bluuebunny/crossref_metadata_2025 huggingface dataset:
Protracted neuronal maturation in a long-lived, highly social rodent
Authors: Faykoo-Martinez Mariela , Collins Troy , Peragine Diana , Malik Manahil , Javed Fiza , Kolisnyk Matthew , Ziolkowski Justine , Jeewa Imaan , Cheng Arthur H. , Lowden Christopher , Mascarenhas Brittany , Cheng Hai-Ying Mary , Holmes Melissa M.
Published: September 2022

Naked mole-rats are a long-lived rodent species (current lifespan >37 years) and an increasingly popular biomedical model. Naked mole-rats exhibit neuroplasticity across their long lifespan. Previous studies have begun to investigate their neurogenic patterns. Here, we test the hypothesis that neuronal maturation is extended in this long-lived rodent. We characterize cell proliferation and neuronal maturation in established rodent neurogenic regions over 12 months following seven days of consecutive BrdU injection. Given that naked mole-rats are eusocial (high reproductive skew where only a few socially-dominant individuals reproduce), we also looked at proliferation in brain regions relevant to the social-decision making network. Finally, we measured co-expression of EdU (newly-born cells), DCX (immature neuron marker), and NeuN (mature neuron marker) to assess the timeline of neuronal maturation in adult naked mole-rats. This work reaffirms the subventricular zone as the main source of adult cell proliferation and suggests conservation of the rostral migratory stream in this species. Our profiling of socially-relevant brain regions suggests that future work which manipulates environmental context can unveil how newly-born cells integrate into circuitry and facilitate adult neuroplasticity. We also find naked mole-rat neuronal maturation sits at the intersection of rodents and long-lived, non-rodent species: while neurons can mature by 3 weeks (rodent-like), most neurons mature at 5 months and hippocampal neurogenic levels are low (like long-lived species). These data establish a timeline for future investigations of longevity- and socially-related manipulations of naked mole-rat adult neurogenesis.
Highly multiplexed selection of RNA aptamers against a small molecule library
Authors: Townshend Brent , Kaplan Matias , Smolke Christina D.
Published: September 2022

Applications of synthetic biology spanning human health, industrial bioproduction, and ecosystem monitoring often require small molecule sensing capabilities, typically in the form of genetically encoded small molecule biosensors. Critical to the deployment of greater numbers of these systems are methods that support the rapid development of such biosensors against a broad range of small molecule targets. Here, we use a previously developed method for selection of RNA biosensors against unmodified small molecules (DRIVER) to perform a selection against a densely multiplexed mixture of small molecules, representative of those employed in high-throughput drug screening. Using a mixture of 5,120 target compounds randomly sampled from a large diversity drug screening library, we performed a 95-round selection and then analyzed the enriched RNA biosensor library using next generation sequencing (NGS). From our analysis, we identified RNA biosensors with at least 2-fold change in signal in the presence of at least 217 distinct target compounds with sensitivities down to 25 nM. Although many of these biosensors respond to multiple targets, clustering analysis indicated at least 150 different small-molecule sensing patterns. We also built a classifier that was able to predict whether the biosensors would respond to a new compound with an average precision of 0.82. Since the target compound library was designed to be representative of larger diversity compound libraries, we expect that the described approach can be used with similar compound libraries to identify aptamers against other small molecules with a similar success rate. The new RNA biosensors (or their component aptamers) described in this work can be further optimized and used in applications such as biosensing, gene control, or enzyme evolution. In addition, the data presented here provide an expanded compendium of new RNA aptamers compared to the 82 small molecule RNA aptamers published in the literature, allowing further bioinformatic analyses of the general classes of small molecules for which RNA aptamers can be found.
Learning and memory function in young people with and without perinatal HIV in England
Authors: Arenas-Pinto Alejandro , Judd Ali , Melvin Diane , Le Prevost Marthe , Foster Caroline , Sturgeon Kate , Winston Alan , Thompson Lindsay C. , Gibb Diana M. , Castro Hannah ,   on behalf of the Adolescents and Adults Living with Perinatal HIV (AALPHI) Steering Committee
Published: September 2022

Learning and memory are important for successful education and career progression. We assess these functions in young people (YP) with perinatal HIV (PHIV) (with or without a previous AIDS-defining illness) and a comparable group of HIV-negative YP. 234 PHIV and 68 HIV-negative YP completed 9 tests; 5 National Institutes of Health (NIH) Toolbox tests (2 executive function, 1 speed of information processing, 2 memory); 2 Hopkins Verbal Learning Test Revised (HVLT-R) (learning (L), delayed recall (R)), and 2 verbal application measures. Z-scores for each test were calculated using normative data and averaged by domain where appropriate. The effect of predictors on test scores in the three domains with the lowest z-scores were analysed using linear regression. 139(59%) and 48(71%) PHIV and HIV-negative YP were female, 202(86%) and 52(76%) Black, and median age was 19 [17, 21] and 18 [16, 21] years respectively. 55(24%) PHIV had a previous Center for Disease Control and Prevention (CDC) class C AIDS-defining diagnosis (PHIV/C). For HVLT-R, there was a trend towards PHIV/C YP having the lowest mean z-scores (L -1.5 (95% CI -1.8,-1.2), R -1.7 (-2.0,-1.4)) followed by PHIV without a CDC C diagnosis (L -1.3 (-1.4,-1.1), R -1.4 (-1.5,-1.2)) and then the HIV-negative group (L -1.0 (-1.3,-0.7), R -1.1 (-1.3,-0.8)); all were greater than 1 SD below the reference mean. The same trend was seen for verbal application measures; however, z-scores were within 1 SD below the reference mean. NIH Toolbox tests were similar for all groups. In multivariable analyses PHIV/C and Black ethnicity predicted lower HVLT-R scores. Black ethnicity also predicted lower executive function scores, however each year increase in age predicted higher scores. In conclusion, cognitive performance in verbal learning and recall fell below population normative scores, and was more pronounced in PHIV/C, supporting wider findings that earlier antiretroviral therapy initiation, before the occurrence of AIDS-defining conditions, may protect aspects of cognitive development.
Nuclei segmentation of HE stained histopathological images based on feature global delivery connection network
Authors: Shi Peng , Zhong Jing , Lin Liyan , Lin Lin , Li Huachang , Wu Chongshu
Published: September 2022

The analysis of pathological images, such as cell counting and nuclear morphological measurement, is an essential part in clinical histopathology researches. Due to the diversity of uncertain cell boundaries after staining, automated nuclei segmentation of Hematoxylin-Eosin (HE) stained pathological images remains challenging. Although better performances could be achieved than most of classic image processing methods do, manual labeling is still necessary in a majority of current machine learning based segmentation strategies, which restricts further improvements of efficiency and accuracy. Aiming at the requirements of stable and efficient high-throughput pathological image analysis, an automated Feature Global Delivery Connection Network (FGDC-net) is proposed for nuclei segmentation of HE stained images. Firstly, training sample patches and their corresponding asymmetric labels are automatically generated based on a Full Mixup strategy from RGB to HSV color space. Secondly, in order to add connections between adjacent layers and achieve the purpose of feature selection, FGDC module is designed by removing the jumping connections between codecs commonly used in UNet-based image segmentation networks, which learns the relationships between channels in each layer and pass information selectively. Finally, a dynamic training strategy based on mixed loss is used to increase the generalization capability of the model by flexible epochs. The proposed improvements were verified by the ablation experiments on multiple open databases and own clinical meningioma dataset. Experimental results on multiple datasets showed that FGDC-net could effectively improve the segmentation performances of HE stained pathological images without manual interventions, and provide valuable references for clinical pathological analysis.
Pan-cancer analysis of co-occurring mutations in RAD52 and the BRCA1-BRCA2-PALB2 axis in human cancers
Authors: Hamid Abdulaziz B. , Frank Lauren E. , Bouley Renee A. , Petreaca Ruben C.
Published: September 2022

In human cells homologous recombination (HR) is critical for repair of DNA double strand breaks (DSBs) and rescue of stalled or collapsed replication forks. HR is facilitated by RAD51 which is loaded onto DNA by either BRCA2-BRCA1-PALB2 or RAD52. In human culture cells, double-knockdowns of RAD52 and genes in the BRCA1-BRCA2-PALB2 axis are lethal. Mutations in BRCA2, BRCA1 or PALB2 significantly impairs error free HR as RAD51 loading relies on RAD52 which is not as proficient as BRCA2-BRCA1-PALB2. RAD52 also facilitates Single Strand Annealing (SSA) that produces intra-chromosomal deletions. Some RAD52 mutations that affect the SSA function or decrease RAD52 association with DNA can suppress certain BRCA2 associated phenotypes in breast cancers. In this report we did a pan-cancer analysis using data reported on the Catalogue of Somatic Mutations in Cancers (COSMIC) to identify double mutants between RAD52 and BRCA1, BRCA2 or PALB2 that occur in cancer cells. We find that co-occurring mutations are likely in certain cancer tissues but not others. However, all mutations occur in a heterozygous state. Further, using computational and machine learning tools we identified only a handful of pathogenic or driver mutations predicted to significantly affect the function of the proteins. This supports previous findings that co-inactivation of RAD52 with any members of the BRCA2-BRCA1-PALB2 axis is lethal. Molecular modeling also revealed that pathogenic RAD52 mutations co-occurring with mutations in BRCA2-BRCA1-PALB2 axis are either expected to attenuate its SSA function or its interaction with DNA. This study extends previous breast cancer findings to other cancer types and shows that co-occurring mutations likely destabilize HR by similar mechanisms as in breast cancers.
Collagen pre-strain discontinuity at the bone—Cartilage interface
Authors: Badar Waqas , Ali Husna , Brooker Olivia N. , Newham Elis , Snow Tim , Terrill Nicholas J. , Tozzi Gianluca , Fratzl Peter , Knight Martin M. , Gupta Himadri S.
Published: September 2022

The bone-cartilage unit (BCU) is a universal feature in diarthrodial joints, which is mechanically-graded and subjected to shear and compressive strains. Changes in the BCU have been linked to osteoarthritis (OA) progression. Here we report existence of a physiological internal strain gradient (pre-strain) across the BCU at the ultrastructural scale of the extracellular matrix (ECM) constituents, specifically the collagen fibril. We use X-ray scattering that probes changes in the axial periodicity of fibril-level D-stagger of tropocollagen molecules in the matrix fibrils, as a measure of microscopic pre-strain. We find that mineralized collagen nanofibrils in the calcified plate are in tensile pre-strain relative to the underlying trabecular bone. This behaviour contrasts with the previously accepted notion that fibrillar pre-strain (or D-stagger) in collagenous tissues always reduces with mineralization, via reduced hydration and associated swelling pressure. Within the calcified part of the BCU, a finer-scale gradient in pre-strain (0.6% increase over ~50μm) is observed. The increased fibrillar pre-strain is linked to prior research reporting large tissue-level residual strains under compression. The findings may have biomechanical adaptative significance: higher in-built molecular level resilience/damage resistance to physiological compression, and disruption of the molecular-level pre-strains during remodelling of the bone-cartilage interface may be potential factors in osteoarthritis-based degeneration.
Case fatality rate and its determinants among admitted stroke patients in public referral hospitals, Northwest, Ethiopia: A prospective cohort study
Authors: Ayehu Gashaw Walle , Yitbarek Getachew Yideg , Jemere Tadeg , Chanie Ermias Sisay , Feleke Dejen Getaneh , Abebaw Sofonias , Zewde Edgeit , Atlaw Daniel , Agegnehu Assefa , Mamo Ayele , Degno Sisay , Azanaw Melkalem Mamuye
Published: September 2022

According to the global burden of disease 5.5 million deaths were attributable to stroke. The stroke mortality rate is estimated to be seven times higher in low-income countries compared to high-income countries. The main aim of the study was to assess the 28 days case fatality rate and its determinants among admitted stroke patients in public referral hospitals, in Northwest Ethiopia. A hospital-based prospective cohort study was conducted from December 2020 to June 2021. The study population was 554 stroke patients. Based on Akakian Information Criteria, the Gompertz model was fitted to predict the hazard of death. The study included admitted stroke patients who were treated in the general medical ward and neurology ward. The mean age of the participants was 61 ± 12.85 years and 53.25% of the patients were female. The 28-days case fatality rate of stroke was 27.08%. The results from Gompertz parametric baseline hazard distribution revealed that female sex adjusted hazard rate (AHR = 0.27, 95% CI:0.18–0.42), absence of a family history of chronic disease (AHR = 0.50, 95%CI:0.29–0.87), good GCS score (AHR = 0.21, 95% CI:0.09–0.50) and the absence of complication during hospital admission (AHR = 0.16, 95% CI:0.08–0.29) were factors which decrease hazard of 28 days case fatality rate. While, hemorrhagic stroke sub-type (AHR = 1.38, 95% CI:1.04–3.19), time from symptom onset to hospital arrival (AHR = 1.49, 95% CI:1.57–2 .71), time from confirmation of the diagnosis to initiation of treatment (AHR = 1.03, 95% CI:1.01–1.04), a respiratory rate greater than 20 (AHR = 7.21, 95% CI:3.48–14.9), and increase in NIHSS score (AHR = 1.16, 95% CI:1.10–1.23) were factors increasing hazard of 28 days case fatality rate of stroke. At 28-days follow-up, more than one-fourth of the patients have died. The establishment of separate stroke centers and a network of local and regional stroke centers with expertise in early stroke evaluation and management may address challenges.
Improved runoff forecasting based on time-varying model averaging method and deep learning
Authors: Ran Jinlou , Cui Yang , Xiang Kai , Song Yuchen
Published: September 2022

In order to improve the accuracy and stability of runoff prediction. This study proposed a dynamic model averaging method with Time-varying weight (TV-DMA). Using this method, an integrated prediction model framework for runoff prediction was constructed. The framework determines the main variables suitable for runoff prediction through correlation analysis, and uses TV-DMA and deep learning algorithm to construct an integrated prediction model for runoff. The results demonstrate that the current monthly runoff, the runoff of the previous month, the current monthly temperature, the temperature of the previous month and the current monthly rainfall were the variables suitable for runoff prediction. The results of runoff prediction show that the TV-DMA model has the highest prediction accuracy (with 0.97 Nash-efficiency coefficient (NSE)) and low uncertainty. The interval band of uncertainty was 33.3%-65.5% lower than single model. And the prediction performance of the single model and TV-DMA model in flood season is obviously lower than that in non-flood season. In addition, this study indicate that the current monthly runoff, rainfall and temperature are the important factor affecting the runoff prediction, which should be paid special attention in the runoff prediction.
Photobiomodulation, as additional treatment to traditional dressing of hard-to-heal venous leg ulcers, in frail elderly with municipality home healthcare
Authors: Degerman Marianne , Öhman Micael , Bertilson Bo C.
Published: September 2022

The main objectives of the study were to explore whether laser Photobiomodulation (PBM) in addition to traditional dressing of hard-to-heal venous leg ulcer, reduced healing time of the ulcer and if the duration of the ulcer before PBM impacted the treatment time with PBM to healing. The intervention group was frail, elderly patients with home healthcare in the municipality of Skellefteå, registered in the Swedish quality registry RiksSar for ulcer treatment with hard-to-heal venous leg ulcer. The control group with equivalent physical conditions was obtained from the same quality registry. Definition of hard-to-heal ulcer was six weeks duration or more. The PBM was performed two times per week with laser type infrared GaAs, 904nm, 60mW, and 700Hz, targeting lymphatic area and ulcer area. Laser type red visible, GaAllnp, 635nm, 75mW and 250Hz, targeting ulcer area. The intervention group treated with PBM in addition to traditional dressing healed significantly faster than the control group with a mean of 123 days (p = 0.0001). Duration of the ulcer before PBM did not impact the healing time. To conclude, the findings indicate that using PBM in addition to dressing may have multiple benefits on hard-to-heal venous leg ulcer, saving valuable time and resources for patients, healthcare providers, and institutions.
In vitro sepsis induces Nociceptin/Orphanin FQ receptor (NOP) expression in primary human vascular endothelial but not smooth muscle cells
Authors: Bird Mark F. , Gallacher-Horley Barbara , McDonald John , McVey David G. , Al-Janabi Fatin , Guerrini Remo , Calo Girolamo , Ye Shu , Thompson Jonathan P. , Lambert David G.
Published: September 2022

Sepsis is a dysregulated host response to infection that can cause widespread effects on other organs including cardiovascular depression, hypotension and organ failure. The receptor for Nociceptin/Orphanin FQ (N/OFQ), NOP is expressed on immune cells and these cells can release the peptide. Exogenous N/OFQ can dilate blood vessels and this peptide is increased in animal and human sepsis. We hypothesise that NOP receptors are present on vascular endothelial cells and therefore provide the target for released N/OFQ to cause vasodilation and hence hypotension. Using human umbilical vein endothelial cells (HUVEC) and human vascular smooth muscle cells (HVSMC) freshly prepared from umbilical cords and up to passage 4, we assessed NOP mRNA expression by Polymerase Chain Reaction (PCR), NOP surface receptor expression using a fluorescent NOP selective probe (N/OFQATTO594) and NOP receptor function with N/OFQ stimulated ERK1/2 phosphorylation. As an in vitro sepsis mimic we variably incubated cells with 100ng/ml Lipopolysaccharide and Peptidoglycan G (LPS/PepG). HUVECs express NOP mRNA and this was reduced by ~80% (n = 49) after 24–48 hours treatment with LPS/PepG. Untreated cells do not express surface NOP receptors but when treated with LPS/PepG the reduced mRNA was translated into protein visualised by N/OFQATTO594 binding (n = 49). These NOP receptors in treated cells produced an N/OFQ (1μM) driven increase in ERK1/2 phosphorylation (n = 20). One (of 50) HUVEC lines expressed NOP mRNA and receptor protein in the absence of LPS/PepG treatment. In contrast, HVSMC expressed NOP mRNA and surface receptor protein (n = 10) independently of LPS/PepG treatment. These receptors were also coupled to ERK1/2 where N/OFQ (1μM) increased phosphorylation. Collectively these data show that an in vitro sepsis mimic (LPS/PepG) upregulates functional NOP expression in the vascular endothelium. Activation of these endothelial receptors as suggested from in vivo whole animal work may contribute to the hypotensive response seen in sepsis. Moreover, blockade of these receptors might be a useful adjunct in the treatment of sepsis.
Health hazards related to using masks and/or personal protective equipment among physicians working in public hospitals in Dhaka: A cross-sectional study
Authors: Mahmud Reaz , Joy K. M. Nazmul Islam , Rassel Mohammad Aftab , Monayem Farhana Binte , Datta Ponkaj Kanti , Hossain Mohammad Sharif , Hoque Mohammad Mahfuzul , Habib S. M. Habibur Rahman , Munna Nazmul Hoque , Ahmed Mohiuddin , Sayeed S. K. Jakaria Been , Rahman Motlabur , Chowdhury Ahmed Hossain , Hossain Mohammad Zaid , Ahmed Kazi Gias Uddin , Miah Md. Titu , Rahman Md. Mujibur
Published: September 2022

Background

Wearing masks or personal protective equipment (PPE) has become an integral part of the occupational life of physicians due to the coronavirus disease 2019 (COVID-19) pandemic. Most physicians have been developing various health hazards related to the use of different protective gears. This study aimed to determine the burden and spectrum of various health hazards associated with using masks or PPE and their associated risk factors.

Methods

This cross-sectional survey was conducted in Dhaka Medical College from March 01–May 30, 2021, among physicians from different public hospitals in Dhaka, Bangladesh. We analyzed the responses of 506 physicians who completed case record forms through Google forms or hard copies.

Findings

The mean (SD) age of the respondents was 35.4 [7.7], and 69.4% were men. Approximately 40% were using full PPE, and 55% were using N-95 masks. A total of 489 (96.6%) patients experienced at least one health hazard. The reported severe health hazards were syncope, severe dyspnea, severe chest pain, and anaphylaxis. Headache, dizziness, mood irritation, chest pain, excessive sweating, panic attack, and permanent facial disfigurement were the minor health hazards reported. Extended periods of work in the COVID-19-unit, reuse of masks, diabetes, obesity, and mental stress were risk factors for dyspnea. The risk factors for headaches were female sex, diabetes, and previous primary headaches. Furthermore, female sex and reusing masks for an extended period (> 6 h) were risk factors for facial disfigurement. The risk factors for excessive sweating were female sex and additional evening office practice for an extended period.

Conclusions

Healthcare workers experienced several occupational hazards after using masks and PPE. Therefore, an appropriate policy is required to reduce such risks.
Cyclical depressurization degranulates platelets in an agonist-free mechanism of platelet activation
Authors: Velasquez-Mao Aaron J. , Velasquez Mark , Vandsburger Moriel H.
Published: September 2022

Activation of circulating platelets by receptor binding and subsequent coagulation events are defined by a well characterized physiological response. However, the growing prevalence of chronic kidney disease (CKD) and implication of platelet-released factors in worsening cardiovascular outcomes with hemodialysis warrant further investigation into the mechanobiology of platelet degranulation. The significant drops in pressure caused by high friction across the hemodialysis flow circuit present an overlooked platelet stimulant not involving immobilization as a driver for cytoskeletal rearrangement. In this study, platelets from healthy and dialysis (pre- and post-treatment) donors were cyclically depressurized in static suspension to measure changes in physiology by integrin αIIbβ3activation and surface P-selectin expression. The progressive increase in CD62P with no changes in PAC1 over pressure-cycling duration regardless of uremia signifies that hydrostatic depressurization involves a novel agonist-free mechanism leading to platelet degranulation as a unique case in which CD62P and PAC1 do not interchangeably indicate platelet activation. Subsequent stimulation using ADP further suggests that sustained depressurization regimens desensitize integrin αIIbβ3activation. Variability in platelet response caused by uremia and CKD are observed by elevated baseline PAC1 in pre-dialysis samples, PAC1 retention after ADP exposure, and maximum CD62P with ADP independent of pressure. Theory for hydrostatic pressure-induced degranulation circumventing integrin-initiated signal transduction is here presented based on the Starling Equation.
Psychosocial working conditions and chronic low-grade inflammation in geriatric care professionals: A cross-sectional study
Authors: Kaltenegger Helena C. , Weigl Matthias , Becker Linda , Rohleder Nicolas , Nowak Dennis , Quartucci Caroline
Published: September 2022

Background

Chronic low-grade inflammation has been suggested as a key factor in the association between stress exposure and long-term health. Care work is recognized as a profession with a high degree of job stress and health risks. However, for care professionals, the study base on inflammatory activity due to adverse working conditions is limited.

Objective

The aim of this study was to explore associations between self-reported psychosocial working conditions and care professionals’ biomarkers of systemic low-grade inflammation.

Methods

N= 140 geriatric care professionals (79.3% females, mean age = 44.1 years) of six care facilities were enrolled in a cross-sectional study consisting of standardized medical examinations and employee surveys. Standardized questionnaires were used for evaluation of psychosocial work characteristics (work overload, job autonomy, social support) based on Karasek’s job strain model. Blood samples were drawn for two biomarkers of inflammatory activity: C-reactive protein (CRP) and leukocyte count. Analyses comprised uni- and multivariate logistic and linear regression analyses.

Results

We determined a proportion of 5.4% of care professionals with increased low-grade inflammation. We further observed a relationship between job autonomy and CRP, such that reports of high job autonomy were associated with increased levels of CRP (adjusted OR = 4.10, 95% CI [1.10, 15.26],p= .035), which was robust in additional analyses on further potential confounders. No significant associations with participants’ leukocyte numbers were found.

Conclusions

This exploratory study contributes to the research base on links between workplace stress and ensuing illness in care professionals. Our findings may help to identify risk and protective factors of the work environment for chronic low-grade inflammation. The results require further scrutiny, and future prospective studies on associations of psychosocial working conditions, low-grade inflammation and long-term health outcomes in care professionals are needed.
Denoising diffusion weighted imaging data using convolutional neural networks
Authors: Cheng Hu , Vinci-Booher Sophia , Wang Jian , Caron Bradley , Wen Qiuting , Newman Sharlene , Pestilli Franco
Published: September 2022

Diffusion weighted imaging (DWI) with multiple, high b-values is critical for extracting tissue microstructure measurements; however, high b-value DWI images contain high noise levels that can overwhelm the signal of interest and bias microstructural measurements. Here, we propose a simple denoising method that can be applied to any dataset, provided a low-noise, single-subject dataset is acquired using the same DWI sequence. The denoising method uses a one-dimensional convolutional neural network (1D-CNN) and deep learning to learn from a low-noise dataset, voxel-by-voxel. The trained model can then be applied to high-noise datasets from other subjects. We validated the 1D-CNN denoising method by first demonstrating that 1D-CNN denoising resulted in DWI images that were more similar to the noise-free ground truth than comparable denoising methods, e.g., MP-PCA, using simulated DWI data. Using the same DWI acquisition but reconstructed with two common reconstruction methods, i.e. SENSE1 and sum-of-square, to generate a pair of low-noise and high-noise datasets, we then demonstrated that 1D-CNN denoising of high-noise DWI data collected from human subjects showed promising results in three domains: DWI images, diffusion metrics, and tractography. In particular, the denoised images were very similar to a low-noise reference image of that subject, more than the similarity between repeated low-noise images (i.e. computational reproducibility). Finally, we demonstrated the use of the 1D-CNN method in two practical examples to reduce noise from parallel imaging and simultaneous multi-slice acquisition. We conclude that the 1D-CNN denoising method is a simple, effective denoising method for DWI images that overcomes some of the limitations of current state-of-the-art denoising methods, such as the need for a large number of training subjects and the need to account for the rectified noise floor.
Using dynamic microsimulation to project cognitive function in the elderly population
Authors: Wei Yifan , Heun-Johnson Hanke , Tysinger Bryan
Published: September 2022

Background

A long-term projection model based on nationally representative data and tracking disease progression across Alzheimer’s disease continuum is important for economics evaluation of Alzheimer’s disease and other dementias (ADOD) therapy.

Methods

The Health and Retirement Study (HRS) includes an adapted version of the Telephone Interview for Cognitive Status (TICS27) to evaluate respondents’ cognitive function. We developed an ordered probit transition model to predict future TICS27 score. This transition model is utilized in the Future Elderly Model (FEM), a dynamic microsimulation model of health and health-related economic outcomes for the US population. We validated the FEM TICS27 model using a five-fold cross validation approach, by comparing 10-year (2006–2016) simulated outcomes against observed HRS data.

Results

In aggregate, the distribution of TICS27 scores after ten years of FEM simulation matches the HRS. FEM’s assignment of cognitive/mortality status also matches those observed in HRS on the population level. At the individual level, the area under the receiver operating characteristic (AUROC) curve is 0.904 for prediction of dementia or dead with dementia in 10 years, the AUROC for predicting significant cognitive decline in two years for mild cognitive impairment patients is 0.722.

Conclusions

The FEM TICS27 model demonstrates its predictive accuracy for both two- and ten-year cognitive outcomes. Our cognition projection model is unique in its validation with an unbiased approach, resulting in a high-quality platform for assessing the burden of cognitive decline and translating the benefit of innovative therapies into long-term value to society.
UDP-glucose dehydrogenase (UGDH) activity is suppressed by peroxide and promoted by PDGF in fibroblast-like synoviocytes: Evidence of a redox control mechanism
Authors: Chandrasekaran Ramya , Mathieu Colleen , Sheth Rishi , Cheng Alexandre P. , Fong David , McCormack Robert , El-Gabalawy Hani , Alishetty Suman , Paige Mikell , Hoemann Caroline D.
Published: September 2022

UDP-glucose dehydrogenase (UGDH) generates essential precursors of hyaluronic acid (HA) synthesis, however mechanisms regulating its activity are unclear. We used enzyme histostaining and quantitative image analysis to test whether cytokines that stimulate HA synthesis upregulate UGDH activity. Fibroblast-like synoviocytes (FLS, from N = 6 human donors with knee pain) were cultured, freeze-thawed, and incubated for 1 hour with UDP-glucose, NAD+ and nitroblue tetrazolium (NBT) which allows UGDH to generate NADH, and NADH to reduce NBT to a blue stain. Compared to serum-free medium, FLS treated with PDGF showed 3-fold higher UGDH activity and 6-fold higher HA release, but IL-1beta/TGF-beta1 induced 27-fold higher HA release without enhancing UGDH activity. In selected proliferating cells, UGDH activity was lost in the cytosol, but preserved in the nucleus. Cell-free assays led us to discover that diaphorase, a cytosolic enzyme, or glutathione reductase, a nuclear enzyme, was necessary and sufficient for NADH to reduce NBT to a blue formazan dye in a 1-hour timeframe. Primary synovial fibroblasts and transformed A549 fibroblasts showed constitutive diaphorase/GR staining activity that varied according to supplied NADH levels, with relatively stronger UGDH and diaphorase activity in A549 cells. Unilateral knee injury in New Zealand White rabbits (N = 3) stimulated a coordinated increase in synovial membrane UGDH and diaphorase activity, but higher synovial fluid HA in only 2 out of 3 injured joints. UGDH activity (but not diaphorase) was abolished by N-ethyl maleimide, and inhibited by peroxide or UDP-xylose. Our results do not support the hypothesis that UGDH is a rate-liming enzyme for HA synthesis under catabolic inflammatory conditions that can oxidize and inactivate the UGDH active site cysteine. Our novel data suggest a model where UGDH activity is controlled by a redox switch, where intracellular peroxide inactivates, and high glutathione and diaphorase promote UGDH activity by maintaining the active site cysteine in a reduced state, and by recycling NAD+ from NADH.
Improved performance with automatic sound management 3 in the MED-EL SONNET 2 cochlear implant audio processor
Authors: Kurz Anja , Rak Kristen , Hagen Rudolf
Published: September 2022

Objectives

The SONNET 2 audio processor features ambient noise reduction (ANR), transient-noise reduction (TNR), and adaptive intelligence (AI). The primary aim of this study was to evaluate if using these features improves speech perception in noise, subjective listening effort, and sound quality.

Design

In this prospective longitudinal study, twenty adult SONNET users were fitted with the SONNET 2 audio processor, configured either as a default SONNET (no ANR/TNR/AI), with mild ANR/TNR, with strong ANR/TNR, with mild AI, and with strong AI. Speech perception in noise was assessed in speech and stationary noise from the front (S0N0); speech, stationary noise, and transient noise from the front (S0N0T0); and speech from the front in spatially-distributed stationary noise (S0N±45N±135). Listening effort, subjective sound quality, and device/setup preference were assessed.

Results

In the S0N0 setup, speech perception in noise was significantly better with the SONNET 2 when using ANR/TNR in the mild setup than with the SONNET or the SONNET 2 in the default SONNET configuration. In the S0N±45N±135 setup, speech understanding was significantly better in all four SONNET 2 configurations than with the SONNET or the SONNET 2 in the default SONNET configuration (a 1.26–2.55 dB SRT80 benefit). Subjects tolerated consistently lower signal-to-noise values with the SONNET 2 configurations using ANR/TNR than with the default SONNET configuration in all listening effort categories. All SONNET 2 configurations using ANR/TNR were preferred and better rated in speech in stationary and/or transient noise compared to the default SONNET configuration. Sound quality and pleasantness were better in those SONNET 2 configurations. Subjects strongly preferred the SONNET 2 configurations over the SONNET configuration.

Conclusions

The new front-end features implemented in the SONNET 2 audio processor objectively improve speech perception in noise. Subjects preferred the SONNET 2, over the SONNET, in the presence of stationary and transient noise.
Seasonal shedding of coronavirus by straw-colored fruit bats at urban roosts in Africa
Authors: Montecino-Latorre Diego , Goldstein Tracey , Kelly Terra R. , Wolking David J. , Kindunda Adam , Kongo Godphrey , Bel-Nono Samuel O. , Kazwala Rudovick R. , Suu-Ire Richard D. , Barker Christopher M. , Johnson Christine Kreuder , Mazet Jonna A. K.
Published: September 2022

The straw-colored fruit bat (Eidolon helvum) is a pteropodid whose conservation is crucial for maintaining functional connectivity of plant populations in tropical Africa. Land conversion has pushed this species to adapt to roosting in urban centers across its range. These colonies often host millions of individuals, creating intensive human-bat contact interfaces that could facilitate the spillover of coronaviruses shed by these bats. A better understanding of coronavirus dynamics in these roosts is needed to identify peak times of exposure risk in order to propose evidence-based management that supports safe human-bat coexistence, as well as the conservation of this chiropteran. We studied the temporal patterns of coronavirus shedding in E. helvum, by testing thousands of longitudinally-collected fecal samples from two spatially distant urban roosts in Ghana and Tanzania. Shedding of coronaviruses peaked during the second part of pup weaning in both roosts. Assuming that coronavirus shedding is directly related to spillover risk, our results indicate that exposure mitigation should target reducing contact between people and E. helvum roosts during the pup “weaning” period. This recommendation can be applied across the many highly-populated urban sites occupied by E. helvum across Africa.
Insight into the effect of low temperature treatment on trichome density and related differentially expressed genes in Chinese cabbage
Authors: Sun Peixia , Huang Chuang , Zhang Liping , Wu Dan , Zhang Wei , Yu Shuang , Fu Genying , Cheng Shanhan , Wang Zhiwei , Deng Qin , Zhu Guopeng , Liu Pingwu
Published: September 2022

Trichome is important for help plant resist adversity and external damage. However, it often affects the appearance and taste of vegetables. In the present study, the trichome density of leaves from two Chinese cabbage cultivars with and without trichomes treated at low temperature are analyzed by biological microscope, and the differentially expressed genes related to trichomes formation were screened through transcriptome sequencing. The results showed that the number of leaves trichomes was reduced by 34.7% at low temperature compared with room temperature. A total of 661 differentially expression genes effecting trichomes formation were identified at the CT vs C, LCT vs LC, CT vs LCT. Several differentially expression genes from every comparison group were enriched in plant hormone signal transduction and amino acid biosynthesis pathway. Combined with the central genes obtained by WGCNA analysis, five candidate genes Bra029778, Bra026393, Bra030270, Bra037264 and Bra009655 were screened. qRT-PCR analysis verified that the gene expression differences were in line with the trend of transcriptome data. This study not only found possible new key genes and laid a foundation for revealing the molecular mechanism regulating the formation of trichome in Chinese cabbage, but also provided a new way to study plant surface trichomes.
Beyond opioid prescribing: Evaluation of a substance use disorder curriculum for OBGYN residents
Authors: Martin Caitlin E. , Thakkar Bhushan , Cox Lauren , Johnson Elisabeth , Jones Hendrée E. , Connolly AnnaMarie
Published: September 2022

Objective

Amidst the current opioid crisis, there is a need for better integration of substance use disorder screening and treatment across specialties. However, there is no consensus regarding how to best instruct OBGYN trainees in the clinical skills related to opioid and other substance use disorders (SUD). Study objectives were (1) to assess the effectiveness a SUD curriculum to improve self-reported competence among OBGYN residents and (2) to explore its effectiveness to improve attending evaluations of residents’ clinical skills as well as its feasibility and acceptability from the resident perspective.

Methods

A pilot 3-session curriculum was developed and adapted to SUD screening and treatment which included readings, didactics, and supervised outpatient clinical experiences for OBGYN post-graduate year 1 (PGY-1) residents rotating through an integrated OBGYN-SUD clinic. Eighteen residents completed pre and post clinical skills self-assessments (SUD screening, counseling, referring, Motivational Interviewing) using an adapted Zwisch Rating Scale (range 1–5). Scores were compared between time points using paired t-tests. Sub-samples also (a) were evaluated by the attending on three relevant Accreditation Council for Graduate Medical Education Milestones (ACGME) milestone sets using the web-based feedback program, myTIPreport (n = 10) and (b) completed a qualitative interview (n = 4).

Results

All PGY-1s (18/18) across three academic years completed the 3-session SUD curriculum. Clinical skill self-assessments improved significantly in all areas [SUD Screening (2.44 (0.98) vs 3.56 (0.62), p = <0.01); Counseling (1.81 (0.71) vs 3.56 (0.51), p = < .01; Referring (2.03 (0.74) vs 3.17 (0.71), p = < .01; Motivational Interviewing (1.94 (1.06) vs 3.33 (0.69), p = < .01)]. Milestone set levels assigned by attending evaluations (n = 10) also improved. Qualitative data (n = 4) revealed high acceptability; all curriculum components were viewed positively, and feedback was provided (e.g., desire for more patient exposures).

Conclusion

A pilot SUD curriculum tailored for OBGYN PGY-1 residents that goes beyond opioid prescribing to encompass SUD management is feasible, acceptable and likely effective at improving SUD core clinical skills.
The polarization of politics and public opinion and their effects on racial inequality in COVID mortality
Authors: Lo Adeline , Pifarré i Arolas Héctor , Renshon Jonathan , Liang Siyu
Published: September 2022

Evidence from the early months of the COVID-19 pandemic in the U.S. indicated that the virus had vastly different effects across races, with black Americans faring worse on dimensions including illness, hospitalization and death. New data suggests that our understanding of the pandemic’s racial inequities must be revised given the closing of the gap between black and white COVID-related mortality. Initial explanations for inequality in COVID-related outcomes concentrated on static factors—e.g., geography, urbanicity, segregation or age-structures—that are insufficient on their own to explain observed time-varying patterns in inequality. Drawing from a literature suggesting the relevance of political factors in explaining pandemic outcomes, we highlight the importance of political polarization—the partisan divide in pandemic-related policies and beliefs—that varies over time and across geographic units. Specifically, we investigate the role of polarization through two political factors, public opinion and state-level public health policies, using fine-grained data on disparities in public concern over COVID and in state containment/health policies to understand the changing pattern of inequality in mortality. We show that (1) apparent decreases in inequality are driven by increasing total deaths—mostly among white Americans—rather than decreasing mortality among black Americans (2) containment policies are associated with decreasing inequality, likely resulting from lower relative mortality among Blacks (3) as the partisan disparity in Americans who were “unconcerned” about COVID increased, racial inequality in COVID mortality decreased, generating the appearance of greater equality consistent with a “race to the bottom’’ explanation as overall deaths increased and substantively swamping the effects of containment policies.
Ice slurry ingestion improves physical performance during high-intensity intermittent exercise in a hot environment
Authors: Morito Akihisa , Inami Takayuki , Hirata Akihiro , Yamada Satoshi , Shimomasuda Masatsugu , Haramoto Maki , Kato Keita , Tahara Shigeyuki , Oguma Yuko , Ishida Hiroyuki , Kohtake Naohiko
Published: September 2022

Ice slurry ingestion enhances exercise performance by lowering the core body temperature. However, an operational issue related to this ingestion is the requirement for a high intake of 7.5 g·kg-1 to produce the desired effects. We investigated the effects of the intake of low amounts of ice slurry at −2°C on the tympanic temperature and exercise performance during repeated high-intensity intermittent exercises in a hot environment. This study was a randomized, crossover study, with a 6-day washout period. Twelve university rugby union players performed two 30-min sessions of high-intensity intermittent exercises separated by a 15-min half-time break on a cycle ergometer in a hot environment (28.8°C ± 0.1°C, 49.5% ± 0.6% relative humidity). The participants ingested 450 g of −2°C-ice slurry (ICE), or a 30°C-beverage (CON) having the same composition as ICE, or 30°C-water (WAT) during the half-time break. The tympanic temperature and skin temperature were measured as the physiological data, and the peak power and mean power as the exercise performance data. The tympanic temperature at the half-time break and beginning of the 2nd session was significantly lower in the ICE group as compared with the CON and WAT groups. The skin temperature at the half-time break was significantly lower in the ICE group as compared with the WAT group. While the peak power and mean power during the 2nd session were significantly greater in the ICE group as compared with the CON and WAT groups. Our findings suggest that even the intake of lower amounts, as compared with those used in previous studies, of low-temperature ice slurry can reduce the body temperature and improve the peak power. These results suggest that intake of low-temperature ice slurry as a strategy for internal body cooling is useful for improving endurance exercise performance in hot environments.
Individual and intimate-partner factors associated with cervical cancer screening in Central Uganda
Authors: Isabirye Alone
Published: September 2022

Intimate-partner factors have a significant effect on the uptake of services that affect maternal reproductive health outcomes. There is limited research on intimate-partner factors associated with cervical cancer screening. Therefore, this article examines the intimate-partner correlates of cervical cancer screening among married women in Central Uganda. We conducted a cross-sectional survey in Wakiso and Nakasongola districts in Central Uganda. A total of 656 married women aged 25–49 participated in the study. Frequency distributions for descriptive statistics and Pearson chi-squared tests were done to identify the association of selected individual explanatory variables and intimate-partner factors with cervical cancer screening. Finally, multivariable complementary log-log regressions were used to estimate intimate-partner factors associated with women’s cervical cancer screening uptake in Central Uganda. About 2 in 10 (20%) of the participants had been screened for cervical cancer. The following characteristics when examined separately in relation to the uptake of cervical cancer screening service and were significant: woman’s age, education attainment, occupation, wealth index, parity, male partner’s age, and male partner’s emotional support. After adjusting for independent factors, cervical cancer screening was significantly associated with women who had; attained secondary (AOR = 2.19; CI 1.18–4.06) compared to none/ primary education, and received partner’s emotional support (AOR = 30.06; CI 13.44–67.20) compared to those who did not receive partner’s emotional support. In Central Uganda, cervical cancer screening among married women was significantly associated with women’s education, and partner’s emotional support. These factors point to the importance of intimate-partner factors. Therefore, more effort should be directed at encouraging men’s participation. This should be supplemented with empowering women through education to increase uptake of screening services.