bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoantibodies to Annexin A2 and cerebral thrombosis: Insights from a mouse model
Authors: Weiss Ronen , Bushi Doron , Mindel Ekaterina , Bitton Almog , Diesendruck Yael , Gera Orna , Drori Tali , Zmira Ofir , Aharoni Shay Anat , Agmon-Levin Nancy , Kashi Oren , Benhar Itai , Golderman Valery , Orion David , Chapman Joab , Shavit-Stein Efrat
Published: February 2021

Introduction

Antiphospholipid syndrome (APS) is an autoimmune disorder manifested by thromboembolic events, recurrent spontaneous abortions and elevated titers of circulating antiphospholipid antibodies. In addition, the presence of antiphospholipid antibodies seems to confer a fivefold higher risk for stroke or transient ischemic attack. Although the major antigen of APS is β2 glycoprotein I, it is now well established that antiphospholipid antibodies are heterogeneous and bind to various targets. Recently, antibodies to Annexin A2 (ANXA2) have been reported in APS. This is of special interest since data indicated ANXA2 as a key player in fibrinolysis. Therefore, in the present study we assessed whether anti-ANXA2 antibodies play a pathological role in thrombosis associated disease.

Materials and Methods

Mice were induced to produce anti-ANXA2 antibodies by immunization with ANXA2 (iANXA2) and control mice were immunized with adjuvant only. A middle cerebral artery occlusion stroke model was applied to the mice. The outcome of stroke severity was assessed and compared between the two groups.

Results

Our results indicate that antibodies to ANXA2 lead to a more severe stroke as demonstrated by a significant larger stroke infarct volume (iANXA2 133.9 ± 3.3 mm3 and control 113.7 ± 7.4 mm3; p = 0.017) and a more severe neurological outcome (iANXA2 2.2 ± 0.2, and control 1.5 ± 0.18; p = 0.03).

Conclusions

This study supports the hypothesis that auto-antibodies to ANXA2 are an independent risk factor for cerebral thrombosis. Consequently, we propose screening for anti-ANXA2 antibodies should be more widely used and patients that exhibit the manifestations of APS should be closely monitored by physicians.
Body Image as a Mediator Between Gender and Quality of Life Among Patients With Diabetic Foot Ulcers in Indonesia
Authors: Putri Ni Made Manik Elisa , Yasmara Deni , Yen Miao-Fen , Pan Shin-Chen , Fang Su-Ying
Published: February 2021

Introduction:

Foot ulcers cause women in Indonesia to lose opportunities to participate in religious and cultural activities due to the inability to wear certain footwear. This study examined body image as a mediator in the relationship between gender and quality of life (QoL) among patients with diabetic foot ulcer (DFU) in Indonesia.

Method:

A cross-sectional design with convenience sampling was used to recruit participants at the Surgical Outpatient Department and Wound Care Clinic in Bali, Indonesia. The Diabetic Foot Ulcer Scale–Short Form and the body image domain of the Body Investment Scale were administered.

Results:

We found gender differences in participants’ ( n = 201) QoL and body image ( p < .05). Body image fully mediated the effect of the relationship between gender and QoL (B = 6.68; 95% confidence interval [3.14, 10.52]) and explained 39.13% of the variance.

Discussion:

Health care providers should consider patients’ religious beliefs in DFU education and consider women’s body image issues. Diabetes foot ulcer may prevent women from performing religious rituals, thus, influencing their QoL. Protective strategies to prevent DFU among women in Indonesia warrant further development.
Reciprocal Peer Coaching and Teaching Teams’ Use of Pyramid Model Practices
Authors: Golden Adrienne K. , Hemmeter Mary Louise , Edmonds Marisa , Ledford Jennifer R.
Published: February 2021

A multiple probe design across behaviors, replicated across teaching teams, was used to evaluate the effectiveness of training plus reciprocal peer coaching on teaching teams’ implementation of Pyramid Model (PM) practices. In this study, teaching teams (three dyads and one triad) were provided with training around the use of targeted PM practices and reciprocal peer coaching. Coaching required teachers within each team to observe and provide feedback to one another around their use of targeted PM practices. Data from this study indicate reciprocal peer coaching is an effective and efficient way for early childhood teaching teams to increase their use of PM practices. Increased use of PM practices generalized across classroom activities and maintained following the removal of peer coaching. Results, limitations, impacts on the field, and next steps are discussed.
Achieving superficial femoral venous access in a critically ill COVID-19 patient in the prone position
Authors: Ostroff Matthew , Ismail Mourad , Weite ToniAnn
Published: February 2021

A 63-year-old obese male was admitted with acute respiratory failure secondary to COVID-19. Day 13 the patient decompensated, lapsing into a critical stage of severe acute respiratory distress syndrome, requiring immediate prone positioning. The Rapid Response Team managed the emergency intervention for intubation but was unable to establish central access with the patient in the prone position. A consult to the Vascular Access Team succeeded in establishing central catheter placement with an ultrasound-guided mid-thigh superficial femoral 55-centimeter triple lumen catheter. The terminal tip of the catheter was confirmed in the mid portion of the inferior vena cava.
Hemodialysis catheter heparin lock related bleeding: Hemorrhagic shock every other day
Authors: Marques Joana , Duarte Tiago Isidoro , Cotovio Patrícia , Borges André , Germano Nuno
Published: February 2021

Catheter dysfunction is an important cause of catheter loss. In order to prevent this, locking solutions with minimal risk of systemic anticoagulation are used to ensure catheter patency. At present the most commonly used solutions are either heparin or sodium citrate. According to the literature use of sodium citrate may be advantageous in reducing bleeding events. We report a case of hemorrhagic shock following hemodialysis catheter lock with heparin, reversed after switching solution to sodium citrate.
Study on the stiffness degradation in concrete continuous beam with externally prestressed CFRP tendons under fatigue loading
Authors: Li Xing , Zhang Jiwen , Cheng Jun
Published: February 2021

This paper presents fatigue behaviors and the stiffness degradation law of concrete continuous beams with external prestressed carbon fiber-reinforced polymer (CFRP) tendons. Three specimens were tested under fatigue loading, and the influence of different load levels on the stiffness degradation and fatigue life were studied, and it was found that the stiffness degradation of three test specimens exhibited a three-stage change rule, namely rapid decrease, stable degradation, and sharp decline, but there are obvious differences in the rate and amplitude of stiffness degradation. The load level has a significant influence on the fatigue life of the test specimens. An analytical model with load level considered was proposed to calculate the residual stiffness and predict the stiffness degradation, which is in good agreement with the test results. The model of stiffness degradation presents a possible solution for practical engineering applications of concrete continuous beams with externally prestressed CFRP tendons subjected to different fatigue loadings.
What do over-trained athletes and patients with neurodegenerative diseases have in common? Mitochondrial dysfunction
Authors: Ostojic Sergej M , Ratgeber Laszlo , Olah Andras , Betlehem Jozsef , Pongras Acs
Published: February 2021

Under pathological conditions and excessive stress, mitochondria may experience a severe and irreversible loss of function. Both strenuous exhaustive exercise and neurodegenerative disorders appear to share defects in mitochondrial function that may fiercely disrupt the integrity and homeostasis of the organelle, leading to perennial pathological substrates. Here, we overview similarities of mitochondrial dysfunction in two conditions and discuss possible areas of interdisciplinary collaboration and research translation between sports medicine and neurology.
Anterograde and Retrograde Approach With Through-and-Through Wiring Technique to Treat a Ruptured and Extremely Tortuous Giant Popoliteal Artery Aneurism
Authors: Valle Raleigh Juan , Chas José , Bluro Ignacio , Rabellino Martin
Published: February 2021

Purpose:

This technical note aims to show a challenging endovascular treatment approach of a giant and tortuous ruptured popliteal artery aneurism

Materials and Methods:

An 86-year-old male patient was admitted for acute lower right limb ischemia. Angio-MSCT showed highly calcified superficial femoral artery, with a 180° bend in distal portion, followed by a large popliteal aneurism (63 × 61 mm) with a large extent hematoma (142 × 112 × 104 mm). Endovascular approach was chosen due to high morbidity.

Results:

Anterior puncture of right superficial femoral artery was performed under ultrasound guidance. Despite various intents, the 0.035 hydrophilic coated wire could not be crossed distally through the aneurism. Retrograde access was performed via tibio-peroneal trunk under fluoroscopic guidance with a micropuncture set. A stiff 0.035″ Glidewire® was successfully advanced into the proximal portion of the aneurism through a 5F vertebral catheter externalized with a snare from the femoral sheath obtaining a “through-and-through wire” technique. Tightening of both ends of the wire helped gain support and straightened curves. Two stent grafts were implanted with no residual leak at 1 month follow-up.

Conclusion:

Anterograde and retrograde approach was useful to perform a through-and-through wire technique in a challenging case of a tortuous ruptured popliteal artery aneurism.
Interacting effects of political social media use, political discussion and political trust on civic engagement: Extending the differential gains model
Authors: Su Yan , Xiao Xizhu
Published: February 2021

The differential gains model has lent credence to the fact that the positive association between news consumption and political engagement differs across people who discuss politics more often and those who do not. This study extends the original differential gains model by incorporating a second moderator, political trust, and replicating in three Asian societies: Japan, Taiwan, and Mainland China. In addition to the main associations, results lent partial support to the original hypothesis in the context of Japan. Moreover, a three-way interaction emerged in China Mainland. That is, among Chinese who have higher levels of political social media use, those who discuss politics more often and distrust political institutions showed higher levels of civic engagement. This study advances the original differential gains model into a moderated moderation model. Beyond the communicative factors, results revealed the importance of political trust in buffering media effects.
Hear-and-avoid for unmanned air vehicles using convolutional neural networks
Authors: Wijnker Dirk , van Dijk Tom , Snellen Mirjam , de Croon Guido , De Wagter Christophe
Published: February 2021

To investigate how an unmanned air vehicle can detect manned aircraft with a single microphone, an audio data set is created in which unmanned air vehicle ego-sound and recorded aircraft sound are mixed together. A convolutional neural network is used to perform air traffic detection. Due to restrictions on flying unmanned air vehicles close to aircraft, the data set has to be artificially produced, so the unmanned air vehicle sound is captured separately from the aircraft sound. They are then mixed with unmanned air vehicle recordings, during which labels are given indicating whether the mixed recording contains aircraft audio or not. The model is a convolutional neural network that uses the features Mel frequency cepstral coefficient, spectrogram or Mel spectrogram as input. For each feature, the effect of unmanned air vehicle/aircraft amplitude ratio, the type of labeling, the window length and the addition of third party aircraft sound database recordings are explored. The results show that the best performance is achieved using the Mel spectrogram feature. The performance increases when the unmanned air vehicle/aircraft amplitude ratio is decreased, when the time window is increased or when the data set is extended with aircraft audio recordings from a third party sound database. Although the currently presented approach has a number of false positives and false negatives that is still too high for real-world application, this study indicates multiple paths forward that can lead to an interesting performance. Finally, the data set is provided as open access.
Prognostic and clinicopathological significance of hypoxia-inducible factors 1α and 2α in hepatocellular carcinoma: a systematic review with meta-analysis
Authors: Méndez-Blanco Carolina , Fernández-Palanca Paula , Fondevila Flavia , González-Gallego Javier , Mauriz José L.
Published: February 2021

Background:

Hepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) have been shown to contribute to tumor progression and therapy resistance in HCC. We evaluated the prognostic and clinicopathological significance of HIF-1α and HIF-2α in HCC patients.

Methods:

We systematically searched Embase, Cochrane, PubMed, Scopus and Web of Science (WOS) from inception to 1 June 2020 for studies evaluating HIF-1α and/or HIF-2α expression in HCC. Selected articles evaluate at least one factor by immunohistochemistry (IHC) in HCC patients who underwent surgical resection, and its relationship with prognosis and/or clinicopathological features. Study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CDR42020191977). We meta-analyzed the data extracted or estimated according to the Parmar method employing STATA software. We evaluated the overall effect size for the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), as well as heterogeneity across studies with the I2 statistic and chi-square-based Q test. Moreover, we conducted subgroup analysis when heterogeneity was substantial. Publication bias was assessed by funnel plot asymmetry and Egger’s test.

Results:

HIF-1α overexpression was correlated with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and clinicopathological features including Barcelona Clinic Liver Cancer (BCLC), capsule infiltration, intrahepatic metastasis, lymph node metastasis, tumor–node–metastasis (TNM), tumor differentiation, tumor number, tumor size (3 cm), vascular invasion and vasculogenic mimicry. We also detected a possible correlation of HIF-1α with alpha-fetoprotein (AFP), cirrhosis, histological grade, tumor size (5 cm) and albumin after subgroup analysis. Initially, only DFS/RFS appeared to be associated with HIF-2α overexpression. Subgroup analysis denoted that HIF-2α overexpression was related to OS and capsule infiltration.

Conclusions:

HIF-1α and HIF-2α overexpression is related to poor OS, DFS/RFS and some clinicopathological features of HCC patients, suggesting that both factors could be useful HCC biomarkers.
Diagnostic and surgical challenges in disseminated tuberculosis presenting as acute abdomen during COVID-19 pandemic
Authors: Rajput Deepak , Kumar Shashank , Rai Ankit , Chezhian S
Published: February 2021

Due to the lack of much insight into the SARS-CoV-2 and overlapping symptoms and signs with other respiratory infections, diagnosis and management is often challenging in chest ailments particularly tuberculosis.
The Pre-Loaded Set-Screw in InterTAN Nail: Should It Be Tightened or Not Tightened in Pertrochanteric Hip Fractures
Authors: Du Shou-Chao , Wang Xiu-Hui , Chang Shi-Min
Published: February 2021

Background:

InterTAN is a specific type of cephalomedullary nail with a twin interlocking de-rotation and compression screw, which has inherent ability of anti-rotation. Whether to tighten or not to tighten the preloaded setscrew to allow or not allow secondary sliding in InterTan nail is controversial in clinical practice.

Methods:

We retrospectively collected 4 nonunion cases of unstable pertrochanteric femur fractures (AO/OTA-31A2), all were treated with InterTan nail and the preloaded setscrew was tightened in order to prevent further secondary sliding and femoral neck shortening.

Results:

After 6 months to 2 years follow-up, the fractures showed nonunion in radiography and the patients complained slight to middle degrees of pain, and had to use walking stick assistant in activities of daily life. Tightening the pre-loaded setscrew to prevent postoperative secondary sliding as static constructs might keep the femoral neck length, but lose the opportunity of telescoping for fracture impaction, and take the risk of healing complications, such as fracture nonunion, femoral head cutout or nail breakage.

Conclusions:

As the harm outweighs benefit, we advocate the preloaded setscrew in InterTan nail should not be tightened in standard-obliquity pertrochanteric hip fractures (AO/OTA-31A1 and A2).
Lung function and cardiovascular disease: a two-sample Mendelian randomisation study
Authors: Higbee Daniel H. , Granell Raquel , Sanderson Eleanor , Davey Smith George , Dodd James W.
Published: February 2021

Background

Observational studies suggest an association between reduced lung function and risk of coronary artery disease and ischaemic stroke, independent of shared cardiovascular risk factors such as cigarette smoking. We use the latest genetic epidemiological methods to determine whether impaired lung function is causally associated with an increased risk of cardiovascular disease.

Methods and findings

Mendelian randomisation uses genetic variants as instrumental variables to investigate causation. Preliminary analysis used two-sample Mendelian randomisation with lung function single nucleotide polymorphisms. To avoid collider bias, the main analysis used single nucleotide polymorphisms for lung function identified from UKBiobank in a multivariable Mendelian randomisation model conditioning for height, body mass index and smoking.

Multivariable Mendelian randomisation shows strong evidence that reduced forced vital capacity (FVC) causes increased risk of coronary artery disease (OR 1.32, 95% CI 1.19–1.46 per standard deviation). Reduced forced expiratory volume in 1 s (FEV1) is unlikely to cause increased risk of coronary artery disease, as evidence of its effect becomes weak after conditioning for height (OR 1.08, 95% CI 0.89–1.30). There is weak evidence that reduced lung function increases risk of ischaemic stroke.

Conclusion

There is strong evidence that reduced FVC is independently and causally associated with coronary artery disease. Although the mechanism remains unclear, FVC could be taken into consideration when assessing cardiovascular risk and considered a potential target for reducing cardiovascular events. FEV1and airflow obstruction do not appear to cause increased cardiovascular events; confounding and collider bias may explain previous findings of a causal association.
Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model
Authors: Heyckendorf Jan , Marwitz Sebastian , Reimann Maja , Avsar Korkut , DiNardo Andrew R. , Günther Gunar , Hoelscher Michael , Ibraim Elmira , Kalsdorf Barbara , Kaufmann Stefan H.E. , Kontsevaya Irina , van Leth Frank , Mandalakas Anna M. , Maurer Florian P. , Müller Marius , Nitschkowski Dörte , Olaru Ioana D. , Popa Cristina , Rachow Andrea , Rolling Thierry , Rybniker Jan , Salzer Helmut J.F. , Sanchez-Carballo Patricia , Schuhmann Maren , Schaub Dagmar , Spinu Victor , Suárez Isabelle , Terhalle Elena , Unnewehr Markus , Weiner January , Goldmann Torsten , Lange Christoph
Published: February 2021

Background

The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB.

Methods

Adult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points.

Results

50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9–0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001).

Conclusion

Biomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.
Chest radiography or computed tomography for COVID-19 pneumonia? Comparative study in a simulated triage setting
Authors: Sverzellati Nicola , Ryerson Christopher J. , Milanese Gianluca , Renzoni Elisabetta A. , Volpi Annalisa , Spagnolo Paolo , Bonella Francesco , Comelli Ivan , Affanni Paola , Veronesi Licia , Manna Carmelinda , Ciuni Andrea , Sartorio Carlotta , Tringali Giulia , Silva Mario , Michieletti Emanuele , Colombi Davide , Wells Athol U.
Published: February 2021

Introduction

For the management of patients referred to respiratory triage during the early stages of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic, either chest radiography or computed tomography (CT) were used as first-line diagnostic tools. The aim of this study was to compare the impact on the triage, diagnosis and prognosis of patients with suspected COVID-19 when clinical decisions are derived from reconstructed chest radiography or from CT.

Methods

We reconstructed chest radiographs from high-resolution CT (HRCT) scans. Five clinical observers independently reviewed clinical charts of 300 subjects with suspected COVID-19 pneumonia, integrated with either a reconstructed chest radiography or HRCT report in two consecutive blinded and randomised sessions: clinical decisions were recorded for each session. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and prognostic value were compared between reconstructed chest radiography and HRCT. The best radiological integration was also examined to develop an optimised respiratory triage algorithm.

Results

Interobserver agreement was fair (Kendall'sW=0.365, p<0.001) by the reconstructed chest radiography-based protocol and good (Kendall'sW=0.654, p<0.001) by the CT-based protocol. NPV assisted by reconstructed chest radiography (31.4%) was lower than that of HRCT (77.9%). In case of indeterminate or typical radiological appearance for COVID-19 pneumonia, extent of disease on reconstructed chest radiography or HRCT were the only two imaging variables that were similarly linked to mortality by adjusted multivariable models

Conclusions

The present findings suggest that clinical triage is safely assisted by chest radiography. An integrated algorithm using first-line chest radiography and contingent use of HRCT can help optimise management and prognostication of COVID-19.
Unravelling the chemical exposome in cohort studies: routes explored and steps to become comprehensive
Authors: Huhn Sebastian , Escher Beate I. , Krauss Martin , Scholz Stefan , Hackermüller Jörg , Altenburger Rolf
Published: February 2021

Environmental factors contribute to the risk for adverse health outcomes against a background of genetic predisposition. Among these factors, chemical exposures may substantially contribute to disease risk and adverse outcomes. In fact, epidemiological cohort studies have established associations between exposure against individual chemicals and adverse health effects. Yet, in daily life individuals are exposed to complex mixtures in varying compositions. To capture the totality of environmental exposures the concept of the exposome has been developed. Here, we undertake an overview of major exposome projects, which pioneered the field of exposomics and explored the links between chemical exposure and health outcomes using cohort studies. We seek to reflect their achievements with regard to (i) capturing a comprehensive picture of the environmental chemical exposome, (ii) aggregating internal exposures using chemical and bioanalytical means of detection, and (iii) identifying associations that provide novel options for risk assessment and intervention. Various complementary approaches can be distinguished in addressing relevant exposure routes and it emerges that individual exposure histories may not easily be grouped. The number of chemicals for which human exposure can be detected is substantial and highlights the reality of mixture exposures. Yet, to a large extent it depends on targeted chemical analysis with the specific challenges to capture all relevant exposure routes and assess the chemical concentrations occurring in humans. The currently used approaches imply prior knowledge or hypotheses about relevant exposures. Typically, the number of chemicals considered in exposome projects is counted in dozens—in contrast to the several thousands of chemicals for which occurrence have been reported in human serum and urine. Furthermore, health outcomes are often still compared to single chemicals only. Moreover, explicit consideration of mixture effects and the interrelations between different outcomes to support causal relationships and identify risk drivers in complex mixtures remain underdeveloped and call for specifically designed exposome-cohort studies.
S-conLSH: alignment-free gapped mapping of noisy long reads
Authors: Chakraborty Angana , Morgenstern Burkhard , Bandyopadhyay Sanghamitra
Published: February 2021

Background

The advancement of SMRT technology has unfolded new opportunities of genome analysis with its longer read length and low GC bias. Alignment of the reads to their appropriate positions in the respective reference genome is the first but costliest step of any analysis pipeline based on SMRT sequencing. However, the state-of-the-art aligners often fail to identify distant homologies due to lack of conserved regions, caused by frequent genetic duplication and recombination. Therefore, we developed a novel alignment-free method of sequence mapping that is fast and accurate.

Results

We present a new mapper called S-conLSH that usesSpacedcontext basedLocalitySensitiveHashing. With multiple spaced patterns, S-conLSH facilitates a gapped mapping of noisy long reads to the corresponding target locations of a reference genome. We have examined the performance of the proposed method on 5 different real and simulated datasets. S-conLSH is at least 2 times faster than the recently developed method lordFAST. It achieves a sensitivity of 99%, without using any traditional base-to-base alignment, on human simulated sequence data. By default, S-conLSH provides an alignment-free mapping in PAF format. However, it has an option of generating aligned output as SAM-file, if it is required for any downstream processing.

Conclusions

S-conLSH is one of the first alignment-free reference genome mapping tools achieving a high level of sensitivity. Thespaced-context is especially suitable for extracting distant similarities. The variable-length spaced-seeds or patterns add flexibility to the proposed algorithm by introducing gapped mapping of the noisy long reads. Therefore, S-conLSH may be considered as a prominent direction towards alignment-free sequence analysis.
Ranking cancer drivers via betweenness-based outlier detection and random walks
Authors: Erten Cesim , Houdjedj Aissa , Kazan Hilal
Published: February 2021

Background

Recent cancer genomic studies have generated detailed molecular data on a large number of cancer patients. A key remaining problem in cancer genomics is the identification of driver genes.

Results

We propose BetweenNet, a computational approach that integrates genomic data with a protein-protein interaction network to identify cancer driver genes. BetweenNet utilizes a measure based on betweenness centrality on patient specific networks to identify the so-calledoutlier genesthat correspond to dysregulated genes for each patient. Setting up the relationship between the mutated genes and the outliers through a bipartite graph, it employs a random-walk process on the graph, which provides the final prioritization of the mutated genes. We compare BetweenNet against state-of-the art cancer gene prioritization methods on lung, breast, and pan-cancer datasets.

Conclusions

Our evaluations show that BetweenNet is better at recovering known cancer genes based on multiple reference databases. Additionally, we show that the GO terms and the reference pathways enriched in BetweenNet ranked genes and those that are enriched in known cancer genes overlap significantly when compared to the overlaps achieved by the rankings of the alternative methods.
Rapid evolution and molecular convergence in cryptorchidism-related genes associated with inherently undescended testes in mammals
Authors: Chai Simin , Tian Ran , Bi Juanjuan , Xu Shixia , Yang Guang , Ren Wenhua
Published: February 2021

Background

The mammalian testis is an important male exocrine gland and spermatozoa-producing organ that usually lies in extra-abdominal scrotums to provide a cooler environment for spermatogenesis and sperm storage. Testicles sometimes fail to descend, leading to cryptorchidism. However, certain groups of mammals possess inherently ascrotal testes (i.e. testes that do not descend completely or at all) that have the same physiological functions as completely descended scrotal testes. Although several anatomical and hormonal factors involved in testicular descent have been studied, there is still a paucity of comprehensive research on the genetic mechanisms underlying the evolution of testicular descent in mammals and how mammals with ascrotal testes maintain their reproductive health.

Results

We performed integrative phenotypic and comparative genomic analyses of 380 cryptorchidism-related genes and found that the mammalian ascrotal testes trait is derived from an ancestral scrotal state. Rapidly evolving genes in ascrotal mammals were enriched in the Hedgehog pathway—which regulates Leydig cell differentiation and testosterone secretion—and muscle development. Moreover, some cryptorchidism-related genes in ascrotal mammals had undergone positive selection and contained specific mutations and indels. Genes harboring convergent/parallel amino acid substitutions between ascrotal mammals were enriched in GTPase functions.

Conclusions

Our results suggest that the scrotal testis is an ancestral state in mammals, and the ascrotal phenotype was derived multiple times in independent lineages. In addition, the adaptive evolution of genes involved in testicular descent and the development of the gubernaculum contributed to the evolution of ascrotal testes. Accurate DNA replication, the proper segregation of genetic material, and appropriate autophagy are the potential mechanisms for maintaining physiological normality during spermatogenesis in ascrotal mammals. Furthermore, the molecular convergence of GTPases is probably a mechanism in the ascrotal testes of different mammals. This study provides novel insights into the evolution of the testis and scrotum in mammals and contributes to a better understanding of the pathogenesis of cryptorchidism in humans.
Integrated analyses of the transcriptome and small RNA of the hemiparasitic plant Monochasma savatieri before and after establishment of parasite-host association
Authors: Chen Lanlan , Guo Qiaosheng , Zhu Zaibiao , Wan Hefang , Qin Yuhao , Zhang Hui
Published: February 2021

Background

Monochasma savatieri is a medicinal root hemiparasitic herb that extracts water and nutrients from the host plant via a haustorium. M. savatieri exhibits an enhanced growth after the establishment of parasite-host associations, but little is known about the molecular mechanism responsible. In this study, endogenous hormones, RNA sequencing and small RNA sequencing analysis were performed on M. savatieri before and after establishment of parasite-host associations.

Results

When grown with the host, decreased contents of jasmonic acid (JA) and indole-3-acetic acid (IAA) and increased abscisic acid (ABA) content were observed in M. savatieri with the established parasitic relationship. When grown with the host, 46,424 differentially expressed genes (DEGs) and 162 differentially expressed miRNAs (DEmiRs) were identified in the comparison between M. savatieri with the established parasitic relationship and without the established parasitic relationship. Analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that these DEGs and targets of DEmiRs mostly participated in plant hormone signal transduction, starch and sucrose metabolism, carbohydrate metabolism, cell growth and death, and transport and catabolism. Furthermore, correlation analysis of mRNA and miRNA revealed that 10 miRNA-target pairs from novel_mir65, novel_mir40, novel_mir80, miR397-5p_1, novel_mir36, novel_mir25 and novel_mir17 may have important roles in regulating the parasitic development of M. savatieri.

Conclusions

Our study not only expands the understanding of enhanced growth in M. savatieri after the establishment of parasite-host associations, but also first provides abundant resources for future molecular and genetic studies in M. savatieri.
Anesthetic protocol for right ventricular dysfunction management in heart transplantation: systematic review, development and validation
Authors: Barros Lucas Nepomuceno , Uchoa Ricardo Barreira , Mejia Juan Alberto Cosquillo , Nunes Rogean Rodrigues , Barros Denise Araujo Silva Nepomuceno , Rodrigues Filho Filadelfo
Published: February 2021

Background

Right Ventricular Dysfunction (RVD) is the most frequent intraoperative hemodynamic complication in Heart Transplantation (HTx). RVD occurs in 0.04–1.0% of cardiac surgeries with cardiotomy and in 20–50% of HTx, with mortality up to 75%. No consensus has been established for how anesthesiologists should manage RVD, with management methods many times remaining unvalidated.

Methods

We conducted a systematic review, following PRISMA guidelines, to create an anesthetic protocol to manage RVD in HTx, using databases that include PubMed and Embase, until September 2018 based on inclusion and exclusion criteria. The articles screening for the systematic review were done two independent reviewers, in case of discrepancy, we consulted a third independent reviewer. Based on the systematic review, the anesthetic protocol was developed. The instrument selected to perform the validation of the protocol was AGREE II, for this purpose expert anesthetists were recruited to do this process. The minimum arbitration score for domains validation cutoff of AGREE II is arbitered to 70%. This study was registered at PROSPERO (115600).

Results

In the systematic review, 152 articles were included. We present the protocol in a flowchart with six steps based on goal-directed therapy, invasive monitoring, and transesophageal echocardiogram. Six experts judged the protocol and validated it.

Conclusion

The protocol has been validated by experts and new studies are needed to assess its applicability and potential benefits on major endpoints.
In-hospital and 30-day major adverse cardiac events in patients referred for ST-segment elevation myocardial infarction in Dhaka, Bangladesh
Authors: Akhtar Zubair , Aleem Mohammad Abdul , Ghosh Probir Kumar , Islam A. K. M. Monwarul , Chowdhury Fahmida , MacIntyre C. Raina , Fröbert Ole
Published: February 2021

Background

There is a paucity of data regarding acute phase (in-hospital and 30-day) major adverse cardiac events (MACE) following ST-segment elevation myocardial infarction (STEMI) in Bangladesh. This study aimed to document MACE during the acute phase post-STEMI to provide information.

Methods

We enrolled STEMI patients of the National Institute of Cardiovascular Disease, Dhaka, Bangladesh, from August 2017 to October 2018 and followed up through 30 days post-discharge for MACE, defined as the composite of all-cause death, myocardial infarction, and coronary revascularization. Demographic information, cardiovascular risk factors, and clinical data were registered in a case report form. The Cox proportional hazard model was used for univariate and multivariate analysis to identify potential risk factors for MACE.

Results

A total of 601 patients, mean age 51.6 ± 10.3 years, 93% male, were enrolled. The mean duration of hospital stay was 3.8 ± 2.4 days. We found 37 patients (6.2%) to experience an in-hospital event, and 45 (7.5%) events occurred within the 30 days post-discharge. In univariate analysis, a significantly increased risk of developing 30-day MACE was observed in patients with more than 12 years of formal education, diabetes mellitus, or a previous diagnosis of heart failure. In a multivariate analysis, the risk of developing 30-day MACE was increased in patients with heart failure (hazard ratio = 4.65; 95% CI 1.64–13.23).

Conclusions

A high risk of in-hospital and 30-day MACE in patients with STEMI exists in Bangladesh. Additional resources should be allocated providing guideline-recommended treatment for patients with myocardial infarction in Bangladesh.
Conceptualising natural and quasi experiments in public health
Authors: de Vocht Frank , Katikireddi Srinivasa Vittal , McQuire Cheryl , Tilling Kate , Hickman Matthew , Craig Peter
Published: February 2021

Background

Natural or quasi experiments are appealing for public health research because they enable the evaluation of events or interventions that are difficult or impossible to manipulate experimentally, such as many policy and health system reforms. However, there remains ambiguity in the literature about their definition and how they differ from randomized controlled experiments and from other observational designs. We conceptualise natural experiments in the context of public health evaluations and align the study design to the Target Trial Framework.

Methods

A literature search was conducted, and key methodological papers were used to develop this work. Peer-reviewed papers were supplemented by grey literature.

Results

Natural experiment studies (NES) combine features of experiments and non-experiments. They differ from planned experiments, such as randomized controlled trials, in that exposure allocation is not controlled by researchers. They differ from other observational designs in that they evaluate the impact of events or process that leads to differences in exposure. As a result they are, in theory, less susceptible to bias than other observational study designs. Importantly, causal inference relies heavily on the assumption that exposure allocation can be considered ‘as-if randomized’. The target trial framework provides a systematic basis for evaluating this assumption and the other design elements that underpin the causal claims that can be made from NES.

Conclusions

NES should be considered a type of study design rather than a set of tools for analyses of non-randomized interventions. Alignment of NES to the Target Trial framework will clarify the strength of evidence underpinning claims about the effectiveness of public health interventions.
Incidence and risk factors of COVID-19-like symptoms in the French general population during the lockdown period: a multi-cohort study
Authors:   for the SAPRIS study group, Carrat Fabrice , Touvier Mathilde , Severi Gianluca , Meyer Laurence , Jusot Florence , Lapidus Nathanael , Rahib Delphine , Lydié Nathalie , Charles Marie-Aline , Ancel Pierre-Yves , Rouquette Alexandra , de Lamballerie Xavier , Zins Marie , Bajos Nathalie
Published: February 2021

Background

Our main objectives were to estimate the incidence of illnesses presumably caused by SARS-CoV-2 infection during the lockdown period and to identify the associated risk factors.

Methods

Participants from 3 adult cohorts in the general population in France were invited to participate in a survey on COVID-19. The main outcome was COVID-19-Like Symptoms (CLS), defined as a sudden onset of cough, fever, dyspnea, ageusia and/or anosmia, that lasted more than 3 days and occurred during the 17 days before the survey. We used delayed-entry Cox models to identify associated factors.

Results

Between April 2, 2020 and May 12, 2020, 279,478 participants were invited, 116,903 validated the questionnaire and 106,848 were included in the analysis. Three thousand thirty-five cases of CLS were reported during 62,099 person-months of follow-up. The cumulative incidences of CLS were 6.2% (95% Confidence Interval (95%CI): 5.7%; 6.6%) on day 15 and 8.8% (95%CI 8.3%; 9.2%) on day 45 of lockdown. The risk of CLS was lower in older age groups and higher in French regions with a high prevalence of SARS-CoV-2 infection, in participants living in cities > 100,000 inhabitants (vs rural areas), when at least one child or adolescent was living in the same household, in overweight or obese people, and in people with chronic respiratory diseases, anxiety or depression or chronic diseases other than diabetes, cancer, hypertension or cardiovascular diseases.

Conclusion

The incidence of CLS in the general population remained high during the first 2 weeks of lockdown, and decreased significantly thereafter. Modifiable and non-modifiable risk factors were identified.
Association between head circumference at two years and second and fifth year cognition
Authors: Koshy Beena , Srinivasan Manikandan , Murugan Timiri Palani , Bose Anuradha , Christudoss Pamela , Mohan Venkata Raghava , John Sushil , Roshan Reeba , Kang Gagandeep
Published: February 2021

Background

Head circumference (HC) measurement is routinely not performed in early childhood and there is conflicting information about its utility in literature. The current study analyses the association between HC at two years of age and cognition at two and five years of age.

Methods

A community based birth-cohort recruited between 2010 and 2012 was followed up till five years of age in an urban slum in Vellore, India. Children were recruited at birth after informed parental consent by consecutive sampling using eligibility criteria of healthy new-born, singleton pregnancy and family’s availability in the study area during follow-up. HC measured at two years of age was used as the exposure variable to calculate association with cognition at both two and five years of age. Cognitive domain of Bayley scale of infant development was used at two years of age and Wechsler Preschool Primary Scales of Intelligence at five years.

Results

Of the 251 enrolled children, 138 (55%) were girls and 71 (30%) belonged to lower socioeconomic status. At 2 years, 8.81% of children had HC < − 3SD. Compared to children with HC z-scores ≥ − 2 SD, those with measurements < − 3 SD had a lower cognition scores by − 2.21 [95% CI: − 3.87 - -0.56] at 2 years. Also, children with HC < − 3 SD at two years scored significantly lower scores in cognitive domains of verbal, − 7.35 [95% CI: − 11.78 - -2.92] and performance, − 7.07 [95% CI: − 11.77 - -2.36] intelligence at five years.

Conclusions

This study showed that smaller HC at 2 years of age was negatively associated with cognition at both 2 and 5 years of age. Early childhood HC measurements can be utilised as a cheaper screening tool to identify children at risk in LMIC settings. Further studies can confirm these findings in diverse settings.
The effect of online multimedia psychoeducational interventions on the resilience and perceived stress of hospitalized patients with COVID-19: a pilot cluster randomized parallel-controlled trial
Authors: Shaygan Maryam , Yazdani Zahra , Valibeygi Adib
Published: February 2021

Background

There is evidence suggesting that quarantine might have undesirable psychological impacts on the patients. Therefore, it is important to seek for ways to increase the resilience and alleviate the psychological pressure of the patients who are quarantined due to infection with COVID-19. The present study was conducted to assess an online multimedia psychoeducational intervention regarding the feasibility, adherence, patient satisfaction and effectiveness on resilience and perceived stress of patients hospitalized with confirmed COVID-19.

Method

This was a pilot cluster randomized parallel-controlled trial with hospital wards as the units of randomization. Participants in this fully online trial were 50 consecutive patients who were hospitalized in 2 hospitals in Shiraz, after being diagnosed with COVID-19. Before the beginning of the intervention, four inpatient wards inside two of the hospitals were randomly assigned to either intervention or control conditions. All eligible participants in the wards allocated to the intervention condition received online multimedia psychoeducational interventions during the 2 weeks, whilst the patients in the wards allocated to the control condition were offered the opportunity to receive telephone-based psychological counseling if needed. Psychoeducational interventions mainly included cognitive–behavioural techniques, stress management techniques, mindfulness-based stress reduction and positive psychotherapy. The patients were assessed regarding resilience and perceived stress at baseline and after two weeks.

Results

Of 27 patients starting multimedia psychoeducational interventions, 26 (96.29%) completed post-assessments. A high level of adherence (80.76%) and satisfaction (Mean = 29.42; SD = 4.18) with the online multimedia psychoeducational interventions was found. Compared with the control group, the patients who used online multimedia psychoeducational interventions reported greater resilience (Meanintervention = 81.74; Meancontrol = 72.86; adjusted t (46) = 2.10;p = 0.04; CI: 0.39 to 17.38; dppc2 = 0.83) and fewer perceived stress (Meanintervention = 22.15; Meancontrol = 29.45; adjusted t (46) = 2.66;p = 0.01; CI: − 12.81 to − 1.78; dppc2 = − 0.77) after 2 weeks.

Discussion

The findings of the present study provided a successful first attempt at implementing feasible online multimedia psychoeducational interventions to promote resilience and mitigate stress among the patients who were hospitalized due to infection with COVID-19. The present results could help mental health professionals to determine which psychological techniques should be emphasized to promote patients’ resilience in the context of COVID-19 disease.

Trial registration

Iranian Registry of Clinical Trials,IRCT20201001048893N1. Retrospectively registered, 29 Jan 2021.