bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV drug resistance in various body compartments
Authors: van Zyl Gert U. , Dorfman Jeffrey R. , Kearney Mary F.
Published: June 2022

Purpose of review

HIV drug resistance testing using blood plasma or dried blood spots forms part of international guidelines. However, as the clinical utility of assessing drug resistance in other body compartments is less well established, we review this for blood cells and samples from other body compartments.

Recent evidence

Although clinical benefit is not clear, drug resistance testing in blood cells is often performed when patients with suppressed plasma viral loads require a treatment substitution. In patients with HIV neurocognitive disease, cerebral spinal fluid (CSF) drug resistance is rarely discordant with plasma but has nevertheless been used to guide antiretroviral drug substitutions. Cases with HIV drug resistance in genital fluids have been documented but this does not appear to indicate transmission risk when blood plasma viral loads are suppressed.

Drug-resistant variants, which may be selected in tissues under conditions of variable adherence and drug penetration, appear to disseminate quickly, and become detectable in blood. This may explain why drug resistance discordance between plasma and these compartments is rarely found. Partial compartmentalization of HIV populations is well established for the CSF and the genital tract but other than blood plasma, evidence is lacking to support drug resistance testing in body compartments.
Transcriptomics of angiotensin II-induced long noncoding and coding RNAs in endothelial cells
Authors: Bu Shuhan , Nguyen Hien C. , Michels David C.R. , Rasheed Berk , Nikfarjam Sepideh , Singh Rohan , Wang Lynn , Patel Darshil A. , Singh Shweta , Qadura Mohammad , Singh Krishna K.
Published: June 2022

Objective:

Angiotensin II (Ang II)-induced endothelial dysfunction plays an important role in the pathogenesis of cardiovascular diseases such as systemic hypertension, cardiac hypertrophy and atherosclerosis. Recently, long noncoding RNAs (lncRNAs) have been shown to play an essential role in the pathobiology of cardiovascular diseases; however, the effect of Ang II on lncRNAs and coding RNAs expression in endothelial cells has not been evaluated. Accordingly, we sought to evaluate the expression profiles of lncRNAs and coding RNAs in endothelial cells following treatment with Ang II.

Methods:

Human umbilical vein endothelial cells (HUVECs) were cultured and treated with Ang II (10−6 mol/l) for 24 h. The cells were then profiled for the expression of lncRNAs and mRNAs using the Arraystar Human lncRNA Expression Microarray V3.0.

Results:

In HUVECs following Ang II treatment, from a total of 30 584 lncRNA targets screened, 25 targets were significantly upregulated, while 69 were downregulated. In the same HUVECs samples, from 26 106 mRNA targets screened, 28 targets were significantly upregulated and 67 were downregulated. Of the differentially expressed lncRNAs, RP11-354P11.2 and RP11-360F5.1 were the most upregulated (11-fold) and downregulated (three-fold) lncRNAs, respectively. Assigning the differentially regulated genes into functional groups using bioinformatics reveals numerous genes involved in the nucleotide excision repair and ECM-receptor interaction.

Conclusion:

This is the first study to profile the Ang II-induced differentially expressed lncRNAs and mRNAs in human endothelial cells. Our results reveal novel targets and substantially extend the list of potential candidate genes involved in Ang II-induced endothelial dysfunction and cardiovascular diseases.
Practical guide for the management of hypertensive disorders during pregnancy
Authors: Antza Christina , Stabouli Stella , Kotsis Vasilios
Published: June 2022

Hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia, are a worldwide health problem. Hypertensive disorders of pregnancy affect more than 10% of pregnancies and are associated with increased mortality and morbidity for both mother and fetus. Although patients’ outcomes and family's experience will always be the primary concern regarding hypertensive complications during pregnancy, the economic aspect of this disease is also worth noting. Compared with normotensive pregnancies, those related with hypertension resulted in an excess increase in hospitalization and healthcare cost. Hence, the focus of this review is to analyze hypertensive disorders of pregnancy and to present practical tips with clear instructions for the clinical management of hypertensive disorders of pregnancy. This overview offers a detailed approach from the diagnosis to treatment and follow-up of a pregnant women with hypertension, evidence based, to support these instructions.
Prolonged Breastfeeding and the Risk of Plasmodium vivax Infection and Clinical Malaria in Early Childhood: A Birth Cohort Study
Authors: Pincelli Anaclara , Cardoso Marly A. , Malta Maíra B. , Nicolete Vanessa C. , Soares Irene S. , Castro Marcia C. , Ferreira Marcelo U. ,   on behalf of the MINA-Brazil Study Working Group
Published: June 2022

Background:

Relatively few Amazonian infants have clinical malaria diagnosed, treated and notified before their first birthday, either because they are little exposed to an infection or remain asymptomatic once infected. Here we measure the proportion of children who have experienced Plasmodium vivax infection and malaria by 2 years of age in the main transmission hotspot of Amazonian Brazil.

Methods:

We measured IgG antibodies to 3 blood-stage P. vivax antigens at the 1- and 2-year follow-up assessment of 435 participants in a population-based birth cohort. Children’s malaria case notifications were retrieved from the electronic database of the Ministry of Health. We used multiple Poisson regression models to identify predictors of serologically proven P. vivax infection and clinical vivax malaria during the first 2 years of life.

Results:

Overall, 23 [5.3%; 95% confidence interval (CI): 3.5–7.8%) children had antibodies to ≥2 antigens detected during at least one follow-up assessment, consistent with past P. vivax infection(s). Fifteen (3.4%; 95% CI: 2.1–5.6%) children had clinical vivax episodes notified during the first 2 years of life; 7 of them were seronegative. We estimate that half of the infections remained unnotified. Children born to women who experienced P. vivax infection during pregnancy were more likely to be infected and develop clinical vivax malaria, while those breast-fed for ≥12 months had their risk of being P. vivax-seropositive (which we take as evidence of blood-stage P. vivax infection during the first 2 years of life) decreased by 79.8% (95% CI: 69.3–86.7%).

Conclusion:

P. vivax infections in early childhood are underreported in the Amazon, are associated with anemia at 2 years of age, and appear to be partially prevented by prolonged breastfeeding.
Early Mobilization for a Patient With a Right Ventricular Assist Device With an Oxygenator
Authors: MacFarlane Sheena , Lee Vanessa , Simonds Adrienne H. , Alvarez Samantha , Carty Samantha , Ewers Kevin H. , Kelly Victoria R. , Linden Parker , Moskal Amanda L.
Published: June 2022

Background:

Physical therapists and occupational therapists safely provide early mobilization (EM) to patients requiring mechanical circulatory support (MCS). Limited EM studies are available on patients with a right ventricular assist device with an oxygenator (Oxy-RVAD).

Purpose:

The case report describes the EM course and functional outcomes of EM for a patient with Oxy-RVAD with central cannulation in the intensive care unit (ICU).

Case Description:

A 40-year-old man was admitted for a spontaneous pneumothorax. His hospital course included acute deep vein thrombosis and pulmonary embolism with worsening of interstitial lung disease and cardiomyopathy, requiring emergent pulmonary thromboendarterectomy and subsequent Oxy-RVAD. A multidisciplinary team initiated EM 3 days after cannulation.

Outcomes:

The patient safely participated in 6 EM sessions, which included both physical therapy and occupational therapy, over 10 days on MCS with no major adverse events. Clinically meaningful improvements were noted on the ICU Mobility Scale score (3 points) and the John Hopkins Highest Level of Mobility (1 point). The patient received a heart-lung transplant on the 11th day of Oxy-RVAD support.

Discussion:

EM for patients on MCS with central cannulation, including those on Oxy-RVAD, is safe and feasible and can result in clinically significant functional gains. A framework for clinical decision-making regarding EM eligibility is presented.
Effects of Occupational Stress and Health Behaviors on Heart Rate Variability in Live-Fire Instructors
Authors: Shin Inchan , Kong So Yeon , Park Gwan-Jin , Shin Dong-Min , Chai Hyun-Seok , Kim Young min , Lee Ji-Han , Kim Sang-Chul
Published: June 2022

Objectives

This study aimed to identify the association between the healthrelated characteristics and the subscales of occupational stress of live fire instructors and heart rate variability (HRV).

Methods

We conducted questionnaire survey on a general health checkup for 15 live fire instructors. Occupational stress and HRV parameters were measured to determine the association between health behavior, including smoking, drinking, exercise, and sleep-related disorders, and occupational stress of live fire instructors and HRV parameters using Spearman’s rank correlation coefficient.

Results

Smoking, insomnia, and job insecurity, a subscale of occupational stress measurement, showed negative Spearman rank correlations with HRV.

Conclusions

Insomnia, smoking, and job insecurity (due to occupational stress) among live fire instructors were associated with decreased HRV.
Video Learning of Surgical Procedures: A Randomized Comparison of Microscopic, 2- and 3-Dimensional Endoscopic Ear Surgery Techniques
Authors: Niederhauser Laura , Fink Raffael D. , Mast Fred W. , Caversaccio Marco , Anschuetz Lukas
Published: June 2022

Background

Video learning of surgical procedures helps trainees gain an initial understanding of the complex anatomy and the surgical procedure. Because no comparative studies have yet examined which microsurgical approach to the middle ear is most suitable for video learning, the authors investigated objective and subjective outcomes for medical trainees observing microscopic, 2-dimensional (2D) endoscopic, and 3- dimensional (3D) endoscopic ear surgeries.

Methods

Sixty-two medical students (min. 3rd year) from the University Hospital of Bern watched three standardized videos of a type I tympanoplasty surgery recording, conducted with a microscope, a 2D endoscope, and a 3D endoscope, respectively. The authors measured participants’ learning outcome, eye movements, cognitive load, and subjective preferences.

Results

Of the 62 participants included in the study, 14 were male (22.58%), and mean age was 24.44 years (range: 21–29). Learning outcome was highest after watching the 3D endoscopic video (mean [SD], 59.48% [20.57%]). Differences in score were statistically significant: 2D endoscopic video (mean difference: –6.56%, 95% CI: –13.02 to –0.10%), microscopic video (mean difference: –13.82%, 95% CI: –20.27 to –7.36%). Participants showed lowest average eye fixation duration when watching the 3D endoscopic video (mean [SD], 307 ms [109 ms]), with statistically significant differences to the 2D endoscopic video (mean difference: –139 ms, 95% CI: –185 to –93 ms), and the microscopic video (mean difference: –264 ms, 95% CI: –310 to –218 ms). Participants reported lowest cognitive load for the 2D and 3D endoscopic videos. Ratings on discomfort, usability, naturalness, depth perception, and image quality were in favor of the 3D endoscopic video.

Conclusion

The 3D endoscopic technique offers many advantages for video learning in terms of knowledge gain, visual field exploration, and subjective evaluation. To optimize learning effects in trainees, the authors recommend the use of endoscopes in middle ear surgery and, if available, using 3D technology.
Wait and Scan Management of Intra-canalicular Vestibular Schwannomas: Analysis of Growth and Hearing Outcome
Authors: Saleh Essam , Piccirillo Enrico , Migliorelli Andrea , Piroli Piera , Kihlgren Caterina , Sanna Mario
Published: June 2022

Objective

To report on the results of intracanalicular vestibular schwannomas (ICVS) that were managed by wait and scan and to analyze the possible predictors of tumor growth and hearing deterioration throughout the observation period.

Study Design

A retrospective case series.

Setting

Quaternary referral center for skull base pathologies.

Patients

Patients with sporadic ICVS managed by wait and scan.

Intervention

Serial resonance imaging (MRI) with size measurement and serial audiological evaluation.

Main Outcome Measure

Tumor growth defined as 2 mm increase of maximal tumor diameter, further treatment, and hearing preservation either maintain initial modified Sanna hearing class, or maintain initial serviceable hearing (class A/B).

Results

339 patients were enrolled. The mean follow-up was 36.5±31.7 months with a median of 24 months. Tumor growth occurred in 141 patients (40.6%) either as slow growth (SG) in 26.3% of cases or fast growth (FG) in 15.3% of cases. Intervention was performed in only 64 cases (18.8%). Out of 271 patients who underwent hearing analysis, 86 patients (33.5%) showed hearing deterioration to a lower hearing class of the modified Sanna classification. Tumor growth and older age were predictors of hearing deterioration. Of the 125 cases with initial serviceable hearing (Class A/B), 91 cases (72.8%) maintained serviceable hearing at last follow-up. Tumor growth and a worse initial pure tone average (PTA) were predictors of hearing deterioration.

Conclusions

Wait and scan management of ICVS is a viable option and only 18.8% of patients needed further treatment. Hearing tends to deteriorate over time.
Impact of Sclerotic Lesions on the Surgical Outcome of Cholesteatoma
Authors: Motegi Masaomi , Yamamoto Yutaka , Akutsu Taisuke , Kurihara Sho , Takahashi Masahiro , Sampei Sayaka , Sano Hiromi , Yamamoto Kazuhisa , Sakurai Yuika , Kojima Hiromi
Published: June 2022

Objective

Cholesteatoma is occasionally accompanied by excessive calcification and presumably has different osteogenic dynamics compared to noncholesteatomous chronic otitis media. Cholesteatoma-related sclerotic lesions through the temporal bone can pose manipulatory difficulties, possibly leading to worse surgical outcomes or complications. Therefore, we compared surgical outcomes of cholesteatomas with and without sclerotic lesions.

Study design

Retrospective cohort study.

Setting

Tertiary academic medical center.

Patients

Consecutive ears with acquired cholesteatomas requiring primary resection between January 2009 and December 2019. The ears followed up for <1 year were excluded.

Interventions

Tympanoplasty with/without mastoidectomy.

Main Outcome Measures

Prevalence and location of sclerotic lesion, comorbid fistulae, postoperative air-bone gap, recidivism, and complications.

Results

Overall, 19 (6.4%) of 299 ears had sclerotic lesions. More than two-thirds (68.4%) of sclerotic lesions were located adjacent to the lateral semicircular canal (LSC). Among ears with sclerotic lesions adjacent to the LSC, 46.2% had a comorbid fistula in the LSC. The prevalence of labyrinth fistula was significantly greater in ears with sclerotic lesions (42.1%) than in ears without sclerotic lesions (5.0%) (p < 0.0001, Fisher’s exact test). Sensorineural hearing deterioration was significantly higher in ears with sclerotic lesions than in ears without (p = 0.0004, Fisher’s exact test). Multivariate logistic regression analysis demonstrated that the presence of sclerotic lesions was a significant prognostic factor for residual disease (odds ratio [95% confidence interval]: 6.820 [2.055–22.633], p = 0.0017).

Conclusions

Surgeons should be conscious of preoperative identification of sclerotic lesions adjacent to one of the semicircular canals, possibly leading to postoperative sensorineural hearing deterioration or residual cholesteatoma.
Round Window Electrocochleography to Low Frequency Tones in Pediatric Cochlear Implant Recipients with and Without Auditory Neuropathy Spectrum Disorder: Separating Hair Cell and Neural Contributions Using a Computational Model
Authors: Fontenot Tatyana E. , Giardina Christopher K. , Brown Kevin D. , Fitzpatrick Douglas C.
Published: June 2022

Hypothesis

Characterize the contribution of the auditory nerve neurophonic (ANN) to electrocochleography (ECochG) of pediatric cochlear implant (CI) recipients with and without auditory nerve spectrum disorder (ANSD).

Background

ECochG is an emerging technique for predicting outcomes in CI recipients. Its utility may be increased by separating the cochlear microphonic (CM), produced by hair cells, from the ANN, the evoked potential correlate of neural phase-locking, which are mixed in the ongoing portion of the response to low frequency tone bursts.

Methods

Responses to tone bursts of different frequency and intensities were recorded from the round window of pediatric CI recipients. Separation of the CM and ANN was performed using a model of the underlying processes that lead to the shapes of the observed waveforms.

Results

Preoperative mean pure tone amplitudes of the included ANSD (n = 36) and non-ANSD subjects (n = 123), were similar (89.5 and 93.5, p = 0.1). Total of 1,024 ECochG responses to frequency and intensity series were recorded. The mean correlation (r) between the input and the modeled signals was 0.973 ± 0.056 (standard deviation). The ANN magnitudes were higher in the ANSD group (ANOVAs, F = 26.5 for frequency and 21.9 for intensity, df’s = 1, p’s < 0.001). However, its relative contribution to the overall signal was lower (ANOVAs, F = 25.8 and 12.1, df = 1, p’s < 0.001).

Conclusions

ANN was detected in low frequency ECochG responses but not high frequency responses in both ANSD and non-ANSD subjects. ANSD subjects, evidence of neural contribution in responses to low frequency stimuli was highly variable and often comparable to signals recorded in non-ANSD subjects. The computational model revealed that on average the ANN comprised a lower proportion of the overall signal than in non-ANSD subjects.
Intrahepatic triglyceride content: influence of metabolic and genetics drivers
Authors: Dearlove David J. , Hodson Leanne
Published: June 2022

Purpose of review

Intrahepatic triglyceride (IHTG) content is determined by substrate flux to, fatty acid synthesis and partitioning within, and triglyceride disposal from the liver. Dysregulation of these processes may cause IHTG accumulation, potentially leading to nonalcoholic fatty liver disease. The aetiology of IHTG accumulation has not been fully elucidated; however, environmental factors and heritability are important. Here, we review recent evidence regarding the contribution of metabolic and genetic components of IHTG accumulation.

Recent findings

Obesity and insulin resistance are the primary metabolic drivers for IHTG accumulation. These risk factors have pronounced and seemingly overlapping effects on all processes involved in determining IHTG content. The strong and interchangeable associations between obesity, insulin resistance and IHTG make it challenging to determine their relative contributions. Genome-wide association studies have identified a growing list of single nucleotide polymorphisms associated with IHTG content and recent work has begun to elucidate their mechanistic effects. The mechanisms underlying metabolic and genetic drivers of IHTG appear to be distinct.

Both metabolic and genetic factors influence IHTG content by apparently distinct mechanisms. Further work is needed to determine metabolic and genetic interaction effects, which may lead to more personalized and potentially efficacious therapeutic interventions. The development of a comprehensive polygenic risk score for IHTG content may help facilitate this.
The effectiveness of the Congo red dot paper test in hypertensive disorders of pregnancy in women of African ancestry
Authors: Khaliq Olive P. , Phoswa Wendy N. , Moodley Jagidesa
Published: June 2022

Introduction:

Hypertensive disorders of pregnancy such as preeclampsia is a global maternal and fetal health burden which has led to increased morbidity and mortality rates. Currently, the common diagnostic test that is used worldwide include blood pressure measurement and urine dip stick test. Another diagnostic test that is not commonly used is Congo Red Dot paper test is. Therefore, the main objective of this systematic review is to evaluate the effectiveness of the Congo Red Dot paper test in the diagnosis of pre-eclampsia.

Methods:

Article searching published from 2014 to 2021 will be done on PubMed, EMBASE, MEDLINE, Cochrane Library, Google scholar and Science direct. The eligibility of the studies will be screened in accordance to the selection criteria by 2 independent reviewers. The quality and risk of bias of eligible studies will be performed by both reviewers using the Hoy tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool in accordance to the measured outcomes. A data charting table will be used to extract background information and process the data items from each eligible study. The data will be analyzed using Review Manager 5.3 (RevMan 5.3) software.

Ethics and dissemination:

We anticipate finding a large number of studies reporting on the effectiveness of the Congo Red Dot paper test in the diagnosis pre-eclampsia. The study will be disseminated electronically and in print. It will also be presented to conferences related to hypertensive disorders of pregnancy.

Systematic review registration:

International prospective Register of Systematic Reviews (PROSERO) number: CRD42021283679.
Esophageal adenocarcinoma phenotypes and risk factors
Authors: Sawas Tarek , Katzka David A.
Published: June 2022

Purpose of review

The incidence of esophageal adenocarcinoma (EAC) has increased significantly over the last several decades. The majority of EAC patients present without a prior history of Barrett's esophagus (BE). As a result, endoscopic surveillance has made a suboptimal impact on EAC survival. These concerns raise serious question whether the time has come to take a different direction. The aim of this article is to review evolving evidence of EAC phenotypes and risk factors.

Recent findings

A recent study has identified two phenotypes of EAC based on the presence or absence of intestinal metaplasia (IM) in the background of the tumor (BE/IM and non-BE/IM). The study found that one-half of patients with EAC have the non-BE/IM phenotype, which is associated with more aggressive behavior and worse survival. A retrospective review demonstrates that the proportion of the two phenotypes has been stable over the last decades. Similarly, the increasing incidence of EAC cannot be explained by an increased frequency of new, unique risk factors but rather by a higher prevalence of already known risk factors. Emerging data also demonstrates that, whereas reflux symptoms are an unreliable feature for screening regardless of phenotype, the absence of reflux symptoms is more common for the non-BE/IM. Differences in the degree of genomic methylation and immune response might explain the two phenotypes at a genomic level.

EAC phenotypes have implications for tumor behavior and phenotypic differences might underlie our suboptimal screening efforts. Future screening efforts should not uniformly rely on reflux symptoms as a prerequisite for screening and should consider alternatives to the current screening strategy.
Recent insights on functional heartburn and reflux hypersensitivity
Authors: Savarino Edoardo , Marabotto Elisa , Savarino Vincenzo
Published: June 2022

Purpose of review

Rome IV experts have proposed that gastroesophageal reflux disease (GERD) should be diagnosed only in patients with abnormal esophageal acid exposure, and that reflux hypersensitivity (RH) and functional heartburn (FH) both should be considered functional conditions separate from GERD. Although past and recent evidence support that FH can be completely distinguished from GERD, the concept that RH is not GERD is highly questionable. This review attempts to provide current data on these issues.

Recent findings

Many recent investigations have provided new data on the different pathophysiological features characterizing RH and FH. Major differences have emerged from analyses of impedance-pH monitoring studies using the novel impedance metrics of baseline impedance (an index of mucosal integrity) and the rate of postreflux swallow-induced peristaltic waves (a reflection of the integrity of esophageal chemical clearance).

The better ability to interpret impedance-pH tracings together with earlier data on the different prevalence of microscopic esophagitis in RH and FH patients, and recent studies documenting poor therapeutic efficacy of pain modulators and good results of antireflux surgery for RH support recategorization of RH within the GERD world. Further research is needed to correctly phenotype patients who have heartburn without mucosal breaks, and to guide their effective management.
Racial and ethnic disparities in coronavirus disease 2019 disease incidence independent of comorbidities, among people with HIV in the United States
Authors: Bender Ignacio Rachel A. , Shapiro Adrienne E. , Nance Robin M. , Whitney Bridget M. , Delaney Joseph A.C. , Bamford Laura , Wooten Darcy , Karris Maile Y. , Mathews William C. , Kim Hyang Nina , Keruly Jeanne , Burkholder Greer , Napravnik Sonia , Mayer Kenneth H. , Jacobson Jeffrey , Saag Michael , Moore Richard D. , Eron Joseph J. , Willig Amanda L. , Christopoulos Katerina A. , Martin Jeffrey , Hunt Peter W. , Crane Heidi M. , Kitahata Mari M. , Cachay Edward R. ,   for the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS)†
Published: June 2022

Objectives:

To define the incidence of clinically detected coronavirus disease 2019 (COVID-19) in people with HIV (PWH) in the United States and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19.

Design:

Observational study within the CFAR Network of Integrated Clinical Systems cohort in seven cities during 2020.

Methods:

We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4+ cell count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores.

Results:

Among 16 056 PWH in care, of whom 44.5% were black, 12.5% were Hispanic, with a median age of 52 years (IQR 40–59), 18% had a current CD4+ cell count less than 350 cells/μl, including 7% less than 200; 95.5% were on antiretroviral therapy (ART), and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and black PWH respectively, than non-Hispanic white PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or black identity, lowest historical CD4+ cell count less than 350 cells/μl (proxy for CD4+ nadir), current low CD4+ : CD8+ ratio, diabetes, and obesity.

Conclusion:

Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWH. PWH with immune exhaustion as evidenced by lowest historical CD4+ cell count or current low CD4+ : CD8+ ratio had greater risk of COVID-19.
Nationwide Management of Trauma in Child Abuse
Authors: Joseph Bellal , Sakran Joseph V. , Obaid Omar , Hosseinpour Hamidreza , Ditillo Michael , Anand Tanya , Zakrison Tanya L.
Published: June 2022

Objective:

Child abuse is a major cause of childhood injury, morbidity, and death. There is a paucity of data on the practice of abuse interventions among this vulnerable population. The aim of our study was to identify the factors associated with interventions for child abuse on a national scale.

Methods:

Retrospective analysis of 2017 to 2018 American College of Surgeons (ACS) Pediatric Trauma Quality Improvement Program (TQIP). All children presenting with suspected/confirmed child abuse and an abuse report filed were included. Patients with missing information regarding abuse interventions were excluded. Outcomes were abuse investigations initiated among those with abuse reports, and change of caregiver at discharge among survivors with an investigation initiated. Multivariable regression analyses were performed.

Results:

A total of 7774 child abuse victims with an abuse report were identified. The mean age was 5±5 years, 4221 (54%) patients were White, 2297 (30%) Black, 1543 (20%) Hispanic, and 5298 (68%) had government insurance. The most common mechanism was blunt (63%), followed by burns (10%) and penetrating (10%). The median Injury Severity Score was 5 (1–12). The most common form of abuse was physical (92%), followed by neglect (6%), sexual (3%), and psychological (0.1%). The most common perpetrator of abuse was a care provider/teacher (49.5%), followed by a member of the immediate family (30.5%), or a member of the extended/step/foster family (20.0%). Overall, 6377 (82%) abuse investigations were initiated for those with abuse reports. Of these, 1967 (33%) resulted in a change of caregiver. Black children were more likely to have abuse investigated, and Black and Hispanic children were more likely to experience change of caregiver after investigations, while privately insured children were less likely to experience both.

Conclusions:

Significant racial, ethnic, and socioeconomic disparities exist in the nationwide management of child abuse. Further studies are strongly warranted to understand contributing factors and possible strategies to address them.

Level of Evidence:

Level III—therapeutic/care management.
Preexisting atrial fibrillation and myocardial infarction: only 10% of infarcts directly linked to atrial fibrillation
Authors: Putot Alain , Monin Antoine , Belkouche Alban , Chagué Frédéric , Zeller Marianne , Cottin Yves
Published: June 2022

The aim of the study was to evaluate the incidence and prognosis of type 1 myocardial infarction (T1MI) and type 2 MI (T2MI) in patients with acute MI and known atrial fibrillation (AF) to identify MI directly linked to AF. Among the 669 patients, four patients with hyperthyroidism were excluded, and among the remaining 665 patients, about two-thirds were diagnosed with T1MI, and the remaining third were diagnosed with T2MI. AF was the direct cause of MI in 9.8% of our overall population [1.8% of T1MI type C (coronary embolism), 4.9% of T2MI type A and 3.1% of T2MI type B]. Among patients with T2MI, 30-day mortality was lower when the trigger was AF than for the other triggers, for both type 2A (6% vs. 11%) and type 2B (0% vs. 13%). Most cases of AF-related MI are, thus, T2MI, for which therapeutic guidelines are lacking. Given the diverse triggers in T2MI, a specific approach using etiological patterns is needed to properly determine the optimal therapeutic.
Arthrobacter cavernae sp. nov., a novel actinobacterium isolated from sediment of karst cave
Authors: Fang Zheng , Zhao Xiaoyong , Wu Qingshan , Li Shixia , Liu Qiuping , Tan Leitao , Weng Qingbei
Published: June 2022

A novel, Gram-stain-positive, aerobic, non-endospore-forming, non-motile and rod-shaped bacterium designated PO-11T was isolated from sediment of karst cave collected in Libo county, Guizhou Province, PR China. The isolate grew optimally on R2A agar at 25 °C, pH 8.0 and with 0.5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that PO-11T belonged to the genus

Arthrobacter

and was most closely related to

Arthrobacter methylotrophus

TGAT (98.3 % sequence similarity),

Arthrobacter alkaliphilus

LC6T (97.7 %) and

Arthrobacter ramosus

CCM1646T (97.1 %). Genome sequencing revealed a genome size of 4 073 119 bp and the genomic DNA G+C content was 66.16 mol%. Its DNA–DNA relatedness values with

A. methylotrophus

TGAT,

A. alkaliphilus

LC6T and

A. ramosus

CCM1646T were 23.0, 22.9 and 23.2 %, respectively. The main fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The major respiratory quinone was MK-9(H2). The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, glycolipid, phosphatidylethanolamine, phosphatidylinositol and unidentified lipids. Thus, based on phylogenetic and phenotypic and chemotaxonomic data, strain PO-11T represents a novel species of the genus

Arthrobacter

, for which the name Arthrobacter cavernae sp. nov. is proposed. The type strain is strain PO-11T (=CCTCC AB 2021070T=LMG 32459T).
PhiPipe: a multi-modal MRI data processing pipeline with test-retest reliability and predicative validity assessments
Authors: Hu Yang , Li Qingfeng , Qiao Kaini , Zhang Xiaochen , Chen Bing , Yang Zhi
Published: June 2022

Magnetic Resonance Imaging (MRI) has been one of the primary instruments to measure the properties of the human brain non-invasively in vivo. MRI data generally needs to go through a series of processing steps (i.e., a pipeline) before statistical analysis. Currently, the processing pipelines for multi-modal MRI data are still rare, in contrast to single-modal pipelines. Furthermore, the reliability and validity of the output of the pipelines are critical for the MRI studies. However, the reliability and validity measures are not available or adequate for almost all pipelines.

Here, we present PhiPipe, a multi-modal MRI processing pipeline. PhiPipe could process T1-weighted, resting-state BOLD, and diffusion-weighted MRI data and generate commonly used brain features in neuroimaging. We evaluated the test-retest reliability of PhiPipe’s brain features by computing intra-class correlations (ICC) in four public datasets with repeated scans. We further evaluated the predictive validity by computing the correlation of brain features with chronological age in three public adult lifespan datasets. The multi-variate reliability and predictive validity of the PhiPipe results were also evaluated. The results of PhiPipe were consistent with previous studies, showing comparable or better reliability and validity when compared with two popular single-modality pipelines, namely DPARSF and PANDA.

The publicly available PhiPipe provides a simple-to-use solution to multi-modal MRI data processing. The accompanied reliability and validity assessments could help researchers make informed choices in experimental design and statistical analysis. Furthermore, this study provides a framework for evaluating the reliability and validity of image processing pipelines.
Mechanical Loading due to Muscle Movement Regulates Establishment of the Collagen Network in the Developing Murine Skeleton
Authors: Ahmed S. , Rogers A.V. , Nowlan N. C.
Published: June 2022

Mechanical loading is critical for collagen network maintenance and remodelling in adult skeletal tissues, but the role of loading in collagen network formation during development is poorly understood. We test the hypothesis that mechanical loading is necessary for the onset and maturation of spatial localisation and structure of collagens in prenatal cartilage and bone, using in vivo and in vitro mouse models of altered loading. The majority of collagens studied were aberrant in structure or localisation, or both, when skeletal muscle was absent in vivo. Using in vitro bioreactor culture system, we demonstrate that mechanical loading directly modulates the spatial localisation and structure of collagens II and X. Furthermore, we show that mechanical loading in vitro rescues aspects of collagens II and X development from the effects of fetal immobility. In conclusion, our findings show that mechanical loading is a critical determinant of collagen network establishment during prenatal skeletal development.

Teaser (One line)

Mechanical loading is required for normal establishment and maturation of key collagens during prenatal skeletal development.
Modeling the USA Winter 2021 Update and Spring 2022 CoVID-19 Resurgence
Authors: Eng Genghmun
Published: June 2022

Every USA wave, including this latest Spring 2022 Resurgence has been successfully modeled using:

with N (t) being the total number of new CoVID-19 cases above a prior baseline, and tR setting the pandemic wave doubling time tdbl = tR (In 2). The parameters {αS ; δo} measure mitigation efforts among the uninfected population. Here, {αS> 0} is associated with Social Distancing and vaccinations ; while {δo> 0} is associated with mask-wearing, which results in faster post-peak drop-offs. The predicted pandemic wave end is when the calculated N (t) stops increasing.

The USA Winter 2021 Resurgence resulted in fewer Omicron CoVID-19 cases than calculated in our prior medrxiv.org preprint*, due to an increased δo component, which gives ∼3/11/22 as the predicted wave end. A relatively quiet CoVID-19 period ensued until ∼4/16/22, when a new Omicron variant caused the present Spring 2022 CoVID-19 resurgence.

The recent CoVID-19 waves have decreasing tR values, with the Spring 2022 tR≈ 3.55 days (tdbl ≈ 2.46 days) value being the shortest since the initial 2020 pandemic, indicating increasingly infectious variants. The Winter 2021 and the present Spring 2022 CoVID-19 resurgences have identical αS ≈ 0.043 / day values, but the δo> 0 mask-wearing parameter decreased from δo ≈ 3. 14 × 10−3/ day to δo ≈ 1. 145 × 10−3/ day, giving the Spring 2022 wave a longer tail, and an expected end date of 8/25/22, with these wave totals:

When all the USA CoVID-19 waves are combined, it gives:

assuming no future CoVID-19 Resurgences (with 5 Figures).

*(10.1101_2022.02.04.22270491)
Phyloformer: towards fast and accurate phylogeny estimation with self-attention networks
Authors: Nesterenko Luca , Boussau Bastien , Jacob Laurent
Published: June 2022

Abstract

An important problem in molecular evolution is that of phylogenetic reconstruction, that is, given a set of sequences descending from a common ancestor, the reconstruction of the binary tree describing their evolution from the latter. State-of-the-art methods for the task, namely Maximum likelihood and Bayesian inference, have a high computational cost, which limits their usability on large datasets. Recently researchers have begun investigating deep learning approaches to the problem but so far these attempts have been limited to the reconstruction of quartet tree topologies, addressing phylogenetic reconstruction as a classification problem. We present here a radically different approach with a transformer-based network architecture that, given a multiple sequence alignment, predicts all the pairwise evolutionary distances between the sequences, which in turn allow us to accurately reconstruct the tree topology with standard distance-based algorithms. The architecture and its high degree of parameter sharing allow us to apply the same network to alignments of arbitrary size, both in the number of sequences and in their length. We evaluate our network Phyloformer on two types of simulations and find that its accuracy matches that of a Maximum Likelihood method on datasets that resemble training data, while being significantly faster.
Dynamic DNA methylation contributes to carryover effects and beneficial acclimatization in geoduck clams
Authors: Putnam Hollie M. , Trigg Shelly A. , White Samuel J. , Spencer Laura H. , Vadopalas Brent , Natarajan Aparna , Hetzel Jonathan , Jaeger Erich , Soohoo Jonathan , Gallardo-Escárate Cristian , Goetz Frederick W. , Roberts Steven B.
Published: June 2022

Given the rapidly changing global climate, there is a growing need to understand the acclimatory basis of animal response to environmental change. To investigate the role of DNA methylation in environmental acclimatization, we generated a reference genome and surveyed the physiology and DNA methylomes of juvenile geoduck clams, Panopea generosa, under differing seawater pH regimes. Juveniles were initially exposed to one of three seawater pH conditions, followed by ambient common-garden conditions, then a second reciprocal exposure to ambient pH or pH 7.4. Within 10 days of the initial low pH exposure, juvenile clams showed decreased shell size relative to ambient pH with corresponding differential DNA methylation. Following four months of ambient common-garden conditions, juveniles initially exposed to low pH compensatorily grew larger, with DNA methylation indicative of these phenotypic differences, demonstrating epigenetic carryover effects persisted months after initial exposure. Functional enrichment analysis of differentially methylated genes revealed regulation of signal transduction through widespread changes in the Wnt signaling pathways that influence cell growth, proliferation, tissue and skeletal formation, and cytoskeletal change. After 10 days of secondary exposure to pH 7.4, naive juvenile clams were more sensitive to low pH compared to those initially exposed, showing reduced growth and having nearly a 2-fold greater change in DNA methylation. Collectively, this new genomic resource and coordinated phenotypic and methylomic response support that epigenetic mechanisms underlie acclimatization to provide beneficial phenotypes.
Arabidopsis mutants representing each of the four Mediator modules reveal unique functions in the transcriptional response to salt stress
Authors: Karamat Fazelaat , Vergara Alexander , Blomberg Jeanette , Crawford Tim , Lehotai Nóra , Rentoft Matilda , Strand Åsa , Björklund Stefan
Published: June 2022

Changes in growth environment trigger stress responses in most organisms. The mechanisms mediating these responses are only partly understood and involve signaling pathways and transcription factors. Mediator is a conserved co-regulator complex required for transcriptional regulation of all eukaryotic protein-encoding genes. However, its function in abiotic stress responses is elusive. We here describe global gene expression changes triggered by salt stress in Arabidopsis. To explore the involvement of Mediator in salt stress response we characterized med9, med16, med18, and cdk8 mutants representing each of the four modules of Mediator. Our transcriptome data revealed enrichment of shared and specific cis-elements corresponding to unique transcription factors in promoters of mis-regulated genes for each mutant. We show that individual Mediator subunits interact with specific transcription factors to generate a transcriptional stress response and that the mutant phenotypes support the transcriptome data. med16 and med18, and to some extent cdk8, display defects in abscisic acid and anthocyanin metabolism and we identify signal molecules, transcription factors and target genes involved in these pathways as dysregulated in the Mediator mutants. Our results reveal how signals from different stress response pathways are dependent on and integrated by Mediator subunits to coordinate a functional response to salt stress.
SPLASH: a statistical, reference-free genomic algorithm unifies biological discovery
Authors: Chaung Kaitlin , Baharav Tavor Z. , Henderson George , Zheludev Ivan N. , Wang Peter L. , Salzman Julia
Published: June 2022

Today’s genomics workflows typically require alignment to a reference sequence, which limits discovery. We introduce a new unifying paradigm, SPLASH (Statistically Primary aLignment Agnostic Sequence Homing), an approach that directly analyzes raw sequencing data to detect a signature of regulation: sample-specific sequence variation. The approach, which includes a new statistical test, is computationally efficient and can be run at scale. SPLASH unifies detection of myriad forms of sequence variation. We demonstrate that SPLASH identifies complex mutation patterns in SARS-CoV-2 strains, discovers regulated RNA isoforms at the single cell level, documents the vast sequence diversity of adaptive immune receptors, and uncovers biology in non-model organisms undocumented in their reference genomes: geographic and seasonal variation and diatom association in eelgrass, an oceanic plant impacted by climate change, and tissue-specific transcripts in octopus. SPLASH is a new unifying approach to genomic analysis that enables an expansive scope of discovery without metadata or references.

One-sentence summary

SPLASH is a unifying, statistically driven approach to biological discovery from raw sequencing data, bypassing alignment.
Predicting Confrontation Naming in the Logopenic Variant of Primary Progressive Aphasia
Authors: Jebahi Fatima , Nickels Katlyn Victoria , Kielar Aneta
Published: June 2022

Naming difficulties are prominent and pervasive in the logopenic variant of primary progressive aphasia (lvPPA) and are related to its underlying deficits in phonological processing. Importantly, some words appear to be more vulnerable to deterioration than others. We hypothesize that these differences can be explained, in part, by words’ unique psycholinguistic properties. Our study investigated the role of psycholinguistic properties of words, along with their underlying psycholinguistic factors, on confrontation naming performance in individuals with lvPPA. Naming accuracy data were collected from 10 individuals with lvPPA using the Boston Naming Test (BNT). For each test item, values were extracted for frequency, contextual diversity, age of acquisition (AoA), word length, phonological neighborhood density (PND), concreteness, semantic neighborhood density (SND), familiarity, arousal, and valence. We examined the effects of these psycholinguistic properties on naming accuracy using logistic regression analyses at the individual level and multiple linear regression analysis at the group level. Age of acquisition emerged as the strongest psycholinguistic predictor of naming accuracy in lvPPA at both the individual and group levels. Given that AoA and frequency are highly correlated, mediation analyses were performed to identify the relationships between AoA, frequency, and naming accuracy. The influence of AoA on naming accuracy was only partially mediated by frequency. Principal component analysis was performed to extract fundamental factors of the psycholinguistic properties. Four principal psycholinguistic factors were extracted. These were interpreted as “lexical-semantic usage”, “phonological simplicity”, “semantic disembodiment”, and “semantic pleasantness”. These factor scores were entered into multiple linear and logistic regression analyses to investigate their relative contribution to naming accuracy in lvPPA. Results indicated that “lexical-semantic usage”, “semantic disembodiment”, and “semantic pleasantness” predicted naming performance at the group level. Additionally, “lexical-semantic usage” and “semantic disembodiment” emerged as significant predictors at the individual level. The effects of the psycholinguistic properties and their factors and their theoretical implications are discussed in the context of phonological deficits in lvPPA and models of word naming.

Highlights:

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Age of acquisition (AoA) predicts naming in lvPPA

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The effect of AoA on naming corresponds with lvPPA’s phonological impairment

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The effect of AoA on naming is mostly direct and partially mediated by frequency

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PCA-extracted psycholinguistic factors independently predict naming in lvPPA

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Factors related to lexical semantics, semantics, and emotionality affect naming