bluuebunny/crossref_metadata_2025 huggingface dataset:
Poorly differentiated thyroid carcinoma arising from substernal goiter: a case report
Authors: Apelian Shant , Ismail Sawsan , Roumieh Dommar , Saad Bassam , Alshehabi Zuheir
Published: March 2024

Introduction and importance:

Poorly differentiated thyroid carcinomas represent a rare heterogeneous group of malignant tumors that constitute ~2–4% of all thyroid neoplasms. Substernal goiter (SG) is defined as an enlargement of the thyroid gland that is located below the thoracic inlet. Malignant neoplasms arising from a SG were reported in only 2–3% of cases.

This case report has been reported in line with the Surgical CAse REport (SCARE) Criteria.
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Case presentation:

This article presents a 54-year-old Syrian female who presented at our institution due to dysphagia, dyspnea, cervical swelling, and loss of appetite. Following clinical and radiological examinations, total thyroidectomy with lymph node dissection was performed. Microscopic examination revealed an infiltrative growth pattern of insular, trabecular, and solid formations of epithelial cells with scant eosinophilic cytoplasm, hyperchromatic nuclei, and bizarre mitotic figures with areas of necrosis. Subsequently, the final diagnosis was confirmed as a multifocal poorly differentiated thyroid carcinoma arising from a SG.

Clinical discussion:

The heterogeneity of histologic features of poorly differentiated thyroid carcinoma represents a diagnostic challenge. Diagnosis of poorly differentiated thyroid carcinomas is based on the Turin Criteria, which highlights histopathological features. Computed tomography plays a major role in SG for further evaluation.

Conclusion:

In this manuscript, the authors aimed to present a unique case report with challenging diagnostic features including the rapid development of an infiltrative poorly differentiated thyroid carcinoma from a SG highlighting the importance of a detailed histopathological examination of thyroid nodules in the absence of significant medical history.
Syrian child carrying multiple pathogenic variants in MBOAT7 and MT-TS1 genes: a case report on neurodevelopmental phenotypes and mitochondrial inheritance
Authors: Kousa Alyamama , Ahmed Reem , Alasmar Pr.Diana
Published: March 2024

Introduction:

The authors identify two patterns of inheritance in a Syrian child from consanguineous parents. The membrane-bound O-acyltranferase domain-containing7 (MBOAT7) gene encodes Lysophosphatidylinositol acyltranferase (LPIAT1), which is responsible for the neurodevelopment of the brain cortex. Patients with MBOAT7 variants exhibit pathogenic nervous manifestations such as global developmental delays affecting speech and motor function, intellectual disability (ID), poor coordination, and seizures, with or without MRI abnormalities. MT_TS1, the mitochondrial tRNASer(UCN) gene, is a hotspot for pathogenic mutations causing variable mitochondrial phenotypes, including hearing impairment (HI), ataxia and cognitive impairment.

Clinical presentation:

The authors present a case of a 4-year-old child with motor and speech delay, truncal hypotonia, visual tic, poor coordination, autistic features and generalized seizures at 7 months of age. After normal results from lab tests and MRI imaging, along with the family’s history of neurological disorders, genetic analysis was necessary to diagnose and assess the possibility of genetic counselling. Next-generation sequencing (NGS) showed two variable variants in the MBOAT7 and MT-TS1 genes. The first mutation is a homozygous variant of uncertain significance in the MBOAT7 gene, associated with the autosomal recessive Mental retardation type 57. The second variant is a heteroplasmic pathogenic variant in the MT-TS1 gene, indicative of mitochondrial disorders.

Conclusion:

The presence of the MBOAT7 and MT-TS1 gene variants in the same child is noteworthy. The authors must keep genetic mutations of MBOAT7 and MT-TS1 gene in mind as a differential diagnosis for intellectual disability, seizures and autistic features in children, especially in consanguineous families.
Wandering spleen in a postpartum female: a case report
Authors: Rasheed Omeed , Wassouf Ali , Abo Al Shamat Aiman , Daoud Raghad , Knaj Duaa , Ahmad Ghanem
Published: March 2024

Introduction and importance:

Wandering spleen (WS) is a rare condition that occurs when the spleen is not in its normal anatomical location, but in the abdominal or pelvic cavity. The mechanism of this condition may be due to dysfunction of ligaments that fixate the spleen in its position. Female hormonal alterations during pregnancy and other unknown causes in children may also play role in an ectopic spleen.

Case presentation:

The authors report a case of a 34-year-old woman who presented to the emergency department with intermittent abdominal pain that persisted after childbirth without other symptoms.

Clinical discussion:

Clinically the symptoms are varied and abdominal pain is the most common presentation. Radiological investigation of WS include ultrasound, MRI, and CT, which is the most preferred tool. Treatments after the diagnosis include splenectomy or splenopexy either through laparoscopy or laparotomy.

Conclusion:

Physicians should include ectopic spleen as a differential diagnosis in a multiparous woman with the presentation of acute or chronic abdominal pain.
On-the-Job Learning: Bright Spots of Governmental Public Health Employee Reflections on the COVID-19 Response
Authors: Madsen Emilie R. , Schaffer Kay , Hare Bork Rachel , Yeager Valerie A.
Published: March 2024

This article is one of 3 research briefs that highlight valuable experiences and opportunities that can be thought of as “bright spots” of the governmental public health workforce's pandemic response. Using PH WINS 2021 data, we qualitatively examined responses to an open-ended survey question about workforce experiences during the pandemic response. On-the-job learning was emphasized as a critical component of employees' experiences. Seven “on-the-job learning” subthemes were identified among 91 responses. Findings indicate that the pandemic facilitated opportunities for on-the-job learning for various skills and workplace activities. Public health employees were appreciative of the opportunity to gain new technical and practical skills including communicating with the public and to experience new roles and responsibilities. Respondents reported other related benefits including career growth and leadership opportunities. Highlighting these unexpected benefits of the COVID-19 pandemic is important for employee morale and continued workforce development planning.
Teamwork and Collaboration: Bright Spots of Governmental Public Health Employee Reflections on the COVID-19 Response
Authors: Madsen Emilie R. , Schaffer Kay , Hare Bork Rachel , Yeager Valerie A.
Published: March 2024

The public health emergency response following the outbreak of COVID-19 necessitated greater internal public health agency teamwork and external collaboration. Building on previous research, this article is the third of 3 research briefs that highlight “bright spots” or valuable experiences and opportunities from the COVID-19 response. Using PH WINS 2021 data, we qualitatively examined responses to a question about pandemic workforce experiences. Teamwork and collaboration were emphasized as a critical component of employees' experiences. Across 260 responses, 7 subthemes emerged, generally commemorating the ways that the response effort and employees were supported by teamwork and collaboration. Findings highlight the value of ongoing cross-division teamwork within agencies, the role of leaders in teamwork, and that lessons from teamwork/collaboration experiences can inform organizational system improvements. Maintaining and expanding on improved external collaboration and partnerships should be prioritized for preparing for future emergency events and serving public health communities on a daily basis.
Public Health Nurses’ Proficiencies and Training Needs in an Emergency Response: A Cross-Sectional Observational Study
Authors: Kett Paula M. , Shahrir Shahida , Bekemeier Betty
Published: March 2024

Objective:

To address gaps in understanding the public health nursing workforce regarding competencies recognized as critical during an emergency response.

Design, Setting, and Participants:

A cross-sectional observational study using data with information on local health department staff- and organizational-level characteristics collected from across the United States in 2021. We used logistic regression to estimate the association between 2 binary nurse-specific predictors—(1) whether the staff person was a nurse and (2) whether the staff worked in a local health department that was “nurse-led” (directed by a nurse)—and reported proficiencies important to the COVID-19 response. Models controlled for relevant local health department and community characteristics.

Results:

In the sample, 19% were nurses and 37% were at nurse-led health departments. Nurse versus nonnurse staff had higher odds of reporting proficiencies in skills related to Justice, Equity, Diversity, and Inclusion and in the skill “identifying/applying evidence-based approaches to address public health issues.” However, nurses, compared with their nonnurse peers, had higher odds of reporting training needs in domains related to community engagement, policy engagement, and cross-sectoral collaboration. Conversely, staff at nurse-led health departments, compared with non–nurse-led staff, had higher odds of reporting proficiencies in many of these same areas, including “collaborating across the public health system” and “influencing policies external to the organization that affect community health.” There were no areas in which nurse-led staff had lower odds of reporting proficiencies or higher odds of identifying training needs.

Conclusions:

Findings from this study highlight areas of strength for public health nurses, particularly strengths related to diversity, equity, and inclusion, as well as areas where more training is needed. Such findings can help guide future public health nurse workforce development as well as underscore the value of public health nursing leadership and staff at local health departments for supporting community health.
What are relevant predictors of physical activity in older adults with lower limb loss (LLL)? Results of a retrospective analysis
Authors: Rash Isabelle , Miller William C. , Tao Gordon , Payne Michael W.
Published: March 2024

Background:

People with lower limb loss (LLL) have reduced physical activity (PA). There is evidence of physical and psychosocial predictors of PA in older adults with limb loss. However, these 2 areas (physical/psychosocial) have not been evaluated in the same analysis.

Objectives:

To describe and identify predictors of PA in individuals with LLL.

Study design:

Cross-sectional study.

Methods:

Secondary analysis of data from a multisite Canadian randomized control trial involving community-dwelling prosthetic ambulators with unilateral transtibial or transfemoral amputation (N = 72). The dependent variable was the Physical Activity Scale for the Elderly. Potential predictors were four step square test, 2-minute walk test, Short Physical Performance Battery, Life Space Assessment, walking while talking test, and Activities-specific Balance Confidence scale.

Results:

Seventy-two community-dwelling lower limb prosthesis users were enrolled. The sample included 62 male participants (86%), and 58 participants (81%) had transtibial amputation. The average age of participants was 65 (8.9) years, and for 49 participants (70%), the amputation was over 24 months ago. The total mean Standard Deviation (SD) Physical Activity Scale for the Elderly score was 153.2 (88.3), with scores of 148.1 (11.4) and 184.5 (24.7) for male and female participants, respectively. Regression analysis identified Life Space Assessment (β = 1.15, p = 0.007) and Short Physical Performance Battery (β = 3.51, p = 0.043) as statistically significant predictors accounting for 25% of the variance in PA.

Conclusions:

Community mobility and physical performance are the most meaningful predictors of PA. Future research should examine additional factors (e.g., environment, motivation). Understanding the predictors for PA after LLL would improve clinical practice as clinicians would have increased knowledge to modify and improve training.
Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: results from a multinational clinical trial
Authors: Crowell Trevor A. , Ritz Justin , Zheng Lu , Naqvi Asma , Cyktor Joshua C. , Puleo Joseph , Clagett Brian , Lama Javier R. , Kanyama Cecilia , Little Susan J. , Cohn Susan E. , Riddler Sharon A. , Collier Ann C. , Heath Sonya L. , Tantivitayakul Pornphen , Grinsztejn Beatriz , Arduino Roberto C. , Rooney James F. , van Zyl Gert U. , Coombs Robert W. , Fox Lawrence , Ananworanich Jintanat , Eron Joseph J. , Sieg Scott F. , Mellors John W. , Daar Eric S. ,   for the AIDS Clinical Trials Group (ACTG) A5354/EARLIER Study Team
Published: March 2024

Objective:

To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses.

Design:

Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia.

Methods:

HIV DNA was measured at week 48 of ART in 5 million CD4+ T cells by sensitive qPCR assays targeting HIV gag and pol. Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env, gag, nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines.

Results:

From 2017 to 2019, 188 participants initiated ART during Fiebig stages I (n = 6), II (n = 43), III (n = 56), IV (n = 23), and V (n = 60). Median age was 27 years (interquartile range 23–38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels (P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4+ or CD8+ T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest.

Conclusion:

Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.
Characterisation of anhydro-sialic acid transporters from mucosa-associated bacteria
Authors: Wu Yunhan , Bell Andrew , Thomas Gavin H. , Bolam David N. , Sargent Frank , Juge Nathalie , Palmer Tracy , Severi Emmanuele
Published: March 2024

A corrigendum of this article has been published full details can be found at 10.1099/mic.0.001476

Sialic acid (Sia) transporters are critical to the capacity of host-associated bacteria to utilise Sia for growth and/or cell surface modification. While N-acetyl-neuraminic acid (Neu5Ac)-specific transporters have been studied extensively, little is known on transporters dedicated to anhydro-Sia forms such as 2,7-anhydro-Neu5Ac (2,7-AN) or 2,3-dehydro-2-deoxy-Neu5Ac (Neu5Ac2en). Here, we used a Sia-transport-null strain of Escherichia coli to investigate the function of members of anhydro-Sia transporter families previously identified by computational studies. First, we showed that the transporter NanG, from the Glycoside-Pentoside-Hexuronide:cation symporter family, is a specific 2,7-AN transporter, and identified by mutagenesis a crucial functional residue within the putative substrate-binding site. We then demonstrated that NanX transporters, of the Major Facilitator Superfamily, also only transport 2,7-AN and not Neu5Ac2en nor Neu5Ac. Finally, we provided evidence that SiaX transporters, of the Sodium-Solute Symporter superfamily, are promiscuous Neu5Ac/Neu5Ac2en transporters able to acquire either substrate equally well. The characterisation of anhydro-Sia transporters expands our current understanding of prokaryotic Sia metabolism within host-associated microbial communities.
Effects on antioxidant, whitening, and anti-wrinkle improvement of ethanol extracts from fermented Trigonotis radicans var. sericea by Lactobacillus brevis
Authors: Jeong Da-Eun , Kim Ji-Hye , Kim Byung-Oh , Cho Young-Je
Published: March 2024

This study was designed to compare the effects on antioxidant, whitening, and anti-wrinkle improvement of 60% ethanol extracts from Trigonotis radicans var. sericea (TR) and Lactobacillus brevis-fermented T. radicans var. sericea (FTR). The total phenolics contents of TR was 18.6 mg/g, and FTR was 18.2 mg/g. The HPLC analysis confirmed more phenolic compounds were produced in FTR by bioconversion than in TR. The FTR showed higher 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity than TR. The results of the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation decolorization assay, FTR and TR showed higher activity than BHT (positive control). The FTR (1.21-1.29 PF) showed higher antioxidant protection factor (PF) activity than the TR (1.15-1.22 PF) and showed higher tyrosinase, collagenase and elastase inhibitory activities. This results showed L. brevis-fermentation of Trigonotis radicans var. sericea changed the composition profile and has effects on antioxidant, whitening and anti-wrinkle improvement.
The protective effect of Eucommia ulmoides leaves on high glucose-induced oxidative stress in HT-29 intestinal epithelial cells
Authors: Lee Han Su , Kim Jong Min , Lee Hyo Lim , Go Min Ji , Kim Ju Hui , Eo Hyun Ji , Kim Chul-Woo , Heo Ho Jin
Published: March 2024

This study investigated the protective effect of the aqueous extract of Eucommia ulmoides leaves (AEEL) against high glucose-induced human colon epithelial HT-29 cells. The 2,2'-azino-bis (3-ethyl benzothiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging activities, ferric reducing/antioxidant power (FRAP), and malondialdehyde (MDA) analyses indicated that AEEL had significant antioxidant activities. The 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay showed that AEEL increased cell viability against high glucose-, H2O2-, and lipopolysaccharide (LPS)-induced cytotoxicity in HT-29 cells. Also, the 2'-7'-dichlorodihydrofluorescein diacetate (DCF-DA) assay indicated that AEEL decreased intracellular reactive oxygen species (ROS) against high glucose-, H2O2-, and lipopolysaccharide (LPS)-induced cytotoxicity in HT-29 cells. AEEL showed inhibitory activities against α-glucosidase and inhibited the formation of advanced glycation end products (AGEs). AEEL showed significant positive effects on the viability and titratable acidity of L. brevis. The high-performance liquid chromatogram (HPLC) analysis identified chlorogenic acid and rutin as the major compounds of AEEL. These results suggested that AEEL has the potential to be used as a functional food source to suppress blood glucose levels and protect the gut from high glucose-induced oxidative stress.
Quality characteristics of muffins added with fresh ginseng and different amounts of Gryllus bimaculatus powder
Authors: Kim Ji Hye , Kim Jiyoon , Kim Jung Soo , Kim Insun , Nam Inju , Lim Jeong-Ho , Choe Deokyeong , Moon Kwang-Deog
Published: March 2024

Edible insects, such as the two-spotted cricket (Gryllus bimaculatus, GB), have high nutritional value but are not widely consumed because of their appearance and smell. Consequently, the development of foods containing these insects in less recognizable forms, e.g., flour-like powders, has drawn considerable attention. Herein, we investigated the quality characteristics of muffins prepared from wheat flower supplemented with fresh ginseng (5%) and GB (0, 10, 20, and 40%) powders. GB loading was negatively correlated with muffin volume, height, moisture content, and textural properties (hardness, springiness, cohesiveness, and chewiness) and positively correlated with crude protein content and antioxidant properties. Significant (p<0.05) color differences were observed between samples with different GB loadings. The contents of hexanal and nonanal, which are the major volatiles responsible for off-flavor, increased with increasing GB loading, and the number of volatiles maximized at 40% GB. Sensory preference decreased in the order of 0% GB>10% GB≈20% GB>40% GB. Based on these results, a GB loading of 20% offered the best trade-off between attractiveness and nutritional value. Thus, this study promotes the widespread use of GB in the food industry and the development of various edible-insect-based food products.
Clinical characterization of new-onset chronic musculoskeletal pain in Long COVID: a cross-sectional study
Authors: Khoja Omar , Silva-Passadouro Bárbara , Cristescu Elena , McEwan Katie , Doherty Derek , O’Connell Fiona , Ponchel Frederique , Mulvey Matthew , Astill Sarah , Tan Ai Lyn , Sivan Manoj
Published: March 2024

Purpose

New-onset chronic musculoskeletal (MSK) pain is one of the common persistent symptoms in Long COVID (LC). This study investigated its clinical characteristics, underlying mechanisms, and impact on function, psychological health, and quality of life.

Patients and methods

30 adults (19 female, 11 male) with LC and new-onset chronic MSK pain underwent clinical examination, Quantitative Sensory Testing (QST), and blood tests for inflammatory markers, and completed the following outcome measures: Timed Up and Go test (TUG), handgrip strength test, COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), Brief Pain Inventory (BPI), Pain Self-Efficacy Questionnaire (PSEQ), Pain Catastrophizing Scale (PCS), International Physical Activity Questionnaire - short form (IPAQ-sf), Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and EuroQol Five Dimensions health-related quality of life (EQ-5D-5L).

Results

New-onset chronic MSK pain was widespread and continuous in nature, and worse in the joints. When compared to normative values reported in the literature: a) QST revealed mechanical hyperalgesia, heightened temporal summation of pain, and hypoesthesia to vibration stimuli, which is strongly suggestive of central sensitization; b) Plasma cytokine assays indicated distinct pro-inflammatory profiles; c) TUG time indicated reduced balance and mobility; d) handgrip strength revealed general weakness; e) physical activity was lower ; and f) there were moderate levels of depression and anxiety with lower self-efficacy scores and lower levels of pain catastrophizing. LC symptoms were of moderate severity (44.8/100), moderate functional disability (22.8/50) and severely compromised overall health (2.6/10) when compared to pre-COVID scores.

Conclusion

New-onset chronic MSK pain in LC tends to be widespread, constant, and associated with weakness, reduced function, depression, anxiety, and reduced quality of life. There is associated central sensitization and proinflammatory state in the condition. Further research is essential to explore the longitudinal progression and natural evolution of the new-onset chronic MSK pain in LC.
Pediatric Diabetic Ketoacidosis (PDKA) among newly diagnosed diabetic patients at Dilla University Hospital, Dilla, Ethiopia: prevalence and predictors
Authors: oyamo Dinberu
Published: March 2024

Background

Diabetic ketoacidosis is a morbid complication of diabetes mellitus, and its occurrence at diagnosis has rarely been studied in Ethiopia, despite the many cases seen in the pediatric population.

Objective

To know the prevalence of diabetic ketoacidosis (DKA) among patients with newly diagnosed diabetes mellitus and identify avoidable risk factors.

Method

This institution-based retrospective cross-sectional study was conducted from December 25, 2018 to December 25, 2022. Newly diagnosed type1 diabetes mellitus (DM) patients with age < 15 years were included in the study. DKA was diagnosed based on clinical presentation and blood glucose and urine ketone levels. A data collection form was prepared to collect sociodemographic and clinical data. Descriptive, bivariate, and multivariate logistic regression analyses were performed to identify the risk factors.

Result

Among the admitted 61 newly diagnosed T1DM pediatric patients, DKA was the first presentation in 37 patients making 60.7% of newly diagnosed T1DM. Mean age at diagnosis was 8(±3.85) years and females were affected more. Clinical presentation revealed vomiting accompanied by signs of dehydration (32.4%), with polysymptoms (29.7%) being the most common. Infectious morbidity occurred in 26 patients, 21 of whom were in the DKA group. Inadequate knowledge of signs and symptoms of DM adjusted odds ratio (AOR=0.07(0.019-0.0897), absence of a family history of DM (AOR=0.129 (0.019-0.897), and presence of infection prior to diagnosis of DKA (AOR=11.69(1.34-10.1) were potential predictors for the development of DKA among newly diagnosed T1DM patients

Conclusion

A very high number of children present with DKA at the initial diagnosis of diabetes mellitus (DM), which is attributed to inadequate knowledge of the signs and symptoms of DM and the masking effect of concomitant infections in these children. Healthcare professionals should endeavor to suspect and screen children. Continuous awareness creation of DM at the health professional and community levels is encouraged to diagnose diabetes mellitus earlier and to decrease the prevalence of DKA as an initial presentation.
Insulin resistance, and not β-cell impairment, mediates association betweenMycobacterium tuberculosissensitization and type II diabetes mellitus among US adults
Authors: Magodoro IM , Aluoch A , Claggett B , Nyirenda MJ , Siedner MJ , Wilkinson KA , Wilkinson RJ , Ntusi NAB
Published: March 2024

Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection withMycobacterium tuberculosis (M.tb)by mechanisms that remain to be fully explained. We evaluated association betweenM.tbsensitization and T2DM among U.S adults and, via formal mediation analysis, the extent to which this association is mediated by insulin resistance and/or β-cell failure. These evaluations accounted for demographic, socio-economic, behavioral and clinical characteristics. T2DM was assessed by fasting plasma glucose, 2-hour oral glucose tolerance testing and HbA1c; homoeostasis model assessment 2 (HOMA2) was used to estimate β-cell dysfunction (HOMA2-B) and insulin resistance (HOMA2-IR); whileM.tbsensitization status was ascertained by tuberculin skin testing (TST). Exposure toM.tbwas associated with increased risk for T2DM, likely driven by an increase in insulin resistance. Definitive prospective studies examining incident T2DM following tuberculosis are warranted.

Research in Context

What is already known about this subject?

Accumulating evidence suggests that pre-diabetes and new-onset type 2 diabetes mellitus (T2DM) may be a long-term complication of exposure toMycobacterium tuberculosis(M.tb) via mechanisms that remain to be unraveled

What is the key question?

To what extent do insulin resistance and β-cell failure mediate the association betweenM.tbsensitization with T2DM among US adults?

What are the new findings?

M.tbsensitization is characterized by distinct glucose metabolic disturbances manifesting as increased risk of T2DM and isolated impaired fasting glucose (IFG)

Insulin resistance, and not β-cell impairment, likely independently mediate the observed diabetogenic effects ofM.tbsensitization

How might this impact on clinical and/or public health practice in the foreseeable future?

If corroborated by prospective studies, both TB programs and individual clinical care must incorporate monitoring of serum glucose and long-term metabolic outcomes

This will be particularly urgent in sub-Saharan Africa and South-East Asia where scarce health resources coincide with overlapping endemic TB and epidemic T2DM
The Investigation of Nonlinear Variability Underlying Postural Control in The Injure-Limb in Individuals with and without Chronic Ankle Instability
Authors: Sugimoto Yuki A. , McKeon Patrick O. , Rhea Christopher K. , Schmitz Randy J. , Henson Robert A. , Mattacola Carl G. , Ross Scott E.
Published: March 2024

Background

Less flexible and adaptable sensorimotor systems reflect in movement variability in individuals with Chronic Ankle Instability (CAI), which may limit their ability to detect relevant information using a variety of primary sensory feedback. Thus, the aim of the study was to investigate underlying biological noise pertaining to postural control in single-limb stance during increased environmental constraints with sensory feedback manipulations in individuals with and without CAI.

Methods

Forty-two individuals with and without CAI participated in the study. A one-way ANOVA was utilized to examine group differences in biological noise underlying postural control during the SOT conditions in single-limb stance.

Results

Individuals with CAI demonstrated significantly lower SampEN while maintaining posture during Condition 5 (P=.037) and Condition 6 (P=.030), where they were forced to exclusively rely on vestibular feedback, in single-limb stance compared to healthy controls.

Discussion

Individuals with CAI did not demonstrate decreased movement variability pertaining to postural control during all six SOT conditions. Those participants with CAI only displayed decreased movement variability when they were forced to executively rely on vestibular feedback while maintaining posture in the injured-limb compared to healthy controls.
Genetic liability for anxiety associates with treatment response to the monoamine stabilizer OSU6162 in alcohol dependence
Authors: Hong Mun-Gwan , Khemiri Lotfi , Guterstam Joar , Franck Johan , Jayaram-Lindström Nitya , Melas Philippe A.
Published: March 2024

OSU6162, a monoamine stabilizer, has demonstrated efficacy in reducing alcohol and anxiety-related behaviors in preclinical settings. In a previous randomized, double-blind, placebo-controlled trial involving patients with alcohol dependence (AD), we found that OSU6162 significantly reduced craving for alcohol, but did not alter drinking behaviors. In the present study, we explored the hypothesis that genetic predispositions related to AD or associated traits, might influence the response to OSU6162 treatment in original trial participants (N=56). To investigate this, we calculated polygenic risk scores (PRSs) over several statistical significance thresholds from genome-wide association studies on (i) alcohol use disorder and alcohol consumption (N=200-202k), (ii) problematic alcohol use (N=435k), (iii) drinks per week (N=666k), (iv) major depression (N=500k), and (v) anxiety (using both case-control comparisons and quantitative anxiety factor scores, N=17-18k). Linear regression analyses assessing the interaction effects between PRSs and treatment type (OSU6162 or placebo) identified significant associations when considering anxiety factor scores (FDR<0.05). Specifically, in OSU6162-treated AD individuals, there was a negative correlation between anxiety factor PRS (at the genome-wide significance threshold that included one genetic variant) and several drinking outcomes, including number of drinks consumed, percentage of heavy drinking days, and changes in blood phosphatidylethanol (PEth) levels. These correlations were absent in the placebo group. While preliminary, these findings suggest the potential utility of anxiety PRS in predicting response to OSU6162 treatment in AD. Further research using larger cohorts and more comprehensive genetic data is necessary to confirm these results and to advance personalized medicine approaches in alcohol use disorder.
Application of Quantum Tensor Networks for Protein Classification
Authors: Kundu Debarshi , Ghosh Archisman , Ekambaram Srinivasan , Wang Jian , Dokholyan Nikolay , Ghosh Swaroop
Published: March 2024

Computational methods in drug discovery significantly reduce both time and experimental costs. Nonetheless, certain computational tasks in drug discovery can be daunting with classical computing techniques which can be potentially overcome using quantum computing. A crucial task within this domain involves the functional classification of proteins. However, a challenge lies in adequately representing lengthy protein sequences given the limited number of qubits available in existing noisy quantum computers. We show that protein sequences can be thought of as sentences in natural language processing and can be parsed using the existing Quantum Natural Language framework into parameterized quantum circuits of reasonable qubits, which can be trained to solve various proteinrelated machine-learning problems. We classify proteins based on their sub-cellular locations—a pivotal task in bioinformatics that is key to understanding biological processes and disease mechanisms. Leveraging the quantum-enhanced processing capabilities, we demonstrate that Quantum Tensor Networks (QTN) can effectively handle the complexity and diversity of protein sequences. We present a detailed methodology that adapts QTN architectures to the nuanced requirements of protein data, supported by comprehensive experimental results. We demonstrate two distinct QTNs, inspired by classical recurrent neural networks (RNN) and convolutional neural networks (CNN), to solve the binary classification task mentioned above. Our top-performing quantum model has achieved a 94% accuracy rate, which is comparable to the performance of a classical model that uses the ESM2 protein language model embeddings. It’s noteworthy that the ESM2 model is extremely large, containing 8 million parameters in its smallest configuration, whereas our best quantum model requires only around 800 parameters. We demonstrate that these hybrid models exhibit promising performance, showcasing their potential to compete with classical models of similar complexity.
Reproductive restraint to avoid the costs of reproductive conflict in a cooperatively breeding mammal
Authors: Birch Graham , Nichols Hazel J. , Mwanguhya Francis , Cant Michael A. , Blount Jonathan D.
Published: March 2024

The costs of reproductive conflict can be an important factor shaping the evolution of life histories in animal societies. These costs may change as individuals age and grow, and with within-group competition. Social costs of reproductive conflict have been invoked to explain why females might gain from delaying maturity or ceasing reproduction midway through life, but not in males. Here we analyze more than 20 years of data to understand how individual male banded mongooses adjust their reproductive activity in response to the costs of reproductive conflict. In banded mongooses groups multiple female breeders enter oestrus synchronously and males compete to mate guard the females. The oldest and heaviest males in the group gained the greatest share of paternity, while younger and lighter males obtained little or no paternity. Those lighter males that are reproductively active paid disproportionate survival costs. Our results suggest that by delaying or suppressing reproduction early in life, males may reduce their mortality. Males may also avoid inflicting costs on their male kin by queuing. These results from an egalitarian cooperative breeding mammal may provide a rare example of voluntary reproductive restraint, although we cannot discount reproductive suppression by rival males.
Adaptation to visual sparsity enhances responses to infrequent stimuli
Authors: Gou Tong , Matulis Catherine A , Clark Damon A
Published: March 2024

Sensory systems adapt their response properties to the statistics of their inputs. For instance, visual systems adapt to low-order statistics like mean and variance to encode the stimulus efficiently or to facilitate specific downstream computations. However, it remains unclear how other statistical features affect sensory adaptation. Here, we explore how Drosophila's visual motion circuits adapt to stimulus sparsity, a measure of the signal's intermittency not captured by low-order statistics alone. Early visual neurons in both ON and OFF pathways alter their responses dramatically with stimulus sparsity, responding positively to both light and dark sparse stimuli but linearly to dense stimuli. These changes extend to downstream ON and OFF direction-selective neurons, which are activated by sparse stimuli of both polarities, but respond with opposite signs to light and dark regions of dense stimuli. Thus, sparse stimuli activate both ON and OFF pathways, recruiting a larger fraction of the circuit and potentially enhancing the salience of infrequent stimuli. Overall, our results reveal visual response properties that increase the fraction of the circuit responding to sparse, infrequent stimuli.
Sensory and perceptual decisional processes underlying the perception of reverberant auditory environments
Authors: García-Lázaro Haydée G , Teng Santani
Published: March 2024

Reverberation, a ubiquitous feature of real-world acoustic environments, exhibits statistical regularities that human listeners leverage to self-orient, facilitate auditory perception, and understand their environment. Despite the extensive research on sound source representation in the auditory system, it remains unclear how the brain represents real-world reverberant environments. Here, we characterized the neural response to reverberation of varying realism by applying multivariate pattern analysis to electroencephalographic (EEG) brain signals. Human listeners (12 male and 8 female) heard speech samples convolved with real-world and synthetic reverberant impulse responses and judged whether the speech samples were in a “real” or “fake” environment, focusing on the reverberant background rather than the properties of speech itself. Participants distinguished real from synthetic reverberation with ∼75% accuracy; EEG decoding reveals a multistage decoding time course, with dissociable components early in the stimulus presentation and later in the peri-offset stage. The early component predominantly occurred in temporal electrode clusters, while the later component was prominent in centro-parietal clusters. These findings suggest distinct neural stages in perceiving natural acoustic environments, likely reflecting sensory encoding and higher-level perceptual decision-making processes. Overall, our findings provide evidence that reverberation, rather than being largely suppressed as a noise-like signal, carries relevant environmental information and gains representation along the auditory system. This understanding also offers various applications; it provides insights for including reverberation as a cue to aid navigation for blind and visually impaired people. It also helps to enhance realism perception in immersive virtual reality settings, gaming, music, and film production.

SIGNIFICANCE

In real-world environments, multiple acoustic signals coexist, typically reflecting off innumerable surrounding surfaces as reverberation. While reverberation is a rich environmental cue and a ubiquitous feature in acoustic spaces, we do not fully understand how our brains process a signal usually treated as a distortion to be ignored. When asking human participants to make perceptual judgments about reverberant sounds during EEG recordings, we identified distinct, sequential stages of neural processing. The perception of acoustic realism first involves encoding low-level reverberation acoustic features and their subsequent integration into a coherent environment representation. This knowledge provides insights for enhancing realism in immersive virtual reality, music, and film production, and using reverberation to guide navigation for blind and visually impaired people.
Effect of spatial overdispersion on confidence intervals for population density estimated by spatial capture–recapture
Authors: Efford Murray G. , Fletcher David
Published: March 2024

Spatially explicit capture–recapture models are used widely to estimate the density of animal populations. The population is represented by an inhomogeneous Poisson process, where each point is the activity center of an individual and density corresponds to the intensity surface. Estimates of average density are robust to unmodeled inhomogeneity, but the coverage of confidence intervals is poor when the intensity surface is stochastic. Poor coverage is due to overdispersion of the number of detected individualsnwith respect to the fitted Poisson distribution. We investigated overdispersion from stochastic generating models (log-Gaussian Cox process and Thomas cluster process). Variation in a scalar measure of local density – the detection-weighted mean density – predicts overdispersion when the generating process is known. A previously proposed correction for overdispersion was successful only in limited cases: rigorous correction for spatial overdispersion requires prior knowledge of the generating process. The problem is lessened by assuming population size to be fixed, but this assumption cannot be justified for common study designs.
Age-dependent somatic expansion of theATXN3CAG repeat in the blood and buccal cell DNA of individuals with spinocerebellar ataxia type 3
Authors: Sidky Ahmed M. , Melo Ana Rosa Vieira , Kay Teresa T. , Raposo Mafalda , Lima Manuela , Monckton Darren G.
Published: March 2024

Spinocerebellar ataxia type 3 (SCA3), a currently untreatable disorder, is caused by the expansion of a genetically unstable polyglutamine-encoding complex CAG repeat in theATXN3gene. Longer alleles are generally associated with earlier onset and frequent intergenerational expansions mediate the anticipation observed in this disorder. Somatic expansion of the repeat has also been implicated in disease progression and slowing the rate of somatic expansion in patients has recently been proposed as a therapeutic strategy. Here, we utilised high-throughput ultra-deep MiSeq amplicon sequencing of theATXN3repeat to precisely define the number of repeats, the exact sequence structure, the phased genotype of an adjacent single nucleotide polymorphism and to accurately quantify somatic expansion in blood and buccal cell DNA samples of a cohort of individuals with SCA3 from the Azores islands (Portugal). We revealed systematic mis-sizing of theATXN3repeat and high levels of inaccuracy of the traditional fragment length analysis approach that have important implications for attempts to identify modifiers of clinical and molecular phenotypes, including genetic instability. Quantification of somatic expansion in blood DNA revealed the expected effects of age and CAG repeat length, although the effect of repeat length was surprisingly modest with much stronger associations with age at sampling. We also observed an association of the downstream rs12895357 single nucleotide polymorphism with the rate of somatic expansion, and a higher level of somatic expansion in buccal cell DNA compared to blood. Although the levels of somatic expansion are much lower per repeat unit, the average level of somatic expansion at theATXN3locus in SCA3 patients is much higher than is typically observed at theHTTlocus in Huntington disease patients. These data suggest that theATXN3locus in SCA3 patients in blood or buccal cell DNA might serve as a good biomarker for clinical trials testing suppressors of somatic expansion with peripheral exposure.
Increased malondialdehyde and nitric oxide formation, lowered total radical trapping capacity coupled with psychological stressors largely predict the phenome of first-episode mild depression in undergraduate students
Authors: Brinholi Francis F. , Vasupanrajit Asara , Semeão Laura de O. , Michelin Ana Paula , Matsumoto Andressa K. , Almulla Abbas F. , Tunvirachaisakul Chavit , Barbosa Decio S. , Maes Michael
Published: March 2024

Undergraduate students are frequently afflicted by major depressive disorder (MDD). Oxidative and nitrosative stress (O&NS) has been implicated in the pathophysiology of MDD. There is no information regarding whether mild outpatient MDD (SDMD) and first episode SDMD (FE-SDMD) are accompanied by O&NS. The current study compared lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced protein oxidation products, nitric oxide metabolites (NOx), thiol groups, plasma total antioxidant potential (TRAP), and paraoxonase 1 activities among SDMD and FE-SDMD patients versus healthy controls. We found that SDMD and FE-SDMD exhibit elevated MDA and NOx, and decreased TRAP and LOOH as compared with controls. There was a significant and positive correlation between O&NS biomarkers and adverse childhood experiences (ACEs), and negative life events (NLEs). O&NS pathways, NLEs and ACEs accounted for 51.7% of the variance in the phenome of depression, and O&NS and NLS explained 42.9% of the variance in brooding. Overall, these results indicate that SDMD and FE-SDMD are characterized by reduced total antioxidant defenses and increased aldehyde and NOx production. The combined effects of oxidative and psychological stressors substantially predict the manifestation of SDMD. The differences with multi-episode MDD are attributed to specific effects of recurrence of illness and staging of illness.
Assessing the value and knowledge gains from an online tick identification and tick-borne disease management course for the Southeastern United States
Authors: Lippi Catherine A. , Gaff Holly D. , White Alexis L. , Ryan Sadie J.
Published: March 2024

Background

Tick-borne diseases are a growing public health threat in the United States. Despite the prevalence and rising burden of tick-borne diseases, there are major gaps in baseline knowledge and surveillance efforts for tick vectors, even among vector control districts and public health agencies. To address this issue, an online tick training course (OTTC) was developed through the Southeastern Center of Excellence in Vector-Borne Diseases (SECOEVBD) to provide a comprehensive knowledge base on ticks, tick-borne diseases, and their management.

Methods

The OTTC consisted of training modules covering topics including tick biology, tick identification, tick-borne diseases, and public health, personal tick safety, and tick surveillance. The course was largely promoted to vector control specialists and public health employees throughout the Southeastern US. We collected assessment and survey data on participants to gauge learning outcomes, perceptions of the utility of knowledge gained, and barriers and facilitators to applying the knowledge in the field.

Results

The OTTC was successful in increasing participants’ baseline knowledge across all course subject areas, with the average score on assessment increasing from 62.6% (pre-course) to 86.7% (post-course). More than half of participants (63.6%) indicated that they would definitely use information from the course in their work. Barriers to using information identified in the delayed assessment included lack of opportunities to apply skills (18.5%) and the need for additional specialized training beyond what the OTTC currently offers (18.5%), while the main facilitator (70.4%) for applying knowledge was having opportunities at work, such as an existing tick surveillance program.

Conclusions

Overall, this OTTC demonstrated capacity to improve knowledge in a necessary and underserved public health field, and more than half of participants use or plan to use the information in their work. The geographic reach of this online resource was much larger than simply for the Southeastern region for which it was designed, suggesting a much broader need for this resource. Understanding the utility and penetrance of training programs such as these is important for refining materials and assessing optimal targets for training.