bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Wearing the Elevation Training Mask During Low-intensity Cycling Exercise on Intraocular Pressure
Authors: Vera Jesús , Jiménez Raimundo , Redondo Beatríz , Perez-Castilla Alejandro , García-Ramos Amador
Published: February 2021

Précis:

Low-intensity aerobic exercise is recommended to reduce intraocular pressure (IOP) levels. However, this effect depends on several factors. We found that using an elevation training mask (ETM) during low-intensity aerobic exercise causes an IOP rise.

Purpose:

The aim was to assess the influence of wearing an ETM on IOP during low-intensity endurance training.

Methods:

Sixteen physically active young adults (age=23.9±2.9 y) cycled during 30 minutes at 10% of maximal power production with and without an ETM in 2 different days and randomized order. A rebound tonometer was used to measure IOP at baseline, after a warm-up of 5 minutes, during cycling (6, 12, 18, 24, and 30 min), and recovery (5 and 10 min) by rebound tonometry.

Results:

The use of an ETM significantly affects the IOP behaviour during exercise (P<0.001, ηp²=0.66). In the ETM condition, there was an IOP increment during exercise (P<0.001, ηp²=0.28) whereas an IOP-lowering effect was observed in the control condition (P<0.001, ηp²=0.41). Post hoc comparisons showed that there were greater IOP values during exercise in the ETM condition in comparison to the control condition (average IOP difference=3.7±2.2 mm Hg; corrected P<0.01, and the Cohen d’s >1.10, in all cases).

Conclusion:

Low-intensity endurance exercise causes an increment in IOP when it is performed wearing an ETM and a decrease in IOP when the air flow is not restricted (control condition). Therefore, the ETM should be discouraged during low-intensity endurance exercise for individuals who need to reduce IOP levels (eg, glaucoma patients or those at risk). However, the external validity of these results needs to be addressed in future studies with the inclusion of glaucoma patients.
Immunophenotypic Spectrum and Genomic Landscape of Refractory Celiac Disease Type II
Authors: Soderquist Craig R. , Lewis Suzanne K. , Gru Alejandro A. , Vlad George , Williams Eli S. , Hsiao Susan , Mansukhani Mahesh M. , Park David C. , Bacchi Carlos E. , Alobeid Bachir , Green Peter H. , Bhagat Govind
Published: February 2021

Refractory celiac disease type II (RCD II), also referred to as “cryptic” enteropathy-associated T-cell lymphoma (EATL) or “intraepithelial T-cell lymphoma,” is a rare clonal lymphoproliferative disorder that arises from innate intraepithelial lymphocytes. RCD II has a poor prognosis and frequently evolves to EATL. The pathogenesis of RCD II is not well understood and data regarding the immunophenotypic spectrum of this disease and underlying genetic alterations are limited. To gain further biological insights, we performed comprehensive immunophenotypic, targeted next-generation sequencing, and chromosome microarray analyses of 11 RCD II cases: CD4−/CD8− (n=6), CD8+ (n=4), and CD4+ (n=1), and 2 of 3 ensuing EATLs. Genetic alterations were identified in 9/11 (82%) of the RCD II cases. All 9 displayed mutations in members of the JAK-STAT signaling pathway, including frequent, recurrent STAT3 (7/9, 78%) and JAK1 (4/9, 44%) mutations, and 9/10 evaluable cases expressed phospho-STAT3. The mutated cases also harbored recurrent alterations in epigenetic regulators (TET2, n=5 and KMT2D, n=5), nuclear factor-κB (TNFAIP3, n=4), DNA damage repair (POT1, n=3), and immune evasion (CD58, n=2) pathway genes. The CD4−/CD8− and other immunophenotypic subtypes of RCD II exhibited similar molecular features. Longitudinal genetic analyses of 4 RCD II cases revealed stable mutation profiles, however, additional mutations were detected in the EATLs, which occurred at extraintestinal sites and were clonally related to antecedent RCD II. Chromosome microarray analysis demonstrated copy number changes in 3/6 RCD II cases, and 1 transformed EATL with sufficient neoplastic burden for informative analysis. Our findings provide novel information about the immunophenotypic and genomic characteristics of RCD II, elucidate early genetic events in EATL pathogenesis, and reveal potential therapeutic targets.
Image Quality Improvement of Dynamic Contrast-Enhanced Gradient Echo Magnetic Resonance Imaging by Iterative Denoising and Edge Enhancement
Authors: Gassenmaier Sebastian , Herrmann Judith , Nickel Dominik , Kannengiesser Stephan , Afat Saif , Seith Ferdinand , Hoffmann Rüdiger , Othman Ahmed E.
Published: February 2021

Objectives

The aim of this study was to investigate the impact of a novel edge enhancement and iterative denoising algorithm in 1.5-T T1-weighted dynamic contrast-enhanced (DCE) gradient echo (GRE) magnetic resonance imaging of the abdomen on image quality, noise levels, diagnostic confidence, and lesion detectability.

Materials and Methods

Fifty patients who underwent a clinically indicated magnetic resonance imaging with DCE imaging of the abdomen between June and August 2020 were included in this retrospective, monocentric, institutional review board–approved study. For DCE imaging, a series of 3 volume interpolated breath-hold examinations (VIBEs) was performed. The raw data of all DCE imaging studies were processed twice, once using standard reconstruction (DCES) and again using an edge enhancement and iterative denoising approach (DCEDE). All imaging studies were randomly reviewed by 2 radiologists independently regarding noise levels, arterial contrast, sharpness of vessels, overall image quality, and diagnostic confidence using a Likert scale ranging from 1 to 4, with 4 being the best. Furthermore, lesion detectability was evaluated using the same ranking system.

Results

All 50 imaging studies were successfully reconstructed with both methods. Interreader agreement (Cohen κ) was substantial to perfect for both readers. Arterial contrast and sharpness of vessels were rated superior by both readers with a median of 4 in DCEDE versus a median of 3 in DCES (P < 0.001). Furthermore, noise levels as well as overall image quality were rated higher with a median of 4 in DCEDE compared with a median of 3 in DCES (P < 0.001). Lesion detectability was evaluated to be superior in DCEDE with a median of 4 versus DCES with a median of 3 (P < 0.001). Consequently, diagnostic confidence was also rated to be superior in DCEDE with a median of 4 versus DCES with a median of 3 (P < 0.001).

Conclusions

Iterative denoising and edge enhancement are feasible in DCE imaging of the abdomen providing superior arterial contrast, noise levels, and overall image quality. Furthermore, lesion detectability and diagnostic confidence were significantly improved using this novel reconstruction method. Further reduction of acquisition time might be possible via reduction of increased noise levels using this presented method.
Topical Timolol Combined Intralesional Injection of Diprospan in the Treatment of Elevated Localized Mixed Infantile Hemangiomas and a Discussion for Proper Timing for Injection
Authors: Zhang Jing-Yue , Lan Shi-Jie , Liu Meng , Yang Tian-Ye , Liu Shan-Shan , Rong Li
Published: February 2021

Background:

Although infantile hemangiomas (IHs) are usually self-limiting, residual elevated appearance may remain. Topical beta-blockers are effective in superficial IHs management, while intralesionally injected diprospan is effective at treating deep, localized IHs. A single application of topical timolol or injected diprospan has obvious limitations. Therefore, for elevated, localized mixed IHs, we applied topical timolol combined with intralesionally injected diprospan, using their respective advantages to maximize benefits.

Purpose:

To evaluate the clinical efficacy and safety of topical timolol combined with intralesionally injected diprospan for the treatment of elevated, localized mixed IHs and identify the optimal injection time.

Methods:

Infants with elevated, localized mixed IHs in the proliferative phase were treated with injected diprospan combined with topical timolol between March 2018 and March 2020. The injection was administered only when the tumor surface was higher than that of the surrounding tissue. The patients were asked to return every 4 weeks for a treatment response evaluation, and complications were recorded.

Results:

Thirty-six patients with elevated, localized mixed IHs (thickness >3 mm on Doppler ultrasound) were recruited. The mean age at treatment initiation was 3.58 ± 1.50 months (range: 1.00–6.00 months). The follow-up period ranged from 9 to 24 months. Considering the size of the IH at the end of treatment, regression was observed in 31 (86.1%) cases, stabilization was observed in 5 (13.9%) cases, and no treatment failure was observed. All the IHs improved in color and height after treatment.

Conclusion:

Topical timolol combined with intralesionally injected diprospan is an effective and safe treatment for elevated, localized mixed IH. The injection is needed only when we forecast the elevated tissue may remain after regression.
Determining the Level of Importance of Variables in Predicting Kidney Transplant Survival Based on a Novel Ranking Method
Authors: Taherkhani Nasrin , Sepehri Mohammad Mehdi , Khasha Roghaye , Shafaghi Shadi
Published: February 2021

Background.

Kidney transplantation is the best alternative treatment for end-stage renal disease. To optimal use of donated kidneys, graft predicted survival can be used as a factor to allocate kidneys. The performance of prediction techniques is highly dependent on the correct selection of predictors. Hence, the main objective of this research is to propose a novel method for ranking the effective variables for predicting the kidney transplant survival.

Methods.

Five classification models were used to classify kidney recipients in long- and short-term survival classes. Synthetic minority oversampling and random undersampling were used to overcome the imbalanced class problem. In dealing with missing values, 2 approaches were used (eliminating and imputing them). All variables were categorized into 4 levels. The ranking was evaluated using the sensitivity analysis approach.

Results.

Thirty-four of the 41 variables were identified as important variables, of which, 5 variables were categorized in very important level (“Recipient creatinine at discharge,” “Recipient dialysis time,” “Donor history of diabetes,” “Donor kidney biopsy,” and “Donor cause of death”), 17 variables in important level, and 12 variables in the low important level.

Conclusions.

In this study, we identify new variables that have not been addressed in any of the previous studies (eg, AGE_DIF and MATCH_GEN). On the other hand, in kidney allocation systems, 2 main criteria are considered: equity and utility. One of the utility subcriteria is the graft survival. Our study findings can be used in the design of systems to predict the graft survival.
Neural versus alternative integrative systems: molecular insights into origins of neurotransmitters
Authors: Moroz Leonid L. , Romanova Daria Y. , Kohn Andrea B.
Published: February 2021

Transmitter signalling is the universal chemical language of any nervous system, but little is known about its early evolution. Here, we summarize data about the distribution and functions of neurotransmitter systems in basal metazoans as well as outline hypotheses of their origins. We explore the scenario that neurons arose from genetically different populations of secretory cells capable of volume chemical transmission and integration of behaviours without canonical synapses. The closest representation of this primordial organization is currently found in Placozoa, disk-like animals with the simplest known cell composition but complex behaviours. We propose that injury-related signalling was the evolutionary predecessor for integrative functions of early transmitters such as nitric oxide, ATP, protons, glutamate and small peptides. By contrast, acetylcholine, dopamine, noradrenaline, octopamine, serotonin and histamine were recruited as canonical neurotransmitters relatively later in animal evolution, only in bilaterians. Ligand-gated ion channels often preceded the establishment of novel neurotransmitter systems. Moreover, lineage-specific diversification of neurotransmitter receptors occurred in parallel within Cnidaria and several bilaterian lineages, including acoels. In summary, ancestral diversification of secretory signal molecules provides unique chemical microenvironments for behaviour-driven innovations that pave the way to complex brain functions and elementary cognition.

This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens'.
Reafference and the origin of the self in early nervous system evolution
Authors: Jékely Gáspár , Godfrey-Smith Peter , Keijzer Fred
Published: February 2021

Discussions of the function of early nervous systems usually focus on a causal flow from sensors to effectors, by which an animal coordinates its actions with exogenous changes in its environment. We propose, instead, that much early sensing was
reafferent
; it was responsive to the consequences of the animal's own actions. We distinguish two general categories of reafference—translocational and deformational—and use these to survey the distribution of several often-neglected forms of sensing, including gravity sensing, flow sensing and proprioception. We discuss sensing of these kinds in sponges, ctenophores, placozoans, cnidarians and bilaterians. Reafference is ubiquitous, as ongoing action, especially whole-body motility, will almost inevitably influence the senses. Corollary discharge—a pathway or circuit by which an animal tracks its own actions and their reafferent consequences—is not a necessary feature of reafferent sensing but a later-evolving mechanism. We also argue for the importance of reafferent sensing to the evolution of the
body-self
, a form of organization that enables an animal to sense and act as a single unit.

This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.
Ruminiclostridium herbifermentans sp. nov., a mesophilic and moderately thermophilic cellulolytic and xylanolytic bacterium isolated from a lab-scale biogas fermenter fed with maize silage
Authors: Rettenmaier Regina , Kowollik Marie-Louise , Klingl Andreas , Liebl Wolfgang , Zverlov Vladimir
Published: February 2021

An anaerobic bacterial strain, designated MA18T, was isolated from a laboratory-scale biogas fermenter fed with maize silage. Cells stained Gram-negative and performed Gram-negative in the KOH test. The peptidoglycan type was found to be A1y-meso-Dpm direct. The major cellular fatty acids were C14 : 0 iso, C15 : 0 iso, anteiso and iso DMA as well as a C16 unidentified fatty acid. Oxidase and catalase activities were absent. Cells were slightly curved rods, motile, formed spores and measured approximately 0.35 µm in diameter and 3.0–5.0 µm in length. When cultivated on GS2 agar with cellobiose, round, arched, shiny and slightly yellow-pigmented colonies were formed. The isolate was mesophilic to moderately thermophilic with a growth optimum between 40 and 48 °C. Furthermore, neutral pH values were preferred and up to 1.2 % (w/v) NaCl supplemented to the GS2 medium was tolerated. Producing mainly acetate and ethanol, MA18T fermented arabinose, cellobiose, crystalline and amorphous cellulose, ribose, and xylan. The genome of MA18T consists of 4 817 678 bp with a G+C content of 33.16 mol%. In the annotated protein sequences, cellulosomal components were detected. Phylogenetically, MA18T is most closely related to

Ruminiclostridium sufflavum

DSM 19573T (76.88 % average nucleotide identity of the whole genome sequence; 97.23 % 16S rRNA gene sequence similarity) and can be clustered into one clade with other species of the genus

Ruminiclostridium

, family

Oscillospiraceae

, class

Clostridia

. Based on morphological, physiological and genetic characteristics, this strain represents a novel species in the genus

Ruminiclostridium

. Therefore, the name Ruminiclostridium herbifermentans sp. nov. is proposed. The type strain is MA18T (=DSM 109966T=JCM 39124T).
OX2: Understanding the pattern of symptoms for pancreatic neuroendocrine neoplasms (PNENs) to improve the early diagnosis of pancreatic cancer: analysis of the QResearch database
Authors:   Investigators, Liao Weiqi , Clift Ashley , Patone Martina , Coupland Carol , Hippisley-Cox Julia
Published: February 2021

This article is the study protocol and statistical analysis plan for the project. This study is set up to identify and quantify “red flag” symptoms associated with the diagnosis of Pancreatic Neuroendocrine Neoplasm (PNEN) and compare these with the symptoms associated with Pancreatic Ductal Adenocarcinoma (PDAC). The results of this study will inform the evidence base for the refinement of the QCancer (Pancreas) tools, which have been integrated into the UK NHS primary care computer systems, to improve the early recognition of PNEN.
Neuromotor Prosthetic to Treat Stroke-Related Paresis
Authors: Serruya Mijail D. , Napoli Alessandro , Satterthwaite Nicholas , Kardine Joseph , McCoy Joseph , Grampurohit Namrata , Talekar Kiran , Middleton Devon , Mohamed Feroze , Kogan Michael , Sharan Ashwini , Wu Chengyuan , Rosenwasser Robert
Published: February 2021

Abstract

Background

Functional recovery of independent arm movement typically plateaus within six months following a stroke, leaving chronic motor deficits. This feasibility study tested whether a wearable, powered exoskeletal orthosis, driven by a percutaneous, implanted brain–computer interface (BCI), using the activity of neurons in the precentral gyrus in the affected cortical hemisphere, could restore voluntary upper extremity function in a person with chronic hemiparetic subsequent to a cerebral hemispheric stroke of subcortical gray and white matter and cortical gray matter.

Methods

One person with chronic hemiparetic stroke with upper-limb motor impairment used a powered elbow-wrist-hand orthosis that opened and closed the affected hand using cortical activity, recorded from four 64-channel microelectrode arrays implanted in the ipsilesional precentral gyrus, based on decoding of spiking patterns and high frequency field potentials generated by imagined hand movements using technology and decoding methods used for people with other causes of paralysis. The system was evaluated in a home setting daily for 12 weeks.

Results

Robust single unit activity, modulating with attempted or imagined movement, was present throughout the precentral gyrus areas. The participant was able to acquire voluntary control over a hand-orthosis BCI, with a score of 10 points on the Action Research Arm Test (out of 53) using the BCI, compared to 0 without any device, and 5 using myoelectric control. Orthosis-powered hand-opening was faster with BCI control compared to myoelectric control, on a standardized object-movement task.

Conclusions

The findings demonstrate the therapeutic potential of an implantable BCI system coupled to a brace to “electrically bypass” the stroke and promote neurally driven limb function. The participant’s ability to rapidly acquire voluntary control over otherwise paralyzed hand opening, more than 18 months after a subcortical stroke, lays the foundation for a fully implanted movement restoration system.
Implementation of an in-house real-time reverse transcription-PCR assay for the rapid detection of the SARS-CoV-2 Marseille-4 variant
Authors: Bedotto Marielle , Fournier Pierre-Edouard , Houhamdi Linda , Levasseur Anthony , Delerce Jeremy , Pinault Lucile , Padane Abdou , Chamieh Amanda , Tissot-Dupont Hervé , Brouqui Philippe , Sokhna Cheikh , Azar Eid , Saile Rachid , Mboup Souleymane , Bitam Idir , Colson Philippe , Raoult Didier
Published: February 2021

Introduction

The SARS-CoV-2 pandemic has been associated with the occurrence since summer 2020 of several viral variants that overlapped or succeeded each other in time. Those of current concern harbor mutations within the spike receptor binding domain (RBD) that may be associated with viral escape to immune responses. In our geographical area a viral variant we named Marseille-4 harbors a S477N substitution in this RBD.

Materials and methods

We aimed to implement an in-house one-step real-time reverse transcription-PCR (qPCR) assay with a hydrolysis probe that specifically detects the SARS-CoV-2 Marseille-4 variant.

Results

All 6 cDNA samples from Marseille-4 variant strains identified in our institute by genome next-generation sequencing (NGS) tested positive using our Marseille-4 specific qPCR, whereas all 32 cDNA samples from other variants tested negative. In addition, 39/42 (93%) respiratory samples identified by NGS as containing a Marseille-4 variant strain and 0/26 samples identified as containing non-Marseille-4 variant strains were positive. Finally, 1,585/2,889 patients SARS-CoV-2-diagnosed in our institute, 10/277 (3.6%) respiratory samples collected in Algeria, and none of 207 respiratory samples collected in Senegal, Morocco, or Lebanon tested positive using our Marseille-4 specific qPCR.

Discussion

Our in-house qPCR system was found reliable to detect specifically the Marseille-4 variant and allowed estimating it is involved in more than half of our SARS-CoV-2 diagnoses since December 2020. Such approach allows the real-time surveillance of SARS-CoV-2 variants, which is warranted to monitor and assess their epidemiological and clinical characterics based on comprehensive sets of data.
Morphological Patterns Of Anemia Among Under Five Children On Prevention Of Mother-To-Child Transmission (PMTCT) Programmes In Masogo Sub-County Hospital, Kisumu County, Kenya
Authors: Awuor Silas O. , Eric Omwenga O. , Musyoki Stanslaus , Daud Ibrahim I. , Nyangaresi Robert O. , Mugah Peter , Mukunzi Beatrice
Published: February 2021

Background

Anaemia during childhood adversely affects mental, physical and social development of the children, therefore morphological patterns of anaemia in under-five children are considered essential for classification, diagnosis and management.

Aim

This study aimed at assessing morphological patterns, the prevalence and associated factors of anaemia among under-five children on Prevention of Mother-To-Child Transmission (PMTCT) programmes in Masogo sub-county hospital, Kisumu County, Kenya.

Method

A cross-sectional health facility-based study was conducted among 175 children aged 6 to 59 months who attended clinic for the PMTCT programme for the period of January 2020 to December 2020. Pretested and structured questionnaires were used to collect socioeconomic and demographic characteristics of the family and child. Capillary blood sample was collected from each child for malaria parasite and Peripheral Blood Film (PBF) examination.

Result

Complete blood counts indicate that microcytic pattern was the most common, representing 30 (42.3%) followed by microcytic hypochromic pattern 20 (28.2%), normocytic normochromic pattern with 11 (15.5%) and lastly dimorphic pattern with 10 (14.0%). High prevalence of anaemia was observed in children who were urban dwellers (50.0%), in children whose mothers aged 18-27 years (44.0%) and had no formal education (48.1%). Besides, the high prevalence rate of anaemia was found among children with a family monthly income of less than 500 Ksh. (46.9%), early (<6 months) introduction of complementary foods (71.4%)

Conclusion

This study has revealed that the prevalence of anaemia in children less than five years is high and is a severe public health problem in the study area. Therefore, the policymakers should make a strategy that can reduce poverty and increase the awareness to women on breastfeeding, nutrition, and other associated factors to reduce anaemia.
Tau-PET and in vivo Braak-staging as a prognostic marker in Alzheimer’s disease
Authors: Biel Davina , Brendel Matthias , Rubinski Anna , Buerger Katharina , Janowitz Daniel , Dichgans Martin , Franzmeier Nicolai ,   for the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: February 2021

INTRODUCTION

Tau pathology in Alzheimer’s disease tracks clinical status more closely than beta-amyloid. Thus, tau-PET may be a promising prognostic marker for cognitive decline. Here, we systematically compared tau-PET and Braak-staging vs. amyloid-PET as predictors of cognitive decline.

METHODS

We included 396 cognitively normal to dementia subjects with18F-Flutemetamol/18F-Florbetapir-amyloid-PET,18F-Flortaucipir-tau-PET and ~2-year cognitive assessments. Annual cognitive change rates were calculated via linear-mixed models. We determined global amyloid-PET, global tau-PET, and tau-PET-based Braak-stage (Braak0/BraakI+/BraakI-IV+/BraakI-VI+/Braakatypical+). In bootstrapped linear regression, we assessed whether tau-PET outperformed amyloid-PET in predicting cognitive decline. Using ANCOVAs, we tested whether later Braak-stage predicted accelerated cognitive decline and determined Braak-stage-specific conversion risk to MCI or dementia.

RESULTS

Global tau-PET was a better predictor of cognitive decline than global amyloid-PET (p<0.001). Advanced Braak-stage was associated with faster cognitive decline (p<0.001) and elevated clinical conversion risk.

DISCUSSION

Tau-PET and Braak-staging show promise for predicting patient-specific risk of clinical AD progression.
Identification of transdiagnostic psychiatric disorder subtypes using unsupervised learning
Authors: Pelin Helena , Ising Marcus , Stein Frederike , Meinert Susanne , Meller Tina , Brosch Katharina , Winter Nils R. , Krug Axel , Leenings Ramona , Lemke Hannah , Nenadic Igor , Heilmann-Heimbach Stefanie , Forstner Andreas J. , Nöthen Markus M. , Opel Nils , Repple Jonathan , Pfarr Julia , Ringwald Kai , Schmitt Simon , Thiel Katharina , Waltemate Lena , Winter Alexandra , Streit Fabian , Witt Stephanie , Rietschel Marcella , Dannlowski Udo , Kircher Tilo , Hahn Tim , Müller-Myhsok Bertram , Andlauer Till F. M.
Published: February 2021

Psychiatric disorders show heterogeneous clinical manifestations and disease trajectories, with current classification systems not accurately reflecting their molecular etiology. This heterogeneity impedes timely and targeted treatment. Our study aimed to identify diagnostically mixed psychiatric patient clusters that share clinical and genetic features and may profit from similar therapeutic interventions. We used unsupervised high-dimensional data clustering on deep clinical data to identify transdiagnostic groups in a discovery sample (N=1250) of healthy controls and patients diagnosed with depression, bipolar disorder, schizophrenia, schizoaffective disorder, and other psychiatric disorders. We observed five diagnostically mixed clusters and ordered them based on severity. The least impaired cluster 0, containing most healthy controls, was characterized by general well-being. Clusters 1-3 differed predominantly regarding levels of maltreatment, depression, daily functioning, and parental bonding. Cluster 4 contained most patients diagnosed with psychotic disorders and exhibited the highest severity in many dimensions, including medication load. MDD patients were present in all clusters, indicating that we captured different disease stages or subtypes. We replicated all but the smallest cluster 1 in an independent sample (N=622). Next, we analyzed genetic differences between clusters using polygenic scores (PGS) and the psychiatric family history. These genetic variables differed mainly between clusters 0 and 4 (prediction AUC=81%; significant PGS: cross-disorder psychiatric risk, schizophrenia, and educational attainment). Our results confirm that psychiatric disorders consist of heterogeneous subtypes sharing molecular factors and symptoms. The identification of transdiagnostic clusters advances our understanding of the heterogeneity of psychiatric disorders and may support the development of personalized treatment regimes.
Using Machine Learning to Predict Mortality for COVID-19 Patients on Day Zero in the ICU
Authors: Jamshidi Elham , Asgary Amirhossein , Tavakoli Nader , Zali Alireza , Esmaily Hadi , Jamaldini Seyed Hamid , Daaee Amir , Babajani Amirhesam , Kashi Mohammad Ali Sendani , Jamshidi Masoud , Rahi Sahand Jamal , Mansouri Nahal
Published: February 2021

Rationale

Given the expanding number of COVID-19 cases and the potential for upcoming waves of infection, there is an urgent need for early prediction of the severity of the disease in intensive care unit (ICU) patients to optimize treatment strategies.

Objectives

Early prediction of mortality using machine learning based on typical laboratory results and clinical data registered on the day of ICU admission.

Methods

We studied retrospectively 263 COVID-19 ICU patients. To find parameters with the highest predictive values, Kolmogorov-Smirnov and Pearson chi-squared tests were used. Logistic regression and random forest (RF) algorithms were utilized to build classification models. The impact of each marker on the RF model predictions was studied by implementing the local interpretable model-agnostic explanation technique (LIME-SP).

Results

Among 66 documented parameters, 15 factors with the highest predictive values were identified as follows: gender, age, blood urea nitrogen (BUN), creatinine, international normalized ratio (INR), albumin, mean corpuscular volume, white blood cell count, segmented neutrophil count, lymphocyte count, red cell distribution width (RDW), and mean cell hemoglobin along with a history of neurological, cardiovascular, and respiratory disorders. Our RF model can predict patients outcomes with a sensitivity of 70% and a specificity of 75%.

Conclusions

The most decisive variables in our model were increased levels of BUN, lowered albumin levels, increased creatinine, INR, and RDW along with gender and age. Complete blood count parameters were also crucial for some patients. Considering the importance of early triage decisions, this model can be a useful tool in COVID-19 ICU decision-making.
Investigation of association of rare, functional genetic variants with heavy drinking and problem drinking in exome sequenced UK Biobank participants
Authors: Curtis David
Published: February 2021

Aims

The study aimed to identify specific genes and functional genetic variants affecting susceptibility to two alcohol related phenotypes: heavy drinking and problem drinking.

Methods

Phenotypic and exome sequence data was downloaded from the UK Biobank. Reported drinks in the last 24 hours was used to define heavy drinking while responses to a mental health questionnaire defined problem drinking. Gene-wise weighted burden analysis was applied, with genetic variants which were rarer and/or had a more severe functional effect being weighted more highly. Additionally, previously reported variants of interest were analysed inidividually.

Results

Of exome sequenced subjects, for heavy drinking there were 8,166 cases and 84,461 controls while for problem drinking there were 7,811 cases and 59,606 controls. No gene was formally significant after correction for multiple testing but three genes possibly related to autism were significant at p < 0.001,FOXP1, ARHGAP33andCDH9, along withVGFwhich may also be of psychiatric interest. Well established associations with rs1229984 inADH1Band rs671 inALDH2were confirmed but previously reported variants inALDH1B1andGRM3were not associated with either phenotype.

Conclusions

This large study fails to conclusively implicate any novel genes or variants. It is possible that more definitive results will be obtained when sequence data for the remaining UK Biobank participants becomes available and/or if data can be obtained for a more extreme phenotype such as alcohol dependence disorder. This research has been conducted using the UK Biobank Resource.

Short summary

Tests for association of rare, functional genetic variants with heavy drinking and problem drinking confirm the known effects of variants inADH1BandALDH2but fail to implicate novel variants or genes. Results for three genes potentially related to autism suggest they might exert a protective effect.
Ventilation rate assessment by carbon dioxide levels in dental treatment rooms
Authors: Huang Qirong , Marzouk Tamer , Cirligeanu Razvan , Malmstrom Hans , Eliav Eli , Ren Yan-Fang
Published: February 2021

Objectives

The purpose of the present study was to monitor and evaluate CO2 levels in dental operatories using a consumer-grade CO2 sensor and determine the utility and accuracy of various methods using CO2 levels to assess ventilation rate in dental clinics. We aim to find a practical tool for dental practitioners to conveniently and accurately monitor CO2 levels and assess the ventilation rates in their office in order to devise a pragmatic and effective strategy for ventilation improvement in their work environment.

Methods

Mechanical ventilation rate in air change per hour (ACHVENT) of 10 dental operatories was first measured with an air velocity sensor and air flow balancing hood. CO2 levels were measured in these rooms to analyze the effects of ventilation rate and number of persons in the room on CO2 accumulation. Ventilation rates were estimated using natural steady state CO2 levels during dental treatments and experimental CO2 concentration decays by dry ice or mixing baking soda and vinegar. We compared the differences and assessed the correlations between ACHVENT and ventilation rates estimated by steady states CO2 model with low (0.3 L/min, ACHSS30) or high (0.46 L/min, ACHSS46) CO2 generation rates, by CO2 decay constants using dry ice (ACHDI) or baking soda (ACHBV), and by time needed to remove 63% of excess CO2 generated by dry ice (ACHDI63%) or baking soda (ACHBV63%).

Results

ACHVENT varied from 3.9 to 35.0 with a mean of 13.2 (±10.6) in the 10 dental operatories. CO2 accumulation occurred in rooms with low ventilation (ACHVENT≤6) and more persons (n>3) but not in those with higher ventilation and less persons. ACHSS30 and ACHSS46 correlated well with ACHVENT (r=0.83, p=0.003), but ACHSS30 was more accurate for rooms with low ACHVENT. Ventilation rates could be reliably estimated using CO2 released from dry ice or baking soda. ACHVENT was highly correlated with ACHDI (r=0.99), ACHBV(r=0.98), ACHDI63%(r=0.98), and ACHBV63% (r=0.98). There were no statistically significant differences between ACHVENT and ACHDI63% or ACHBV63%.

Conclusions

Dental operatories with low ventilation rates and overcrowding facilitate CO2 accumulations. Ventilation rates could be reliably calculated by observing the changes in CO2 levels after a simple mixing of household baking soda and vinegar in dental settings. Time needed to remove 63% of excess CO2 generated by baking soda could be used to accurately assess the ventilation rates using a consumer-grade CO2 sensor and a basic calculator.
COVID-19 prevention behaviour over time in Australia: Patterns and long-term predictors from April to July 2020
Authors: Ayre J , Cvejic E , McCaffery K , Copp T , Cornell S , Dodd RH , Pickles K , Batcup C , Isautier JMJ , Nickel B , Dakin T , Bonner C
Published: February 2021

Background

In Australia in March 2020 a national public health directive required that non-essential workers stay at home, except for essential activities. These restrictions began easing in May 2020 as community transmission slowed.

Purpose

This study investigated changes in COVID-19 prevention behaviours from April-July 2020, and psychosocial predictors of these behaviours.

Methods

1,843 participants in Australia completed a national COVID-19 survey in April, with monthly follow-up over four months. Principal components analysis (PCA) combined self-reported adherence across seven prevention behaviours. Multivariable regression models explored baseline (April) correlates of behaviour in June (a period of low community transmission) and July (a period of increasing community transmission).

Results

On average, participants agreed with statements of adherence for all behaviours (means all above 4 out of 7). PCA identified two behaviour types: ‘distancing’ (e.g. staying 1.5m away) and ‘hygiene’ (e.g. washing hands), explaining 28.3% and 24.2% of variance, respectively. Distancing declined each month (p’s<.001), whereas hygiene remained relatively stable. For distancing, stronger perceptions of societal risk, self-efficacy to maintain distancing, and greater perceived social obligation at baseline were associated with adherence in June and July (p’s<0.05). For hygiene, the only significant correlate of adherence in June and July was belief that one’s actions could prevent infection of family members (p<.001).

Conclusions

High adherence to COVID-19 prevention behaviours were reported; however, distancing behaviours tended to decrease over time. Belief in social responsibility may be an important aspect to consider in encouraging distancing behaviours. Different policy approaches may be needed for different behavioural categories.
Symptoms of COVID-19 infection and magnitude of antibody response in a large community-based study
Authors: McDade Thomas W. , Schrock Joshua M. , D’Aquila Richard , Mustanski Brian , Benbow Nanette , Vaught Lauren A. , Reiser Nina L. , Velez Matt E. , Hsieh Ryan R. , Ryan Daniel T. , Saber Rana , McNally Elizabeth M. , Demonbreun Alexis R.
Published: February 2021

Background

The majority of COVID-19 cases are asymptomatic, or minimally symptomatic with management in the home. Little is known about the frequency of specific symptoms in the general population, and how symptoms predict the magnitude of antibody response to SARS-CoV-2 infection.

Methods

We quantified IgG antibodies against the SARS-CoV-2 receptor binding domain (RBD) in home-collected dried blood spot samples from 3,365 adults participating in a community-based seroprevalence study in the city of Chicago, USA, collected between June 24 and November 11, 2020.

Results

17.8% of the sample was seropositive for SARS-CoV-2. A cluster of symptoms (loss of sense of smell or taste, fever, shortness of breath, muscle or body aches, cough, fatigue, diarrhea, headache) was associated with stronger anti-RBD IgG responses among the seropositives. 39.2% of infections were asymptomatic, and 2 or fewer symptoms were reported for 66.7% of infections. Total number of symptoms was positively but weakly associated with IgG response: Median anti-RBD IgG was 0.95 ug/mL for individuals with 3 or more symptoms, in comparison with 0.61 ug/mL for asymptomatic infections.

Conclusion

We document high rates of asymptomatic and mild infection in a large community-based cohort, and relatively low levels of anti-SARS-CoV-2 IgG antibody in the general population of previously exposed individuals.
Assessment of Vaccination and Underreporting on COVID-19 Infections in Turkey Based On Effective Reproduction Number
Authors: Akman Yıldız Tuğba , Köse Emek , Tuncer Necibe
Published: February 2021

In this paper, we introduce a SEIR type COVID-19 model where the infected class is further divided into subclasses with individuals in intensive care (ICUs) and ventilation units. The model is validated with the symptomatic COVID-19 cases, deaths, and the number of patients in ICUs and ventilation units as reported by Republic of Turkey, Ministry of Health for the period March 11, 2020 through May 30, 2020 when the nationwide lockdown is in order. COVID-19 interventions in Turkey are incorporated into the model to detect the future trend of the outbreak accurately. We tested the effect of underreporting and we found that the peaks of the disease differ significantly depending on the rate of underreporting, however, the timing of the peaks remains constant.

The lockdown is lifted on June 1, and the model is modified to include a time dependent transmission rate which is linked to the effective reproduction number ℛt through basic reproduction number ℛ0. The modified model captures the changing dynamics and peaks of the outbreak successfully. With the onset of vaccination on 13 January 2021, we augment the model with the vaccination class to investigate the impact of vaccination rate and efficacy. We observe that vaccination rate is a more critical parameter than the vaccine efficacy to eliminate the disease successfully.
Adaptive plasticity in development rate and genetic variance in survival increase the potential for adapting to novel environments
Authors: Walter Greg M. , Terranova Delia , la Spina Enrico , Majorana Mari , Pepe Giuseppe , du Plessis Sarah , Clark James , Cozzolino Salvatore , Cristaudo Antonia , Hiscock Simon J. , Bridle Jon R.
Published: February 2021

Plasticity in early development is expected to be crucial for helping natural populations adjust to environmental change. Where such plasticity fails to maintain fitness, genetic variance in plasticity or survival could help populations adapt to the novel conditions. To test this prediction, we used two closely related, but ecologically distinct, species of Sicilian daisy (Senecio, Asteraceae) adapted to high and low elevations on Mount Etna. Using a paternal half-sibling breeding design, we generated seeds of both species and planted them across an elevational gradient representing the native range of each species, and two intermediate elevations. We tracked mortality and measured the number of days it took seedlings to establish. We found that each species survived better at their native elevation, and better than the species from the other habitat. Genetic variance in relative survival was near zero within the native range, but increased in the novel environments for both species. Plasticity increased development time at higher elevations. At novel elevations, selection was in the direction of plasticity for the low-elevation species, but the opposite direction for the high-elevation species. Genetic variance for greater plasticity was associated with higher survival, but only for the low-elevation species. Together, these results suggest that while genetic variance in survival increased for both species, genetic variance for adaptive plasticity differs among species. Understanding adaptive potential in novel environments therefore needs to consider how species vary in their capacity and underlying genetic variation for adaptive plasticity.
Estimated SARS-CoV-2 Seroprevalence in Children and Adolescents in Mississippi, May Through September 2020
Authors: Hobbs Charlotte V. , Drobeniuc Jan , Kittle Theresa , Williams John , Byers Paul , Panayampalli Subbian S. , Stephenson Meagan , Kim Sara S. , Patel Manish M. , Flannery Brendan ,   CDC COVID-19 Response Team,   CDC COVID-19 Task Force Microbial Pathogenesis and Immune Response Laboratory.
Published: February 2021

Case-based tracking of COVID-19 in children and adolescents may underestimate infection, and compared with adults there is little pediatric SARS-CoV-2 seroprevalence data. To assess evidence of previous SARS-CoV-2 infections among children and adolescents in Mississippi, serologic testing for antibodies to SARS-CoV-2 was conducted on a convenience sample of residual serum specimens collected for routine laboratory testing by an academic medical center laboratory during May 17 through September 19, 2020. Seroprevalence by calendar month was standardized to the state population by race/ethnicity; cumulative numbers of infections were estimated by extrapolating seroprevalence to all those aged <18 years in Mississippi. Serum specimens from 1,603 individuals were tested; 175 (10.9%) were positive for SARS-CoV-2 antibodies. Among 1,579 (98.5%) individuals for whom race/ethnicity was known, the number testing positive was 16 (23.2%) of 69 Hispanic individuals, 117 (13.0%) of 901 non-Hispanic Black individuals and 30 (5.3%) of 565 non-Hispanic White individuals. Population-weighted seroprevalence estimates among those aged <18 years increased from 2.6% in May to 16.9% in September 2020. Cumulative numbers of infections extrapolated from seroprevalence data, however, were estimated at 117,805 (95% confidence interval [CI] = 68,771–168,708), suggesting that cases in children and adolescents are much higher than what was reported to the Mississippi State Department of Health (9,044 cases during this period). Further data to appreciate the burden of pediatric disease to inform public health policy is urgently needed.
Uncorrected cardiac malformation is the major risk factor for death in patients with dextrocardia
Authors: Lu Xiaofeng , Dang Wenzhu , Li Shenglin , Wang Xu , Gao Bingren , Liu Debin
Published: February 2021

Background/Objectives

Dextrocardia is rare in the general population. We aimed to analyze the clinical characteristics and risk factors for survival rate of dextrocardia patients during 2013 to 2018 in our hospital, through a specialized Hospital Information System.

Methods

A retrospective study of patients with dextrocardia was performed through Hospital Information System. International Classification of Diseases 10 was searched to identify eligible cases from January 2013 to December 2018 in our hospital. Medical records were reviewed to acquire the basic information of dextrocardia patients.

Results

Among 9304 patients diagnosed with congenital heart disease in past six years, 48 (0.51%) had dextrocardia. Among 48 dextrocardia patients, 28 (58.33%) had situs inversus viscerum, 20 (41.67%) had cardiac malformation, nine (18.75%) had other malformations and 16 (33.33%) had no malformation. Compared with patients with uncorrected cardiac malformation, patients without cardiac malformation were older (43.5000 vs 0.4583 years, P<0.001). The dextrocardia patients’ age of onset correlated significantly with cardiac malformation. Multivariable logistic model showed the significant risk factor for survival rate was uncorrected cardiac malformation (odds ratio, 22.2391; P <0.001). However, situs inversus (odds ratio, 1.9750; P= 0.4399) or pneumonia (odds ratio, 4.2610; P= 0.0849) itself was not a significant risk factor for survival rate. Kaplan–Meier plot shown that dextrocardia patients with uncorrected cardiac malformation had lower survival rate than those without cardiac malformation (P<0.0001), and there is no significant difference between healthy cohort and patients with pure dextrocardia with or without situs inversus (P=0.25).

Conclusions

Dextrocardia remains a rare finding in population, even in the group of patients with known congenital heart disease. Dextrocardia was associated with various malformations besides cardiac malformation. Uncorrected cardiac malformation, which should be paid high attention in the developing countries, is the main risk factor for death in patients with dextrocardia, and pure dextrocardia with or without situs inversus has no effect on survival rate of dextrocardia patients.