bluuebunny/crossref_metadata_2025 huggingface dataset:
BLAKORinputs to the BNST regulate social stress-escalated alcohol consumption
Authors: Paliarin Franciely , Duplantis Chelsea , Doré Evan , Basavanhalli Samhita , Weiser Emma , Jones Tameka W. , Maiya Rajani
Published: November 2024

Background

Aversive social experiences can lead to escalated drug consumption and increase the risk of relapse to drug seeking. Individuals who consume alcohol to alleviate the effects of social stress are more likely to develop an alcohol use disorder (AUD). Repeated social defeat stress (SDS) enhances the rewarding and reinforcing effects of alcohol. However, the neural mechanisms that underlie social stress-escalated alcohol drinking are not well understood. Here we explored the role of the dynorphin/kappa opioid receptor (Dyn/KOR) system in regulating social stress-escalated alcohol consumption.

Methods

Male and female mice were subjected to repeated SDS for 10 days following which they were left undisturbed in their home cages. They were then subject to intermittent access (IA) two-bottle choice alcohol consumption procedure. The effects of systemic and BNST-specific KOR antagonism using the selective KOR antagonist NorBNI on stress-escalated drinking were evaluated. Using chemogenetic approaches inOprk1-Cremice, we examined the role of KOR expressing cells in the basolateral amygdala (BLAKORs) and BLAKOR-BNST pathway in social stress-escalated alcohol consumption.

Results

Repeated SDS increased alcohol consumption and preference in both males and females. Systemic KOR antagonism attenuated SDS-escalated alcohol consumption in both males and females. BNST -specific KOR antagonism also attenuated stress-escalated drinking in males. Finally, selective chemogenetic activation of BLAKORsand BKAKOR-BNST pathway attenuated social stress-escalated alcohol consumption in both sexes.

Conclusion

Our results suggest a significant role for BLAKORprojections to the BNST in regulating social stress-escalated alcohol consumption. Our results provide further evidence that the Dyn/KOR system maybe a viable target for medications development to tareat comorbid stress and AUD.
Sudden sensory events trigger modality-independent responses across layers in the mouse neocortex
Authors: Benusiglio Diego , Asari Hiroki
Published: November 2024

Sudden sensory events trigger widespread electrocortical responses and noticeable changes in an animal’s behavior. It remains unclear, though, how this “surprise” signal is generated via afferent sensory input and represented by neuronal ensembles. Using in vivo electrophysiology, here we recorded the activity of different cortical areas across layers in awake head-fixed mice, while presenting sensory stimuli of different modalities and saliencies. When brief, salient stimuli were delivered at long intervals, we found prominent responses across cortical areas regardless of the stimulus modalities, resembling those observed in human electroencephalography. These responses were larger and emerged earlier in the infragranular layer than in the granular layer of the primary sensory cortex. At short inter-stimulus intervals, in contrast, only modality-specific responses were observed in the corresponding primary sensory cortex. These results indicate that sensory information travels through multiple ascending pathways, in particular, supra-modal surprise signals via non-classical sensory pathways to the cortex.
Critical role of Spatio-Temporally Regulated Maternal RNAs in Zebrafish Embryogenesis
Authors: Kushawah Gopal , Amaral Danielson Baia , Hassan Huzaifa , Gogol Madelaine , Nowotarski Stephanie H. , Bazzini Ariel A.
Published: November 2024

The maternal-to-zygotic transition shifts regulatory control from maternal to zygotic messenger RNAs (mRNA) through maternal mRNA degradation. While temporal aspects of maternal mRNA decay are known, spatial mechanisms remain underexplored. Using CRISPR-Cas9 and CRISPR-Cas13d systems, we functionally dissected the contribution of maternal versus zygotic fractions and overcame challenges of studying embryonic lethal genes. We identified differentially distributed maternal mRNAs in specific cells and evidenced the critical role of five maternal mRNAs,cth1, arl4d, abi1b, foxaandlhx1a,in embryogenesis. Further, we focused on the functionally uncharacterizedcth1gene, revealing its essential role in gametogenesis and embryogenesis.Cth1acts as a spatio-temporal RNA decay factor regulating mRNA stability and accumulation of its targets in a spatio-temporal manner through 3’UTR recognition during early development. Furthermore,Cth13’UTR drives its spatio-temporal RNA localization. Our findings provide new insights into spatio-temporal RNA decay mechanisms and highlight dual CRISPR-Cas strategies in studying embryonic development.

Highlights

Differentially distributed marginal maternal RNAs have a critical role in early embryogenesis.

Cas13d complements the Cas9 limitation to study the functions of embryonic lethal genes.

Cth1is essential for gametogenesis and early embryonic development.

Cth1is a maternal RNA decay factor required for spatio-temporal RNA regulation.

3’UTR ofCth1drives its spatio-temporal RNA dynamics.
The Tailtag System: Tracking Multiple Mice in a Complex Environment Over a Prolonged Period Using ArUco Markers
Authors: Coulombe Vincent , Rivera Arturo Marroquín , Monfared Sadegh , Roussel David-Alexandre , Leboulleux Quentin , Peralta Modesto R. , Gosselin Benoit , Labonté Benoit
Published: November 2024

Despite recent advancements, safely and reliably tracking individual movements over extended periods, particularly within complex social groups, remains challenging. Traditional methods like colour coding, tagging, and RFID tracking, while effective, have notable practical limitations. State-of-the-art neural network-based trackers often struggle to maintain individual identities in large groups for more than a few seconds. Fiducial tags like ArUco codes present a potential solution by enabling accurate tracking and identity management, yet their topical application on mammals has proven difficult without frequent human intervention. In this study, we introduce the Tailtag system: a non-invasive, ergonomic tail ring embedded with an ArUco marker. This system includes a comprehensive parameter optimization guide along with practical guidelines on marker selection. Our Tailtag system demonstrated the ability to automatically and reliably track individual mice in social colonies of up to 20 individuals over a period of seven days without performance degradation, facilitating a detailed analysis of social dynamics in naturalized environments.
Systematic screen of RNA binding proteins that enhance circular RNA translation
Authors: Lu Qianyun , Wang Siqi , Ye Yanwen , Yang Yun , Wang Zefeng
Published: November 2024

Translatable circular RNAs (circRNAs) have emerged as a promising alternative to linear mRNA as new therapeutics due to its improved stability. The translation of circRNAs is mainly driving by internal ribosome entry site (IRES) or IRES-like elements, which is under regulation by varioustrans-acting RNA binding proteins (RBPs). Here we designed a cell-based system to systematically screen RBPs that enhance translation of circRNAs, and identified a total of 68 proteins as putative activators of noncanonical translation. These translation activators mainly involved in the functions of RNA processing, ribosomal biogenesis and translation initiation. Furthermore, we developed a machine learning algorithm to extract common sequence features of these activators, which predicted more potential RBPs with translation activator activities. The newly identified and predicted activators were subsequently demonstrated to promote the IRES-mediated circRNA translation in a context-dependent fashion. This investigation provides new insights to discover functions for IREStrans-acting factors and to expand the toolbox for engineered RBPs in RNA synthetic biology.
SARS-CoV-2 JN.1 reveals attenuated pathogenicity and airborne transmission
Authors: Liu Ruixue , Jin Qiushi , Wang Wenqi , Zhang Cheng , Zhang Hang , Li Bing , Yan Fang , Xia Xianzhu , Li Jianmin , Wang Xuefeng , Gao Yuwei
Published: November 2024

JN.1 is a subvariant of SARS-CoV-2 Omicron BA.2.86 lineage that was predominant worldwide in early 2024, of which the in vivo characteristics are largely unknown. Our results demonstrated that the replication of JN.1 was more efficient than that of the parental BA.2 in Vero cells, which demonstrated low dependence on TMPRSS2. Compared to Omicron variants BA.2 and XBB EG.5.1, JN.1 replicated less efficiently in hACE2 mouse lungs of which the intranasal infection was not lethal to hACE2 mice and led to weaker immune dysregulation. On a more sensitive, aged hACE2 hamster model, JN.1 led to a lower mortality rate and no weight loss, corresponding well with the low preference in lower airways. Lower amounts of viruses in nasal washes and exhaled aerosols were detected in JN.1 infected wildtype hamsters than EG.5.1, and consistently, JN.1 also exhibited largely reduced airborne transmission. Moreover, the poor transmission was also clearly demonstrated even by using hamsters expressing hACE2 receptors in the whole airway. Thus both pathogenicity and airborne transmission of JN.1 were demonstrated to be largely attenuated.

Importance

Currently, SARS-CoV-2 JN.1 and its subvariants have fully replaced the previous dominant XBB lineage around the world. Although the strong immune evasion of JN.1 has been distinctly revealed, its in vivo pathogenicity and airborne transmission remained unclear. By using multiple Omicron-sensitive rodent models, our findings demonstrated that the pathogenicity of JN.1 was largely attenuated. The weak airborne transmission of JN.1 in wildtype and hACE2 hamsters was consistent with the reported relative lower transmissibility in human, and the using of airway-expressing hACE2 hamsters ulteriorly eliminates the potential bias in viral transmission studies induced by receptor divergence between animal models and human. These findings uncover the in vivo virological characteristics of SARS-CoV-2 novel lineage, providing insights for communicable disease control.
The impact of psychological treatment on catastrophization and pharmacological response in chronic migraine: A single-center experience
Authors: Sepe Federica Nicoletta , Lanni Claudia , De Michelis Daniele , Lancia Giacomo
Published: November 2024

Abstract

Background

We aimed to assess the impact of pain catastrophizing, measured using the Italian version of the Pain Catastrophizing Scale (PCS), on the clinical response of patients with chronic migraine to anti-CGRP monoclonal antibodies combined with a multidisciplinary approach, including psychological treatment.

Methods

25 Outpatients from SS. Antonio e Biagio e Cesare Arrigo headache clinic randomly assigned to receive Galcanezumab, Erenumab, or Fremanezumab. Their clinical response was evaluated over six months using various measures, including reducing the number of days with migraine per month, and quality of life using Headache Impact Test (HIT 6), MIgraine Disability Assessment Score questionnaire (MIDAS), and Beck’s Inventory Scale (BDI II) scales to assess comorbid depression.

Results

We established a strong correlation between HIT 6 and PCS, with coefficients of 0.81 and 0.88 atT1andT2, respectively. Furthermore, we found no significant correlation between PCS and the other scales, such as MIDAS, as with any pharmacological therapies.

Conclusion

This study aims to clearly define the impact of a multidisciplinary approach including a psychological follow-up on a particular clinical phenotype of chronic migraines and their tendency to catastrophize, but more extended data are needed.
Observational Report on Functional SARS-CoV-2 Immune Responses in Immune Competent and Compromised Individuals
Authors: Peek Laura J , Patrick Alicia , Givens Niki , D’Alessio Brittany , Weaver Amanda , Jackson Leisa , White Thomas J , Pestano Gary A
Published: November 2024

Objectives

Durable immune responses against SARS-CoV-2 are generally observed in previously infected individuals. Immunocompromised individuals may show less durable responses. Investigation of immune responses is needed to inform individuals on whether measures such as boosters may be advisable.

Methods

Three SARS-CoV-2 ELISA tests were utilized to monitor responses in 82 individuals in the United States [nucleocapsid protein (N)-specific antibody and spike RBD (receptor binding domain)-specific neutralizing antibody (nAb), and spike-specific interferon-γ (IFN-γ) release by T cells]. De-identified case reports highlight results for this cohort; 21 previously infected and vaccinated, 57 never infected and vaccinated, 2 breakthrough infections post-vaccination and 2 neither infected nor vaccinated.

Results

The vaccines generated nAb responses in naïve donors, and in previously infected individuals with waning responses, immunosuppression, or weak infection responses. The cutoff for the nAb potency was established at 41.1 IU/mL when calibrated to the WHO International Standard (IU) using the NCI SARS-CoV-2 Standard. This relationship has the critical potential to allow comparisons of nAb measures to be utilized in studies of correlates of protection. Further, previously infected donors demonstrated robust T cell activity, while vaccinated and infection-naïve individuals had lower responses.

Conclusions

Calibrated ELISA tests may aid broad vaccination strategies given their low cost and wide accessibility. Additional studies that relate measures of the adaptive responses to immunity from serious disease and infection are needed.
Assessing and managing bone-health and fracture risk in Parkinson’s disease: the BONE PARK 2 protocol
Authors: Naylor Katie C , Tenison Emma , Hardcastle Sarah A , Lyell Veronica , Gregson Celia L , Henderson Emily J
Published: November 2024

Background

In Parkinson’s disease (PD) the propensity to fall and the higher risk of osteoporosis converge yielding a high fracture risk. Updated National Osteoporosis Guideline Group (NOGG) guidance recommends that PD should trigger a risk assessment, for example using the FRAX tool, yet clinical pathways remain sub-optimal. To address this, we generated an algorithm for the assessment and management of bone-health specifically in PD.

Methods

Within the Proactive and Integrated Management and Empowerment in Parkinson’s Disease randomised controlled trial (PRIME-UK RCT), bone-health metrics were collected, and all participants were offered a DXA scan. The FRAX tool was used to obtain the 10-year probability of hip and major osteoporotic fracture (MOF), and the resulting NOGG risk- category recorded. Probabilities were recalculated including femoral-neck bone mineral density (FN-BMD) and/or with numeric adjustment for recurrent falls, and results compared.

Results

Among 182 people with parkinsonism (mean age 73.8 years, 65% male, median disease duration 5-years), 28.0% reported a prior fragility fracture, and 40.7% recurrent falls over the previous year. 28.6% had MOF above NOGG intervention thresholds (IT); whilst 12.1% had a FN-BMD T-Score ≤-2.5. Recalculation of FRAX with FN-BMD (n=182) reduced fracture MOF and hip fracture probabilities; 12 (6.6%) deescalated below the IT, and 16 (8.8%) moved above the IT.

Conclusions

This 2024 BONE-PARK algorithm is informed by both the latest NOGG Guidelines and novel findings in a ‘real-world’ population. The algorithm will aid bone health assessment people with PD.

Key points

Bone-health in Parkinson’s is under-recognised and under-treated, and we have demonstrated an ongoing treatment gap.

In this population, we have demonstrated DXA is feasible but infrequently changes treatment.

Our Parkinson’s specific guidance supports clinicians and patients to recognise, investigate and treat fracture risk.
Time-restricted eating and exercise training before and during pregnancy for people with increased risk of gestational diabetes: the BEFORE THE BEGINNING randomised controlled trial
Authors: Sujan MAJ , Skarstad HMS , Rosvold G , Fougner SL , Follestad T , Salvesen KÅ , Moholdt T
Published: November 2024

Objective

To determine the effect of a pre-pregnancy lifestyle intervention on glucose tolerance in people at higher risk of gestational diabetes mellitus (GDM).

Design

Randomised controlled trial.

Setting

University hospital in Trondheim, Norway.

Participants

167 people with at least one risk factor for GDM who contemplated pregnancy.

Intervention

The participants were randomly allocated (1:1) to a lifestyle intervention or a standard care control group. The intervention consisted of exercise training and time-restricted eating, started pre-pregnancy and continued throughout pregnancy. Exercise volume was set using a physical activity metric that translates heart rate into a score (Personal Activity Intelligence, PAI), with the goal of ≥ 100 weekly PAI-points. Time-restricted eating involved consuming all energy within ≤ 10 hours/day, ≥ 5 days per week.

Main outcome measures

2-hour plasma glucose level in an oral glucose tolerance test (OGTT) in gestational week 28. The primary analysis used an intention-to-treat principle.

Results

From 02.10.2020 to 12.05.2023, we included 167 participants: 84 in intervention and 83 in control, out of whom 111 became pregnant (56 in intervention and 55 in control). One participant in the intervention group was excluded from the analysis because of pre-pregnancy diabetes. Pregnancy data from one participant in the control group were excluded from the analysis because of twin pregnancy. Time to pregnancy was 112 days (SD 105) in the intervention (INT) group and 83 days (SD 69) in the control (CON) group (p = .087). The intervention had no significant effect on 2-hour plasma glucose level in an OGTT in gestational week 28 (mean difference, 0.48 mmol/L, 95% confidence interval [CI], -0.05 to 1.01, p = .077). There was no evidence of between-group differences in other measures of glycaemic control before or during pregnancy. The intervention did not significantly influence GDM prevalence rates in gestational week 12 (INT 5.5%, CON 5.6%, p = 1.000) or gestational week 28 (INT 14.5%, CON 11.1%, p = .592). In gestational week 28, the intervention group had gained less weight (2.0 kg, 95% CI, -3.3 to -0.8, p = .002) and fat mass (-1.5 kg, 95% CI, -2.5 to -0.4, p = .008) than the control group. Participants could adhere to the ≤ 10-hour eating window and maintain ≥ 100 PAI per rolling week pre-pregnancy, but adherence to both intervention components decreased during pregnancy.

Conclusions

A combination of time-restricted eating and exercise training started before and continued throughout pregnancy had no significant effect on glycaemic control in late pregnancy, but our findings suggest that the intervention lowered gestational weight and fat mass gain in people with increased risk of GDM.

Trial registration

ClinicalTrials.govNCT04585581
A systematic review of the methodological considerations inCampylobacterburden of disease studies
Authors: Tumulty Megan , Di Bari Carlotta , Devleesschauwer Brecht , Pires Sara M. , Kabir Zubair
Published: November 2024

Background

Campylobacteriosis is a major zoonotic and foodborne disease (FBD), posing a substantial social and health economic burden on human health. Burden of disease (BoD) studies, which increasingly use the disability-adjusted life years (DALYs) metric, provide comprehensive insights into disease effects. However, the complexity of DALY calculations, combined with diverse causative agents and research gaps, complicates cross-regional comparisons. This review evaluates existingCampylobacterBoD studies and interrogates their methodological approaches and assumptions in quantifying DALYs.

Methods/Principal Findings

A systematic search of PubMed, EMBASE, Web of Science, and selected grey literature databases was conducted to identify existingCampylobacterBoD studies. Studies assessing the BoD methodology and calculation using the DALY framework were considered. In total, 23 studies met the predefined inclusion criteria. Of these, 19 were single-country studies, while 4 were multi-country analyses. A significant data gap exists, with limited or no studies from low- and middle-income countries, exemplified by just one study obtained from Rwanda. Most studies used an incidence- and pathogen-based approach to estimate DALYs, excluding social weighting, in line with the Global Burden of Disease (GBD) study. Methodological discrepancies were noted, especially in disability weight (DW) assignment, health state classification, and life expectancy table usage. Most single-country studies (n=8) used national life tables rather than universal ones, challenging cross-country comparisons due to a lack of standardisation.

Conclusion

Significant variations in the methodological approaches and assumptions forCampylobacterBoD studies exist. Addressing these disparities is essential for harmonising methodological design choices using the DALYs metric to inform evidence-based public health policies and interventions.

PROSPERO Registration Number

The protocol for this study was registered with the International Prospective Register of Systematic Reviews (PROSPERO), which can be accessed under the registration numberCRD42023414973.
Diverse ancestry GWAS for advanced age-related macular degeneration in TOPMed-imputed and Ophthalmologically-confirmed 16,108 cases and 18,038 controls
Authors: Gorski Mathias , Grunin Michelle , Herold Janina M. , Fröhlich Benedikt , Behr Merle , Wheeler Nicholas , Bush William S. , Song Yeunjoo E. , Zhu Xiaofeng , Blanton Susan H. , Pericak-Vance Margaret A. , Heid Iris M. , Haines Jonathan L. ,   International Age-related Macular Degeneration Genomics Consortium
Published: November 2024

Age-related macular degeneration (AMD) is a leading cause of blindness with $344 billion dollars global costs. In 2016, the International Age-related Macular Degeneration Genomics Consortium devised genomic data on ∼50,000 individuals (IAMDGC 1.0) and identified 52 variants across 34 loci associated with advanced AMD in European ancestry. We have now analyzed a more densely imputed version (IAMDGC 2.0) and performed cross-ancestry GWAS in 16,108 advanced AMD cases and 18,038 AMD-free controls. This identified 28 loci at P<5×10−8, including two additional AMD loci compared to IAMDGC 1.0 (SERPINA1andCPN1). Fine-mapping supported one ancestry-shared signal aroundHTRA1/ARMS2and nine signals aroundCFHwithout African ancestry contribution. The 52-variant genetic risk score with and the 44-variant score withoutCFH-variants predicted advanced AMD not only in EUR, but also in AFR and ASN (AUC=0.80/0.75, 0.65/0.64, 0.80/0.79, respectively). Our results indicate that the genetic underpinning of advanced AMD is mostly shared between ancestries.
Prediction of Outcomes in Infants with Hydrops Fetalis by Mode of Delivery: A Retrospective Cohort from a Low-Resource Setting in Kenya
Authors: Amubuomombe Philippe P. , Kosgei Wycliffe K. , Tonui K. Philiph , Mogeni Richard M. , Mutindi K. , Esendi Sarah K. , Ngeleche Ruth , Nyongesa Paul , Koech Irene , Jesani Jignesh K. , Wanjama Esther , Hirani Rajshree K. , Chesire Emily , Oeri Donah , Chepkemboi Audrey K. , Makasi Deborah V. , Shroff Vahista J. , Kipchumba Bett C. , Mishra Pallavi , Kirwa Philip , Hamza Amgad , Aruasa Wilson K. , Mwangi Ann , Orang’o Elkanah O.
Published: November 2024

BACKGROUND

Hydrops fetalis is a condition associated with increased perinatal and neonatal mortality and morbidity. The overall survival rate of infants diagnosed with hydrops fetalis is currently estimated to be 27%, despite advanced intrauterine and neonatal care. Factors that contribute to poor perinatal and neonatal outcomes have been identified; however, little is known about the existing specific tool for predicting perinatal outcomes by mode of delivery.

OBJECTIVE

This study aimed to determine whether cesarean section improves the perinatal outcomes of infants with hydrops fetalis in low-resource settings.

STUDY DESIGN

This was a retrospective cohort study in which 102 medical records of pregnancies complicated by hydrops fetalis were retrieved. For all included women, transabdominal ultrasound was performed during pregnancy as part of the standard diagnostic modality for hydrops fetalis. The medical records of all pregnant women and their newborns were retrieved and reviewed to collect information related to the outcomes by mode of delivery, either cesarean section or vaginal delivery. The pregnant women were divided into the following 4 classes based on the severity of hydrops fetalis determined by obstetric ultrasound findings: class I (mild features of hydrops fetalis), II (moderate features of hydrops fetalis), III (moderately severe features of hydrops fetalis), and IV (severe features of hydrops fetalis). The significance of the obtained data was set at a two-tailed p<0.05.

RESULTS

This cohort study estimated the proportion of hydrops fetalis to be 0.8%. Nonimmune hydrops fetalis was the common type, accounting for 75.6% of all cases. The 7-day survival rate was estimated to be 42.2%. There was no statistically significant association between the mode of delivery and perinatal survival (pv=0.84). Survival increased, especially in class II patients (47.5%), while survival was similarly low between class III and IV patients (22.5%). A statistically significant association was between class and survival (pv <0.001).

CONCLUSION

Cesarean section delivery does not improve the perinatal outcomes of hydrops fetalis infants. Creating a validated tool for predicting the perinatal outcomes of infants with hydrops fetalis by mode of delivery is useful for assisting in decision-making and predicting perinatal outcomes.
The impact of Option B+ policy on engagement in HIV care and viral suppression among pregnant women living with HIV in South Africa
Authors: Nattey Cornelius , Maskew Mhairi , Jinga Nelly , Wise Amy , van Dongen Nicola , Brizido Thalia Ferreira , Mudau Maanda , Technau Karl-G , Clouse Kate
Published: November 2024

Background

Early access to HIV care impacts maternal outcomes and the risk of vertical transmission of HIV Option B+, a policy that mandates offering all pregnant women living with HIV (PWLH) lifelong antiretroviral therapy (ART) irrespective of their CD4 count, has been adopted across sub-Saharan Africa, including South Africa since 2015. This study aimed to assess the impact of Option B+ on engagement in HIV care and viral suppression among pregnant women in South Africa.

Methods

This observational study used data from pregnant women living with HIV who delivered at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa from 2013-2017. Linkage to a national HIV laboratory cohort (the NHLS National HIV cohort) was used to ascertain engagement in HIV care prior to antenatal care (ANC) entry and viral load outcomes. Analyses were stratified by the pre-Option B+ (2013-2015) and Option B+ (2016-2017) eras. We compared engagement rates before and during the Option B+ era and assessed factors associated with HIV care engagement and viral suppression. Risk ratios were estimated using log-binomial regression.Results:Among 4,865 PWLH, 65% had evidence of prior engagement in HIV care. Prior engagement in care was higher during the Option B+ era (66%) compared to the pre-Option B+ era (55%) (p<0.001). Younger women (18-24 years) were less likely to engage in HIV care than those aged 25-34 years (aRR 0.8, 95% CI: 0.6-0.9). Women with CD4 counts <200 cells/mm³ were less likely to have been engaged in care prior to pregnancy compared to those with CD4 ≥500 (aRR 0.6, 95% CI: 0.6-0.7). Primigravid women had a 30% lower likelihood of earlier HIV care engagement compared to those with 2-3 pregnancies (aRR 0.7, 95% CI: 0.5-0.8). Overall viral suppression was higher in women reporting prior ART use compared to those with no prior HIV care (33% vs. 19%, p<0.001). During the four-year study period, the proportion of PWLH who had a viral load recorded but were not virally suppressed ranged from 22-36%.

Conclusion

The Option B+ policy led to increased engagement in HIV care prior to pregnancy. However, high prevalence of unsuppressed viral load during the Option B+ era highlights the need for continued monitoring and support to sustain the benefits of this policy. Pregnancy and antenatal care services remain an essential portal of entry to HIV care among PWLH in South Africa. Interventions to improve early ANC attendance and maternal engagement in HIV care prior to pregnancy are critical to eliminate vertical HIV transmission.
Frontiers of cervical cancer research: an analysis from the top 100 most influential articles in the field
Authors: Liang Lei , Song Chuangxiu , Chang Chun , Chen Shichao , Yang Bo , Sun Li
Published: November 2024

Backgroung

Cervical cancer (CC) is one of the common gynecological malignancies, which has a serious negative impact on the quality of life of patients, and brings huge economic pressure and burden to society. The most effective treatment for CC has become an important issue worldwide.

Method

In order to determine the current research hotspots and development trends in a particular field, we conducted a bibliometric analysis of the top 100 cited papers. To achieve this, we searched for the top 100 most cited papers on the Science Citation Index Expanded (SCI Expanded) on the Web of Science (WOS), based on the CCS (citation count score). We then reviewed relevant literature from different years, countries/regions, institutions, authors, keywords, and references. Using VOS viewer and Cite Space software, we constructed a knowledge map, and finally compiled the relevant information we retrieved from the literature using Excel. Through this process, we were able to make predictions about the current focus and trends in the field.

Results

Between 2013 and 2023, numerous journals published the top 100 cited research papers. The International Agency for Research on Cancer and the American Cancer Society were the most cited institutions. The United States contributed the most papers, followed by France and England. The top 5 keyword co-occurrences were cervical cancer, women, human papillomavirus, United States, and colorectal cancer. Cluster analysis results suggest that future research in CCS may focus on prophylaxis and HPV vaccination.

Conclusion

Bibliometric analysis can quickly and intuitively identify the focus and boundaries of cervical cancer research. Our findings suggest that prophylaxis and HPV vaccination may be the focus and trend for future research on cervical cancer.
Exploring influenza vaccination coverage and determinants through digital participatory surveillance
Authors: Kelley Kathleen , Gozzi Nicolò , Mazzoli Mattia , Paolotti Daniela
Published: November 2024

Background:

Vaccination is key for mitigating the impact of recurring seasonal influenza epidemics. Despite the efficacy and safety of influenza vaccines, achieving optimal vaccination uptake remains a challenge. This study aimed to explore the determinants of influenza vaccination uptake using data from Influweb, the Italian node of the InfluenzaNet participatory surveillance network, and to compare self-reported vaccination rates with data from official sources.

Methods

This study utilizes a longitudinal dataset of self-reported vaccination statuses from Italian participants across the 2011-2021 flu seasons. Logistic regression models were used to identify factors associated with vaccination uptake, while vaccination coverage of the Influweb population was compared with national data. Post-stratification weights were applied to account for demographic differences between the Influweb sample and the general population.

Results

The analysis reveals that individuals using public transport, those living with minors, and residents of the Islands macro-region are less likely to receive the influenza vaccination. On the other hand, university-educated individuals, and those on medication for chronic diseases are more likely to be vaccinated. Age also plays a role: individuals aged 44 and under are less likely to vaccinate compared to those aged 45-65, while those over 65 are more likely to do so. Furthermore, higher cumulative influenza-like illness incidence rates within a macro-region are associated with increased vaccination uptake, suggesting that local epidemic dynamics may influence individual decisions. Finally, the impact of COVID-19 pandemic was associated with an increase in influenza vaccination uptake. Comparison of the Influweb data to nationally reported vaccination rates revealed higher coverage for self-reported vaccination. This could be linked to the voluntary nature of the survey, possibly attracting a more health-conscious cohort.

Conclusions

Our study found that individuals living with minors and those relying on public transportation have lower odds of being vaccinated, despite having a higher documented risk of respiratory virus exposure. These findings highlight the importance of continued public health efforts targeting vulnerable groups and raising awareness about the risks of forgoing vaccination. The complex interplay of socioeconomic, demographic, and public health context significantly shapes vaccination decisions, emphasizing the need for tailored public health campaigns.
Rural-Urban Disparities of Alzheimer's Disease and Related Dementias: A Scoping Review
Authors: Kramer Mackenzie , Cutty Maxwell , Knox Sara , Alekseyenko Alexander , Mollalo Abolfazl
Published: November 2024

Background & Aim: The rising age of the global population has made Alzheimer's Disease and Related Dementias (ADRD) a critical public health problem, with significant health-related disparities observed between rural and urban areas. However, no previous reviews have examined the scope and determinant factors contributing to rural-urban disparities of ADRD-related health outcomes. This study aims to systematically collate and synthesize peer-reviewed articles on rural-urban disparities in ADRD, identifying key determinants and research gaps to guide future research. Methods: We conducted a systematic search using key terms related to rural-urban disparities and ADRD without restrictions on geography or study design. Five search engines (MEDLINE, CINAHL, Web of Science, PubMed, and Scopus) were utilized to identify relevant articles. The search was performed on August 16, 2024, and included articles published from 2000 onward. Results: 62 articles met the eligibility criteria for data extraction and synthesis. Most articles were published after 2010 (90.3%) and were concentrated in the US, China, and Canada (64.5%). A majority had cross-sectional (59.7%) or cohort study designs (24.2%), primarily examining prevalence (40.3%) or incidence (11.3%). Findings often indicated a higher prevalence and incidence in rural areas, although inconsistent rural-urban classification systems were noted. Common risk factors included female gender, lower education level, lower income, and comorbidities such as diabetes and cerebrovascular diseases. Environmental (12.9%) and lifestyle (14.5%) factors for ADRD have been less explored. The statistical methods used were mainly traditional analyses (e.g., logistic regression) and lacked advanced techniques such as machine learning or causal inference methods. Conclusion: The gaps identified in this review emphasize the need for future research in underexplored geographic regions and encourage the use of advanced methods to investigate understudied factors, such as environmental, lifestyle, and genetic influences.
Mental Tasks Induce Common Modulations of Oscillations in Cortex and Spinal Cord
Authors: Ofner Patrick , Farina Dario , Mehring Carsten
Published: November 2024

We investigated whether power modulations of cortical oscillations induced by mental tasks are paralleled by the same modulations in spinal motor neurons. We recruited 15 participants and recorded high-density electromyography signals (HD-EMG) from the tibialis anterior muscle, as well as electroencephalography (EEG) signals. The cumulative spike train (CST) was computed from the activity of spinal motor neurons decoded from HD-EMG signals. The participants performed sustained dorsiflexion concurrent with foot motor imagery, hand motor imagery, mental arithmetic, or no specific mental task. We found significant power correlations between CST and EEG across trials irrespective of the mental task and across mental tasks at the intra-muscular coherence peak (τtrial= 0.08 ± 0.10,τtask= 0.33 ± 0.19, respectively; mean ± std. dev.). CST power in beta and low-gamma bands could provide a novel control signal for neural interface applications, as power changes in these bands are not translated into actual force changes. To evaluate the potential of CST bands as a control signal, we classified the mental tasks from CST bandpower with a linear classifier and obtained classification accuracies slightly but significantly above chance level (30% ± 5%; chance level = 25%). These results show for the first time that mental tasks can modulate the power of cortical and spinal oscillations concurrently. This supports the notion that movement-unrelated oscillations can leak down from the cortex to the spinal level. We further show that mental tasks can be classified from CST, although further research is necessary to boost the classification performance to an adequate level for neural interface applications.

Significance Statement

Spike trains of spinal motor neurons have frequency components below 10 Hz that are translated into muscle force changes. These spike trains also contain oscillations above 10 Hz that do not directly produce force changes, and currently lack a clear functional interpretation. Our findings indicate that these oscillations can, at least in part, be remnants of force-unrelated cortical oscillations that propagate down to spinal motor neurons. This propagation enables the decoding of modulations of cortical oscillations evoked by mental tasks at the level of spinal motor neurons. We evaluate the decoding of these oscillation modulations for potential neural interface applications.
Exploring Mechanisms of Action in Combinatorial Therapies through Solubility Alterations: Advancing AML Treatment
Authors: Gholizadeh Elham , Zangene Ehsan , Vadadokhau Uladzislau , Ritz Danilo , Miettinen Juho J. , Soliymani Rabah , Baumann Marc , Wilhelm Mathias , Heckman Caroline A. , Saei Amir A. , Jafari Mohieddin
Published: November 2024

Acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis. Although treatments like allogeneic hematopoietic stem cell transplantation and high-dose chemotherapy can potentially cure younger patients in some cases, challenges such as relapse and treatment-related toxicities remain significant. Combination therapy has been a cornerstone in AML treatment, offering enhanced efficacy by leveraging the synergistic effects of multiple agents. However, high toxicity levels and the genetic heterogeneity of AML complicate the identification of effective and universally applicable drug regimens. To address these challenges, we introduce CoPISA workflow (Proteome Integral Solubility/Stability Alteration Analysis for Combinations), an innovative method designed to study drug-target interactions specifically within combination therapies. CoPISA detects changes in protein solubility/stability that occur only when two drugs are used together, revealing cooperative mechanisms that single-drug treatments cannot achieve. We applied this method to two highly effective and low-toxicity drug combinations in AML, previously introduced by our group: LY3009120-sapanisertib (LS) and ruxolitinib-ulixertinib (RU). CoPISA workflow utilizes advanced proteomic tools to investigate both primary and secondary target effects, providing a deeper understanding of how combination therapies influence multiple signaling pathways to overcome resistance. Furthermore, we propose a novel concept termed “conjunctional inhibition”, where the combined action of drugs induces biological responses that cannot be achieved by individual agents. This approach introduces a transformation in designing combinatorial therapies and offers new directions for more effective treatments in AML and other complex diseases.
Cell fate determination is associated with changes in competing transcriptional units in the humanGATA1andGATA2lineage-determining transcription factors
Authors: Anderson Erik M , Li Hongchuan , Ruesch Michael , Wright Paul W , Freud Aharon G , Anderson Stephen K
Published: November 2024

The GATA1 and GATA2 transcription factors play a central role in early cell fate decisions in hematopoietic progenitor cells. Although the switch from GATA2 to GATA1 occupancy at GATA-binding sites in erythroblast-specific genes has been extensively studied, the underlying molecular mechanisms controlling this switch are not fully elucidated. An antisense promoter in the 5’ region of theGATA2gene produces a long non-coding RNA that has been shown to affectGATA2transcription and erythroblast differentiation. The recent identification of an antisense promoter in the first intron of theGATA1gene indicates that similar promoter competition mechanisms operate in these genes, potentially controlling GATA1/GATA2 levels in a probabilistic manner. In the current study we perform a comprehensive evaluation ofGATA1andGATA2transcripts in human CD34+progenitors either freshly isolated or differentiated in vitro and the human leukemia cell lines K562 and HL60. The ratio of competing sense and antisense transcripts varied significantly with differentiation status, suggesting that promoter competition controls cell fate decisions. Treatment of HL60 cells with differentiating agents resulted in significant changes in the ratio ofGATA2sense to antisense promoter activity, in agreement with previous results showing that sense and antisense transcription are associated with distinct cellular phenotypes.
Enhancement and validation of the antibiotic resistance prediction performance of a cloud-based genetics processing platform for Mycobacteria
Authors: Westhead Jeremy , Baker Catriona S , Brouard Marc , Colpus Matthew , Constantinides Bede , Hall Alexandra , Knaggs Jeff , Lopes Alves Marcela , Spies Ruan , Thai Hieu , Surrell Sarah , Govender Kumeren , Peto Timothy EA , Crook Derrick W , Omar Shaheed V , Turner Robert , Fowler Philip W
Published: November 2024

Tuberculosis remains a global health problem. Making it easier and quicker to identify which antibiotics an infection is likely to be susceptible to will be a key part of the solution. Whilst whole-genome sequencing offers many advantages, the processing of the genetic reads to produce the relevant public health and clinical information is, surprisingly, often the responsibility of the end user which inhibits uptake. Here we describe our Mycobacterial genetics processing pipeline and its deployment in a cloud-based platform. For antibiotic resistance prediction we have implemented the second edition of the WHO catalogue of resistance-associated variants. We validate the resistance prediction performance by constructing and processing a diverse dataset of 2,663 publicly-availableM. tuberculosissamples with published drug susceptibility testing (DST) data and find that identifying a sample as resistant if it contains a minor allele known to be associated with resistance increases sensitivity. By only considering high confidence DST results we are able to show that both isoniazid and rifampicin achieve sensitivities and specificities in excess of 95%.
Influenza Virus Enhances Bacterial Growth in the Lungs through Weakening Capsule Receptor-Mediated Bacterial Capture by Neutrophils
Authors: Fang Yujie , Ma Wenxia , Qian Chenyun , Hu Jiao , Tian Xianbin , Huang Xueting , Lai Wenlong , Wu Li , An Haoran , Zhang Jing-Ren
Published: November 2024

Certain serotypes of encapsulated bacteria are more associated with severe pneumonia than others, but the biological reason behind this association has remained largely unknown. This study has uncovered a causal relationship between capsule serotype and virulence phenotype ofStreptococcus pneumoniae, a leading cause of community-acquired pneumonia, in mice using isogenic bacteria. Certain high-virulence (HV) serotypes persist in the lungs and lead to severe pneumonia, whereas the low-virulence (LV) serotypes are effectively cleared. The capsule type-dependent difference in virulence is determined by the capsule-binding receptors, which recognize the capsular polysaccharides of the LV serotypes (but not the HV serotypes) and enable pathogen capture by neutrophils through complement activation. The capsule receptor-driven immunity of lung neutrophils is significantly compromised by pre-infection of influenza virus, which enhances the survival and virulence of the LVS. pneumoniaeserotypes, and recurs in the heightened pathogenicity ofHaemophilus influenzae. This study not only unravels the long-sought mechanistic mystery of serotype-dependent virulence in bacterial lung infections, but also provides an explanation for the well-known pathogenesis synergism between influenza virus and respiratory bacteria.

Graphical abstract
CHARACTERIZATION OF RECOMBINASE ACTIVITY ACROSS CELLULAR GROWTH PHASES
Authors: Gonzalez-Colell M. , Macia J.
Published: November 2024

Recombinases, which are enzymes that catalyze targeted DNA modifications, hold significant potential in synthetic biology. Their capacity to precisely manipulate genetic material enables the construction of complex genetic circuits that can be dynamically reconfigured in response to environmental stimuli. Such capabilities are essential for developing synthetic organisms tailored for specific functions, including biosensing, bioremediation, and pharmaceutical production. Therefore, characterizing the dynamics of recombinases is crucial for the innovative design of cellular devices. A deeper understanding of how recombinases interact with DNA in various conditions can improve the efficiency and control of genetic modifications, thereby enhancing both the functionality and reliability of synthetic biological systems.

This study presents a detailed examination of the dynamics and efficiency of the serine recombinase Bxb1, focusing on its behavior under controlled expression inEscherichia coli. It highlights the significant influence of cellular growth phases (exponential and stationary) on the efficiency of recombinase-mediated gene expression. Our findings show that recombinase activity is maintained during stationary phase, which is critical to ensure ongoing recombination without the need for the continuous presence of an inducer.

In experiments, we quantified the recombination efficiency of Bxb1 by monitoring expression of green fluorescent protein (GFP) as a reporter. Optimal expression of Bxb1, which maximized the recombination efficiency, occurred during exponential phase. However, once the culture reached stationary phase, accumulated Bxb1 continued to facilitate recombination, although GFP expression levels plateaued due to reduced cellular activity.

These insights are relevant for synthetic biology applications where precise control of genetic functions is necessary.