bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of International Medical Graduates in Academic Plastic Surgery
Authors: Egro Francesco M. , Lai Julia , Muthiah Nallammai , Smith Brandon T. , Nguyen Vu T.
Published: March 2022

Background:

International medical graduates play a significant role in meeting U.S. health care needs, and contribute to a more diverse provider workforce. This study aimed to determine the prevalence, characteristics, and academic productivity of plastic surgery international medical graduate faculty.

Methods:

A cross-sectional study was conducted to compare characteristics of international medical graduates against domestic medical graduates including demographics, trainings, academic ranks, leadership positions, number of publications and citations, and Hirsch index.

Results:

International medical graduates represent 10.3 percent of all 918 academic plastic surgeons in the United States, with the majority having graduated from India (16.8 percent), Brazil (8.4 percent), and the United Kingdom (8.4 percent). International medical graduates were more likely to have graduated from independent programs (OR, 5.7; p < 0.0001) and to have completed research fellowship (OR, 2.1; p = 0.0001) and burn fellowship (OR, 6.5; p < 0.0001). Programs led by international medical graduate chairs employed more international medical graduate faculty (21 percent versus 9 percent; p < 0.0001). International medical graduates had comparable Hirsch indices, number of publications, and citations, but received less National Institutes of Health funding ($32,020 versus $223,365). International medical graduates also had comparable rates of attaining leadership positions such as fellowship director and chair but required fewer years of experience to become residency director (8.3 years versus 17.3 years).

Conclusions:

The contribution of international medical graduates in academic plastic surgery was evident based on research productivity, academic ranks, and leadership positions. International medical graduates are more likely to be employed in programs led by international medical graduate chairs. This study may help guide aspiring international medical graduate academics and aid in hiring decisions at academic institutions.
Quality Improvement: A Primer for Plastic Surgeons
Authors: Drinane James J. , Desemone James , Patel Ash
Published: March 2022

It is the duty of all health care workers to improve the quality of care and patient outcomes. Quality improvement is a component of health policy required by residency accrediting bodies and is a mandatory component of postgraduate medical education. It is imperative for plastic surgeons to develop skills in quality improvement to ensure that they can cope with increased patient volumes while ensuring that their patients have access to care that is safe, equitable, effective, efficient, timely, and patient-centered. This article discusses techniques and tools often used in quality improvement. Challenges encountered with quality improvement initiatives are discussed, and recommendations on how to handle them as they occur are offered. This primer provides a foundation for plastic surgeons and their staff to guide their quality improvement efforts. A hypothetical quality improvement project is used as an example to illustrate the concepts of quality improvement in this primer.
A Markov Analysis of Surgical versus Medical Management of Chronic Migraines
Authors: Yesantharao Pooja S. , Lee Erica , Klifto Kevin M. , Colakoglu Salih , Dellon A. Lee , Reddy Sashank K.
Published: March 2022

Background:

Refractory chronic migraine is a common and debilitating neurologic condition, affecting over 8 million people in the United States. It is associated with billions of dollars in lost productivity annually. Novel medical (anti–calcitonin gene-related peptide antibodies) and surgical treatment modalities have emerged for chronic migraine in recent years. The current study investigated the cost-utility of surgical versus medical management of refractory chronic migraine.

Methods:

A Markov cohort analysis using hybrid Monte Carlo patient simulation was performed to compare surgical decompression versus erenumab for the treatment of refractory chronic migraine in adults. Both societal and payer perspectives were considered. Primary model outcomes included incremental cost-effectiveness ratio, or cost per quality-adjusted life-year gained.

Results:

Over a 5-year period, migraine surgery was associated with an increase of 0.2 quality-adjusted life-year per patient when compared to erenumab. In terms of costs, the results demonstrated a $19,337 decrease in direct medical costs and a $491 decrease in indirect costs (productivity lost) for the surgery cohort compared to erenumab. Because surgery improved quality of life and decreased costs compared to erenumab, even when considering revision surgery needs, surgery was the overall dominant treatment in terms of cost-effectiveness. Sensitivity analyses demonstrated that surgery was cost-effective compared to erenumab when patients required therapy for at least 1 year.

Conclusions:

Surgical deactivation of migraine trigger sites may pose a cost-effective approach to treating refractory chronic migraine in adults. This is especially the case when patients are anticipated to require therapy for more than 1 year.
Extramedullary Plasmacytoma
Authors: Wu Fengyu , Yu Mingming , Shi Bin , Yu Qian , Wang Zhenguang
Published: March 2022

A 66-year-old woman having intermittent abdominal distention for 2 months was referred to our hospital. An enhanced abdominal CT scan showed multiple hepatic lesions, suspected of metastases. An 18F-FDG PET/CT scan, which was performed to seek primary tumor, showed multiple lesions with intense 18F-FDG uptake in the liver and lymph nodes located in cardiophrenic angle, abdominal cavity, and retroperitoneal space. All 18F-FDG–avid lesions were suspected of metastases. However, no suspected primary tumor was identified by the 18F-FDG PET/CT scan, which prompted the liver biopsy. Pathologic analysis revealed the presence of plasmacytoma.
Role of 68Ga-DOTATOC PET/CT in Insulinoma According to 3 Different Contexts: A Retrospective Study
Authors: Moreau Pierre-Louis , Aveline Cyrielle , Christin-Maitre Sophie , Chanson Philippe , Dubreuil Olivier , Rusu Timofei , Montravers Françoise
Published: March 2022

Objective

The aim of this study was to assess the performance of 68Ga-DOTATOC PET/CT in the detection and extension of insulinomas according to 3 different contexts: sporadic benign, sporadic metastatic, and multiple endocrine neoplasia type 1 (MEN1).

Patients and Methods

The data of 71 adult patients who underwent 68Ga-DOTATOC PET/CT for suspected or confirmed sporadic insulinoma, suspicion of insulinoma in the context of MEN1, follow-up of metastatic insulinoma, or suspicion of recurrence of insulinoma were retrospectively analyzed. Pathological examination or strong clinical and biological findings were used as standards of truth.

Results

For the assessment of a confirmed sporadic insulinoma in 17 patients, the sensitivity of SR-PET was 75%, including 2 patients for whom metastatic lesions had been revealed by SR-PET. For 35 patients with a suspicion of insulinoma, the sensitivity was 39%. In 10 patients followed up for metastatic insulinoma, the sensitivity was 100%. For 5 patients with a history of MEN1, interpretation of SR-PET was difficult, as 3 of them presented with multiple pancreatic uptake foci. The global sensitivity of SR-PET in all insulinomas excluding those with a MEN1 story was 64% (100% for metastatic insulinomas, 62% for benign insulinomas), with a specificity of 89%.

Conclusions

68Ga-DOTATOC PET/CT is a useful examination tool for the assessment of insulinomas in selected contexts, with very high performance for the detection and extension workup of metastatic insulinomas and high specificity for the detection of sporadic benign insulinomas. The examination should be completed with GLP-1 receptor PET when it is negative or in a MEN1 context.
Severe Thrombocytopenia in Patients With Advanced Neuroendocrine Tumor Treated With Peptide Receptor Radioligand Therapy
Authors: Naveed Ahmad Junid A. , Schroeder Brett B. , Ruhoy Steven M. , Kennecke Hagen F. , Lin Bruce S.
Published: March 2022

Background

Peptide receptor radioligand therapy (PRRT) was Food and Drug Administration approved in 2018 for the treatment of unresectable somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (NETs) and provides an important option for patients with advanced disease. A known adverse effect of this treatment is hematologic toxicity, although usually transient. We present 3 patients with metastatic gastroenteropancreatic NETs treated with PRRT who were evaluated for severe persistent thrombocytopenia.

Methods

Three patients who commenced therapy with PRRT were known to proceed to a bone marrow (BM) biopsy for persistent severe thrombocytopenia and were included in this study. These patients were identified retrospectively and evaluated for their tumor properties, including immunohistochemical markers, treatment modalities, and clinical outcomes.

Results

All 3 patients had metastatic NETs that progressed on prior lines of therapy and were treated with 1 to 4 doses of177Lu-DOTATATE 7.4 GBq (200 mCi) before developing grade 3 (25,000 to 50,000/μL) refractory thrombocytopenia. All patients had concurrent bone metastases, and 2 of the 3 had baseline grade 1 thrombocytopenia. In all 3 cases, BM biopsy documented widespread tumor infiltration.

Conclusions

Severe refractory thrombocytopenia after PRRT is rare and may result from numerous known causes, including radiation-induced myelotoxicity, myelodysplastic syndrome, and tumor BM infiltration. We present 3 cases of thrombocytopenia related to persistent or progressive BM metastasis. Although known bone metastasis is not a contraindication to PRRT, thrombocytopenia may be a manifestation of tumor progression and should be considered when making decisions about continuation of therapy.
Access, Utilization, and Implementation of Research Among Rehabilitation Nurses: A Qualitative Study
Authors: Mitro Jessica Pope , Pomeroy J. Mary Louise , Osman Sarah , Matta Virina , Cai Cindy , Garfinkel Steven , Weinstein Ali A.
Published: March 2022

Purpose

This study aimed to understand rehabilitation nurses’ perceptions of research information, related barriers, and avenues for future research, specifically in those caring for individuals with burn injury, spinal cord injury, or traumatic brain injury.

Design

Qualitative semistructured interviews were conducted.

Methods

Eighteen interviews were conducted. A thematic network approach identified codes and developed basic, organizing, and global themes.

Results

Researchers identified factors that facilitated research uptake, determined organizational structures that support research culture, and described nurse engagement with literature.

Conclusions

Although participants desired to engage with the research literature, they identified barriers including time constraints, heavy workloads, and lack of access. To facilitate research uptake, research must be easily accessible, be easily digestible, and include clinical practice recommendations. Research must expand its scope to address issues relevant to the rehabilitation population.

Clinical Relevance

Our findings may be used to drive improvements in research competence, facilitate knowledge translation, and support evidence-based practice among rehabilitation nurses.
Glove Dressing for Initial Management of Hand Burns
Authors: Ratliff Rachel , King Amy , Lineaweaver William
Published: March 2022

Initial hand dressings for burned hands should be compatible with preservation of skin substitutes and grafts, splinting, and active motion. We have developed a standardized glove dressing directed at these requirements. Early experience with this glove dressing has included feasible clinical application, 7- to 10-minute application time, and 90% preservation of total active range of motion in a normal hand placed in the dressing under test conditions.
Metabolic Responses to Severe Burn Injury
Authors: Herndon David , Zhang Feng , Lineaweaver William
Published: March 2022

Management of the metabolic responses to severe burn injury is recognized as a fundamental part of burn care. Definition of burn hypermetabolism is being refined to subcellular and genomic levels, and treatment concepts are need to be refined into increasingly sophisticated strategies.
Chaperone Use During Plastic Surgery Physical Examinations
Authors: Cuccolo Nicholas G. , Crystal Dustin T. , Girard Alisa O. , Johnson Anna Rose , Ibrahim Ahmed M.S. , Sinkin Jeremy C. , Lin Samuel J. , Agag Richard L.
Published: March 2022

Background

Medical chaperones often play an important role during physical examinations, providing patient comfort and serving as medicolegal witness. The purpose of this study was to evaluate and compare practices regarding chaperone use by plastic surgery attendings and trainees.

Methods

A voluntary survey was distributed to members of the American Council of Academic Plastic Surgeons. The survey included a standardized set of questions regarding physician demographics, nature of practice training, and current practices pertaining to chaperone use. Data were analyzed in a descriptive fashion. Ordinal logistic regression models were used to identify predictors of chaperone use.

Results

We received 167 responses, of which 107 (64.1%) were attendings and 60 (35.9%) were trainees. In total, 78.3% of the respondents were male and 21.7% were female. Routine use of chaperones was reported at 58.6%. Compared with plastic surgery trainees, attending surgeons were 12.8 times more likely to use a chaperone during sensitive examinations (P < 0.001). In addition, male respondents were 6.43 times more likely than their female counterparts to involve a chaperone during sensitive examinations (P < 0.001). Forty-eight percent of the trainees acknowledged receiving education regarding chaperone use, and this cohort was 7 times more likely to use a chaperone when compared with trainees who had not received chaperone instruction (P < 0.001).

Conclusions

This study highlights the wide variability of chaperone use among plastic surgery attendings and trainees. Integration and standardization of chaperone education within plastic surgery training may be an effective technique to promote this practice and lead to improved patient-provider clinical experiences.
Sex chromosomes, sex ratios and sex gaps in longevity in plants
Authors: Marais Gabriel A. B. , Lemaître J-F.
Published: March 2022

In animals, males and females can display markedly different longevity (also called sex gaps in longevity, SGL). Sex chromosomes contribute to establishing these SGLs. X-hemizygosity and toxicity of the Y chromosomes are two mechanisms that have been suggested to reduce male longevity (Z-hemizygosity and W toxicity in females in ZW systems). In plants, SGLs are known to exist, but the role of sex chromosomes remains to be established. Here, by using adult sex ratio as a proxy for measuring SGLs, we explored the relationship between sex chromosomes and SGLs across 43 plant species. Based on the knowledge accumulated in animals, we specifically asked whether: (i) species with XY systems tend to have female-biased sex ratios (reduced male longevity) and species with ZW ones tend to have male-biased sex ratios (reduced female longevity); and (ii) this pattern was stronger in heteromorphic systems compared to homomorphic ones. Our results tend to support these predictions although we lack statistical power because of a small number of ZW systems and the absence of any heteromorphic ZW system in the dataset. We discuss the implications of these findings, which we hope will stimulate further research on sex differences in lifespan and ageing across plants.

This article is part of the theme issue ‘Sex determination and sex chromosome evolution in land plants’.
Some thoughts about the words we use for thinking about sex chromosome evolution
Authors: Charlesworth Deborah
Published: March 2022

Sex chromosomes are familiar to most biologists since they first learned about genetics. However, research over the past 100 years has revealed that different organisms have evolved sex-determining systems independently. The differences in the ages of systems, and in how they evolved, both affect whether sex chromosomes have evolved. However, the diversity means that the terminology used tends to emphasize either the similarities or the differences, sometimes causing misunderstandings. In this article, I discuss some concepts where special care is needed with terminology. The following four terms regularly create problems: ‘sex chromosome’, ‘master sex-determining gene’, ‘evolutionary strata’ and ‘genetic degeneration’. There is no generally correct or wrong use of these words, but efforts are necessary to make clear how they are to be understood in specific situations. I briefly outline some widely accepted ideas about sex chromosomes, and then discuss these ‘problem terms’, highlighting some examples where careful use of the words helps bring to light current uncertainties and interesting questions for future work.

This article is part of the theme issue ‘Sex determination and sex chromosome evolution in land plants’.
Comparative evaluation of Panther Fusion and real-time PCR for detection of Burkholderia pseudomallei in spiked human blood
Authors: Gassiep Ian , Bauer Michelle J. , Page Melissa , Harris Patrick N. A. , Norton Robert
Published: March 2022

Introduction. Melioidosis is an infection that most commonly presents with bacteraemia. Culture-based laboratory methods can result in a significant delay to organism identification. Molecular diagnostic techniques have a high sensitivity and rapid time to diagnosis. A decreased time to diagnosis is likely to improve patient outcomes.

Aim. To compare the Panther Fusion automated molecular instrument to an in-house method for the detection of

Burkholderia pseudomallei

directly from spiked human whole-blood samples.

Results. The in-house method detected 11/12 (92 %) samples with a

B. pseudomallei

concentration of 2.5–4.5×102 c.f.u. ml−1. The Panther was less reliable, detecting only 8/14 (75 %) samples with a similar bacterial concentration. The Panther was able to detect 12/12 (100 %) spiked blood culture-positive samples.

Conclusion. The direct detection of

B. pseudomallei

from patient blood on presentation to a healthcare facility will significantly decrease time to diagnosis. We describe an in-house real-time PCR method with the lowest reported limit of detection to date. Due to lower sensitivity, the Panther Fusion would be best used as a diagnostic method directly from a positive blood culture.
Miniphocaeibacter halophilus sp. nov., an ammonium-tolerant acetate-producing bacterium isolated from a biogas system
Authors: Schnürer Anna , Singh Abhijeet , Bi Shaojie , Qiao Wei , Westerholm Maria
Published: March 2022

An anaerobic bacterial strain, designated AMB_01T, recovered from mesophilic propionate enrichment of a high-ammonia biogas digester, was characterised using phenotypic and molecular taxonomic methods. Cells of AMB_01T are coccus-shaped and often occur arranged as diplococci or sarcina. Growth occurred at 20–45 °C, initial pH 5.5–8.5 and with up to 0.7 M NH4Cl, with optimum growth at 37–42 °C and pH 8.0. AMB_01T achieved high cell density and highest acetate production when grown on carbohydrates, including monomers, disaccharides and polysaccharides, such as glucose, maltose, cellobiose and starch. The strain was also able to use amino acids and some organic acids and alcoholic compounds for growth. Acetate was formed as the main product and yeast was not required for growth. The major cellular fatty acids were summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B), C18 : 1ω7, C14 : 0, C16 : 0 and summed feature 3 (C16 : 1ω7 and/or iso-C15 : 0 2OH). The highest 16S rRNA gene sequence similarity found was with

Miniphocaeibacter massiliensis

(96.6 %), within the family

Peptoniphilaceae

, phylum Bacillota (Firmicutes). The genomic DNA G+C content was 29.0 mol%. An almost complete set of genes for the acetyl-CoA pathway was found. Genome comparisons between AMB_01T and close relatives showed highest digital DNA–DNA hybridisation to

Finegoldia magna

(23 %), highest average nucleotide identity with genome nucleotide and amino acid sequences to

M. massiliensis

(72 and 73 %, respectively) and highest average nucleotide identity (87 %) with

Schnuerera ultunensis

, indicating that AMB_01T represents a novel species. Analysis of genomic, chemotaxonomic, biochemical and physiological data confirmed that strain AMB_01T represents a novel species, for which the name Miniphocaeibacter halophilus sp. nov. is proposed. The type strain is AMB_01T (=DSM 110247T=JCM 39107 T).
A fast and sensitive absolute quantification assay for the detection of SARS-CoV□2 peptides using Parallel Reaction Monitoring Mass Spectrometry
Authors: Gajbhiye Akshada , Nalbant Atakan , Heunis Tiaan , Sidgwick Frances , Porter Andrew , Taha Yusri , Trost Matthias
Published: March 2022

The on-going SARS-CoV-2 (COVID-19) pandemic has called for an urgent need for rapid and high-throughput methods for mass testing for early detection, prevention and surveillance of the disease. Here, we tested if targeted parallel reaction monitoring (PRM) quantification using high resolution Orbitrap instruments can provide the sensitivity and speed required for a high-throughput method that could be used for clinical diagnosis. Here we report a high-throughput and sensitive PRM-MS assay that enables absolute quantification of SARS-CoV-2 nucleocapsid peptides with short turn-around times. Concatenated peptides (QconCAT) synthesized using isotopically labelled SARS-CoV-2 were used for absolute quantification. We developed a fast and high-throughput S-trap-based sample preparation method, which was then successfully utilized for testing 25 positive and 25 negative heat-inactivated nasopharyngeal swab samples for SARS-CoV-2 detection. The method was able to differentiate between negative and positive patients accurately within its limits of detection. Moreover, extrapolating from the QconCAT absolute quantification, our data show that patients with Ct values as low as 17.5 have NCAP protein amounts of around 7.5 pmol in swab samples. The present high-throughput method could potentially be utilized in specialized clinics as an alternative tool for detection of SARS-CoV-2.
Medical students’ crisis-induced stress and the association with social support
Authors: Broks Vera M.A. , Stegers-Jager Karen M. , van der Waal Jeroen , Van den Broek Walter W. , Woltman Andrea M.
Published: March 2022

Background

Medical schools are challenged to guard student wellbeing due to the potential negative impact of the COVID-19 outbreak on top of the already high prevalence of mental distress. Whereas social support is generally associated with less crisis-induced stress, it is unknown whether this applies to medical students during the COVID-19 outbreak.

Objectives

The impact of the COVID-19 outbreak on perceived stress of medical students was assessed by comparing their perceived stress levels during the outbreak to both their own baseline and the previous cohort’s pre-COVID-19 stress levels. Then, the association between social support and COVID-19 induced stress was assessed.

Methods

Dutch Year-1 medical students of cohort 2019 (n=99) completed the 14-item Perceived Stress Scale (PSS-14) at two time points: baseline (pre-COVID-19) and final measurement (COVID-19). Social support - emotional-informational support and club membership - was assessed during the final measurement. PSS and social support scores were compared to similar measurements of cohort 2018 (n=196). Students’ baseline stress levels, gender and study performance were controlled for when comparing two cohorts.

Results

Stress levels did not differ statistically significant between both pre-COVID-19 measurements of cohort 2018 and baseline cohort 2019. During the COVID-19 outbreak, cohort 2019 showed significantly higher stress levels compared to baseline (paired t-test: t=6.07, p<.001) and compared to cohort 2018 (linear regression: B=4.186, p<.001). Only during the COVID-19 outbreak, higher levels of social support - i.e. emotional-informational support (B=-0.75, p<.001) and club membership (B=-3.68, p<.01) - were associated with lower levels of stress.

Conclusions

During the COVID-19 outbreak, the perceived stress of medical students was higher - especially for students with lower levels of social support. Our results suggest that medical schools should optimize social support to minimize crisis-induced stress.
Missorting of Plasma miRNAs in Aging and Alzheimer’s Disease
Authors: Čarna Maria , Novotny Jan S. , Dragišič Neda , Slavik Hanuš , Sheardova Kateřina , Geda Yonas E. , Vyhnalek Martin , Laczo Jan , Hort Jakub , Mao Zixu , Rissman Robert A. , Hajduch Marian , Dammer Eric B. , Stokin Gorazd B.
Published: March 2022

Aging is the greatest risk factor for Alzheimer’s disease (AD)1, a pervasive cognitive disorder with unsettled etiology. The precise role of aging in AD, however, remains poorly understood. Accumulating evidence documents the dysregulation of circulating microRNAs (miRNA) separately in aging2,3and AD4. Considering miRNAs play a role in aging and longevity5,6, we comprehensively test which aging-associated miRNA changes are observed in AD, and change in AD beyond aging in the circulating miRNA network. Here we show that plasma miRNAs in aging are downregulated and preferentially targeted to extracellular vesicle (EV) content, while in AD, miRNAs are further downregulated and of exclusive EV origin. We further show that miRNAs in AD display altered proportions of motifs relevant to their loading into EVs7,8and secretion propensity9. Considering endosomes play a role in the genesis of EVs10,11and are compromised early in AD12, these findings implicate endosomal pathology underlying the AD plasma miRNA profile and its potential as a mechanistic AD biomarker. Striking similarities between plasma miRNA profiles in aging and AD further suggest that the AD miRNA network profile reflects a pathological exacerbation of the aging process whereby physiological suppression of AD pathology by plasma miRNAs becomes insufficient.
A 16-Month Longitudinal Investigation of Risk and Protective Factors for Mental Health Outcomes Throughout Three National Lockdowns and a Mass Vaccination Campaign: Evidence from a Weighted Israeli Sample During COVID-19
Authors: Hertz-Palmor Nimrod , Ruppin Shachar , Matalon Noam , Mosheva Mariela , Dorman-Ilan Shirel , Avinir Asia , Mekori-Domachevsky Ehud , Hasson-Ohayon Ilanit , Gross Raz , Gothelf Doron , Pessach Itai M.
Published: March 2022

Background

The COVID-19 pandemic is an ongoing global crisis, with a multitude of factors that affect mental health worldwide. Here, we explore potential predictors for the emergence and maintenance of depression, anxiety, and posttraumatic stress symptoms (PTSS) in the general population in Israel.

Methods

Across the span of 16 months, 2,478 people completed a repeated self-report survey which inquired psychiatric symptoms and pandemic related stress factors (PRSF). PRSF were divided into four clusters of environmental stressors: financial, health-related, fatigue and sense of protection by authorities. We applied mixed-effects linear models to assess how each stressor contributes to depression, anxiety and PTSS at each time point, alongside a longitudinal exploration among participants who completed at least two consecutive surveys (n=400).

Results

Fatigue was the strongest predictor for depression, anxiety and PTSS at all time points (standardized βbetween 0.28-0.60,p<.0001), and predicted deterioration overtime (βbetween 0.22-0.36,p<.0001). Financial concerns associated with depression and anxiety at all time points (βbetween 0.13- 0.26,p<.01), and with their deterioration overtime (βbetween 0.16-0.18,p<.0001), while health related concerns were uniquely associated with anxiety and PTSS at all time points (βbetween 0.14-0.29,p<.01) and their deterioration (βbetween 0.11-0.16,p<.001), but not with depression. Improvement in sense of protection overtime associated with decrease in depression and anxiety (βbetween −0.09 to −0.16,p<.01).

Conclusions

Our findings accentuate the multitude of risk factors for psychiatric morbidity during COVID-19, and the dynamics in their association with different aspects of psychopathology at various time points.
Comparison of Phase Angle Using Bioelectrical Impedance Analysis According to Device Type and Examination Posture
Authors: Yang Jihyun , Chun Byung Chul , Kim Jeehyun , Lee Jae-myeong
Published: March 2022

Background

Bioelectrical impedance analysis (BIA) is gaining popularity as a body composition assessment tool for patients. Although it has been studied and validated in different populations, age groups, and clinical settings, including critically ill patients, there are concerns about BIA reproducibility and reliability in different device types and postures. This study aimed to evaluate the reliability of BIA according to different devices, postures, and lead types.

Methods

Cross-sectional observational data of 74 healthy volunteers (32 women and 42 men) were collected. We used two types of devices, three types of postures (standing, sitting, and lying), and two lead types (clamp lead and adhesive lead) to measure the whole-body phase angle (phA) at a single frequency of 50 kHz. The measurements were validated using the intraclass correlation coefficient (ICC) and Bland–Altman plot analysis.

Results

All phA measurements recorded with two types of devices, three different postures, and two types of leads were equivalent to each other (mean ICC = 0.9932, 95% confidence interval (CI) 0.9905–0.0053). The average mean difference in phA was 0.31 (95% CI 0.16– 0.46). The largest phA value was measured using BWA with an adhesive-type lead in the lying position. There were no differences between standing and sitting positions.

Conclusion

This is the first study to show the consistency and reliability of BIA in measuring phA using different devices, lead types, and postures. This could provide the confidence that BIA can be used in various clinical settings.
Who Does What to Whom? Graph Representations of Action-Predication in Speech Relate to Psychopathological Dimensions of Psychosis
Authors: Nikzad Amir H. , Cong Yan , Berretta Sarah , Hänsel Katrin , Cho Sunghye , Pradhan Sameer , Behbehani Leily , DeSouza Danielle , Liberman Mark Y. , Tang Sunny X.
Published: March 2022

Graphical representations of speech generate powerful computational measures related to psychosis. Previous studies have mostly relied on structural relations between words as the basis of graph formation, i.e. connecting each word to the next in a sequence of words. Here, we introduced a method of graph formation grounded in semantic relationships by identifying elements that act upon each other (action relation) and contents of those actions (predication relation). Speech from picture description and open-ended narrative tasks were collected from a cross-diagnostic group of healthy volunteers and people with psychotic as well as non-psychotic disorders. Recordings were transcribed and underwent automated language processing, including semantic role labeling to identify action and predication relations. Structural and semantic graph features were computed using static and dynamic (moving-window) techniques. Compared to structural graphs, semantic graphs were more highly correlated with dimensional psychosis symptoms. Dynamic features also outperformed static features, and samples from picture descriptions were more informative than narrative responses for psychosis diagnoses and symptom dimensions. Overall, semantic graphs capture unique and clinically meaningful information about psychosis and related symptom dimensions. These features, particularly when derived from semi-structured tasks using dynamic measurement, are meaningful additions to the repertoire of computational linguistic methods in psychiatry.
A simple and viable approach to estimate population trends
Authors: Schlemmer Mario
Published: March 2022

Changes in population abundances over time are of central concern for environmental conservation and the understanding of population dynamics. The standard slope estimator has restricting assumptions and lacks a constant range, which makes its interpretation less intuitive. Herein, more robust measures of trend. It is based on proportional difference and can be used for data on various scale types. If it is applied to ranks it yields the correlation coefficient. Related measures of association are described that assess the relationship between species, including a rank-order correlation that is sensitive to top ranks and a correlation for continuous data that is more robust than the correlation coefficient. All proposed measures have a range between –1 and +1. Furthermore, they can provide a common ground for evaluating trend strength and strength of association for populations undergoing very different dynamics.
Hemispheric lateralization in older adults who habitually play darts: a cross-sectional study using functional near-infrared spectroscopy
Authors: Toyofuku Koki , Hiwa Satoru , Tanioka Kensuke , Hiroyasu Tomoyuki , Takeda Masaki
Published: March 2022

Exercise training integrating physical and cognitive activities is gaining attention because of its potential benefits for brain health. This study focuses on exercise training using a dart game called Wellness Darts. Wellness Darts is a sport involving throwing darts and walking to pull them out of the board, memorizing the score, and subtracting it from the total score, thus allowing the performance of two tasks simultaneously: exercise and calculation. It is expected to maintain and improve cognitive function, and whether the continual dart training affects brain function is of great interest. Before conducting the longitudinal study revealing its effect on brain function, we aimed to cross-sectionally confirm the difference in hemispheric lateralization between expert and non-expert players. Functional near-infrared spectroscopy (fNIRS) was used to measure brain activity for three groups: an expert older group who practiced darts continually, a non-expert older control group, and a non-expert younger control group. Their brain activity patterns were quantified by lateralization index (LI) and compared between groups. The results showed that the younger and the expert older groups had significantly higher LI values than the non-expert older group and did not differ between the expert older and the younger groups. Our results suggest that the Wellness Darts possibly promote hemispheric lateralization.
Frequency-specific neural signatures of perceptual content and perceptual stability
Authors: Hardstone Richard , Flounders Matthew , Zhu Michael , He Biyu J.
Published: March 2022

In the natural environment, we often form stable perceptual experiences from ambiguous and fleeting sensory inputs. Which neural activity underlies the content of perception and which neural activity supports perceptual stability remains an open question. We used a bistable perception paradigm involving ambiguous images to behaviorally dissociate perceptual content from perceptual stability, and magnetoencephalography (MEG) to measure whole-brain neural dynamics in humans. Combining multivariate decoding and neural state-space analyses, we found frequency band-specific neural signatures that underlie the content of perception and promote perceptual stability, respectively. Across different types of images, non-oscillatory neural activity in the slow cortical potential (SCP, <5 Hz) range supported the content of perception. By contrast, perceptual stability is influenced by the amplitude of alpha and beta oscillations. In addition, neural activity underlying perceptual memory, which supports perceptual stability when sensory input is temporally removed from view, also encodes elapsed time. Together, these results reveal distinct neural mechanisms that support the content vs. stability of visual perception.
Epigenetic changes associated with hyperglycaemia exposure in the longitudinal D.E.S.I.R. cohort
Authors: Khamis Amna , Ning Lijiao , Balkau Beverley , Bonnefond Amélie , Canouil Mickaёl , Roussel Ronan , Froguel Philippe
Published: March 2022

Aim

Understanding DNA methylation dynamics associated with progressive hyperglycaemia exposure could provide early diagnostic biomarkers and an avenue for delaying type 2 diabetes (T2D) disease. We aimed to identify DNA methylation changes during a 6-year period associated with early hyperglycaemia exposure using the longitudinal D.E.S.I.R. cohort.

Methods

We selected individuals with progressive hyperglycaemia exposure based on T2D diagnostic criteria: 27 with long-term exposure, 34 with short-term exposure and 34 normoglycaemic controls. DNA from blood at inclusion and at the 6-years visit was subjected to methylation analysis using 850K methylation-EPIC arrays. A linear mixed model was used to perform an epigenome-wide association study (EWAS) and identify methylated changes associated with hyperglycaemia exposure during 6-year time-period.

Results

We did not identify differentially methylated sites that reached FDR-significance in our cohort. Based on EWAS, we focused our analysis on methylation sites that had a constant effect during the 6-years across the hyperglycaemia groups compared to controls and found the most statistically significant site was the reported cg19693031 probe (TXNIP). We also performed an EWAS with HbA1c, using the inclusion and the 6-years methylation data and did not identify any FDR-significant CpGs.

Conclusions

Our study reveals that DNA methylation changes are not robustly associated with hyperglycaemia exposure or HbA1c during a short-term period, however, our top loci indicate potential interest and should be replicated in larger cohorts.
Young adults who improve performance during dual-task walking show more flexible reallocation of cognitive resources: A Mobile Brain-Body Imaging (MoBI) study
Authors: Patelaki Eleni , Foxe John J. , Mazurek Kevin A. , Freedman Edward G.
Published: March 2022

In young adults, pairing a taxing cognitive task with walking can have different effects on gait and cognitive task performance. In some cases, performance clearly declines whereas in others compensatory mechanisms maintain performance even under dual-task conditions. This study set out to investigate the preliminary finding of behavioral improvement in Go-NoGo response inhibition task performance during walking compared to sitting, which was observed at the piloting stage. Mobile Brain/Body Imaging (MoBI) was used to record electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and behavioral responses in the cognitive task, during sitting or walking on a treadmill. In a cohort of twenty-six (26) young adults, fourteen (14) participants improved in measures of cognitive task performance while walking compared to sitting. These participants exhibited walking-related EEG amplitude reductions over frontal brain scalp regions during key stages of inhibitory control (conflict monitoring, control implementation and pre-motor stages), accompanied by reduced stride-to-stride variability and faster responses to stimuli compared to those who did not improve. In contrast, the twelve (12) participants who did not improve exhibited no EEG amplitude differences across physical condition. The neural activity changes associated with performance improvement during dual tasking hold promise as cognitive flexibility markers that can potentially help assess cognitive decline in aging and neurodegeneration.
Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine
Authors: Arunachalam Prabhu S. , Feng Yupeng , Ashraf Usama , Hu Mengyun , Edara Venkata Viswanadh , Zarnitsyna Veronika I. , Aye Pyone Pyone , Golden Nadia , Green Kristyn W. M. , Threeton Breanna M. , Maness Nicholas J. , Beddingfield Brandon J. , Bohm Rudolf P. , Dufour Jason , Russell-Lodrigue Kasi , Miranda Marcos C. , Walls Alexandra C. , Rogers Kenneth , Shirreff Lisa , Ferrell Douglas E , Deb Adhikary Nihar R. , Fontenot Jane , Grifoni Alba , Sette Alessandro , O’Hagan Derek T. , Van Der Most Robbert , Rappuoli Rino , Villinger Francois , Kleanthous Harry , Rappaport Jay , Suthar Mehul S. , Veesler David , Wang Taia T. , King Neil P. , Pulendran Bali
Published: March 2022

Despite the remarkable efficacy of COVID-19 vaccines, waning immunity, and the emergence of SARS-CoV-2 variants such as Omicron represents a major global health challenge. Here we present data from a study in non-human primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine, consisting of RBD (receptor binding domain) on the I53-50 nanoparticle, adjuvanted with AS03, currently in Phase 3 clinical trial (NCT05007951). Vaccination induced robust neutralizing antibody (nAb) titers that were maintained at high levels for at least one year after two doses (Pseudovirus nAb GMT: 2207, Live-virus nAb GMT: 1964) against the ancestral strain, but not against Omicron. However, a booster dose at 6-12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited equivalent and remarkably high neutralizing titers against the ancestral as well as the Omicron variant. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Importantly, vaccination resulted in protection against Omicron infection in the lung (no detectable virus in any animal) and profound suppression of viral burden in the nares (median peak viral load of 7567 as opposed to 1.3×107 copies in unvaccinated animals) at 6 weeks post final booster. Even at 6 months post vaccination, there was significant protection in the lung (with 7 out of 11 animals showing no viral load, 3 out of 11 animals showing ~20-fold lower viral load than unvaccinated controls) and rapid control of virus in the nares. These results highlight the durable cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine platform.
Herpesvirus Reactivations in Critically-Ill COVID-19 Patients with Autoantibodies Neutralizing Type I Interferons
Authors: Busnadiego Idoia , Abela Irene A. , Frey Pascal M. , Hofmaenner Daniel A. , Scheier Thomas C. , Schuepbach Reto A. , Buehler Philipp K. , Brugger Silvio D. , Hale Benjamin G.
Published: March 2022

Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with pre-disposition to severe COVID-19. Here, we screened for such autoantibodies in 103 critically-ill COVID-19 patients in a tertiary intensive care unit in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFNα or anti-IFNα/anti-IFNω IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFNα IgG. Strikingly, all patients with plasma anti-IFNα IgG also had anti-IFNα IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for SARS-CoV-2 infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically-ill COVID-19 cohort appeared to predict herpesvirus (herpes simplex viruses types 1 and 2, HSV-1/-2; and/or cytomegalovirus, CMV) reactivations, which are linked to worse clinical outcomes. Indeed, all seven tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesvirus reactivations, and analysis revealed that these patients were substantially more likely to experience CMV reactivation than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for systemic steroid treatment (odds ratio 7.28, 95%-CI 1.14-46.31, p=0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates herpesvirus reactivations in critically-ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options.
De novo mutation hotspots in homologous protein domains identify function-altering mutations in neurodevelopmental disorders
Authors: Wiel Laurens , Hampstead Juliet E. , Venselaar Hanka , Vissers Lisenka E. L. M. , Brunner Han G. , Pfundt Rolph , Vriend Gerrit , Veltman Joris A. , Gilissen Christian
Published: March 2022

Variant interpretation remains a major challenge in medical genetics. We developed Meta-Domain HotSpot (MDHS) to identify mutational hotspots across homologous protein domains. We applied MDHS to a dataset of 45,221 de novo mutations (DNMs) from 31,058 patients with neurodevelopmental disorders (NDDs) and identified three significantly enriched missense DNM hotspots in the ion transport protein domain family (PF00520). The 37 unique missense DNMs that drive enrichment affect 25 genes, 19 of which were previously associated with NDDs. 3D protein structure modelling supports function-altering effects of these mutations. Hotspot genes have a unique expression pattern in tissue, and we used this pattern alongside in silico predictors and population constraint information to identify candidate NDD-associated genes. We also propose a lenient version of our method, which identifies 32 hotspot positions across 16 different protein domains. These positions are enriched for likely pathogenic variation in clinical databases and DNMs in other genetic disorders.
Treatment response prediction: Is model selection unreliable?
Authors: Augustin David , Wang Ken , Walz Antje-Christine , Lambert Ben , Clerx Michael , Robinson Martin , Gavaghan David
Published: March 2022

Quantitative modelling has become an essential part of the drug development pipeline. In particular, pharmacokinetic and pharmacodynamic models are used to predict treatment responses in order to optimise clinical trials and assess the safety and efficacy of dosing regimens across patients. It is therefore crucial that treatment response predictions are reliable. However, the data available to fit models are often limited, which can leave considerable uncertainty about the best model to use. Common practice is to select the model that is most consistent with the observed data based on the Akaike information criterion (AIC). Another popular approach is to average the predictions across the subset of models consistent with the data. In this article, we argue that both approaches can lead to unreliable predictions, as treatment responses typically display nonlinear dynamics, so models can be consistent with the observed dynamics, whilst predicting incorrect treatment responses. This is especially the case when predicting treatment responses for either times or dosing regimens that go beyond the observed dynamics. Across a range of experiments on both real laboratory data and synthetically derived data onNeisseria gonorrhoeaeresponse to ciprofloxacin, we show that probabilistic averaging of models results in more reliable treatment response predictions.