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A cell atlas of the human fallopian tube throughout the menstrual cycle and menopause

Exploring data literacy self-perception among Indonesian high school students

Data is becoming increasingly ubiquitous today, and data literacy has emerged an essential skill in the workplace. Therefore, it is necessary to equip high school students with data literacy skills in order to prepare them for further learning and future employment. In Indonesia, there is a growing shift towards integrating data literacy in the high school curriculum. As part of a pilot intervention project, academics from two leading Universities organised data literacy boot camps for high school students across various cities in Indonesia. The boot camps aimed at increasing participants’ awareness of the power of analytical and exploration skills, which in turn, would contribute to creating independent and data-literate students. This paper explores student participants’ self-perception of their data literacy as a result of the skills acquired from the boot camps. Qualitative and quantitative data were collected through student surveys and a focus group discussion, and were used to analyse student perception post-intervention. The findings indicate that students became more aware of the usefulness of data literacy and its application in future studies and work after participating in the boot camp. Of the materials delivered at the boot camps, students found the greatest benefit in learning basic statistical concepts and applying them through the use of Microsoft Excel as a tool for basic data analysis. These findings provide valuable policy recommendations that educators and policymakers can use as guidelines for effective data literacy teaching in high schools.

Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases

AbstractAccurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer’s disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls. We identify significant inter-individual variability in overall CSF levels of brain-derived proteins, which could not be attributed to specific disease associations. Using linear modelling, we show that adjusting for median CSF levels of brain-derived proteins increases the diagnostic accuracy of proteins previously identified as altered in CSF in the context of neurodegenerative disorders. We further demonstrate a simplified approach for the adjustment using pairs of correlated proteins with opposite alteration in the diseases. With this approach, the proteins adjust for each other and further increase the biomarker performance through additive effect. When comparing the diseases, two proteins—neurofilament medium and myelin basic protein—showed increased levels in ALS compared to other diseases, and neurogranin showed a specific increase in AD. Several other proteins showed similar trends across the studied diseases, indicating that these proteins likely reflect shared processes related to neurodegeneration. Overall, our findings suggest that accounting for inter-individual variability is crucial in future studies to improve the identification and performance of relevant biomarkers. Importantly, we highlight the need for multi-disease studies to identify disease-specific biomarkers.

Review on natural hydrogen wells safety

A new extended Chen distribution for modelling COVID-19 data

In this paper, we propose a new flexible statistical distribution, the Topp-Leone Exponentiated Chen distribution, to model real-world data effectively, with a particular focus on COVID-19 data. The motivation behind this study is the need for a more flexible distribution that can capture various hazard rate shapes (e.g., increasing, decreasing, bathtub) and provide better fitting performance compared to existing models such as the Chen and exponentiated Chen distributions. The principal results include the derivation of key statistical properties such as the probability density function, cumulative distribution function, moments, hazard rate function, and order statistics. Maximum likelihood estimation is employed to estimate the parameters of the TLEC distribution, and simulation studies demonstrate the efficiency of the maximum likelihood method. The innovation of this work is further validated by applying the TLEC distribution to real COVID-19 data, where it outperforms several related models. The study concludes with significant insights into how the TLEC distribution provides a more accurate and flexible approach to modeling real-world phenomena.

Accelerated aging modulates the toxicological properties of the diazo tattoo pigment PO13

Ionizable polymeric micelles (IPMs) for efficient siRNA delivery

Factors associated with adherence to antiretroviral therapy among HIV-positive adolescents and young adult patients attending HIV care and treatment clinic at Bombo Hospital in Tanga region-Tanzania

Background Adherence to HIV treatment regimens involves the consistent and correct intake of all prescribed medications. The implementation of antiretroviral therapy (ART) program has significantly reduced mortality among adolescents living with HIV. However, adherence to ART is lower among adolescents compared to other sub-populations and even lower in sub-Saharan Africa. The factors influencing ART adherence are context-specific and vary across countries and regions. In the Tanzanian context, there is a paucity of data regarding these factors. Methodology This cross-sectional study involved 385 adolescents and young adults living with HIV receiving treatment at Bombo Hospital Referral Hospital’s Care and Treatment Clinic, in Tanga, Tanzania. To assess adherence, a one-month self-recall medication adherence scale was used while a structured questionnaire was used to gather data on determinants of adherence. Data were collected using Google Forms and subsequently exported as a Microsoft Excel file. The data were then entered into Stata software version 15 for cleaning for descriptive and logistic regression analyses. Results More than a third (35.3%) of adolescents and young adults living with HIV in Tanga were not adherent to the effective and available ART. Adolescents and young adults living in households experiencing moderate food insecurity were 67% less likely to adhere to ART (95%CI 0.16–0.66) compared to those who were food secure. Those with secondary education were 2.3 times more likely to adhere to ART (95%CI 1.02–5.23), compared to those without formal education. While participants who consistently obtain their ART at the clinic were more 4.2 times more likely to adhere to medication (95%CI 1.29–13.72), those experiencing ART side effects were 39% less likely to adhere to ART (95%CI 0.38–0.98). Conclusion More than one-third of adolescents and young adults were not adherent to ART in Tanga, Tanzania. Addressing such unprecedented challenges calls for efforts targeting adolescents and young adults with limited education, from households with food insecurity, and ensuring counseling and management of ART side effects.

Discovery of potent anti-toxoplasmosis drugs from secondary metabolites in Citrus limon (lemon) leaves, supported in-silico study

Abstract Toxoplasmosis induced by Toxoplasma gondii is a well-known health threat, that prompts fatal encephalitis increased with immunocompromised patients, in addition, it can cause chorioretinitis, microcephaly, stillbirth in the fetus and even led to death. Standard therapy uses sulfadiazine and pyrimethamine drugs revealed beneficial results during the acute stage, however, it has severe side effects. UPLC-ESI-MS/MS used to explore C. limon MeOH ext. constituents, which revealed a list of 41 metabolites of different classes encompasses; unsaturated fatty acid, tricarboxylic acids, phenolic aldehyde, phenolic acids, phenolic glycosides, coumarins, sesquiterpene lactone, limonoid, steroid and flavonoids. C. limon MeOH ext. and the isolates reduced significantly the number of T. gondii tachyzoites. Consequently, histopathological examination, proved significant reduction in the number of mononuclear inflammatory cells in the kidney and liver sections, besides, lowering the number of shrunken and degenerative neurons in the brain sections of infected mice. Molecular docking study was performed targeted certain receptors, which are important for the life cycle fundamentals for the parasite mobility including invasion and egress, and further molecular dynamics simulation was conducted to get insights into the structural changes of the formed complexes, along with a pharmacophoric mapping approach, that confirmed the need for a free hydroxyl group and/or a phenolic substituted one, in order to form HB, Hyd/Aro and ML interactions, through which, cell cycle disruption via iron chelation, could be achieved. In addition, the ADMIT properties of all identified metabolites were predicted.

Emergence of ferroelectricity in Sn-based perovskite semiconductor films by iminazole molecular reconfiguration

AbstractFerroelectric semiconductors have the advantages of switchable polarization ferroelectric field regulation and semiconductor transport characteristics, which are highly promising in ferroelectric transistors and nonvolatile memory. However, it is difficult to prepare a Sn-based perovskite film with both robust ferroelectric and semiconductor properties. Here, by doping with 2-methylbenzimidazole, Sn-based perovskite [93.3 mol% (FA0.86Cs0.14)SnI3 and 6.7 mol% PEA2SnI4] semiconductor films are transformed into ferroelectric semiconductor films, owing to molecular reconfiguration. The reconfigured ferroelectric semiconductors exhibit a high remanent polarization (Pr) of 23.2 μC/cm2. The emergence of ferroelectricity can be ascribed to the hydrogen bond enhancement after imidazole molecular doping, and then the spatial symmetry breaks causing the positive and negative charge centers to become non-coincident. Remarkably, the transistors based on perovskite ferroelectric semiconductors have a low subthreshold swing of 67 mv/dec, which further substantiates the superiority of introducing ferroelectricity. This work has developed a method to realize Sn-based ferroelectric semiconductor films for electronic device applications.

Correction: Genetic differentiation at extreme latitudes in the socially plastic sweat bee Halictus rubicundus

Exploring the spatiotemporal effects of urban scale and urban vitality on S&D balance in the Yangtze River Delta, China from 2015 to 2025

Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial

AbstractEarly therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.7–NR, median follow-up 50 months). The secondary endpoint, biochemical PFS, was 48.6 months (95% CI: 39.9–NR) and coincided with or preceded SLiM-CRAB in eight patients. For additional secondary objectives, the overall response rate was 93% with 31% achieving complete response (CR) and 45% very good partial response (VGPR) or better. CR correlated strongly with the absence of SLiM-CRAB and biochemical progression. MRD-negativity (10-5 sensitivity) predicted a 5-year biochemical PFS of 100% versus 40% in MRD-positive patients (p = 0.051), demonstrating that deep responses significantly improve time to progression. Exploratory single-cell RNA sequencing linked tumor MHC class I expression to proteasome inhibitor response, and a lower proportion of GZMB+ T cells within clonally expanded CD8+ T cells associated with suboptimal outcomes.

The involvement of Elf5 in regulating keratinocyte proliferation and differentiation processes in skin

Skin and hair development is regulated by multitude of programs of activation and silencing of gene expression to maintain normal skin and hair follicle (HF) development, homeostasis, and cycling. Here, we have identified E74-like factor 5 (Elf5) transcription factor, as a novel regulator of keratinocyte proliferation and differentiation processes in skin. Expression analysis has revealed that Elf5 expression was localised and elevated in stem/progenitor cell populations of both the epidermis (basal and suprabasal) and in HF bulge and hair germ stem cell (SCs) compartments during skin and hair development and cycling. Expressional and functional analysis using RT-qPCR, western blot and colony forming assays, revealed that Elf5 plays an important role in regulating keratinocyte proliferation and differentiation processes as well as potentially determining cell fate by regulating the stem/progenitor cell populations in skin and HFs. These data will provide a platform for pharmacological manipulation of Elf5 in skin, leading to advancements in many areas of research, including stem cell, regenerative medicine, and ageing.

Deciphering antioxidant interactions via data mining and RDKit

Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning

Utilization of transitional care management services and 30-day readmission

Transitional care management (TCM) visits have been shown to reduce 30-day readmissions, but it is unclear whether the decrease arises from the TCM visit itself or from clinic-level changes to meet the requirements of the TCM visits. We conducted a cross-sectional analysis using data from Northwell Health to examine the association between the type of post-discharge follow-up visits (TCM visits versus non-TCM visits based on billing) and 30-day readmission. Furthermore, we assessed whether being seen by a provider who frequently utilizes TCM visits or the TCM visit itself was associated with 30-day readmission. We included adult patients hospitalized to Medicine service and subsequent follow-up visits within two weeks of discharge between February 24, 2018, and February 24, 2020. We examined 1) post-discharge follow-up visit type (TCM visit versus non-TCM visit) and 2) provider characteristics (frequent TCM visit utilization or not). The primary outcome was unplanned hospital readmission within 30 days following hospital discharge. After propensity matching, TCM follow-up visits were associated with decreased 30-day readmissions (hazard ratio = 0.74 [0.63–0.88]) compared to non-TCM visits. Among patients with non-TCM follow-up visits, those seen by a provider who frequently used TCM visits had decreased odds (OR = 0.84 [0.71–0.99]) of 30-day readmission compared to those seen by providers who did not use TCM visits regularly. Among patients who followed up with providers who frequently use TCM visits, TCM visits were associated with decreased 30-day readmission compared to patients with non-TCM visits (OR = 0.78 [0.62–0.98]). The study has limitations, including the health system database not capturing all out-of-network follow-up visits. The reduction in 30-day readmission associated with TCM visits likely arises from both the visit itself and being seen by a provider who frequently uses TCM visits.

Genome-wide association studies in lettuce reveal the interplay of seed age, color, and germination under high temperatures

Abstract Thermoinhibition, the suppression of seed germination by high temperatures, is an adaptive trait that ensures successful seedling establishment in natural environments. While beneficial for wild plants, thermoinhibition can adversely affect crop yields due to uneven and reduced germination rates, particularly in the face of climate change. To understand the genetic basis of thermoinhibition, we conducted a comprehensive genetic analysis of a diverse panel of Lactuca spp. accessions. Our findings revealed that L. serriola , a wild ancestor of cultivated lettuce, showed relaxed thermoinhibition response compared to cultivated lettuce, suggesting that this trait may have been positively selected during early domestication in the Mediterranean region with hot, dry summers. Additionally, we found that thermoinhibition intensified with seed age but was less pronounced in dark-colored seeds, which showed increased germination under high temperatures. Genome-wide association studies identified genomic regions associated with thermoinhibition, including genes involved in ethylene and ABA signaling. Interestingly, some of these regions were also linked to seed color, suggesting a potential genetic coupling between black seed color and reduced thermoinhibition. These results highlighted the complex interplay between thermoinhibition, seed color, and domestication in lettuce, indicating a complicated nature of thermoinhibition regulation. By elucidating the genetic architecture of thermoinhibition, our study provides a valuable foundation for breeding strategies to enhance lettuce resilience to climate change.

Quantum-limited stochastic optical neural networks operating at a few quanta per activation

Abstract Energy efficiency in computation is ultimately limited by noise, with quantum limits setting the fundamental noise floor. Analog physical neural networks hold promise for improved energy efficiency compared to digital electronic neural networks. However, they are typically operated in a relatively high-power regime so that the signal-to-noise ratio (SNR) is large (>10), and the noise can be treated as a perturbation. We study optical neural networks where all layers except the last are operated in the limit that each neuron can be activated by just a single photon, and as a result the noise on neuron activations is no longer merely perturbative. We show that by using a physics-based probabilistic model of the neuron activations in training, it is possible to perform accurate machine-learning inference in spite of the extremely high shot noise (SNR  ~ 1). We experimentally demonstrated MNIST handwritten-digit classification with a test accuracy of 98% using an optical neural network with a hidden layer operating in the single-photon regime; the optical energy used to perform the classification corresponds to just 0.038 photons per multiply-accumulate (MAC) operation. Our physics-aware stochastic training approach might also prove useful with non-optical ultra-low-power hardware.

A NOTCH3 pathogenic variant influences osteogenesis and can be targeted by antisense oligonucleotides in induced pluripotent stem cells

Lateral Meningocele Syndrome (LMS), a disorder associated with NOTCH3 pathogenic variants, presents with neurological, craniofacial and skeletal abnormalities. Mouse models of the disease exhibit osteopenia that is ameliorated by the administration of Notch3 antisense oligonucleotides (ASO) targeting either Notch3 or the Notch3 mutation. To determine the consequences of LMS pathogenic variants in human cells and whether they can be targeted by ASOs, induced pluripotent NCRM1 and NCRM5 stem (iPS) cells harboring a NOTCH36692-93insC insertion were created. Parental iPSCs, NOTCH36692-93insC and isogenic controls, free of chromosomal aberrations as determined by human CytoSNP850 array, were cultured under conditions of neural crest, mesenchymal and osteogenic cell differentiation. The expected cell phenotype was confirmed by surface markers and a decline in OCT3/4 and NANOG mRNA. NOTCH36692-93insC cells displayed enhanced expression of Notch target genes HES1, HEY1, 2 and L demonstrating a NOTCH3 gain-of-function. There was enhanced osteogenesis in NOTCH36692-93insC cells as evidenced by increased mineralized nodule formation and ALPL, BGLAP and BSP expression. ASOs targeting NOTCH3 decreased both NOTCH3 wild type and NOTCH36692-93insC mutant mRNA by 40% in mesenchymal and 90% in osteogenic cells. ASOs targeting the NOTCH3 insertion decreased NOTCH36692-93insC by 70–80% in mesenchymal cells and by 45–55% in osteogenic cells and NOTCH3 mRNA by 15–30% and 20–40%, respectively. In conclusion, a NOTCH3 pathogenic variant causes a modest increase in osteoblastogenesis in human iPS cells in vitro and NOTCH3 and NOTCH3 mutant specific ASOs downregulate NOTCH3 transcripts associated with LMS.