bluuebunny/crossref_metadata_2025 huggingface dataset:
An update on factors affecting umbilical cord care among mothers: A review
Authors: Obeagu Emmanuel Ifeanyi , Obeagu Getrude Uzoma
Published: July 2024

Umbilical cord care remains a critical aspect of newborn health, yet practices vary significantly across different cultures and healthcare settings. This paper aims to provide an updated synthesis of the factors influencing umbilical cord care among mothers. The umbilical cord is a vital link between the fetus and the placenta during pregnancy, but after birth, it requires proper care to prevent infections. Numerous factors influence a mother’s approach to umbilical cord care, including cultural beliefs, socio-economic status, access to healthcare information, and traditional practices passed down through generations. Understanding these factors is crucial for healthcare providers to offer tailored guidance and support to mothers, ensuring the optimal care for newborns. This paper examines recent research and literature encompassing diverse cultural perspectives, socio-economic considerations, healthcare access, and educational interventions related to umbilical cord care. It also highlights the impact of technological advancements, such as telemedicine and digital health platforms, in disseminating crucial information to mothers, especially in remote or underserved areas. Moreover, the review delves into the role of healthcare professionals in promoting evidence-based practices and addressing misconceptions regarding umbilical cord care. It emphasizes the importance of culturally sensitive and context-specific interventions in enhancing maternal knowledge and practices related to neonatal care. In conclusion, this review presents an updated overview of the multifactorial influences on umbilical cord care among mothers. It calls for continued research and concerted efforts to bridge gaps in knowledge, cultural beliefs, and healthcare access, ultimately contributing to the promotion of optimal newborn health outcomes.
Multiple myeloma with secondary amyloidosis: Dysphagia as the first symptom: A case report
Authors: Xue Bing , Li Liang , Ma Shanshan
Published: July 2024

Rationale:

Multiple myeloma (MM) with secondary amyloidosis (AL) is a rare clonal plasma cell proliferation disease, which causes dysfunction of multiple organs and tissues. We report a case of dysphagia as the first symptom in a patient with MM and secondary AL.

Patient concerns:

The patient was a 73-year-old female, was admitted to our hospital, because of progressive dysphagia for 4 months and limb weakness for 1 month.

Diagnoses:

The bone marrow smear and pathology diagnosis revealed the presence of MM, while the biceps myopathy diagnosis indicated AL.

Interventions:

The VCD regimen consisted of bortezomib at a dosage of 1.9 mg on days 1, 8, 15, and 22, cyclophosphamide 0.4 g on days 1, 8, and 15, and dexamethasone at a dosage of 40 mg on days 1, 8, 15, and 22. The patient simultaneously received comprehensive treatment including anti-infective therapy, enhanced cardiac function, and nutritional support.

Outcomes:

The M protein in the blood and urine protein were negative, indicating a reduction in bone marrow plasma cells to 2%. Flow cytometric analysis revealed a minimal percentage 0.04%. As a result, complete remission was achieved.

Lessons:

The clinical manifestations of MM exhibit a wide range, with the symptoms of secondary injury causing significant disturbing, while the atypical symptoms of extramedullary manifestations pose challenges in diagnosing the disease.
A rare cause of small bowel obstruction caused by duodenum-derived aggressive fibromatosis with β-catenin T41A mutation: A case analysis
Authors: Zhao Dewen , Wang Xinguang
Published: July 2024

Rationale:

Aggressive fibromatosis (AF) is a fibroblastic/myofibroblastic tumor known for its locally aggressive properties. Intra-abdominal AF primarily occurs in the small intestine mesentery, ileocolic mesocolon, omentum, retroperitoneum, and pelvis, and rarely originates from the intestinal wall. Here, we report a rare case of small bowel obstruction caused by duodenum-derived AF with β-catenin (CTNNB1) T41A mutation.

Patient concerns:

A 35-year-old male had a 4-month history of abdominal pain, nausea, and vomiting, which gradually worsened over time.

Diagnoses:

Based on the results of CT examination, histopathology and Sanger sequencing, the patient was diagnosed with small bowel obstruction caused by duodenum-derived AF.

Interventions:

Due to the extensive adhesion between the tumor and surrounding tissue, it is extremely challenging to completely remove the tumor through surgical resection with negative margins in this case. In order not to damage the function of surrounding vital organs, gastrojejunostomy was performed to relieve the symptoms of small bowel obstruction.

Outcomes:

The patient experienced a successful recovery. It is important to note that this patient is still at risk of local recurrence and requires regular follow-up.

Lessons:

The best treatment should be taken based on the individual patient to relieve symptoms and improve quality of life. Moreover, histopathology plays a crucial role in diagnosing and differentiating duodenum-derived AF. The detection of mutations in exon 3 of the CTNNB1 has become strong evidence for diagnosing duodenum-derived AF.
Collaborative Care Cost-Sharing and Referral Rates in Colorado
Authors: Cliff Betsy Q. , Xie Tiffany H. , Laiteerapong Neda
Published: July 2024

Background:

Collaborative care integrates mental health treatment into primary care and has been shown effective. Yet even in states where its use has been encouraged, take-up remains low and there are potential financial barriers to care.

Objective:

Describe patient out-of-pocket costs and variations in referral patterns for collaborative care in Colorado.

Research Design:

Retrospective observational study using administrative medical claims data to identify outpatient visits with collaborative care. For individuals with ≥1 visit, we measure spending and visits at the month level. Among physicians with billings for collaborative care, we measure prevalence of eligible patients with collaborative care utilization.

Subjects:

Patients with Medicare, Medicare Advantage, or commercial health insurance in Colorado, 2018–2019

Outcomes:

Out-of-pocket costs (enrollee payments to clinicians), total spending (insurer+enrollee payments to clinicians), percent of patients billed collaborative care.

Results:

Median total spending (insurer+patient cost) was $48.32 (IQR: $41–$53). Median out-of-pocket cost per month in collaborative care was $8.35 per visit (IQR: $0–$10). Patients with commercial insurance paid the most per month (median: $15); patients with Medicare Advantage paid the least (median: $0). Among clinicians billing for collaborative care (n=193), a mean of 12 percent of eligible patients utilized collaborative care; family practice and advanced practice clinicians' patients utilized it most often.

Conclusions:

Collaborative care remains underused with fewer than 1 in 6 potentially eligible patients receiving care in this setting. Out-of-pocket costs varied, though were generally low; uncertainty about costs may contribute to low uptake.
A Systematic Review and Meta-analysis of the Impact of the COVID-19 Pandemic on Access to HIV Pre-exposure Prophylaxis: Lessons for Future Public Health Crises
Authors: Wulandari Luh Putu Lila , Negara Srila Nirmithya Salita , Mashuri Yusuf Ari , Wahyuningtias Siska Dian , Putra I. Wayan Cahyadi Surya Distira , Subronto Yanri W. , Ahmad Riris Andono , Thabrany Hasbullah , Guy Rebecca , Law Matthew , Hammoud Mohamed , Bavinton Benjamin B. , Kaldor John , Medland Nicholas , Liverani Marco , Probandari Ari , Boettiger David , Wiseman Virginia
Published: July 2024

Background:

The World Health Organization is committed to strengthening access to pre-exposure prophylaxis (PrEP) for HIV prevention and its integration into primary care services. Unfortunately, the COVID-19 pandemic has disrupted the delivery of primary care, including HIV-related services. To determine the extent of this disruption, we conducted a systematic review and meta-analysis of the changes in access to PrEP services during the pandemic and the reasons for these changes.

Methods:

A search was conducted using PubMed, Scopus, Embase, PsycINFO, and Cinahl for studies published between January 2020 and January 2023. Selected articles described self-reported disruptions to PrEP service access associated with the COVID-19 pandemic or its responses. Pooled effect sizes were computed using a random-effects model.

Results:

Thirteen studies involving 12,652 PrEP users were included in our analysis. The proportion of participants reporting a disruption in access to PrEP services during the COVID-19 pandemic ranged from 3% to 56%, with a pooled proportion of 21% (95% confidence intervals: 8% to 38%). Social restrictions, financial constraints, and limited health insurance coverage were key factors affecting access to PrEP services during the pandemic.

Conclusions:

To our knowledge, this is the first meta-analysis to quantify the extent of disruptions to accessing PrEP services because of the COVID-19 pandemic. To increase the ability of primary care services to maintain PrEP services during public health crises, a mixture of strategies is worth considering. These include multi-month PrEP prescriptions, telehealth services, deployment of peer support groups to provide a community-based service or home delivery, and provision of financial support interventions.
Update on RYR1-related myopathies
Authors: Ogasawara Masashi , Nishino Ichizo
Published: July 2024

Purpose of review

RYR1-related myopathy (RYR1-RM) is a group of myopathies caused by mutations in the RYR1 gene, which encodes the ryanodine receptor 1 (RYR1). This review discusses recent advances in the clinical features, pathology, pathogenesis, and therapeutics of RYR1-RM.

Recent findings

Although treatments such as salbutamol, pyridostigmine, and N-acetylcysteine have been explored as potential therapies for RYR1-RM, none have been conclusively proven to be effective. However, recent clinical trials of Rycal ARM210 in patients with RYR1-RM have shown promising results, including reduced fatigue and improved proximal muscle strength.

Recent advances in three-dimensional structural analysis of RYR1 channels, facilitated by cryo-electron microscopy (cryo-EM), have elucidated the distinct molecular mechanisms underlying RYR1 functionality. Additionally, high-throughput screening methods, including FRET-based and endoplasmic reticulum Ca2+-based assays, have been successful in identifying potential candidates for the treatment of RYR1-RM.

Recent advances in clinical and pathological understanding have provided new insights into RYR1-RM. Novel pathomechanisms elucidated by cryo-EM and rapid screening methods have led to the identification of several promising drug candidates. We are hopeful about the potential of Rycal, other new drugs, and gene therapy, offering a promising outlook for the future.
The role of human involvement and support in digital mental health interventions for people with schizophrenia spectrum disorders: a critical review
Authors: Arnautovska Urska , Milton Alyssa , Trott Mike , Soole Rebecca , Siskind Dan
Published: July 2024

Purpose of review

Schizophrenia spectrum disorders (SDD) are characterized by a complex array of psychosis symptoms, and typically require ongoing and long-term support, including pharmacological and nonpharmacological management. Digital mental health interventions (DMHIs) have been suggested as a novel therapeutic approach to enable low-cost, scalable improvements in quality of care for adults living with SSD. However, the types and role of human involvement and support within DMHIs is currently unknown.

Recent findings

Several recent systematic reviews and meta-analyses have investigated the potential efficacy of DMHIs for people with SSD, with scant yet emerging systematic evidence on the effects of human support within DMHIs on mental health outcomes. Further, several recent individual studies examined the efficacy of DMHIs with human support among people with SSD and provided valuable insights into the potential key elements of such support on outcomes relevant to this population.

The current critical review provides the first narrative synthesis of available evidence to guide clinicians and intervention develops in designing DMHIs with adequate human support that may enhance long-term outcomes of people living with SSD.
Enrichment culture evaluation and characterization of Streptococcus agalactiae among pregnant women in Japan
Authors: Nakano Satoshi , Koide Shota , Hosaka Yumiko , Hasegawa Yuri , Ishida-Kuroki Kasumi , Kawakami Sayoko , Hayashi Wataru , Yu Liansheng , Kayama Shizuo , Miyashita Noriko , Nagata Koh , Miura Shoko , Sugawara Yo , Miyazaki Hiroaki , Miura Kiyonori , Sugai Motoyuki
Published: July 2024

Introduction. Maternal screening tests and prophylactic antibiotics are important to prevent neonatal and infant group B streptococcal (GBS) infections.

Hypothesis/Gap Statement. The performance of enrichment broth media for GBS screening that are available in Japan is unclear. Whole-genome data of GBS isolates from pregnant women in Japan is lacking.

Aim. The aim of this study was to compare the protocol performance of six enrichment broths and two subculture agar plates, which were all available in Japan, for GBS detection. In addition, we showed whole-genome data of GBS isolates from pregnant women in Japan.

Methodology. We collected 133 vaginal-rectal swabs from pregnant women visiting clinics and hospitals in Nagasaki Prefecture, Japan, and compared the protocol performance of 6 enrichment broths and 2 subculture agar plates. All GBS isolates collected in this study were subjected to whole-genome sequencing analysis.

Results. We obtained 133 vaginal-rectal swabs from pregnant women at 35–37 weeks of gestation from 8 private clinics and 2 local municipal hospitals within Nagasaki Prefecture, Japan. The detection rate of the protocol involving the six enrichment broths and subsequent subcultures varied between 95.5 and 100 %, depending on the specific choice of enrichment broth. The GBS carriage rate among pregnant women in this region was 18.8 %. All 25 isolates derived from the swabs were susceptible to penicillin, whereas 48 and 36 % of the isolates demonstrated resistance to erythromycin and clindamycin, respectively. The distribution of serotypes was highly diverse, encompassing seven distinct serotypes among the isolates, with the predominant serotype being serotype V (n = 8). Serotype V isolates displayed a tendency towards increased resistance to erythromycin and clindamycin, with all resistant isolates containing the ermB gene.

Conclusion. There was no difference in performance among the culture protocols evaluated in this study. GBS strains isolated from pregnant women appeared to have greater genomic diversity than GBS strains detected in neonates/infants with invasive GBS infections. To confirm this result, further studies with larger sample sizes are needed.
A high-throughput assay identifies molecules with antimicrobial activity against persister cells
Authors: Petersen Maiken Engelbrecht , Hansen Liva Kjær , Mitkin Alexander Alexandrovich , Kelly Nicholas M. , Wood Thomas Keith , Jørgensen Nis Pedersen , Østergaard Lars Jørgen , Meyer Rikke Louise
Published: July 2024

Introduction. Persister cells are transiently non-growing antibiotic-tolerant bacteria that cause infection relapse, and there is no effective antibiotic therapy to tackle these infections.

Gap statement. High-throughput assays in drug discovery are biased towards detecting drugs that inhibit bacterial growth rather than killing non-growing bacteria. A new and simple assay to discover such drugs is needed.

Aim. This study aims to develop a simple and high-throughput assay to identify compounds with antimicrobial activity against persister cells and use it to identify molecular motifs with such activity.

Methodology. We quantified Staphylococcus aureus persister cells by enumeration of colony forming units after 24 h ciprofloxacin treatment. We first quantified how the cell concentration, antibiotic concentration, growth phase and presence/absence of nutrients during antibiotic exposure affected the fraction of persister cells in a population. After optimizing these parameters, we screened the antimicrobial activity of compound fragments to identify molecular structures that have activity against persister cells.

Results. Exponential- and stationary-phase cultures transferred to nutrient-rich media displayed a bi-phasic time-kill curve and contained 0.001–0.07% persister cells. A short rifampicin treatment resulted in 100% persister cells for 7 h, after which cells resumed activity and became susceptible. Stationary-phase cultures displayed a low but constant death rate but ultimately resulted in similarly low survival rates as the exponential-phase cultures after 24 h ciprofloxacin treatment. The persister phenotype was only maintained in most of the population for 24 h if cells were transferred to a carbon-free minimal medium before exposure to ciprofloxacin. Keeping cells starved enabled the generation of high concentrations of S. aureus cells that tolerate 50× MIC ciprofloxacin, and we used this protocol for rapid screening for biocidal antibiotics. We identified seven compounds from four structural clusters with activity against antibiotic-tolerant S. aureus. Two compounds were moderately cytotoxic, and the rest were highly cytotoxic.

Conclusion. Transferring a stationary-phase culture to a carbon-free minimal medium for antimicrobial testing is a simple strategy for high-throughput screening for new antibiotics that kill persister cells. We identified molecule fragments with such activity, but further screening is needed to identify motifs with lower general cytotoxicity.
A variational deep-learning approach to modeling memory T cell dynamics
Authors: van Dorp Christiaan H. , Gray Joshua I. , Paik Daniel H. , Farber Donna L. , Yates Andrew J.
Published: July 2024

Mechanistic models of dynamic, interacting cell populations have yielded many insights into the growth and resolution of immune responses. Historically these models have described the behavior of pre-defined cell types based on small numbers of phenotypic markers. The ubiquity of deep pheno-typing therefore presents a new challenge; how do we confront tractable and interpretable mathematical models with high-dimensional data? To tackle this problem, we studied the development and persistence of lung-resident memory CD4 and CD8 T cells (TRM) in mice infected with influenza virus. We developed an approach in which dynamical model parameters and the population structure are inferred simultaneously. This method uses deep learning and stochastic variational inference and is trained on the single-cell flow-cytometry data directly, rather than on the kinetics of pre-identified clusters. We show that during the resolution phase of the immune response, memory CD4 and CD8 T cells within the lung are phenotypically diverse, with subsets exhibiting highly distinct and time-dependent dynamics. TRMheterogeneity is maintained long-term by ongoing differentiation of relatively persistent Bcl-2hi CD4 and CD8 TRMsubsets which resolve into distinct functional populations. Our approach yields new insights into the dynamics of tissue-localized immune memory, and is a novel basis for interpreting time series of high-dimensional data, broadly applicable to diverse biological systems.
Loss of the systemic vitamin A transporter RBPR2 affects the quantitative balance between chromophore and opsins in visual pigment synthesis
Authors: Radhakrishnan Rakesh , Leung Matthias , Lor Anjelynt , More Swati , Lobo Glenn P.
Published: July 2024

The distribution of dietary vitamin A/all-transretinol (ROL) throughout the body is critical for maintaining retinoid function in peripheral tissues and for generating visual pigments for photoreceptor cell function. ROL circulates in the blood bound to the retinol binding protein 4 (RBP4) as RBP4-ROL. Two membrane receptors, RBPR2 in the liver and STRA6 in the eye are proposed to bind circulatory RBP4 and this mechanism is critical for internalizing ROL into cells. Here, we present a longitudinal investigation towards the importance of RBPR2 and influence of the diet on systemic retinoid homeostasis for visual function. Age matchedRbpr2-KO (Rbpr2-/-) and wild-type (WT) mice were fed either a vitamin A sufficient (VAS) or a vitamin A deficient (VAD) diet. At 3- and 6-months, we performed retinoid quantification of ocular and non-ocular tissues using HPLC analysis and complemented the data with visual physiology, rhodopsin quantification by spectrophotometry, and biochemical analysis. At 3-months and compared to WT mice,Rbpr2-/-mice fed either vitamin A diets displayed lower scotopic and photopic electroretinogram (ERG) responses, which correlated with HPLC analysis that revealedRbpr2-/-mice had significantly lower hepatic and ocular retinoid content. Interestingly, with the exception of the liver, long-term feeding ofRbpr2-/-mice with a VAS diet promoted all-transretinol accumulation in most peripheral tissues. However, even under VAS dietary conditions significant amounts of unliganded opsins in rods, together with decreased visual responses were evident in aged mice lacking RBPR2, when compared to WT mice. Together, our analyses characterize the molecular events underlying nutritional blindness in a novel mouse model and indicate that loss of the liver specific RBP4-ROL receptor, RBPR2, influences systemic retinoid homeostasis and rhodopsin synthesis, which causes profound visual function defects under severe vitamin A deficiency conditions.
A molecular view into the structure and dynamics of phase-separated chromatin
Authors: Golembeski Andrew , Lequieu Joshua
Published: July 2024

The organization of chromatin is critical for gene expression, yet the underlying mechanisms responsible for this organization remain unclear. Recent work has suggested that phase separation might play an important role in chromatin organization, yet the molecular forces that drive chromatin phase separation are poorly understood. In this work we interrogate a molecular model of chromatin to quantify the driving forces and thermodynamics of chromatin phase separation. By leveraging a multiscale approach, our molecular model is able to reproduce chromatin’s chemical and structural details at the level of nanometers, yet remain efficient enough to simulate chromatin phase separation across 100 nm length scales. We first demonstrate that our model can reproduce key experiments of phase separating nucleosomal arrays, and then apply our model to quantify the interactions that drive their formation into chromatin condensates with either liquid- or solid-like material properties. We next use our model to characterize the molecular structure within chromatin condensates and find that this structure is irregularly ordered and is inconsistent with existing 30 nm fiber models. Lastly we examine how post-translational modifications can modulate chromatin phase separation and how the acetylation of chromatin can lead to chromatin decompaction while still preserving phase separation. Taken together, our work provides a molecular view into the structure and dynamics of phase-separated chromatin and provides new insights into how phase separation might manifest in the nucleus of living cells.
Peripheral Skeletal Muscle Alterations in Adults Born Preterm: An Observational Comparative Study
Authors: Deprez Alyson , El-Jalbout Ramy , Cloutier Anik , Gagnon Dany H. , Hamelin Andréa Gagnon , Mathieu Marie-Eve , Kugathasan Thiffya A , Dumont Nicolas A. , Nuyt Anne Monique , Luu Thuy Mai
Published: July 2024

Prematurity is associated with reduced exercise capacity, which relies on the integrity of the cardiovascular, pulmonary, and skeletal muscle systems. Our animal model mimicking prematurity-associated conditions showed altered muscle composition and atrophy in adulthood. This study aimed to compare muscle composition and strength in adults born preterm versus full-term controls. This observational cohort study recruited 55 adults born preterm, ≤29 weeks’ of gestation and 53 full-term controls who underwent musculoskeletal ultrasound imaging to assess morphology of the rectus femoris at rest and during a maximal voluntary contraction. Maximal voluntary contraction of the hands and legs were measured by manual dynamometry. In adults born preterm, there was a reduction in muscle strength (handgrip: -4.8 kg, 95% CI -9.1, -0.6; knee extensor: -44.6 N/m, 95% CI -63.4, -25.8) and muscle area (-130 mm2, 95% CI -207, -53), which was more pronounced with a history of bronchopulmonary dysplasia. Muscle stiffness was increased in the preterm group (0.4 m/s, 95% CI 0.04, 0.7). Prematurity is associated with alterations in skeletal muscle composition, area, and function in adulthood. These findings highlight the necessity to implement preventive and/or curative approaches to improve muscle development and function following preterm birth to enhance overall health in this population.

What’s known on This Subject

Preterm birth is associated with reduced exercise capacity. However, the impact of preterm birth on skeletal muscle, a critical player of exercise capacity, in adulthood remains unclear.

What This Study Adds

Our findings provide novel insights into the potential long-term effects of preterm birth and the contributions of bronchopulmonary dysplasia on peripheral muscle-related health outcomes, such as muscle composition (reduced muscle area and increased muscle stiffness) and function (reduced muscle strength).
PRMT1-SFPQ regulates intron retention to control matrix gene expression during craniofacial development
Authors: Raulino Lima Julia , Ungvijanpunya Nicha , Chen Qing , Park Greg , Vatankhah Mohammadreza , Rosen Tal , Chai Yang , Merrill Amy E. , Peng Weiqun , Xu Jian
Published: July 2024

Spliceosomopathies, which are a group of disorders caused by defects in the splicing machinery, frequently affect the craniofacial skeleton and limb, but the molecular mechanism underlying this tissue-specific sensitivity remains unclear. Splicing factors and small nuclear ribonucleoproteins (snRNPs) are core components of splicing machinery, and splicing factors are further controlled by post-translational modifications, among which arginine methylation is one of the most frequent modifications. To determine the splicing mechanisms in cranial neural crest cells (CNCCs), which give rise to the majority of craniofacial skeleton, we focused on upstream regulators for splicing proteins responsible for arginine methylation, protein arginine methyltransferases (PRMT). These enzymes catalyze arginine methylation of splicing factors to modify splicing factor expression and activity, influencing the splicing product. PRMT1 is the highest expressing enzyme of the PRMT family in CNCCs and its role in craniofacial development is evident based on our earlier investigation, where CNCC-specific Prmt1 deletion caused cleft palate and mandibular hypoplasia. In the present study, we uncover roles of PRMT1 in CNCCs in the regulation of intron retention, a type of alternative splicing where introns are retained in the mature mRNA sequence. Mandibular primordium of Prmt1-deficient embryos demonstrated an increase in the percentage of intron-retaining mRNA of matrix genes, which triggered NMD, causing a reduction in matrix transcript expression. We further identified SFPQ as a substrate of PRMT1 that depends on PRMT1 for arginine methylation and protein expression in the developing craniofacial structures. Depletion of SFPQ in CNCCs phenocopied PRMT1 deletion in that matrix, Wnt signaling components and neuronal gene transcripts contained higher IR and exhibited lower expression. We further recognized gene length as a common feature among SFPQ-regulated genes in CNCCs. Altogether, these findings demonstrate that the PRMT1-SFPQ pathway modulates matrix Wnt signaling components and neuronal gene expression via intron retention in CNCCs during craniofacial development.
Trends in prevalence and determinants of unintended pregnancy among Bangladeshi women from 2007 to 2018: A comparative analysis of multiple Demographic Health Surveys
Authors: Karim Farhana , Khan Abdullah Nurus Salam , Chowdhury Mohiuddin Ahsanul Kabir , Haque Tahmidul , Rokonuzzaman SM , Lotus Sharif Uddin , Billah Sk Masum , Khan Muhammad Sanowar , Siraj Md. Shahjahan
Published: July 2024

Background

Unintended pregnancy is a global challenge, particularly prevalent in developing regions, with significant negative impacts on women’s health and well-being. Bangladesh has made progress in fertility decline but still faces challenges due to high rates of unintended pregnancies, unsafe abortions, and limited contraceptive use.

Methods

The analysis utilized secondary data from the Bangladesh Demographic and Health Surveys (BDHS) conducted in 2007, 2011, 2014, and 2017-18. The surveys employed a nationally representative sampling frame using a two-stage sampling technique, covering residential households across Bangladesh. The study included 28042 ever-married women aged 15-49 from the four surveys. Descriptive statistics and chi-squared tests examined the relationships between the explanatory and dependent variables. Binary logistic regression was performed to determine the adjusted effects of the selected factors, presenting the results as odds ratios (OR) with 95% confidence intervals (CI). Stata 15 software was used for data analysis, with (p < 0.05) considered statistically significant.

Results

The percentage of unintended pregnancies decreased from 29% in 2007 to 21% in 2017-18. Mothers aged 20-29 years had lower likelihood of unintended pregnancy (OR: 0.73-0.81), compared to aged 30 years and above (OR: 1.40). Mothers with secondary education were more likely to have unintended pregnancy in 2007 (OR: 1.28), but less likely in 2011 (OR: 0.75). Employed mothers had higher likelihood of unintended pregnancy (OR: 1.19-1.31), while Muslim mothers had higher likelihood in 2011 and 2014 (OR: 1.33-1.53), but lower likelihood in 2017-18 (OR: 0.73). Unmet need for contraception was consistently associated with higher odds of unintended pregnancy (OR: 2.12-3.94).

Conclusion

Unintended pregnancies in Bangladesh have decreased over the past decade, but still pose challenges for women’s reproductive health. Targeted efforts are needed to address factors such as poverty, education, contraception access, and cultural norms to further reduce unintended pregnancies and improve maternal and child well-being.
Pond Water Microbiome Taxa Profiles and Antibiotic Resistance Genes Associated with Acidity and Tannins
Authors: Vaccaro Maya , Pilat Andrew M , Gusmano Logan , Pham Minh T. N. , Barich Daniel , Gibson Audrey , Epalle Mwi , Frost Dominick J , Volin Elianajoy , Slimak Zachary C. , Menke Chelsea C , Fennessy M Siobhan , Slonczewski Joan L
Published: July 2024

Microbial communities of small freshwater bodies are poorly understood. Four ponds in Knox County, Ohio, were sampled over two years to investigate the relationship between the microbial taxa profiles, antibiotic resistance genes (ARGs), and environmental factors such as pH and tannin concentrations. For each site, microbial communities were collected by filtration and metagenomes were analyzed by short-read sequencing. Taxa profiles were predicted by the Kraken2/Bracken pipelines. Bacterial taxa with high abundance in these ponds included Betaproteobacteria (Polynucleobacter and Methylopumilus) and Actinobacteria (Planktophila, Nanopelagicus, and Mycolicibacterium). One pond, a former quarry with elevated pH, showed high prevalence of Cyanobacteria with a seasonal shift from Synechococcus to Planktothrix in the fall. Planktothrix increase was associated with acidification. ARGs were quantified using the ShortBRED pipeline to detect and quantify hits to a marker set derived from the Comprehensive Antibiotic Resistance Database (CARD). The top two ARGs with the largest marker hits encode components of a Stenotrophomonas drug efflux pump powered by proton-motive force (smeABC) and a mycobacterial global regulator that activates a drug pump and other cell defenses (mtrA). Pump function and global activation of transcription incur large energy expenditures, whose fitness cost may increase at high external pH where the cell's proton-motive force is diminished. The smeABC and mtrA prevalence showed a modest correlation with acidifying conditions (low pH and high tannins) which contribute a large transmembrane pH difference to the proton-motive force, thus increasing the cell's energy available for pump function and global gene expression. Compared to rivers and lakes, pond microbial ecosystems are understudied despite close contact with agriculture and recreation. Environmental microbes offer health benefits as well as hazards for human contact. Small water bodies may act as reservoirs for drug-resistant organisms and transfer of antibiotic resistance genes. Yet, the public is rarely aware of the potential for exposure to ARG-carrying organisms in recreational water bodies. Little is known about the capacity for freshwater microbial communities to remediate drug pollution and which biochemical factors may select against antibiotic resistance genes. This study analyzes the bacterial taxa composition and ARG prevalence including possible influence of factors such as pH and tannic acid levels.
Hardware-Free Testing for Antimicrobial Resistance Using Artificial Intelligence
Authors: Chakraborty Purbali , Doganay Mert Tunca , Tozluyurt Abdullah , Hujer Andrea M. , Bonomo Robert A. , Draz Mohamed S.
Published: July 2024

Antimicrobial resistance (AMR) is one of the most challenging public health problems, and implementation of effective and accessible testing solutions is an ever-increasing unmet need. Artificial intelligence (AI) offers a promising avenue for enhanced testing performance and accuracy. We introduce an AI system specifically designed for rapid AMR testing, eliminating the requirement for bulky hardware and extensive automation. Our system incorporates a novel approach for nanotechnology-empowered intelligent diagnostics (NEIDx), leveraging nanoparticles to enable novel AI-based advanced systems for detection. We employ catalytic nanoparticle-based NEIDx coupled with magnetic separation to facilitate the direct detection of AMR-associated enzymes from blood samples. This is achieved through the formation of easily visible and detectable large bubbles, a process streamlined by AI running on a cellphone. We evaluated the performance of our AI system using two clinically relevant AMR enzymes: Klebsiella pneumoniae carbapenemase-2 (KPC-2) and Sulfhydryl variable-1 (SHV-1) β-lactamases. The system demonstrated qualitative detection with a sensitivity of 82.61% (CI of 79.7 - 85.5%) and a specificity of 92.31% (CI of 90.3 - 94.3%) in blood samples, respectively. This innovative approach holds significant promise for advancing point-of-care diagnostics and addressing the urgent need for rapid and accessible AMR testing in diverse healthcare settings.
Low-dose chemotherapy combined with delayed immunotherapy in the neoadjuvant treatment of non-small cell lung cancer and dynamic monitoring of the drug response in peripheral blood
Authors: Liang Chaoyang , Song Qi , Zhou Wenhao , Li Na , Xiong Qi , Pan Chaohu , Zhao Shaohong , Yan Xiang , Zhang Xiaoling , Long Yaping , Guo Juntang , Wang Tao , Shi Weiwei , Sun Shengjie , Yang Bo , Dong Zhouhuan , Luo Haitao , Li Jie , Hu Yi , Yang Bo
Published: July 2024

Background: Despite chemo-immunotherapy has been applied to the neoadjuvant treatment of non-small cell lung cancer (NSCLC), the impacts of dosage and the order of medication on treatment efficacy and safety remain largely unexplored. We originally designed an exploratory study to investigate the efficacy and safety of reduced-dose chemotherapy combined with delayed immunotherapy as well as the dynamic changes of circulating tumor DNA (ctDNA) and T cell receptor (TCR) during the therapy. Methods: Patients with clinical stage IIA to IIIA resectable NSCLC were treated with 2 cycles of reduced-dose platinum-based chemotherapy on day 1 combined with immunotherapy on day 5. The same postoperative modified adjuvant therapy regimen was administered for 2 cycles. Plasma samples at different time-points were collected and performed with T cell receptor (TCR) and circulating tumor DNA (ctDNA) sequencing. Results: 38 patients received modified chemo-immunotherapy. The proportion of patients exhibiting complete response and partial response was 5.3% and 68.4%, respectively. The confirmed objective response rate was 73.7%. Radiological downstaging was achieved in 39.5%. Major pathologic response and complete pathologic response were observed in 47.4% and 31.6% of patients, respectively. Only one patient experienced grade 3 adverse event. Further analyses revealed that this modified chemo-immunotherapy led to the expansion of predominant TCR clones and reduction of tumor burden after the first cycle of chemotherapy. Conclusion: The promising clinical efficacy and low side effects of modified neoadjuvant chemo-immunotherapy position it as a prospective and innovative strategy for NSCLC.
Psilocybin mushrooms and public health in Brazil: a low-risk adverse event profile calls for evidence-based regulatory discussions
Authors: Nogueira Marcel , García-Hernández Solimary , Roberto Gleicy Sotéro , Marques Leonardo Zanella
Published: July 2024

Background

Current drug policy classifies psilocybin, a substance produced by psychoactive mushrooms, as having a high potential for abuse, neglecting its therapeutic properties. We aimed to investigate if psilocybin mushrooms pose a risk to Brazilian public health compared to other toxic agents and whether evidence-based regulatory discussions are needed.

Methods

A retrospective cross-sectional study was conducted following STROBE guidelines. Data were obtained from the Sistema de Agravos de Notificação (SINAN) on adverse events reported from 2007 to 2022. Participants were categorized into three groups: drug abuse, psilocybin mushrooms, and unknown mushrooms. Clinical outcomes assessed included non-hospitalization, hospitalization, and death. Associations between variables were analyzed using the Chi-square test.

Results

A total of 112,451 individuals sought medical attention for drug abuse-related adverse events. Among them, men constituted the majority (n = 79,514; 70.7%), followed by whites (n = 37,565; 33.4%) and those aged 26-35 (n = 29,163; 25.9%) (p < 0.001). Alcohol was the primary toxic agent (n = 71,824; 49.2%) (p < 0.001). The psilocybin mushroom group reported 13 adverse events, and the unknown mushroom group recorded 51 adverse events. Hospitalization rates were 19.5% (n = 21,923) for drug abuse, 46.2% (n = 6) for psilocybin mushrooms (0.02% of all hospitalizations) (99% CI: 10.6% - 81.6%), and 23.5% (n = 12) for unknown mushrooms (0.04% of hospitalizations) (99% CI: 8.3% - 38.7%). The mortality rate was 1.8% (n = 2035) for drug abuse, with no fatalities in the psilocybin or unknown mushroom groups. Most hospitalizations involved alcohol (45.0%), and deaths were mainly associated with cocaine (33.3%).

Conclusion

Our findings suggest that psilocybin mushrooms have a low-risk profile for adverse events, although underreporting may be a factor. This study highlights the need for evidence-based regulatory discussions to prevent arbitrary arrests and ensure safe access to psilocybin for clinical and ceremonial use.
First-born twin has a higher risk of acute leukemia in a population-based assessment of cancer in twins in California, and lower than anticipated rate of twin concordance
Authors: Nickels Eric M , Zhou Naying , Wiemels Joseph L
Published: July 2024

We assessed cancer concordance, cancer incidence in the healthy twin of cancer probands, and cancer risk in relation to birth order in pediatric and adolescent/young adult twins via a population-based study in California from 1982-2022. Twin subjects born in California between 1982-2017 who were diagnosed with leukemia from 0-39 years of age were identified through linked birth and California Cancer Registry (1988-2022) data. Two concordant-twin leukemias cases were identified across 255 total twin pairs with leukemia for an overall rate of leukemia concordance of 0.9%. One concordant twin pair was identified among 199 pairs with lymphoid leukemia (0.5%) and one within 34 pairs with acute myeloid leukemia (2.9%). A significant association was identified between twin plurality birth order and development of leukemia (OR 1.18, 95% CI 1-1.39, P=0.049), an effect which was strongest in lymphoid leukemias (2.21, 1.44-3.39, P=1.65e-4). Assessment of DNA methylation markers associated with birth order showed significantly reduced methylation in first-born twin cases compared to second-born (P=8.53e-12) in a subset of 41 twins discordant for lymphoid leukemia. Overall cancer concordance in twins was comparable to the lower range of previous estimates from different world regions. Concordance in lymphoid leukemias was quite lower than expected, indicating concordant leukemia is rarer than previously appreciated. We identified a strong association between twin plurality birth order and development of pediatric cancer. While the underlying cause of this finding is uncertain, we identified significant differences in DNA methylation at previously described sites associated with birth order, suggesting a similar biological mechanism.
mBRSET: A Portable Retina Fundus Photos Benchmark Dataset for Clinical and Demographic Prediction
Authors: Wu Chenwei , Restrepo David , Nakayama Luis Filipe , Ribeiro Lucas Zago , Shuai Zitao , Barboza Nathan Santos , Vieira Sousa Maria Luiza , Fitterman Raul Dias , Alves Pereira Alexandre Durao , Saito Regatieri Caio Vinicius , Stuchi Jose Augusto , Malerbi Fernando Korn , Andrade Rafael E.
Published: July 2024

This paper introduces mBRSET, the first publicly available retina dataset captured using handheld retinal cameras in real-life, high-burden scenarios, comprising 5,164 images from 1,291 patients of diverse backgrounds. This dataset addresses the lack of ophthalmological data in low- and middle-income countries (LMICs) by providing a cost-effective and accessible solution for ocular screening and management. Portable retinal cameras enable applications outside traditional hospital settings, such as community health screenings and telemedicine consultations, thereby democratizing healthcare. Extensive metadata that are typically unavailable in other datasets, including age, sex, diabetes duration, treatments, and comorbidities, are also recorded. To validate the utility of mBRSET, state-of-the-art deep models, including ConvNeXt V2, Dino V2, and SwinV2, were trained for benchmarking, achieving high accuracy in clinical tasks diagnosing diabetic retinopathy, and macular edema; and in fairness tasks predicting education and insurance status. The mBRSET dataset serves as a resource for developing AI algorithms and investigating real-world applications, enhancing ophthalmological care in resource-constrained environments.
Unveiling the Structural Proteome of an Alzheimer’s Disease Rat Brain Model
Authors: Samani Elnaz Khalili , Naimul Hasan S.M. , Waas Matthew , Keszei Alexander F. A. , Xu Xiaoxiao , Heydari Mahtab , Hill Mary Elizabeth , McLaurin JoAnne , Kislinger Thomas , Mazhab-Jafari Mohammad T.
Published: July 2024

Studying native protein structures at near-atomic resolution in crowded environment presents a challenge. Consequently, understanding the structural intricacies of proteins within pathologically affected tissues often relies on mass spectrometry and proteomic analysis. In this study, we utilized electron cryomicroscopy (cryo-EM) and a specific method of analysis called Build and Retrieve (BaR) to investigate structural characteristics of protein complexes such as post-translational modification, active site occupancy, and arrested conformational state in Alzheimer’s Disease (AD) using brain lysate from a rat model (TgF344-AD) of the disease. Our findings reveal novel insights into the architecture of these complexes, which we corroborate through mass spectrometry analysis. Interestingly, it has been shown that the dysfunction of these protein complexes extends beyond AD, implicating them in cancer, as well as other neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, and Schizophrenia. By elucidating the structural details of these complexes, our work not only enhances our understanding of disease pathology but also suggests new avenues for future approaches in therapeutic intervention.
Therapeutic Peptide SS-31 Modulates Membrane Binding and Aggregation of Alpha-Synuclein and Restores Impaired Mitochondrial Function
Authors: Stefaniak Ewelina , Cui Beiyuan , Sun Kexin , Yan Xucheng , Teng Xiangyu , Ying Liming
Published: July 2024

Membrane binding and aggregation properties of alpha-synuclein are closely associated with Parkinson's disease and a class of related syndromes named as synucleinopathy. This study explored the potential of SS-31 (Elamipretide), a therapeutic tetrapeptide with alternating cationic and aromatic residues and known properties of mitochondrial inner membrane binding and oxidative stress reduction, in modulating alpha-synuclein interaction with the lipid membranes and mitigating impairment of mitochondrial function induced by alpha-synuclein oligomers. It was demonstrated by both fluorescence correlation spectroscopy and fluorescence anisotropy that SS-31 displaces both wild-type and N-terminus acetylated alpha-synuclein from negatively charged small unilamellar vesicles in a dose-dependent manner. Thioflavin-T assay and transmission electron microscopy (TEM) showed that SS-31 inhibits membrane-induced alpha-synuclein aggregation and alters the morphology of alpha-synuclein fibrils. Moreover, Seahorse Mito Stress Test indicated that SS-31 restores impaired mitochondrial function in alpha-synuclein oligomer-treated neuroblastoma cells. Finally, confocal imaging revealed that SS-31 hinders cellular uptake of alpha-synuclein oligomers, possibly by modifying cell membrane electrostatics. These findings underscore the multifaceted protective role of SS-31 against mitochondrial dysfunction caused by alpha-synuclein aggregation. Consequently, SS-31 emerges as a promising therapeutic candidate to attenuate neurodegeneration pertinent to alpha-synuclein misfolding and aggregation. There is a good potential for further refinement of such peptide against many diseases linked to mitochondrial dysfunction and oxidative stress.