bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in hypertension clinical practice guidelines: a global comparison
Authors: Philip Richu , Beaney Thomas , Appelbaum Nick , Gonzalvez Carmen Rodriguez , Koldeweij Charlotte , Golestaneh Amelia Kataria , Poulter Neil , Clarke Jonathan M.
Published: May 2021

Background

Hypertension is the largest single contributor to the global burden of disease, affecting an estimated 1.39 billion people worldwide. Clinical practice guidelines (CPGs) can aid in the effective management of this common condition, however, inconsistencies exist between CPGs, and the extent of this is unknown. Understanding the differences in CPG recommendations across income settings may provide an important means of understanding some of the global variations in clinical outcomes related to hypertension.

Aims

This study aims to analyse the variation between hypertension CPGs globally. It aims to assess the variation in three areas: diagnostic threshold and staging, treatment and target blood pressure (BP) recommendations in hypertension.

Methods

A search was conducted on the MEDLINE repository to identify national and international hypertension CPGs from 2010 to May 2020. An additional country-specific grey-literature search was conducted for all countries and territories of the world as identified by the World Bank. Data describing the diagnosis, staging, treatment and target blood pressure were extracted from CPGs, and variations between CPGs for these domains were analysed.

Results

Forty-eight CPGs from across all World Bank income settings were selected for analysis. Ninety-six per cent of guidelines defined hypertension as a clinic-based BP of ≥140/90 mmHg, and 87% of guidelines recommended a target BP of < 140/90 mmHg. In the pharmacological treatment of hypertension, eight different first-step, 17 different second-step and six different third-step drug recommendations were observed. Low-income countries preferentially recommended diuretics (63%) in the first-step treatment, whilst high-income countries offered more choice between antihypertensive classes. Forty-four per cent of guidelines, of which 71% were from higher-income contexts recommended initiating treatment with dual-drug therapy at BP 160/100 mmHg or higher.

Conclusion

This study found that CPGs remained largely consistent in the definition, staging and target BP recommendations for hypertension. Extensive variation was observed in treatment recommendations, particularly for second-line therapy. Variation existed between income settings; low-income countries prescribed cheaper drugs, offered less clinician choice in medications and initiated dual therapy at later stages than higher-income countries. Future research exploring the underlying drivers of this variation may improve outcomes for hypertensive patients across clinical contexts.
Low expression of CHRDL1 and SPARCL1 predicts poor prognosis of lung adenocarcinoma based on comprehensive analysis and immunohistochemical validation
Authors: Deng Huan , Hang Qingqing , Shen Dijian , Zhang Yibi , Chen Ming
Published: May 2021

Purpose

Exploring the molecular mechanisms of lung adenocarcinoma (LUAD) is beneficial for developing new therapeutic strategies and predicting prognosis. This study was performed to select core genes related to LUAD and to analyze their prognostic value.

Methods

Microarray datasets from the GEO (GSE75037) and TCGA-LUAD datasets were analyzed to identify differentially coexpressed genes in LUAD using weighted gene coexpression network analysis (WGCNA) and differential gene expression analysis. Functional enrichment analysis was conducted, and a protein–protein interaction (PPI) network was established. Subsequently, hub genes were identified using the CytoHubba plug-in. Overall survival (OS) analyses of hub genes were performed. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (THPA) databases were used to validate our findings. Gene set enrichment analysis (GSEA) of survival-related hub genes were conducted. Immunohistochemistry (IHC) was carried out to validate our findings.

Results

We identified 486 differentially coexpressed genes. Functional enrichment analysis suggested these genes were primarily enriched in the regulation of epithelial cell proliferation, collagen-containing extracellular matrix, transforming growth factor beta binding, and signaling pathways regulating the pluripotency of stem cells. Ten hub genes were detected using the maximal clique centrality (MCC) algorithm, and four genes were closely associated with OS. The CPTAC and THPA databases revealed that CHRDL1 and SPARCL1 were downregulated at the mRNA and protein expression levels in LUAD, whereas SPP1 was upregulated. GSEA demonstrated that DNA-dependent DNA replication and catalytic activity acting on RNA were correlated with CHRDL1 and SPARCL1 expression, respectively. The IHC results suggested that CHRDL1 and SPARCL1 were significantly downregulated in LUAD.

Conclusions

Our study revealed that survival-related hub genes closely correlated with the initiation and progression of LUAD. Furthermore, CHRDL1 and SPARCL1 are potential therapeutic and prognostic indicators of LUAD.
Anticancer effects of bifidobacteria on colon cancer cell lines
Authors: Faghfoori Zeinab , Faghfoori Mohammad Hasan , Saber Amir , Izadi Azimeh , Yari Khosroushahi Ahmad
Published: May 2021

Background

Colorectal cancer (CRC), with a growing incidence trend worldwide, is resistant to apoptosis and has uncontrolled proliferation. It is recently reported that probiotic microorganisms exert anticancer effects. The genus Bifidobacterium, one of the dominant bacterial populations in the gastrointestinal tract, has received increasing attention because of widespread interest in using it as health-promoting microorganisms. Therefore, the present study aimed to assess the apoptotic effects of some bifidobacteria species on colon cancer cell lines.

Methods

The cytotoxicity evaluations performed using MTT assay and FACS-flow cytometry tests. Also, the effects of five species of bifidobacteria secretion metabolites on the expression level of anti- or pro-apoptotic genes including BAD, Bcl-2, Caspase-3, Caspase-8, Caspase-9, and Fas-R studied by real-time polymerase chain reaction (RT-PCR) method.

Results

The cell-free supernatant of all studied bifidobacteria significantly decreased the survival rates of colon cancer cells compared with control groups. Flow cytometric and RT-PCR results indicated that apoptosis is induced by bifidobacteria secretion metabolites and the mechanism for the action of bifidobacteria species in CRC prevention could be down-regulation and up-regulation of anti-apoptotic and, pro-apoptotic genes.

Conclusions

In the present study, different bifidobacteria species showed anticancer activity on colorectal cancer cells through down-regulation and up-regulation of anti-apoptotic and pro-apoptotic genes. However, further studies are required to clarify the exact mechanism of apoptosis induction by bifidobacteria species.
Impact of sleep duration, physical activity, and screen time on health-related quality of life in children and adolescents
Authors: Wong Carlos K. H. , Wong Rosa S. , Cheung Jason P. Y. , Tung Keith T. S. , Yam Jason C. S. , Rich Michael , Fu King-Wa , Cheung Prudence W. H. , Luo Nan , Au Chi Ho , Zhang Ada , Wong Wilfred H. S. , Fan Jiang , Lam Cindy L. K. , Ip Patrick
Published: May 2021

Background

Existing studies on health-related quality of life (HRQoL) mainly covered single growth stages of childhood or adolescence and did not report on the trends in the relationships of HRQoL with sleep duration, physical activity, and screen time. This study aimed to establish the population norm of HRQoL in children and adolescents aged 6–17 years and examine the associations of screen time, sleep duration, and physical activity with HRQoL in this population.

Methods

We conducted a large-scale cross-sectional population-based survey study of Hong Kong children and adolescents aged 6 to 17 years. A representative sample of students were interviewed to assess their HRQoL using PedsQL and EQ-5D-Y-5L. Multivariable homoscedastic Tobit regression with linear form or restricted cubic spline of predictors was used to analyze the associations between screen time, sleep duration, and HRQoL. Multiple imputation by chained equations was performed to deal with missing data.

Results

A total of 7555 respondents (mean age 11.5, SD 3.2; 55.1% female) were sampled. Their EQ VAS scores, PedsQL physical summary scores, and psychosocial summary scores were positively correlated with sleep duration and moderate/vigorous activity but was negatively correlated with screen time.

Conclusions

Children and adolescents who had longer exposure to screen, shorter sleep duration, and lower physical activity levels appeared to have poorer HRQoL as assessed by PedsQL and EQ-5D-Y-5L. Advice and guidance on screen time allocation for children and adolescents should be provided at the levels of school, community, and family.
Relative independence of upper limb position sense and reaching in children with hemiparetic perinatal stroke
Authors: Kuczynski Andrea M. , Kirton Adam , Semrau Jennifer A. , Dukelow Sean P.
Published: May 2021

Background

Studies using clinical measures have suggested that proprioceptive dysfunction is related to motor impairment of the upper extremity following adult stroke. We used robotic technology and clinical measures to assess the relationship between position sense and reaching with the hemiparetic upper limb in children with perinatal stroke.

Methods

Prospective term-born children with magnetic resonance imaging-confirmed perinatal ischemic stroke and upper extremity deficits were recruited from a population-based cohort. Neurotypical controls were recruited from the community. Participants completed two tasks in the Kinarm robot: arm position-matching (three parameters: variability [Varxy], contraction/expansion [Areaxy], systematic spatial shift [Shiftxy]) and visually guided reaching (five parameters: posture speed [PS], reaction time [RT], initial direction error [IDE], speed maxima count [SMC], movement time [MT]). Additional clinical assessments of sensory (thumb localization test) and motor impairment (Assisting Hand Assessment, Chedoke-McMaster Stroke Assessment) were completed and compared to robotic measures.

Results

Forty-eight children with stroke (26 arterial, 22 venous, mean age: 12.0 ± 4.0 years) and 145 controls (mean age: 12.8 ± 3.9 years) completed both tasks. Position-matching performance in children with stroke did not correlate with performance on the visually guided reaching task. Robotic sensory and motor measures correlated with only some clinical tests. For example, AHA scores correlated with reaction time (R = − 0.61, p < 0.001), initial direction error (R = − 0.64, p < 0.001), and movement time (R = − 0.62, p < 0.001).

Conclusions

Robotic technology can quantify complex, discrete aspects of upper limb sensory and motor function in hemiparetic children. Robot-measured deficits in position sense and reaching with the contralesional limb appear to be relatively independent of each other and correlations for both with clinical measures are modest. Knowledge of the relationship between sensory and motor impairment may inform future rehabilitation strategies and improve outcomes for children with hemiparetic cerebral palsy.
The prevalence of depression, stress and anxiety symptoms in patients with chronic heart failure
Authors: Tsabedze Nqoba , Kinsey Jamie-Leigh Hayes , Mpanya Dineo , Mogashoa Vanessa , Klug Eric , Manga Pravin
Published: May 2021

Background

Mental health illnesses are associated with frequent hospitalisation and an increased risk of all-cause mortality. Despite the high prevalence of depression in patients with chronic heart failure (CHF), there is a paucity of data on this subject from low and middle-income countries (LMIC). The aim of this study was to determine the prevalence of depression, anxiety, and stress symptoms in patients attending a dedicated CHF clinic.

Methods

A prospective study was conducted at an outpatient heart failure clinic in a tertiary academic centre. The study participants completed a Depression, Anxiety and Stress (DASS-21) questionnaire to screen for the presence and severity of depression, anxiety and stress symptoms. Furthermore, the Minnesota Living with Heart Failure Questionnaire (MLHFQ) was completed and used to evaluate the impact of CHF on health-related quality of life (QoL). Descriptive statistics were used to describe patients' characteristics and logistic regression analysis to identify predictors of symptoms of depression.

Results

The study population comprised of 103 patients, predominantly female (62.1%) with a median age of 53 (interquartile range 38–61) years. Symptoms of depression were reported by 52.4%, with 11.6% reporting symptoms suggestive of extremely severe depression. Anxiety was diagnosed in 53.4% of patients and extremely severe anxiety was reported by 18.4% of patients. Fifty patients were classified as stressed, and only 7.7% had extremely severe stress. More than half of the patients (54.4%) were in New York Heart Association functional class I. The mean left ventricular ejection fraction in the entire cohort was 30% (SD =  ± 11.1%). In the multivariable logistic regression model, the MLHFQ score [odds ratio (OR) 1.04, 95% CI:1.02–1.06, p = 0.001] and the six-minute walk test [OR 0.99, 95% CI: 0.98–0.99, p = 0.014] were identified as independent predictors of depression.

Conclusion

Depression and anxiety symptoms were found in over half of patients attending the CHF clinic. We recommend that mental health screening should be routinely performed in patients with CHF. Prospective, adequately powered, multicentre studies from LMIC investigating the impact of depression, anxiety and stress on CHF outcomes such as health-related QoL, hospitalisation and mortality are required.
Serotonergic gene-to-gene interaction is associated with mood and GABA concentrations but not with pain-related cerebral processing in fibromyalgia subjects and healthy controls
Authors: Ellerbrock Isabel , Sandström Angelica , Tour Jeanette , Fanton Silvia , Kadetoff Diana , Schalling Martin , Jensen Karin B. , Sitnikov Rouslan , Kosek Eva
Published: May 2021

The neurotransmitter serotonin, involved in the regulation of pain and emotion, is critically regulated by the 5‐HT1Aautoreceptor and the serotonin transporter (5-HTT). Polymorphisms of these genes affect mood and endogenous pain modulation, both demonstrated to be altered in fibromyalgia subjects (FMS). Here, we tested the effects of genetic variants of the 5‐HT1Areceptor (CC/G-carriers) and 5-HTT (high/intermediate/low expression) on mood, pain sensitivity, cerebral processing of evoked pain (functional MRI) and concentrations of GABA and glutamate (MR spectroscopy) in rostral anterior cingulate cortex (rACC) and thalamus in FMS and healthy controls (HC). Interactions between serotonin-relevant genes were found in affective characteristics, with genetically inferred high serotonergic signalling (5-HT1ACC/5-HTThighgenotypes) being more favourable across groups. Additionally, 5‐HT1ACC homozygotes displayed higher pain thresholds than G-carriers in HC but not in FMS. Cerebral processing of evoked pressure pain differed between groups in thalamus with HC showing more deactivation than FMS, but was not influenced by serotonin-relevant genotypes. In thalamus, we observed a 5‐HT1A-by-5-HTT and group-by-5-HTT interaction in GABA concentrations, with the 5-HTT high expressing genotype differing between groups and 5‐HT1Agenotypes. No significant effects were seen for glutamate or in rACC. To our knowledge, this is the first report of this serotonergic gene-to-gene interaction associated with mood, both among FMS (depression) and across groups (anxiety). Additionally, our findings provide evidence of an association between the serotonergic system and thalamic GABA concentrations, with individuals possessing genetically inferred high serotonergic signalling exhibiting the highest GABA concentrations, possibly enhancing GABAergic inhibitory effects via 5-HT.
Twenty-six years of involvement with cystic echinococcosis: a case report
Authors: Safari Hosein , Mirzavand Somayeh , Rafiei Abdollah , Beiromvand Molouk
Published: May 2021

Introduction

Spinal hydatidosis, a zoonotic disease caused by infection with Echinococcus spp. larvae, is rare, but its treatment remains a significant medical challenge. Approximately 70% of patients with spinal hydatidosis have lesions in their liver, 0–15% have lung involvement, and only 0.5–2% have bone involvement.

Case presentation

Here we report a 38-year-old Iranian man with spinal hydatidosis, who had a history of eight times surgery in over of 26 years due to hydatid cyst in the liver, lungs, and chest wall. At the most recent admission to hospital he presented with chest pain, paraplegia, and urinary incontinence. Magnetic resonance imaging revealed thoracic spinal hydatid disease. He underwent surgery, and the hydatid cysts were completely removed. Lower extremity forces recovered dramatically and completely within 4 weeks.

Conclusion

Spinal hydatidosis is a rare disease, but it is associated with a high degree of morbidity, mortality, and poor prognosis. Because of the infiltrative nature of hydatid disease, surgery alone is rarely curative. The current case study demonstrates the importance of a suitable surgical approach, adequate intraoperative prophylaxis to prevent cyst rupture, and prolonged complete paraplegia.
Unilateral frosted branch angiitis in an human immunodeficiency virus-infected patient with concurrent COVID-19 infection: a case report
Authors: Lim Tsu Hong , Wai Yong Zheng , Chong Jia Cherng
Published: May 2021

Background

Frosted branch angiitis (FBA) is an uncommon ocular sign with multiple causes. With the recent outbreak of coronavirus disease 2019 (COVID-19), many cases of ocular manifestation in association with this disease have been reported. However, as yet we have no complete understanding of this condition. We report here the first case of FBA in a human immunodeficiency virus-infected patient with coexisting cytomegalovirus (CMV) and COVID-19 infection.

Case presentation

A 33-year-old Malay man with underlying acquired immunodeficiency syndrome receiving highly active antiretroviral therapy was referred to the Opthalmology Department with complaints of blurry vision for the past 2 months. He had tested positive for and been diagnosed with COVID-19 1 month previously. Clinical examination of the fundus revealed extensive perivascular sheathing of both the artery and vein suggestive of FBA in the right eye. Laboratory testing of nasal swabs for COVID-19 polymerase chain reaction (PCR) and serum CMV antibody were positive. The patient was then admitted to the COVID-19 ward and treated with intravenous ganciclovir.

Conclusion

Clinicians should be aware of and take the necessary standard precautions for possible coexistence of COVID-19 in an immunocompromised patient presenting with blurred vision, eye redness, dry eye and foreign body sensation despite the absence of clinical features suggestive of COVID-19. Whether FBA is one of the ocular signs of co-infection of COVID-19 and CMV remains unknown. Further studies are needed to provide more information on ocular signs presented in patients with concurrent COVID-19 and CMV infections.
Early response of monocyte-derived macrophages from vaccinated and non-vaccinated goats against in vitro infection with Mycobacterium avium subsp. paratuberculosis
Authors: Arteche-Villasol Noive , Gutiérrez-Expósito Daniel , Vallejo Raquel , Espinosa Jose , Elguezabal Natalia , Ladero-Auñon Iraia , Royo Marcos , del Carmen Ferreras María , Benavides Julio , Pérez Valentín
Published: May 2021

Paratuberculosis is a disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (Map). Vaccination is the most cost-effective control method. However, despite the fact that macrophages are the main target cells for this pathogen, the precise mechanisms behind the response of the macrophage to Map infection and how it is modified by vaccination are yet poorly understood. The aim of this study was to investigate the effect of Silirum® vaccination in the early immune response of caprine monocyte-derived macrophages (CaMØs). Peripheral blood mononuclear cells (PBMCs) were obtained from vaccinated and non-vaccinated goats, cultured in vitro until differentiation to macrophages and infected with Map. After a 24 h incubation, Map viability and DNA were assessed in culture by viable colony count and real time quantitative polymerase chain reaction (qPCR). In addition, Map phagocytosis and expression of IL-10, IL-12, IFN-γ, TNF-α, IL-17A, IL-1β, iNOS, IL-6 and MIP-1β were also evaluated through immunofluorescence labelling and reverse transcriptase qPCR (RT-qPCR), respectively. A significant reduction of Map viability was observed in both supernatants (P < 0.05) and CaMØs (P < 0.001) from the vaccinated group. Similarly, the percentage of infected CaMØs and the number of internalized Map by CaMØs (P < 0.0001) was higher in the vaccinated group. Finally, iNOS (P < 0.01) and IL-10 were significantly up-regulated in CaMØs from vaccinated goats, whereas only MIP-1β was up-regulated in non-vaccinated animals (P < 0.05). These results show that vaccination modifies the immune response of CaMØs, suggesting that the phagocytosis and microbiocidal activity of macrophages against Map is enhanced after vaccination.
Perceived inequity, professional and personal fulfillment by women intensivists in France
Authors:   FEMMIR Group for the SRLF Trial Group, Hauw-Berlemont Caroline , Aubron Cécile , Aissaoui Nadia , Bodet-Contentin Laetitia , Boissier Florence , Fartoukh Muriel Sarah , Jourdain Mercedes , Le Marec Julien , Pestel Julia , Salmon Gandonnière Charlotte , Tamion Fabienne , Hamzaoui Olfa
Published: May 2021

Background

The medical workforce has been feminized for the last two decades worldwide. Nonetheless, women remain under-represented among intensivists. We conducted a survey among French women intensivists to assess their professional and personal quality of life and their perception of potential gender discrimination at work.

Methods

We conducted an observational descriptive study by sending a survey, designed by the group FEMMIR (FEmmes Médecins en Médecine Intensive Réanimation), to women intensivists in France, using primarily the Société de Réanimation de Langue Française (SRLF) mailing list. The questionnaire was also available online between September 2019 and January 2020 and women intensivists were encouraged to answer through email reminders. It pertained to five main domains, including demographic characteristics, work position, workload and clinical/research activities, self-fulfillment scale, perceived discrimination at work and suggested measures to implement.

Results

Three hundred and seventy-one women responded to the questionnaire, among whom 16% had an academic position. Being a woman intensivist and pregnancy were both considered to increase difficulties in careers’ advancement by 31% and 73% of the respondents, respectively. Almost half of the respondents (46%) quoted their quality of life equal to or lower than 6 on a scale varying from 1 (very bad quality of life) to 10 (excellent quality of life). They were 52% to feel an imbalance between their personal and professional life at the cost of their personal life. Gender discrimination has been experienced by 55% of the respondents while 37% confided having already been subject of bullying or harassment. Opportunities to adjust their work timetable including part-time work, better considerations for pregnant women including increasing the number of intensivists and the systematic replacement during maternity leave, and the respect of the law regarding the paternity leave were suggested as key measures to enable better professional and personal accomplishment by women intensivists.

Conclusion

In this first large French survey in women intensivists, we pointed out issues felt by women intensivists that included an imbalance between professional and personal life, a perceived loss of opportunity due to the fact of being a woman, frequent reported bullying or harassment and a lack of consideration of the needs related to pregnancy and motherhood.
End-to-end speech emotion recognition using a novel context-stacking dilated convolution neural network
Authors: Tang Duowei , Kuppens Peter , Geurts Luc , van Waterschoot Toon
Published: May 2021

Amongst the various characteristics of a speech signal, the expression of emotion is one of the characteristics that exhibits the slowest temporal dynamics. Hence, a performant speech emotion recognition (SER) system requires a predictive model that is capable of learning sufficiently long temporal dependencies in the analysed speech signal. Therefore, in this work, we propose a novel end-to-end neural network architecture based on the concept of dilated causal convolution with context stacking. Firstly, the proposed model consists only of parallelisable layers and is hence suitable for parallel processing, while avoiding the inherent lack of parallelisability occurring with recurrent neural network (RNN) layers. Secondly, the design of a dedicated dilated causal convolution block allows the model to have a receptive field as large as the input sequence length, while maintaining a reasonably low computational cost. Thirdly, by introducing a context stacking structure, the proposed model is capable of exploiting long-term temporal dependencies hence providing an alternative to the use of RNN layers. We evaluate the proposed model in SER regression and classification tasks and provide a comparison with a state-of-the-art end-to-end SER model. Experimental results indicate that the proposed model requires only 1/3 of the number of model parameters used in the state-of-the-art model, while also significantly improving SER performance. Further experiments are reported to understand the impact of using various types of input representations (i.e. raw audio samples vs log mel-spectrograms) and to illustrate the benefits of an end-to-end approach over the use of hand-crafted audio features. Moreover, we show that the proposed model can efficiently learn intermediate embeddings preserving speech emotion information.
Seasonal influence of tuberculosis diagnosis in Rwanda
Authors: Uwamahoro Doris , Beeman Aly , Sharma Vinay K. , Henry Michael B. , Garbern Stephanie Chow , Becker Joseph , Harfouche Fairuz Despujos , Rogers Alexis Perez , Kendric Kayla , Guptill Mindi
Published: May 2021

Background

Tuberculosis (TB) remains a major global health concern. Previous research reveals that TB may have a seasonal peak during the spring and summer seasons in temperate climates; however, few studies have been conducted in tropical climates. This study evaluates the influence of seasonality on laboratory-confirmed TB diagnosis in Rwanda, a tropical country with two rainy and two dry seasons.

Methods

A retrospective chart review was performed at the University Teaching Hospital-Kigali (CHUK). From January 2016 to December 2017, 2717 CHUK patients with TB laboratory data were included. Data abstracted included patient demographics, season, HIV status, and TB laboratory results (microscopy, GeneXpert, culture). Univariate and multivariable logistic regression (adjusted for age, gender, and HIV status) analyses were performed to assess the association between season and laboratory-confirmed TB diagnoses.

Results

Patients presenting during rainy season periods had a lower odds of laboratory-confirmed TB diagnosis compared to the dry season (aOR=0.78, 95% CI 0.63–0.97, p=0.026) when controlling for age group, gender, and HIV status. Males, adults, and people living with HIV were more likely to have laboratory-confirmed TB diagnosis. On average, more people were tested for TB during the rainy season per month compared to the dry season (120.3 vs. 103.3), although this difference was not statistically significant.

Conclusion

In Rwanda, laboratory-confirmed TB case detection shows a seasonal variation with patients having higher odds of TB diagnosis occurring in the dry season. Further research is required to further elucidate this relationship and to delineate the mechanism of season influence on TB diagnosis.
Tumor-Infiltrating Lymphocytes, Tumor Mutational Burden, and Genetic Alterations in Microsatellite Unstable, Microsatellite Stable, or Mutant POLE/POLD1 Colon Cancer
Authors: Keshinro Ajaratu , Vanderbilt Chad , Kim Jin K. , Firat Canan , Chen Chin-Tung , Yaeger Rona , Ganesh Karuna , Segal Neil H. , Gonen Mithat , Shia Jinru , Stadler Zsofia , Weiser Martin R.
Published: May 2021

PURPOSE

To characterize the relationship between tumor-infiltrating lymphocytes (TIL), tumor mutational burden (TMB), and genetic alterations in microsatellite stable (MSS), microsatellite instability (MSI), or mutant POLE/POLD1 colon cancer.

MATERIALS AND METHODS

Four hundred ninety-nine resected stage I-III colon tumors treated between 2014 and 2019 were assessed for TIL; somatic mutations, copy number alterations, and structural changes in > 400 oncogenes; and MSI status.

RESULTS

Of the 499 tumors analyzed, 313 were MSS, 175 were MSI, and 11 had POLE/POLD1 pathogenic mutations. Both the percentage of tumors with a high level of TIL (≥ 4 lymphocytes per high-power field) and the median TMB differed significantly between the three phenotypes: MSS, 4.5% and 6 mutations/Mb; MSI, 68% and 54 mutations/Mb; POLE/POLD1, 82% and 158 mutations/Mb ( P < .05). Within each phenotype, TMB did not vary significantly with TIL level. Among MSI tumors, the median number of frameshift indels was significantly higher in tumors with high levels of TIL (20 v 17; P = .018). In the MSS group, significantly higher proportions of tumors with high levels of TIL had mutations in the transforming growth factor-β (36% v 12%; P = .01), RAS (86% v 54%; P = .02), and Hippo (7% v 1%; P = .046) pathways; in contrast, TP53 alterations were associated with low levels of TIL (74% v 43%; P = .01).

CONCLUSION

The association between TIL, TMB, and genetic alterations varies significantly between MSI, MSS, and mutant POLE/POLD1 colon tumors. These differences may help explain tumoral immunity and lead to predictors of response to immunotherapy.
Estimation and Inference by Stochastic Optimization: Three Examples
Authors: Forneron Jean-Jacques , Ng Serena
Published: May 2021

This paper illustrates two algorithms designed in Forneron and Ng (2020): the resampled Newton-Raphson (rNR) and resampled quasi-Newton (rQN) algorithms, which speed up estimation and bootstrap inference for structural models. An empirical application to BLP shows that computation time decreases from nearly five hours with the standard bootstrap to just over one hour with rNR and to only 15 minutes using rQN. A first Monte Carlo exercise illustrates the accuracy of the method for estimation and inference in a probit IV regression. A second exercise additionally illustrates statistical efficiency gains relative to standard estimation for simulation-based estimation using a dynamic panel regression example.
Using Longitudinal Data to Explore the Gender Gap for Academic Economists
Authors: Bedard Kelly , Lee Maxine , Royer Heather
Published: May 2021

There are widespread gender inequities within the economics discipline. In this paper, we collect and analyze new longitudinal salary and personnel data from top economics departments at public institutions. A panel spanning 2005 to 2018 allows us to follow individuals and facilitates the examination of gender gaps in career progression, salary growth, and mobility. Using these data, we document the growth of salary gender gaps with the length of time in the profession, emerging roughly 10 years after the start of one's career. Some of these gaps are attributable to women moving through academic ranks more slowly than men.
Machine Learning about Treatment Effect Heterogeneity: The Case of Household Energy Use
Authors: Knittel Christopher R. , Stolper Samuel
Published: May 2021

We use causal forests to evaluate the heterogeneous treatment effects (TEs) of repeated behavioral nudges toward household energy conservation. The average response to treatment is a monthly electricity reduction of 9 kilowatt-hours (kWh), but the full distribution of responses ranges from -40 to +10 kWh. Households learn to reduce more over time, conditional on having responded in year one. Pre-treatment consumption and home value are the most commonly used predictors in the forest. The results suggest the ability to use machine learning techniques for improved targeting and tailoring of treatment.
Sectoral Effects of Social Distancing
Authors: Barrot Jean-Noël , Grassi Basile , Sauvagnat Julien
Published: May 2021

The outbreak of the COVID-19 virus has led many states to take the drastic measures of social distancing. Using US executive order, occupation, and survey data, we measure the fall in labor supply due to these measures. Starting from a model of production networks, we analyze the sectoral effects of these labor shocks for the United States. We find that nonlinearities in the production network account for around half of the drop in GDP associated to the implementation of social distancing measures. The model also generates realistic dispersion in sectoral output change.
Skin necrosis and calcifications after extravasation of vancomycin: a localised form of calciphylaxis?
Authors: Zenati Nora , Khouri Charles , Schwebel Carole , Blaise Sophie
Published: May 2021

Vancomycin is a tricyclic glycopeptide antibiotic produced from Streptococcus orientalis. There is much variation in the literature with regard to the recommended dose, dilution rate and type of infusion. Given the vesicant properties of vancomycin at supratherapeutic doses (>10mg/ml), tissue damage including blistering and necrosis have been reported. We report a rare case of bilateral cutaneous necrosis induced by accidental extravasation of vancomycin when being intravenously administered. The skin surrounding the injection site was marked by the appearance of subcutaneous calcifications. The development of iatrogenic skin calcinosis has not yet been described for the extravasation of vancomycin. The mechanism underlying the calcinosis observed in our case remains unclear, but we hypothesised a form of localised calciphylaxis induced by a local triggering factor. The ulcers progressed to re-epithelialisation following necrosis debridement and local conservative treatments. Given the increased prevalence of meticillin-resistant Staphylococcus aureus, which has prompted clinicians to gradually increase vancomycin dosage, clinicians should be aware of the high risk of skin toxicity in cases of vancomycin high-dose extravasation.
Geology and Natural Gas in Collegeport Field, Matagorda County, Texas
Authors: Fleming Curtis C.
Published: May 2021

The Collegeport field is perhaps unique as the first and largest Miocene dry-gas discovery in the coastal trend of the Upper Gulf Coast region of Texas. This anticlinal field is 3 by 6 mi and has 11,000 acres proved productive by 41 wells. Gas production currently is from 14 reservoirs in upper and middle Miocene sandstone ranging from 1,900 to 5,600 ft in depth. Four reservoirs have been depleted. Oil production is from a small, isolated reservoir at the east end of the field. Most of the reservoirs are sandstone lenses limited to the field area.

The field is fully developed in the Miocene gas sands. Current annual gas production is 17.5 billion cu ft. Field reserves are about 60 per cent depleted.

Gas mixtures differ little according to depth and areal location. Methane content averages between 98 and 99 per cent, and heating values average about 1,000 BTU per cubic foot of gas.
La relación entre la formación superior y la inserción profesional en países latinoamericanos
Authors: Chávez Molina Eduardo , Fernández Melián María Clara
Published: May 2021

El artículo tiene como propósito analizar la situación del empleo de los profesionales con nivel educativo superior en distintos países de América Latina, observando específicamente las distancias y correspondencias existentes entre las credenciales educativas y la calificación del empleo. Nuestra observación pone el acento en este punto, ¿cuán posible es obtener una inserción profesional adecuada de los egresados de la educación superior según los últimos datos existentes en Latinoamérica considerando el contexto de desarrollo de cada uno de los países seleccionados? En esa línea, los interrogantes que nos orientan son: ¿la inserción ocupacional de los universitarios es parecida entre varones y mujeres? A su vez, la edad también aparece como una variable sintomática de las experiencias, habilidades, y de la consolidación de los estudios formales; la forma de consolidación laboral implica claras diferencias respecto del tipo de inserción y resultados económicos de acuerdo con la edad del ocupado/a. Por último, nos preguntamos: ¿en qué ramas u ocupaciones se observan las mayores similitudes y divergencias? Para ello, utilizamos los datos de la Encuesta Latinobarómetro de Argentina, Bolivia, Brasil, Chile, Colombia, Costa Rica, Rep. Dominicana, Ecuador, El Salvador, Guatemala, Honduras, México, Nicaragua, Panamá, Paraguay, Perú, Uruguay y Venezuela. Así como también la información proveniente del Índice de Desarrollo Humano de Naciones Unidas, para dar el contexto en el cual se desarrolla dicha inserción en cada país.
Temperature-insensitive directional transverse load sensor based on dual side-hole fiber Bragg grating
Authors: He Jun , Xu Baijie , Ju Shuai , Hou Maoxiang , Guo Kuikui , Xu Xizhen , Wang Ying , Liu Shen , Wang Yiping
Published: May 2021

We propose and demonstrate a temperature-insensitive directional transverse load sensor based on a fiber Bragg grating (FBG) inscribed in a section of dual side-hole fiber (DSHF). The application of transverse load results in an effective change in the refractive index and, consequently, changes in the DSHF birefringence. The directional transverse load response of the fabricated DSH-FBG was studied by monitoring the wavelength separations with transverse load applied in different direction with 15° increments. The load sensitivity exhibited two maxima and two minima in a polar coordinate system, achieving a maximum value of 699 pm/(N/mm) for transverse load applied along the slow axis and a minimum value of 285 pm/(N/mm) for transverse load applied along the fast axis. Subsequently, a finite element analysis (FEA) was conducted to simulate the resulting strain distribution of the DSHF with applied directional transverse load. The temperature response of the DSH-FBG transverse load sensor was also tested, yielding a low sensitivity of 1.5 × 10−2 pm/°C. Hence, the compact size, directional transverse load sensitivity, and temperature insensitivity of this device make it suitable for intelligent transverse load monitoring.
Glyphosate inhibits melanization and increases susceptibility to infection in insects
Authors: Smith Daniel F. Q. , Camacho Emma , Thakur Raviraj , Barron Alexander J. , Dong Yuemei , Dimopoulos George , Broderick Nichole A. , Casadevall Arturo
Published: May 2021

Melanin, a black-brown pigment found throughout all kingdoms of life, has diverse biological functions including UV protection, thermoregulation, oxidant scavenging, arthropod immunity, and microbial virulence. Given melanin’s broad roles in the biosphere, particularly in insect immune defenses, it is important to understand how exposure to ubiquitous environmental contaminants affects melanization. Glyphosate—the most widely used herbicide globally—inhibits melanin production, which could have wide-ranging implications in the health of many organisms, including insects. Here, we demonstrate that glyphosate has deleterious effects on insect health in 2 evolutionary distant species, Galleria mellonella (Lepidoptera: Pyralidae) and Anopheles gambiae (Diptera: Culicidae), suggesting a broad effect in insects. Glyphosate reduced survival of G. mellonella caterpillars following infection with the fungus Cryptococcus neoformans and decreased the size of melanized nodules formed in hemolymph, which normally help eliminate infection. Glyphosate also increased the burden of the malaria-causing parasite Plasmodium falciparum in A. gambiae mosquitoes, altered uninfected mosquito survival, and perturbed the microbial composition of adult mosquito midguts. Our results show that glyphosate’s mechanism of melanin inhibition involves antioxidant synergy and disruption of the reaction oxidation–reduction balance. Overall, these findings suggest that glyphosate’s environmental accumulation could render insects more susceptible to microbial pathogens due to melanin inhibition, immune impairment, and perturbations in microbiota composition, potentially contributing to declines in insect populations.
Molecular dynamics shows complex interplay and long-range effects of post-translational modifications in yeast protein interactions
Authors: Šoštarić Nikolina , van Noort Vera
Published: May 2021

Post-translational modifications (PTMs) play a vital, yet often overlooked role in the living cells through modulation of protein properties, such as localization and affinity towards their interactors, thereby enabling quick adaptation to changing environmental conditions. We have previously benchmarked a computational framework for the prediction of PTMs’ effects on the stability of protein-protein interactions, which has molecular dynamics simulations followed by free energy calculations at its core. In the present work, we apply this framework to publicly available data on Saccharomyces cerevisiae protein structures and PTM sites, identified in both normal and stress conditions. We predict proteome-wide effects of acetylations and phosphorylations on protein-protein interactions and find that acetylations more frequently have locally stabilizing roles in protein interactions, while the opposite is true for phosphorylations. However, the overall impact of PTMs on protein-protein interactions is more complex than a simple sum of local changes caused by the introduction of PTMs and adds to our understanding of PTM cross-talk. We further use the obtained data to calculate the conformational changes brought about by PTMs. Finally, conservation of the analyzed PTM residues in orthologues shows that some predictions for yeast proteins will be mirrored to other organisms, including human. This work, therefore, contributes to our overall understanding of the modulation of the cellular protein interaction networks in yeast and beyond.
Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images
Authors: Currant Hannah , Hysi Pirro , Fitzgerald Tomas W. , Gharahkhani Puya , Bonnemaijer Pieter W. M. , Senabouth Anne , Hewitt Alex W. ,   UK Biobank Eye and Vision Consortium,   International Glaucoma Genetics Consortium, Atan Denize , Aung Tin , Charng Jason , Choquet Hélène , Craig Jamie , Khaw Peng T. , Klaver Caroline C. W. , Kubo Michiaki , Ong Jue-Sheng , Pasquale Louis R. , Reisman Charles A. , Daniszewski Maciej , Powell Joseph E. , Pébay Alice , Simcoe Mark J. , Thiadens Alberta A. H. J. , van Duijn Cornelia M. , Yazar Seyhan , Jorgenson Eric , MacGregor Stuart , Hammond Chris J. , Mackey David A. , Wiggs Janey L. , Foster Paul J. , Patel Praveen J. , Birney Ewan , Khawaja Anthony P.
Published: May 2021

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
A novel genotype of Hantaan orthohantavirus harbored by Apodemus agrarius chejuensis as a potential etiologic agent of hemorrhagic fever with renal syndrome in Republic of Korea
Authors: Park Kyungmin , Kim Won-Keun , Lee Seung-Ho , Kim Jongwoo , Lee Jingyeong , Cho Seungchan , Lee Geum-Young , No Jin Sun , Lee Keun Hwa , Song Jin-Won
Published: May 2021

Background

Orthohantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. Despite the significant mortality and morbidity, effective antiviral therapeutics for orthohantavirus infections are currently unavailable. This study aimed to investigate the prevalence of HFRS-associated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern Republic of Korea (ROK).

Methodology/Principal findings

We collected small mammals on Jeju Island during 2018–2020. We detected the Hantaan virus (HTNV)-specific antibodies and RNA using an indirect immunofluorescence assay test and reverse transcription-polymerase chain reaction onApodemus agrarius chejuensis(A.chejuensis). The prevalence of anti-HTNV antibodies among rodents was 14.1%. A total of six seropositive mouse harbored HTNV RNA. The amplicon-based next-generation sequencing provided nearly full-length tripartite genomic sequences of six HTNV harbored byA.chejuensis. Phylogenetic and tanglegram analyses were conducted for inferring evolutionary relationships between orthohantaviruses with their reservoir hosts. Phylogenetic analysis showed a novel distinct HTNV genotype. The detected HTNV genomic sequences were phylogenetically related to a viral sequence derived from HFRS patient in southern ROK. Tanglegram analysis demonstrated the segregation of HTNV genotypes corresponding toApodemus spp. divergence.

Conclusions/Significance

Our results suggest thatA.chejuensis-borne HTNV may be a potential etiological agent of HFRS in southern ROK. Ancestral HTNV may infectA.chejuensisprior to geological isolation between the Korean peninsula and Jeju Island, supporting the co-evolution of orthohantaviruses and rodents. This study arises awareness among physicians for HFRS outbreaks in southern ROK.
The IL-10GFP (VeRT-X) mouse strain is not suitable for the detection of IL-10 production by granulocytes during lung inflammation
Authors: Özkan Müge , Eskiocak Yusuf Cem , Wingender Gerhard
Published: May 2021

The clear and unequivocal identification of immune effector functions is essential to understand immune responses. The cytokine IL-10 is a critical immune regulator and was shown, for example, to limit pathology during various lung diseases. However, the clear identification of IL-10-producing cells is challenging and, therefore, reporter mouse lines were developed to facilitate their detection. Several such reporter lines utilize GFP, including the IL-10GFP(VeRT-X) reporter strain studied here. In line with previous reports, we found that this IL-10GFPline faithfully reports on the IL-10 production of lymphoid cells. However, we show that the IL-10GFPreporter is not suitable to analyse IL-10 production of myeloid cells during inflammation. During inflammation, the autofluorescence of myeloid cells increased to an extent that entirely masked the IL-10-specific GFP-signal. Our data illustrate a general and important technical caveat using GFP-reporter lines for the analysis of myeloid cells and suggest that previous reports on effector functions of myeloid cells using such GFP-based reporters might require re-evaluation.