartile range, 0.24–10.00/< 0.2–10.85 μg/mL as the range. The regression line for the standard filter method or the dilute method were y = 0.935x + 0.154 or y = 0.933x + 0.162, respectively. The standard filter method or the dilute method showed 11.4% samples (4/35, 95%CI 3.2–26.7%) or 8.8% samples (3/34, 95%CI 1.9–23.7%) out of the acceptable measurement error range, respectively.

Conclusion

Measurement of serum voriconazole concentration by LM1010 can be acceptable in clinical TDM practice.
Efficacy and safety of Cineole (Soledum®) in the treatment of patients with acute bronchitis: results of an open-label randomized clinical phase III study
Authors: Kardos Peter , Khaletskaya Olga , Kropova Olga
Published: November 2021

Background

Cineole has documented anti-inflammatory, expectorant, and mucolytic properties and has shown to be a valuable treatment option in different airway diseases. Our study examined whether a therapy with Cineole as add on to an antiviral therapy can relieve symptoms of acute bronchitis, and accelerate recovery in everyday practice.

Methods

In an open-label, randomized, parallel-group phase III clinical trial, 132 patients diagnosed with “acute bronchitis” or “acute tracheobronchitis” were included and treated with 3 × 200 mg of Cineole on top of antiviral treatment, or antiviral treatment alone (Ingavirin® 90 mg), per day for 4–9 days. The primary outcome measure was the change in cough frequency assessed in a Cough Frequency Assessment Scale, secondary outcomes were the total Bronchitis Severity Scale (BSS), as well as individual symptoms of the BSS score. Adverse events were collected for safety analysis. The study sites were located in Russia.

Results

After 4 days of therapy, there was a significant difference between the groups in favour of the patients treated with Cineole which persisted until the end of the study. At that time, cough during the day, assessed by the Cough Frequency Assessment Scale, was absent in 14 patients in the Cineole group (21.5%), compared to 4 (6.2%) patients in the control arm (p = 0.0203), which was replicated using the BSS individual cough score. In addition, significant improvements in the individual symptoms of the BSS in patients taking Cineole were documented.

The study drug showed good tolerability without differences to antiviral treatment and results were in line with previous experiences with this drug.

Conclusions

Assessment after 4 days of treatment with additional Cineole showed a significant reduction of cough frequency and other symptoms of acute bronchitis compared to antiviral treatment alone. In addition, patients recovered faster from the disease. Additional treatment with Cineole is a valuable treatment option in acute bronchitis.

Trial registration

Ministry of Health, Russia, No. 592. Registered 19 October 2015.
Drivers of understory plant communities in Sierra Nevada mixed conifer forests with pyrodiversity
Authors: Wilkin Kate , Ponisio Lauren , Fry Danny L. , Collins Brandon M. , Moody Tadashi , Stephens Scott L.
Published: November 2021

Background

Fire suppression in western North America increased and homogenized overstory cover in conifer forests, which likely affected understory plant communities. We sought to characterize understory plant communities and their drivers using plot-based observations from two contemporary reference sites in the Sierra Nevada, USA. These sites had long-established natural fire programs, which have resulted in restored natural fire regimes. In this study, we investigated how pyrodiversity—the diversity of fire size, severity, season, and frequency—and other environment factors influenced species composition and cover of forest understory plant communities.

Results

Understory plant communities were influenced by a combination of environmental, plot-scale recent fire history, and plot-neighborhood pyrodiversity within 50 m. Canopy cover was inversely proportional to understory plant cover, Simpson’s diversity, and evenness. Species richness was strongly influenced by the interaction of plot-based fire experience and plot-neighborhood pyrodiversity within 50 m.

Conclusions

Pyrodiversity appears to contribute both directly and indirectly to diverse understory plant communities in Sierra Nevada mixed conifer forests. The indirect influence is mediated through variability in tree canopy cover, which is partially related to variation in fire severity, while direct influence is an interaction between local and neighborhood fire activity.
Role of DWI in evaluation of HCC after radiofrequency ablation compared to dynamic MRI using MRI (3 T)
Authors: Elrefaey Hasan Bahaa Mohamed , Abd ElHamid Hanaa Abd ElKader , Khater Nivan Hany , ElGendy Waseem , Abdelrahman Ahmed S.
Published: November 2021

Background

The purpose of this study was to investigate the diagnostic performance of diffusion weight imaging (DWI), apparent diffusion coefficient (ADC) map, normalized ADC liver, and normalized ADC spleen compared to the dynamic contrast-enhanced MRI (DCE-MRI) in the evaluation of residual hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) using 3 T (T) magnetic resonance imaging (MRI).

Results

A prospective study was performed on 40 patients with radiofrequency-ablated HCC, and 15 (37.5%) patients had viable lesion post-RFA, while 25 (62.5%) had non-viable lesions. DCE-MRI had a sensitivity, specificity, and accuracy of 100%, 100%, and 100%, respectively, compared to DWI which had a sensitivity, specificity, and accuracy of 80%, 88%, and 85%, respectively, for identifying post-RFA viable HCC. The sensitivity, specificity, and accuracy of ADC at a cutoff value of 1.01 × 10−3 mm2/s were 80%, 100%, and 97.1%, respectively. The optimal cutoff value of normalized ADC liver was 0.81 with a sensitivity of 73.3%, specificity of 96%, and accuracy of 92.8%. The sensitivity, specificity, and accuracy of normalized ADC spleen at a cutoff value of 1.22 were 80%, 92%, and 91.1%, respectively.

Conclusions

DWI-MRI is a reliable technique for assessing HCC after radiofrequency ablation. DWI-MRI with ADC may be used as an alternate sequence for assessing radiofrequency-ablated lesions in individuals who have a contraindication to the contrast media, and the normalized ADC value may be of additional benefit.
The Tietz syndrome associated with cardiac malformation: a case report with literature review
Authors: Lakhdar Youssef , Abou El Houda Hind , Mounji Houda , Elfakiri Mehdi , Rochdi Youssef , Moutaouakil Abdeljalil , Raji Abdelaziz
Published: November 2021

Background

Tietz syndrome is a very rare clinical entity characterized by the association of profound bilateral congenital sensorineural deafness and generalized hypopigmentation of skin, eyes, and integuments (snow white appearance). It is an autosomal dominant syndrome due to a mutation in the melanocyte inducing transcription factor (MITF) gene. The association of a heart malformation has never been reported in this syndrome.

Case presentation

We report two cases of two cousins aged 5 years and 20 months respectively with a history of first degree consanguineous parents. Both girls presented with diffuse hypopigmentation of the skin, blond hair, blue eyes, and bilateral diffuse retinal hypopigmentation at ocular fundus exam. Bilateral profound sensorineural hearing loss was confirmed by auditory brainstem response in both cases. Echocardiography revealed a cardiac malformation such as interventricular communication in the older cousin and interatrial communication in the younger cousin. The family investigation did not reveal a similar case among ancestors. The diagnosis of Tietz syndrome was based on clinical criteria and pedigree. The older cousin underwent a total optical correction and a right unilateral cochlear implantation followed by speech therapy with a satisfactory result after a follow-up of two years. Unfortunately, the little cousin died following a head trauma.

Conclusions

Tietz syndrome is a rare autosomal dominant genetic disorder, characterized by generalized albinism with bilateral profound hearing loss. It results from a nontruncating mutation in the basic domain of in the MITF gene. Its management must include, in addition to hearing and ophthalmic rehabilitation, the research and treatment of cardiac malformations which may be life-threatening.
CAR-T Cells Targeting TSHR Demonstrate Safety and Potent Preclinical Activity Against Differentiated Thyroid Cancer
Authors: Li Hanning , Zhou Xiang , Wang Ge , Hua Dongyu , Li Shuyu , Xu Tao , Dong Menglu , Cui Xiaoqing , Yang Xue , Wu Yonglin , Cai Miaomiao , Liao Xinghua , Zhang Tongcun , Yang Zhifang , Du Yaying , Li Xingrui
Published: November 2021

Background

Chimeric antigen receptor T cells (CAR-Ts) have demonstrated remarkable efficacy in hematological cancers but have not yet translated in treating solid tumors. The significant hurdles limiting CAR-T therapy were from a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present TSH receptor (TSHR) as a putative target for CAR-T therapy of differentiated thyroid cancer (DTC).

Methods

We undertook a large-scale screen on thyroid cancer tissues and multiple internal organs through bioinformatical analysis and immunohistochemistry to date TSHR expression. Using 3 previously described monoclonal antibodies, we generated 3 third-generation CAR-Ts. We tested anti-TSHR CAR-T in vitro activity by T-cell function and killing assay. Then we tested preclinical therapeutical efficacy in a xenograft mouse model of DTC and analyzed mice’s physical conditions and histological abnormalities to evaluate anti-TSHR CAR-T’s safety.

Results

TSHR is highly and homogeneously expressed on 90.8% (138/152) of papillary thyroid cancer, 89.2% (33/37) of follicular thyroid cancer, 78.2% (18/23) of cervical lymph node metastases, and 86.7% of radioactive iodine resistance diseases. We developed 3 novel anti-TSHR CAR-Ts from monoclonal antibodies M22, K1-18, and K1-70; all 3 CAR-Ts mediate significant antitumor activity in vitro. Among these, we demonstrate that K1-70 CAR-T can have therapeutical efficacy in vivo, and no apparent toxicity has been observed.

Conclusion

TSHR is a latent target antigen of CAR-T therapy for DTC. Anti-TSHR CAR-T could represent a therapeutic option for patients with locoregional relapsed or distant metastases of thyroid cancer and should be tested in carefully designed clinical trials.
Primary Hyperparathyroidism Is Associated With Shorter QTc Intervals, but Not Arrhythmia
Authors: Stewart Latoya A , Steinl Gabrielle K , Huang Bernice L , McManus Catherine , Lee James A , Kuo Jennifer H , Walker Marcella D
Published: November 2021

Context

Primary hyperparathyroidism (PHPT) is associated with subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited.

Objective and Design

Retrospective cross-sectional comparison of cardiac conduction in patients with PHPT or thyroid disease (TD).

Participants and Setting

Patients ≥40 years old who underwent parathyroidectomy or thyroidectomy at a single tertiary institution from 2013 to 2018.

Methods and Outcomes

Demographics and preoperative electrocardiogram (EKG) parameters were compared using the Mann-Whitney U, chi-square test, and linear regression.

Results

A total of 1242 patients were included: 49.8% PHPT (n = 619) and 50.2% TD (n = 623). Median age was 60.5 years [interquartile range (IQR) 53.6-67.9]. Compared to controls, PHPT patients had higher median serum calcium [10.7 mg/dL (IQR 10.4-11.1) vs 9.5 mg/dL (IQR 9.3-9.8), P < 0.001] as expected, as well as, a higher prevalence of hyperlipidemia (49% vs 36%, P < 0.001) and hypertension (50.1% vs 42.2%, P < 0.01). Based on EKG, there was no difference in PR interval or the prevalence of arrhythmia, atrioventricular block, ST segment/T wave changes, premature ventricular complexes, right bundle branch block, or left bundle branch block after adjusting for covariates. The PHPT group had a lower mean corrected QT interval (414 ± 24) ms vs 422 ± 24 ms, P < 0.01), adjusted for covariates. Serum calcium predicted QTc independently of age, sex, and other covariates.

Conclusions

In the largest study to date, PHPT patients had shorter QTc intervals compared to TD controls but no increased prevalence of arrhythmia based on preoperative EKG.
Post-infarction ventricular septal rupture with a contained right ventricular pseudoaneurysm formation
Authors: Melina Giovanni , Polidori Tiziano , Caruso Damiano , Rucci Carlotta , Tremamunno Giuseppe , Bianchini Roberto , Autore Camillo , Laghi Andrea
Published: November 2021

Mechanical complication of acute myocardial infarction, such as left ventricular free-wall or septal rupture, pseudo-aneurysm or true aneurysm, are uncommon but potentially fatal conditions, that require an early diagnosis and management. We describe a case of post-infarction ventricular septal rupture with pseudoaneurysm formation included in the right ventricle.
Are simple verbal instructions sufficient to ensure that bladder volume does not deteriorate prostate position reproducibility during spot scanning proton therapy?
Authors: Nishioka Kentaro , Gotoh Kento , Hashimoto Takayuki , Abe Takashige , Osawa Takahiro , Matsumoto Ryuji , Yokota Isao , Katoh Norio , Kinoshita Rumiko , Yasuda Koichi , Yakabe Toshiaki , Yoshimura Takaaki , Takao Seishin , Shinohara Nobuo , Aoyama Hidefumi , Shimizu Shinichi , Shirato Hiroki
Published: November 2021

Objectives:

The purpose of this study is to investigate whether verbal instructions are sufficient for bladder volume (BV) control not to deteriorate prostate position reproducibility in image-guided spot scanning proton therapy (SSPT) for localized prostate cancer.

Methods:

A total of 268 treatment sessions in 12 consecutive prostate cancer patients who were treated with image-guided SSPT with fiducial markers were retrospectively analyzed. In addition to strict rectal volume control procedures, simple verbal instructions to void urine one hour before the treatment were used here. The BV was measured by a Bladder Scan just before the treatment, and the prostate motion was measured by intraprostatic fiducial markers and two sets of X-ray fluoroscopy images. The correlation between the BV change and prostate motion was assessed by linear mixed-effects models and systematic and random errors according to the reproducibility of the BV.

Results:

The mean absolute BV change during treatment was from −98.7 to 86.3 ml (median 7.1 ml). The mean absolute prostate motion of the patients in the left-right direction was −1.46 to 1.85 mm; in the cranial-caudal direction it was −6.10 to 3.65 mm, and in the anteroposterior direction −1.90 to 5.23 mm. There was no significant relationship between the BV change and prostate motion during SSPT. The early and late genitourinary and gastrointestinal toxicity was minimal with a minimum follow up of 4.57 years.

Conclusions:

Simple verbal instructions about urination was suggested to be sufficient to control the BV not to impact on the prostate motion and clinical outcomes in image-guided SSPT. Careful attention to BV change is still needed when the seminal vesicle is to be treated.

Advances in knowledge:

Our data demonstrated that there was no apparent relationship between BV changes and prostate position reproducibility and simple verbal instruction about urination could be sufficient for image-guided SSPT.
KnowMore: an automated knowledge discovery tool for the FAIR SPARC datasets
Authors: Quey Ryan , Schiefer Matthew A. , Kiran Anmol , Patel Bhavesh
Published: November 2021

Background: This manuscript provides the methods and outcomes of KnowMore, the Grand Prize winning automated knowledge discovery tool developed by our team during the 2021 NIH SPARC FAIR Data Codeathon. The National Institutes of Health Stimulating Peripheral Activity to Relieve Conditions (NIH SPARC) program generates rich datasets from neuromodulation researches, curated according to the Findable, Accessible, Interoperable, and Reusable (FAIR) SPARC data standards. Currently, the process of simultaneously comparing and analyzing multiple SPARC datasets is tedious because it requires investigating each dataset of interest individually and downloading all of them to conduct cross-analyses. It is crucial to enhance this process to enable rapid discoveries across SPARC datasets.

Methods: To fill this need, we created KnowMore, a tool integrated into the SPARC Portal that only requires the user to select their datasets of interest to launch an automated discovery process. KnowMore uses several SPARC resources (Pennsieve, o²S²PARC, SciCrunch, protocols.io, Biolucida), data science methods, and machine learning algorithms in the back end to generate various visualizations in the front end intended to help the user identify potential similarities, differences, and relations across the datasets. These visualizations can lead to a new discovery, new hypothesis, or simply guide the user to the next logical step in their discovery process.

Results: The outcome of this project is a SPARC portal-ready code architecture that helps researchers to use SPARC datasets more efficiently and fully leverages their FAIR characteristics. The tool has been built and documented such that more data analysis methods and visualization items could be easily added.

Conclusions: The potential for automated discoveries from SPARC datasets is huge given the unique SPARC data ecosystem promoting FAIR data practices, and KnowMore has only demonstrated a small highlight of what could be achieved to speed up discoveries from SPARC datasets.
Socio-demographic and social support factors related to substance use in South African in-school adolescents: Insights from the Girls Achieve Power (GAP Year) trial in three peri-urban settings
Authors: Gordon Kerry , Kutywayo Alison , Frade Sasha , Naidoo Nicolette , Mullick Saiqa
Published: November 2021

Background: Substance use is a significant public health problem worldwide, with consequences including violence, risky behaviours, and even death. Substance use amongst adolescents is increasing in South Africa, and limited research on frequency, risk and protective factors means that prevention interventions are difficult to design. This paper aims to describe and discuss factors associated with substance use among school-going adolescents in three peri-urban South African settings.

Methods: A cross-sectional analysis was conducted using baseline data from participants in the Girls Achieve Power (GAP Year) trial. Grade 8 learners (N=2383), aged 11-18, were recruited from 26 lowest quintile public high schools in three townships: Soweto and Thembisa in Gauteng Province, and Khayelitsha in Western Cape Province. A baseline survey gathered demographic and behavioural data. Questions relevant to substance use and social support were used for this analysis. Multivariate logistic regression analyses were conducted to identify factors associated with substance use. The final variables were included in an unadjusted and adjusted logistic regression for current substance use, and a multinomial logistic regression for frequency of substance use.

Results: A total of 22.5% (534) of participants indicated they had ever used substances. Being male was strongly associated with substance use (P<0.001), and less strongly with frequency of substance use. Age significantly predicted substance use, with older adolescents being more likely to engage in substance use (P<0.001); having a parent/guardian employed was negatively associated with substance use (P=0.021). Family-related social support variables were predictive of substance use. Being able to count on friends when things went wrong was predictive of lower frequency of substance use (P=0.019).

Conclusions: These results can inform the targeting of prevention interventions to males and younger learners, as well as ensuring youth interventions build family and peer support to make substance use less likely and less frequent.
Effect of resident and assessor gender on entrustment-based observational assessment in an internal medicine residency program
Authors: Weber Danielle E. , Kinnear Benjamin , Kelleher Matthew , Klein Melissa , Sall Dana , Schumacher Daniel J. , Zhang Nanhua , Warm Eric , Schauer Daniel P.
Published: November 2021

Background: Implicit gender bias leads to differences in assessment. Studies examining gender differences in resident milestone assessment data demonstrate variable results. The purpose of this study was to determine if observational entrustment scores differ by resident and assessor gender in a program of assessment based on discrete, observable skills. 

Methods: We analyzed overall entrustment scores and entrustment scores by Accreditation Council for Graduate Medical Education (ACGME) core competency for 238 residents (49% female) from 396 assessors (38% female) in one internal medicine residency program from July 2012 to June 2019. We conducted analyses at 1-12 months, 1-36 months, 1-6 months, 7-12 months, and 31-36 months. We used linear mixed-effect models to assess the role of resident and assessor gender, with resident-specific and assessor-specific random effect to account for repeated measures. 

Results: Statistically significant interactions existed between resident and assessor gender for overall entrustment at 1-12 months (p < 0.001), 1-36 months (p< 0.001), 1-6 months (p<0.001), 7-12 months (p=0.04), and 31-36 months (p<0.001). However, group differences were not statistically significant. In several instances an interaction was significant between resident and assessor gender by ACGME core competency, but there were no statistically significant group differences for all competencies at any time point. When applicable, subsequent analysis of main effect of resident or assessor gender independently of one another revealed no statistically significant differences.  

Conclusions: No significant differences in entrustment scores were found based on resident or assessor gender in our large, robust entrustment-based program of assessment. Determining the reasons for our findings may help identify ways to mitigate gender bias in assessment.
Health professionalism and health profession education in the 21st century
Authors: Ploylearmsang Chanuttha
Published: November 2021

The dramatic, rapid and uncertain changes from the 20th to the 21st century are called global megatrends. Such trends are the emerging and re-emerging infectious diseases, an aging society, environmental hazards, behavioural risks, and more complicated lifestyles of humans in the digital age with advanced information technology (IT) that impact much on epidemiological transitions, health security and healthcare.  Health professionals are the key persons for dealing with these challenging healthcare trends. The next generation of health professionals should be equipped with high professionalism especially for the components of humanism that artificial intelligence (AI) cannot replicate. Moreover, interprofessional collaborative teamwork among health professionals is a required skill for working in dynamic transitions such as the coronavirus disease 2019 (COVID-19) pandemic. Interprofessional education (IPE) is one of the essential strategies for enhancing teamwork skills in learners. Six previously reported trends in health profession education for the 21st century are summarized, including interprofessional education, longitudinal integrated clinical education, understanding partnerships and social determination of health in patients, life-long learning, competency-based skills changeable over time, and AI and IT integrated in education. The connection among megatrends, trends in healthcare, health professionalism and health professional’s education will be important issues in academia for both health educators and health professionals.