bluuebunny/crossref_metadata_2025 huggingface dataset:
Removal of Contaminated Personal Protective Equipment With and Without Supervision. A Randomized Crossover Simulation-Based Study
Authors: Somri Mostafa , Hochman Ohad , Somri-Gannam Lina , Gaitini Luis , Paz Alona , Bumard Tami , Gómez-Ríos Manuel Á.
Published: April 2023

Introduction

Personal protective equipment (PPE) reduces the risk of pathogens reaching the skin and clothing of health care personnel. We hypothesize that doffing PPE following verbal instructions by a supervisor is more effective in reducing contamination compared with doffing without verbal instructions. Our primary aim was to determine contamination rates with and without supervised doffing. The secondary aim was to determine the number and localization of contaminated body sites and PPE removal times in both groups.

Methods

Staff members of Bnai Zion Medical Center participated in this single-center, randomized simulation study (NCT05008627). Using a crossover design, all participants donned and doffed the PPE twice, once under guidance from a trained supervisor and then independently without supervision (group A), or vice versa (group B). Participants were randomized to either group A or B using a computer-generated random allocation sequence. The PPE was “contaminated” with Glo Germ on the thorax, shoulders, arms, hands, legs, and face shield. After doffing the PPE, the participant was examined under ultraviolet light to detect traces of contamination. The following variables were collected: contamination rates, the number and localization of contaminated body sites, and PPE doffing time.

Results

Forty-nine staff members were included. In group A, the contamination rate was significantly lower (8% vs. 47%; χ2 = 17.19; p < 0.001). The sites most frequently contaminated were the neck and hands. Mean PPE doffing time under verbal instructions was significantly longer [mean (SD): 183.98 (3.63) vs. 68.43 (12.75) seconds, P < 0.001] compared with unsupervised doffing.

Conclusions

In a simulated setting, PPE doffing following step-by-step verbal instructions from a trained supervisor reduces the rate of contamination but prolongs doffing time. These findings could have important implications for clinical practice and could further protect health care workers against contamination from emerging and high-consequence pathogens.
The Correlation of Diabetes Mellitus and Urinary Retention From Intravesical OnabotulinumtoxinA Injection for Overactive Bladder
Authors: Takashima Yoko , Handler Stephanie , Laus Katharina , Eckhardt Sarah , Whitaker Taylor , Tenggardjaja Christopher , Yazdany Tajnoos
Published: April 2023

Importance and Objectives

The objective was to determine whether patients with diabetes mellitus (DM) treated with intravesical onabotulinumtoxinA (BoNT) injection for overactive bladder (OAB) had increased urinary retention requiring clean intermittent catheterization (CIC), as well as the impact of disease duration and severity. We hypothesize that patients with DM will have higher rates of retention after BoNT injection.

Study Design

We performed a retrospective cohort analysis of women in the Kaiser Permanente Southern California Health System who underwent BoNT injection for OAB, excluding women with a history of urinary retention or neurogenic bladder.

Results

We identified 565 patients, 410 in the control group and 155 in the DM group. No significant difference was found in the rate of CIC (9% in the control group versus 5.8% in the DM group, P = 0.2), voiding dysfunction, and peak postprocedure postvoid residual volume (PVR). Patients with diabetes had a significantly increased rate of postprocedure urinary tract infection (UTI; 27.6% versus 38.1%, P = 0.02). Urinary tract infection was significantly associated with urinary retention (adjusted odds ratio [OR], 2.26; 95% confidence interval [CI], 1.02–4.99; P = 0.045) and peak PVR ≥200 mL (adjusted OR, 2.42; 95% CI, 1.15–5.06; P = 0.019). Diabetic disease duration and severity were not a predictor of urinary retention, elevated PVR, or voiding dysfunction; however, the presence of ≥1 disease-related complication was a predictor of UTI (adjusted OR, 2.81; 95% CI, 1.34–5.91; P = 0.006).

Conclusions

Diabetic patients had a similar rate of urinary retention requiring CIC after BoNT injection for OAB compared with nondiabetic patients. Diabetic patients had an increased risk of UTI based on disease severity.
Fucoxanthin protects retinal ganglion cells and promotes parkin-mediated mitophagy against glutamate excitotoxicity
Authors: Lian Wei , Hu Xinxin , Zhang Juntao , Wu Yufei , Zhao Na , Ma Haixia , He Hengqian , Lu Qinkang
Published: April 2023

Objective

To clarify whether fucoxanthin plays a protective role and regulates parkin-mediated mitophagy on retinal ganglion cells (RGCs) against glutamate excitotoxicity.

Methods

The excitotoxicity model of primary RGCs was carried out with glutamate. Mitochondrial membrane potential was measured by JC-1 kit (Abcam, USA). The apoptotic rate and cytotoxicity were detected by Hoechst staining and lactate dehydrogenase (LDH) kit (Takara, Japan). Mitochondria was assessed by MitoTracker staining and confocal microscopy. The mRNA levels and protein expression levels of Bax, Bcl-2, parkin, optineurin, LC3, and LAMP1 in RGCs were analyzed by quantitative PCR and immunoblotting. Finally, the mitochondrial health score and mitophagy were assessed by transmission electron microscopy.

Results

Fucoxanthin increased the mitochondrial membrane potential of RGCs, reduced cytotoxicity, and decreased apoptosis in RGCs under glutamate excitotoxicity. It also enhanced expression levels of parkin, optineurin, and LAMP1, and upgraded the ratio of LC3-II to LC3-I. Meanwhile, fucoxanthin increased LC3 and MitoTracker co-localization staining. In addition, up-regulated mitochondrial health score, and the number of autophagosomes and mitophagosomes were observed in fucoxanthin-treated RGCs under glutamate excitotoxicity.

Conclusion

Fucoxanthin may exert its neuroprotective effect on RGCs via promoting parkin-mediated mitophagy under glutamate excitotoxicity. The neuroprotective effect of fucoxanthin in glaucomatous neurodegeneration and ocular diseases characterized by impaired mitophagy warrants further investigation.
Does MOED Rhyme with FRUIT? An event-related potential study of cross-language rhyming
Authors: Botezatu Mona Roxana
Published: April 2023

The study aimed to characterize the event-related potentials signature elicited by visual rhyme judgements across two alphabetic orthographies that differ in depth (shallow: Dutch; deep: English) and by spelling-sound consistency in a deep L2-English orthography. Twenty-four Dutch-English bilinguals who varied on measures of L2-English proficiency, made rhyme judgments of semantically unrelated Dutch-English word pairs presented sequentially in the visual modality, while behavioral and electrophysiological responses were recorded. The spelling-sound consistency of target words was varied systematically. Nonrhyming targets elicited a larger N450 amplitude than rhyming targets, indicating sensitivity to mismatching phonology across languages. English target words with consistent spelling-sound mappings elicited less negative N250 amplitudes when preceded by rhyming Dutch primes. Overall, event-related potentials revealed robust responses to phonological mismatch, but subtle responses to spelling-sound inconsistency in L2-English. Results suggest that bilingual readers of a shallow L1 orthography who are immersed in an L1-speaking environment may not tune into the degree of spelling-sound consistency of a deep L2 orthography.
Electroacupuncture intervention on stress-induced cardiac autonomic imbalance in rats involves corticotropin-releasing hormone system activity
Authors: Zhu Li , Ye Zhen , Zhang Mengting , Xu Weichen , Wang Ruwen , Wu Shengbing , Gao Heren
Published: April 2023

Autonomic imbalance is a core aspect of stress response that strongly correlates to cardiovascular diseases. Enhanced activity of the central corticotropin-releasing hormone (CRH) system may result in autonomic imbalance to cause cardiovascular responses in a stress state. Electroacupuncture at PC6 acupoints has been demonstrated to prevent and treat cardiovascular diseases. In this study, we aim to demonstrate the protective role of electroacupuncture at PC6 in ameliorating cardiac autonomic imbalance and investigate the underlying mechanisms in immobilization stress rats. Four groups were subjected. Immobilization stress was applied to three groups. And the rats in two electroacupuncture-intervened groups exerted electroacupuncture at PC6 or tail respectively. Then, we performed ECG recording for heart rate variability (HRV) analysis, and rats were sacrificed after experiments for biological analysis. HRV analysis indicated that electroacupuncture at PC6 improved the enhanced low-frequency band of the power spectrum (LF), the reduced high-frequency band of the power spectrum (HF), and the enhanced LF/HF ratio caused by immobilization stress. Besides, electroacupuncture at PC6 significantly decreased phosphorylated tyrosine hydroxylase expression and increased acetylcholine esterase expression in heart of immobilization stress rats. Furthermore, electroacupuncture at PC6 significantly decreased CRH level and CRH 1 type receptor and CRH 2 type receptor (CRHR2) expressions in the rostral ventrolateral medulla (RVLM), and CRH level and CRHR2 expression in the nucleus of the solitary tract (NTS) of immobilization stress rats. Our findings suggest that electroacupuncture at PC6 can ameliorate stress-induced cardiac autonomic imbalance by modulating the CRHergic input in the RVLM and NTS.
Age-dependent effects of resveratrol in hypothalamic astrocyte cultures
Authors: Leite Santos Camila , K. Vizuete Adriana Fernanda , Becker Weber Fernanda , Thomaz Natalie K. , Bobermin Larissa Daniele , Gonçalves Carlos-Alberto , Quincozes-Santos André
Published: April 2023

Objectives

The hypothalamus plays critical roles in maintaining brain homeostasis and increasing evidence has highlighted astrocytes orchestrating several of hypothalamic functions. However, it remains unclear how hypothalamic astrocytes participate in neurochemical mechanisms associated with aging process, as well as whether these cells can be a target for antiaging strategies. In this sense, the aim of this study is to evaluate the age-dependent effects of resveratrol, a well-characterized neuroprotective compound, in primary astrocyte cultures derived from the hypothalamus of newborn, adult, and aged rats.

Methods

Male Wistar rats (2, 90, 180, and 365 days old) were used in this study. Cultured astrocytes from different ages were treated with 10 and 100 μM resveratrol and cellular viability, metabolic activity, astrocyte morphology, release of glial cell line-derived neurotrophic factor (GDNF), transforming growth factor β (TGF-β), tumor necrosis factor α (TNF-α), interleukins (IL-1β, IL-6, and IL-10), as well as the protein levels of Nrf2 and HO-1 were evaluated.

Results

In vitro astrocytes derived from neonatal, adults, and aged animals changed metabolic activity and the release of trophic factors (GDNF and TGF-β), as well as the inflammatory mediators (TNF-α, IL-1β, IL-6, and IL-10). Resveratrol prevented these alterations. In addition, resveratrol changed the immunocontent of Nrf2 and HO-1. The results indicated that the effects of resveratrol seem to have a dose- and age-associated glioprotective role.

Conclusion

These findings demonstrate for the first time that resveratrol prevents the age-dependent underlying functional reprogramming of in vitro hypothalamic astrocytes, reinforcing its antiaging activity, and consequently, its glioprotective role.
Suppression of perceptual sensitivity to digital nerve stimulation induced by afferent volley from digital nerve of contralateral homologous finger
Authors: Fukuda Shiho , Tsujinaka Ryo , Oda Hitoshi , Hamada Naoki , Matsuoka Masakazu , Hiraoka Koichi
Published: April 2023

The purpose of the present study is to investigate whether perceptual sensitivity to digital nerve stimulation is modulated by the afferent volley from the digital nerve of a contralateral finger. Fifteen healthy humans participated in this study. A test stimulus was given to the right-hand index finger, and a conditioning stimulus was given to one of the five fingers on the left hand 20, 30, or 40 ms before the test stimulus. The perceptual threshold of the finger stimulation was measured. The perceptual threshold of the test stimulus was significantly increased by a conditioning stimulus to the left-hand index finger given 40 ms before the test stimulus. In contrast, the threshold was not significantly changed by a conditioning stimulus to any finger other than the index finger. Perceptual sensitivity to digital nerve stimulation is suppressed by the afferent volley from the digital nerve of the contralateral homologous finger. This means that the afferent volley from the digital nerve suppresses the homologous finger representation in the ipsilateral somatosensory areas. These findings can be explained by the view that the afferent volley from the digital nerve of the index finger projects to the index finger representation in the contralateral primary sensory cortex and that the interhemispheric transcallosal inhibitory drive is provided from the secondary sensory cortex to the homologous finger representation in the contralateral secondary sensory cortex.
Interaction of the synthetic cannabinoid WIN55212 with tramadol on nociceptive thresholds and core body temperature in a chemotherapy-induced peripheral neuropathy pain model
Authors: Haddad Mansour , Alsalem Mohammad , Saleh Tareq , Jaffal Sahar M. , Barakat Noor A. , El-Salem Khalid
Published: April 2023

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse effect of many anticancer drugs. Current strategies for the management of CIPN pain are still largely unmet. The aim of this study is to investigate the antinociceptive potential of combining tramadol with the synthetic cannabinoid WIN55212, and to evaluate their associated adverse effects, separately or in combination, in a CIPN rat model, and to investigate their ability to modulate the transient receptor potential vanilloid 1 (TRPV1) receptor activity. Von Frey filaments were used to determine the paw withdrawal threshold in adult male Sprague–Dawley rats (200–250 g) following intraperitoneal (i.p) injection of cisplatin. Single cell ratiometric calcium imaging was used to investigate WIN55212/tramadol combination ability to modulate the TRPV1 receptor activity. Both tramadol and WIN55212 produced dose-dependent antinociceptive effect when administered separately. The lower dose of tramadol (1 mg/kg) significantly enhanced the antinociceptive effects of WIN55212 without interfering with core body temperature. Mechanistically, capsaicin (100 nM) produced a robust increase in [Ca2+]i in dorsal root ganglia (DRG) neurons ex vivo. Capsaicin-evoked calcium responses were significantly reduced upon pre-incubation of DRG neurons with only the highest concentration of tramadol (10 µM), but not with WIN55212 at any concentration (0.1, 1 and 10 µM). However, combining sub-effective doses of WIN55212 (1 µM) and tramadol (0.1 µM) produced a significant inhibition of capsaicin-evoked calcium responses. Combining WIN55212 with tramadol shows better antinociceptive effects with no increased risk of hypothermia, and provides a potential pain management strategy for CIPN.
PK1 from
Drosophila
obscurin is an inactive pseudokinase with scaffolding properties
Authors: Zacharchenko Thomas , Dorendorf Till , Locker Nicolas , Van Dijk Evert , Katzemich Anja , Diederichs Kay , Bullard Belinda , Mayans Olga
Published: April 2023

Obscurins are large filamentous proteins with crucial roles in the assembly, stability and regulation of muscle. Characteristic of these proteins is a tandem of two C-terminal kinase domains, PK1 and PK2, that are separated by a long intrinsically disordered sequence. The significance of this conserved domain arrangement is unknown. Our study of PK1 from
Drosophila
obscurin shows that this is a pseudokinase with features typical of the CAM-kinase family, but which carries a minimalistic regulatory tail that no longer binds calmodulin or has mechanosensory properties typical of other sarcomeric kinases. PK1 binds ATP with high affinity, but in the absence of magnesium and lacks detectable phosphotransfer activity. It also has a highly diverged active site, strictly conserved across arthropods, that might have evolved to accommodate an unconventional binder. We find that PK1 interacts with PK2, suggesting a functional relation to the latter. These findings lead us to speculate that PK1/PK2 form a pseudokinase/kinase dual system, where PK1 might act as an allosteric regulator of PK2 and where mechanosensing properties, akin to those described for regulatory tails in titin-like kinases, might now reside on the unstructured interkinase segment. We propose that the PK1-interkinase-PK2 region constitutes an integrated functional unit in obscurin proteins.
A case of atypical vivax malaria with a global review of reports on myriads of morpho-variations in parasitized red blood cells
Authors: Biswal Debasish , Mirdha Bijay Ranjan
Published: April 2023

Plasmodium vivax, one of the major species associated with human malaria, continues to be a major public health problem in many parts of the world. Numerous studies related to vivax malaria have described quantitative haematological findings (level of haemoglobin, thrombocytopaenia, haematocrit values), but diverse morphological changes of parasite forms within infected red blood cells (iRBCs) have been mentioned only in few studies. Here we report a case of a 13-year-old boy who presented with fever, significant low platelet counts and hypovolaemia that created a diagnostic dilemma. Detection of microgametocytes by microscopic examinations, further confirmed by multiplex nested PCR assays and response to anti-malarials, helped to make the diagnosis. We present an atypical case of vivax malaria with a review of morpho-variations of iRBCs and have summarized the characteristics that aid in creating increased awareness among laboratory health professionals and public health workers.
Non typhoidal Salmonella causing urinary tract infection in a young male with renal calculi and phimosis – Necessity for serotype identification
Authors: Sriramajayam Lavanya , Boopathy Vijayaraghavan Krishna Mohan , Appalaraju Boppe
Published: April 2023

Introduction:
Non typhoidal Salmonella (NTS) causes urinary tract infections infrequently and are usually associated with presence of genitourinary abnormalities.
Case Presentation:
We report a case of immunocompetant male in his early 20s with phimosis presented with history of dysuria and burning micturition for 4 months. A renal ultrasonography showed presence of bilateral intrarenal calculi. Urine analysis revealed presence of non typhoidal Salmonella. Automated identification systems performed poorly in identification of serotype. On serotyping, it was identified as Salmonella enteritidis in the referral centre. The patient was managed with oral antibiotics.
Conclusion:
This report highlights the issues inaccurate identification of NTS even with advanced automated systems and early initiation of therapy based on the knowledge of local susceptibility patterns. Furthermore, UTI in immunocompetent individuals by non typhoidal salmonellae should always be investigated further to rule out genitourinary abnormalities and appropriate antibiotics must be started to avoid chronicity and complications.
ICTV Virus Taxonomy Profile: Coronaviridae 2023
Authors: Woo Patrick C. Y. , de Groot Raoul J. , Haagmans Bart , Lau Susanna K. P. , Neuman Benjamin W. , Perlman Stanley , Sola Isabel , van der Hoek Lia , Wong Antonio C. P. , Yeh Shiou-Hwei
Published: April 2023

The family Coronaviridae includes viruses with positive-sense RNA genomes of 22–36 kb that are expressed through a nested set of 3′ co-terminal subgenomic mRNAs. Members of the subfamily Orthocoronavirinae are characterized by 80–160 nm diameter, enveloped virions with spike projections. The orthocoronaviruses, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome-related coronavirus are extremely pathogenic for humans and in the last two decades have been responsible for the SARS and MERS epidemics. Another orthocoronavirus, severe acute respiratory syndrome coronavirus 2, was responsible for the recent global COVID-19 pandemic. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Coronaviridae which is available at www.ictv.global/report/coronaviridae.
Human SARS-CoV-2 challenge resolves local and systemic response dynamics
Authors: Lindeboom Rik G.H. , Worlock Kaylee B. , Dratva Lisa M. , Yoshida Masahiro , Scobie David , Wagstaffe Helen R. , Richardson Laura , Wilbrey-Clark Anna , Barnes Josephine L. , Polanski Krzysztof , Allen-Hyttinen Jessica , Mehta Puja , Sumanaweera Dinithi , Boccacino Jacqueline , Sungnak Waradon , Huang Ni , Mamanova Lira , Kapuge Rakesh , Bolt Liam , Prigmore Elena , Killingley Ben , Kalinova Mariya , Mayer Maria , Boyers Alison , Mann Alex , Teixeira Vitor , Janes Sam M. , Chambers Rachel C. , Haniffa Muzlifah , Catchpole Andrew , Heyderman Robert , Noursadeghi Mahdad , Chain Benny , Mayer Andreas , Meyer Kerstin B. , Chiu Christopher , Nikolić Marko Z. , Teichmann Sarah A.
Published: April 2023

The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the cellular disease dynamics remains limited. In our unique COVID-19 human challenge study we used single cell genomics of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in 16 seronegative individuals challenged with preAlpha-SARS-CoV-2. Our analyses revealed rapid changes in cell type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific timepoints or infection status. We observed that the interferon response in blood precedes the nasopharynx, and that nasopharyngeal immune infiltration occurred early in transient but later in sustained infection, and thus correlated with preventing sustained infection. Ciliated cells showed an acute response phase, upregulated MHC class II while infected, and were most permissive for viral replication, whilst nasal T cells and macrophages were infected non-productively. We resolve 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our novel computational pipeline (Cell2TCR) identifies activated antigen-responding clonotype groups and motifs in any dataset. Together, we show that our detailed time series data (covid19cellatlas.org) can serve as a “Rosetta stone” for the epithelial and immune cell responses, and reveals early dynamic responses associated with protection from infection.
Racial disparities, environmental exposures, and SARS-CoV-2 infection rates: A racial map study in the USA
Authors: Xu Wenyan , Jiang Bin , Webster Chris , Sullivan William C. , Lu Yi , Chen Na , Yu Zhaowu , Chen Bin
Published: April 2023

Since the onset of the COVID-19 pandemic, researchers mainly examined how socio-economic, demographic, and environmental factors are related to disparities in SARS-CoV-2 infection rates. However, we don’t know the extent to which racial disparities in environmental exposure are related to racial disparities in SARS-CoV-2 infection rates. To address this critical issue, we gathered black vs. white infection records from 1416 counties in the contiguous United States. For these counties, we used 30m-spatial resolution land cover data and racial mappings to quantify the racial disparity between black and white people’s two types of environmental exposure, including exposures to various types of landscape settings and urban development intensities. We found that racial disparities in SARS-CoV-2 infection rates and racial disparities in exposure to various types of landscapes and urban development intensities were significant and showed similar patterns. Specifically, less racial disparity in exposure to forests outside park, pasture/hay, and urban areas with low and medium development intensities were significantly associated with lower racial disparities in SARS-CoV-2 infection rates. Distance was also critical. The positive association between racial disparities in environmental exposures and racial disparity in SARS-CoV-2 infection rates was strongest within a comfortable walking distance (approximately 400m).

Highlights

Racial dot map and landcover map were used for population-weighted analysis.

Racial disparity in environmental exposures and SARS-CoV-2 infection were linked.

Forests outside park are the most beneficial landscape settings.

Urban areas with low development intensity are the most beneficial urban areas.

Landscape and urban exposures within the 400m buffer distances are most beneficial.
Covid-19 Vaccine Booster Cadence by Immunocompromised Status
Authors: Yechezkel Matan , Faust Jeremy Samuel , Netzer Doron , Razi-Benita Talish , Shmueli Erez , Arbel Ronen , Yamin Dan
Published: April 2023

Background

Data suggest that vaccine effectiveness against Covid-19-associated hospital admission and mortality is augmented with booster doses, but the benefit wanes within several months. However, the CDC recently concluded that second doses of bivalent vaccines this Spring were not warranted because existing data were insufficient to analyze the benefits of such a strategy. Therefore, our objective was to assess whether routinely boosting high-risk populations at least every 6 months may be warranted, depending on age and immune status.

Methods

Utilizing a database of 3,574,243 members of Clalit Health Services (CHS), we analyzed the medical records of individuals who received none, or at least one dose of the BNT162b2 mRNA COVID-19 vaccine between January 1, 2021, and April 5, 2022. We examined the risk of moderate-to-severe Covid-19 hospitalization or death stratified by age group, immune status and time since receipt of the last vaccine dose during the early Omicron wave in Israel (December 20, 2021 to April 5, 2022). The number needed to vaccinate (NNV) was calculated as the inverse of the absolute risk reduction for various subgroups and Covid-19 waves.

Results

Eligibility criteria were met by 3,381,480 CHS members. The absolute risk of Covid-19 moderate-to severe hospitalization or death during the Omicron wave increased with age, immunocompromised status, and time since receipt of the last vaccine dose. The NNVs varied greatly by age and immune status and were contingent on various disease prevalence scenarios. Among the severely immunocompromised, boosting at the start of the Omicron wave had an NNV ranging from 87 (95% CI 70-109) in persons ages ≥80 to 1,037 (95% CI 999 -1,513) in persons ages 12-59. In the lower prevalence periods, the NNV for 6-month booster cadencing remained favorable for immunocompromised people in all age groups and immunocompetent people ages ≥60.

Conclusions

Our study provides evidence for the potential benefit of a routine 6-month cadence for Covid-19 boosters for the highest-risk groups, and possibly more frequently, even during relatively lower Covid-19 prevalence.
Effect of introducing ethambutol and integrating drugs into fixed-dose tablets on mortality in patients with tuberculosis
Authors: Diaz-Quijano Fredi Alexander , Bartholomay Patricia , Andrade Kleydson B. , Pelissari Daniele M. , Arakaki-Sanchez Denise , Costa Fernanda D. , Pinheiro Rejane Sobrino
Published: April 2023

At the end of 2009, due to the increase in primary resistance to isoniazid, the Brazilian Ministry of Health established changes in the treatment regimen for tuberculosis. The changes included the addition of ethambutol as the fourth drug in the intensive treatment phase and the integration of the four drugs into fixed-dose combination tablets. The introduction of fixed combination doses also led to changes in the dosage of isoniazid and pyrazinamide in the intensive and maintenance phases.

Objective

To estimate the effect of changing the tuberculosis treatment regimen on all-cause mortality and, secondly, outcomes such as mortality due to tuberculosis, cure, and loss to follow-up.

Methods

We compared the cohorts of people diagnosed with tuberculosis from 2008 to 2013, aged ten years or older, who started treatment for tuberculosis in Brazil before and after the change in the regimen adopted in 2009 (n: 145528 vs. 161264). Data were extracted from the Notifiable Diseases (Sinan) and Mortality (SIM) information systems. The missing data were imputed, and the effects were estimated using multilevel logistic models, with the state as the aggregation cluster. A directed acyclic graph guided the selection of covariates.

Results

The current (modified) regimen was not associated with significant changes in all-cause mortality (Relative Risk [RR]: 1.01; 95% confidence interval [95%CI]: 0.98 – 1.04), or tuberculosis mortality (RR: 0.98; 95%CI: 0.95 – 1.02). For cure, when transfers and missing outcome data (MOD) were considered an absence of outcome, there were no differences between treatments. When they were assumed as cured or imputed, the cure was less frequent in the current treatment. When transfers and MOD were imputed or considered an absence of loss to follow-up, the latter was more frequent in the current treatment. There were no differences in loss to follow-up between treatments when transfers and MOD were interpreted as that outcome.

Conclusion

The implementation of the modified treatment regimen was not associated with increased mortality in tuberculosis patients. Although there was a lower record of cures and a higher frequency of loss to follow-up during the second period, the sensitivity analysis indicated that a reduction in transfers and unknown outcomes could explain these associations.
Association of Free Triiodothyronine with Long-Term Prognosis in Hypertrophic cardiomyopathy patients with HFpEF: A Dual center research study
Authors: Meng Xiangbin , Wang Jing-Jia , Gao Jun , Zhang Kuo , Wen Jun , Wang Xu-Liang , Wang Yuan-Geng-Shuo , Zheng Ji-Lin , Liu Yu-Peng , Song Jing-Jing , Yang Jie , Zheng Yi-Tian , Li Chen , Wang Wen-Yao , Shao Chunli , Tang Yi-Da
Published: April 2023

Objective

The objective of this study was to identify prognostic factors in Hypertrophic cardiomyopathy patients with HFpEF, with a particular focus on the role of FT3 levels.

Research Design and Methods

We conducted a retrospective cohort study of 992 patients with HFpEF who were admitted to our two medical centers between 2009 and 2019. We collected demographic and clinical data, including FT3 levels, and conducted univariate and multivariate Cox analyses, KM survival curve analysis, and RSC curve analysis to identify prognostic factors and evaluate the non-linear predictive value of FT3.

Results

We found that age, atrial fibrillation, and NT-proBNP levels were all significant prognostic factors in patients with heart failure. Additionally, FT3 levels were a significant independent predictor of all-cause mortality and cardiac transplantation. Patients with lower FT3 levels had worse long-term prognoses, and the critical value of FT3 was 2.885.

Conclusions

Our findings suggest that FT3 levels are an important prognostic factor in patients with heart failure and should be considered when evaluating patient outcomes. Clinicians should monitor FT3 levels and consider interventions to maintain or improve thyroid function in patients with heart failure.

Article Highlights

FT3 levels are a significant independent predictor of all-cause mortality and cardiac transplantation in Hypertrophic cardiomyopathy patients with HFpEF

Patients with hypertrophic cardiomyopathy combined with HFpEF have a poorer long-term prognosis with lower FT3 levels, with a critical FT3 value of 2.885

Age, atrial fibrillation, and NT-proBNP levels were also significant prognostic factors in Hypertrophic cardiomyopathy patients with HFpEF

Clinicians should monitor FT3 levels and consider interventions to maintain or improve thyroid function in Hypertrophic cardiomyopathy patients with HFpEF.
A diagnostic and economic evaluation of the complex artificial intelligence algorithm aimed to detect 10 pathologies on the chest CT images
Authors: Chernina V. Yu. , Belyaev M.G. , Silin A.Yu. , Avetisov I.O. , Pyatnitskiy I.A. , Petrash E.A. , Basova M.V. , Sinitsyn V.E. , Omelyanovsky V.V. , Gombolevskiy V.A.
Published: April 2023

Background

Artificial intelligence (AI) technologies can help solve the significant problem of missed findings in radiology studies. An important issue is assessing the economic benefits of implementing AI.

Aim

to evaluate the frequency of missed pathologies detection and the economic potential of AI technology for chest CT, validated by expert radiologists, compared with radiologists without access to AI in a private medical center.

Methods

An observational, single-center retrospective study was conducted. The study included chest CTs without IV contrast performed from 01.06.2022 to 31.07.2022 in "Yauza Hospital" LLC, Moscow. The CTs were processed using a complex AI algorithm for ten pathologies: pulmonary infiltrates, typical for viral pneumonia (COVID-19 in pandemic conditions); lung nodules; pleural effusion; pulmonary emphysema; thoracic aortic dilatation; pulmonary trunk dilatation; coronary artery calcification; adrenal hyperplasia; osteoporosis (vertebral body height and density changes). Two experts analyzed CTs and compared results with AI. Further routing was determined according to clinical guidelines for all findings initially detected and missed by radiologists. The lost potential revenue (LPR) was calculated for each patient according to the hospital price list.

Results

From the final 160 CTs, the AI identified 90 studies (56%) with pathologies, of which 81 studies (51%) were missing at least one pathology in the report. The "second-stage" LPR for all pathologies from 81 patients was RUB 2,847,760 ($37,251 or CNY 256,218). LPR only for those pathologies missed by radiologists but detected by AI was RUB 2,065,360 ($27,017 or CNY 185,824).

Conclusion

Using AI for chest CTs as an "assistant" to the radiologist can significantly reduce the number of missed abnormalities. AI usage can bring 3.6 times more benefits compared to the standard model without AI. The use of complex AI for chest CT can be cost-effective.
COL6A3-derived endotrophin mediates the effect of obesity on coronary artery disease: an integrative proteogenomics analysis
Authors: Yoshiji Satoshi , Lu Tianyuan , Butler-Laporte Guillaume , Carrasco-Zanini-Sanchez Julia , Chen Yiheng , Liang Kevin , Willett Julian Daniel Sunday , Su Chen-Yang , Wang Shidong , Adra Darin , Ilboudo Yann , Sasako Takayoshi , Forgetta Vincenzo , Farjoun Yossi , Zeberg Hugo , Zhou Sirui , Hultström Michael , Machiela Mitchell , Wareham Nicholas J. , Mooser Vincent , Timpson Nicholas J. , Langenberg Claudia , Richards J. Brent
Published: April 2023

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity has broad effects on circulating protein levels, we investigated circulating proteins that mediate the effects of obesity on coronary artery disease (CAD), stroke, and type 2 diabetes—since doing so may prioritize targets for therapeutic intervention. By integrating proteome-wide Mendelian randomization (MR) screening 4,907 plasma proteins, colocalization, and mediation analyses, we identified seven plasma proteins, including collagen type VI α3 (COL6A3). COL6A3 was strongly increased by body mass index (BMI) (β= 0.32, 95% CI: 0.26–0.38,P= 3.7 × 10-8per s.d. increase in BMI) and increased the risk of CAD (OR = 1.47, 95% CI:1.26–1.70,P= 4.5 × 10-7per s.d. increase in COL6A3). Notably, COL6A3 is cleaved at its C-terminus to produce endotrophin, which was found to mediate this effect on CAD. In single-cell RNA sequencing of adipose tissues and coronary arteries,COL6A3was highly expressed in cell types involved in metabolic dysfunction and fibrosis. Finally, we found that body fat reduction can reduce plasma levels of COL6A3-derived endotrophin, thereby highlighting a tractable way to modify endotrophin levels. In summary, we provide actionable insights into how circulating proteins mediate the effect of obesity on cardiometabolic diseases and prioritize endotrophin as a potential therapeutic target.
Time series analysis of daily data of COVID-19 reported cases in Japan from January 2020 to February 2023
Authors: Sumi Ayako
Published: April 2023

This study investigatbed temporal variational structures of the COVID-19 pandemic in Japan using a time series analysis incorporating maximum entropy method (MEM) spectral analysis, which produces power spectral densities (PSDs). This method was applied to daily data of COVID-19 cases in Japan from January 2020 to February 2023. The analyses confirmed that the PSDs for data in both the pre- and post-Tokyo Olympics periods show exponential characteristics, which are universally observed in PSDs for time series generated from nonlinear dynamical systems, including the so-called susceptible/exposed/infectious/recovered (SEIR) model, well-established as a mathematical model of temporal variational structures of infectious disease outbreaks. The magnitude of the gradient of exponential PSD for the pre-Olympics period was smaller than that of the post-Olympics period, because of the relatively high complex variations of the data in the pre-Olympics period caused by a deterministic, nonlinear dynamical system and/or undeterministic noise. A 3-dimensional spectral array obtained by segment time series analysis indicates that temporal changes in the periodic structures of the COVID-19 data are already observable before the commencement of the Tokyo Olympics and immediately after the introduction of mass and workplace vaccination programs. Lessons from theoretical studies for measles control programs may be applicable to COVID-19.
Detection of distant familial relatedness in biobanks for identification of undiagnosed carriers of a Mendelian disease variant: application to Long QT syndrome
Authors: Lancaster Megan C. , Chen Hung-Hsin , Shoemaker M. Benjamin , Fleming Matthew R. , Baker James T. , Polikowsky Hannah G. , Samuels David C. , Huff Chad D. , Roden Dan M. , Below Jennifer E.
Published: April 2023

Importance

The diagnosis and study of rare genetic disease is often limited to referral populations, leading to underdiagnosis and a biased assessment of penetrance and phenotype.

Objective

To develop a generalizable method of genotype inference based on distant relatedness and to deploy this to identify undiagnosed Type 5 Long QT Syndrome (LQT5) rare variant carriers in a non-referral population.

Participants

We identified 9 LQT5 probands and 3 first-degree relatives referred to a single Genetic Arrhythmia clinic, each carrying D76N (p.Asp76Asn), the most common variant implicated in LQT5. The non-referral population consisted of 69,879 ancestry-matched subjects in BioVU, a large biobank that links electronic health records to dense array data. Participants were enrolled from 2007-2022. Data analysis was performed in 2022.

Exposures

We developed and applied a novel approach to genotype inference (Distant Relatedness for Identification and Variant Evaluation, or DRIVE) to identify shared, identical-by-descent (IBD) large chromosomal segments in array data.

Main Outcomes and Measures

We sought to establish genetic relatedness among the probands and to use genomic segments underlying D76N to identify other potential carriers in BioVU. We then further studied the role of D76N in LQT5 pathogenesis.

Results

Genetic reconstruction of pedigrees and distant relatedness detection among clinic probands using DRIVE revealed shared recent common ancestry and identified a single long shared haplotype. Interrogation of the non-referral population in BioVU identified a further 23 subjects sharing this haplotype, and sequencing confirmed D76N carrier status in 22, all previously undiagnosed with LQT5. The QTc was prolonged in D76N carriers compared to BioVU controls, with 40% penetrance of QTc ≥ 480 msec. Among D76N carriers, a QTc polygenic score was additively associated with QTc prolongation.

Conclusions and Relevance

Detection of IBD shared chromosomal segments around D76N enabled identification of distantly related and previously undiagnosed rare-variant carriers, demonstrated the contribution of polygenic risk to monogenic disease penetrance, and further established LQT5 as a primary arrhythmia disorder. Analysis of shared chromosomal regions spanning disease-causing mutations can identify undiagnosed cases of genetic diseases.
Epidemiology ofPlasmodium malariaeandPlasmodium ovalespp. in a highly malaria-endemic country: a longitudinal cohort study in Kinshasa Province, Democratic Republic of Congo
Authors: Sendor Rachel , Banek Kristin , Kashamuka Melchior Mwandagalirwa , Mvuama Nono , Bala Joseph A. , Nkalani Marthe , Kihuma Georges , Atibu Joseph , Thwai Kyaw L. , Svec W. Matthew , Goel Varun , Nseka Tommy , Lin Jessica T. , Bailey Jeffrey A. , Emch Michael , Carrel Margaret , Juliano Jonathan J. , Tshefu Antoinette , Parr Jonathan B.
Published: April 2023

Background

Increasing reports suggest that non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa, but their epidemiology is not well-defined. This is particularly true in regions of highP. falciparumendemicity such as the Democratic Republic of Congo (DRC), where 12% of the world’s malaria cases and 13% of deaths occur.

Methods and Findings

The cumulative incidence and prevalence of P. malariae and P. ovale spp. infection detected by real-time PCR were estimated among children and adults within a longitudinal study conducted in seven rural, peri-urban, and urban sites from 2015-2017 in Kinshasa Province, DRC. Participants were sampled at biannual household survey visits (asymptomatic) and during routine health facility visits (symptomatic). Participant-level characteristics associated with non-falciparum infections were estimated for single- and mixed-species infections. Among 9,089 samples collected from 1,565 participants over a 3-year period, the incidence of P. malariae and P. ovale spp. infection was 11% (95% CI: 9%-12%) and 7% (95% CI: 5%-8%) by one year, respectively, compared to a 67% (95% CI: 64%-70%) one-year cumulative incidence of P. falciparum infection. Incidence continued to rise in the second year of follow-up, reaching 26% and 15% in school-age children (5-14yo) for P. malariae and P. ovale spp., respectively. Prevalence of P. malariae, P. ovale spp., and P. falciparum infections during household visits were 3% (95% CI: 3%-4%), 1% (95% CI: 1%-2%), and 35% (95% CI: 33%-36%), respectively. Non-falciparum malaria was more prevalent in rural and peri-urban vs. urban sites, in school-age children, and among those with P. falciparum co-infection. A crude association was detected between P. malariae and any anemia in the symptomatic clinic population, although this association did not hold when stratified by anemia severity. No crude associations were detected between non-falciparum infection and fever prevalence.

Conclusions

P. falciparumremains the primary driver of malaria morbidity and mortality in the DRC. However, non-falciparum species also pose an infection risk across sites of varying urbanicity and malaria endemicity within Kinshasa, DRC, particularly among children under 15 years of age. AsP. falciparuminterventions gain traction in high-burden settings like the DRC, continued surveillance and improved understanding of non-falciparum infections are warranted.
Stage-dependent biomarker changes in spinocerebellar ataxia type 3
Authors: Faber Jennifer , Berger Moritz , Carlo Wilke , Hübener-Schmid Jeannette , Schaprian Tamara , Santana Magda M , Grobe-Einsler Marcus , Onder Dement , Koyak Berkan , Giunti Paola , Garcia-Moreno Hector , Gonzalez-Robles Cristina , Lima Manuela , Raposo Mafalda , Vieira Melo Ana Rosa , de Almeida Luís Pereira , Silva Patrick , Pinto Maria M , van de Warrenburg Bart P. , van Gaalen Judith , Jeroen de Vries Jeroen , Oz Gulin , Joers James M. , Synofzik Matthis , Schöls Ludger , Riess Olaf , Infante Jon , Manrique Leire , Timmann Dagmar , Thieme Andreas , Jacobi Heike , Reetz Kathrin , Dogan Imis , Onyike Chiadikaobi , Povazan Michal , Schmahmann Jeremy , Ratai Eva-Maria , Schmid Matthias , Klockgether Thomas
Published: April 2023

Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies for SCA3, precise knowledge of stage-dependent fluid and MRI biomarker changes is needed.

We analyzed cross-sectional data of 292 SCA3 mutation carriers including 57 pre-ataxic individuals, and 108 healthy controls from the European Spinocerebellar ataxia type 3/Machado-Joseph Disease Initiative (ESMI) cohort. Blood concentrations of mutant ATXN3 and neurofilament light (NfL) were determined, and volumes of pons, cerebellar white matter (CWM) and cerebellar grey matter (CGM) were measured on MRI.

Mutant ATXN3 concentrations were high before and after ataxia onset, while NfL continuously increased and deviated from normal 11.9 years before onset. Pons and CWM volumes decreased, but the deviation from normal was only 2.0 years (pons) and 0.3 years (CWM) before ataxia onset. We propose a staging model of SCA3 that includes an initial asymptomatic carrier stage followed by the biomarker stage defined by absence of ataxia, but a significant rise of NfL. The biomarker stage leads into the ataxia stage, defined by manifest ataxia.

The present analysis provides a robust framework for further studies aiming at elaboration and differentiation of the staging model of SCA3.