bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Contribution of Noncommunicable and Infectious Diseases to the Effect of Depression on Mortality: A Longitudinal Causal Mediation Analysis
Authors: Didden Christiane , Egger Matthias , Folb Naomi , Maartens Gary , Rohner Eliane , Kassanjee Reshma , Mesa-Vieira Cristina , Kriel Ayesha , Seedat Soraya , Haas Andreas D. 
Published: October 2024

Background:
The increased prevalence of physical diseases among individuals with mental illness contributes to their increased risk of mortality. However, the mediating role of specific diseases in the effect of mental illness on mortality is not well understood.

Method:
We conducted a longitudinal causal mediation analysis using data from beneficiaries of a South African medical insurance scheme from 2011 to 2020. We estimated the overall effect of major depressive disorder (MDD) on mortality and evaluated reductions in this overall effect through hypothetical interventions on the risks of mediating physical diseases using an interventional effects approach. Monte Carlo simulation-based g-computation was used for estimation.

Results:
Among 981,540 individuals, 143,314 (14.6%) were diagnosed with MDD. Mortality risk after 8 years was 6.5% under MDD, and 5.3% under no MDD (risk ratio 1.23, 95% CI = 1.19, 1.26). Overall, 43.4% of this disparity could be attributed to higher rates of physical comorbidities due to MDD. Cardiovascular diseases accounted for 17.8%, followed by chronic respiratory diseases (8.6%), cancers (7.5%), diabetes and chronic kidney disease (5.8%), tuberculosis (4.3%), and HIV (2.7%).

Conclusion:
Within the privately insured population of South Africa, MDD is associated with increased mortality. We found that noncommunicable diseases, rather than infectious diseases, are important mediators of the effect of MDD on mortality.
Prevalence of HCV HVR1 insertions and their role in antibody evasion
Authors: Olesen Christina Holmboe , Collignon Laura , Velázquez-Moctezuma Rodrigo , Fanalista Margherita , Fahnøe Ulrik , Mollerup Sarah , Schneider Uffe V. , Holmbeck Kenn , Bukh Jens , Prentoe Jannick 
Published: October 2024

Background and Aims:
Chronic HCV infection afflicts around 50 million people globally, causing ~250,000 deaths yearly. An effective vaccine needs to overcome high viral diversity and HCV’s ability to evade neutralizing antibodies (NAbs). Rapid antigenic drift in the N-terminal motif of envelope protein E2, named HVR1, is critically involved in NAb evasion through an incompletely understood mechanism involving viral entry factors. The canonical length of HVR1 is 27 amino acids, but insertions of 2–4 amino acids were described in patients infected with genotype 1b. We aimed to determine whether HVR1 insertions may be underreported due to extreme HVR1 variability.

Approach and Results:
We observed a 0.7% HVR1 insertion prevalence in routine next-generation sequencing patient contigs. Thus, we performed a direct sequence analysis of E1E2 sequences from 131 patients infected with HCV. Interestingly, we observed that 3% of patients harbored viruses (genotypes 1a, 2b, and 3a) with dominant HVR1 insertions. Insertion of longer noncanonical HVR1s into HCV cell culture recombinants frequently caused loss of fitness. However, culture-viable viruses with HVR1 insertions were fully viable in vivo. Interestingly, in adapted genotype 1b recombinants with HVR1 insertions, we found internal HVR1 deletions that increased antibody sensitivity, which surprisingly correlated more with reduced LDLr than reduced SR-BI dependency, indicating a role of LDLr in NAb evasion. Conversely, HVR1 insertions had no effect on receptor dependency; however, they modulated epitope-specific NAb sensitivity.

Conclusions:
HVR1 insertion prevalence and NAb sensitivity modulation represent a mechanism by which HCV evades emerging NAbs during infection.
Resolution of Macular Confluent Drusen During the Development and Spontaneous Closure of an Eccentric Full-Thickness Macular Hole
Authors: Aoki Shuichiro , Ueda Kohei , Kitamoto Kohdai , Azuma Keiko , Obata Ryo 
Published: October 2024

Purpose:
To describe a unique case of drusen resolution accompanying the spontaneous closure of an eccentric full-thickness macular hole (FTMH).

Methods:
This study is a case report.

Results:
A 71-year-old male exhibited confluent drusen in the right eye beneath the fovea. During regular follow-up, an eccentric FTMH developed in the right eye and closed spontaneously. Concurrently, the confluent drusen showed rapid regression without signs of geographic atrophy or macular neovascularization. Visual acuity remained stable throughout the monitoring period.

Conclusion:
This case suggests that drusen regression can occur alongside spontaneous FTMH closure without surgical intervention. This adds to the current understanding of the pathology and treatment for drusen.
Optic Nerve Sheath Fenestration: A Retrospective Review of Its Safety, Efficacy, and Impact on Optical Coherence Tomography
Authors: Gupta Lalita , Vora Paras , Benningfield Max , Altman Emily A. , Sudhakar Padmaja , Timoney Peter J. 
Published: October 2024

Purpose:
This study aimed to evaluate the safety and efficacy of optic nerve sheath fenestration using visual acuity, perimetry, and optical coherence tomography.

Methods:
A retrospective review of patients who underwent an optic nerve sheath fenestration at an academic center between 2016 and 2021 was performed with institutional review board approval. Outcome measures included visual acuity, perimetric mean deviation, optic disc edema grade, improvement in symptoms, and intraoperative and postoperative complications. Optical coherence tomography data collected included macular ganglion cell volume and thickness, as well as retinal nerve fiber layer thickness. Preoperative baseline data and 1-, 6-, and 12-month postoperative data were collected. Repeated measures with a mixed-effects model were used for continuous data, and linear regression analyses were performed.

Results:
A total of 55 patients (86 eyes) underwent optic nerve sheath fenestration, via a medial transconjunctival approach by the same orbital surgeon. After 12-month follow-up, visual acuity (P < 0.05), perimetric mean deviation (P < 0.05), and optic disc edema (P < 0.001) improved in the operative eye. Retinal nerve fiber layer thickness decreased from a mean of 165 to 92 µm (P < 0.001). Macular ganglion cell volume was found to have a small decrease from baseline and correlated well with visual acuity, contrast sensitivity testing, and perimetric mean deviation (P < 0.001).

Conclusions:
Optic nerve sheath fenestration performed via a medial transconjunctival approach is a safe and effective method to preserve vision in patients with papilledema, particularly in cases of fulminant or progressive idiopathic intracranial hypertension. Quantitative measurements of the macular ganglion cell layer can serve as a useful adjunct to other diagnostic testing.
The importance of equity in transplant oncology
Authors: Kodali Sudha , Brombosz Elizabeth W. , Abdelrahim Maen , Mobley Constance M. 
Published: October 2024

Purpose of review
Transplant oncology encompasses and utilizes liver transplantation (LT) in combination with other aspects of cancer care to offer improved long-term outcomes for patients with liver cancer, but not all patients have equal access and ability to undergo LT. Social determinants of health may negatively impact a patient's ability to receive liver-related oncologic care, including LT. This review highlights recent work exposing gaps in access to LT, including transplant oncology, and interventions to ameliorate these disparities.

Recent findings
Members of racial and ethnic minorities and indigenous groups, females, socioeconomically disadvantaged persons, and patients from rural areas are less likely to undergo LT. Recent studies have also described programs that have successfully mitigated some of the barriers in access to transplant oncology that these patients experience, including targeted outreach programs and access to virtual healthcare.

Summary
Disparities in access to LT for liver cancer are increasingly well described, but additional research is needed to find effective ways to ameliorate these differences.
A Comprehensive Pangenome Approach to Exploring the Probiotic Potential ofWeissella Confusa
Authors: Hossain Md. Saddam , Tuli Shanjana Rahman , Fatima Nigar , Ali Sobur , Moon Shovan Basak , Hashem Abu 
Published: October 2024

AbstractBackgroundFermented foods harbour the bacteriumWeissella confusa, which has probiotic properties but can potentially act as an opportunistic pathogen in humans and animals. Using pangenome analysis, our study aimed to improve the classification and identify functional traits of publicly availableW. confusagenomes, focusing on evaluating their potential as probiotics.MethodThe genomic sequence of 120 strains ofW. confusawas acquired from the NCBI RefSeq database. The downloaded sequences underwent a quality verification and filtering process. Ultimately, the chosen genomes were examined for comparative genomic analysis. We employed Roary to investigate the pangenome ofW. confusa. Fisher’s exact test was utilised to analyse contingency tables, with a significance threshold of p < 0.05 (two-tailed).ResultsOur investigation revealed that the pangenome ofW. confusacomprises 1100 core genes, 184 soft-core genes, 1407 shell genes, and 7006 cloud genes. This finding emphasises the “open” aspect of theW. confusapangenome. The comparison of genomes showed that there were no acquired antibiotic resistance genes. However, the strains had different amounts of prophage regions, CRISPR arrays, and plasmids. Our research identified probiotic marker genes (PMGs), with the majority (78%) found in the core and soft-core genomes of various strains ofW. confusa.ConclusionsAn extensive investigation of theW. confusapangenome has concluded that it could be useful as a probiotic. Additional research is necessary to thoroughly evaluate the potential risks.
Decoding the biogenesis of HIV-induced CPSF6 puncta and their fusion with the nuclear speckle
Authors: Tomasini Chiara , Cuche Celine , Ay Selen , Collard Maxence , Cui Bin , Rashid Mohammad , Bhattacharjee Shaoni , Buchrieser Julian , Luchsinger Charlotte , Bertelli Cinzia , Uversky Vladimir N. , Diaz-Griffero Felipe , Di Nunzio Francesca 
Published: October 2024

SummaryViruses rely on host cellular machinery for replication. After entering the nucleus, the HIV genome accumulates in nuclear niches where it undergoes reverse transcription and integrates into neighboring chromatin, promoting high transcription rates and new virus progeny. Despite anti-retroviral treatment, viral genomes can persist in these nuclear niches and reactivate if treatment is interrupted, likely contributing to the formation of viral reservoirs. The post-nuclear entry dynamics of HIV remain unclear, and understanding these steps is critical for revealing how viral reservoirs are established.In this study, we elucidate the formation of HIV-induced CPSF6 puncta and the domains of CPSF6 essential for this process. We also explore the roles of nuclear speckle scaffold factors, SON and SRRM2, in the biogenesis of these puncta. Through genetic manipulation and depletion experiments, we demonstrate the key role of the intrinsically disordered region of SRRM2 in enlarging nuclear speckles in the presence of the HIV capsid.We identify the FG domain of CPSF6 as essential for both puncta formation and binding to the viral core, which serves as the scaffold for CPSF6 puncta. While the low-complexity regions (LCRs) modulate CPSF6 binding to the viral capsid, they do not contribute to puncta formation, nor do the disordered mixed charge domains (MCDs) of CPSF6. These results demonstrate how HIV evolved to hijack host nuclear factors, enabling its persistence in the host.Of note, this study provides new insights into the underlying interactions between host factors and viral components, advancing our understanding of HIV nuclear dynamics and offering potential therapeutic targets for preventing viral persistence.HighlightsThe formation of HIV-induced CPSF6 puncta is critical for restoring HIV-1 nuclear reverse transcription (RT).CPSF6 protein lacking the FG peptide cannot bind to the viral core, thereby failing to form HIV-induced CPSF6 puncta.The FG peptide, rather than low-complexity regions (LCRs) or the mixed charge domains (MCDs) of the CPSF6 protein, drives the formation of HIV-induced CPSF6 puncta.HIV-induced CPSF6 puncta form individually and later fuse with nuclear speckles (NS) via the intrinsically disordered region (IDR) of SRRM2.
Indicators of improved emotion behaviour in 6–14-year-old children following a 4-week placebo controlled prebiotic supplement intervention at home with a parent
Authors: Johnstone Nicola , Kadosh Kathrin Cohen 
Published: October 2024

AbstractIn this double-blind placebo-controlled randomised intervention we investigated the potential benefits of a prebiotic supplement on children’s well-being in a home setting. The primary aim was to determine if this supplement could effectively reduce anxiety, improve mood, and enhance cognitive function, similar to findings in young adults.Fifty-three healthy children, aged 6 to 14, participated in an 8-week trial. The trial consisted of three testing time points; day zero marked the baseline measurement (T1) followed by a 28-day supplement intervention period during which they consumed 5.5 grams of galactooligosaccharides (GOS) daily under parental guidance. Endline measures (T2) were conducted on the last day of supplement consumption, with a final follow-up testing session (T3) on day 56. Primary outcomes were trait anxiety using a questionnaire and emotional behavior in a dot-probe task on responses to positive and negative images. Secondary outcomes encompassed depression levels, cognitive function tests, and dietary intake recorded in a 4-day food diary. Additionally, we explored whether parents’ emotional behavior had an impact on children’s responses.While our statistical analysis did not reveal significant effects of GOS, there were noteworthy trends. Trait anxiety levels decreased over time in both groups, with a more pronounced decrease in the GOS group. The GOS group exhibited reduced negative emotional responses compared to the placebo group, and post-trial depression levels decreased in the GOS group over time. Although parental emotional responses correlated with various emotional outcomes in children, they did not influence the intervention effects. In conclusion, these findings suggest positive trends in line with our hypotheses however further investigation with greater statistical power would be beneficial.
Unlocking the potential of wearable device wear time to enhance postpartum depression screening and detection
Authors: Hurwitz Eric , Meltzer-Brody Samantha , Butzin-Dozier Zachary , Patel Rena C. , Elhadad Noémie , Haendel Melissa A. 
Published: October 2024

AbstractPostpartum depression (PPD) is a mood disorder affecting one in seven women after childbirth that is often under-screened and under-detected. If not diagnosed and treated, PPD is associated with long-term developmental challenges in the child and maternal morbidity. Wearable technologies, such as smartwatches and fitness trackers (e.g., Fitbit), offer continuous and longitudinal digital phenotyping for mood disorder diagnosis and monitoring, with device wear time being an important yet understudied aspect. Using theAll of UsResearch Program (AoURP) dataset, we assessed the percentage of days women with PPD wore Fitbit devices across pre-pregnancy, pregnancy, postpartum, and PPD periods, as determined by electronic health records. Wear time was compared in women with and without PPD using linear regression models. Results showed a strong trend that women in the PPD cohort wore their Fitbits more those without PPD during the postpartum (PPD: mean=72.9%, SE=13.8%; non-PPD: mean=58.9%, SE=12.2%,P-value=0.09) and PPD time periods (PPD: mean=70.7%, SE=14.5%; non-PPD: mean=55.6%, SE=12.9%,P-value=0.08). We hypothesize this may be attributed to hypervigilance, given the common co-occurrence of anxiety symptoms among women with PPD. Future studies should assess the link between PPD, hypervigilance, and wear time patterns. We envision that device wear patterns with digital biomarkers like sleep and physical activity could enhance early PPD detection using machine learning by alerting clinicians to potential concerns facilitating timely screenings, which may have implications for other mental health disorders.
Intestinal parasitic infections associated with nutritional status and inflammatory markers among young children in Huye district, Rwanda
Authors: Twahirwa Wellars , Nyandwi Xavier , Iradukunda Jean D’Amour , Muneza Jean Felix , Kanimba Philbert , Adefaye Khadijat O. , Gahamanyi Noel , Rujeni Nadine 
Published: October 2024

ABSTRACTBackgroundIntestinal parasitic infections (IPIs) are a public health issue affecting young children in low and middle income countries (LMICs). These factors may induce malnutrition, as well as systemic and/or intestinal inflammation, depending on the species, intensity of infection, and host response. This study aimed at determining the effect of intestinal parasites on nutritional status and inflammatory responses in pre- and school-aged children in rural areas of the southern province of Rwanda.MethodsA cross-sectional study involving 127 children under 12 years of age was conducted at two health centers in Huye District, Southern Province, Rwanda, from January to February 2022. A structured questionnaire was used to collect sociodemographic information, feeding habits, anthropometric measurements, and information on infection/malnutrition risk factors. Stool samples were collected to test for intestinal parasites by using microscope, while serum was collected to measure (anti)inflammatory markers [interleukin-10 (IL-10), tumour necrosis factor-alpha (TNF-α), total protein, and C-reactive protein (CRP)].ResultsThe overall prevalence of IPIs was 38.6%, with non-pathogenicEntamoeba colibeing the most prevalent (21.3%), followed byAscaris lumbricoides(18.1%),Entamoeba histolytica(11.8%), andTrichuris trichiura(1.6%). Coinfections accounted for 12.6% of the infections. Moreover, 48.0%, 25.2%, and 9.4% of the children were stunted, underweight, and stunted, respectively. Underweight, IL-10, and total protein levels were significantly associated with IPIs. Our findings also indicated that food supplements had a significant positive effect on stunting.ConclusionAscaris lumbricoides,Entamoeba histolytica, andTrichuris trichiurawere the predominant parasites. Intestinal parasitic infections in preschool children and schoolchildren affect the nutritional status, possibly through chronic inflammation. Further mechanistic investigations will shed more light on the regulation of the inflammatory response.
Hospital environments harbor chlorhexidine tolerant bacteria potentially linked to chlorhexidine persistence in the environment
Authors: Shen Jiaxian , Weng Yuhan , Shimada Tyler , Karan Meghana , Watson Andrew , Medernach Rachel L. , Young Vincent B. , Hayden Mary K. , Hartmann Erica M. 
Published: October 2024

AbstractA One Health approach is essential in combating antibiotic and antimicrobial resistance. Chlorhexidine (di)gluconate (CHG), a widely used antiseptic in medical intensive care units (MICU), has recently come under scrutiny. However, studies on CHG tolerance, particularly in interconnected indoor environments, are limited. We comprehensively explored CHG tolerance in MICU environments from chemical, microbial, and molecular perspectives. Using microcosm experiments and field surveys, we demonstrated that CHG, if transferred from patient skin to environments, can persist on surfaces despite cleaning and disinfection and decrease to sublethal levels for clinically relevant bacteria. We detected widespread CHG-tolerant bacteria (≥ 18.75 µg/mL), including opportunistic pathogens (e.g.,Pseudomonas aeruginosa,Stenotrophomonas maltophilia,Elizabethkingia miricola), with minimum inhibitory concentrations up to 512 μg/mL. Sink drains emerged as critical hotspots, and indoor air as a potential transport mechanism. We observed indications of bacterial persistence, increased tolerance, in-situ evolution, and dissemination across MICU rooms. Molecular analyses revealed heterogeneous and largely unexplored CHG resistance mechanisms and identified resistance determinant candidates, particularlyqacEdelta1-carrying, plasmid-borne multidrug-resistant cassettes. Our findings underscore the importance of understanding human-environment and chemical-microbe interactions to preserve chlorhexidine’s efficacy and inform infection prevention strategies. We advocate for integrated environmental management and clinical interventions under the One Health framework.
Salmonellaexploits host- and bacterial-derived β-alanine for replication inside host macrophages
Authors: Ma Shuai , Yang Bin , Sun Yuyang , Wang Xinyue , Guo Houliang , Liu Ruiying , Ye Ting , Kang Chenbo , Chen Jingnan , Jiang Lingyan 
Published: October 2024

AbstractSalmonellais a major foodborne pathogen that can effectively replicate inside host macrophages to establish life-threatening systemic infections.Salmonellamust utilize diverse nutrients for growth in nutrient-poor macrophages, but which nutrients are required for intracellularSalmonellagrowth is largely unknown. Here, we found that either acquisition from the host or de novo synthesis of a nonprotein amino acid, β-alanine, is critical forSalmonellareplication inside macrophages. The concentration of β-alanine is decreased inSalmonella-infected macrophages, while the addition of exogenous β-alanine enhancesSalmonellareplication in macrophages, suggesting thatSalmonellacan uptake host-derived β-alanine for intracellular growth. Moreover, the expression ofpanD,the rate-limiting gene required for β-alanine synthesis inSalmonella,is upregulated whenSalmonellaenters macrophages. Mutation ofpanDimpairedSalmonellareplication in macrophages and colonization in the mouse liver and spleen, indicating that de novo synthesis of β-alanine is essential for intracellularSalmonellagrowth and systemic infection. Additionally, we revealed that β-alanine influencesSalmonellaintracellular replication andin vivovirulence by increasing expression of the zinc transporter genesznuABC,which in turn facilitates the uptake of the essential micronutrient zinc bySalmonella. Taken together, these findings highlight the important role of β-alanine in the intracellular replication and virulence ofSalmonella, andpanDis a promising target for controlling systemicSalmonellainfection.