bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnitude, Associated Factors and Immediate Outcomes of Non-Reassuring Fetal Heart Rate Status Among Laboring Mothers at South Gondar Zone Public Hospitals, North, West Ethiopia, 2022; Cross Sectional Study
Authors: Belete Ewunetu , Bazezew Yibelu , Desta Melaku , Misganaw Dawit , Tefera Mitiku
Published: October 2022

Background

Non-reassuring fetal heart rate status (NRFHRS) is an abnormal fetal heart rate monitoring which necessitates immediate intervention. It is one of the common reducible causes of perinatal morbidity and mortality in developing countries. Despite there is limited data on the magnitude, associated factors and its outcomes in Ethiopia.

Objective

To assess the magnitude, associated factors and immediate outcomes of non-reassuring fetal heart rate status among laboring mothers at South Gondar zone public hospitals, northwest Ethiopia 2022.

Methods

An institutional-based cross-sectional study was conducted from June 1-30, 2022. A total of 586 laboring mothers were included. The participants were selected through systematic sampling method. Bivariable and multivariable logistic regression analysis were carried out. OR with 95% CI was used and statistically significant variables were declared if p < 0.05 in multivariable analysis.

Result

The magnitude of NRFHRS was 21.16% (95%, CI: 17.9-24.7) with a response rate of 97.34%. Primigravida [AOR= 1.86, 95% CI: 1.03-3.37], anemia [AOR= 4.59, 95% CI: 1.87-11.30], referred [AOR= 1.95, 95% CI: 1.07-3.55], induction of labor [AOR= 3.78, 95% CI: 1.20-11.9], meconium-stained amniotic fluid [AOR= 14.13, 95% CI: 7.53-26.50], prolonged rupture of membrane [AOR= 11.70), 95% CI: 5.40-25.34] and low birth weight [AOR=5.08, 95% CI: 2.20-11.74] were significantly associated with NRFHRS. 4.8% of fetus was still birth.

Conclusion

In this study the magnitude of NRFHRS was high compared to studies in Africa. Being primigravida, anemic, referred, induction of labor, meconium-stained amniotic fluid, prolonged rupture of membrane and low birth weight were significantly associated with NRFHRS. Assigning adequate number of midwifes for good labor follow-up, properly counsel on nutrition and iron and folic acid and give due attention on labor follow-up would minimize NRFHRS.
Emerging Technologies and Global Health: Generating Bibliometric Evidence for Innovation Management
Authors: Wu Sheng , Dhaou Soumaya Ben , Soares Delfina
Published: October 2022

The author withdrew this manuscript owing to rewriting theory, all constructs, and correction and revision according to the peer review comments during the development and discussion phase of the research. Therefore, the author would not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Engineering Highly Thermostable Cas12b via De Novo Structural Analyses for One-Pot Detection of Nucleic Acids
Authors: Nguyen Long T. , Rananaware Santosh R. , Yang Lilia G. , Macaluso Nicolas C. , Ocana-Ortiz Julio E. , Meister Katelyn S. , Pizzano Brianna L.M. , Sandoval Luke Samuel W. , Hautamaki Raymond C. , Fang Zoe R. , Joseph Sara M. , Shoemaker Grace M. , Carman Dylan R. , Chang Liwei , Rakestraw Noah R. , Zachary Jon F. , Guerra Sebastian , Perez Alberto , Jain Piyush K.
Published: October 2022

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based diagnostics have elevated nucleic acid detection in terms of sensitivity, specificity, and rapidity in recent years. CRISPR-Cas systems can be combined with a pre-amplification step in a one-pot reaction to simplify workflow and reduce carryover contamination. Here, we report an engineered Cas12b system from Brevibacillus (eBrCas12b) with improved thermostability that falls within the optimal range (60-65°C) of the Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP). Using de novo structural analyses via DeepDDG and HotSpot Wizard based on Alpha Fold and SWISS-MODEL predicted structures, mutations were introduced into the REC and RuvC domains of wild-type BrCas12b to tighten the hydrophobic cores of the protein, thereby enhancing its stability at high temperatures. We expressed, purified, and systematically characterized 49 BrCas12b variants with an emphasis on functionality and thermostability. The assay utilizing eBrCas12b, which we coined SPLENDID (Single-pot LAMP-mediated engineered BrCas12b for nucleic acid detection of infectious diseases), exhibits robust trans-cleavage activity up to 67°C in a one-pot setting—4°C and 7°C higher than wild-type BrCas12b and AapCas12b, respectively. We further validated SPLENDID clinically in 40 Hepatitis C (HCV) positive and 40 negative serum samples. A specificity of 97.5%, an accuracy of 90.0%, and a sensitivity of 82.5% were achieved. Results can be obtained via one-pot testing in as little as 20 minutes. With the extraction process, the entire assay can be performed in under an hour. Therefore, we believe that SPLENDID has the potential to become a widely universal platform for the detection of infectious diseases.
Glucoregulatory Reprogramming in Male Mice Offspring Induced by Maternal Transfer of Indoor Flame Retardant Endocrine Disruptors
Authors: Kozlova Elena V. , Chinthirla Bhuvaneswari D. , Bishay Anthony E. , Pérez Pedro A. , Denys Maximillian E. , Krum Julia M. , DiPatrizio Nicholas V. , Currás-Collazo Margarita C.
Published: October 2022

Polybrominated diphenyl ethers (PBDEs) are commercially used as indoor flame retardants that penetrate biota and bioaccumulate in human tissues, including breast milk. PBDEs have been associated with endocrine disruption, diabetes and metabolic syndrome (MetS) in humans and animals. However, their sex-specific diabetogenic effects are not completely understood. Our past works show diabetogenic effects of the commercial penta-mixture of PBDEs, DE-71, in perinatally exposed C57Bl/6 female mice. As a comparison, in the current study, the effects of DE-71 on glucose homeostasis in male offspring were examined. C57BL/6 dams were exposed to DE-71 at 0.1 mg/kg/d (L-DE-71), 0.4 mg/kg/d (H-DE-71) or received corn oil vehicle (VEH/CON) for a total of 10 wks, including gestation and lactation. Male offspring were examined in adulthood and DE-71 exposure produced hypoglycemia upon extended fasting. In vivo glucose challenge testing showed marked intolerance (H-DE-71) and incomplete clearance (L- and H-DE-71). Moreover, L-DE-71-exposed mice showed altered glucose responses to insulin, especially incomplete glucose clearance and/or utilization. In addition, L-DE-71 produced elevated levels of plasma glucagon and the incretin GLP-1 but no changes were detected on insulin. These alterations, which represent relevant criteria used clinically to diagnose diabetes, were accompanied with reduced hepatic glutamate dehydrogenase enzymatic activity, elevated adrenal epinephrine and decreased thermogenic brown adipose tissue mass, which may indicate several organ system targets of PBDEs. Liver levels of several endocannabinoid species were not altered by perinatal exposure to DE-71 in males. Our findings demonstrate that chronic low exposure to PBDEs in mothers can reprogram glucose homeostasis and glucoregulatory hormones in male offspring. Previous findings using female offspring showed altered glucose homeostasis that aligned with a contrasting diabetogenic phenotype. We summarize the results of the current work generated in males in light of previous findings on females. Taken together, these findings, combined with our prior results, offer a comprehensive account of sex-dependent effects of maternally transferred environmentally relevant PBDEs on glucose homeostasis and glucoregulatory endocrine dysregulation.
Perturbation of mitochondrial Ca2+ homeostasis activates cross-compartmental proteostatic response in Arabidopsis
Authors: Zhang Xiaoyan , Ma Chongyang , Bao Xinyue , Zhang Shenyu , Zayed Omar , Zhang Zhengjing , Tang Kai , Xie Shaojun , Wang Yunsheng , Zhang Dayong , Xu Huawei , Jia Huifang , Wang Xinying , Lei Qianyan , Wang Xiaocui , Zhang Junli , Dinesh-Kumar Savithramma P , Song Chun-Peng , Zhu Jian-Kang , Zhu Xiaohong
Published: October 2022

Mitochondrial Ca2+ (mtCa2+) homeostasis is essential to mitochondrial functions. However, how mtCa2+ homeostasis is achieved and the consequences of impaired mtCa2+ homeostasis in plants is poorly understood. Here, we demonstrate a critical role for mitochondrial Ca2+ uniporter (MCU) in the control of mtCa2+ uptake for mtCa2+ homeostasis in planta by characterizing MCU mutants and overexpressed plants. Impaired MCU-controlled mtCa2+ homeostasis (iMUCH) in gain-of-function and loss-of-function MCU plants causes the misregulation of mitochondrial gene expression that triggers mitonuclear protein imbalance. Transcriptome integrated with proteomics analysis reveal activation of multiple compartmental UPR gene expression and decrease of cytosolic translation with selective repression of ribosome and RNA modification protein synthesis upon iMUCH. Intriguingly, TOR signalling is not involved in cytosolic translational response to iMUCH, but the reduction of eIFα phosphorylation is evident under iMUCH induced mitochondrial stress. Thus, our study unveils the essential functions of MCU proteins for mtCa2+ homeostasis, and the involvement of MCU-controlled mtCa2+ homeostasis in mitochondrial stress dependent regulation of protein synthesis for cellular proteostasis that is connected to plant growth and stress resistance.
Epigenetic aging waves: Artificial intelligence detects clustering of switch points in DNA methylation rate in defined sex-dependent age periods
Authors: Segev Elad , Shahal Tamar , Konstantinovsky Thomas , Marcus Yonit , Shefer Gabi , Ebenstein Yuval , Pasmanik-Chor Metsada , Stern Naftali
Published: October 2022

Background

Aging is linked to hypermethylation of CpG sites on promoters and enhancers, along with loss of methylation in intergenic zones. That such changes are not necessarily a continuous process is exemplified by the extensive changes in DNA methylation during development with another significant time of change during adolescence. However, the relation between age and DNA methylation during adult life has not been systematically evaluated. In particular, potential changes in methylation trends in the same CpGs over the years that may occur with aging remain largely unexplored.

Methods

Here we set out to determine the average trends by age of the CpG sites represented in the Illumina 450 platform, based on data from 2143 subjects of the age range of 20 to 80 years, compiled from 24 different cohorts. Using several mathematical procedures, we initially separated stationary probes from probes whose methylation changes with age. Among the latter, representing ∼20% of the probes, we then focused on the identification of CpG sites with switch points, i.e., a point where a stable trend of change in the age-averaged methylation is replaced by another linear trend.

Results

Using several mathematical modeling steps, we generated a machine learning model that identified 5175 CpG sites with switch points in age-related changes in the trend of methylation over the years. Switch points reflect acceleration, deceleration or change of direction of the alteration of methylation with age. The 5175 switch points were limited to 2813 genes in three waves, 80% of which were identical in men and women. A medium-size wave was seen in the early forties, succeeded by a dominant wave as of the late fifties, lasting up to 8 years each. Waves appeared∼4-5 years earlier in men. No switch points were detected on CpGs mapped to the X chromosome.

Conclusion

In non-stationary CpG sites, concomitant switch points in age related changes in methylations can be seen in a defined group of sites and genes, which cluster in 3 age- and sex-specific waves.
High-throughput cell spheroid production and assembly analysis by microfluidics and deep learning
Authors: Trossbach Martin , Åkerlund Emma , Langer Krzysztof , Seashore-Ludlow Brinton , Joensson Haakan N.
Published: October 2022

3D cell culture models are an important tool in translational research but have been out of reach for high-throughput screening due to complexity, requirement of large cell numbers and inadequate standardization. Here, we present a high-throughput workflow to produce and characterize the formation of miniaturized spheroids using deep learning. We train a convolutional neural network (CNN) for cell ensemble morphology classification, benchmark it against more conventional image analysis, and characterize spheroid assembly determining optimal surfactant concentrations and incubation times for spheroid production for three cell lines with different spheroid formation properties. Notably, this format is compatible with large-scale spheroid production and screening. The presented workflow and CNN offer a template for large scale minispheroid production and analysis and can be extended and re-trained to characterize morphological responses in spheroids to additives, culture conditions and large drug libraries.
Inflammation drives age-induced loss of tissue resident macrophages
Authors: Adé Kémy , Coronilla Javier Saenz , Obino Dorian , Weinberger Tobias , Kaiser Caroline , Mella Sébastien , Chen Cheng , Katsimpardi Lida , Werts Catherine , Li Han , Dardenne Pascal , Lallemand Yvan , Gomez Perdiguero Elisa
Published: October 2022

Low-grade chronic systemic inflammation, or inflammageing, is a hallmark of ageing and a risk factor for both morbidity and mortality in elderly people. Resident macrophages are tissue homeostasis sentinels that are embedded in their tissue of residence since embryonic development, thus been exposed to cumulative tissue insults throughout life. Therefore, resident macrophages, among other immune cells, emerge as potential key contributors to age-associated tissue dysfunction. Contrary to what is currently postulated, we demonstrate here that the pool of embryo-derived resident macrophages exhibits an age-dependent depletion in liver, and other solid organs and that they are not replaced by Hematopoietic Stem Cell (HSCs)-derived monocytes throughout life. Further, we demonstrate that gradual, cumulative inflammation during ageing induces this specific loss of tissue resident macrophages. Preserving a “youthful” density of resident macrophages attenuates classical hallmarks of liver age-associated dysfunction.

The pool of embryo-derived resident macrophages dwindles with age in most tissues, without compensation from Hematopoietic Stem Cell (HSC)-derived cells. This loss is not due to impaired self-renewal in old tissues but rather to increased cell death, which is driven by sustained inflammation. Attenuating inflammation sensing during ageing prevents age-induce macrophage loss and improves hallmarks of liver ageing.
On the origins of phenotypic parallelism in benthic and limnetic stickleback
Authors: Dean Laura L. , Magalhaes Isabel Santos , D’Agostino Daniele , Hohenlohe Paul , MacColl Andrew D. C.
Published: October 2022

Rapid evolution of similar phenotypes in similar environments, giving rise toin situparallel adaptation, is an important hallmark of ecological speciation. However, what appears to bein situadaptation can also arise by dispersal of divergent lineages from elsewhere. We test whether two contrasting phenotypes repeatedly evolved in parallel, or have a single origin, in an archetypal example of ecological adaptive radiation: benthic-limnetic three-spined stickleback (Gasterosteus aculeatus) across species-pair and solitary lakes in British Columbia. We identify two genomic clusters across freshwater populations, which differ in benthic-limnetic divergent phenotypic traits and separate benthic from limnetic individuals in species pair lakes. Phylogenetic reconstruction and niche evolution modelling both suggest a single evolutionary origin for each of these clusters. We detected strong phylogenetic signal in benthic-limnetic divergent traits, suggesting they are ancestrally retained. Accounting for ancestral state retention, we identify local adaptation of body armour due to the presence of an intraguild predator, the sculpin (Cottus asper) and environmental effects of lake depth and pH on body size. Taken together, our results imply a predominant role for retention of ancestral characteristics in driving trait distribution, with further selection imposed on some traits by environmental factors.
Validation of the linear regression method to evaluate population accuracy and bias of predictions for non-linear models
Authors: Yu Haipeng , Fernando Rohan L , Dekkers Jack CM
Published: October 2022

Background

The linear regression method (LR) was proposed to estimate population bias and accuracy of predictions, while addressing the limitations of commonly used cross-validation methods. The validity and behavior of the LR method have been provided and studied for linear model predictions but not for non-linear models. The objectives of this study were to 1) provide a mathematical proof for the validity of the LR method when predictions are based on conditional mean, 2) explore the behavior of the LR method in estimating bias and accuracy of predictions when the model fitted is different from the true model, and 3) provide guidelines on how to appropriately partition the data into training and validation such that the LR method can identify presence of bias and accuracy in predictions.

Results

We present a mathematical proof for the validity of the LR method to estimate bias and accuracy of predictions based on the conditional mean, including for non-linear models. Using simulated data, we show that the LR method can accurately detect bias and estimate accuracy of predictions when an incorrect model is fitted when the data is partitioned such that the values of relevant predictor variables differ in the training and validation sets. But the LR method fails when the data are not partitioned in that manner.

Conclusions

The LR method was proven to be a valid method to evaluate the population bias and accuracy of predictions based on the conditional mean, regardless of whether it is a linear or non-linear function of the data. The ability of the LR method to detect bias and estimate accuracy of predictions when the model fitted is incorrect depends on how the data are partitioned. To appropriately test the predictive ability of a model using the LR method, the values of the relevant predictor variables need to be different between the training and validation sets.
Machine learning on large-scale proteomics data identifies tissue- and cell type-specific proteins
Authors: Claeys Tine , Menu Maxime , Bouwmeester Robbin , Gevaert Kris , Martens Lennart
Published: October 2022

Using data from 183 public human data sets from PRIDE, a machine learning model was trained to identify tissue and cell-type specific protein patterns. PRIDE projects were searched with ionbot and tissue/cell type annotation was manually added. Data from physiological samples were used to train a Random Forest model on protein abundances to classify samples into tissues and cell types. Subsequently, a one-vs-all classification and feature importance were used to analyse the most discriminating protein abundances per class. Based on protein abundance alone, the model was able to predict tissues with 98% accuracy, and cell types with 99% accuracy. The F-scores describe a clear view on tissue-specific proteins and tissue-specific protein expression patterns. In-depth feature analysis shows slight confusion between physiologically similar tissues, demonstrating the capacity of the algorithm to detect biologically relevant patterns. These results can in turn inform downstream uses, from identification of the tissue of origin of proteins in complex samples such as liquid biopsies, to studying the proteome of tissue-like samples such as organoids and cell lines.
Selective accumulation of matrix proteins inside of peroxisomal subdomains
Authors: Ast Julia , Bäcker Nils , Martorana Domenica , Renicke Christian , Stehlik Thorsten , Heimerl Thomas , Taxis Christof , Bange Gert , Bölker Michael , Sandrock Björn , Schink Kay Oliver , Freitag Johannes
Published: October 2022

Formation of specialized reaction spaces prevents interference between distinct cellular pathways. Peroxisomes are cellular compartments involved in a large diversity of metabolic processes. How peroxisomes differentiate into subpopulations and by which mechanism intraorganellar domains are formed remains largely elusive. Here, we report on enzymes from the fungusUstilago maydis, which accumulate inside of peroxisomal subdomains. We describe a short peptide motif (Thr-Ile-Ile-Val) sufficient to trigger focal localization. Mining for proteins with similar motifs uncovered several peroxisomal matrix proteins that accumulate in intraorganellar foci. These foci are enriched in the enzyme urate oxidase – a typical constituent of the paracrystalline core of peroxisomes. Upon peroxisome proliferation uneven distribution of focal structures results in the formation of peroxisome subpopulations with different protein content. The underlying principle of subdomain formation is evolutionary conserved in mammalian peroxisomes and formation of similar foci was also observed inside of mitochondria. We propose that peroxisomal proteins show an individual propensity to self-assemble. This formation of protein aggregates appears to be a ubiquitous driving force to spatially organize the peroxisomal proteome.
Misuse of Historical Data to Determine Past Distribution Range and Migratory Patterns of the Patagonian Huemul Misleads Conservation Targets
Authors: Corti Paulo , Díaz Norma I.
Published: October 2022

Historical information is widely used to understand mammals’ distribution dynamics and drivers, and it has been worldwide acknowledged by conservation programmes. Although these records have some limitations such as spatial and temporal accuracy, non-standardized sampling, geographical imprecisions, and levels of bias, they can fulfil a useful function to set reference conditions, priorities, and conservation goals. In the case of huemul (Hippocamelus bisulcus), an endemic cervid of shrubby and forested habitats from the Andes Mountains of southern Argentina and Chile, some reports suggest its historical presence in the steppe biome. This led Flueck et al. (2022) to assume that the past distribution of the huemul extended as far as the Atlantic coast and even in Tierra del Fuego, proposing that the altitudinal migratory tradition has been broken. Here, we carried out a qualitative and quantitative analysis of the written sources used by the authors to support their assumptions. We conclude that there are errors, uncertainties, and questionable interpretations on the use of historical data that do not add more value, instead, add mostly confusion with the misleading potential of conservation efforts on huemul.
On the reliability of wearable technology: A tutorial on measuring heart rate and heart rate variability in the wild
Authors: Dudarev Veronica , Barral Oswald , Zhang Chuxuan , Davis Guy , Enns James T.
Published: October 2022

Wearable sensors are quickly making their way into psychophysiological research, as they allow collecting longitudinal and ecologically valid data. The present tutorial considers fidelity of physiological measurement with wearable sensors, focusing on reliability. We elaborate why ensuring reliability for wearables is important and offer statistical tools for assessing wearable reliability for between participants and within-participant designs. The framework offered here is illustrated using several brands of commercially available heart rate sensors. Our hope is that by systematically quantifying measurement reliability, researchers will be able to make informed choices about specific wearable devices and measurement procedures that meet their research goals.
Cytoophidia maintain the integrity of Drosophila follicle epithelium
Authors: Wang Qiao-Qi , You Dong-Dong , Liu Ji-Long
Published: October 2022

CTP synthase (CTPS) forms a filamentous structure termed the cytoophidium in all three domains of life. The female reproductive system of Drosophila is an excellent model for studying the physiological function of cytoophidia. Here, we use CTPSH355A, a point mutation that destroys the cytoophidium-forming ability of CTPS, to explore the in vivo function of cytoophidia. In CTPSH355A egg chambers, we observe the ingression and increased heterogeneity of follicle cells. In addition, we find that the cytoophidium-forming ability of CTPS, rather than the protein level, is the cause of the defects observed in CTPSH355A mutants. To sum up, our data indicate that cytoophidia play an important role in maintaining the integrity of follicle epithelium.
Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in obesity
Authors: Hall Liam G , Czeczor Juliane K. , Connor Timothy , Botella Javier , De Jong Kirstie A. , Renton Mark C. , Genders Amanda J. , Venardos Kylie , Martin Sheree D. , Bond Simon T. , Aston-Mourney Kathryn , Howlett Kirsten F. , Campbell James A , Collier Greg R. , Walder Ken R. , McKenzie Matthew , Ziemann Mark , McGee Sean L.
Published: October 2022

There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. While some common aetiological mechanisms are known, the role of amyloid beta 42 (Aβ42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ42, which is increased from adipose tissue of obese mice and is associated with higher plasma Aβ42. Increasing circulating Aβ42levels in non-obese mice had no effect on systemic glucose homeostasis but had obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. These effects on cardiac function were not observed when circulating levels of the closely related Aβ40isoform were increased. Administration of an Aβ neutralising antibody prevented obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aβ neutralising antibody administration in established obesity prevented further deterioration of cardiac function. Multi-contrast transcriptomic analyses revealed that Aβ42impacted pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aβ42inhibited mitochondrial function. These data reveal a role for systemic Aβ42in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure.
Spatial cell fate manipulation of human pluripotent stem cells by controlling the microenvironment using photocurable hydrogel
Authors: Wang Zhe , Numada Akira , Wagai Fumi , Oda Yusuke , Ohgushi Masatoshi , Maki Koichiro , Adachi Taiji , Eiraku Mototsugu
Published: October 2022

Human pluripotent stem cells (hPSCs) dynamically respond to their chemical and physical microenvironment, dictating their behavior. However, conventional in vitro studies predominantly employ plastic culture wares, which offer a simplified representation of the in vivo microenvironment. Emerging evidence underscores the pivotal role of mechanical and topological cues in hPSC differentiation and maintenance. In this study, we cultured hPSCs on hydrogel substrates with spatially controlled stiffness.

The use of culture substrates that enable precise manipulation of spatial mechanical properties holds promise for better mimicking in vivo conditions and advancing tissue engineering techniques. We designed a photocurable polyethylene glycol–polyvinyl alcohol (PVA-PEG) hydrogel, allowing for spatial control of surface stiffness and geometry at a micrometer scale. This versatile hydrogel can be functionalized with various extracellular matrix (ECM) proteins. Laminin 511-functionalized PVA-PEG gel effectively supports the growth and differentiation of hPSCs.

Moreover, by spatially modulating the stiffness of the patterned gel, we achieved spatially selective cell differentiation, resulting in the generation of intricate, patterned structures.

Summary statement

A new hydrogel substrate enables spatial control of surface stiffness at the micrometer level, enabling local differentiation of hPSC and facilitating complex pattern formation.
Foot form and function: Variable and versatile, yet sufficiently related to predict one from the other
Authors: Schuster Robert W. , Cresswell Andrew , Kelly Luke A.
Published: October 2022

The modern human foot is a complex structure thought to play an important role in our ability to walk and run efficiently. Comparisons of our feet to those of our evolutionary ancestors and closest living relatives have linked the shape of several foot components (e.g., the longitudinal and transverse arches, size of the heel and length of the toes) to specific mechanical functions. But since foot shape varies widely across the modern human population, this study aimed to investigate how closely foot shape, deformation and joint mechanics during various locomotor tasks are actually linked. And whether the latter can be accurately predicted based entirely on the former two. A statistical shape-function model (SFM) was constructed by performing a principal component analysis on 100 participants’ three-dimensional foot scans, and joint angles and moments captured during level, uphill, and downhill walking and running. This SFM revealed that the main sources of variation were the longitudinal and transverse arches, relative foot proportions and toe shape along with their associated joint mechanics. However, each of these only accounted for a small proportion of the overall variation in foot shape, deformation and joint mechanics, most likely due to the high structural complexity and variability of the foot. Nevertheless, a leave-one-out analysis showed that the SFM can be used to accurately predict the joint angles and moments of a new foot based only on its shape. These results have implications and potential applicability across numerous fields, such as evolutionary anthropology, podiatry, orthopaedics and footwear design.
Home working and its association with social and mental wellbeing at different stages of the COVID-19 pandemic: Evidence from seven UK longitudinal population surveys
Authors: Wels Jacques , Wielgoszewska Bożena , Moltrecht Bettina , Booth Charlotte , Green Michael J , Hamilton Olivia KL , Demou Evangelia , Gessa Giorgio Di , Huggins Charlotte , Zhu Jingmin , Santorelli Gillian , Silverwood Richard J. , Kopasker Daniel , Shaw Richard J. , Hughes Alun , Patalay Praveetha , Steves Claire , Chaturvedi Nish , Porteous David , Rhead Rebecca , Katikireddi Srinivasa Vittal , Ploubidis George B.
Published: October 2022

Background

Home working rates have increased since the COVID-19 pandemic’s onset, but the health implications of this transformation are unclear. We assessed the association between home working and social and mental wellbeing through harmonised analyses of seven UK longitudinal studies.

Methods

We estimated associations between home working and measures of psychological distress, low life satisfaction, poor self-rated health, low social contact, and loneliness across three different stages of the COVID-19 pandemic (T1= Apr-Jun 2020 – first lockdown, T2=Jul-Oct 2020 – eased restrictions, T3=Nov 2020-Mar 2021 – second lockdown), in seven population-based cohort studies using modified Poisson regression and meta-analyses to pool results across studies.

Findings

Among 34,131 observations spread over three time points, we found higher rates of home working at T1 and T3 compared with T2, reflecting lockdown periods. Home working was not associated with psychological distress at T1 (RR=0.92, 95%CI=0.79-1.08) or T2 (RR=0.99, 95%CI=0.88-1.11), but a detrimental association was found with psychological distress at T3 (RR=1.17, 95%CI=1.05-1.30). Poorer psychological distress associated with home working was observed for those educated to below degree level at T2 and T3. Men working from home reported poorer self-reported health at T2.

Interpretation

No clear evidence of an association between home working and mental wellbeing was found, apart from greater risk of psychological distress associated with home working during the second lockdown, but differences across sub-groups may exist. Longer term shifts to home working might not have adverse impacts on population wellbeing in the absence of pandemic restrictions but further monitoring of health inequalities is required.

Funding

National Core Studies, funded by UKRI, NIHR and the Health and Safety Executive.
Clinical profiling of specific diagnostic subgroups of women with chronic pelvic pain
Authors: Demetriou Lysia , Krassowski Michal , Mendes Pedro Abreu , Garbutt Kurtis , Vitonis Allison F. , Wilkins Elizabeth , Coxon Lydia , Arendt-Nielsen Lars , Aziz Qasim , Birch Judy , Horne Andrew W , Hoffman Anja , Hummelshoj Lone , Lunde Claire E , Meijlink Jane , Perro Danielle , Rahmioglu Nilufer , Terry Kathryn L. , Pogatzki-Zahn Esther , Sieberg Christine B , Treede Rolf-Detlef , Becker Christian M , Cruz Francisco , Missmer Stacey A , Zondervan Krina T , Nagel Jens , Vincent Katy
Published: October 2022

Chronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis. We aim to explore whether specific subgroups of women with CPP report different clinical symptoms and differing impact of pain on their quality of life (QoL).

The study is part of the Translational Research in Pelvic Pain (TRiPP) project which is a cross-sectional observational cohort study. The study includes 769 female participants of reproductive age who completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this population we defined a control group (reporting no pelvic pain, no bladder pain syndrome, and no endometriosis diagnosis, N=230) and four pain groups: endometriosis-associated pain (EAP, N=237), interstitial cystitis/bladder pain syndrome (BPS, N=72), comorbid endometriosis-associated pain and BPS (EABP, N=120), and pelvic pain only (PP, N=127).

Clinical profiles of women with CPP (13-50 years old) show variability of clinical symptoms. The EAP and EABP groups scored higher than the PP group (p<0.001) on the pain intensity scales for non-cyclical pelvic pain and higher than both the BPS and PP groups (p<0.001) on the dysmenorrhoea scale. The EABP group also had significantly higher scores for dyspareunia (p<0.001), even though more than 50% of sexually active participants in each pain group reported interrupting and/or avoiding sexual intercourse due to pain in the last 12 months.

Scores for the QoL questionnaire (SF-36) reveal that CPP patients had significantly lower QoL across all SF-36 subscales (p<0.001). Significant effects were also observed between the pain groups for pain interference with their work (p<0.001) and daily lives (p<0.001), with the EABP suffering more compared to the EAP and PP groups (p<0.001).

Our results demonstrate the negative impact that chronic pain has on CPP patients’ QoL and reveal an increased negative impact of pain on the comorbid EABP group. Furthermore, it demonstrates the importance of dyspareunia in women with CPP. Overall, our results demonstrate the need for further exploration of interventions targeting QoL more broadly and suggest that novel approaches to classifying women with CPP are needed.
A Nursing Philosophy of Women Empowerment Based on Self Efficacy toward Sexual and Reproductive Health
Authors: Pradanie Retnayu , Pandin Moses Glorino Rumambo , Yunitasari Esti
Published: October 2022

Introduction

Sexual and reproductive health of women will affect their health in general at every stage of their lives. Empowerment of women is a strategic step to improving health status. Nurses have an essential role to empower women to improve their health. Women empowerment can be built by improving their self-efficacy. This paper aimed to provide a review of articles about the role of nurses and strategies to empower women in sexual and reproductive health based on self-efficacy.

Method

This paper is the result of a literature review. Data were accessed from the database of Scopus, Pubmed, and Ebscohost limited on publication in 2017-2022. Twelve journal articles were selected using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Results

The results of the article review obtained information about the important role of women in the health sector, factors associated with sexual and reproductive health, nursing philosophy women health, women empowerment models for sexual and reproductive health, and strategies to increase women empowerment through self-efficacy enhancement.

Conclusion

An evidence-based practice approach found that women empowerment is a strategic step for health development. The women empowerment program still needs to be developed because it can increase their capacity in maintaining health.
Using deep convolutional neural networks to predict patients age based on ECGs from an independent test cohort
Authors: Singstad Bjørn-Jostein , Tavashi Belal
Published: October 2022

Electrocardiography is one of the most frequently used methods to evaluate cardiovascular diseases. However, the last decade has shown that deep convolutional neural networks (CNN) can extract information from the electrocardiogram (ECG) that goes beyond traditional diagnostics, such as predicting a persons age. In this study, we trained two different 1-dimensional CNNs on open datasets to predict age from a persons ECG.

The models were trained and validated using 10 seconds long 12-lead ECG records, resampled to 100Hz. 59355 ECGs were used for training and cross-validation, while 21748 ECGs from a separate cohort were used as the test set. We compared the performance achieved on the cross-validation with the performance on the test set. Furthermore, we used cardiologist annotated cardiovascular conditions to categorize the patients in the test set in order to assess whether some cardiac condition leads to greater discrepancies between CNN-predicted age and chronological age.

The best CNN model, using an Inception Time architecture, showed a significant drop in performance, in terms of mean absolute error (MAE), from cross-validation on the training set (7.90 ± 0.04 years) to the performance on the test set (8.3 years). On the other hand, the mean squared error (MSE) improved from the training set (117.5 ± 2.7 years2) to the test set (111 years2). We also observed that the cardiovascular condition that showed the highest deviation between predicted and biological age, in terms of MAE, was the patients with pacing rhythm (10.5 years), while the patients with prolonged QT-interval had the smallest deviation (7.4 years) in terms of MAE.

This work contributes to existing knowledge of age prediction using deep CNNs on ECGs by showing how a trained model performs on a test set from a separate cohort to that used in the training set.
Impact of vaccination on COVID-19-associated admissions to critical care in England: a population cohort study of linked data
Authors: Harrison David A , Watkinson Peter J , Doidge James C , Shankar-Hari Manu , Mouncey Paul R , Patone Martina , Coupland Carol A C , Hippisley-Cox Julia , Rowan Kathryn M
Published: October 2022

Introduction

This study aims to explore the impact of COVID-19 vaccination on critical care by examining associations between vaccination and admission to critical care with COVID-19 during England’s Delta wave, by age group, dose, and over time.

Methods

We used linked routinely-collected data to conduct a population cohort study of patients admitted to adult critical care in England for management of COVID-19 between 1 May and 15 December 2021. Included participants were the whole population of England aged 18 years or over (44.7 million), including 10,141 patients admitted to critical care with COVID-19. The intervention was vaccination with one, two, or a booster/three doses of any COVID-19 vaccine.

Results

Compared with unvaccinated patients, vaccinated patients were older (median 64 years for patients receiving two or more doses versus 50 years for unvaccinated), with higher levels of severe comorbidity (20.3% versus 3.9%) and immunocompromise (15.0% versus 2.3%). Compared with patients who were unvaccinated, those vaccinated with two doses had a relative risk reduction (RRR) of between 90.1% (patients aged 18–29, 95% CI, 86.8% to 92.7%) and 95.9% (patients aged 60–69, 95% CI, 95.5% to 96.2%). Waning was only observed for those aged 70+, for whom the RRR reduced from 97.3% (91.0% to 99.2%) to 86.7% (85.3% to 90.1%) between May and December but increased again to 98.3% (97.6% to 98.8%) with a booster/third dose.

Conclusion

Important demographic and clinical differences exist between vaccinated and unvaccinated patients admitted to critical care with COVID-19. While not a causal analysis, our findings are consistent with a substantial and sustained impact of vaccination on reducing admissions to critical care during England’s Delta wave, with evidence of waning predominantly restricted to those aged 70+.
Site-Specific Knockdown of Microglia in the Locus Coeruleus Regulates Hypervigilant Responses to Social Stress in Female Rats
Authors: Pate Brittany S. , Bouknight Samantha J. , Harrington Evelynn N. , Mott Sarah E. , Augenblick Lee M. , Smiley Cora E. , Morgan Christopher G. , Calatayud Brittney M. , Martinez-Muniz Gustavo A. , Thayer Julian F. , Wood Susan K.
Published: October 2022

Background

Women are at increased risk for psychosocial stress-related anxiety disorders, yet mechanisms regulating this risk are unknown. Psychosocial stressors activate microglia, and the resulting neuroimmune responses that females exhibit heightened sensitivity to may serve as an etiological factor in their elevated risk. However, studies examining the role of microglia during stress in females are lacking.

Methods

Microglia were manipulated in the stress-sensitive locus coeruleus (LC) of female rats in the context of social stress in two ways. First, intra-LC lipopolysaccharide (LPS; 0 or 3μg/side, n=5-6/group), a potent TLR4 agonist and microglial activator, was administered. One hour later, rats were exposed to control or an aggressive social defeat encounter between two males (WS, 15-min). In a separate study, females were treated with intra-LC or intra-central amygdala mannosylated liposomes containing clodronate (m-CLD; 0 or 25μg/side, n=13-14/group), a compound toxic to microglia. WS-evoked burying, cardiovascular responses, and sucrose preference were measured. Brain and plasma cytokines were quantified, and cardiovascular telemetry assessed autonomic balance.

Results

Intra-LC LPS augmented the WS-induced burying response and increased plasma corticosterone and interleukin-1β (IL-1β). Further, the efficacy and selectivity of microinjected m-CLD was determined. In the context of WS, intra-LC m-CLD attenuated the hypervigilant burying response during WS as well as the accumulation of intra-LC IL-1β. Intra-central amygdala m-CLD had no effect on witness stress-evoked behavior.

Conclusions

These studies highlight an innovative method for depleting microglia in a brain region specific manner and indicate that microglia in the LC differentially regulate hypervigilant WS-evoked behavioral and autonomic responses.

HIGHLIGHTS

Intra-LC LPS augments behavioral and physiological responses to social stress

Mannosylated liposomal clodronate site-specifically reduces microglial expression

Microglia within the locus coeruleus regulate stress-evoked behavior in female rats
Leaf hydraulic maze; Differential effect of ABA on bundle-sheath, palisade, and spongy mesophyll hydraulic conductance
Authors: Yaaran Adi , Erez Eyal , Procko Carl , Moshelion Menachem
Published: October 2022

Leaf hydraulic conductance (Kleaf) facilitates the movement of water for transpiration, enabling continual CO2uptake while the plant maintains its water status. We hypothesized that bundle-sheath and mesophyll cells play key roles in regulating the radial flow of water out of the xylem under optimal and stress conditions. To examine that hypothesis, we generated transgenicArabidopsisplants that were insensitive to abscisic acid (ABA) in their bundle sheath (BSabi) or mesophyll (MCabi) cells. Both BSabi and MCabi plants showed greater Kleafand transpiration under optimal conditions. Yet, the stomatal apertures, stomatal indices and vein densities of the BSabi plants were similar to those of WT plants. MCabi plants had larger stomatal apertures, a higher stomatal index and greater vascular diameter and biomass, relative to the WT and BSabi. In response to xylem-fed ABA, both transgenic and WT plants reduced their Kleafand transpiration. However, leaf water potential was reduced only in the WT. The membrane osmotic water permeability (Pf) of the WTs’ spongy mesophyll was higher than that of its palisade mesophyll. Moreover, only the spongy cells reduced theirPfin response to ABA. ABA-insensitive spongy mesophyll cells had a lowPf; whereas ABA-insensitive bundle-sheath cells had a higherPf.Palisade cells maintained a lowPfat all ABA levels. ABA increased the symplastic water pathway, but its contribution to Kleafwas negligible. We suggest that the bundle sheath–spongy mesophyll pathway may control Kleafto maintain steady-state conditions in the palisade cells and optimal whole-leaf water-use efficiency.
Tregcells drive MYCN-mediated immunosuppression and tumor aggressiveness in high-risk neuroblastoma
Authors: Qin Xiaodan , Lam Andrew , Zhang Xu , Sengupta Satyaki , Iorgulescu J. Bryan , Zuo Tao , Floru Alexander E. , Meara Grace , Lin Liang , Lloyd Kenneth , Kwok Lauren , Smith Kaylee , Nagaraju Raghavendar T. , Meijers Rob , Ceol Craig , Liu Ching-Ti , Alexandrescu Sanda , Wu Catherine J. , Keskin Derin B. , George Rani E. , Feng Hui
Published: October 2022

Solid tumors, especially those with aberrant MYCN activation, harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance1,2, yet the underlying mechanisms are elusive and effective strategies to tackle this challenge are lacking. Here we demonstrated the crucial role of T regulatory (Treg) cells in MYCN-mediated immune repression and tumor aggression using high-risk neuroblastoma (NB) as a model system. Human MYCN-activated NB attracts CD4+Tregcells, which are also found enriched in MYCN-high primary patient samples. ZebrafishMYCN-overexpressing neural crests recruit Cd4+cells before tumor formation and induce an immunosuppressive microenvironment, thereby promoting tumor onset and progression. Strikingly, disruption of Tregcells through depletion of forkhead box protein 3a restores anti-tumor immunity and impairs NB development. Together, our studies establish Tregcells as the key driver of MYCN-mediated immunosuppression and tumor aggressiveness, providing mechanistic insights and therapeutic implications.