bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of boundary slip by interfacial nanobubbles: A perspective from molecular dynamics simulations
Authors: Yang Haichang , Zeng Binglin , Zhang Xuehua , Xing Yaowen , Gui Xiahui , Cao Yijun
Published: February 2023

Enhancing boundary slip using interfacial nanobubbles (INBs) has gained significant interest in nanofluidic transport. In this study, we conducted a comprehensive investigation on the influence of INBs on boundary conditions for both smooth and rough substrates using molecular dynamics simulations. We analyzed the impact of INB protrusion angle, coverage percentage, quantity, and fluidity on the slip length. Our results showed that INBs always increase the slip length on a smooth substrate, with a linear increase in slip length observed with increasing surface coverage. On a rough substrate, we found that the protrusion angle, quantity, and fluidity of INBs play a crucial role in determining the slip length. Smaller protrusion angles and fewer quantities of INBs were found to be more favorable for enhancing the slip length when the INB coverage is fixed, while the correlation between boundary slip and INB quantity depended on the wetting state of the substrate when the size of the INBs was fixed with a low protrusion angle. Additionally, we revealed that the fluidity of gas molecules inside the INBs dominated the enhancement of slip length by INBs. Overall, our findings are expected to provide valuable insight into drag reduction based on INBs.
Dynamics of the restricted vortex problem with a honeycomb configuration
Authors: Xie An , Liu Qihuai
Published: February 2023

In this paper, we have investigated the restricted 14-vortex problem with a honeycomb configuration similar to the football surface pattern. First, we give a sufficient condition for the existence of honeycomb configurations and obtain the instability of configurations. Then, we establish the equation of motion of the tracer particle for the restricted 14-vortex problem and analyze the stability and distribution of equilibrium points and singular points. As can be seen from the global phase diagram of system, there are only four types of orbits: equilibrium points, homoclinic orbits, heteroclinic orbits, and periodic orbits.
Structural integrity and performance investigations of a novel chemically treated cellulosic paper corn/polyester sustainable biocomposites
Authors: AL-Oqla Faris M , Hayajneh Mohammed T , Hoque M E
Published: February 2023

Facilitating finding low-cost renewable and sustainable environmental functional alternative materials for green products has been recently emphasized. Lignocellulosic materials are of such potential alternatives to enhance the modern cleaner production theme. In this work, several structural parameters, reinforcement conditions, and chemical treatments have been investigated to reveal their effects on the final desired mechanical performance of lignocellulosic corn/polyester composites for sustainable green products. Low-cost treatment solutions as sodium chloride, phosphoric and citric acids were considered for Mediterranean corn agro waste lignocellulosic fibers. Results have revealed that superior mechanical performance enhancements were occurred for the produced bio-composites. It was demonstrated that prepared composites were capable of enhancing the tensile strength as well as modulus for all types of treatment. About 157% tensile strength enhancement was achieved in case of 30 wt.% fiber content when treated with phosphoric and citric acids. Moreover, sodium chloride treatment was capable of achieving 81 MPa for the 20 wt.% fiber loading comparable to 54.7 MPa for the matrix. The modulus of elasticity property was also enhanced more than 600% for the untreated fibers and sodium chloride treated ones. This obviously demonstrates the potential of such low-cost fiber/low cost treatment synergy to fabricate potential green materials for sustainable industrial applications as well as enhance evaluating such materials from various technical stand points for the future sustainable cleaner production.
Prevalence and significance of relative apical sparing in aortic stenosis: insights from an echo and cardiovascular magnetic resonance study of patients referred for surgical aortic valve replacement
Authors: Abecasis João , Lopes Pedro , Santos Rita Reis , Maltês Sérgio , Guerreiro Sara , Ferreira António , Freitas Pedro , Ribeiras Regina , Andrade Maria João , Manso Rita Theias , Ramos Sancia , Gil Victor , Masci Pier Giorgio , Cardim Nuno
Published: February 2023

Aims

This study aims to assess the prevalence of relative apical sparing pattern (RASP) in patients with severe symptomatic aortic stenosis (AS), referred for surgical aortic valve replacement (AVR), to evaluate its significance, possible relation to amyloid deposition, and persistence after surgery.

Methods and results

Prospective study of 150 consecutive patients [age 73 (interquartile range: 68–77), 51% women], with severe symptomatic AS referred to surgical AVR. All patients underwent cardiac magnetic resonance (CMR) before surgery. RASP was defined by [average apical longitudinal strain (LS)/(average basal LS + average mid LS)] > 1 by echocardiography. AVR was performed in 119 (79.3%) patients. Both Congo red and sodium sulphate-Alcian blue (SAB) stain were used to exclude amyloid on septal myocardial biopsy. LV remodelling and tissue characterization parameters were compared in patients with and without RASP. Deformation pattern was re-assessed at 3–6 months after AVR.

RASP was present in 23 patients (15.3%). There was no suspicion of amyloid at pre-operative CMR [native T1 value 1053 ms (1025–1076 ms); extracellular volume (ECV) 28% (25–30%)]. None of the patients had amyloid deposition at histopathology. Patients with RASP had significantly higher pre-operative LV mass and increased septal wall thickness. They also had higher N-terminal pro b-type natriuretic peptide (NT-proBNP) levels [1564 (766–3318) vs. 548 (221–1440) pg/mL, P = 0.010], lower LV ejection fraction (53.7 ± 10.5 vs. 60.5 ± 10.2%, P = 0.005), and higher absolute late gadolinium enhancement (LGE) mass [9.7 (5.4–14.1) vs. 4.8 (1.9–8.6) g, P = 0.016] at CMR. Follow-up evaluation after AVR revealed RASP disappearance in all except two of the patients.

Conclusion

RASP is not specific of cardiac amyloidosis. It may also be found in severe symptomatic AS without amyloidosis, reflecting advanced LV disease, being mostly reversible after surgery.
Spatial relationship between mitral valve and ventricular septum assessed by resting echocardiography to diagnose left ventricular outflow tract obstruction in hypertrophic cardiomyopathy
Authors: Verheyen Nicolas , Batzner Angelika , Zach David , Zirlik Andreas , Gerull Brenda , Frantz Stefan , Maack Christoph , Störk Stefan , Seggewiss Hubert , Morbach Caroline
Published: February 2023

Aims

Echocardiographic diagnosis of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) often requires extensive provocative manoeuvers. We investigated, whether echocardiography-derived parameters obtained at rest can aid to determine the presence of LVOTO in persons with HCM.

Methods and results

Consecutive patients with HCM admitted to a referral centre underwent standardized transthoracic echocardiographic examination including provocative manoeuvers. Under resting conditions, the length of mitral leaflets and distances between mitral valve coordinates and ventricular walls were blindly measured in parasternal long axis (PLAX) and apical three-chamber (3ch) views, both at early and late systole. Among 142 patients (mean age 59 ± 13 years, 42% women), 68 (42%) had resting or provocable LVOTO with maximal LVOT gradients ≥30 mmHg. Late-systolic distance between mitral leaflet tip and ventricular septum (TIS) was measurable in 137 participants (96%) in 3ch view and independently associated with LVOTO in multivariable logistic regression analysis. The area under the ROC curve of TIS for the identification of LVOTO was 0.91 [95% confidence interval (CI) 0.87–0.96]. TIS ≤ 14 mm yielded 97% sensitivity and 57% specificity regarding LVOTO. TIS >14 mm ruled out LVOTO with a negative predictive value of 95%. TIS ≤9 mm ruled in LVOTO with a positive predictive value of 92% (sensitivity 73%, specificity 95%). Among 43 patients with TIS between 10 and 14 mm, 35% had LVOTO.

Conclusion

In our study, the novel echocardiographic parameter TIS showed high negative and positive predictive values for LVOTO in HCM. These exploratory results await confirmation in larger collectives and prospective investigations.
Inequities in Mental Health Care Facing Racialized Immigrant Older Adults With Mental Disorders Despite Universal Coverage: A Population-Based Study in Canada
Authors: Lin Shen (Lamson)
Published: February 2023

Objectives

Contemporary immigration scholarship has typically treated immigrants with diverse racial backgrounds as a monolithic population. Knowledge gaps remain in understanding how racial and nativity inequities in mental health care intersect and unfold in midlife and old age. This study aims to examine the joint impact of race, migration, and old age in shaping mental health treatment.

Methods

Pooled data were obtained from the Canadian Community Health Survey (2015–2018) and restricted to respondents (aged ≥45 years) with mood or anxiety disorders (n = 9,099). Multivariable logistic regression was performed to estimate associations between race–migration nexus and past-year mental health consultations (MHC). Classification and regression tree (CART) analysis was applied to identify intersecting determinants of MHC.

Results

Compared to Canadian-born Whites, racialized immigrants had greater mental health needs: poor/fair self-rated mental health (odds ratio [OR] = 2.23, 99% confidence interval [CI]: 1.67–2.99), perceived life stressful (OR = 1.49, 99% CI: 1.14–1.95), psychiatric comorbidity (OR = 1.42, 99% CI: 1.06–1.89), and unmet needs for care (OR = 2.02, 99% CI: 1.36–3.02); in sharp contrast, they were less likely to access mental health services across most indicators: overall past-year MHC (OR = 0.54, 99% CI: 0.41–0.71) and consultations with family doctors (OR = 0.67, 99% CI: 0.50–0.89), psychologists (OR = 0.54, 99% CI: 0.33–0.87), and social workers (OR = 0.37, 99% CI: 0.21–0.65), with the exception of psychiatrist visits (p = .324). The CART algorithm identifies three groups at risk of MHC service underuse: racialized immigrants aged ≥55 years, immigrants without high school diplomas, and linguistic minorities who were home renters.

Discussion

To safeguard health care equity for medically underserved communities in Canada, multisectoral efforts need to guarantee culturally responsive mental health care, multilingual services, and affordable housing for racialized immigrant older adults with mental disorders.
Preparing for the Future While Living in the Present: Older Adults’ Experiences Creating a Legacy of Values
Authors: Neller Sarah A , Cloyes Kristin G , Edelman Linda S , Wong Bob , Baines Barry , Towsley Gail L
Published: February 2023

Background and Objectives

A legacy of values (e.g., legacy letter) is a nonlegal way to intentionally communicate intangible assets (e.g., values, life lessons, and emotional and supportive instruction) with others. There is scant research on legacy creation outside of a palliative care context, and no studies have explored the experiences of community-dwelling older adults creating a legacy of values.

Research Design and Methods

As part of an exploratory sequential mixed methods study, we conducted semistructured interviews with older adults (N = 16) who had previously created a legacy of values. We analyzed transcribed interviews using an interpretive descriptive approach. We iteratively coded interviews deductively with sensitizing concepts identified in the literature (existential well-being, end-of-life preparation and completion, generativity, and resilience), and inductively, based on participants’ descriptions. Codes were categorized by patterns of motivations, content, outcomes, and meaning, and thematically summarized.

Results

We conceptualized the overall experience of creating a legacy of values as Preparing for the Future While Living in the Present and identified 4 themes: Preserving the Intangible for You and for Me, Sharing What I Want You to Know, Obtaining Peace through Reflection and Preparation, and Living into a Continuing Legacy. Participants attained peace, realized their life was not complete, and were challenged to live intentionally through legacy creation.

Discussion and Implications

Creating a legacy of values may concurrently prepare older adults for the end of life and the remainder of life. These findings offer insight into a generative act that can promote intentional living among older adults.
“Thrice Precious Tube!”: Negotiating the Visibility and Efficiency of Early Hearing Aids
Authors: Zdrodowska Magdalena
Published: February 2023

In the nineteenth century, acoustic hearing aids (such as ear trumpets or conversation tubes) became ubiquitous attributes of deaf people from polite society. These prostheses were a visible sign of otherwise invisible deafness. Although some deaf people used hearing aids openly and proudly, and constantly attempted to convince others that using them was nothing to be ashamed of, others wanted to hide these stigmatizing devices. Therefore, they were equally (or even more) concerned with their visibility than with their performance when buying these devices. For this reason, manufacturers tried to design instruments to meet the needs of their customers.

This article investigates two design strategies that were used by ear trumpet producers to maneuver between the troubling visibility of these instruments and their performance: the first is hypervisibility—designing hearing aids as luxurious objects of conspicuous consumption; the second is invisibility, which was achieved with miniaturization and camouflage. Both these aesthetic strategies are considered in the context of Victorian technophilia and regimes of the body. As hearing aids became more accessible to the middle class, design patterns spread beyond elite consumption.
Low genetic diversity among introduced axis deer: comments on the genetic paradox and invasive species
Authors: Buchholz Matthew J , Wright Emily A , Grisham Blake A , Bradley Robert D , Arsuffi Thomas L , Conway Warren C
Published: February 2023

Human-mediated introductions and subsequent establishment and spread of nonnative species have the potential to create a founder effect in such populations, which typically results in low genetic diversity and potential for inbreeding. However, several exotic invasive species exhibit a “genetic paradox” in which they thrive and adapt to novel environments while also avoiding complications from low genetic diversity. Axis deer (Axis axis) were introduced into Texas, Hawaii, South America, Australia, and Croatia during the 19th and 20th centuries and successfully established large populations from a few founding individuals. Mitochondrial (Cytochrome-b, Cytb; displacement loop, D-loop) and nuclear (10 microsatellites) markers were used to assess genetic diversity within and between axis deer populations in Texas and Hawaii and then compared to other introduced (Australia and Croatia) and native (India) populations. Overall, mtDNA divergence was 0.54% (Cytb) and 1.55% (D-loop) indicating high mitochondrial similarity within the species. Further, each invasive population was composed of only one or two mtDNA haplotypes. Microsatellite allele diversity also was low within and between populations in Texas and Hawaii resulting in monomorphic loci and Hardy–Weinberg equilibrium violations in both populations. The low genetic diversity in native Indian axis deer and within and between invasive populations suggests that the introduced populations experienced founder effects following introduction, and yet overcame this potential handicap by undergoing successful establishment and expansion. Axis deer appear to be another successful invasive species characterized by the genetic paradox where they exhibit genetic profiles that suggest inbreeding effects should be imminent, yet display no signs of inbreeding and are highly successful adapting to novel environments.
Is Clozapine-induced Weight Gain Dose-dependent? Results From a Prospective Cohort Study
Authors: Piras Marianna , Chahma Jihane , Ranjbar Setareh , Laaboub Nermine , Grosu Claire , Plessen Kerstin Jessica , von Gunten Armin , Conus Philippe , Eap Chin Bin
Published: February 2023

Background

Antipsychotic-induced metabolic adverse effects are risk factors for cardiometabolic comorbidities. Whether dose lowering could mitigate such effects remains unclear. The present study aims to investigate the associations between clozapine doses and modifications of weight, blood pressure, blood glucose, and lipid levels.

Study Design

Linear mixed-effects models of weight changes over 1 year and of variations of other metabolic parameters over 4 months were applied to a prospective cohort of 115 patients. Age- and sex-stratified analyses of weight changes were also performed.

Study Results

Each 100 mg dose increment of clozapine was associated on average with a +0.48% weight increase (P = .004) over 1 year of treatment. Weight increase was greater for treatment duration ≤3 vs >3 months (+0.84% and +0.47% per month, respectively, P < .001), with a significant association with the dose for durations >3 months (+0.54%, P = .004) and a trend for durations ≤3 months (+0.33%, P = .075). Dose increments of 100 mg were also associated with weight increases of +0.71% among adults (P = .001), +1.91% among the elderly (P < .001) and +1.32% among men (P < .001) with no associations among women (P = .62). Among young adults, weight change was positively associated with doses ≤300 mg/day (+2.19% per 100 mg, P = .001), whereas no association was found with doses >300 mg/day (P = .60). No significant effect of clozapine dose on other metabolic parameters was found.

Conclusions

This study reports a modest effect of clozapine dose increases on weight gain over 1 year with differences among age categories and sexes and no dose effect on other metabolic parameters over 4 months.
Visuospatial Learning Selectively Enhanced by Personalized Transcranial Magnetic Stimulation over Parieto-Hippocampal Network among Patients at Clinical High-Risk for Psychosis
Authors: Tang Yingying , Xu Lihua , Zhu Tianyuan , Cui Huiru , Qian Zhenying , Kong Gai , Tang Xiaochen , Wei Yanyan , Zhang Tianhong , Hu Yegang , Sheng Jianhua , Wang Jijun
Published: February 2023

Background and Hypothesis

Cognitive deficits in visuospatial learning (VSL) are highly associated with an increased risk of developing psychosis among populations with clinical high risk (CHR) for psychosis. Early interventions targeting VSL enhancement are warranted in CHR but remain rudimentary. We investigated whether personalized transcranial magnetic stimulation (TMS) over the left parieto-hippocampal network could improve VSL performance in CHR patients and if it could reduce the risk of psychosis conversion within 1 year.

Study Design

Sixty-five CHR patients were randomized to receive active or sham TMS treatments using an accelerated TMS protocol, consisting of 10 sessions of 20 Hz TMS treatments within 2 days. TMS target was defined by individual parieto-hippocampal functional connectivity and precisely localized by individual structural magnetic resonance imaging. VSL performance was measured using Brief Visuospatial Memory Test-Revised included in measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery (MCCB). Fifty-eight CHR patients completed the TMS treatments and MCCB assessments and were included in the data analysis.

Study Results

We observed significant VSL improvements in the active TMS subgroup (Cohen’s d = 0.71, P < .001) but not in the sham TMS subgroup (Cohen’s d = 0.07, P = .70). In addition, active TMS improved the precision of VSL performance. At a 1-year follow-up, CHR patients who received active TMS showed a lower psychosis conversion rate than those who received sham TMS (6.7% vs 28.0%, χ2 = 4.45, P = .03).

Conclusions

Our findings demonstrate that personalized TMS in the left parieto-hippocampal network may be a promising preventive intervention that improves VSL in CHR patients and reduces the risk of psychosis conversion at follow-up.
Utilizing Handoff Reporting Tools to Improve the Novice Nurse's Workflow
Authors: Garcia Kristelle
Published: February 2023

The novice nurse is task oriented and requires guidance to recognize connections in clinical practice. Novice nurses must learn to prioritize, organize, and differentiate between information that is “nice-to-know” versus “need-to-know” to deliver competent nursing care. Nursing literature makes evident that utilizing communication frameworks increases the delivery of clear communication and improves patient outcomes. Novice nurses require a comprehensive handoff-reporting tool to prompt the novice to engage in critical thinking and facilitate communication within their practice.
Validation and clinical discovery demonstration of a real-world data extraction platform
Authors: Nottke Amanda , Alan Sophia , Brimble Elise , Cardillo Anthony B. , Henderson Lura , Littleford Hana E. , Rojahn Susan , Sage Heather , Taylor Jessica , West-Odell Lisandra , Berk Alexandra
Published: February 2023

Objective

To validate and demonstrate the clinical discovery utility of a novel patient-mediated, medical record collection and data extraction platform developed to improve access and utilization of real-world clinical data.

Methods

Clinical variables were extracted from the medical records of consented patients with metastatic breast cancer. To validate the extracted data, case report forms completed using the structured data output of the platform were compared to manual chart review for 50 patients. To demonstrate the platform’s clinical discovery utility, we assessed associations between time to distant metastasis (TDM) and tumor histology, molecular type, and germlineBRCAstatus in the platform-extracted data of 194 patients.

Results

The platform-extracted data had 97.6% precision (91.98%–100% by variable type) and 81.48% recall (58.15%–95.00% by variable type) compared to manual chart review. In our discovery cohort, the shortest TDM was significantly associated with metaplastic (739.0 days) and inflammatory histologies (1,005.8 days), HR-/HER2- molecular types (1,187.4 days), and positiveBRCAstatus (1,042.5 days) as compared to other histologies, molecular types, and negativeBRCAstatus, respectively. Multivariable analyses did not produce statistically significant results, but the average TDMs are reported.

Discussion

The platform-extracted clinical data are precise and comprehensive. The data can generate clinically-relevant insights.

Conclusion

The structured real-world data produced by a patient-mediated, medical record-extraction platform are reliable and can power clinical discovery.
Initial Experience with Intercostal Insertion of an Extravascular ICD Lead Compatible with Existing Pulse Generators
Authors: Burke Martin C. , Knops Reinoud E. , Reddy Vivek , Aasbo Johan , Husby Michael , Marcovecchio Alan , O’Connor Mark , Sanghera Rick , Scheck Don , Pepplinkhuizen Shari , Ebner Adrian
Published: February 2023

Structured Abstract

Objectives

This study assessed safety and feasibility of a novel extravascular (EV) implantable cardioverter-defibrillator (ICD) lead when inserted anteriorly through a rib space and connected to various commercially available ICD pulse generators (PGs) placed in either a left mid-axillary or left pectoral pocket.

Background

Currently available or investigational, EV-ICDs include a subcutaneous or subxiphoid lead connected to customized EV-ICD PGs. This novel EV-ICD (AtaCor Medical, Inc, San Clemente, CA) employs a unique intercostal implant technique and is designed to function with commercial DF-4 ICD PGs.

Methods

In this non-randomized, single-center, acute study, 36 de novo or replacement transvenous (TV) ICD patients enrolled to receive a concomitant EV-ICD lead inserted through an intercostal space along the left parasternal margin. EV-ICD leads were connected to DF-4 compatible ICD PGs positioned in either a left mid-axillary or pectoral pocket for acute sensing and defibrillation testing. Defibrillation testing started at 30 Joules (J) and stepped down in 10 J increments following conversion success and stepped up in 5 J increments following conversion failure.

Results

Successful acute defibrillation using ≤ 35 J was noted in 100% of left mid-axillary PG subjects (n=27, mean 16.3 ± 8.6 J) and 83% of left pectoral PG subjects (n=6, mean 21.0 ± 8.4 J). All evaluable episodes (n=93) were automatically sensed, detected, and shocked. No serious device-related intraoperative adverse events were observed.

Conclusions

This first-in-human study documented safe and reliable placement of a novel extravascular ICD lead with effective sensing and defibrillation of induced ventricular fibrillation using commercial DF-4 ICD pulse generators.

Condensed Abstract

This study assessed feasibility of intercostal implantation of a novel extravascular implantable cardioverter-defibrillator (ICD) lead designed to function with commercial DF-4 pulse generators (PGs). Lead placement was successful in 33 of 36 attempts (94%). Acute defibrillation with ≤35 J was successful in 27 of 27 left mid-axillary PG subjects (100%) and 5 of 6 left pectoral PG subjects (83%). All evaluable episodes (n=93) were automatically detected. No serious device-related intraoperative adverse events were observed. This study demonstrates feasibility of a novel extravascular ICD lead with effective sensing and defibrillating of induced ventricular fibrillation using commercial DF-4 PGs.
Hypertensive adults exhibit lower myelin content: A multicomponent relaxometry and diffusion MRI study
Authors: Laporte John P. , Faulkner Mary E. , Gong Zhaoyuan , Akhonda Mohammad A.B.S. , Ferrucci Luigi , Egan Josephine M. , Bouhrara Mustapha
Published: February 2023

It is unknown whether hypertension plays any role in cerebral myelination. To fill this knowledge gap, we studied ninety cognitively unimpaired adults, age range 40 to 94 years, that are participants in the Baltimore Longitudinal Study of Aging (BLSA) and the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT) to look for potential associations between hypertension and cerebral myelin content across fourteen white matter brain regions. Myelin content was probed using our advanced multicomponent magnetic resonance (MR) relaxometry method of myelin water fraction (MWF), a direct and specific MR imaging (MRI) measure of myelin content, and longitudinal and transverse relaxation rates (R1andR2), two highly sensitive MRI metrics of myelin content. We also applied diffusion tensor imaging (DTI) MRI to measure fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) values, which are metrics of cerebral microstructural tissue integrity, to provide contact with previous MRI findings. After adjustment of age, sex, systolic blood pressure, smoking status, diabetes status and cholesterol level, our results indicated that participants with hypertension exhibited lower MWF, FA,R1andR2values and higher MD, RD and AxD values, indicating lower myelin content and higher impairment to the brain microstructure. These associations were significant across several white matter regions, particularly in the corpus callosum, fronto-occipital fasciculus, temporal lobes, internal capsules, and corona radiata. These original findings suggest a direct association between myelin content and hypertension, and form the basis for further investigations including longitudinal assessments of this relationship.
A Snapshot of COVID-19 Incidence, Hospitalizations, and Mortality from Indirect Survey Data in China in January 2023
Authors: Ramírez Juan M. , Díaz-Aranda Sergio , Aguilar Jose , Ojo Oluwasegun , Lillo Rosa Elvira , Anta Antonio Fernández
Published: February 2023

In this work we estimate the incidence of COVID-19 in China using online indirect surveys (which preserve the privacy of the participants). The indirect surveys deployed collect data on the incidence of COVID-19, asking the participants about the number of cases, deaths, vaccinated, and hospitalized that they know. The incidence of COVID-19 (cases, deaths, etc.) is then estimated using a modified Network Scale-up Method (NSUM). Survey responses (100, 200 and 1,000, respectively) were collected from Australia, the UK, and China in January 2023. The estimates in Australia and the UK are compared with official data, showing that they are in the confidence intervals or rather close. Cronbach’s alpha values also indicate good confidence in the estimates. The estimates obtained in China are, among others, that 91% of the population is vaccinated, almost 80% had been infected in the last month, and almost 3% in the last 24 hours.
Disability evaluation in patients with Guillain-Barre syndrome and SARS-CoV-2 infection from a neurological reference center in Peru
Authors: Sanchez Boluarte Sofia Stefanie , Quispe Wilfor Aguirre , Sanchez Boluarte Arantxa Noelia , Cuellar Jhon Tacunan , Segura Chávez Darwin Alberto
Published: February 2023

Introduction

several cases of Guillain-Barre Syndrome (GBS) associated with SARS-CoV-2 infection have been described. This study illustrated the demographic, clinical, and neurophysiological characteristics of patients with GBS and COVID-19, as well as associated factors with disability at discharge.

Methods

A retrospective analytical observational study was conducted. It included patients diagnosed with GBS admitted in a national reference center in Peru between 2019 and 2021. Epidemiological, clinical, neurophysiological and cerebrospinal fluid data were analyzed. A multivariate analysis, using the generalized linear model, was performed, considering the presence of disability at discharge as the dependent variable.

Results

81 subjects diagnosed with GBS were included. The mean age was 46.8 years (SD: 15.2), with a predominance of males (61.73%). The most frequent clinical presentation was the classic sensory-motor form in 74 cases (91.36%) with AIDP (82.35%) as the most frequent neurophysiological pattern in the group with COVID-19, while AMAN pattern predominated (59.26%) in those without COVID-19 (p=<0.000). The disability prevalence ratio at discharge between subjects with COVID-19 and those without COVID-19 was 1.89 (CI 1.06–3.34), p=0.030, adjusted for age, sex, and neurophysiological subtype.

Conclusions

The neurophysiologic subtype AIDP, and a higher disability were associated with the presence of COVID-19.
Systematic review and meta-analysis of the accuracy of McIsaac and Centor score in patients presenting to secondary care with Pharyngitis
Authors: Kanagasabai Atchchuthan , Evans Callum , Jones Hayley E , Hay Alastair D , Dawson Sarah , Savović Jelena , Elwenspoek Martha M C
Published: February 2023

Background

Centor and modified Centor (McIsaac) scores are clinical prediction rules used to diagnose group A streptococcus infection in patients with pharyngitis. They aim to identify the patients most likely to benefit from antibiotic treatment and reduce unnecessary antibiotic prescribing.

Objectives

To systematically review the literature on the diagnostic accuracy of McIsaac and Centor, and produce pooled estimates of accuracy at each score threshold, in patients presenting with acute pharyngitis to secondary care.

Data sources

MEDLINE, Embase and Web of science were searched from inception to June 2021.

Eligibility criteria

Studies that included patients who presented with acute pharyngitis to hospital emergency departments and outpatient clinics, reported McIsaac or Centor scores, and used throat cultures and/or rapid antigen detection tests as the reference standard.

Review methods

The review protocol was registered on PROSPERO (CRD42021267413). Study selection was performed by two reviewers independently and risk of bias was assessed using the QUADAS-2 tool. Sensitivities and specificities of McIsaac and Centor scores were pooled at each threshold using bivariate random effects meta-analysis.

Results

The McIsaac score had higher estimated sensitivity and lower specificity relative to Centor scores at equivalent thresholds, but with wide and overlapping confidence regions. Using either score as a triage to rapid antigen detection tests (RADT) to decide antibiotic treatment would reduce antibiotic prescription to non-GAS pharyngitis patients relative to RADT test for everyone, but also reduce antibiotic prescription to GAS patients.

Conclusion

Our findings suggest that high thresholds of either score excludes a proportion of true positive patients from potentially beneficial treatment. The use of a low threshold before a RADT test would reduce antibiotic prescription relative to prescribing based on score only but the economics and clinical effectiveness of this combination strategy needs assessment. We recommend continued use of existing antibiotic prescribing guidelines and patient safety netting.
Deep learning predicts HRD and platinum response from histology slides in breast and ovarian cancer
Authors: Bergstrom Erik N. , Abbasi Ammal , Díaz-Gay Marcos , Galland Loïck , Lippman Scott M. , Ladoire Sylvain , Alexandrov Ludmil B.
Published: February 2023

Breast and ovarian cancers harboring homologous recombination deficiencies (HRD) can benefit from platinum-based chemotherapies and PARP inhibitors. Standard diagnostic tests for detecting HRD utilize molecular profiling, which is not universally available especially for medically underserved populations. Here, we trained a deep learning approach for predicting genomically derived HRD scores from routinely sampled hematoxylin and eosin (H&E)-stained histopathological slides. For breast cancer, the approach was externally validated on three independent cohorts and allowed predicting patients’ response to platinum treatment. Using transfer learning, we demonstrated the method’s clinical applicability to H&E-images from high-grade ovarian tumors. Importantly, our deep learning approach outperformed existing genomic HRD biomarkers in predicting response to platinum-based therapies across multiple cohorts, providing a complementary approach for detecting HRD in patients across diverse socioeconomic groups.

One-Sentence Summary

A deep learning approach outperforms molecular tests in predicting platinum response of HRD cancers from histological slides.
Dynamic functional connectivity MEG features of Alzheimer’s disease
Authors: Jin Huaqing , Ranasinghe Kamalini G , Prabhu Pooja , Dale Corby , Gao Yijing , Kudo Kiwamu , Vossel Keith , Raj Ashish , Nagarajan Srikantan S , Jiang Fei
Published: February 2023

Dynamic resting state functional connectivity (RSFC) characterizes time-varying fluctuations of functional brain network activity. While many studies have investigated static functional connectivity, it has been unclear whether features of dynamic functional connectivity are associated with neurodegenerative diseases. Popular sliding-window and clustering methods for extracting dynamic RSFC have various limitations that prevent extracting reliable features to address this question. Here, we use a novel and robust time-varying dynamic network (TVDN) approach to extract the dynamic RSFC features from high resolution magnetoencephalography (MEG) data of participants with Alzheimer’s disease (AD) and matched controls. The TVDN algorithm automatically and adaptively learns the low-dimensional spatiotemporal manifold of dynamic RSFC and detects dynamic state transitions in data. We show that amongst all the functional features we investigated, the dynamic manifold features are the most predictive of AD. These include: the temporal complexity of the brain network, given by the number of state transitions and their dwell times, and the spatial complexity of the brain network, given by the number of eigenmodes. These dynamic features have high sensitivity and specificity in distinguishing AD from healthy subjects. Intriguingly, we found that AD patients generally have higher spatial complexity but lower temporal complexity compared with healthy controls. We also show that graph theoretic metrics of dynamic component of TVDN are significantly different in AD versus controls, while static graph metrics are not statistically different. These results indicate that dynamic RSFC features are impacted in neurodegenerative disease like Alzheimer’s disease, and may be crucial to understanding the pathophysiological trajectory of these diseases.
Identifying the role of household immunity in driving individual dengue virus infection risk
Authors: Hamins-Puértolas Marco , Buddhari Darunee , Salje Henrik , Cummings Derek A.T. , Fernandez Stefan , Farmer Aaron , Kaewhiran Surachai , Khampaen Direk , Iamsirithaworn Sopon , Thomas Stephen J. , Endy Timothy , Srikiatkhachorn Anon , Rothman Alan L. , Rodriguez-Barraquer Isabel , Anderson Kathryn B.
Published: February 2023

Dengue virus (DENV) infection risk is known to vary substantially, even across small communities, with infections in and around the home driving transmission. However, It remains unclear how the immune status of an individual or household dictate this risk in part due to transmission being dominated by subclinical infections. In this study, we used demographic, household characteristic, and serological data from a multigenerational cohort study of 2860 individuals from 470 households in Kamphaeng Phet, Thailand, to determine the incidence and risk factors for DENV infections. We used hemagglutination inhibition (HAI) antibody titers measured in sequential serum samples to identify subclinical infections through a gradient boosted regression model. This approach identified ∼10% more cases than commonly used methods with approximately 90% of all infections being subclinical. As expected, we found that having higher DENV antibody titers was protective against infection. Individuals were additionally protected if other household members had higher titers suggesting that there are indirect effects of household immunity on the individuals found within a household. Our study provides a framework for inferring subclinical infections and characterizing the epidemiology of DENV infection in households.
Efficient and scalablede novoprotein design using a relaxed sequence space
Authors: Frank Christopher , Khoshouei Ali , de Stigter Yosta , Schiewitz Dominik , Feng Shihao , Ovchinnikov Sergey , Dietz Hendrik
Published: February 2023

Deep learning techniques are being used to design new proteins by creating target backbone geometries and finding sequences that can fold into those shapes. While methods like ProteinMPNN provide an efficient algorithm for generating sequences for a given protein backbone, there is still room for improving the scope and computational efficiency of backbone generation. Here, we report a backbone hallucination protocol that uses a relaxed sequence representation. Our method enables protein backbone generation using a gradient descent driven hallucination approach and offers orders-of-magnitude efficiency enhancements over previous hallucination approaches. We designed and experimentally produced over 50 proteins, most of which expressed well in E. Coli, were soluble and adopted the desired oligomeric state along with the correct composition of secondary structure as measured by CD. Exemplarily,wedetermined 3D electron density maps using single-particle cryo EM analysis for three single-chainde-novoproteins comprising 600 AA which closely matched with the designed shape. These have no structural analogues in the protein data bank (PDB), representing potentially novel folds or arrangement of domains. Our approach broadens the scope of de novo protein design and contributes to accessibility to a wider community.
Chromosome-specific maturation of the epigenome in the Drosophila male germline
Authors: Anderson James , Henikoff Steven , Ahmad Kami
Published: February 2023

Spermatogenesis in the Drosophila male germline proceeds through a unique transcriptional program controlled both by germline-specific transcription factors and by testis-specific versions of core transcriptional machinery. This program includes the activation of genes on the heterochromaticYchromosome, and reduced transcription from theXchromosome, but how expression from these sex chromosomes is regulated has not been defined. To resolve this, we profiled active chromatin features in the testes from wildtype and meiotic arrest mutants and integrate this with single-cell gene expression data from the Fly Cell Atlas. These data assign the timing of promoter activation for genes with germline-enriched expression throughout spermatogenesis, and general alterations of promoter regulation in germline cells. By profiling both active RNA polymerase II and histone modifications in isolated spermatocytes, we detail widespread patterns associated with regulation of the sex chromosomes. Our results demonstrate that theXchromosome is not enriched for silencing histone modifications, implying that sex chromosome inactivation does not occur in the Drosophila male germline. Instead, a lack of dosage compensation in spermatocytes accounts for the reduced expression from this chromosome. Finally, profiling uncovers dramatic ubiquitinylation of histone H2A and lysine-16 acetylation of histone H4 across theYchromosome in spermatocytes that may contribute to the activation of this heterochromatic chromosome.
Retro-miRs: Novel and functional miRNAs originated from mRNA retrotransposition
Authors: Mercuri Rafael L. , Conceição Helena B. , Guardia Gabriela D. A. , Goldstein Gabriel , Vibranovski Maria D. , Hinske Ludwig C. , Galante Pedro A F
Published: February 2023

Background

Reverse transcribed gene copies, or retrocopies, have emerged as a major source of evolutionary novelties. MicroRNAs (miRNAs) are small, highly conserved RNAs molecules among species that serve as key post-transcriptional regulators of gene expression. The birth and subsequent evolution of miRNAs have been addressed, but not fully.

Results

In this study, we carried out a comprehensive investigation of miRNAs origination through retroduplicated mRNA sequences (retrocopies). We identified 17 retroduplicated miRNAs (retro-miRs) that emerged from mRNAs retrocopies. Four of these retro-miRs hadde novoorigination within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and were duplicated along with their host mRNAs. We found that retro-miRs are primates specific, including 5 retro-miRs conserved among all primates and two human-specific retro-miRs. All of the retro-miRs were expressed and had predicted and experimentally validated target genes, with the exception of miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes, such as metabolic processes, cell signaling and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs have a potential oncogenic role in cancer, targeting key cancer genes and being overexpressed in several cancer types, including Liver Hepatocellular Carcinoma and Stomach Adenocarcinoma.

Conclusion

Our findings demonstrate that mRNAs retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play roles in cancer.
Identifying the core genome of the nucleus-forming bacteriophage family and characterization ofErwiniaphage RAY
Authors: Prichard Amy , Lee Jina , Laughlin Thomas G. , Lee Amber , Thomas Kyle P. , Sy Annika , Spencer Tara , Asavavimol Aileen , Cafferata Allison , Cameron Mia , Chiu Nicholas , Davydov Demyan , Desai Isha , Diaz Gabriel , Guereca Melissa , Hearst Kiley , Huang Leyi , Jacobs Emily , Johnson Annika , Kahn Samuel , Koch Ryan , Martinez Adamari , Norquist Meliné , Pau Tyler , Prasad Gino , Saam Katrina , Sandhu Milan , Sarabia Angel Jose , Schumaker Siena , Sonin Aaron , Uyeno Ariya , Zhao Alison , Corbett Kevin , Pogliano Kit , Meyer Justin , Grose Julianne H. , Villa Elizabeth , Dutton Rachel , Pogliano Joe
Published: February 2023

We recently discovered that some bacteriophages establish a nucleus-like replication compartment (phage nucleus), but the core genes that define nucleus-based phage replication and their phylogenetic distribution were unknown. By studying phages that encode the major phage nucleus protein chimallin, including previously sequenced yet uncharacterized phages, we discovered that chimallin-encoding phages share a set of 72 highly conserved genes encoded within seven distinct gene blocks. Of these, 21 core genes are unique to this group, and all but one of these unique genes encode proteins of unknown function. We propose that phages with this core genome comprise a novel viral family we term Chimalliviridae. Fluorescence microscopy and cryo-electron tomography studies ofErwiniaphage vB_EamM_RAY confirm that many of the key steps of nucleus-based replication encoded in the core genome are conserved among diverse chimalliviruses, and reveal that non-core components can confer intriguing variations on this replication mechanism. For instance, unlike previously studied nucleus-forming phages, RAY doesn’t degrade the host genome, and its PhuZ homolog appears to form a five-stranded filament with a lumen. This work expands our understanding of phage nucleus and PhuZ spindle diversity and function, providing a roadmap for identifying key mechanisms underlying nucleus-based phage replication.
Mycobacterium tuberculosis methyltransferase perturbs host epigenetic programming to promote bacterial survival
Authors: Singh Prakruti R , Dadireddy Venkatareddy , Udupa Shubha , Kalladi Shashwath Malli , Shee Somnath , Khosla Sanjeev , Rajmani Raju S , Singh Amit , Ramakumar Suryanarayanarao , Nagaraja Valakunja
Published: February 2023

Mycobacterium tuberculosis(Mtb) has evolved several mechanisms to counter host defense arsenal for its proliferation. We show thatMtbemploys multi-pronged approach to modify host epigenetic machinery for its survival upon infection. It secretes methyltransferase (MTase) Rv2067c into macrophages, trimethylating K79 of histone H3 in non-nucleosomal context. Rv2067c downregulates host MTase DOT1L, decreasing its H3K79me3 mark added nucleosomally on pro-inflammatory response genes. Consequent inhibition of caspase8 dependent apoptosis and enhancement of RIPK3 mediated necrosis results in increased pathogenesis. In parallel, Rv2067c enhances the expression of SESTRIN3, NLRC3 and TMTC1 enabling the pathogen to overcome host inflammatory and oxidative response. We provide structural basis for differential methylation of H3 by Rv2067c and DOT1L. The structure of Rv2067c and DOT1L explain how their action on H3K79 is temporally and spatially separated enabling Rv2067c to effectively intercept the host epigenetic circuit and downstream signalling.