bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiofrequency ablation versus repeat hepatectomy in the treatment of recurrent hepatocellular carcinoma in subcapsular location: a retrospective cohort study
Authors: Wei Fuqun , Huang Qizhen , Zhou Yang , Luo Liuping , Zeng Yongyi
Published: June 2021

Background

Repeat hepatectomy and radiofrequency ablation (RFA) are widely used to treat early recurrent hepatocellular carcinoma (RHCC) located in the subcapsular region, but the optimal treatment strategy remains to be controversial.

Methods

A total of 126 RHCC patients in the subcapsular location after initial radical hepatectomy were included in this study between Dec 2014 and Jan 2018. These patients were divided into the RFA group (46 cases) and the repeat hepatectomy group (80 cases). The primary endpoints include repeat recurrence-free survival (rRFS) and overall survival (OS), and the secondary endpoint was complications. The propensity-score matching (PSM) was conducted to minimize the bias. Complications were evaluated using the Clavien-Dindo classification, and severe complications were defined as classification of complications of ≥grade 3.

Results

There were no significant differences in the incidence of severe complications were observed between RFA group and repeat hepatectomy group in rRFS and OS both before (1-, 2-, and 3-year rRFS rates were 65.2%, 47.5%, and 33.3% vs 72.5%, 51.2%, and 39.2%, respectively, P = 0.48; 1-, 2-, and 3-year OS rates were 93.5%, 80.2%, and 67.9% vs 93.7%, 75.8%, and 64.2%, respectively, P = 0.92) and after PSM (1-, 2-, and 3-year rRFS rates were 68.6%, 51.0%, and 34.0% vs 71.4%, 42.9%, and 32.3%, respectively, P = 0.78; 1-, 2-, and 3-year OS rates were 94.3%, 82.9%, and 71.4% vs 88.6%, 73.8%, and 59.0%, respectively, P = 0.36). Moreover, no significant differences in the incidence of severe complications were observed between the RFA group and repeat hepatectomy group.

Conclusion

Both repeat hepatectomy and RFA are shown to be effective and safe for the treatment of RHCC located in the subcapsular region.
MiR-194-5p enhances the sensitivity of nonsmall-cell lung cancer to doxorubicin through targeted inhibition of hypoxia-inducible factor-1
Authors: Xia Mengning , Sheng Lili , Qu Wei , Xue Xue , Chen Hucheng , Zheng Guoyan , Chen Weigang
Published: June 2021

Background

Despite chemotherapy being a common treatment, an increase in chemoresistance over time is unavoidable. We therefore investigated the role of miR-194-5p in regulating chordoma cell behavior and examined the downstream effectors of miR-194-5p.

Methods

In this study, NSCLC cell lines A549 and H460 were cultured under hypoxic conditions for 1 week to induce drug resistance to doxorubicin (DOX). The connection between miR-194-5p and HIF-1 was revealed by reverse transcription and real-time polymerase chain reaction (RT-qPCR), western blot, and dual-luciferase assays. We used TUNEL staining and the CCK-8 test to assess the sensitivity of NSCLC cells to DOX.

Results

We found that hypoxia-induced NSCLC cells enhanced resistance to DOX. MiR-194-5p was substantially reduced, and HIF-1 was increased in hypoxia-induced drug-resistant NSCLC cells. Moreover, miR-194-5p successfully induced NSCLC cell apoptosis by directly inhibiting HIF-1, thereby enhancing DOX sensitivity.

Conclusions

MiR-194-5p enhanced the sensitivity of NSCLC cells to DOX by directly inhibiting HIF-1. This work provides insights into underlying treatments for drug-resistant NSCLC.
Hospital utilization rates for influenza and RSV: a novel approach and critical assessment
Authors: Johnson Emily K. , Sylte Dillon , Chaves Sandra S. , Li You , Mahe Cedric , Nair Harish , Paget John , van Pomeren Tayma , Shi Ting , Viboud Cecile , James Spencer L.
Published: June 2021

Background

Influenza and respiratory syncytial virus (RSV) contribute significantly to the burden of acute lower respiratory infection (ALRI) inpatient care, but heterogeneous coding practices and availability of inpatient data make it difficult to estimate global hospital utilization for either disease based on coded diagnoses alone.

Methods

This study estimates rates of influenza and RSV hospitalization by calculating the proportion of ALRI due to influenza and RSV and applying this proportion to inpatient admissions with ALRI coded as primary diagnosis. Proportions of ALRI attributed to influenza and RSV were extracted from a meta-analysis of 360 total sources describing inpatient hospital admissions which were input to a Bayesian mixed effects model over age with random effects over location. Results of this model were applied to inpatient admission datasets for 44 countries to produce rates of hospital utilization for influenza and RSV respectively, and rates were compared to raw coded admissions for each disease.

Results

For most age groups, these methods estimated a higher national admission rate than the rate of directly coded influenza or RSV admissions in the same inpatient sources. In many inpatient sources, International Classification of Disease (ICD) coding detail was insufficient to estimate RSV burden directly. The influenza inpatient burden estimates in older adults appear to be substantially underestimated using this method on primary diagnoses alone. Application of the mixed effects model reduced heterogeneity between countries in influenza and RSV which was biased by coding practices and between-country variation.

Conclusions

This new method presents the opportunity of estimating hospital utilization rates for influenza and RSV using a wide range of clinical databases. Estimates generally seem promising for influenza and RSV associated hospitalization, but influenza estimates from primary diagnosis seem highly underestimated among older adults. Considerable heterogeneity remains between countries in ALRI coding (i.e., primary vs non-primary cause), and in the age profile of proportion positive for influenza and RSV across studies. While this analysis is interesting because of its wide data utilization and applicability in locations without laboratory-confirmed admission data, understanding the sources of variability and data quality will be essential in future applications of these methods.
Inter-examinerreliability study of physical examination procedures to assess the cervical spine
Authors: Hariharan Karthik V. , Timko Michael G. , Bise Christopher G. , Sundaram Meenakshi , Schneider Michael J.
Published: June 2021

Objective

The objective of this study was to establish the level of inter-examiner reliability for six common cervical manual and physical examination procedures used to assess the cervical spine.

Materials:

Reliability study that used a convenience sample of 51 patients between the ages of 16–70 years presenting with a chief complaint of neck pain. Two physical therapists independently performed the same series of cervical physical examination procedures on each of the participant. The clinicians were blinded to each other’s findings and the clinical status of the patient. Kappa coefficients (κ) were calculated for levels of agreement between the clinicians for each procedure.

Results

When assessing for asymmetrical motion, excellent levels of reliability (κ range: 0.88–0.96) were observed for the Bilateral Modified Lateral Shear (asymmetry criterion), Bilateral C2 Spinous Kick (asymmetry criterion) and Flexion-Rotation Tests. When pain provocation was used as the indicator of a positive test during palpation of the cervical facet joints, moderate to substantial levels of reliability (κ range: 0.53–0.76) were observed. When patients were instructed not to provide feedback to the clinicians about pain provocation during facet joint palpation and clinicians relied solely on their qualitative assessment of segmental mobility, the level of reliability was lower (κ range: 0.45–0.53). Due to 100 % prevalence of negative findings, Kappa values could not be calculated for the Sharp-Purser test or the Unilateral C2 Spinous Kick Test.

Conclusions

Most physical examination procedures examined in this study demonstrated moderate to excellent levels of inter-examiner reliability. Palpation for segmental mobility without pain provocation demonstrated a lower level of reliability compared to palpation for pain provocation. Correlation with clinical findings is necessary to establish validity and the applicability of these procedures in clinical practice.
Reasonable suspicion in reporting child maltreatment: a survey among German healthcare professionals
Authors: Berthold Oliver , Jud Andreas , Jarczok Marion , Fegert Jörg M. , Clemens Vera
Published: June 2021

Background

With regular contacts to the general child population, healthcare professionals could play an important role in the detection of child maltreatment. However, a majority of child maltreatment cases go unnoticed by the healthcare system. Child protection legislations usually offer terms like “reasonable suspicion” to corner a threshold that warrants reporting to child protection services (CPS) is defined as. The indistinct legal terminology leads to marked differences in the interpretation of this threshold. Therefore, we aimed to systematically assess the understanding of reasonable suspicion and subsequent handling of cases in the German context.

Methods

A cross-sectional online survey was conducted among 2485 physicians and psychotherapists working with children and adolescents. Field access was gained by German professional associations. Via case vignettes, predictors of thresholds for reporting were assessed.

Results

The probability of a report to CPS increased positively with the degree of suspicion for maltreatment. However, even if participants were certain that child maltreatment occurred, 20% did not chose to report to CPS. Training in child protection lowered the professionals’ threshold for reasonable suspicion; experience with child protection cases and good knowledge of the legal framework increased the likelihood to report an alleged situation of child maltreatment to CPS.

Conclusion

Our data show that a significant proportion of health care professionals are uncertain about estimating reasonable suspicion and on how to proceed when there are strong indications for child maltreatment Therefore, data point towards the relevance of training in child protection among healthcare professionals in order to improve detection and adequate handling of cases of child maltreatment.
Landscape and selection of vaccine epitopes in SARS-CoV-2
Authors: Smith Christof C. , Olsen Kelly S. , Gentry Kaylee M. , Sambade Maria , Beck Wolfgang , Garness Jason , Entwistle Sarah , Willis Caryn , Vensko Steven , Woods Allison , Fini Misha , Carpenter Brandon , Routh Eric , Kodysh Julia , O’Donnell Timothy , Haber Carsten , Heiss Kirsten , Stadler Volker , Garrison Erik , Sandor Adam M. , Ting Jenny P. Y. , Weiss Jared , Krajewski Krzysztof , Grant Oliver C. , Woods Robert J. , Heise Mark , Vincent Benjamin G. , Rubinsteyn Alex
Published: June 2021

Background

Early in the pandemic, we designed a SARS-CoV-2 peptide vaccine containing epitope regions optimized for concurrent B cell, CD4+T cell, and CD8+T cell stimulation. The rationale for this design was to drive both humoral and cellular immunity with high specificity while avoiding undesired effects such as antibody-dependent enhancement (ADE).

Methods

We explored the set of computationally predicted SARS-CoV-2 HLA-I and HLA-II ligands, examining protein source, concurrent human/murine coverage, and population coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, sequence conservation, source protein abundance, and coverage of high frequency HLA alleles. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering for surface accessibility, sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites.

Results

From 58 initial candidates, three B cell epitope regions were identified. From 3730 (MHC-I) and 5045 (MHC-II) candidate ligands, 292 CD8+and 284 CD4+T cell epitopes were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we proposed a set of 22 SARS-CoV-2 vaccine peptides for use in subsequent murine studies. We curated a dataset of ~ 1000 observed T cell epitopes from convalescent COVID-19 patients across eight studies, showing 8/15 recurrent epitope regions to overlap with at least one of our candidate peptides. Of the 22 candidate vaccine peptides, 16 (n = 10 T cell epitope optimized; n = 6 B cell epitope optimized) were manually selected to decrease their degree of sequence overlap and then synthesized. The immunogenicity of the synthesized vaccine peptides was validated using ELISpot and ELISA following murine vaccination. Strong T cell responses were observed in 7/10 T cell epitope optimized peptides following vaccination. Humoral responses were deficient, likely due to the unrestricted conformational space inhabited by linear vaccine peptides.

Conclusions

Overall, we find our selection process and vaccine formulation to be appropriate for identifying T cell epitopes and eliciting T cell responses against those epitopes. Further studies are needed to optimize prediction and induction of B cell responses, as well as study the protective capacity of predicted T and B cell epitopes.
Prevalence and risk factors of hemodynamic instability associated with preload-dependence during continuous renal replacement therapy in a prospective observational cohort of critically ill patients
Authors: Chazot Guillaume , Bitker Laurent , Mezidi Mehdi , Chebib Nader , Chabert Paul , Chauvelot Louis , Folliet Laure , David Guillaume , Provoost Judith , Yonis Hodane , Richard Jean-Christophe
Published: June 2021

Background

Hemodynamic instability is a frequent complication of continuous renal replacement therapy (CRRT). Postural tests (i.e., passive leg raising in the supine position or Trendelenburg maneuver in the prone position) combined with measurement of cardiac output are highly reliable to identify preload-dependence and may provide new insights into the mechanisms involved in hemodynamic instability related to CRRT (HIRRT). We aimed to assess the prevalence and risk factors of HIRRT associated with preload-dependence in ICU patients.

We conducted a single-center prospective observational cohort study in ICU patients with acute kidney injury KDIGO 3, started on CRRT in the last 24 h, and monitored with a PiCCO® device. The primary endpoint was the rate of HIRRT episodes associated with preload-dependence during the first 7 days after inclusion. HIRRT was defined as the occurrence of a mean arterial pressure below 65 mmHg requiring therapeutic intervention. Preload-dependence was assessed by postural tests every 4 h, and during each HIRRT episode. Data are expressed in median [1st quartile–3rd quartile], unless stated otherwise.

Results

42 patients (62% male, age 69 [59–77] year, SAPS-2 65 [49–76]) were included 6 [1–16] h after CRRT initiation and studied continuously for 121 [60–147] h. A median of 5 [3–8] HIRRT episodes occurred per patient, for a pooled total of 243 episodes. 131 episodes (54% [CI95% 48–60%]) were associated with preload-dependence, 108 (44%, [CI95% 38–51%]) without preload-dependence, and 4 were unclassified. Multivariate analysis (using variables collected prior to HIRRT) identified the following variables as risk factors for the occurrence of HIRRT associated with preload-dependence: preload-dependence before HIRRT [odds ratio (OR) = 3.82, p < 0.001], delay since last HIRRT episode > 8 h (OR = 0.56, p < 0.05), lactate (OR = 1.21 per 1-mmol L−1 increase, p < 0.05), cardiac index (OR = 0.47 per 1-L min−1 m−2 increase, p < 0.001) and SOFA at ICU admission (OR = 0.91 per 1-point increase, p < 0.001). None of the CRRT settings was identified as risk factor for HIRRT.

Conclusions

In this single-center study, HIRRT associated with preload-dependence was slightly more frequent than HIRRT without preload-dependence in ICU patients undergoing CRRT. Testing for preload-dependence could help avoiding unnecessary decrease of fluid removal in preload-independent HIRRT during CRRT.
Surgery school—who, what, when, and how: results of a national survey of multidisciplinary teams delivering group preoperative education
Authors: Fecher-Jones I. , Grimmett C. , Carter F. J. , Conway D. H. , Levett D. Z. H. , Moore J. A.
Published: June 2021

Background

Group education is increasing in popularity as a means of preparing patients for surgery. In recent years, these ‘surgery schools’ have evolved from primarily informing patients of what to expect before and after surgery, to providing support and encouragement for patients to ‘prehabilitate’ prior to surgery, through improving physical fitness, nutrition and emotional wellbeing.

Method

A survey aimed at clinicians delivering surgery schools was employed to capture a national overview of activity to establish research and practice priorities in this area. The survey was circulated online via the Enhanced Recovery after Surgery UK Society and the Centre for Perioperative Care mailing lists as well as social media.

Results

There were 80 responses describing 28 active and 4 planned surgery schools across the UK and Ireland. Schools were designed and delivered by multidisciplinary teams, contained broadly similar content and were well attended. Most were funded by the National Health Service. The majority included aspects of prehabilitation most commonly the importance of physical fitness. Seventy five percent of teams collected patient outcome data, but less than half collected data to establish the clinical effectiveness of the school. Few describe explicit inclusion of evidence-based behavior change techniques, but collaboration and partnerships with community teams, gyms and local charities were considered important in supporting patients to make changes in health behaviors prior to surgery.

Conclusion

It is recommended that teams work with patients when designing surgery schools and use evidence-based behavior change frameworks and techniques to inform their content. There is a need for high-quality research studies to determine the clinical effectiveness of this type of education intervention.
Effects of supplements differing in fatty acid profile to late gestational beef cows on cow performance, calf growth performance, and mRNA expression of genes associated with myogenesis and adipogenesis
Authors: Shao Taoqi , Ireland Frank A. , McCann Joshua C. , Shike Daniel W.
Published: June 2021

Background

Maternal nutrition during gestation affects fetal development, which has long-term programming effects on offspring postnatal growth performance. With a critical role in protein and lipid metabolism, essential fatty acids can influence the development of muscle and adipose tissue. The experiment investigated the effects of late gestation supplements (77 d prepartum), either rich in saturated and monounsaturated fatty acids (CON; 155 g/cow/d EnerGII) or polyunsaturated fatty acids (PUFA; 80 g/cow/d Strata and 80 g/cow/d Prequel), on cow performance and subsequent calf growth performance as well as mRNA expression in longissimus muscle (LM) and subcutaneous adipose tissue at birth and weaning.

Results

There was no difference (P ≥ 0.34) in cow body weight (BW) or body condition score from pre-supplementation through weaning. Relative concentrations of C18:3n-3 and C20:4n-6 decreased (P ≤ 0.05) to a greater extent from mid-supplementation to calving for PUFA compared with CON cows. Cow plasma C20:0, C20:5n-3, and C22:6n-3 were increased (P ≤ 0.01) in PUFA during supplementation period. At birth, PUFA steers had greater (P = 0.01) plasma C20:5n-3. No differences (P ≥ 0.33) were detected in steer birth BW or dam milk production, however, CON steers tended (P = 0.06) to have greater pre-weaning average daily gain and had greater (P = 0.05) weaning BW compared with PUFA. For mRNA expression in steers: MYH7 and C/EBPβ in LM increased (P ≤ 0.04) to a greater extent from birth to weaning for PUFA compared with CON; MYF5 in LM and C/EBPβ in adipose tissue tended (P ≤ 0.08) to decrease more from birth to weaning for CON compared with PUFA; SCD in PUFA adipose tissue tended (P = 0.08) to decrease to a greater extent from birth to weaning than CON. In addition, maternal PUFA supplementation tended (P = 0.08) to decrease MYOG mRNA expression in LM and decreased (P = 0.02) ZFP423 in adipose tissue during the pre-weaning stage.

Conclusions

Late gestation PUFA supplementation decreased pre-weaning growth performance of the subsequent steer progeny compared with CON supplementation, which could have been a result of downregulated mRNA expression of myogenic genes during pre-weaning period.
Apply machine learning techniques to detect malicious network traffic in cloud computing
Authors: Alshammari Amirah , Aldribi Abdulaziz
Published: June 2021

Computer networks target several kinds of attacks every hour and day; they evolved to make significant risks. They pass new attacks and trends; these attacks target every open port available on the network. Several tools are designed for this purpose, such as mapping networks and vulnerabilities scanning. Recently, machine learning (ML) is a widespread technique offered to feed the Intrusion Detection System (IDS) to detect malicious network traffic. The core of ML models’ detection efficiency relies on the dataset’s quality to train the model. This research proposes a detection framework with an ML model for feeding IDS to detect network traffic anomalies. This detection model uses a dataset constructed from malicious and normal traffic. This research’s significant challenges are the extracted features used to train the ML model about various attacks to distinguish whether it is an anomaly or regular traffic. The dataset ISOT-CID network traffic part uses for the training ML model. We added some significant column features, and we approved that feature supports the ML model in the training phase. The ISOT-CID dataset traffic part contains two types of features, the first extracted from network traffic flow, and the others computed in specific interval time. We also presented a novel column feature added to the dataset and approved that it increases the detection quality. This feature is depending on the rambling packet payload length in the traffic flow. Our presented results and experiment produced by this research are significant and encourage other researchers and us to expand the work as future work.
Examining engineering students’ participation in entrepreneurship education programs: implications for practice
Authors: Shekhar Prateek , Huang-Saad Aileen
Published: June 2021

Background

Recent research has demonstrated the importance of entrepreneurship education programs (EEPs) in the professional development of engineering students. Numerous universities have adopted various forms of EEPs which are typically offered as elective programs. To create suitable programs that will encourage students to seek out EEPs, it is critical to understand the factors that influence student participation in EEPs. Using qualitative research methods, we examined the question “What influences engineering students’ participation in entrepreneurship education programs?” The purpose of our work is to identify and understand the factors impacting engineering student participation in EEPs.

Results

Analysis of 20 semi-structured interviews of undergraduate engineering students was conducted using the first and second cycle coding methods to determine key factors that inform students’ participation in EEPs. We found that student decisions to participate in EEPs are influenced by several factors: entrepreneurial self-efficacy, entrepreneurial intent, attitude, subjective norm, goals, academic transitions, information and resources, social capital, opportunities and challenges, and past participation in EEPs.

Conclusions

Findings demonstrate that students’ non-compulsory participation is not a result of a single act, but is regulated by multiple factors. Explication of these factors using our qualitative results provides actionable guidance for EEPs to encourage engineering students’ participation and offers directions for future research.
Automation of 3D average human body shape modeling using Rhino and Grasshopper Algorithm
Authors: Lee Kyu Sun , Song Hwa Kyung
Published: June 2021

The aim of this study is to develop an automated process for modeling average 3D human body according to body types using both NUBRS-based modeling software Rhinoceros 3D® (Rhino) and Grasshopper as an algorithm editor. First, we categorized men aged 36 to 55 years included in SizeUSA 3D data into the three body types (normal, overweight, and obese), and selected seven samples in each body type. To execute the automated process of generating an average 3D model of their lower bodies in a step-by-step manner, the following procedures were performed: (1) Determine the main reference lines on the 3D-scanned lower bodies, including six horizontal reference lines and six vertical reference lines; (2) Create horizontal and vertical line grids and intersection points (3) Generate an average 3D model in a position that corresponds to the average coordinates of the intersection points (vertex coordinates) of seven samples for each body type. A Grasshopper algorithm was formulated to automatically execute all procedures that had to be repeatedly performed. As a way to verify the average model’s size and shape, the girth measurements of the samples for each body type were averaged, and the results were compared with those of the 3D average body shape. It was found that the deviation was less than 1 cm, which indicates the validity of the 3D modeling approach applied in the present study. Each process was incorporated into commands available in the Rhino interface, and this automation allowed a number of 3D body shape modeling operations to be implemented in a significantly reduced time period.
Editors-in-chief perceptions of patients as (co) authors on publications and the acceptability of ICMJE authorship criteria: a cross-sectional survey
Authors: Cobey Kelly D. , Monfaredi Zarah , Poole Evelyn , Proulx Laurie , Fergusson Dean , Moher David
Published: June 2021

Background

Access to, and awareness of, appropriate authorship criteria is an important right for patient partners. Our objective was to measure medical journal Editors-in-Chief’ perceptions of including patients as (co-)authors on research publications and to measure their views on the application of the ICMJE (International Committee of Medical Journals Editors) authorship criteria to patient partners.

Methods

We conducted a cross-sectional survey co-developed with a patient partner. Editors-in-Chief of English-language medical journals were identified via a random sample of journals obtained from the Scopus source list. The key outcome measures were whether Editors-in-Chief believed: 1) patient partners should be (co-)authors and; 2) whether they felt the ICMJE criteria for authorship required modification for use with patient partners. We also measured Editors-in-Chief description of how their journal’s operations incorporate patient partner perspectives.

Results

One hundred twelve Editors-in-Chief responded to our survey (18.7% response rate; 66.69% male). Participants were able to skip any questions they did not want to answer, so there is missing data for some items. 69.2% (N = 74) of Editors-in-Chief indicated it was acceptable for patient partners to be authors or co-authors on published biomedical research articles, with the remaining 30.8% (N = 33) indicating this would not be appropriate. When asked specifically about the ICMJE authorship criteria, and whether this should be revised to be more inclusive of patient partners, 35.8% (N = 39) indicated it should be revised, 35.8% (N = 39) indicated it should not be revised, and 28.4% (N = 31) were unsure about a revision. 74.1% (N = 80) of Editors-in-Chief did not think patients should be required to have an academic affiliation to published while 16.7% (N = 18) and 9.3% (N = 10) indicated they should or were unsure. 3.6% (N = 4) of Editors-in-Chief indicated their journal had a policy that specifies how patients or patient partners should be considered as authors.

Conclusions

Our findings highlight gaps that may act as barriers to patient partner participation in research. A key implication is the need for education and for consensus building within the biomedical community to establish processes that will facilitate equitable patient partners inclusion.
Factors predicting poor anticoagulant control on warfarin in a Thai population with non-valvular atrial fibrillation (NVAF): the ACAChE score
Authors: Lertsanguansinchai Piyoros , Huntrakul Anurut , Rungpradubvong Voravut , Chokesuwattanaskul Ronpichai , Prechawat Somchai
Published: June 2021

Background

In many low- to middle-income countries in Asia, patients with NVAF usually received warfarin for thromboembolic prevention due to cost-effectiveness. The SAMe-TT2R2 score has been proposed to predict TTR in NVAF patients. However, the SAMe-TT2R2 score has not been much validated in Asian population. Interestingly, it may overestimate patients who had TTR < 65% due to regarding being Asians as a risk factor.

Objectives

To determine the factors predicting poor anticoagulant control on warfarin, create new scoring system, and compare with the SAMe-TT2R2 score in a Thai population with NVAF.

Methods

This is a retrospective study in a tertiary care hospital. We enrolled NVAF patients who received warfarin from January 2014 to December 2018. TTR was calculated based on Rosendaal method. Multiple logistic regression and AUC-ROC curve were used for analysis.

Results

A total of 864 patients were enrolled with mean age of 73.6 ± 11.58 years. The mean TTR was 48.1 ± 25.2%. Using multivariate regression analysis, the predictive factors for TTR < 65% were antiplatelet use (OR 4.49, p ≤ 0.001), LVEF < 40% (OR 1.92, p = 0.037), chronic kidney disease (GFR < 50 ml/min/1.73 m2) (OR 1.68, p = 0.013), history of CHF (OR 1.7, p = 0.047), and age ≥ 75 years (OR 1.4, p = 0.037). Based on the regression coefficients, we developed the new scoring system called ACAChE score [A, antiplatelet use (4 points); C, chronic kidney disease, GFR < 50 ml/min/1.73 m2 (2 points); A, age ≥ 75 years (1 point); Ch, history of CHF (2 points); E, LVEF < 40% (2 points)]. ROC curve showed discrimination performance of the ACAChE score and SAMe-TT2R2 score for prediction of TTR < 65% with the C-statistic of 0.62 (95%CI 0.57–0.65) and 0.54 (95%CI 0.50–0.58), respectively.

Conclusion

In Thai NVAF patients, the ACAChE score (antiplatelet use, chronic kidney disease (GFR < 50 ml/min/1.73 m2), age ≥ 75 years, history of congestive heart failure, and LVEF < 40%) has better prediction for TTR < 65% than SAMe-TT2R2 score. Thus, it expected to guide the selection of oral anticoagulation in Asian patients with NVAF.
Diagnostic accuracy of Leucine-rich α-2 glycoprotein (LRG) as a urinary biomarker in pediatric appendicitis: a prospective observational pilot study from Eastern India
Authors: Mahalik Santosh Kumar , Bandyopadhyay Debapriya , Tripathy Bikasha Bihary , Pati Akash Bihari , Mohanty Manoj Kumar
Published: June 2021

Background

Recently, several serum and urinary biomarkers have been investigated for diagnosis of acute appendicitis. Urinary biomarkers seem to be advantageous in children as it is non-invasive, painless, and easy to perform. Leucine-rich α-2-glycoprotein (LRG) is regarded as a reliable urinary biomarker for the diagnosis of pediatric appendicitis. A prospective observational pilot study was conducted in children presenting with abdominal pain. Assessment of pediatric appendicitis score (PAS), routine blood tests, and measurements of urinary LRG was done. The present study aimed to evaluate the diagnostic accuracy of urine LRG in appendicitis in Indian children and to assess the concentration of urine LRG at which it will guide the management.

Results

LRG had a receiver operating characteristic (ROC) area under the curve (AUC) of 0.586 (95% CI 0.407–0.766). There was no specific cut-off identified using Youden’s index. ROC analysis of the PAS score resulted in an AUC of 0.821 (95% CI 0.691–0.952). Using Youden’s index, the cut-off for PAS scoring was identified as 6.5 with the sensitivity of 80%, the specificity of 76.2%, positive predictive value 76.19%, negative predictive value as 80%, and diagnostic accuracy of 78%.

Conclusions

LRG could not show better diagnostic performance compared to routine blood tests and PAS scores. There was no specific cut-off value at which it will differentiate mesenteric adenitis and acute appendicitis and guide their management. With 78% diagnostic accuracy, PAS score (> 6) is still a better tool for the diagnosis of acute appendicitis.

Trial registration

Clinical Trials Registry Government of India, CTRI/2018/01/011182, Registered on: 08 Jan 2018.
Definition, Prevalence, and Risk Factors of Low Sex Hormone-Binding Globulin in US Adults
Authors: Wang Yutang
Published: June 2021

Context

Lower sex hormone-binding globulin (SHBG) is associated with many diseases including cardiovascular disease, cancer, polycystic ovarian syndrome, arthritis, and liver disease. However, the definition of low SHBG and its prevalence in US adults are unknown.

Objective

To define low SHBG and to determine its prevalence and risk factors in US adults.

Design, Setting, and Participants

This cohort study included adults ≥20 years from the US National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 who had fasting serum SHBG.

Exposures

NHANES coverage during 2013-2016.

Main Outcomes Measures

Definition, prevalence, and risk factors of low SHBG.

Results

This study included 4093 adults (weighted sample size of 204 789 616) with a mean (SD) age of 47.5 (17.0) years. In a “healthy” reference sub-cohort of 1477 adults, low SHBG was defined as SHBG < 12.3 nmol/L in men < 50 years, <23.5 nmol/L in men ≥ 50 years, <14.5 nmol/L in women < 30 years, and <21.9 nmol/L in women ≥ 30 years. The estimated US national prevalence of low SHBG was 3.3% in men, 2.7% in women, and 3.0% overall. Risk factors for this condition in both men and women included higher body mass index, diabetes, ethnicity (being other than Hispanic, non-Hispanic black, or non-Hispanic white), chronic obstructive pulmonary disease, coronary heart disease, and smoking.

Conclusions

This study established the criteria for low SHBG among US adults. The estimated US national prevalence of low SHBG was 3.3% in men and 2.7% in women.
Endocrine Dysfunction in Patients With Myotonic Dystrophy
Authors: Winters Stephen J
Published: June 2021

Myotonic dystrophy is a dominantly inherited multisystem disorder that results from increased CTG repeats in the 3′ region of the myotonic dystrophy protein kinase gene (DMPK). The mutant DMPK mRNA remains in the nucleus and sequesters RNA-binding proteins, including regulators of mRNA splicing. Myotonic dystrophy is characterized by a highly variable phenotype that includes muscle weakness and myotonia, and the disorder may affect the function of many endocrine glands. DMPK mRNA is expressed in muscle, testis, liver, pituitary, thyroid, and bone; the mutated form leads to disruption of meiosis and an increase in fetal insulin receptor-A relative to adult insulin receptor-B, resulting in adult primary testicular failure and insulin resistance predisposing to diabetes, respectively. Patients with myotonic dystrophy are also at increased risk for hyperlipidemia, nonalcoholic fatty liver disease, erectile dysfunction, benign and malignant thyroid nodules, bone fractures, miscarriage, preterm delivery, and failed labor during delivery. Circulating parathyroid hormone and adrenocorticotropic hormone levels may be elevated, but the mechanisms for these associations are unclear. This review summarizes what is known about endocrine dysfunction in individuals with myotonic dystrophy.
Mild Idiopathic Infantile Hypercalcemia—Part 1: Biochemical and Genetic Findings
Authors: Lenherr-Taube Nina , Young Edwin J , Furman Michelle , Elia Yesmino , Assor Esther , Chitayat David , Uster Tami , Kirwin Susan , Robbins Katherine , Vinette Kathleen M B , Daneman Alan , Marshall Christian R , Collins Carol , Thummel Kenneth , Sochett Etienne , Levine Michael A
Published: June 2021

Context

Idiopathic infantile hypercalcemia (IIH), an uncommon disorder characterized by elevated serum concentrations of 1,25 dihydroxyvitamin D (1,25(OH)2D) and low parathyroid hormone (PTH) levels, may present with mild to severe hypercalcemia during the first months of life. Biallelic variants in the CYP24A1 or SLC34A1 genes are associated with severe IIH. Little is known about milder forms.

Objective

This work aims to characterize the genetic associations and biochemical profile of mild IIH.

Methods

This is a cross-sectional study including children between age 6 months and 17 years with IIH who were followed in the Calcium Clinic at the Hospital for Sick Children (SickKids), Toronto, Canada. Twenty children with mild IIH on calcium-restricted diets were evaluated. We performed a dietary assessment and analyzed biochemical measures including vitamin D metabolites and performed a stepwise molecular genetic analysis. Complementary biochemical assessments and renal ultrasounds were offered to first-degree family members of positive probands.

Results

The median age was 16 months. Median serum levels of calcium (2.69 mmol/L), urinary calcium:creatinine ratio (0.72 mmol/mmol), and 1,25(OH)2D (209 pmol/L) were elevated, whereas intact PTH was low normal (22.5 ng/L). Mean 1,25(OH)2D/PTH and 1,25(OH)2D/25(OH)D ratios were increased by comparison to healthy controls. Eleven individuals (55%) had renal calcification. Genetic variants were common (65%), with the majority being heterozygous variants in SLC34A1 and SLC34A3, while a minority showed variants of CYP24A1 and other genes related to hypercalciuria.

Conclusion

The milder form of IIH has a distinctive vitamin D metabolite profile and is primarily associated with heterozygous SLC34A1 and SLC34A3 variants.
Physiological Characterization and Transcriptomic Properties of GnRH Neurons Derived From Human Stem Cells
Authors: Keen Kim L , Petersen Andrew J , Figueroa Alexander G , Fordyce Benjamin I , Shin Jaeweon , Yadav Rachita , Erdin Serkan , Pearce Robert A , Talkowski Michael E , Bhattacharyya Anita , Terasawa Ei
Published: June 2021

Gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus play a key role in the regulation of reproductive function. In this study, we sought an efficient method for generating GnRH neurons from human embryonic and induced pluripotent stem cells (hESC and hiPSC, respectively). First, we found that exposure of primitive neuroepithelial cells, rather than neuroprogenitor cells, to fibroblast growth factor 8 (FGF8), was more effective in generating GnRH neurons. Second, addition of kisspeptin to FGF8 further increased the efficiency rates of GnRH neurogeneration. Third, we generated a fluorescent marker mCherry labeled human embryonic GnRH cell line (mCh-hESC) using a CRISPR-Cas9 targeting approach. Fourth, we examined physiological characteristics of GnRH (mCh-hESC) neurons: similar to GnRH neurons in vivo, they released the GnRH peptide in a pulsatile manner at ~60 min intervals; GnRH release increased in response to high potassium, kisspeptin, estradiol, and neurokinin B challenges; and injection of depolarizing current induced action potentials. Finally, we characterized developmental changes in transcriptomes of GnRH neurons using hESC, hiPSC, and mCh-hESC. The developmental pattern of transcriptomes was remarkably similar among the 3 cell lines. Collectively, human stem cell–derived GnRH neurons will be an important tool for establishing disease models to understand diseases, such as idiopathic hypothalamic hypogonadism, and testing contraceptive drugs.
A functional genetic screen identifies aurora kinase b as an essential regulator of Sox9-positive mouse embryonic lung progenitor cells
Authors: Ah-Cann Casey , Wimmer Verena C. , Weeden Clare E. , Marceaux Claire , Law Charity W. , Galvis Laura , Filby Caitlin E. , Liu Joy , Breslin Kelsey , Willson Tracy , Ritchie Matthew E. , Blewitt Marnie E. , Asselin-Labat Marie-Liesse
Published: June 2021

Development of a branching tree in the embryonic lung is crucial for the formation of a fully mature functional lung at birth. Sox9+ cells present at the tip of the primary embryonic lung endoderm are multipotent cells responsible for branch formation and elongation. We performed a genetic screen in murine primary cells and identified aurora kinase b (Aurkb) as an essential regulator of Sox9+ cells ex vivo. In vivo conditional knockout studies confirmed that Aurkb was required for lung development but was not necessary for postnatal growth and the repair of the adult lung after injury. Deletion of Aurkb in embryonic Sox9+ cells led to the formation of a stunted lung that retained the expression of Sox2 in the proximal airways, as well as Sox9 in the distal tips. Although we found no change in cell polarity, we showed that loss of Aurkb or chemical inhibition of Aurkb caused Sox9+ cells to arrest at G2/M, likely responsible for the lack of branch bifurcation. This work demonstrates the power of genetic screens in identifying novel regulators of Sox9+ progenitor cells and lung branching morphogenesis.
Ca2+ release via InsP3Rs enhances RyR recruitment during Ca2+ transients by increasing dyadic [Ca2+] in cardiomyocytes
Authors: Demydenko Kateryna , Sipido Karin R. , Roderick H. Llewelyn
Published: June 2021

Excitation–contraction coupling (ECC) relies on temporally synchronized sarcoplasmic reticulum (SR) Ca2+ release via ryanodine receptors (RyRs) at dyadic membrane compartments. Neurohormones, such as endothelin-1 (ET-1), that act via Gαq-associated G protein-coupled receptors (GPCRs) modulate Ca2+ dynamics during ECC and induce SR Ca2+ release events involving Ca2+ release via inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs). How the relatively modest Ca2+ release via InsP3Rs elicits this action is not resolved. Here, we investigated whether the actions of InsP3Rs on Ca2+ handling during ECC were mediated by a direct influence on dyadic Ca2+ levels and whether this mechanism contributes to the effects of ET-1. Using a dyad-targeted genetically encoded Ca2+ reporter, we found that InsP3R activation augmented dyadic Ca2+ fluxes during Ca2+ transients and increased Ca2+ sparks. RyRs were required for these effects. These data provide the first direct demonstration of GPCR and InsP3 effects on dyadic Ca2+, and support the notion that Ca2+ release via InsP3Rs influences Ca2+ transients during ECC by facilitating the activation and recruitment of proximal RyRs. We propose that this mechanism contributes to neurohormonal modulation of cardiac function.

This article has an associated First Person interview with the first author of the paper.
Associative learning of non-sugar nectar components: amino acids modify nectar preference in a hawkmoth
Authors: Broadhead Geoffrey T. , Raguso Robert A.
Published: June 2021

The nearly ubiquitous presence of amino acids in the nectar of flowering plants has led to significant interest in the relevance of these compounds to pollinator behavior and physiology. A number of flower-visiting animals exhibit behavioral preferences for nectar solutions containing amino acids, but these preferences vary by species and are often context or condition dependent. Furthermore, the relative strength of these preferences and potential influence on the foraging behavior of flower-visiting animals remains unclear. Here, we used innate preference tests and associative learning paradigms to examine the nectar preferences of the flower-visiting hawkmoth Manduca sexta, in relation to both sugar and amino acid content. Manduca sexta exhibited a strong preference for higher sucrose concentrations, while the effect of amino acids on innate feeding preference was only marginally significant. However, with experience, moths were able to learn nectar composition and flower color associations and to forage preferentially (against innate color preference) for nectar with a realistic amino acid composition. Foraging moths responding to learned color cues of nectar amino acid content exhibited a behavioral preference comparable to that observed in response to a 5% difference in nectar sucrose concentration. These results demonstrate that experienced foragers may assess nectar amino acid content in addition to nectar sugar content and caloric value during nectar-foraging bouts.
Μοριακή επιδημιολογία και μικροβιολογία σεξουαλικώς μεταδιδόμενων νοσημάτων
Authors: Παρθένης Χρήστος
Published: June 2021

Αντικείμενο Σκοπός: Η διερεύνηση και η διάγνωση των σεξουαλικώς μεταδιδόμενων νοσημάτων (ΣΜΝ) συμπεριλαμβανομένου και του HPV και η παρουσία κυτταρολογικών αλλαγών στον τράχηλο σε μια κοόρτη μελέτη με σεξουαλικώς ενεργές γυναίκες στον ελλαδικό χώρο.Υλικό και μέθοδοι: Πραγματοποιήθηκε κυτταρολογία τραχήλου μήτρας και μοριακή τυποποίηση HPV και άλλων ΣΜΝ για 345 ενεργά σεξουαλικά γυναίκες ηλικίας μεταξύ 18 και 45 ετών (μέσος όρος 33.2±7.2 έτη) που προσήλθαν σε γυναικολογική κλινική για έλεγχο διαλογής ρουτίνας. Μελετήθηκε η συσχέτιση του HPV και άλλων ΣΜΝ με την κυτταρολογική εικόνα.Αποτελέσματα: HPV εντοπίστηκε σε 61 γυναίκες (17.7%) και άλλα ΣΜΝ σε 82 (23.8%). Το Ureaplasma spp ήταν το πιο συχνά εντοπιζόμενο παθογόνο, το οποίο βρέθηκε σε 63 (18.2%) γυναίκες και ακολούθησαν το Mycoplasma spp (21 γυναίκες, 25.6%) και το Chlamydia trachomatis (πέντε γυναίκες, 6.1%). Η HPV θετικότητα μόνο (χωρίς τη συνύπαρξη άλλων ΣΜΝ) συσχετίσθηκε με μη φυσιολογική κυτταρολογία (odds ratio 6.9, p<0.001), ενώ γυναίκες που ήταν αρνητικές τόσο για HPV όσο και για τα άλλα ΣΜΝ είχαν μεγαλύτερη πιθανότητα να εμφανίσουν φυσιολογική κυτταρολογία τραχήλου μήτρας (odds ratio 0.36, p<0.01). Δεκαέξι από τις 63 (25.4%) γυναίκες οι οποίες ελέγχθηκαν θετικές για Ureaplasma spp, είχαν υψηλού ρίσκου HPV τύπο (odds ratio 2.3, p=0.02).Συμπεράσματα: Σε έναν πληθυσμό με αυξημένη εμφάνιση του Ureaplasma spp, υπήρχε συσχέτιση αυτού του συγκεκριμένου παθογόνου με υψηλού κινδύνου (υψηλού ρίσκου) HPV λοίμωξη, εύρημα που χρειάζεται περαιτέρω διερεύνηση και μελέτη.
Single motherhood, social independence and non-communicable disease (NCD) outcomes among young females (15-24 years old) in South Africa
Authors: De Wet-Billings Nicole
Published: June 2021

Background: Non-communicable diseases (NCDs) acquired during youth follow into and affect adulthood. The association between young mother’s social independence and NCD status is of policy interest due to its effect on economic and social development. This study aimed to determine the causal relationship between social independence and NCD outcomes among young, single mothers in South Africa.

Methods: Data from the South African National Income Dynamics Survey (NIDS) in 2008 and 2017 was used to determine if single mothers developed hypertension, diabetes or asthma by various indicators of social independence, including highest level of education and employment status. The sample was initially made-up of unmarried females (15-24 years old) without any children in 2008. Both fertility and social independence was followed-up to 2017.

Results: In total, 66 young females developed an NCD by 2017 and 87% (n=57) of these women had a child in the interim period. Employment of young females increased from 4.78% in 2008 to 37.79% in 2017, but completion of secondary or tertiary education declined from 67.94% in 2008 to 56.01% in 2017. In addition, half (50.88%) of the young females were partially independent by 2017, with only 11.03% being fully independent at this time. Finally, logistic regression results showed that the likelihood of developing an NCD increased if young females with children were not socially independent.

Conclusions: The relationship between social independence and NCDs suggest that policies and programmes in South Africa need to incorporate socioeconomic status as a determinant of disease and in particular, need to address socioeconomic indicators as additive measures and not autonomous indicators.