bluuebunny/crossref_metadata_2025 huggingface dataset:
Grade Inflation: A Leadership Opportunity for Schools of Education?
Authors: Zirkel Perry A.
Published: February 2022

Grade inflation pervades American schools from the K–12 level through the graduate level. The trend is particularly pronounced in the humanities fields and in departments, schools, and colleges of education (DSCEs). This problem presents a leadership opportunity for DSCEs to develop and implement a credible and meaningful grade-distribution system.
Inhibition of Musashi-1 enhances chemotherapeutic sensitivity in gastric cancer patient-derived xenografts
Authors: Liu Fan , Yang Huan , Zhang Xinyu , Sun Xianglin , Zhou Jiamin , Li Yuan , Liu Yifei , Zhuang Zhixiang , Wang Guohua
Published: February 2022

Musashi-1 (MSI1), a neural RNA-binding protein, is considered a gastric and intestinal stem cell marker. Although the function of MSI1 in gastric cancer has attracted increasing interest, it is not known whether MSI1 can be used as a biomarker to monitor gastric cancer development and response to treatment. Here, the role of MSI1 in the chemotherapeutic sensitivity of gastric cancer was investigated. Patients with high MSI1 levels had poor outcomes, implicating the gene in the development and progression of the disease. We overexpressed and silenced MSI1 in the human gastric cancer cell lines MKN45 and HGC27, finding that knockdown reduced proliferation, invasion, and migration, while promoting apoptosis. A patient-derived xenograft gastric cancer model was constructed in which mice received chemical drugs, si-MSI1, or a drug-si-MSI1 combination. It was found that blocking MSI1 expression reduced gastric cancer drug tolerance. The combination treatment with si-MSI1 was superior to 5F-dUMP and cisplatin, either separately or in combination, indicating that including si-MSI1 was better than drug therapy alone. Transcriptome sequencing analysis showed that MSI1 altered cell cycle regulation and growth signal transduction, including that of blood vessel epicardial substance (BVES). These results suggest that MSI1 reduces the tolerance of gastric cancer to chemical drugs through modulation of MSI1/BVES signaling.
Circulating primitive murine erythroblasts undergo complex proteomic and metabolomic changes during terminal maturation
Authors: Nemkov Travis , Kingsley Paul D. , Dzieciatkowska Monika , Malik Jeffrey , McGrath Kathleen E. , Hansen Kirk C. , D’Alessandro Angelo , Palis James
Published: February 2022

Primitive erythropoiesis is a critical component of the fetal cardiovascular network and is essential for the growth and survival of the mammalian embryo. The need to rapidly establish a functional cardiovascular system is met, in part, by the intravascular circulation of primitive erythroid precursors that mature as a single semisynchronous cohort. To better understand the processes that regulate erythroid precursor maturation, we analyzed the proteome, metabolome, and lipidome of primitive erythroblasts isolated from embryonic day (E) 10.5 and E12.5 of mouse gestation, representing their transition from basophilic erythroblast to orthochromatic erythroblast (OrthoE) stages of maturation. Previous transcriptional and biomechanical characterizations of these precursors have highlighted a transition toward the expression of protein elements characteristic of mature red blood cell structure and function. Our analysis confirmed a loss of organelle-specific protein components involved in messenger RNA processing, proteostasis, and metabolism. In parallel, we observed metabolic rewiring toward the pentose phosphate pathway, glycolysis, and the Rapoport-Luebering shunt. Activation of the pentose phosphate pathway in particular may have stemmed from increased expression of hemoglobin chains and band 3, which together control oxygen-dependent metabolic modulation. Increased expression of several antioxidant enzymes also indicated modification to redox homeostasis. In addition, accumulation of oxylipins and cholesteryl esters in primitive OrthoE cells was paralleled by increased transcript levels of the p53-regulated cholesterol transporter (ABCA1) and decreased transcript levels of cholesterol synthetic enzymes. The present study characterizes the extensive metabolic rewiring that occurs in primary embryonic erythroid precursors as they prepare to enucleate and continue circulating without internal organelles.
Sex work community participation in criminalized environments: a community-based cohort study of occupational health impacts in Vancouver, Canada: 2010–2019
Authors: Pearson Jennie , Shannon Kate , McBride Bronwyn , Krüsi Andrea , Machat Sylvia , Braschel Melissa , Goldenberg Shira
Published: February 2022

Background

Sex work criminalization and occupational stigma pose barriers to sex workers’ access to support services, including community participation — engagement with sex work specific community organizing at both formalized and grassroots capacities. In light of gaps in evidence regarding impacts of community participation on sex workers’ occupational health in higher-income settings, we evaluated engagement in community participation and associations with occupational sexual health outcomes among sex workers in Vancouver, Canada.

Methods

Prospective data from a community-based cohort of 943 women sex workers in Vancouver, British Columbia (2010–2019). We used logistic regression with generalised estimating equations (GEE) to model correlates of community participation, and a confounder modeling approach to examine the association of community participation on sexually transmitted infection (STI) seropositivity.

Results

Among participants, 38.1% were Indigenous, 31.4% identified as women of colour (e.g., East Asian, Southeast Asian, Black) and 29.3% were im/migrants to Canada. Over a quarter (28.3%, n = 267) serviced in informal indoor spaces, while 38.0% (n = 358) serviced clients in outdoor/public and 31.4% (n = 296) in formal in-call spaces. 8.9% of participants reported sex work community participation at least once over the 9-year study. In multivariable GEE analysis, Indigenous (adjusted odds ratio(aOR) 1.71, 95% confidence interval (CI) 0.88–3.32) and trans women (aOR 4.69, 95%CI 2.43–9.06) had higher odds of community participation; women of colour had lower odds (aOR 0.18, 95%CI 0.06–0.57). In a multivariable GEE confounder model, community participation was independently associated with lower odds of STI seropositivity (aOR 0.66, 95% CI0.45–0.96).

Conclusion

Sex workers who engaged in sex work community participation faced reduced odds of STI seropositivity. Building off reserach evaluating community interventions in low and middle income contexts, our study provides some of the first quantitative evidence on community participation among sex workers in Canada, and is the first to examine this in relation to sexual health outcomes. This research demonstrates the need to scale up community participation access for sex workers, via linguistically diverse community spaces, anti-stigma initiatives, and decriminalization to reduce barriers faced by racialized sex workers and support occupational health and rights for all sex workers.
Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer
Authors: Roy Souvick , Kanda Mitsuro , Nomura Sachiyo , Zhu Zhongxu , Toiyama Yuji , Taketomi Akinobu , Goldenring James , Baba Hideo , Kodera Yasuhiro , Goel Ajay
Published: February 2022

Background

Majority of gastric cancers (GC) are diagnosed at advanced stages which contributes towards their poor prognosis. In view of this clinical challenge, identification of non-invasive biomarker for early diagnosis is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy based assay by using circular RNAs (circRNAs) as molecular biomarkers for early detection of GC.

Methods

We performed systematic biomarker discovery and validation of the candidate circRNAs in matched tissue specimens of GC and adjacent normal mucosa. Next, we translated the discovered circRNA based biomarker panel into serum samples in a training and validation cohort of GC patients (n = 194) and non-disease controls (n = 94) and evaluated their diagnostic performance. In addition, we measured the expression of circRNAs in serum samples of pre- and post-surgical GC patients and evaluated the specificity of circRNAs biomarker panel with respect to other gastro-intestinal (GI) malignancies.

Results

We identified 10-circRNAs in the discovery phase with subsequent validation in a pilot cohort of GC tissue specimens. Using a training cohort of patients, we developed an 8-circRNA based risk-prediction model for the diagnosis of GC. We observed that our biomarker panel robustly discriminated GC patients from non-disease controls with an AUC of 0.87 in the training, and AUC of 0.83 in the validation cohort. Notably, the biomarker panel could robustly identify even early-stage GC patients, regardless of their tumor histology (diffuse vs. intestinal). The decreased expression of circRNAs in post-surgery serum specimens indicated their tumor-specificity and their potential source of origin in the systemic circulation.

Conclusions

We identified a panel of 8-circRNAs as non-invasive, liquid-biopsy biomarkers which might serve as potential diagnostic biomarkers for the early detection of GC.
Chronic appendicitis: two case reports
Authors: Holm Nanna , Rømer Maria Unni , Markova Elena , Buskov Laura Katrine , Hansen Ann-Brit Eg , Rose Michala Vaaben
Published: February 2022

Background

Chronic appendicitis is a condition unfamiliar to many physicians and is often referred to as a controversial diagnosis. This can give rise to diagnostic delay.

Case presentation

We present two cases of chronic appendicitis: a Caucasian female aged 21 years and a Caucasian male aged 34 years. The patients had different clinical presentations, which led the initial investigations in very different directions—tropical infectious disease and possible malignancy, respectively. In both cases, radiological imaging was the key investigation leading to the final surprising diagnosis.

Conclusion

With these two case stories, we wish to draw attention to chronic appendicitis as a possible differential diagnosis in younger patients with chronic or recurrent abdominal pain, particularly if the pain is located in the lower abdomen and is accompanied by fever.
Three-year outcome of local injection of autologous stromal vascular fraction cells and microfat in refractory perianal fistulas of Crohn’s disease
Authors: Guillo Lucas , Grimaud Fanny , Houser Fanny , Prost Caroline , Jouve Elisabeth , Philandrianos Cécile , Abellan Maxime , Veran Julie , Visee Carine , Beyer-Berjot Laura , Desjeux Ariadne , Dignat-George Françoise , Leone Marc , Grimaud Jean-Charles , Sabatier Florence , Serrero Mélanie , Magalon Jérémy
Published: February 2022

Perianal fistulas in Crohn's disease are frequent and disabling, with a major impact on patients' quality of life. Cell-based therapy using mesenchymal stem cells represents new hope for these patients, but long-term efficacy remains challenging. In a pilot study, including patients with refractory complex perianal fistulas, autologous adipose-derived stromal vascular fraction (ADSVF) combined with microfat achieved combined remission in 60% of cases, with a good safety profile at 1 year. The purpose of this study is to assess whether these results were maintained at longer term. The safety and efficacy data of the ten patients were evaluated retrospectively 3 years after injection on the basis of clinical and radiological data. MRI were analysed according to the MAGNIFI-CD score. No adverse event was attributed to the experimental stem-cell treatment. Combined remission was achieved in 7 patients (70%) and associated with a significant improvement in the MAGNIFI-CD MRI score. In conclusion, the safety and efficacy of ADSVF and microfat injection in Crohn's disease fistulas were maintained at 3 years, demonstrating that this innovative strategy is effective in producing a long-lasting healing effect. The ongoing multicentre randomized placebo-controlled trial (NCT04010526) will be helpful to define the place for this approach in the current therapeutic arsenal.
The gut microbiome and antibiotic resistome of chronic diarrhea rhesus macaques (Macaca mulatta) and its similarity to the human gut microbiome
Authors: Yang Shengzhi , Liu Yu , Yang Nan , Lan Yue , Lan Weiqi , Feng Jinyi , Yue Bisong , He Miao , Zhang Liang , Zhang Anyun , Price Megan , Li Jing , Fan Zhenxin
Published: February 2022

Background

Chronic diarrhea is a common disease causing morbidity and mortality of captive rhesus macaques (RMs, Macaca mulatta). Chronic diarrhea in RMs is typically characterized by long-term diarrhea and a weak response to antibiotic treatment. Diarrhea is also a common disease in humans and can cause death. However, the etiology of about half of diarrheal cases of humans is still unclear. Therefore, we performed shotgun metagenomic sequencing to characterize the differences in the gut microbiome and resistome of chronic diarrhea RMs and asymptomatic individuals.

Results

Our results showed Lactobacillus spp. (mainly L. johnsonii, L. reuteri and L. amylovorus) were significantly depleted in chronic diarrhea RM guts compared to asymptomatic individuals (5.2 vs 42.4%). Functional annotation of genes suggested these Lactobacillus spp. carried genes involved in the adhesion of intestinal epithelial cells and production of bacteriocin. Chronic diarrhea RM guts also had a significantly greater abundance of many other gut bacteria, including mucin-degrading bacteria and opportunistic pathogens. The metabolic pathways of chronic diarrhea RM gut microbiome were enriched in aerobactin biosynthesis, while the metabolic pathways of asymptomatic RM gut microbiome were enriched in the production of short-chain fatty acids (SCFAs). Chronic diarrhea RM guts had a significantly greater abundance of antibiotic resistance genes (ARGs), such as ermF, aph(3’)-IIIa, ermB, and floR. The strains isolated from feces and tissue fluid of chronic diarrhea RMs had higher resistance rates to the majority of tested antibiotics, but not cephamycin and carbapenem antibiotics. Gut microbial composition comparisons showed that several captive nonhuman primate (NHP) guts were more similar to the guts of humans with a non-westernized diet than humans with a westernized diet. Chronic diarrhea RM gut microbiome was strikingly similar to rural-living humans with diarrhea and humans with a non-westernized diet than asymptomatic RMs.

Conclusions

Our results suggested chronic diarrhea significantly altered the composition and metabolic pathways of the RM gut microbiome. The frequent use of antibiotics caused antibiotic resistance in chronic diarrhea RM gut microbiome with serious consequences for individual treatment and survival. The findings of this study will help us to improve the effective prevention and treatment of diarrhea in RMs.
Microeukaryotic gut parasites in wastewater treatment plants: diversity, activity, and removal
Authors: Freudenthal Jule , Ju Feng , Bürgmann Helmut , Dumack Kenneth
Published: February 2022

Background

During wastewater treatment, the wastewater microbiome facilitates the degradation of organic matter, reduction of nutrients, and removal of gut parasites. While the latter function is essential to minimize public health risks, the range of parasites involved and how they are removed is still poorly understood.

Results

Using shotgun metagenomic (DNA) and metatranscriptomic (RNA) sequencing data from ten wastewater treatment plants in Switzerland, we were able to assess the entire wastewater microbiome, including the often neglected microeukaryotes (protists). In the latter group, we found a surprising richness and relative abundance of active parasites, particularly in the inflow. Using network analysis, we tracked these taxa across the various treatment compartments and linked their removal to trophic interactions.

Conclusions

Our results indicate that the combination of DNA and RNA data is essential for assessing the full spectrum of taxa present in wastewater. In particular, we shed light on an important but poorly understood function of wastewater treatment – parasite removal.
Feasibility and preliminary efficacy of the LEAD trial: a cluster randomized controlled lifestyle intervention to improve hippocampal volume in older adults at-risk for dementia
Authors: Koblinsky N. D. , Anderson N. D. , Ajwani F. , Parrott M. D. , Dawson D. , Marzolini S. , Oh P. , MacIntosh B. , Middleton L. , Ferland G. , Greenwood C. E.
Published: February 2022

Background

Healthy diet and exercise are associated with reduced risk of dementia in older adults. The impact of diet and exercise interventions on brain health is less consistent, especially with dietary interventions which rely on varying approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counseling approach to improve hippocampal volume among older adults at-risk for dementia.

Methods

Participants with vascular risk factors and subjective cognitive decline or early mild cognitive impairment were cluster randomized in groups of 3–4 to the diet intervention (DIET) or control education (ED) group. All participants engaged in 1 h of supervised exercise per week and additional exercise at home. DIET involved 1 h per week of group-based dietary counseling comprising education, goal setting, and strategy training. ED involved 1 h per week of group-based brain health education classes. Our primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included changes in cognitive function, blood biomarkers, diet, and fitness. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy.

Results

Of 190 older adults contacted, 14 (7%) were eligible and enrolled, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and DIET/ED sessions on average. All 6-month assessments prior to COVID-19 were completed but disruptions to in-person testing resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the study. Preliminary findings did not identify any significant changes in hippocampal volume; however, substantial improvements in diet and HbA1c were observed with DIET compared to ED (d = 1.75 and 1.07, respectively).

Conclusions

High adherence and retention rates were observed among participants and preliminary findings illustrate improvements in diet quality and HbA1c. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated.

Trial registration

ClinicalTrials.gov identifier: NCT03056508.
COVID-19 screening before gastrointestinal procedures
Authors: Eliwa Ahmed , Osman Osman Mohamed , Helal Ahmed , Mohamed Abdelgawad Saied , ElFayoumie Mohammed , Eldamarawy Ramadan , Mostafa Sadek , Elsharkawy Ashraf , Makboul Khaled S. , Elshennawy Salwa I. , Abdelhady Mahmoud , Elbahrawy Ashraf
Published: February 2022

Background

In March 2020, the World Health Organization declared coronavirus 2019 (COVID-19) a global pandemic. We aimed to assess the ability of COVID-19 screening to detect preprocedural infection at the gastrointestinal units. One hundred and three patients indicated for gastrointestinal tract interventional procedures were included. All patients surveyed for COVID-19-related symptoms and COVID-19 rapid IgM/IgG antibodies. Symptomatic and COVID-19 antibody-positive patients further tested for COVID-19 reverse transcriptase by polymerase chain reaction (RT-PCR). All patients contacted, 14 days after the procedure and asked about the possible development of COVID-19. All health care workers (HCWs) (n=18) were screened weekly for COVID-19-related symptoms.

Results

The mean age was 46.11 ± 17.16 years of them 58.25% were males. 2.9% patients had COVID-19-related symptoms and 97.1% were asymptomatic. All symptomatic patients tested positive for COVID-19 IgM antibody and RT-PCR. Among asymptomatic patients 23% had positive COVID-19 antibodies, of them 56.5%patients had positive RT-PCR. One HCW developed COVID-19 during the study. None of the included patients developed new onset of COVID-19 infection, two weeks after the procedure.

Conclusion

COVID-19 antibody test may be a reasonable preprocedural screening method for low-income countries and COVID-19 RT-PCR screening for symptomatic patients and those with positive COVID-19 antibody test.
A review of the essential concepts in diagnosis, therapy, and gender assignment in disorders of sexual development
Authors: Sarma Vivek Parameswara
Published: February 2022

Background

The aim of this article is to review the essential concepts, current terminologies and classification, management guidelines and the rationale of gender assignment in different types of differences/disorders of sexual development.

Main body

The basics of the present understanding of normal sexual differentiation and psychosexual development were reviewed. The current guidelines, consensus statements along with recommendations in management of DSD were critically analyzed to formulate the review. The classification of DSD that is presently in vogue is presented in detail, with reference to old nomenclature. The individual DSD has been tabulated based on various differential characteristics. Two schemes for analysis of DSD types, based on clinical presentation, karyotype and endocrine profile has been proposed here. The risk of gonadal malignancy in different types of DSD is analyzed. The rationale of gender assignment, therapeutic options, and ethical dimension of treatment in DSD is reviewed in detail.

Conclusion

The optimal management of different types of DSD in the present era requires the following considerations: (1) establishment of a precise diagnosis, employing the advances in genetic and endocrine evaluation. (2) A multidisciplinary team is required for the diagnosis, evaluation, gender assignment and follow-up of these children, and during their transition to adulthood. (3) Deeper understanding of the issues in psychosexual development in DSD is vital for therapy. (4) The patients and their families should be an integral part of the decision-making process. (5) Recommendations for gender assignment should be based upon the specific outcome data. (6) The relative rarity of DSD should prompt constitution of DSD registers, to record and share information, on national/international basis. (7) The formation of peer support groups is equally important. The recognition that each subject with DSD is unique and requires individualized therapy remains the most paramount.
WFS1 Gene–associated Diabetes Phenotypes and Identification of a Founder Mutation in Southern India
Authors: Chapla Aaron , Johnson Jabasteen , Korula Sophy , Mohan Nisha , Ahmed Anish , Varghese Deny , Rangasamy Parthiban , Ravichandran Lavanya , Jebasingh Felix , Kumar Agrawal Krishna , Somasundaram Noel , Hesarghatta Shyamasunder Asha , Mathai Sarah , Simon Anna , Jha Sujeet , Chowdry Subhankar , Venkatesan Radha , Raghupathy Palany , Thomas Nihal
Published: February 2022

Context

Wolfram syndrome (WFS) is a rare autosomal recessive disorder characterized by juvenile-onset diabetes, diabetes insipidus, optic atrophy, deafness, and progressive neurodegeneration. However, due to the progressive nature of the disease and a lack of complete clinical manifestations, a confirmed diagnosis of WFS at the time of onset of diabetes is a challenge.

Objective

With WFS1 rare heterozygous variants reported in diabetes, there is a need for comprehensive genetic screening strategies for the early diagnosis of WFS and delineating the phenotypic spectrum associated with the WFS1 gene variants in young-onset diabetes.

Methods

This case series of 11 patients who were positive for WFS1 variants were identified with next-generation sequencing (NGS)–based screening of 17 genemonogenic diabetes panel. These results were further confirmed with Sanger sequencing.

Results

9 out of 11 patients were homozygous for pathogenic/likely pathogenic variants in the WFS1 gene. Interestingly, 3 of these probands were positive for the novel WFS1 (NM_006005.3): c.1107_1108insA (p.Ala370Serfs*173) variant, and haplotype analysis suggested a founder effect in 3 families from Southern India. Additionally, we identified 2 patients with young-onset diabetes who were heterozygous for a likely pathogenic variant or a variant of uncertain significance in the WFS1 gene.

Conclusion

These results project the need for NGS-based parallel multigene testing as a tool for early diagnosis of WFS and identify heterozygous WFS1 variants implicated in young-onset diabetes.
Obesity Due to Steroid Receptor Coactivator-1 Deficiency Is Associated With Endocrine and Metabolic Abnormalities
Authors: Cacciottolo Tessa M , Henning Elana , Keogh Julia M , Bel Lassen Pierre , Lawler Katherine , Bounds Rebecca , Ahmed Rachel , Perdikari Aliki , Mendes de Oliveira Edson , Smith Miriam , Godfrey Edmund M , Johnson Elspeth , Hodson Leanne , Clément Karine , van der Klaauw Agatha A , Farooqi I Sadaf
Published: February 2022

Context

Genetic variants affecting the nuclear hormone receptor coactivator steroid receptor coactivator, SRC-1, have been identified in people with severe obesity and impair melanocortin signaling in cells and mice. As a result, obese patients with SRC-1 deficiency are being treated with a melanocortin 4 receptor agonist in clinical trials.

Objective

Here, our aim was to comprehensively describe and characterize the clinical phenotype of SRC-1 variant carriers to facilitate diagnosis and clinical management.

Methods

In genetic studies of 2462 people with severe obesity, we identified 23 rare heterozygous variants in SRC-1. We studied 29 adults and 18 children who were SRC-1 variant carriers and performed measurements of metabolic and endocrine function, liver imaging, and adipose tissue biopsies. Findings in adult SRC-1 variant carriers were compared to 30 age- and body mass index (BMI)-matched controls.

Results

The clinical spectrum of SRC-1 variant carriers included increased food intake in children, normal basal metabolic rate, multiple fractures with minimal trauma (40%), persistent diarrhea, partial thyroid hormone resistance, and menorrhagia. Compared to age-, sex-, and BMI-matched controls, adult SRC-1 variant carriers had more severe adipose tissue fibrosis (46.2% vs 7.1% respectively, P = .03) and a suggestion of increased liver fibrosis (5/13 cases vs 2/13 in controls, odds ratio = 3.4), although this was not statistically significant.

Conclusion

SRC-1 variant carriers exhibit hyperphagia in childhood, severe obesity, and clinical features of partial hormone resistance. The presence of adipose tissue fibrosis and hepatic fibrosis in young patients suggests that close monitoring for the early development of obesity-associated metabolic complications is warranted.
Approach to the Patient: “Utility of the Copeptin Assay”
Authors: Christ-Crain Mirjam , Refardt Julie , Winzeler Bettina
Published: February 2022

Copeptin derives from the same precursor peptide preprovasopressin as arginine vasopressin (AVP). The secretion of both peptides is stimulated by similar physiological processes, such as osmotic stimulation, hypovolemia, or stress. AVP is difficult to measure due to complex preanalytical requirements and due to technical difficulties. In the last years, copeptin was found to be a stable, sensitive, and simple to measure surrogate marker of AVP release. Different immunoassays exist to measure copeptin. The 2 assays which have most often be used in clinical studies are the original sandwich immunoluminometric assay and its automated immunofluorescent successor. In addition, various enzyme-linked immunosorbent assay have been developed. With the availability of the copeptin assay, the differential diagnosis of diabetes insipidus was recently revisited. The goal for this article is therefore to first review the physiology of copeptin, and second to describe its use as marker for the differential diagnosis of vasopressin-dependent fluid disorders, mainly diabetes insipidus but also hyper- and hyponatremia. Furthermore, we highlight the role of copeptin as prognostic marker in other acute and chronic diseases.
Performance of DHEAS as a Screening Test for Autonomous Cortisol Secretion in Adrenal Incidentalomas: A Prospective Study
Authors: Liu Meng-si , Lou Yuan , Chen Huan , Wang Yi-jie , Zhang Zi-wei , Li Ping , Zhu Da-long
Published: February 2022

Context

Autonomous cortisol secretion (ACS) affects up to 30% of patients with adrenal incidentalomas (AIs). The current guidelines for ACS diagnosis are not decisive. A lower dehydroepiandrosterone sulfate (DHEAS) level is a potential biomarker, but the evidence is conflicting.

Objective

This prospective study aimed to evaluate and validate the ACS screening and diagnostic accuracy of DHEAS.

Methods and patients

Recruited patients with AI were screened for adrenal medullary and cortisol hypersecretion. The diagnosis of ACS was based on a serum cortisol level ≥ 50 nmol/L following a 1-mg dexamethasone suppression test (DST) and a low-dose DST. Age- and sex-specific DHEAS ratios were also calculated.

Results

In the development cohort (45 ACS and 242 non-ACS patients), the areas under the receiver operator characteristic curves (AUCs) of DHEAS and the DHEAS ratio were 0.869 (95% CI 0.824-0.906) and 0.799 (95% CI 0.748-0.844), respectively. The optimal DHEAS cutoff for diagnosing ACS was 60 μg/dL, with a sensitivity of 75.6% (95% CI 60.5-87.1) and a specificity of 81.4% (95% CI 76.4-86.5). The midnight serum cortisol level had moderate diagnostic accuracy [AUC 0.875 (95% CI 0.831-0.911)]. Suppressed adrenocorticotropic hormone (≤2.2 pmol/L) had a lower sensitivity (55.6%), and the 24-hour urinary free cortisol lacked sensitivity and specificity [AUC 0.633 (95% CI 0.603-0.721)]. In the validation cohort (14 ACS and 45 non-ACS patients), the sensitivity and specificity of the optimized DHEAS cutoff were 71.4% (95% CI 41.9-91.6) and 82.2% (95% CI 68.0-92.0), respectively.

Conclusions

A single basal measurement of DHEAS is valuable for identifying ACS. Because of its stability and ease of use, the DHEAS level could be used as an ACS screening test.
Heterozygote Advantage of the Type II Deiodinase Thr92Ala Polymorphism on Intrahospital Mortality of COVID-19
Authors: de Lima Beltrão Fabyan Esberard , de Almeida Beltrão Daniele Carvalhal , Carvalhal Giulia , de Lima Beltrão Fabricia Elizabeth , de Souza Braga Filho Jair , de Brito Oliveira Jocyel , de Jesus Joice dos Santos , Machado Gabriel Jeferson Rodríguez , dos Santos Silva Hatilla , Teixeira Helena Mariana Pitangueira , Rodrigues Juliana Lopes , de Figueiredo Camila Alexandrina Viana , dos Santos Costa Ryan , Hecht Fabio , Bianco Antonio C , da Conceição Rodrigues Gonçalves Maria , Ramos Helton Estrela
Published: February 2022

Context

The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and pulmonary fibrosis.

Objective

Our objectives were to evaluate were cumulative mortality during admission according to Thr92Ala-DIO2 polymorphism.

Methods

Here we conducted an observational, longitudinal, and prospective cohort study to investigate a possible association between the Thr92Ala-DIO2 polymorphism and intrahospital mortality from COVID-19 in adult patients admitted between June and August 2020. Blood biochemistry, thyroid function tests, length of stay, comorbidities, complications, and severity scores were also studied according to Thr92Ala-DIO2 polymorphism.

Results

In total, 220 consecutive patients (median age 62; 48-74 years) were stratified into 3 subgroups: Thr/Thr (n = 79), Thr/Ala (n = 119), and Ala/Ala (n = 23). While the overall mortality was 17.3%, the lethality was lower in Ala/Thr patients (12.6%) than in Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The heterozygous genotype (Thr/Ala) was associated with a 47% reduced risk of intrahospital mortality whereas univariate and multivariate logistic regression adjusted for multiple covariates revealed a reduction that ranged from 51% to 66%. The association of the Thr/Ala genotype with better clinical outcomes was confirmed in a metanalysis of 5 studies, including the present one.

Conclusion

Here we provide evidence for a protective role played by Thr92Ala-DIO2 heterozygosity in patients with COVID-19. This protective effect follows an inheritance model known as overdominance, in which the phenotype of the heterozygote lies outside the phenotypical range of both homozygous.
A Novel Form of Familial Vasopressin Deficient Diabetes Insipidus Transmitted in an X-linked Recessive Manner
Authors: Habiby Reema , Bichet Daniel G , Arthus Marie-Francoise , Connaughton Dervia , Shril Shirlee , Mane Shrikant , Majmundar Amar J , Hildebrandt Friedhelm , Robertson Gary L
Published: February 2022

Context

Familial pituitary diabetes insipidus has been described only in an autosomal dominant or recessive mode of inheritance.

Objective

This work aims to determine the cause of a novel form of familial diabetes insipidus (DI) that is controlled by desmopressin therapy but segregates in an X-linked recessive manner.

Methods

Thirteen members from 3 generations of the kindred with familial DI were studied. Water intake, urine volume, urine osmolality, plasma osmolality, and plasma vasopressin were measured under basal conditions, during fluid deprivation, 3% saline infusion, and water loading. Magnetic resonance images of the posterior pituitary also were obtained. In affected males, the effects of desmopressin therapy and linkage of the DI to markers for chromosome Xq28 were determined. In addition, the genes encoding vasopressin, aquaporin-2, the AVPR2 receptor, and its flanking regions were sequenced.

Results

This study showed that 4 males from 3 generations of the kindred have DI that is due to a deficiency of vasopressin, is corrected by standard doses of desmopressin, and segregates with markers for the AVPR2 gene in Xq28. However, no mutations were found in AVPR2 or its highly conserved flanking regions. Exome sequencing confirmed these findings and also revealed no deleterious variants in the provasopressin and aquaporin-2 genes. The 4 obligate female carriers osmo-regulated vasopressin in the low normal range.

Conclusion

X-linked recessive transmission of DI can be due to a defect in either the secretion or the action of vasopressin. Other criteria are necessary to differentiate and manage the 2 disorders correctly.
Corticotropin-Releasing Factor Aggravates Ischemic Stroke Injury by the Inflammatory Activation of Microglia
Authors: Wu Qiang , Feng Yan , Liu Ling , Liu Yang , Liu Xin , Zhang Liqiao , Li Yanan , Wang Liqun
Published: February 2022

Ischemic stroke is the second leading cause of death worldwide. Therefore, exploring effective and emerging molecular targets for ischemic stroke is a primary task of basic and clinical research. The aim of the present study was to investigate the function of corticotropin-releasing factor (CRF) in ischemic stroke and its related mechanisms, to provide a reference for the treatment of ischemic stroke. CRF, antalarmin, or astressin-2B were used to activate or block the CRF1 (CRF receptor 1) or CRF2 (CRF receptor 2) in BV2 cells and adult male mice, thus constructing a distal middle cerebral artery occlusion (dMCAO) model. CRF not only accelerated microglial activity by promoting transcription and production of inflammatory factors, but also promoted the transformation of activated BV2 cells from a neuroprotective phenotype (M2) to cytotoxic phenotype (M1), and these effects were mediated by the TLR4/NF-κB signaling pathway. These effects can be blocked by antalarmin but not by astressin-2B. CRF significantly aggravated the neurological deficit, increased infarction volume, and exacerbated neuronal injuries. Additionally, CRF significantly improved the levels of TNF-α and phospho-NF-κB in the ischemia penumbra. Finally, CRF significantly increased the number of CD16/Iba-1-positive cells and decreased the number of CD206/Iba-1-positive cells in the ischemia penumbra. These results provide evidence of the proinflammatory role of CRF in an ischemic stroke model and a possible underlying mechanism, which may facilitate the elucidation of potential treatment approaches for ischemic stroke.
Novel KDM6A Kabuki Syndrome Mutation With Hyperinsulinemic Hypoglycemia and Pulmonary Hypertension Requiring ECMO
Authors: Salguero Maria V , Chan Karen , Greeley Siri Atma W , Dyamenahalli Umesh , Waggoner Darrel , del Gaudio Daniela , Rajiyah Tara , Lemelman Michelle
Published: February 2022

Kabuki syndrome (KS) is a multisystem disorder estimated to occur in 1:32 000 newborns. Pathogenic mutations cause the majority but not all cases of KS in either KMT2D or KDM6A. KS can be suspected by phenotypic features, including infantile hypotonia, developmental delay, dysmorphic features, congenital heart defects, and others. Still, many of these features are not readily apparent in a newborn. Although neonatal hypoglycemia has been reported in 8% to 10% of patients with KS, the incidence and severity of hyperinsulinemic hypoglycemia (HH) is not well-studied. We present a full-term female infant with HH who was responsive to low-dose diazoxide. At 3 months of age, she was admitted for septic shock, worsening respiratory status, and severe pulmonary hypertension, requiring extracorporeal membrane oxygenation support. Her neonatal history was notable for hypotonia, dysphagia with aspiration requiring gastrostomy tube placement, and a cardiac defect—hypoplastic aortic arch requiring aortic arch repair. She has characteristic facial features, including prominent eyelashes, long palpebral fissures, and a short nasal columella. Next-generation sequencing for HH revealed a de novo likely pathogenic missense variant in KDM6A gene: c.3479G > T, p.Gly1160Val that was absent from population databases. Genetic testing for causes of HH should include testing of the KS genes KMT2D and KDM6A. Early detection of the underlying genetic defect will help guide management as all reported HH cases associated with KS have been responsive to diazoxide. Affected infants with underlying cardiac conditions may be at higher risk of serious respiratory complications such as pulmonary hypertension.
The Durée of Emancipation and the Crisis of Freedom in Antebellum Black Writing
Authors: Staidum Frederick C.
Published: February 2022

Although the linear trajectories from enslavement to freedom of slave narratives and antislavery novels have been generally accepted, moments of pause and recursiveness at the very instantiation of the narrators’ or protagonists’ emancipation suggest a different, nonlinear temporality. This essay triangulates the various emancipations of Harriet Jacobs in Incidents in the Life of a Slave Girl, Frado in Harriet E. Wilson’s Our Nig, and Solomon Northup in Twelve Years a Slave to reveal how the nonlinearity of their manumission circumscribes the freedom concept in such a way that renders it a crisis. Nineteenth-century French thinker Henri Bergson’s philosophy of durée is taken up as a theoretical and analytical point of departure. Durée, when refracted through postcolonial and Black studies interlocutors, offers a richly multivalent way to conceptualize the contemporaneousness of slavery’s past alongside and within the present and its myriad futures, while also conceiving the multi-directionality of these tenses (e.g., the present can also create a past) and acknowledging the agentive creativity of Black fugitive pursuits. In the end, the essay demonstrates how the latent, arrested, cyclical, and backward temporalities of emancipation are not abstractions but lived materialities engendered by the conditions and contexts of unremitting anti-Blackness and racial capital.
Successful control of a large intrahepatic cholangiocarcinoma treated by transarterial chemo-embolization; a single case report
Authors: Hori Atsushi , Toei Hiroshi , Nakamura Tatsuya , Makitani Kazuhiro , Hori Shinichi
Published: February 2022

Intrahepatic cholangiocarcinoma is hardly diagnosed in early stages as the symptoms are non-specific. Due to an advanced stages at the time of first diagnosis, the therapeutic options for patients with unresectable cholangiocarcinoma are mostly limited to systemic chemotherapy or radiotherapy, but good local control or preferable prognostic effects are hardly obtained. The transarterial chemoembolization had not been a standard of care because of hepatic functional damages caused by lipiodol and gelatin sponge. A newly developed spherical embolic material causes limited hepatic damages might be an option for these patients. It makes it possible to repeat the procedure in a short period. Eventually, better prognosis can be expected using a spherical embolic material. We report a case of a 15 cm locally advanced intrahepatic cholangiocarcinoma treated by chemoembolization using a drug-eluting spherical embolic material and achieved good local tumor control without liver damage. The patient survived longer than 4 years without additional or concomitant treatments.
Modeling anticipated changes in numbers of SARS-CoV-2 infections within communities due to immunization campaigns
Authors: Frey Kurt , Hagedorn Brittany , McCarthy Kevin A. , Hutubessy Raymond , Wang Susan Annemarie
Published: February 2022

Background: As SARS-CoV-2 spread in early 2020, uncertainty about the scope, duration, and impact of the unfolding outbreaks caused numerous countries to interrupt many routine activities, including health services. Because immunization is an essential health service, modeling changes in SARS-CoV-2 infections among communities and health workers due to different vaccination activities was undertaken to understand the risks and to inform approaches to resume services.

Methods: Agent-based modeling examined the impact of Supplemental Immunization Activities (SIAs) delivery strategies on SARS-CoV-2 transmission in communities and health workers for six countries capturing various demographic profiles and health system performance: Angola, Ecuador, Lao PDR, Nepal, Pakistan, and Ukraine.

Results: Urban, fixed-post SIAs during periods of high SARS-CoV-2 prevalence increased infections within the community by around 28 [range:0-79] per 1000 vaccinations. House-to-house SIAs in mixed urban and rural contexts may import infections into previously naïve communities. Infections are elevated by around 60 [range:0-230] per 1000 vaccinations, but outcomes are sensitive to prevalence in health workers and SIA timing relative to peak.

Conclusions: Younger populations experience lower transmission intensity and fewer excess infections per childhood vaccine delivered. Large rural populations have lower transmission intensity but face a greater risk of introduction of SARS-CoV-2 during an SIA.
Large-scale assessment of 7-11-year-olds’ cognitive and sensorimotor function within the Born in Bradford longitudinal birth cohort study
Authors: Hill Liam JB , Shire Katy A. , Allen Richard J , Crossley Kirsty , Wood Megan L , Mason Dan , Waterman Amanda H
Published: February 2022

Background: Cognitive ability and sensorimotor function are crucial aspects of children’s development, and are associated with physical and mental health outcomes and educational attainment. This paper describes cross-sectional sensorimotor and cognitive function data collected on over 15,000 children aged 7-10 years, collected as part of the Born in Bradford (BiB) longitudinal birth-cohort study. Methodological details of the large-scale data collection process are described, along with initial analyses of the data involving the relationship between cognition/sensorimotor ability and age and task difficulty, and associations between tasks.

Method: Data collection was completed in 86 schools between May 2016 and July 2019. Children were tested at school, individually, using a tablet computer with a digital stylus or finger touch for input. Assessments comprised a battery of three sensorimotor tasks (Tracking, Aiming, & Steering) and five cognitive tasks (three Working Memory tasks, Inhibition, and Processing Speed), which took approximately 40 minutes.

Results: Performance improved with increasing age and decreasing task difficulty, for each task. Performance on all three sensorimotor tasks was correlated, as was performance on the three working memory tasks. In addition, performance on a composite working memory score correlated with performance on both inhibition and processing speed. Interestingly, within age-group variation was much larger than between age-group variation.

Conclusions: The current project collected computerised measures of a range of cognitive and sensorimotor functions at 7-10 years of age in over 15,000 children. Performance varied as expected by age and task difficulty, and showed the predicted correlations between related tasks. Large within-age group variation highlights the need to consider the profile of individual children in studying cognitive and sensorimotor development. These data can be linked to the wider BiB dataset including measures of physical and mental health, biomarkers and genome-wide data, socio-demographic information, and routine data from local health and education services.
Understanding the implementation of telepractice in speech and language services for children and adults using a mixed-methods approach
Authors: Shankar Varsha , Ramkumar Vidya , Kumar Shuba
Published: February 2022

Background: Telepractice emerged as a solution to overcome the challenges of access issues in the delivery of healthcare. Telepractice in speech language pathology (SLP) has existed for nearly a decade yet there is a significant knowledge gap with respect to the factors influencing the implementation of telepractice as a routine or long-term, sustained effort. This mixed-methods study aimed to identify implementation factors that influence the provision of telepractice in SLP services.

Method: A mixed-methods study consisting of a scoping review and semi-structured interviews (SSI) was carried out. Articles that described telepractice in SLP were included based on an operational definition of implementation and a set of inclusion criteria.

Results: Data was extracted from 11 studies that were mapped to nine projects in telepractice in SLP. The broad focus areas identified included diagnostics and evaluation, therapeutics and comprehensive assessment, management and follow-up care services. Synchronous/ real-time telepractice methods were always used for the provision of diagnostic testing or when providing therapy services using video conferencing. The ‘professional-facilitator-patient’ model was used most commonly followed by the ‘professional-patient’ model.  Barriers for long-term sustainability included inadequate initial capital investment, lack of reimbursement and payment options, low internet speed and bandwidth, resistance and hesitancy to use telepractice from the patient’s end, lack of organizational policies and uniform regulations. Sustainable source of funding, having a dedicated team of professionals and technicians with clear roles and responsibilities, and inclusion of systematic planning facilitated implementation. 

Conclusion: In general, telepractice in SLP was not explicitly guided by implementation science or framework. The use of implementation frameworks ensures systematic planning and feasibility assessment to inform the scale-up of implementation. Therefore, it would be worthwhile for program implementers to consider these aspects when exploring telepractice services.