bluuebunny/crossref_metadata_2025 huggingface dataset:
Thyroid Eye Disease and Its Association With Diabetes Mellitus: A Major Review
Authors: Gupta Roshmi , Kalra Pramila , Ramamurthy Lakshmi B. , Rath Suryasnata
Published: December 2023

Purpose:

Thyroid eye disease (TED) associated with diabetes mellitus (DM) presents unique challenges. DM is a risk factor for TED. Standard management of TED with glucocorticoids (GC), orbital radiation, or teprotumumab can cause adverse events in poor glycemic control. The authors reviewed the literature on the relationship between TED and DM and the management of co-existing diseases.

Methods:

The authors searched PubMed with keywords “thyroid eye disease,” “diabetes mellitus,” and similar terms from 2013 to 2022. The authors included relevant studies after screening the abstracts. Additional references to the selected studies were included where applicable. Data were extracted from the final articles according to the preplanned outline of the review.

Results:

The initial search yielded 279 abstracts. The final review included 93 articles. TED and DM interact at multiple levels—genetic, immunologic, cellular, nutritional, and metabolic. Both DM and thyroid dysfunction exacerbate the morbidity caused by the other. Metabolic factors also affect the inflammatory pathway for TED. Patients with DM develop TED with greater frequency and severity, necessitating interventions for vision salvage. Agents (GC, teprotumumab, or radiation) used for TED are often unsuitable for treatment with DM, especially if there is poor glycemic control or diabetic retinopathy. There were no studies on using steroid-sparing agents in TED with DM.

Conclusion:

TED and DM co-exist because of multiple intersections in the pathophysiology. Challenges in the treatment include increased TED severity and risk of hyperglycemia and retinopathy. Multidisciplinary teams best undertake treatment of TED with DM.
Fibrocyte Participation in Thyroid-Associated Ophthalmopathy Suggests New Approaches to Therapy
Authors: Smith Terry J.
Published: December 2023

Purpose:

Review the historical context of research and changing therapeutic landscape of thyroid-associated ophthalmopathy (TAO) by focusing on the relationship between TAO, CD34+ fibrocytes, thyrotropin receptor (TSHR), and insulin-like growth factor-I receptor (IGF-IR).

Methods:

A literature review using search terms, including fibrocytes, IGF-IR, TSHR, TAO, and thyroid eye disease.

Results:

The mechanisms involved in TAO have been partially identified. Substantial progress has been made over several decades, including 1) recognizing the interplay between the professional immune system and orbital tissues; 2) TSHR and IGF-IR act interdependently in mediating the pathogenesis of TAO; 3) Multiple cytokines and specific immune cells are involved in activating and remodeling orbital tissue; 4) Recognition of these mechanisms is allowing the development of target therapies such as teprotumumab, a monoclonal antibody IGF-IR inhibitor approved by the US Food and drug administration for treatment of TAO; and 5) It appears that teprotumumab acts on the systemic immune system peripheral to the orbit.

Conclusion:

Additional molecules targeting IGF-IR and other plausible disease mechanisms are currently under development. This activity in the TAO therapeutic space portends even greater improvements in patient care.
Magnetic Resonance Imaging in the Management of Thyroid Eye Disease: A Systematic Review
Authors: Vaishnav Yash J. , Mawn Louise A.
Published: December 2023

Purpose:

MRI may potentially detect active thyroid eye disease prior to elevation of clinical activity score. We aimed to systematically review the existing literature pertaining to MRI thyroid eye disease and to assess the role of MRI in the diagnosis of thyroid eye disease.

Methods:

A Population, Intervention, Comparison, Outcome/Preferred Reporting Items for Systematic Reviews and Meta-Analyses selection criteria was applied to identify studies for inclusion published between the years 2000 and 2023.

Results:

Twenty-four articles were identified for inclusion in the systematic review. All included studies utilized MRI as the imaging modality. MRI sequences used included T2-weighted imaging in 87.5%, T1-weighted imaging in 54.2%, diffusion-weighted imaging in 20.8%, and short tau inversion recovery in 16.7%. The most common parameters quantified were signal intensity ratio in 10 studies (41.7%) and T2-relaxation time in 8 studies (33.3%). Signal intensity ratio and T2-relaxation time were shown to correlate with clinical activity score and identify the phase of the disease.

Conclusions:

MRI has untapped potential for further elucidating the highly complex biological processes in thyroid eye disease. As we move away from clinical activity score as a predictor of response to biologic therapy, MRI may prove more important than ever in the risk-benefit analysis around the use of immunomodulators.
Improving Asthma Action Plan Completion Rates across Five Divisions in an Academic Children’s Hospital
Authors: Alfieri Maria G. , Catalano Katie , Simoneau Tregony , Haynes Linda , Glidden Patricia , Baxi Sachin N. , Yim Ramy , Ethier Benjamin , Holder-Niles Faye F. , McCarty Kendall , Polanco Walters Frinny , Sprecher Eli , Starmer Amy , Gaffin Jonathan M. , Durney Jeffrey , Klements Elizabeth , Esty Brittany
Published: December 2023

Introduction:

Asthma is the most common chronic disease among children. Asthma Action Plans (AAPs) enable asthma self-management tailored to each patient and should be updated annually. At our institution, providers face challenges in creating reliable processes to consistently complete AAPs for patients with asthma. This project’s aim was to increase the percentage of patients across five hospital divisions who have an up-to-date AAP from 80% in May 2021 to 85% by October 1, 2021.

Methods:

We launched a quality improvement (QI) project using the Model for Improvement, focusing on improving AAP completion rates across five hospital divisions providing ambulatory care for asthma patients. The divisions (Adolescent/Young Adult Medicine, Allergy, Pulmonary, and two Primary Care sites) participated in the QI process using tools to understand the problem context. They implemented a cross-divisional AAP completion competition from June to October 2021. Each month during Action Periods, divisions trialed their interventions using Plan-Do-Study-Act cycles. We held monthly Learning Sessions for divisions to collaborate on successful intervention strategies.

Results:

Statistical process control chart analysis demonstrated that the overall AAP completion rate increased from a baseline of 80% to 87% with the initiation of the competition. All divisions showed improvement in AAP completion rates during the active intervention period, but sustainment varied.

Conclusions:

The cross-divisional competition motivated five divisions to improve processes to increase AAP completion rates. This approach effectively fostered engagement and idea sharing to boost performance, and may be considered for other QI projects.
Increasing COVID-19 Immunization Rates through a Vaccination Program for Hospitalized Children
Authors: Mattick Victoria , Nevin Katelyn Cappotelli , Fallon Anne , Darrow Stephanie Northwood , Ramazani Suzanne , Dick Travis , Sosa Tina
Published: December 2023

Introduction:

Inpatient coronavirus disease 2019 (COVID-19) vaccination initiatives offer a novel strategy to eliminate barriers to care, provide access to interprofessional teams, and decrease COVID-19 morbidity and mortality. Our inpatient vaccination initiative aimed to triple the baseline rate of eligible hospitalized children vaccinated against COVID-19 from 0.95% to 2.85% from December 2021 to June 2022.

Methods:

We implemented a COVID-19 vaccination program for pediatric inpatients eligible to receive a dose based on age, current guidelines, and prior doses received. Key drivers included immunization counseling training, identification of eligible patients, and a streamlined workflow. The outcome measure was the percentage of eligible patients who received a vaccine dose during hospitalization. The process measures included the percentage of age-eligible patients who were appropriately screened for prior doses on admission. We designed a clinical decision support system to enhance eligibility identification. The team performed a health equity analysis which stratified patients by social vulnerability index.

Results:

During the study period, the average percentage of eligible hospitalized patients vaccinated increased from 0.9% to 3.5%, representing special cause variation and a centerline shift. The average percentage of age-eligible patients screened for prior vaccine doses on admission increased from 66.5% to 81.5%. Patients were more likely to be vaccinated if their clinician was exposed to the clinical decision support system (P < 0.01). The social vulnerability index analysis showed no significant differences.

Conclusions:

This COVID-19 vaccination initiative highlights how an interprofessional approach can increase vaccination rates in hospitalized children; however, overall inpatient COVID-19 vaccination rates in this setting remained low.
Decreasing Blood Culture Collection in Hospitalized Patients with CAP, SSTI, and UTI
Authors: Combs Monica D. , Liberman Danica B. , Lee Vivian
Published: December 2023

Background:

Blood culture collection in pediatric patients with community-acquired pneumonia (CAP), skin and soft tissue infections (SSTI), and urinary tract infections (UTI) remains high despite evidence of its limited utility. We aimed to decrease the number of cultures collected in children hospitalized for CAP, SSTI, and UTI by 25% over 11 months.

Methods:

Quality improvement initiative at a children’s hospital among well-appearing patients aged 2 months or more to 18 years diagnosed with CAP, SSTI, or UTI. Our primary and secondary outcomes were blood culture collection rate and positivity rate, respectively. Interventions focused on three key drivers: academic detailing, physician awareness of personal performance, and data transparency.

Results:

Over the 2-year study period, there were 105 blood cultures collected in 223 hospitalized patients. Blood culture collection rates demonstrated special cause variation, decreasing from 63.5% to 24.5%. For patients with UTI, 86% (18/21) of blood cultures were negative, whereas 100% were negative for CAP and SSTI. All three patients with bacteremic UTI had a concurrent urine culture growing the same pathogen. Balancing measures remained unchanged, including escalation to a higher level of care and return to the emergency department or hospital within 14 days for the same infection.

Conclusions:

A multifaceted quality improvement approach can reduce blood culture collection for hospitalized patients with CAP, SSTI, and UTI without significant changes to balancing measures. Despite the reduction achieved, the near-universal negative culture results suggest continued overutilization and highlight the need for more targeted approaches to blood culture collection.
Distribution and diversity of type VI secretion system clusters in Enterobacter bugandensis and Enterobacter cloacae
Authors: Anderson Amy J. G. , Morrell Becca , Lopez Campos Guillermo , Valvano Miguel A.
Published: December 2023

Gram-negative bacteria use type VI secretion systems (T6SSs) to antagonize neighbouring cells. Although primarily involved in bacterial competition, the T6SS is also implicated in pathogenesis, biofilm formation and ion scavenging.

Enterobacter

species belong to the ESKAPE pathogens, and while their antibiotic resistance has been well studied, less is known about their pathogenesis. Here, we investigated the distribution and diversity of T6SS components in isolates of two clinically relevant

Enterobacter

species,

E. cloacae

and

E. bugandensis

. T6SS clusters are grouped into four types (T6SSi-T6SSiv), of which type i can be further divided into six subtypes (i1, i2, i3, i4a, i4b, i5). Analysis of a curated dataset of 31 strains demonstrated that most of them encode T6SS clusters belonging to the T6SSi type. All T6SS-positive strains possessed a conserved i3 cluster, and many harboured one or two additional i2 clusters. These clusters were less conserved, and some strains displayed evidence of deletion. We focused on a pathogenic

E. bugandensis

clinical isolate for comprehensive in silico effector prediction, with comparative analyses across the 31 isolates. Several new effector candidates were identified, including an evolved VgrG with a metallopeptidase domain and a Tse6-like protein. Additional effectors included an anti-eukaryotic catalase (KatN), M23 peptidase, PAAR and VgrG proteins. Our findings highlight the diversity of

Enterobacter

T6SSs and reveal new putative effectors that may be important for the interaction of these species with neighbouring cells and their environment.
Cell type-specific loops linked to RNA polymerase II elongation in human neural differentiation
Authors: Titus Katelyn R. , Simandi Zoltan , Chandrashekar Harshini , Paquet Dominik , Phillips-Cremins Jennifer E.
Published: December 2023

DNA is folded into higher-order structures that shape and are shaped by genome function. The role for long-range loops in the establishment of new gene expression patterns during cell fate transitions remains poorly understood. Here, we investigate the link between cell-specific loops and RNA polymerase II (RNAPolII) during neural lineage commitment. We find thousands of loops decommissioned or gainedde novoupon differentiation of human induced pluripotent stem cells (hiPSCs) to neural progenitors (NPCs) and post-mitotic neurons. During hiPSC-to-NPC and NPC-to-neuron transitions, genes changing from RNAPolII initiation to elongation are >4-fold more likely to anchor cell-specific loops than repressed genes. Elongated genes exhibit significant mRNA upregulation when connected in cell-specific promoter-enhancer loops but not invariant promoter-enhancer loops, promoter-promoter loops, or unlooped. Genes transitioning from repression to RNAPolII initiation exhibit slight mRNA increase independent of loop status. Our data link cell-specific loops and robust RNAPolII-mediated elongation during neural cell fate transitions.

Highlights

Thousands of loops are decommissioned and gained upon human iPSC differentiation to NPCs/neurons

Genes transitioning from initiated-to-elongated exhibit robust mRNA upregulation when connected in cell type-specific promoter-enhancer loops

Genes transitioning from repressed-to-initiated exhibit slight increases in mRNA levels independent of loop status

Upon short-term RNAPolII degradation, loops formed by elongated genes are more severely disrupted than those anchoring initiated genes
Molecular and neuronal mechanisms governing sexually dimorphic prioritization of innate behaviors
Authors: Jiang Xinyu , Ma Mingze , Sun Mengshi , Chen Jie , Pan Yufeng
Published: December 2023

Males and females display dimorphic innate behaviors and further prioritize them differently. How the sexually dimorphic behavioral prioritization is mediated is poorly understood. InDrosophila, around 60 pairs of pC1 neurons in males and 6 pairs in females control sexually dimorphic behaviors. We show that an increase of pC1 activity determines the sequential execution of behaviors such as sex, aggression, sleep, and feeding in a sex-specific way. We identify distinct subsets of pC1 neurons in both males and females that regulate different behaviors. We further discover diuretic hormone 44 (DH44) and acetylcholine (ACh) as co-transmitters in pC1 neurons. ACh promotes the execution of each behavior in both sexes, whereas DH44 functions in a sex-specific and activity-dependent manner to establish the sexually dimorphic behavioral outputs. These findings provide a framework for understanding the molecular and cellular mechanisms underlying sexually dimorphic prioritization of innate behaviors.
A discontinuously coupled network of phase oscillators replicate actomyosin cooperation
Authors: Warmington Benjamin , Rossiter Jonathan , Bloomfield-Gadêlha Hermes
Published: December 2023

Groups of non-processive myosin motors exhibit complex and non-linear behaviors when binding to actin. These operate at larger scales and time frames than an individual motor, indicating the presence of a strong cooperative disposition. Limits in contemporary microscopy prevent verification of motor-filament binding dynamics, whilst mathematical models rely on continuum abstractions in which cooperativity is implicit and individual motor behavior cannot be separated from the behaviour of the whole. Understanding the fundamental interactions driving the emergent behaviour in actomyosin therefore remains an open question. Here we suggest that the diversity of empirically observedin-vitrooscillations can be explained by a minimal Kuramoto-style phase oscillator model of actomyosin, where cooperativity is orchestrated by the actomyosin geometry and mechanical environment. The model mirrors the irregular and regular saw-tooth oscillations present inin-vitroactomyosin and sarcomeric ‘SPOC’ experiments with only adjustments of the external mechanical environment, and despite the model’s simplicity. Actomyosin-like behaviour thus arises as a generic property of the discontinuous mechanical coupling in an incommensurate architecture, rather than specific to molecular motor reaction kinetics. We demonstrate a range of synchronising behaviours arising from the cooperative motor dynamics that, once synchronised, are stable over a large range of external forces. These synchronising behaviours arise from the cooperative motor dynamics that, once synchronised, are stable over a large range of external forces. The nature of the synchronisation patterns allow recruitment of rotors as the external force increases, reducing variance in the backbone’s velocity. This is a demonstration of morphological control. Due to interest in this behaviour in contemporary robotics, we build a physical experiment, using electric motors to power our oscillators. Using the experiment we verify both the organisational and control properties of the system. This demonstrates non-biological motors can cooperate similarly to biological motors when working within an actomyosin geometry, suggesting that the actomyosin complex may not depend on motor-specific qualities to achieve its biological function. These findings offer novel insights into synchronising networks of oscillators and have potential applications in emulating actomyosin-like behaviors within contemporary robotics using non-biological motors.
Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons
Authors: Kim Olena , Okamoto Yuji , Brose Nils , Shigemoto Ryuichi , Jonas Peter
Published: December 2023

It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size (RRP) and vesicular release probability (Pr) by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the nearest neighbor distance (NND) between Munc13-1 and CaV2.1 Ca2+channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones (AZs). We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse.
Uncovering the diversity of heterotrophic culturable bacteria within the gut of bay scallopArgopecten purpuratus(Lamarck, 1819) from two geographically distant natural banks
Authors: Serrano Wilbert , Tarazona-Janampa Ulrike I. , Olaechea Raul M. , Valle Sonia
Published: December 2023

We study the bacterial diversity within the gut of the peruvian bay scallopArgopecten purpuratus(Lamarck, 1819) (Mollusca: Pectinidae) collected from two shellfish growing areas in Independence Bay (IB) and Sechura Bay (SB) in Peru. This work aimed to identify isolates of culturable gut-associated microbiota ofA. purpuratusthrough repetitive sequence-based PCR (rep-PCR) and 16S rRNA gene sequences comparison. A total of 20 healthy adult scallops were collected from each location twice, in spring and autumn, 2015 and 2016, respectively.

Fecal pellets from the distal intestinal tract of each individual were extracted, and after pooling, samples were cultivated on general and selective media following standard culture conditions. In order to prevent duplicate sequencing of the ribosomal 16S rRNA gene sequences of the isolates, a pre-screened step by (rep-PCR) amplification utilizing BOXA1R primer was performed, then isolates showing different banding profiles were selected for further sequencing.

Taxonomic distribution based on the 16S rRNA gene comparison of selected strains placed isolates from IB and SB into 29 and 27 different genera, representing 50 and 42 species, respectively. The major proportions of bacterial species found in IB corresponded to the division Firmicutes (46%), whereas the Proteobacteria and Firmicutes were almost equally distributed in (SB) with 38 and 43% respectively. Remarkable, (IB) showed a high number (28%) and diversity of species within the division Actinobacteria compared to (SB); while the speciesSalinimicrobiumsp. of the division Flavobacteria was isolated only in (SB).

Common species in both areas are mainly related to the genusBacillus,while strains of speciesVibrio alginolyticusandV. parahaemoliticuswere common representatives of the Proteobacteria. The intestinal tract ofA. purpuratusmay represent an uninvestigated niche for analyzing the structure of new complex microbial communities. This study showed that the diversity of culturable microbiota within the gut of two populations ofA. purpuratusis significantly different at each location.
FLiPPR: A Processor for Limited Proteolysis (LiP) Mass Spectrometry Datasets Built on FragPipe
Authors: Manriquez-Sandoval Edgar , Brewer Joy , Lule Gabriela , Lopez Samanta , Fried Stephen D.
Published: December 2023

Here, we present FLiPPR, or FragPipe LiP (limited proteolysis) Processor, a tool that facilitates the analysis of data from limited proteolysis mass spectrometry (LiP-MS) experiments following primary search and quantification in FragPipe. LiP-MS has emerged as a method that can provide proteome-wide information on protein structure and has been applied to a range of biological and biophysical questions. Although LiP- MS can be carried out with standard laboratory reagents and mass spectrometers, analyzing the data can be slow and poses unique challenges compared to typical quantitative proteomics workflows. To address this, we leverage the fast, sensitive, and accurate search and label-free quantification algorithms in FragPipe and then process its output in FLiPPR. FLiPPR formalizes a specific data imputation heuristic that carefully uses missing data in LiP-MS experiments to report on the most significant structural changes. Moreover, FLiPPR introduces a new data merging scheme (from ions to cut-sites) and a protein-centric multiple hypothesis correction scheme, collectively enabling processed LiP-MS datasets to be more robust and less redundant. These improvements substantially strengthen statistical trends when previously published data are reanalyzed with the FragPipe/FLiPPR workflow. As a final feature, FLiPPR facilitates the collection of structural metadata to identify correlations between experiments and structural features. We hope that FLiPPR will lower the barrier for more users to adopt LiP-MS, standardize statistical procedures for LiP-MS data analysis, and systematize output to facilitate eventual larger-scale integration of LiP-MS data.
COVID-19 vaccination uptake among healthcare workers in Ghana: A comprehensive analysis of knowledge, attitude, perceived vaccine effectiveness, and health belief model constructs
Authors: Mbele Whiteson , Dako-Gyeke Phyllis , Frans Andreas Ndapewa
Published: December 2023

The novel Coronavirus Disease 19 (COVID-19) caused devastating effects globally, and healthcare workers were among the most affected by the pandemic. To mitigate this impact, healthcare workers were prioritized in COVID-19 vaccination globally and in Ghana. However, hesitancy by healthcare workers to receive the vaccination resulted in delayed control of the pandemic. In Ghana, vaccine acceptance rate among healthcare workers was estimated to be 39.3% in the pre-vaccine rollout period. Consequently, this study assessed uptake of COVID-19 vaccination and associated factors among healthcare workers in Ghana in the post-vaccine roll-out period.

This was an analytical cross-sectional study that used a semi-structured questionnaire to collect data on COVID-19 vaccination uptake and influencing factors from randomly selected 256 healthcare workers in Ayawaso West Municipality, Ghana. Bivariable and Multivariable logistic regression was performed using IBM SPSS version 22 to identify predictors of vaccine uptake and a statistical significance was declared at p<0.05.

More than three-fourths of participants 220 (85.9%) had received at least one dose of the COVID-19 vaccination, while 36 (14.9%) were hesitant. More than half 139 (54.3%) had adequate knowledge about COVID-19 vaccination and the majority 188 (73.4%) had positive perceptions about its effectiveness. Moreover, 218 (85.2%) of HCWs had a positive attitude towards COVID-19 vaccination. Positive attitude towards COVID-19 vaccination (AOR = 4.3; 95% CI: 1.4, 13.0) and high cues to action (AOR = 5.7; 95% CI: 2.2, 14.8) were the factors that significantly predicted uptake of COVID-19 vaccination among healthcare workers.

COVID-19 vaccination among HCWs in Ghana is promising. However, hesitancy to receive the vaccination among a significant proportion of HCWs raises concerns. To ensure vaccination of all healthcare workers, interventions to promote vaccination should target key determinants of vaccination uptake, such as attitude towards the vaccination and cues to action.
Breast and cervical cancer screening among women at reproductive age in Cambodia: A Secondary Analysis of Cambodia Demographic and Health Survey 2022
Authors: Um Samnang , Sopheab Heng
Published: December 2023

Breast and cervical cancers are the most prevalent diagnosed in women worldwide, significantly contributing to maternal morbidity and mortality. We examined socio-demographic and behavioral factors associated with breast and cervical cancer screening among Cambodian women aged 15-49 years old. We analyzed women’s data from the 2022 Cambodia Demographic and Health Survey (CDHS). In total, 19,496 women were interviewed. Multiple logistic regression was performed using STATA V17 to examine factors associated with breast and cervical cancer screening. The proportion of breast and cervical cancer screenings was 10.6% and 15.3%, respectively. After being adjusted, factors independently associated with breast cancer screening included age group 20-29 years [AOR=2.51; 95% CI: 1.55-4.06], 30-39 years [AOR=4.34; 95% CI: 2.66-7.09], and 40-49 years [AOR=4.66; 95% CI: 2.81-7.71], higher education [AOR=1.92; 95% CI: 1.26-2.93], exposure media [AOR=1.66; 95% CI: 1.32-2.10], and rich wealth quintile [AOR=1.50; 95% CI: 1.25-1.80]. Similarly, the odds of having cervical cancer screening were age group 20-29 years [AOR=2.88; 95% CI: 1.76-4.71], 30-39 years [AOR=5.94; 95% CI: 3.58-9.83], and 40-49 years [AOR=7.61; 95% CI: 4.55-12.73], higher education [AOR=1.55; 95% CI: 1.55-2.73], exposure media [AOR=1.62; 95% CI: 1.35,1.95], and rich wealth quintile [AOR=2.14; 95% CI: 1.78-2.58]. In conclusion, this study shows the low screening proportion for both breast and cervical cancers, and it also highlights that socio-economic factors are significantly important in determining the health care seeking for these two main cancer screening services among women aged 15-49 years in Cambodia. Therefore, increase of exposure media with health education focusing on these cancer screenings should be made better accessible to women, particularly those of low socio-economic status.
Determinants of timely administration of the birth dose of hepatitis B vaccine in Senegal in 2019: Secondary analysis of the demographic and health survey
Authors: Bassoum Oumar , Ba Mouhamadou Faly , Sougou Ndeye Mareme , Sow Adama , Seck Ibrahima
Published: December 2023

In developing countries, hepatitis B is spread primarily by the perinatal or horizontal route. Thus, the Senegalese government recommends administering the birth dose of the hepatitis B vaccine (HepB0) within 24 hours of birth. The objective was to identify the determinants of timely administration of HepB0 in Senegal in 2019. A secondary analysis of the demographic and health survey was carried out. The study population consisted of children aged 12 to 23 months. A cluster survey, stratified in urban and rural areas, drawn at two stages, was carried out. Individual interviews were conducted. Logistic regression was applied to estimate the adjusted odds ratio (aOR) and their 95% confidence interval. In total, 1130 children were included. Among them, 48.1% were born to mothers aged 25 to 34, 46.8% were male and 82.6% were born in health facilities. The average time between birth and HepB0 administration was 13.1±46.6 days. Among 747 children vaccinated, only 65.2% were vaccinated within 24 hours of birth. The determinants were maternal age of at least 35 years (aOR= 2.03 [1.29 – 3.20]), primary education of the mother (aOR=1.94 [1.13 – 3. 35]), at least four antenatal care (aOR=1.74 [1.12 – 2.69]), belonging to the central (ORa=0.22 [0.11 – 0.44]) and northern regions (aOR= 0.18 [0.08 – 0.40]), and delivery in a health facility (aOR=3.42 [1.90 – 6.15]). Education and keeping girls in school, local postnatal care in hard-to-reach regions, promotion of antenatal acre and delivery in a health facility should improve the timeliness of HepB0 vaccination.
Awareness, Attitude, and Perception of Telemedicine Among Trinidad and Tobago Population
Authors: Ezinne Ngozika Esther , Bhattarai Dipesh , Anyasodor Anayochukwu Edward , Antwi-Adjei Ellen K. , Ekemiri Kingsley Kene , Armitage James Andrew , Osuagwu Uchechukwu Levi
Published: December 2023

Aim

To assess the awareness, attitude and perception of Trinidad and Tobago population towards telemedicine

Method

A cross-sectional study was conducted using a structured questionnaire on patients that visited health centres in the North Central region. A systematic random sampling method was used to select participants. Descriptive statistics including mean and standard deviation were used to calculate categorical and continuous variables. Comparison between the categorical groups of the demographic variables for each of the three main outcome variables were analysed through one-way analysis of variance (ANOVA). Statistical significance was defined as P<0.05.

Results

A total of 528 participated in the study. Most (60%) of them were female, and aged 21 to 40 years (62.1%). Awareness of telemedicine was 34.4%, but the majority (82.5%) had never used telemedicine before. About half (51.3%) acknowledged the necessity of telemedicine but few (36.4%) were satisfied with the services. Most (64%) were willing to try mobile-based healthcare apps. Concerns over lack of familiarity with telemedicine platforms (44.5%) and result accuracy (15.5%) were the major barriers to using telemedicine. Awareness of telemedicine was significantly associated with being female (P < 0.001), a medical profession (P = 0.004), familiarity in use of computers (P = 0.004) and frequent interaction with doctors online (P < 0.001). Positive attitude towards telemedicine was associated with having a diploma, being a medical professional, being computer literate and frequent interaction with doctor online. Positive perception towards telemedicine was associated with marital status (Single or Previously Married) (P = 0.011), one’s ability to use the computer (P = 0.009), their level of competency in computer usage (P = 0.002), and frequency of interacting with doctors online (P < 0.002).

Conclusion

The study revealed that although the level of telemedicine awareness is low, the majority of respondents demonstrated positive attitude and perception towards telemedicine. The findings suggest the need to educate the public on the benefits of telemedicine and create awareness of its use in T&T.
Perception of butenolides byBacillus subtilisvia the α/β-hydrolase RsbQ
Authors: Melville Kim T , Kamran Muhammad , Yao Jiaren , Costa Marianne , Holland Madeleine , Taylor Nicolas L , Fritz Georg , Flematti Gavin R , Waters Mark T
Published: December 2023

The regulation of behavioural and developmental decisions by small molecules is common to all domains of life. In plants, strigolactones and karrikins are butenolide growth regulators that influence several aspects of plant growth and development, as well as interactions with symbiotic fungi1–3. DWARF14 (D14) and KARRIKIN INSENSITIVE2 (KAI2) are homologous receptors that perceive strigolactones and karrikins, respectively, and that hydrolyse their ligands to effect signal transduction4–7. RsbQ, a homologue of D14 and KAI2 from the Gram-positive bacteriumBacillus subtilis, regulates growth responses to nutritional stress via the alternative transcription factor SigmaB (σB)8,9. However, the molecular function of RsbQ is unknown. Here we show that RsbQ perceives butenolide compounds that are bioactive in plants. RsbQ is thermally destabilised by the synthetic strigolactone GR24 and its desmethyl butenolide equivalent dGR24. We show that, like D14 and KAI2, RsbQ is a functional butenolide hydrolase that undergoes covalent modification of the catalytic histidine residue. Exogenous application of both GR24 and dGR24 inhibited the endogenous signalling function of RsbQin vivo, with dGR24 being 10-fold more potent. Application of dGR24 toB. subtilisphenocopied loss-of-functionrsbQmutations and led to a significant down-regulation of σB-regulated transcripts. We also discovered that exogenous butenolides promoted the transition from planktonic to biofilm growth. Our results suggest that butenolides may serve as inter-kingdom signalling compounds between plants and bacteria to help shape rhizosphere communities.
Control of asparagine homeostasis inBacillus subtilis: Identification of promiscuous amino acid importers and exporters
Authors: Meißner Janek , Königshof Manuel , Wrede Katrin , Warneke Robert , Mardoukhi Mohammad Saba Yousef , Commichau Fabian M. , Stülke Jörg
Published: December 2023

Amino acids are the main building block for proteins. The Gram-positive model bacteriumB. subtilisis able to import all proteinogenic amino acids from the environment as well as to synthesize them. However, the players involved in the acquisition of asparagine have not yet been identified for this bacterium. In this work, we used D-asparagine as a toxic analog of L-asparagine to identify asparagine transporters. This revealed that D-but not L-asparagine is taken up by the malate/lactate antiporter MleN. Specific strains that are sensitive to the presence of L-asparagine due to the lack of the second messenger cyclic di-AMP or due to the intracellular accumulation of this amino acid were used to isolate and characterize suppressor mutants that were resistant to the presence of otherwise growth-inhibiting concentrations of L-asparagine. These screens identified the broad-spectrum amino acid importers AimA and BcaP as responsible for the acquisition of L-asparagine. The amino acid exporter AzlCD allows detoxification of L-asparagine in addition to 4-azaleucine and histidine. This work supports the idea that amino acids are often transported by promiscuous importers and exporters. However, our work also shows that even stereo-enantiomeric amino acids do not necessarily use the same transport systems.

IMPORTANCE

Transport of amino acid is a poorly studied function in many bacteria, including the model organismBacillus subtilis. The identification of transporters is hampered by the redundancy of transport systems for most amino acids as well as by the poor specificity of the transporters. Here, we apply several strategies to use the growth-inhibitive effect of many amino acids under defined conditions to isolate suppressor mutants that exhibit either reduced uptake or enhanced export of asparagine, resulting in the identification of uptake and export systems for L-asparagine. The approaches used here may be useful for the identification of transporters for other amino acids both inB. subtilisand other bacteria as well.
Excess fermentation and lactic acidosis as detrimental functions of the gut microbes in treatment-naive TB patients
Authors: Yunusbaeva Milyausha , Borodina Liliya , Terentyeva Darya , Bogdanova Anna , Zakirova Aigul , Bulatov Shamil , Altinbaev Radick , Bilalov Fanil , Yunusbayev Bayazit
Published: December 2023

Gut microbiota link to host immunity motivated numerous studies of the gut microbiome in tuberculosis (TB) patients. However, these studies did not explore the metabolic capacity of the gut community, which is a key axis of impact on the host’s immunity. We used deep sequencing of fecal samples from 23 treatment-naive TB patients and 48 healthy donors to reconstruct the metabolic capacity and strain/species-level content of the gut microbiome. We show that the strong taxonomic divergence of the gut community in TB patients is explained by the systematic depletion of the commensal flora of the large intestine,Bacteroidetes,and an increase inActinobacteria, Firmicutes, andProteobacteriasuch asStreptococcaceae, Erysipelotrichaceae, Lachnospiraceae,andEnterobacteriaceae.The cumulative expansion of diverse disease-associated pathobionts in patients reached 1/4 of the total gut microbiota, suggesting a heavy toll on host immunity along with MTB infection. Reconstruction of metabolic pathways showed that the microbial community in patients shifted toward rapid growth using glycolysis and excess fermentation to produce acetate and lactate. Higher glucose availability in the intestine likely drives fermentation to lactate and growth, causing acidosis and endotoxemia. Excessive fermentation and lactic acidosis are likely characteristics of TB patients’ disturbed gut microbiomes. Since lactic acidosis strongly suppresses the normal gut flora, directly interferes with macrophage function, and is linked to mortality in TB patients, our findings highlight gut lactate acidosis as a novel research focus and a potential host-directed treatment target that can augment traditional TB treatment.
Adenosine Kinase regulates Sleep Timing and the Homeostatic Sleep Response through Distinct Molecular Pathways
Authors: Wakaf Zeinab , Dang Quang , Ru Yining , Taylor Lewis , Kapoor Sejal , Vasudevan idhar , Dallmann Robert , Jagannath Aarti
Published: December 2023

Sleep behaviour is broadly regulated by two drives, the circadian (Process C), which is orchestrated by the suprachiasmatic nuclei (SCN), and controls sleep timing, and the homeostatic (Process S), which controls sleep amount and the response to sleep deprivation (Borbélyet al., 2016). However, the molecular pathways that mediate their independent effects, and their interactions remain unclear. Adenosine is an important integrator of both processes (Bjorness & Greene, 2009; Jagannathet al., 2021, 2022), such that adenosine levels track and modulate wakefulness, whilst adenosine signalling inhibits the circadian response to light. Therefore, we studied the sleep/circadian behaviour, and cortical and SCN transcriptomic profiles of a mouse model overexpressing Adenosine Kinase (Adk-Tg) (Fedeleet al., 2005), (Palchykovaet al., 2010). We found that overall, the Adk-Tg mouse slept less and showed lower amplitude circadian rhythms with an altered sleep/wake distribution across the 24h day, which correlated with changes in transcription of synaptic signalling genes that would shift the excitatory/inhibitory balance. In addition, the Adk-Tg mouse showed a reduced level of ERK phosphorylation, and attenuation of DNA repair related pathways. After sleep deprivation, however, the Adk-Tg mouse significantly increased relative to wildtype, immediate early gene expression levels including ofArc, but paradoxically reduced ERK phosphorylation. Thus, baseline sleep levels and timing are regulated by ERK signalling, whereas the response to sleep loss is mediated by the alteration of the transcriptomic landscape independently of ERK.
#GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern
Authors: Ives Callum M. , Nguyen Linh , Fogarty Carl A. , Harbison Aoife M. , Durocher Yves , Klassen John S. , Fadda Elisa
Published: December 2023

Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and to structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work we show through over 45 μs of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated byN-glycosylation at N343 and how this glycan’s structural role changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2) and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of theN-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.
From amplicons to strains: The limitations of metabarcoding as criterium in the selection process of biocontrol strains against the pome fruit pathogenNeonectria ditissima
Authors: Russ Lina , Elena Jimenez Georgina , van den Beld Jean Luc , Nijhuis Els , Köhl Jürgen
Published: December 2023

European canker, caused by the fungal pathogenNeonectria ditissima, causes severe economic losses in apple production and conventional control measures are not sufficiently effective. Recently, parts of the endophyte community have been suggested to play a role in the response of the host to the pathogen, potentially leading to higher resistance of apple cultivars to disease outbreaks. In addition, advances on biologically controlling the disease have been booked by the application of fungi isolated at the boundary of cankered and healthy wood tissue. In this study we sought to evaluate if and how metabarcoding analysis can support decisions on selection of biological control agents in a two-steps process: first we profiled fungal and bacterial taxa using Illumina MiSeq sequencing on branches of potted apple trees that had been inoculated with either water or a suspension ofN. ditissimaspores. We combined the knowledge on the metataxonomic profile with quantitative data on theN. ditissimabranch colonisation (with relative abundances and absolute TaqMan qPCR concentrations) to identify taxa that show negative or positive correlations withN. ditissimaDNA concentration. Secondly, we compared our fungal metataxonomic profile to the ITS amplicons of fungal isolates that had been tested for biocontrol potential in bioassays in a previous study. The aim was to possibly link fungal taxa with proven efficacy against the pathogen to the microbiome composition. The only ASVs showing a consistent negative correlation to relative and absoluteN. ditissimaabundance belonged to the bacterial generaKineococcusandHymenobacter. For fungal taxa onlyN. ditissimaitself positively correlated to its increasing abundance, albeit only by rank and neither linearly nor beta binomially. Sequences belonging to the most promising antagonists from the study by Elena et al. (2022) could not be detected in the fungal microbiome profile at all. In addition, the combination of short reads length and high conservation within the chosen amplicon resulted in insufficient resolution to differentiate between a range of different efficacies of isolates belonging to the same genus (i.e.Aureobasidium).
Recovery from social isolation requires dopamine in males, but not the autism-related genenlg3in either sex
Authors: Yost Ryley T. , Scott Andrew M. , Kurbaj Judy M. , Walshe-Roussel Brendan , Dukas Reuven , Simon Anne F.
Published: December 2023

Social isolation causes profound changes in social behaviour in a variety of species including humans, monkeys, mice, bees, and vinegar flies. However, the genetic and molecular mechanisms modulating behavioural responses to both social isolation and social recovery remain to be elucidated. In this study, we quantified the behavioural response of vinegar flies to social isolation through the use of two distinct protocols, one involving flies’ social space preference and the other assessing flies’ sociability, defined as their spontaneous tendencies to form groups. We found that social isolation increased social space and reduced sociability. These effects of social isolation, however, were reversible and could be reduced after 3 days of group housing. Flies with a loss of function ofneuroligin3(ortholog of autism-relatedneuroligingenes) with known increased social space in a socially enriched environment, were still able to recover from social isolation. Using aUAS-TH-RNAi driven in all neurons, we show that dopamine is important for a response to social isolation and recovery in males but not in females. Furthermore, only in males, dopamine levels are reduced after isolation and are not recovered after group housing. Finally, in socially enriched flies with a loss of function ofneuroligin3, dopamine levels are reduced in males, but not in females. We propose a model to explain how dopamine andneuroligin3are involved in the behavioural response to social isolation and its recovery in a dynamic and sex-specific manner.