bluuebunny/crossref_metadata_2025 huggingface dataset:
Redefining Student Learning Objectives for the General Medicine / Primary Care Clinical Clerkship ~ The Way to Implement Community Based Medical Education
Authors: Miyazaki Kei , Ie Kenya , Kitamura Masaru , Takamura Akiteru
Published: September 2021

Background: Mie University is one of the first medical schools to initiate a community-based clinical clerkship in general medicine. The curriculum was developed over fifteen years ago based on the personal expertise of the general medicine faculties. The purpose of this project is to update and revise the curriculum and learning objectives by integrating the ideas of community primary care physicians and university faculties involved in clinical clerkships.Methods: We have conducted semi-structured interviews with community primary care physicians. The interviews were based on keywords extracted from the preliminary research. Two researchers independently reviewed the free-coded interview transcripts, organized them into thematic units using thematic analysis, and then discussed and merged them into one list between the two researchers. This list was shared and discussed among the four researchers to create a new curriculum and learning objectives.Results: Nine primary care physicians participated in group interviews and 11 participated in individual interviews. The following themes were identified: 1.role of primary care 2.contextual care 3.hospital-clinic collaboration 4.multidisciplinary care/inter-professional work 5.work-life balance 6.health economics 7.health promotion 8.health policy 9.common problems/common diseases. Conclusion:We have redefined the learning objectives of the general medicine clinical clerkship. The abstracts have been made more specific, which will be more helpful for both teachers and learners.
Bisphenol S Promotes the Progression of Prostate Cancer by Regulating the Expression of COL1A1 and COL1A2.
Authors: Fang Kai , Li Yang , Zhang Yuqing , Liang Shengjie , Li Simin , Liu Dong
Published: September 2021

In recent decades, Bisphenol S (BPS), which have been considered as alternatives for Bisphenol A (BPA), have become widely used in personal care products, paper products and food. Clarifying the relationship between bisphenol and tumors is of great significance for the treatment and prevention of diseases. In this work, we discovered a new method to predict the correlation between bisphenol interactive genes and tumors. The transcriptome profile and interactive genes of bisphenol were obtained from the Cancer Genome Atlas and Genotype-Tissue Expression, Comparative Toxicology Genomics and PharmMapper database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that interactive genes were mainly enriched in prostate cancer. Gene targetd prediction and gene set variation analysis proved that bisphenol exert potential effects on prostate cancer. The operating characteristic curves and survival analysis showed that role of COL1A1 and COL1A2 in predicting the prognosis of prostate cancer. Cell counting kit-8 assay demonstrated that the cells with BPS-treated could remarkably promote the cell proliferation ability in both PC-3 and LNCap cells. Wound healing assay and the transwell assay demonstrated that the cells with BPS-treated could significantly promote the cell invasion capacity of prostate cells. Two key genes, COL1A1 and COL1A2, were significantly upregulated with BPS-treated in the PC-3 and LNCap cells.
Is Mindful Eating Higher in Individuals With Orthorexia Nervosa ?: A Cross-Sectional Study
Authors: Demirer Büşra , Yardımcı Hülya
Published: September 2021

Purpose

The present study aimed to investigate the relationship between mindful eating and Orthorexia Nervosa (ON) among adults and contribute to establishing ON diagnostic criteria.
Methods

In the current cross-sectional study, 105 females, 92 males (aged 19–64 years), were enrolled whose scores on the Orthorexia Nervosa Questionnaire-15 (ORTO-15) and the Eating Attitudes Test-26 (EAT-26) and SCOFF scales indicated a prevalence of ON and eating disorder risk. In addition, Mindful Eating Questionnaire (MEQ) was applied to participants to determine mindful eating.
Results

In participants with ON, the scores of emotional eating and conscious eating scores, which are MEQ sub-factors, and the total score of MEQ are higher than those who do not have ON (p < 0.05). There was a negative correlation between MEQ and ORTO-15 scores (r = -0.269; p < 0.01). In addition, the one-point increase in the ORTO-15 scores of the participants led to 0.094 decrease in MEQ scores (B = -0.094; SE = 0.021; p < 0.001) and 0.175 decrease in EAT-26 scores (B = -0.175; SE = 0.033; p < 0.001).
Conclusions

The data obtained from our study show that mindful eating of individuals with ON is higher than those who do not have ON and this is important in determining the diagnostic criteria of ON.
Level of evidence:
V, Cross-sectional descriptive study.
A Case of Two Shunts In The Endovascular Treatment of Type II Abernethy Syndrome
Authors: Bombardier Brenden , Alli Adam , Rohr Aaron , Collins Zachary , Raval Kavi
Published: September 2021

Background:Abernethy malformation is a rare condition defined by a congenital extrahepatic portosystemic shunt, often leading to absence or hypoplasia of the intrahepatic portal venous system. Although there are no consensus treatment guidelines, interventional techniques now offer minimally invasive treatment options for Abernethy malformations. This case report describes a case of Abernethy Syndrome Type II where the patient had two separate extrahepatic portosystemic shunts treated with endovascular occlusion with two Amplatzer plugs and demonstrates the feasibility of this treatment for this rare condition. This case was in a young adult, adding to the scarce literature of treatment for Abernethy syndrome in the adult population.Case Presentation:We report a case of a 20-year-old female patient with neurocognitive behavioral difficulty, voracious appetite, and chronic encephalopathy secondary to type II Abernethy malformation with not one, but two extrahepatic portosystemic shunts. The patient had failed medical management and was not a liver transplant candidate. Therefore, she presented to us for an endovascular treatment option. The two shunts were treated with endovascular occlusion using Amplatzer vascular plugs. Following embolization, flow into the hypoplastic portal vein improved with near complete occlusion of flow into the portosystemic shunts, thus restoring blood flow into the native portal system. At 3 month follow up, a CT demonstrated complete occlusion of the two portosystemic shunts, and a portal vein diminutive in caliber. The portal vein measured 7mm in diameter on both pre and post-procedure CT scans. The total volume of the liver was found to be 843 cm3 on pre-procedure CT & 1191 cm3 on post-procedure CT.Conclusions:This report demonstrates the feasibility of using endovascular embolization to treat Abernethy II malformations. The management strategy of Type II Abernethy Syndrome should be to redirect blood flow into the hypoplastic native portal system, allowing for physiologic hepatic metabolism of splanchnic blood, hypertrophy of the portal system, and growth of the liver from the increased trophic flow.
Shared Genetic Loci For Body Fat Storage And Adipocyte Lipolysis In Humans
Authors: Kulyté Agné , Lundbäck Veroniqa , Arner Peter , Strawbridge Rona J. , Dahlman Ingrid
Published: September 2021

Background. Total body fat and central fat distribution are heritable traits and well-established predictors of adverse metabolic outcomes. Lipolysis is the process responsible for the hydrolysis of triacylglycerols stored in adipocytes. To increase our understanding of the genetic regulation of body fat distribution and total body fat, we set out to determine if genetic variants associated with body mass index (BMI) or waist-hip-ratio adjusted for BMI (WHRadjBMI) in genome-wide association studies (GWAS) mediate their effect by influencing adipocyte lipolysis.Methods. We utilized data from the recent GWAS of spontaneous and isoprenaline-stimulated lipolysis in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort. GENiAL consists of 939 participants who have undergone abdominal subcutaneous adipose biopsy for the determination of spontaneous and isoprenaline-stimulated lipolysis in adipocytes. Results. We report 11 BMI and 15 WHRadjBMI loci with SNPs displaying nominal association with lipolysis and allele-dependent gene expression in adipose tissue according to in silico analysis. Functional evaluation of candidate genes in these loci by small interfering RNAs (siRNA)-mediated knock-down in adipose-derived stem cells identified ZNF436 and NUP85 as intrinsic regulators of lipolysis consistent with the associations observed in the clinical cohorts. Furthermore, candidate genes in another BMI-locus (STX17) and two more WHRadjBMI loci (NID2, GGA3, GRB2) control lipolysis alone, or in conjunction with lipid storage, and may hereby be involved in genetic control of body fat.Conclusions. The findings expand our understanding of how genetic variants mediate their impact on the complex traits of fat storage and distribution.
CompoNet: Toward Incorporating Human Perspective in Automatic Music Generation Using Deep Learning
Authors: HekmatiAthar SeyyedPooya , Anwar Mohd
Published: September 2021

The art nature of music makes it difficult, if not impossible, to extract solid rules from composed pieces and express them mathematically. This has led to the lack of utilization of music expert knowledge in the AI literature for automation of music composition. In this study, we employ intervals, which are the building blocks of music, to represent musical data closer to human composers’ perspectives. Based on intervals, we developed and trained OrchNet which translates musical data into and from numerical vector representation. Another model called CompoNet is developed and trained to generate music. Using intervals and a novel monitor-and-inject mechanism, we address the two main limitations of the literature: lack of orchestration and lack of long-term memory. The music generated by CompoNet is evaluated by Turing Test: whether human judges can tell the difference between the music pieces composed by humans versus. generated by our system. The Turing test results were compared using Mann-Whitney U Test, and there was no statistically significant difference between human-composed music versus what our system has generated.
A Comprehensive Study of Microsatellite Instability Testing And Its Comparison With Immunohistochemistry In Gastric And Colorectal Cancers
Authors: Park Yujun , Nam Soo Kyung , Seo Soo Hyun , Park Kyoung Un , Ahn Sang-Hoon , Oh Heung-Kwon , Kim Duck-Woo , Park Do Joong , Kang Sung-Bum , Kim Hyung-Ho , Lee Hye Seung
Published: September 2021

Background Microsatellite instability (MSI) testing was comprehensively analyzed and compared with immunohistochemistry (IHC) for the mismatch repair (MMR) protein in gastric cancer (GC) and colorectal cancer (CRC). Methods PCR-based MSI testing was performed to compare the tumor and non-neoplastic normal tissues using five microsatellites consisting of two mononucleotide (BAT-26, BAT-25) and three dinucleotide (D5S346, D2S123, and D17S250) in 5,676 GC and 2,553 CRC cases. IHC for the MMR protein MLH1 was done in GCs, and IHC for four MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed in CRCs. Reviews were carried out for discordant or indeterminate IHC cases (such as focal loss of expression, equivocal expression, or abnormal expression patterns). Results MSI-high (MSI-H) and MMR-deficient (dMMR) expression was observed in 521 (9.2%) GC and 171 (6.7%) CRC cases. Discordance between MSI testing and IHC as well as indeterminate IHC cases accounted for 54 (0.9%) and 29 (1.1%) cases out of all GC and CRC cases, respectively, but accounted for 9.4% and 14.1% out of 575 GC and 205 CRC cases, respectively, excluding unequivocal microsatellite stable/MSI-low and MMR-proficient (pMMR) expression cases. pMMR expression was observed in most of the MSI-H GCs and CRCs consisting of only one unstable BAT-25 mononucleotide marker or solely of dinucleotide markers. ConclusionsConsidering the low incidence of MSI-H or dMMR expression, discordant or indeterminate IHC and/or MSI results were occasionally identified in GC and CRC cases, requiring complementary testing. These findings provide evidence for MSI testing and MMR IHC in routine clinical practice.
Deep learning methods improve polygenic risk analysis and prediction for Alzheimer’s disease
Authors: Zhou Xiaopu , Chen Yu , Ip Fanny , Jiang Yuanbing , Cao Han , Zhong Huan , Chen Jiahang , Ye Tao , Chen Yuewen , Zhang Yulin , Ma Shuangshuang , Lo Ronnie , Tong Estella , Initiative Alzheimer’s Disease Neuroimaging Initiative Alzheimer’s Dise , Mok Vincent , Kwok Timothy , Guo Qihao , Mok Kin , Shoai Maryam , Hardy John , Chen Lei , Fu Amy , Ip Nancy
Published: September 2021

Recent advances in genetic sequencing have enabled comprehensive genetic analyses of human diseases, resulting in the identification of numerous genetic risk factors for heritable disorders including Alzheimer’s disease (AD). Such analyses enable AD risk prediction well before disease onset, which is critical for early interventions. However, current analytical approaches have limited ability to accurately estimate the risk effects of genetic variants owing to epistatic effects, which have been overlooked in most previous studies, resulting in unsatisfactory disease risk prediction. Herein, we modeled AD polygenic risk using deep learning methods, which outperformed existing models (i.e., weighted polygenic risk score and lasso models) for classifying disease risk. Moreover, by examining the associations between the outcomes from deep learning methods and multi-omics data obtained from our in-house Chinese AD cohorts, we identified the pathways that are potentially regulated by AD polygenic risk, including immune-associated signaling pathways. Thus, our results demonstrate the utility of deep learning methods for modeling the genetic risks of human diseases, which can facilitate both disease risk classification and the study of disease mechanisms.
Post-traumatic Peripheral Vestibular Disorders (Excluding Positional Vertigo): Institutional Experience from University Health Network’s Workplace Safety and Insurance Board Head-Injury Program
Authors: Misale Priyanka , hassannia fatemeh , Dabiri Sasan , Brandstaetter Tom , Rutka John
Published: September 2021

Purpose: Benign paroxysmal positional vertigo has typically been reported to be the most common cause of post-traumatic dizziness. There is however paucity in the literature about other peripheral vestibular disorders post-head injury. This article provides an overview of other causes of non-positional dizziness post-head trauma from our large institutional experience.Methods: The UHN WSIB Neurotology database (n=4,291) between 1998 and 2018 was retrospectively studied for those head-injured workers presenting with non-positional peripheral vestibular disorders. All subjects had a detailed neurotological history and examination and vestibular testing including video nystagmography, video head impulse testing (or a magnetic scleral search coil study), vestibular-evoked myogenic potentials, and audiometry. Imaging studies included routine brain and high-resolution temporal bone CT scans and/or brain MRI.Results: Based on a database of 4,291 head-injured workers with dizziness, 244 were diagnosed with non-positional peripheral vertigo. Recurrent vestibulopathy (RV) was the most common cause of non-positional post-traumatic vertigo. The incidence of Meniere’s disease in the post-traumatic setting did not appear greater than found in the general population. Conclusion: The clinical spectrum pertaining to recurrent vestibulopathy, Meniere’s disease, delayed endolymphatic hydrops, drop attacks, superior semicircular canal dehiscence syndrome, and uncompensated peripheral vestibular loss are discussed.
Machine Learning-based Model for Prediction of Clinical Deterioration in Hospitalized Patients by COVID-19.
Authors: Garcia-Gutierrez Susana , Esteban-Aizpiri Cristobal , Lafuente Iratxe , Barrio Irantzu , Quiros Raul , Quintana Jose M , Uranga Ane , Group. COVID-REDISSEC Working
Published: September 2021

Background

Despite the publication of great number of tools to aid decisions in COVID-19 patients, there is a lack of good instruments to predict clinical deterioration.
Methods

COVID19-Osakidetza is a prospective cohort study recruiting COVID-19 patients. We collected information from baseline to discharge on: sociodemographic characteristics, comorbidities and associated medications, vital signs, treatment received and lab test results. Outcome was need for intensive ventilatory support (with at least standard high-flow oxygen face mask with a reservoir bag for at least 6 hours and need for more intensive therapy afterwards or Optiflow™ high-flow nasal cannula or noninvasive or invasive mechanical ventilation) and/or admission to a critical care unit and/or death during hospitalization. We developed a Catboost model summarizing the findings using Shapley Additive Explanations. Performance of the model was assessed using area under the receiver operating characteristic and prediction recall curves (AUROC and AUPRC respectively) and calibrated using the Hosmer-Lemeshow test.
Results

Overall, 1568 patients were included in the derivation cohort and 956 in the (external) validation cohort. The percentages of patients who reached the composite endpoint were 23.3% vs 20% respectively. The strongest predictors of clinical deterioration were arterial blood oxygen pressure, followed by age, levels of several markers of inflammation (procalcitonin, LDH, CRP) and alterations in blood count and coagulation. Some medications, namely, ATC AO2 (antiacids) and N05 (neuroleptics) were also among the group of main predictors, together with C03 (diuretics). In the validation set, the CatBoost AUROC was 0.79, AUPRC 0.21 and Hosmer-Lemeshow test statistic 0.36.
Conclusions

We present a machine learning-based prediction model with excellent performance properties to implement in EHRs. Our main goal was to predict progression to a score of 5 or higher on the WHO Clinical Progression Scale before patients required mechanical ventilation. Future steps are to externally validate the model in other settings and in a cohort from a different period and to apply the algorithm in clinical practice.
Tocilizumab in Hospitalized Patients with Severe COVID-19: An Open Label, Prospective Study
Authors: Karampitsakos Theodoros , Malakounidou Elli , Papaioannou Ourania , Dimakopoulou Vasilina , Zarkadi Eirini , Katsaras Matthaios , Tsiri Panagiota , Tsirikos Georgios , Georgiopoulou Vasiliki , Oikonomou Ioanna , Davoulos Christos , Velissaris Dimitrios , Sampsonas Fotios , Marangos Markos , Akinosoglou Karolina , Tzouvelekis Argyris
Published: September 2021

Background: Data on the safety and efficacy profile of tocilizumab in patients with severe COVID-19 needs to be enriched.Methods: In this open label, prospective study, we evaluated clinical outcomes in consecutive patients with COVID-19 and PaO2/FiO2<200 receiving tocilizumab plus usual care versus usual care alone. The primary outcome was 28-day mortality. Secondary outcomes included time to discharge, change in PaO2/FiO2 at day 5 and change in WHO progression scale at day 10.Findings: Overall, 114 patients were included in the analysis (tocilizumab plus usual care: 56, usual care: 58). Allocation to usual care was associated with significant increase in 28-day mortality compared to tocilizumab plus usual care [Cox proportional-hazards model: HR: 3.34, (95%CI: 1.21 to 9.30), (p=0.02)]. There was not a statistically significant difference with regards to hospital discharge over the 28-day period for patients receiving tocilizumab compared to usual care [11.0 days (95%CI: 9.0 to 16.0) vs 14.0 days (95%CI: 10.0 to 24.0), HR: 1.32 (95%CI: 0.84 to 2.08), p=0.21]. ΔPaO2/FiO2 at day 5 was significantly higher in the tocilizumab group compared to the usual care group [42.0 (95%CI: 23.0 to 84.7) vs 15.8 (95%CI: -19.4 to 50.3), p=0.03]. ΔWHO scale at day 10 was significantly lower in the tocilizumab group compared to the usual care group (-0.5±2.1 vs 0.6±2.6, p=0.005). Conclusion: This is the first study administrating tocilizumab in patients with COVID-19 based on PaO2/FiO2. Tocilizumab improved survival and other clinical outcomes in hospitalized patients with COVID-19 and PaO2/FiO2<200 irrespective of systemic inflammatory markers levels.
Medical Educators’ Experiences On Medically Unexplained Symptoms and Intercultural Communication—An Expert Focus Group Study
Authors: Sallay Viola , Martos Tamás , Lucza Lilla , Weiland Anne , Stegers‐Jager Karen M. , Vermeir Peter , Mariman An Noelle Margareta , Csabai Márta
Published: September 2021

Background

Medically unexplained symptoms (MUS) are highly prevalent and remain challenging in healthcare and medical education, along with the increase in the importance of intercultural issues regarding MUS. However, less is known about the challenges of professionally addressing patients with MUS in the interprofessional and intercultural contexts. Thus, the present study aims to provide the first exploration of the experiences of medical specialists regarding treating MUS in intercultural contexts and inputs for training development on the intercultural aspects of MUS.
Methods

Three focus groups (total n = 13) consisting of medical specialists from a Hungarian university who were teaching at the medical faculty in intercultural settings and also worked for the university health services were interviewed. The topics covered the participants' personal experiences on addressing MUS and the challenges of intercultural communication and the intercultural educational context. Thematic analysis was used to yield a qualitative account of the interviews as guided by the research questions.
Results

Representing the different aspects of medical specialists, the study identified three main themes in the experiences of medical specialists, namely, 1) the need to adapt to the personal world of patients and search for common frames to understand MUS, 2) the need to discover methods for adapting to cultural differences and 3) the need to enhance the interprofessional coordination of knowledge and practices.
Conclusions

The results are in line with the distinct conclusions of previous studies. Moreover, an integrated educational program on the intercultural aspects of MUS may address the main themes separately and, subsequently, support their integration. Therefore, the study discusses the manner in which an integrated educational program on the intercultural aspects of MUS may address the needs recognized in these aspects.
Topological phase transition and charge-spin coupling in the kagome metal YMn6Sn6
Authors: Siegfried Peter , Bhandari Hari , Jones D , Ghimire Madhav , Dally Rebecca , Poudel L , Bleuel M , Lynn Jeffrey , Mazin Igor , Ghimire Nirmal
Published: September 2021

The Fermi surface (FS) is essential for understanding the properties of metals. It can change under both conventional symmetry-breaking phase transitions and Lifshitz transitions (LTs), where the FS, but not the crystal symmetry, changes abruptly. Magnetic phase transitions involving uniformly rotating spin textures are conventional in nature, requiring strong spin-orbit coupling (SOC) to influence the FS topology and generate measurable properties. LTs driven by a continuously varying magnetization are rarely discussed. Here we present two such manifestations in the magnetotransport of the kagome magnet YMn6Sn6; one caused by changes in the magnetic structure and another by a magnetization-driven LT. The former yields a 10% magnetoresistance enhancement without a strong SOC, while the latter a 45% reduction in the resistivity. These phenomena offer a unique view into the interplay of magnetism and electronic topology, crucial for understanding the rare-earth counterparts, such as TbMn6Sn6, recently shown to harbor novel correlated topological physics.
Effective Capacity Analysis of Reconfigurable Intelligent Surfaces Aided NOMA Network
Authors: Li Geng , Liu Huiling , Huang Gaojian , Li Xingwang , Raj Bichu , Kara Ferdi
Published: September 2021

The future sixth generation (6G) is going to face the significant challenges of massive connections and green communication. Recently, reconfigurable intelligent surfaces (RIS) and non-orthogonal multiple access (NOMA) have been proposed as two key technologies to address the above problems. Motivated by this fact, we consider a downlink RIS-aided NOMA system, where the base station seeks to communicate with two NOMA users with the aid of a RIS. Considering future network supporting real-time service, we investigate the system performance with the view of effective capacity (EC), which is an important evaluation metric of sensitive to delay sensitive system. Based on this basis, we derive the analytical expressions of the EC of the near and far users. To obtain more useful insights, we deduce the analytical approximation expressions of the EC in the low signal-to-noise-ratio (SNR) approximation by utilizing Taylor expansion. In order to compare, we provide the results of orthogonal multiple access (OMA). It is found that 1) The number of RIS components and the transmission power of the base station have important effects on the performance of the considered system model. 2) Compared with OMA, NOMA system has higher effective capacity due to the short transmission time.
Integrated Halo Model And Hydrodynamic Simulation For Optimization Oil Production In Crystalline Fractured Reservoirs
Authors: Thanh Hung Vo , Lee Kang-Kun
Published: September 2021

Basement formation is known as the unique reservoir in the world. The fractured basement reservoir was contributed a large amount of oil and gas for Vietnam petroleum industry. However, the geological modelling and optimization of oil production is still a challenge for fractured basement reservoirs. Thus, this study aims to introduce the efficient workflow construction reservoir models for proposing the field development plan in a fractured crystalline reservoir. First, the Halo method was adapted for building the petrophysical model. Then, Drill stem history matching is conducted for adjusting the simulation results and pressure measurement. Next, the history-matched models are used to conduct the simulation scenarios to predict future reservoir performance. The possible potential design has four producers and three injectors in the fracture reservoir system. The field prediction results indicate that this scenario increases approximately 8 % oil recovery factor compared to the natural depletion production. This finding suggests that a suitable field development plan is necessary to improve sweep efficiency in the fractured oil formation. The critical contribution of this research is the proposed modelling and simulation with less data for the field development plan in fractured crystalline reservoir. This research's modelling and simulation findings provide a new solution for optimizing oil production that can be applied in Vietnam and other reservoirs in the world.
Expression of the Laminin-5γ2 Chain Is Associated With Acquisition of Malignant Traits in Ovarian Serous and Mucinous Tumors.
Authors: Tajika Yosuke , Imura Johji , Noguchi Akira , Orita Megumi , Nakajima Yuki , Minamisaka Takashi , Takagi Kohji , Tanaka Shinichi , Shima Tomoko , Nakashima Akitoshi
Published: September 2021

BackgroundOvarian tumors are predominantly of epithelial origin and are currently divided into three groups: Adenoma, borderline tumor, and adenocarcinoma by the presence or absence of invasion and cellular atypia. However, it is difficult to assess invasion, so a more objective biomarker would be desirable. Laminin-5 (Lam5) is a protein that constitutes the extracellular matrix of the basement membrane, and it is composed of three short-chain subunits. One of them, the Lam5γ2 chain (Lam5γ2), has been reported to be expressed in some malignant tumors and is suggested to be related to tumor cell invasion. Against this background, we investigated immunohistologically whether the Lam5γ2 would be useful as a marker to predict invasion in ovarian serous and mucinous tumors.MethodsImmunohistochemistry for Lam5γ2 was performed on a total of 80 cases of serous and mucinous tumor adenomas, borderline tumors, and adenocarcinomas, and the differences in the localization of Lam5γ2 expression were observed.ResultsThe basement membrane expression of Lam5γ2 tended to be preserved or had disappeared in half of the adenomas and borderline serous tumors. In all cases of adenocarcinoma, the expression on the basement membrane had disappeared. The frequency of expression in tumor cells increased in the order of adenoma, borderline tumor, adenocarcinoma. In particular, in most adenocarcinoma cases a cytoplasmic expression was observed. The same tendency was noted in mucinous tumors, and the basement membrane expression tended to disappear in the order of adenoma, borderline tumor and adenocarcinoma. Many cases of adenocarcinoma were observed among the tumor cells. In adenocarcinoma cases of both types of tumor, many tumor cells showed prominent cytoplasmic expression particularly in the microinvasive foci and in the invasive front.ConclusionsThe disappearance of Lam5γ2 from the basement membrane and its aberrant expression in serous and mucinous tumor cells may serve as a phenotype for invasiveness.
Effect Size of Rituximab on Pulmonary Function in the Treatment of Connective-Tissue Disease-Related Interstitial Lung Disease: A Systematic Review and Meta-Analysis
Authors: Zhao Yuanchen , Gao Yang , Petnak Tananchai , Cheungpasitporn Wisit , Thongprayoon Charat , Zhang Xing , Moua Teng
Published: September 2021

BACKGROUND: Rituximab (RTX) has been previously reported as directed treatment in patients with connective-tissue disease-related interstitial lung diseases (CTD-ILD). A systematic assessment of treatment effect size on pulmonary function outcomes and related adverse effects in patients with CTD-ILD has not been previously reported.METHODS: We performed a systematic review and meta-analysis of published reports from PubMed, Embase, and Cochrane Libraries. Randomized and non-randomized controlled trials, case-control, cohort, and case series (with five or more cases) containing individual pulmonary function data and adverse effects were included. Study endpoints were pre and post treatment change in percent predicted forced vital capacity (FVC %) and diffusion capacity for carbon monoxide (DLCO%), along with reported drug-related adverse events. RESULTS: Twenty studies totaling 411 patients were identified with 14 included in the meta-analysis of pulmonary function and six in the descriptive review. Random effects meta-analysis of pre and post-treatment pulmonary function findings demonstrated increases in FVC% (n =296) (mean difference (MD) 4.57%, [95% CI 2.63-6.51]) and DLCO% (n = 246) (MD 5.0% [95% CI 2.71-7.29]) after RTX treatment. RTX treatment-related adverse effects were reported in 13.6% of the pooled cohort. CONCLUSIONS: A systematic assessment of post-treatment effect size suggests a potential role for RTX in stabilizing or improving lung function in patients with CTD-ILD, with a modest but not insignificant adverse effect profile.
MEG cortical microstates: spatiotemporal characteristics, dynamic functional connectivity and stimulus-evoked responses
Authors: Tait Luke , Zhang Jiaxiang
Published: September 2021

EEG microstate analysis is an approach to study brain states and their fast transitions in healthy cognition and disease. A key limitation of conventional microstate analysis is that it must be performed at the sensor level, and therefore gives limited anatomical insight. Here, we generalise the microstate methodology to be applicable to source-reconstructed electrophysiological data. Using simulations of a neural-mass network model, we first established the validity and robustness of the proposed method. Using MEG resting-state data, we uncovered ten microstates with distinct spatial distributions of cortical activation. Multivariate pattern analysis demonstrated that source-level microstates were associated with distinct functional connectivity patterns. We further demonstrated that the occurrence probability of MEG microstates were altered by auditory stimuli, exhibiting a hyperactivity of the microstate including the auditory cortex. Our results support the use of source-level microstates as a method for investigating brain dynamic activity and connectivity at the millisecond scale.
Feasibility Trial of an Integrated Treatment "Activate for Life" for Physical and Mental Well-being in Older Adults
Authors: Hernandez-Tejada Melba A , Nagel Alexis , Madisetti Mohan , Balasubramanian Sundar , Kelechi Teresa
Published: September 2021

This paper describes feasibility and patient satisfaction for an integrated treatment to address multiple health outcomes in a sample of older adults living in a low-income independent residence facility and their own homes in the community. Specifically, 30 older adults were offered the opportunity to participate in a feasibility study of different components of Activate for Life treatment targeting balance and physical strength (Otago Exercise Program), breathing retraining (Gentle Yoga and Yogic Breathing), and mental health (Behavioral Activation for Depression). Three treatment combinations were compared in a randomized repeated measures design to determine if adding components to the existing Otago program were feasible and if this affected patient satisfaction. Arm1: the Otago strength and balance program alone (n = 10); Arm 2: Otago + Gentle Yoga and Yogic Breathing (n = 10); and Arm 3: Otago + Gentle Yoga and Yogic Breathing + Behavioral Activation (we named this combination ‘Activate for Life’ n = 10). Dependent measures included recruitment rate, session completion characteristics, and satisfaction with the program. Overall, study and treatment components proved feasible, and participants reported high satisfaction with all 3 Arms.
Subcutaneous Emphysema Complicating Convalescent Stage of Measles in a Malnourished Indigent Child: A Case Report from North-western Nigeria.
Authors: Na'uzo Aliyu Mamman , Sanni Usman Abiola , Lawal Taslim Olatunde , Musa Tawakaltu Lilly , Gabriel Ojumo Opeyemi , Abdullahi Zainab , Habib Muhammad Ibrahim
Published: September 2021

Background: Measles is a highly infectious vaccine preventable viral disease that runs a devastating course in developing countries due to its association with malnutrition and poor immunization coverage. Among the complications of measles, pneumonia accounts for most measles-associated morbidity and mortality. However, subcutaneous emphysema is a rare complication of measles that can be challenging to manage and may portend poor outcome if untreated. Case presentation: We present a case of a 2yr old un-immunized rural dweller with massive subcutaneous emphysema comorbid with malnutrition complicating convalescent stage of measles. The child failed to improve with conservative management but responded to closed thoracostomy tube drainage (CTTD) through an underwater seal bottle with intermittent negative pressure wound therapy (NPWT). The child spent 47days on admission during which the treatment was supported by faith-based organization and social welfare unit of the hospital.ConclusionSubcutaneous emphysema is a rare complication of measles infection that can be challenging to manage especially when comorbid with malnutrition in an indigent child. Multi-disciplinary team approach and the use of CTTD with NPWT is an effective management measure which can shorten the duration of hospital stay.
Efficacy of BioFire FilmArray Gastrointestinal Panel (FGP) to Reduce Hospital Costs Associated With Contact Isolation: A Pragmatic Randomized Controlled Trial
Authors: DiDiodato Giulio , Allan Ashley , Bradbury Nellie , Brown Julia , Cruise Kelly , Jedrzejko Christopher , MacDonald Valerie , Pigeon Jessica , Sturgeon Amanda , Yellenik Daniel
Published: September 2021

Background: Molecular syndromic panels can rapidly detect common pathogens responsible for acute gastroenteritis in hospitalized patients. Their impact on both patient and healthcare system outcomes is uncertain compared to conventional stool testing. This randomized trial evaluates the impact of molecular testing on in-hospital resource utilization compared to conventional stool testing.Methods: Hospitalized patients with acute diarrheal illness were randomized 1:1 to either conventional or molecular stool testing with the BioFire FilmArray gastrointestinal panel (FGP). The primary outcome was duration of contact isolation, and secondary outcomes included other in-hospital resource utilization such as diagnostic imaging and antimicrobial use. Results: A total of 156 patients were randomized. Randomization resulted in a balanced allocation of patients across all 3 age strata (<18, 18-69, ≥70 years old). The proportion of positive stools was 20.5% vs 29.5% in the control and FGP groups, respectively (p=0.196). The median duration of contact isolation was 51 hours (interquartile range (iqr) 66) and 69 hours (iqr 81) in the conventional and FGP groups, respectively (p=0.0513). There were no significant differences in other in-hospital resource utilization between groups. Conclusions: There were no differences in in-hospital resource utilization observed between FGP and conventional stool testing groups. Trials Registration: ClinicalTrials.gov NCT04189874
Association Between Obesity-Related Dyspnea in Daily Living, Lung Function and Body Composition Analyzed by DXA: A Prospective Study of 130 Patients
Authors: Hagenburg Jean , Bertin Eric , Salmon Jean-Hugues , Thierry Aurore , Perotin Jeanne-Marie , Dormoy Valerian , Dury Sandra , Bolko Lois , Lebargy François , Deslee Gaetan , Launois Claire
Published: September 2021

Background Obesity is a risk factor for dyspnea. However, investigations of daily living obesity-related dyspnea are limited and its mechanisms remain unclear. We aimed to analyze the relationships between dyspnea in daily living, lung function, and body composition in patients with obesity.Methods One-hundred and thirty patients (103 women/27 men), candidate for bariatric surgery, with a mean ± SD Body Mass Index (BMI) of 44.8 ± 6.8 kg/m² were included. Dyspnea was assessed by the modified Medical Research Council (mMRC) scale. Comorbidities, laboratory parameters, pulmonary function tests, arterial blood gases, six-minute walk test (6MWT), handgrip strength, and DXA body composition were analyzed.Results Thirty-one percent of patients exhibited disabling dyspnea in daily living (mMRC ≥ 2). Compared with patients without disabling dyspnea (mMRC < 2), significant dyspnea (mMRC ≥ 2) was associated with a lower 6MWT distance (395 ± 103 m vs 457 ± 73 m, p<0.001), lower lung volumes including Expiratory Reserve Volume (42 ± 28 % vs 54 ± 27%, p=0.024), Vital Capacity (95 ± 14 vs 106 ± 15%, p<0.001) and Forced expiratory volume in one second (95 ± 13 vs 105 ± 15%, p=0.002), a higher BMI (48.2 ± 7.7 vs 43.2 ± 5.7 kg/m², p=0.001) and a higher percentage of fat mass in the trunk (46 ± 5 vs 44 ± 5 p=0.012) and android region (52 ± 4 vs 51 ± 4%, p=0.024). There was no difference regarding comorbidities (except hypertension), laboratory parameters, and sarcopenia markers between patients with (mMRC ≥ 2) and without (mMRC < 2) disabling dyspnea. Conclusion Dyspnea in patients with obesity is associated with a reduction in lung volumes and a higher percentage of fat mass in central body regions. How dyspnea and body composition may change with interventions like physical activity or bariatric surgery remains to be investigated. Trial Registration Reims University Hospital Institutional Review Board (IRB-17-10-2012).
Implementing the use of objective medication adherence data in routine clinical practice via the digital CFHealthHub platform: situation analysis and strategy development using the theoretical domains framework
Authors: Girling Carla , Packham Anna , Robinson Louisa , Arden Madelynne A , Hind Daniel , Wildman Martin J
Published: September 2021

Background Preventative inhaled treatments preserve lung function and reduce exacerbations in Cystic Fibrosis (CF). Self-reported adherence to these treatments is over-estimated. An online platform (CFHealthHub) has been developed with patients and clinicians to display real-time objective adherence data from dose-counting nebulisers, so that clinical teams can offer informed treatment support. Methods In this paper, we identify pre-implementation barriers to healthcare practitioners performing two key behaviours: accessing objective adherence data through the website CFHealthHub and discussing medication adherence with patients. We aimed to understand barriers during the pre-implementation phase, so that appropriate strategy could be developed for the scale up of implementing objective adherence data in 19 CF centres. Thirteen semi-structured interviews were conducted with healthcare practitioners working in three UK CF centres. Qualitative data were coded using the Theoretical Domains Framework (TDF), which describes 14 validated domains to implementation behaviour change. Results Analysis indicated that an implementation strategy should address all 14 domains of the TDF to successfully support implementation. Participants did not report routines or habits for using objective adherence data in clinical care. Examples of salient barriers included skills, beliefs in consequences, and social influence and professional roles. The results also affirmed a requirement to address organisational barriers. Relevant behaviour change techniques were selected to develop implementation strategy modules using the behaviour change wheel approach to intervention development. ConclusionsThis paper demonstrates the value of applying the TDF at pre-implementation, to understand context and to support the development of a situationally relevant implementation strategy. Contribution to the literature· Research indicates that the implementation of healthcare innovations may be more likely to succeed when context and theory are taken into consideration. · In this study, healthcare professionals identified barriers to two behaviours that were key to the implementation of a national Cystic Fibrosis (CF) healthcare innovation. By coding barriers to the Theoretical Domains Framework (TDF), a contextually relevant implementation strategy was developed, with a focus on clinician behaviour change. · The study highlights the challenges CF teams face when implementing new remote monitoring of medication adherence, and provides an important opportunity to apply the TDF in the pre-implementation phase of a healthcare innovation.
Adjuvant Chemotherapy Following Combined Induction Chemotherapy and Concurrent Chemoradiotherapy Improves Survival in N2-3-positive Nasopharyngeal Carcinoma Patients
Authors: Tao Hao-Yun , Liu Hui , He Cai-Xian , Li Ran , Du Kun-Peng , Yuan Ya-Wei , Zheng Rong-Hui
Published: September 2021

Objective: This study aimed to explore the clinical value of adjuvant chemotherapy (ACT) in locoregionally advanced nasopharyngeal carcinoma (LANC) following concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT).Methods: We included 839 newly diagnosed LANC patients in the study. ICT plus CCRT (ICT+CCRT group) was administered to 443 patients and 396 patients who received ACT after receiving ICT plus CCRT (ICT+CCRT+ACT group). Univariate and multivariate Cox regression analyses were carried out in this study. Furthermore, to balance the study and control groups, propensity score matching (PSM) was applied.Results: 373 pairs of LANC patients were obtained after the PSM analysis. We found that ACT following ICT+CCRT had no significant effect on improving the survival of LANC patients. By further exploring the ICT+CCRT+ACT regimen, we excluded N0-1-positive patients and performed PSM in the ICT+CCRT and ICT+CCRT+ACT groups again. Each group consisted of 237 patients. Kaplan-Meier analysis revealed that there was a difference between the ICT+CCRT and ICT+CCRT+ACT groups in terms of the 5-year overall survival (OS) (78.9% vs. 85.0%, P = 0.034), disease-free survival (DFS) (73.4% vs. 81.7%, P = 0.029), and distant metastasis-free survival (DMFS) (84.9% vs. 76.0%, P = 0.019). In addition, the ICT+CCRT+ACT group had a higher incidence of grade 3-4 acute leukocytopenia/neutropenia.Conclusion: Compared with ICT+CCRT, ACT following ICT plus CCRT can reduce distant metastasis of N2-3-positive LANC and improve the OS and DFS of these patients, thus demonstrating higher clinical feasibility.
On the Physical Origin of the Semiannual 1 Component of Surface Air Temperature over 2 Mid-latitude and Subpolar Oceans
Authors: Yang Fucheng , Wu Zhaohua
Published: September 2021

With the understanding that seasonal cycle of the temperature are forced principally by the annually evolving solar irradiance, many previous studies have defined seasonal cycle of surface air temperature (SAT) as the sum of yearly-period sinusoidal component and its harmonics, especially semiannual component. In mid-latitude and subpolar regions, the ratio between the semiannual and annual components of solar irradiance is negligibly small but that of the SAT over oceans is not, which remains to be understood. In this study, a simple energy budget model including main energy sources and sinks of oceanic mixed layer is designed to understand this puzzle. It is revealed that, when the oceanic mixed layer is prescribed as a layer of constant depth, the phase and amplitude of the modeled SAT is not consistent with that of the observation. However, when the annually changing heat capacity of the oceanic mixed layer is included, both the amplitude and phase of the modeled SAT share these of the observed SAT, proving that the semiannual component of SAT over mid-latitude and subpolar oceans is a result of the heat capacity-varying oceanic mixed layer in response to annually evolving solar irradiance.
Irradiated Fibroblasts Increase Interleukin-6 Expression and Induce Migration of Head and Neck Squamous Cell Carcinoma
Authors: Suzuki Shinsuke , Toyoma Satoshi , Kawasaki Yohei , Yamada Takechiyo
Published: September 2021

Background
The cytotoxic effect of radiation plays an important role in the treatment of head and neck cancer. However, irradiation is known to lead to the migration of various cancer cells, including those of head and neck cancer. Recently, fibroblasts in the cancer microenvironment have been reported to be involved in this mechanism. Nevertheless, the mechanism underlying the migration of head and neck cancer cells remains unclear. The purpose of this study was to elucidate this migration mechanism induced by irradiation in terms of the interaction of head and neck cancer cells with fibroblasts.
Methods
We used the head and neck squamous cell carcinoma (HNSCC) cell lines SAS and FaDu as well as fibroblast cell lines. These cells were irradiated and their viability was compared. In fibroblasts, changes in interleukin-6 (IL-6) secretion caused by irradiation were measured by enzyme-linked immunosorbent assay (ELISA). The cell migration ability of cancer cells was evaluated via a migration assay using a semipermeable membrane. HNSCC cells were cocultured with irradiated and nonirradiated fibroblasts, and their migration ability under each condition was compared. We also examined the effect of IL-6 on the migration of HNSCC cells. Furthermore, to investigate the effect of fibroblast-derived IL-6 on the migration ability of HNSCC cells, we conducted a coculture study using IL-6 neutralizing antibody.
Results
Irradiation reduced the survival of HNSCC cells, whereas fibroblasts were resistant to irradiation. Irradiation also increased IL-6 secretion by fibroblasts. Migration of HNSCC cells was enhanced by coculture with fibroblasts and further enhanced by coculture with irradiated fibroblasts. We also confirmed that the migration of HNSCC cells was induced by IL-6. The enhanced migration of cancer cells caused by coculturing with fibroblasts was canceled by the IL-6 neutralizing antibody.
Conclusion
These results show that fibroblasts survive irradiation and induce the migration ability of HNSCC cells through increased secretion of IL-6.