bluuebunny/crossref_metadata_2025 huggingface dataset:
In Silico Docking for Inhibition Neuropilin-1 (SARS-CoV-2 Receptor) by Some Natural and Approved Drugs
Authors: G.Seadawy Mohamed , Shamel Mohamed , Ahmed Aya , Zekri Abdel Rahman N.
Published: November 2020

Severe Acute Respiratory Syndrome Coronavirus2 (SARS-CoV-2) attached to Angiotensin Converting Enzyme 2 (ACE2) as human receptor. The Spike (S) protein of this virus is responsible for host cell penetration and attachment. This viral glycoprotein is synthesized as a precursor in infected cells and, to be active, must be cleaved to two associated polypeptides: S1 and S2 1, 2. We made Insilco docking between the spike protein and Neuropilin-1 using Cluspro 2.0 software. Therefore, Neuropilin-1 becomes host factor for SARS-CoV-2 infection. Our study revealed that some drugs and natural compounds success in inhibition of binding between the virus and its new receptor with Insilco docking data.
Predicting Survival in Patients With Acute Decompensated Heart Failure Complicated by Cardiogenic Shock
Authors: Morici Nuccia , Viola Giovanna , Antolini Laura , Martello Michela Dal , Sacco Alice , Bottiroli Maurizio , Pappalardo Federico , Villanova Luca , Ponti Laura De , Vecchia Carlo La , Frigerio Maria , Oliva Fabrizio , Fried Justin , Colombo Paolo , Garan Arthur R
Published: November 2020

Background: Acute decompensated heart failure (ADHF) complicated by cardiogenic shock (CS) has unique pathophysiological background requiring specific patient stratification, management and therapeutic targets. Accordingly, the aim of this study was to derive a simple stratification tool to predict survival in patients with ADHF complicated by CS. Methods and results: We analyzed data from a historic cohort of 87 ADHF-CS consecutive patients, eligible to heart replacement therapy (HRT), enrolled between 2015 and 2019. The association between selected independent variables (age, lactates and creatinine, ALC-shock score) and 28-day overall mortality was investigated through a multivariable logistic model. Predictive validity was assessed throughout an internal and external validation and compared to the Cardshock score. A nomogram was developed for predicting 28-day mortality. Overall 28-day mortality was 34%. Among patients who survived, 38 (67%) were treated with HRT: heart transplantation was performed in 68%, the remaining received an LVAD. The ALC-shock score showed better discrimination (Area Under the Curve-AUC- 0.82; 95% CI 0.73-0.91) as compared to the Cardshock score (AUC 0.67; 95% CI 0.55-0.79) (p = 0.009) to predict 28-days overall mortality. In the validation cohort the AUC for the ALC-shock score was 0.66. Conclusions: A model including age, lactates and creatinine on admission (ALC-Shock score) could be considered to predict short-term mortality in CS-ADHF patients in order to drive towards a treatment intensification. Disclosures: Dr. Garan is supported by National Institutes of Health Grant No. KL2TR001874 and has received honoraria from Abiomed. Dr. Colombo reports institutional grant support from Abbott Vascular. None of the listed entities has had any involvement with the development of the manuscript. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.Research ethics: This study was approved by the Local Ethics Committee of Milano Area 3 of the ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162 Milano (reference number: 543-23092020).
Giant Intraparenchymal Meningioma in a Female Child: Case Report and Literature Review
Authors: Guo Huachao , Ma Zhen , Wen Shuo , Wang Yong , Wang Jiaguang , Wang Yushe
Published: November 2020

Background: ntraparenchymal meningiomas without dural attachment are extremely rare, especially in female children. To our knowledge, fibrous intraparenchymal meningioma located in the temporal lobe has never been reported in female children. The significance in the differential diagnosis of lesions in the temporal lobe should be emphasized.Case presentation: A 12-year-old girl was admitted to our hospital, complaining of recurrent generalized seizures for 2 months. Magnetic resonance imaging demonstrated a solid lesion located in the temporal lobe. The lesion underwent gross total resection. Histopathological examination indicated that the lesion was a fibrous meningioma. Postoperative rehabilitation was uneventful. Conclusions: This case report presents an extremely unusual intraparenchymal fibrous meningioma of the temporal lobe with peritumoral edema and reviewed 20 intraparenchymal meningioma cases in children and to discuss the clinical presentation and treatment, differential diagnosis, and radiological features.
MiR-20b-5p Targets KIF23 to Suppress Cell Proliferation and Migration in Osteosarcoma
Authors: Wang Zhongyuan , Wang Jian , Gao Yuzhong , Wang Chuanbao , Cui Yuteng , Zou Zhi
Published: November 2020

Background: MicroRNAs (miRNAs) are closely correlated with the development of cancer. Here, the main goal of this study was to analyze the biological function of miR-20b-5p in osteosarcoma (OS). Methods: The expression of miR-20b-5p and kinesin family member 23 (KIF23) was determined using quantitative real time PCR and western blot analysis, respectively. The correlation between miR-20b-5p or KIF23 expression and the clinicopathological characteristics of OS was evaluated using Chi-square test. Functional experiments, including CCK-8, flow cytometry and transwell assay were performed to analyze cell proliferation, cell cycle distribution and apoptosis, and migration. The association between miR-20b-5p and KIF23 was confirmed by luciferase reporter assay.Results: Firstly, we observed that miR-20b-5p expression was significantly decreased, while kinesin family member 23 (KIF23) expression was increased in OS tissues. Moreover, miR-20b-5p expression was inversely correlated with KIF23 expression in OS tissues. Clinically, decreased miR-20b-5p expression was significantly associated with increased metastasis and increased KIF23 mRNA expression level was remarkedly correlated with increased tumor size. Overexpression of miR-20b-5p significantly suppressed cell proliferation and migration, as well as caused G0/G1 phase arrest and apoptosis in OS cells (U2OS and MG-63). Mechanistically, miR-20b-5p directly targeted to the 3’-UTR of KIF23 and negatively regulated its expression in OS cells. Moreover, KIF23 knockdown imitated, while overexpression abolished the effects on U2OS cell proliferation, G1/S transition, apoptosis and migration induced by miR-20b-5p overexpression. Furthermore, KIF23 overexpression reversed the miR-20b-5p-induced downregulation of CDK4, Cyclin D1, Bcl-2, PCNA, Ki-67 and N-cadherin, as well as upregulation of Bad and E-cadherin in U2OS cells.Conclusions: In conclusion, miR-20b-5p directly targeted the 3'UTR of KIF23 mRNA to inhibit the proliferation and migration of human OS cells in vitro, which might be a promising candidate target for OS treatment.
CircRNA CircRIMS is Overexpressed in Esophageal Squamous Cell Carcinoma and Downregulate miR-613 through Methylation to Increase Cell Proliferation
Authors: Wan Haijun , Yuan Bosi , Jiang Kang , Wei Juan , Feng Xiaoyue , Sun Bo , Wang Fangyu
Published: November 2020

BackgroundEsophageal squamous cell carcinoma (ESCC) as the most common subtype of esophageal cancer accounts for about 95% of all cases. CircRNA CircRIMS has been characterized as an oncogenic circRNA in gastric cancer, while its role in other cancers is unknown. This study aimed to explore the role of CircRIMS in esophageal squamous cell carcinoma (ESCC). MethodsTissues collected from 60 ESCC patients were used in this study. The expression of CircRIMS and miR-613 were detected by RT-qPCRs. The 60 ESCC patients were followed up for 5 years to evaluate the prognostic value of CircRIMS for ESCC. The role of CircRIMS in regulating the expression of miR-613 and methylation was assess by overexpression experiments and RT-qPCRs. The role of CircRIMS and miR-613 in regulating cell proliferation was analyzed by BrdU assay. ResultsWe found that CircRIMS was overexpressed in ESCC and predicted poor survival. In addition, miR-613 was downregulated in ESCC and inversely correlated with CircRIMS. In ESCC cells, overexpression of CircRIMS decreased the expression levels of miR-613 and increased the methylation of miR-613 gene. Cell proliferation assay showed that overexpression of CircRIMS reduced the inhibitory effects of overexpression of miR-613 on cell proliferation. Conclusions﻿CircRIMS may downregulate miR-613 through methylation to increase cell proliferation in ESCC.
Validation of Mini-Mental Adjustment to Cancer Scale in A Moroccan Sample of Breast Cancer Women
Authors: RAGALA Mohammed El Amine , HILALY Jaouad El , AMAADOUR Lamiae , OMARI Majid , ASRI Achraf El , ATASSI Mariam , BENBRAHIM Zineb , MELLAS Naoufal , rhazi Karima El , HALIM Karima , ZARROUQ Btissame
Published: November 2020

Background: The Mini-Mental Adjustment to Cancer Scale (Mini-MAC) instrument is commonly used worldwide by professionals of oncology, but the scale has not, up to date, been validated in Arabic and Moroccan context, and there is absence of data in the Moroccan population. This study aims to validate the Mini-MAC, translated and adapted to the Arabic language and Moroccan culture, in women with breast cancer.Methods: The Mini-MAC instrument was administered to 203 breast cancer women, receiving medical care in the university Hospital of Fez city. A cross-sectional validation study using exploratory factor analysis and Confirmatory factor analysis was carried out.Results: Confirmatory factor analysis confirmed Watson’s original structure underlying the Mini-MAC items: Helpless/Hopeless, Anxious Preoccupation, Fighting Spirit, Cognitive Avoidance, and Fatalism. Absolute, incremental, and parsinmonious fit indices showed a high significant level of acceptance confirming a good performance of the measurement model. The instrument showed sufficient reliability and convergent validity demonstrated by acceptable values of composite reliability (CR =0.93–0.97), and average variance extracted (AVE= 0.66 - 0.93), respectively. The square roots of AVE were higher than factor-factor pairs correlations, and the Heterotrait-Monotrait ratio of correlations values were lesser than 0.85, indicating an acceptable discriminant validity. Conclusions: reliability; and both convergent and discriminant validity tests indicated that The Arabic version of the Mini-MAC had a good performance and may serve as a valid tool measuring psychological responses to cancer diagnosis and treatment.
Prophylactic heparin and risk of orotracheal intubation or death in patients with mild or moderate COVID-19 pneumonia
Authors: Vergori Alessandra , Lorenzini Patrizia , Lepri Alessandro Cozzi , Donno Davide Roberto , Gualano Gina , Nicastri Emanuele , Iacomi Fabio , Marchioni Luisa , Campioni Paolo , Schininà Vincenzo , Cicalini Stefania , Agrati Chiara , Capobianchi Maria Rosaria , Girardi Enrico , Ippolito Giuseppe , Vaia Francesco , Petrosillo Nicola , Antinori Andrea , Taglietti Fabrizio
Published: November 2020

Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia.Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50-77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95%CI 3.2-26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7-15.9) in those exposed to pLMWH;p-value=0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95%CI 0.51-3.79) for patients with an admission PaO2/FiO2 < 300 mmHg and 0.27 (0.03-2.18) for those with PaO2/FiO2 >300 mmHg;p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.
Prevalence and associated risk factors for childhood strabismus in Lhasa, Tibet, China: a cross-sectional, school-based study
Authors: He Hailong , Fu Jing , Meng Zhaojun , Chen Weiwei , Li Lei , Zhao Xinyu
Published: November 2020

Background: To estimate the prevalence of strabismus and associated risk factors among grade one school children in Lhasa, Tibet, China. Methods: The Lhasa Childhood Eye Study (LCES) was a cross-sectional, school-based childhood study conducted in Grade one students from primary schools in Lhasa, Tibet, China. Comprehensive ophthalmic examinations and basic systematic examinations were evaluated. A questionnaire survey contained information about children, as well as parents’ information was sent to the corresponding parents of eligible children. The prevalence of strabismus and its 95% confidence interval was estimated. Univariate and multivariate logistic regression analyses were conducted to determine the associated risk factors. Results: A total of 1942 eligible grade one students were enrolled, of which 1856 participants completed all procedures. The average age was 6.83±0.46 years, 53% of participants were boys and 1762 were the Tibetan Minority. Over all, the prevalence of strabismus was 68/1856(3.7%) (95%CI: 2.81,4.52), with no difference between the ages, genders, ethnics and BMI, while tilt one's head when writing may be a risk factor for strabismus ( P =0.004). Strabismus students had the mean best corrected visual acuity 0.16±0.28(LogMAR), over 50% patients with esotropia are hyperopia, participants who have stereopsis impairments showed a significant difference between esotropia and exotropia ( P= 0.026). Conclusions: The prevalence of strabismus in LCES was 3.7%, higher than previous reports from Chinese childhood epidemiology studies. Strabismus is a common contributing factor to amblyopia. Tilt one's head when writing may be a risk factor. Patients with esotropia are more likely to affect stereopsis and be the refractive state of hyperopia.
Multiplex ligation-dependent probe amplification identifies copy number changes in normal and undetectable karyotype MDS patients
Authors: Ma Jing , Ai xiaofei , Wang Jinhuan , Xing Limin , Tian Chen , Yang Hongliang , Yu Yong , Zhao Haifeng , Wang Xiaofang , Zhao Zhigang , Wang Yafei , Cao Zeng
Published: November 2020

Background Chromosomal abnormalities play an important role in classification and prognostication of myelodysplastic syndromes (MDS) patients. However, more than 50% low risk MDS patients harbor a normal karyotype. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for the detection of cytogenetic aberrations in MDS patients. Methods To characterize the subset of MDS with normal karyotype or failed chromosome banding analysis, we analyzed 144 patient samples with normal karyotype or undetectable through regular chromosome banding, which were subjected to parallel comparison via fluorescence in situ hybridization (FISH) and MLPA. Results MLPA identifies copy number changes in 16.7% of 144 MDS patients and we observed a significant difference in overall survival (OS) (median OS: undefined vs 27 months, p=0.0071) in patients with normal karyotype proved by MLPA, versus aberrant karyotype cohort as determined by MLPA. Interestingly, patients with undetectable karyotype via regular chromosome banding indicated inferior outcome. Conclusion Collectively, MDS patients with normal or undetectable karyotype via chromosome banding analysis can be further clarified by MLPA, providing more prognostic information that benefit for individualized therapy.
End-stage knee osteoarthritis with and without sarcopenia and the effect of knee arthroplasty – a prospective cohort study
Authors: Ho Kevin Ki-Wai , Lau Lawrence Chun-Man , Chau Wai Wang , Poon Queena , Chung Kwong-Yin , Wong Ronald Man-Yeung
Published: November 2020

Background:Sarcopenia often accompanies osteoarthritis (OA), which is managed by total knee arthroplasty (TKA) in the late stage. Recent studies have suggested a higher risk of post-operative complications after TKA in sarcopenic OA subjects, but whether TKA can benefit them similar to non-sarcopenic subjects remains unexplored. This study aimed to examine the dynamic, mutual impact of sarcopenia and TKA in a one-year post-operative period.Methods: This prospective cohort study was conducted between 2015 to 2018 at our hospital. Patients with end-stage OA of the knee waiting for TKA were recruited into the study. Primary outcome measures were change in muscle strength, mass and function. Secondary outcome measures were quality of life (QOL) measurements for pain, psychological and physical health.Results: Fifty-eight patients were recruited, of which 79.3% were female and 32.8% already had sarcopenia at baseline. The average age of sarcopenic subjects and non-sarcopenic subjects was comparable (67.89±7.07 vs. 67.92±6.85; p=0.99), but sarcopenic subjects had a lower body mass index (BMI) (25.64±2.64 vs. 28.57±4.04; p=0.01). There was a statistically significant improvement in walking speed (10.24±5.35 vs. 7.69±2.68, p<0.01) and muscle strength in both sarcopenic and non-sarcopenic patients after TKA. This was accompanied by an improvement trend in muscle mass in all subjects. There was no change in handgrip power before and after TKA and subsequent follow-up (19.31±5.92 vs. 18.98±6.37 vs. 19.36±7.66; p=0.97). QOL measured before, after and at follow-up with WOMAC (total: 42.27±15.98 vs. 20.65±15.24 vs. 16.65±18.13) and SF12v2 (PCS: 33.06±8.55 vs. 38.96±8.01 vs. 40.67±7.93) revealed progressive significant improvement (both comparisons p≤0.01). Further analysis with the IPAQ also found increased engagement of high-intensity activities.Conclusions: This study showed that sarcopenia among patients with end-stage OA of the knee is not uncommon, but both sarcopenic and non-sarcopenic OA patients achieved significant clinical and functional improvement after TKA. Further studies with an larger sample size and different ethnicities could help ascertain a beneficial role of TKA in sarcopenic OA subjects.
Virtual Reality as a Measure to Reduce Stress of Night-Shift Anesthesiologists: Study Protocol for a Cross-Over Design Trial
Authors: Chen Chaojin , Chen Liubing , Shen Ning , Luo Chenfang , Wang Ren , Fang Hongyi , Zhang Qi , Hei Ziqing
Published: November 2020

Background: Because of the severe deficiency of global anesthesia workforce, anesthesiologists are forced to face work overload and more night shifts, which can disturbe the biological rhythm and cause major stress and depression, causing negative even devastating outcomes for both themselves and the patients eventually. Virtual reality (VR) as a new measure to reduce stress and pain for patients, has been widely used in biomedical fields.The purpose of the study is to evaluate the potential effectiveness of VR technology in reducing the stress of night-shift anesthesiologists.Methods: In this randomized controlled, cross-over design, single-center clinical trial, a total of 30 anesthesiologists are enrolled and randomized in a 1:1 allocation to either the VR immersion group (intervention group) or the routine night-shift group (control group) with a washout of 1 week. Anesthesiologists in the intervention group undergo VR immersion for twice while anesthesiologists in the control group will not watch VR videos during the night shift. The primary outcome is the difference between two groups about the score of NASA-TLX scale. Secondary outcomes include the score of CPSS, VAS and MFI-20 scales, satisfaction degree of the participants, heart rate (HR), blood pressure (BP), the incidence of arrhythmia as well as incidence of chest tightness, headache, palpitations.Discussion: It is unknown whether the use of VR technology during the night shift can reduce the stress of night-shift anesthesiologists. With the widely use of VR technology, a positive result of the trial could spur the hospital to apply the technology to reduce the stress of night shift doctors in every department as well as offer a relatively relaxed working environment.Trial registration: ChiCTR2000031025 on March 21, 2020.
Connected Diagnostics to improve accurate diagnosis, treatment, and conditional payment of malaria services in Kenya.
Authors: Duijn Shannen Van , Siteyi Angela , Smith Sherzel , Milimo Emmanuel , Stijvers Leon , Oguttu Monica , Amollo Michael , Okeyo Edward , Dayo Lilyana , Kwambai Titus , Onyango Dickens , de Wit Tobias Rinke
Published: November 2020

Background: In sub-Saharan Africa, the material and human capacity to diagnose patients reporting with fever to healthcare providers is largely insufficient. Febrile patients are typically treated presumptively with antimalarials and/or antibiotics. Such over-prescription can lead to drug resistance and involves unnecessary costs to the health system. International funding for malaria is currently not sufficient to control malaria. Transition to domestic funding is challenged by UHC efforts and recent COVID-19 outbreak. Herewith we present a digital approach to improve efficiencies in diagnosis and treatment of malaria in endemic Kisumu, Kenya: Connected Diagnostics. The objective of this study is to evaluate the feasibility, user experience and clinical performance of this approach in Kisumu.Methods: Our intervention was performed Oct 2017 – Dec 2018 across five private providers in Kisumu. Patients were enrolled on M-TIBA platform, diagnostic test results digitized, and only positive patients were digitally entitled to malaria treatment. Data on socio-demographics, healthcare transactions and medical outcomes were analysed using standard descriptive quantitative statistics. Provider perspectives were gathered by 19 semi-structured interviews.Results: In total 11,689 febrile patients were digitally tested through five private providers. Malaria positivity ranged from 7.4% to 30.2% between providers, significantly more amongst the poor (p< 0.05). Prescription of antimalarials was substantially aberrant from National Guidelines, with 28% over-prescription (4.6%-63.3% per provider) and prescription of branded versus generic antimalarials differing amongst facilities and correlating with the socioeconomic status of clients. Challenges were encountered transitioning from microscopy to RDT.Conclusion: We provide full proof-of-concept of innovative Connected Diagnostics to use digitized malaria diagnostics to earmark digital entitlements for correct malaria treatment of patients. This approach has large cost-saving and quality improvement potential.
Tele-ECG consulting and outcomes on primary care patients in a low-to-middle income population: The first experience from Makassar Telemedicine Program, Indonesia
Authors: Mappangara Idar , Qanitha Andriany , Uiterwaal Cuno S. P. M. , Henriques Jose P. S. , de Mol Bastianus A. J. M.
Published: November 2020

Background: Telemedicine has been a popular tool to overcome the lack of access to healthcare facilities, primarily in underprivileged populations. We aimed to describe and assess the implementation of a tele-electrocardiography (ECG) program in primary care settings in Indonesia, and subsequently examine the short- and mid-term outcomes of patients who have received tele-ECG consultation.Methods: ECG recordings from thirty primary care centers were transmitted to Makassar Cardiac Center, Indonesia from January to July 2017. We cross-sectionally measured the performance of this tele-ECG program, and prospectively sent a detailed questionnaire to general practitioners (GPs) at the primary care centers. We performed follow-up at 30 days and at the end of study period to assess the patient outcomes. Results: Of 505 recordings, all (100%) ECGs were qualified for analysis, and about half showed normal findings. The mean age of participants was 53.3 ± 13.6 years, and 40.2% were male. Most (373, 73.9%) of these primary care patients exhibited manifested CVD symptom with at least one risk factor. Male patients had more ischemic ECGs compared to women (p<0.01), while older age (>55 years) was associated with ischemic or arrhythmic ECGs (p<0.05). Factors significantly associated with a normal ECG were younger age, female gender, lower blood pressure and heart rate, and no history of previous cardiovascular disease (CVD) or medication. More patients with an abnormal ECG had a history of hypertension, known diabetes, and were current smokers (p<0.05). Of all tele-consultations, GPs reported 95% of satisfaction rate, and 296 (58.6%) used tele-ECG for an expert opinion. Over the total follow-up (14 ± 6.6 months), seven (1.4%) patients died and 96 (19.0%) were hospitalized for CVD. Of 88 patients for whom hospital admission was advised, 72 (81.8%) were immediately referred within 48 hours following the tele-ECG consultation. Conclusions: Tele-ECG can be implemented in Indonesian primary care settings with limited resources and may assist GPs for immediate triage, resulting in higher rate of early hospitalization for indicated patients.
A systematic review assessing the under-representation of elderly adults in COVID-19 trials
Authors: Prendki Virginie , Tau Noam , Avni Tomer , Falcone Marco , Huttner Angela , Kaiser Laurent , Paul Mical , Leibovici-Weissmann Yaara , Yahav Dafna
Published: November 2020

BackgroundCoronavirus disease (COVID-19) has caused a pandemic threatening millions of people worldwide. Yet studies specifically assessing the geriatric population are scarce. We aimed to examine the participation of elderly patients in therapeutic or prophylactic trials on COVID-19.MethodsIn this review, randomized controlled trials (RCTs; n=12) comparing therapeutic or prophylactic interventions registered on preprint repositories and/or published since December 2019 were analyzed. We searched in PubMed, leading journals websites, and preprint repositories for RCTs and large observational studies. We aimed to describe the age of included patients, the presence of an upper age limit and of adjusted analyses on age, any exclusion criteria that could limit participation of elderly adults such as comorbidities, cognitive impairment, limitation of life expectancy; and the assessment of long-term outcomes such as the need of rehabilitation or institutionalization. Mean participant ages were reported and compared with observational studies.ResultsTwelve RCTs assessing drug therapy for COVID-19 were included. Mean age of patients included in RCTs was 56.3 years. An upper age limit was applied in three published trials (25%) and in 200/650 (31%) trials registered at clinicaltrials.gov. One trial reported a subgroup analysis in patients ≥65. Patients were excluded for liver-function abnormalities in eight trials, renal disease in six, cardiac disease or risk of torsade de pointes in five, and four for cognitive or mental criteria, which are frequent comorbidities in the oldest patients. Only three trials allowed a family member to provide consent. Patients enrolled in RCTs were on average 20 years younger than those included in large (n≥1000) observational studies. Seven studies had as their primary outcome a clinical endpoint, but none reported cognitive, functional or quality of life outcomes or need for rehabilitation or long-term care facility placement.ConclusionsElderly patients are clearly underrepresented in RCTs, although they comprise the population hardest hit by the COVID-19 pandemic. Long-term outcomes such as the need of rehabilitation or institutionalization were not reported. Future investigations should target specifically this vulnerable population.
A 4-gene signature predicts prognosis of uterine serous carcinoma
Authors: Chen Hui , Li Lingjun , Qin Ping , Xiong Hanzhen , Chen Ruichao , Zhang Minfen , Jiang Qingping
Published: November 2020

Background: Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer that accounts for up to 40% of endometrial cancer deaths, creating an urgent need for prognostic biomarkers. Methods: USC RNA-Seq data and corresponding patients’ clinical records were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Univariate cox, Lasso, and Multivariate cox regression analyses were conducted to forge a prognostic signature. Multivariable and univariable cox regression analysis and ROC curve evaluated the prediction efficiency both in the training and testing sets. Results: We uncovered 1385 genes dysregulated in 110 cases of USC tissue relative to 113 cases of normal uterine tissue. Functional enrichment analysis of these genes revealed the involvement of various cancer-related pathways in USC. A novel 4‐gene signature (KRT23, CXCL1, SOX9 and ABCA10) of USC prognosis was finally forged by serial regression analyses. Overall patient survival (OS) and recurrence-free survival (RFS) were significantly lower in the high-risk group relative to the low-risk group in both the training and testing sets. The area under the ROC curve of the 4-gene signature was highest among clinicopathological features in predicting OS and RFS. The 4-gene signature was found to be an independent prognostic indicator in USC and was a superior predictor of OS in early stage of USC. Conclusions: Our findings highlight the potential of the 4-gene signature as a guide for personalized USC treatment.
Risk factors for postoperative delirium and subsyndromal delirium in older surgical patients in the surgical ward: a prospective observational study
Authors: Kanno Maya , Doi Mana , Kubota Kazumi , Kanoya Yuka
Published: November 2020

Background: Postoperative delirium (POD) among older patients is a common, serious disease and is associated with a high incidence of negative outcomes. For early detection of POD and subsyndromal delirium (SSD), this study was conducted to identify risk factors of POD and SSD in older patients who were scheduled for surgery in a surgical ward.Methods: This was a prospective observational study. Study participants were older than 65 years, underwent urology surgery, and were hospitalized in the surgical ward between April and September 2019. Both POD and SSD were assessed by using the Confusion Assessment Method (CAM) on the preoperative day, the day of surgery, and postoperative days 1–3 by the surgical ward nurses. SSD was defined as the presence of one or more CAM criteria and the absence of a diagnosis of delirium based on the CAM algorithm. Personal characteristics, clinical data, cognitive function, physical functions, laboratory test results, medication use, type of surgery and anesthesia, and use of physical restraint were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for POD and SSD.Results: A total of 101 participants (mean age 74.9 years) were enrolled; 19 (18.8%) developed POD and SSD. The use of bed sensors (odds ratio 10.2, p=.001) were identified as risk factors for POD and SSD.Conclusions: Our study shows that the use of bed sensors might be related to the development of POD and SSD among older patients in surgical wards.
Development and validation of models to predict cesarean delivery among low-risk nulliparous women at term: a retrospective study in China
Authors: Sun Fangcan , Han Bing , Wu Fangfang , Shen Qianqian , Shen Minhong , Chen Youguo
Published: November 2020

Background A prediction algorithm to identify women with high risk of an emergency cesarean could help reduce morbidity and mortality associated with labor. The objective of the present study was to derive and validate a simple model to predict intrapartum cesarean delivery for low-risk nulliparous women in Chinese population.Methods We conducted a retrospective cohort study of low-risk nulliparous women with singleton, term, cephalic pregnancies. A predictive model for cesarean delivery was derived using univariate and multivariable logistic regression from the hospital of the First Affiliated Hospital of Soochow University. External validation of the prediction model was then performed using the data from Sihong county People’s Hospital. A new nomogram was established based on the development cohort to predict the cesarean. The ROC curve, calibration plot and decision curve analysis were used to assess the predictive performance.Results The intrapartum cesarean delivery rates in the development cohort and the external validation cohort were 8.79% (576/6,551) and 7.82% (599/7,657). Multivariable logistic regression analysis showed that maternal age, height, BMI, weight gained during pregnancy, gestational age, induction method, meconium-stained amniotic fluid and neonatal sex were independent factors affecting cesarean outcome. We had established two prediction models according to fetal sex was involved or not. The AUC was 0.782 and 0.774, respectively. The two prediction models were well-calibrated with Hosmer-Lemeshow test P=0.263 and P=0.817, respectively. Decision curve analysis demonstrated that two models had clinical application value, and they provided greatest net benefit between threshold probabilities of 4% to 60%. And internal validation using Bootstrap method demonstrated similar discriminatory ability. We external validated the model involving fetal sex, for which the AUC was 0.775, while the slope and intercept of the calibration plot were 0.979 and 0.004, respectively. On the external validation set, another model had an AUC of 0.775 and a calibration slope of 1.007. The online web server was constructed based on the nomogram for convenient clinical use.Conclusions Both two models established by these factors have good prediction efficiency and high accuracy, which can provide the reference for clinicians to guide pregnant women to choose an appropriate delivery mode.
Use of intravenous sodium bicarbonate in neonatal intensive care units in Italy: a nationwide survey.
Authors: Massenzi Luca , Aufieri Roberto , Donno Silvia , Agostino Rocco , Dotta Andrea
Published: November 2020

Background: Metabolic Acidosis (MA) is a disturbance of the acid-base balance that can occur in preterm and critically ill term neonates due to different etiologies. Intravenous sodium bicarbonate (SB) has been traditionally used to correct such unbalance, despite the lack of evidence about its safety and efficacy. In literature, reported undesirable effects of treatment with SB in neonates include worsening of intracellular acidosis, impairment of myocardial function, cerebral blood flow fluctuations and intracranial hemorrhage. A national survey was conducted by the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology with the aim to assess and describe attitudes and practices concerning the use of SB, particularly for the treatment of MA in Italian NICUs. Methods: A questionnaire regarding treatment of MA and SB prescription habits was sent to the directors of 120 Italian NICUs from June 2017 to March 2018. Results: The survey response rate was 97.5% (117/120 centers). Findings showed that in 55% of the surveyed NICUs (64/117 units) it is common practice to correct MA with intravenous SB. On the other hand, the remaining 45% of the units try to solve the metabolic disturbances adopting different approaches (improving perfusion, adjusting ventilation parameters or increasing blood volume). Moreover, to prevent the occurrence of MA, 37.6% of the NICUs (44/117) include buffer salts (lactate, acetate or both) in parenteral nutrition prescriptions. SB is also used as a treatment for other conditions, mainly pathologies with bicarbonate loss and tubular acidosis (respectively in 53.8% and 32.5% of the NICUs). Conclusion: This survey showed how SB is a commonly used treatment for MA in more than half of Italian NICUs, with indications and prescription criteria that significantly vary across centers. Based on current knowledge, it is reasonable to suggest that the management of neonatal MA should be firstly directed to identify the underlying disorders. Thus, the use of SB should be reserved only for selected cases, also considering the severity of SB adverse effects and the lack of evidence about its efficacy. Guidance for the management of MA is required to harmonize practices and reduce the use of potentially inappropriate and unsafe treatments.
Expression patterns of ciliopathy genes ARL3 and CEP120 reveal roles in multisystem development
Authors: Powell L , Barroso-Gil M , Clowry Gavin J , Devlin Laura A , Molinari Elisa , Ramsbottom Simon A , Miles Colin G , Sayer John
Published: November 2020

Background: Joubert syndrome and related disorders (JSRD) and Jeune syndrome are multisystem ciliopathy disorders with overlapping phenotypes. There are a growing number of genetic causes for these rare syndromes, including the recently described genes ARL3 and CEP120.Methods: We sought to explore the developmental expression patterns of ARL3 and CEP120 in humans to gain additional understanding of these genetic conditions. We used an RNA in situ detection technique called RNAscope to characterise ARL3 and CEP120 expression patterns in human embryos and foetuses in collaboration with the MRC-Wellcome Trust Human Developmental Biology Resource.Results: Both ARL3 and CEP120 are expressed in early human brain development, including the cerebellum and in the developing retina and kidney, consistent with the clinical phenotypes seen with pathogenic variants in these genes.Conclusions: This study provides insights into the potential pathogenesis of JSRD by uncovering the spatial expression of two JSRD-causative genes during normal human development.
Effects of texture properties of semi-solid food on the sensory test for pharyngeal swallowing effort in the older adults
Authors: Park Jin-Woo , Lee Seul , Yoo Byoungseung , Nam Kiyeon
Published: November 2020

Background: Increasing viscosity can reduce the risk of aspiration into the airway, but excessively thickened food may require more force and effort. We assumed that semi-solid foods with similar viscosities will behave differently in the oropharynx and there might exist the possibility that properties other than viscosity may have clinical relevance. This study aimed to find out the texture of semi-solid foods that affects the effort of pharyngeal swallow in the older adults. Methods: Nine kinds of semi-solid foods not requiring mastication were selected for texture profile analysis (TPA), and included whipped cream, mayonnaise, soft tofu, mango pudding, boiled mashed pumpkin, boiled mashed potatoes, boiled mashed sweet potatoes, red bean paste, and peanut butter. Hardness, adhesiveness and cohesiveness of each food were measured three times by using the rheometer. A blinded sensory test using a 9-point hedonic scale was also conducted in eighteen older adults people to investigate how much effort was required to swallow food, and how much of the food remained in the pharynx after swallowing. The correlation between texture and sensory outcome was statistically analyzed.Results: Foods that belonged to the same viscosity category showed different texture values, and the participants also rated different scores respectively. Only adhesiveness among three properties was significantly correlated with the sensory test. (r= 0.882, p=0.002 for difficult to swallow, r=0.879, p=0.002 for sense of residue).Conclusions: Adhesiveness was the most important property of the semi-solid foods, requiring most efforts in pharyngeal swallow in the older adults. If we select and provide food having low adhesiveness value in the same viscosity category, there might be the possibility to make it easier to swallow in older adults.
The Effect of Salinity on Enterocytozoon hepatopenaei Infection in Penaeus vannamei Under Experimental Conditions
Authors: Aranguren Luis Fernando , Alghamdi Faris , De Belder Katrien , Lin J. , Mai Hung N. , Millabas Jasmine , Alrehaili Y. , Alazwari Anwer , Algetham Saif , Dhar Arun K.
Published: November 2020

Background: Enterocytozoon hepatopenaei (EHP) is an enteric pathogen that affects Penaeus vannamei and Penaeus monodon shrimp in many SE Asian countries. In the western hemisphere, EHP was reported for the first time in 2016 in farmed P. vannamei in Venezuela. Anecdotal evidence suggests that EHP is more prevalent in grow-out ponds where the salinity is high (>15 parts per thousand (ppt)) compared to grow-out ponds with low salinities (<5 ppt). Considering that P. vannamei is an euryhaline species, we were interested in knowing if EHP can propagate in P. vannamei in low salinities.Results: In this study, we described an experimental infection using fecal strings as a source inoculum. Specific Pathogen Free (SPF) P. vannamei were maintained at three different salinities (2 ppt, 15 ppt, and 30 ppt) while continuously challenged using feces from known EHP-infected P. vannamei over a period of three weeks. The fecal strings, used as a source of EHP inocula in the challenges, was sufficient to elicit an infection in shrimp maintained at the three salinities. The infectivity of EHP in shrimp reared at 2 ppt, 15 ppt, and 30 ppt salinities was confirmed by PCR and histopathology. The prevalence and the severity of the EHP infection was higher at 30 ppt than at 2 ppt and 15 ppt.Conclusion: The data suggests that fecal strings are a reliable source of EHP inoculum to conduct experimental challenges via the fecal-oral route. An EHP infection can occur at a salinity as low as 2 ppt, however, the prevalence and the severity of the EHP infection is higher at a salinity of 30 ppt.
An Improved BM25 for Clinical Decision Support in Precision Medicine Based on Co-word Analysis and Cuckoo Search
Authors: Zhang Zicheng
Published: November 2020

Background: Retrieving gene and disease information from a very large collection of biomedical abstracts to provide doctors with clinical decision support is one of the important research directions of Precision Medicine.Method: We propose a new method for the retrieval of biomedical articles utilizing expanded word and co-word implementations and conducting Cuckoo Search to optimize parameters of the retrieval function in the final stage of the proposed method. The specific goal is to retrieve biomedical abstracts of articles addressing treatments. The method employed in this manuscript first implements the BM25 algorithm to compute the score of the abstract, then we propose a method utilizing the BM25, an improved version of BM25, to compute the scores of expanded words and co-word that lead to a composite retrieval function. Afterward, the retrieval function is optimized using Cuckoo Search. The proposed method is utilized to find both disease and gene in the abstract of the same biomedical article. By doing so, the relevance of articles would tend to increase so would the score of the biomedical article. Besides, the manuscript discusses the influence of different parameters on the retrieval algorithm and summarizes the parameters to meet various retrieval needs.Results: All data are taken from medical articles provided in the Text Retrieval Conference (TREC) utilizing Clinical Decision Support (CDS) Tracks of 2017, 2018, and 2019 in Precision Medicine. 120 standard topics are tested. Three test indicators are employed to make comparisons among the methods utilized. To conduct comparable experiments, only the BM25 algorithm and its improved version of it are utilized. The experimental results show that the proposed algorithm achieves both better results and ranking outcomes.Conclusion: The proposed algorithm, an improved version of the BM25 algorithm, utilizes both co-word implementation and Cuckoo Search and verifies that the proposed algorithm produces better results on a large number of experimental sets. On the other hand, a relatively simple query expansion method is implemented in this manuscript. As a future direction of this research, both the ontology and semantic network to expand the query vocabulary is planned to be conducted.
Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors
Authors: Mukai Yuki , Hayashi Yuichiro , Koike Izumi , Koizumi Toshiyuki , Sugiura Madoka , Oguri Senri , Takano Shoko , Kioi Mitomu , Sato Mizuki , Mitsudo Kenji , Hata Masaharu
Published: November 2020

Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.
IL-17A polymorphism (rs2275913) and levels are associated with preeclampsia pathogenesis in Chinese patients
Authors: Lang Xiao , Liu Wei , Hou Yanyan , Zhao Wenxia , Yang Xingyu , Chen Lan , Yan Qi , Cheng Weiwei
Published: November 2020

Background: Preeclampsia (PE) is a pregnancy-related condition that affects both the infant and the mother. Although the role of various inflammatory molecules in PE has been demonstrated, the importance of pro-inflammatory molecules such as IL-17A, IL-23 is not well understood. In the present investigation, a potential association of common genetic variants in the IL-17A and IL-23A genes with PE was investigated. Methods: 115 PE clinically diagnosed patients who registered to the International Peace Maternity and Child Health Hospital were enrolled in this research. 102 pregnant women and 147 healthy Chinese women were also included. ELISA was used to measure IL-17A and IL-23 serum levels in all enrolled subjects. Common genetic polymorphisms in IL-17A (rs 2275913, rs1974226, and rs1974226), IL-23A (rs11171806), and IL-12B (rs3212227) were genotyped using the PCR-RFLP or TaqMan probe-based method. Results: Elevated serum IL-17A levels were found in PE patients compared to pregnant (P<0.0001) and healthy women (P<0.0001). However, IL-23 levels were comparable across various clinical groups. In addition, heterozygous (GA) and minor allele (A) for IL-17A (rs2275913) and IL-23A (rs11171806) were more prevalent in PE patients compared to pregnant women indicating an important role in the predisposition to PE growth. Interestingly, IL-17A (r 2275913) mutants were associated with elevated IL-17A levels relative to wild type (GG). Conclusions: IL-17A (rs2275913) variants are associated with higher serum levels of cytokine, and predisposed PE development.