bluuebunny/crossref_metadata_2025 huggingface dataset:
Harmonic Analysis of Hemodynamic Status at Different Pregnancy Stages Using Photoplethysmography
Authors: Chen Chih Yu , Wang Sheng Hung , Wang Tien Chung , Wang Gin Chung
Published: July 2023

Background: During pregnancy, major physiological changes occur in every system. Understanding the hemodynamic changes in different stages of pregnancy can help to identify abnormal states during pregnancy. Harmonic analysis could be a useful tool in monitoring the state of the ventricular-arterial system during pregnancy. The aim of this study was to investigate the specific statistical relationships between changes in harmonic indices during different stages of pregnancy. Methods: A Total of 380 women (190 pregnant women and 190 age-matched non-pregnant women), with ages ranging from 20 to 45, were enrolled in the study. The visit measured the subject’s hemodynamic parameters including heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and photoplethysmography (PPG). SBP and DBP were evaluated by an automatic blood pressure monitor. PPG signal were continuously recorded for 12-seconds using a PPG sensor. Spectrum analysis of the PPG signal was performed to evaluate the first five harmonic components (C1 – C5) and harmonic phases (P1 – P5). Result: A comparison between pregnant women and non-pregnant women showed that the non-pregnant women had lower DBP, C3, C5 and P5 (p<0.05). Waist Circumference, Heart rate, C2, C4 and P2 were higher in pregnant women. Logistic regression analysis was used to determine the associations between pregnancy and harmonics indices. C2, C4 and P3 were positively and P1 and P4 were negatively associated with pregnancy after controlling age, BMI, waist circumference, heart rate, SBP and DBP. Conclusion: The results of this study provide information on the changes in the harmonic frequency components during various stages of pregnancy. The harmonic components of the PPG signal have independent predictive value for changes in a woman's physiology during pregnancy. Since non-invasive PPG measurements can be performed frequently and easily, in the future, it is possible that the hemodynamic changes from some pregnancy-related disorders could be studied by harmonic analysis.
Dorsal-Ventral Gradient of Activin Regulates Strength of GABAergic Inhibition along Longitudinal Axis of Mouse Hippocampus in an Activity-Dependent Fashion
Authors: Valero-Aracama Maria Jesus , Zheng Fang , Alzheimer Christian
Published: July 2023

The functional and neurophysiological distinction between dorsal and ventral hippocampus affects also GABAergic inhibition. In line with his notion, ventral CA1 pyramidal cells displayed a more dynamic and effective response to inhibitory input compared to their dorsal counterparts. We posit that this difference is effected by the dorsal-ventral gradient of activin A, a member of the transforming growth factor-β family, which is increasingly recognized for its modulatory role in brain regions involved in cognitive functions and affective behavior. Lending credence to this hypothesis, we found that in slices from transgenic mice expressing a dominant-negative mutant of activin receptor IB (dnActRIB), inhibitory transmission was enhanced only in CA1 neurons of dorsal hippocampus, where basal activin A level is much higher than in ventral hippocampus. We next asked how a rise in endogenous activin A would affect GABAergic inhibition along the longitudinal axis of the hippocampus. We performed ex vivo recordings from wild type and dnActRIB mice after overnight exposure to an enriched environment (EE), which engenders a robust increase in activing A levels in both dorsal and ventral hippocampi. Compared to control mice from standard cages, the behaviorally induced surge in activin A produced a decline in ventral inhibition, an effect that was absent in slices from dnActRIB mice. Underscoring the essential role of activin in the EE-associated modulation of ventral inhibition, this effect was mimicked by acute application of recombinant activin A in control slices. In summary, both genetic and behavioral manipulations of activin receptor signaling affected the dorsal-ventral difference in synaptic inhibition, suggesting that activin A regulates the strength of GABAergic inhibition in a region-specific fashion.
Long COVID and Serious Side Reactions to mRNA-Based Vaccines (VSITV) Are Mainly Spike Protein-Induced Thrombotic Vasculitis
Authors: palacios castrillo Ronald
Published: July 2023

Abstract Long COVID syndrome, known as Long COVID, refers to a series of debilitating symptoms that arise after infection with the SARS-CoV-2 virus. These symptoms are similar to those experienced by some people after vaccination with vaccines based on mRNA platforms (Pfizer, Moderna). With more than 200 million Long COVID patients worldwide and an increase in cases of moderate to severe reactions after administration of mRNA vaccines (VSITV), the effects on quality of life and economics are significant, for what is necessary to pay urgent attention to understand its pathophysiology and to provide an adequate diagnosis and treatment. In this article, we describe our perspective that both Long COVID and common side effects of mRNA vaccines (VSITV) induce persistent and prolonged expression of the spike protein (SPIKE) in various tissues and organs of the body. This would induce coagulopathy, microscopic vasculitis, and endothelitis as the main drivers of the disease, and may also cause or worsen other common pathologies in Long COVID, such as mast cell activation syndrome, dysautonomia, and sudden deaths due to arrhythmias and heart attacks, reports of which continue to rise. Given that the SARS-CoV-2 spike protein can independently induce fibrinoid microclot formation, platelet activation, and endothelitis, we predict that the persistence of the spike protein will be a key mechanism driving ongoing coagulopathy in Long COVID and in the VSITV. We discuss various treatment goals to address coagulopathy, endothelitis, and vasculitis and predict that treatment, especially if given early, with a combination of anticoagulants, antiplatelets, corticosteroids, and rapamycin/everolimus, will provide significant relief for many patients.
Bootstrap Approach for Principal Component Analysis Method; Cases studies
Authors: Kalantan Zakiah I. , Alharbi Lujain , Binhimd Sulafah
Published: July 2023

Analyzing big data poses a great challenge for numerous researchers to explore the data structure. Dimension reduction methods can be used to reduce data dimensionality, taking it from occupying a high-dimensional space to existing in a lower-dimensional space while retaining as much information as possible. Principal Component Analysis is one of the most popular used to reduce the dimensional space. The bootstrap sample is obtained by randomly sampling n times with replacement from the original sample, the method provides easy tool to understand the interactive component and develop the process. There are not enough researches discussed the stability of PCA method using bootstrap method. In this paper, the bootstrap method is used to analyze the stability of PCA results and to estimate the number of PCA in efficient way. The method is used to estimate the number of PCA that needed to classify the data set, and the effectiveness of the discussed techniques is demonstrated through real data sets.
Disparities in Neonatal Mortalities in the United States
Authors: Qattea Ibrahim , Aly Hany , Burdjalov Maria
Published: July 2023

Abstract:

Objective: We aimed to look for the mortality of Black and White Neonates and compare the Black and White neonates' mortalities after stratifying the population by many significant epidemiologic and hospital factors. We utilized the National Inpatient Sample (NIS) dataset over seven years from 2012 through 2018 for all neonates ≤ 28 days of age in all hospitals in the USA.

Design/Method: We utilized the National Inpatient Sample (NIS) dataset over seven years from 2012 through 2018 for all neonates ≤ 28 days of age in all hospitals in the USA. Neonatal characteristics used in the analysis included ethnicity, sex, household income, and type of healthcare insurance. Hospital characteristics were urban teaching, urban non-teaching, and rural. Hospital location was classified according to the 9 U.S. Census Division regions.

Results: Neonatal mortality continues to be higher in Black: 21,975 (0.63%) and in White was: 35495 (0.28%), Government-supported health insurance was significantly more among Black populations when compared to White (68.8% vs. 35.3% p<0.001). Household income differed significantly; almost half (49.8%) of the Black population has income ≤ 25th percentile vs. 22.1% in White. There was a significant variation in mortality in different U.S. locations. In the Black population, the highest mortality was in the West North Central division (0.72%), and the lower mortality was in the New England division (0.51%), whereas in the White population, the highest mortality was in the East South-Central division (0.36%), and the lowest mortality was in the New England division (0.21%).
Trend analysis showed a significant decrease in mortality in Black and White populations over the years, but when stratifying the population by sex, types of insurance, the household income, the type of hospitals, the mortality was consistently higher in Black groups throughout the study years,

Conclusions: Disparities in neonatal mortality continue to be higher in Black; There was a significant variation in mortality in different U.S. locations. In the Black population, the highest mortality was in the West North Central division, and the lower mortality was in the New England division, whereas in the White population, the highest mortality was in the East South-Central division, and the lowest mortality was in the New England division.
There has been a significant decrease in mortality in Black and White populations over the years, but when stratifying the population by many significant epidemiologic and hospital factors, the mortality was consistently higher in Black groups throughout the study years.
Association of Denture Use and Chewing Ability with Cognitive Function Analysed Using Panel Data from Korea Longitudinal Study of Aging (2006–2018)
Authors: Jun Nu-Ri , Kim Jae-Hyun , Jang Jong-Hwa
Published: July 2023

Very poor oral health, common among older adults, is associated with cognitive decline.This study aimed to investigate the association between denture use, chewing ability, and cognitive function in Korean middle-aged adults using samples representing middle-aged people at the national level. This longitudinal study included 9,998 middle-aged adults via Korea Longitudinal Study of Aging 7th special survey data. Denture use, chewing ability, health-related factors, and general characteristics were assessed by the Computer Assisted Personal Interview. After controlling general characteristics using a generalized estimating equation model, the association of denture use and MMSE scores with chewing ability of those with or without dentures and MMSE scores were analysed. Twenty-four percent of participants wore dentures among them, 35.1% complained of difficulty chewing when wearing dentures. Among participants who did not wear dentures, 16.4% complained of difficulty chewing. MMSE scores were lower among denture-wearers than non-denture wearers (β = -0.026, p < 0.001). In both groups, MMSE scores decreased with chewing difficulty and were significantly reduced among non-denture wearers (p < 0.05). Chewing ability was closely associated with cognitive function. Given the negative effect of difficulty chewing on cognitive function, maintaining chewing ability should be of great concern.
Design and Analysis of Query Models Database Preservation Information Systems Digitization of History and Endowments; Case Study of History and Waqf of Sumedang Larang Kingdom Indonesia
Authors: Sudrajat R. , Ruchjana Budi Nurani , Abdullah Atje Setiawan , Budiarto Rahmat
Published: July 2023

Historical and Endowment Properties are different from Heritage and cultural Properties, as Historical and Endowment properties are governed by a unique set of laws that Waqf recipients must abide by. Property that is entrusted is usually in the form of buildings, land or valuables which in preservation is not limited to time as long as the property can be utilized. Reliable information technology is needed to ensure data security both digitally and physically, while the rapid development of information technology demands information openness and this will be a challenge in itself. The objectives of this study include examining the collection of historical databases and endowments, the relationship between digital data and physical data and management organizations. The method of how to design a query model to display data is then analyzed whether the data conforms to the rules in waqf management. The results are expected to bring up accurate data between digital data and physical data and if there are differences into findings for the next analysis.
Observational Studies of Ocean Fronts: A Systematic Review of Chinese-Language Literature
Authors: Shen Xin-Tang , Belkin Igor M
Published: July 2023

This review will serve as an entry point for international researchers who would like to tap into the vast scientific potential of Chinese-language literature on oceanic fronts. We focused on observational studies in descriptive physical oceanography of marine fronts. A thorough bibliographic search netted 93 papers published in 1982-2023, with a sharp increase of the total number of papers after 2010. This trend continued unabated through the early 2020s. Regionally, the overwhelming majority of papers is focused on the China Seas, particularly the East China Seas (Bohai, Huanghai, and Donghai, especially the Yangtze River Plume) and northern South China Sea (Guangdong Shelf). Elsewhere, a number of papers were dedicated to the Southern Ocean and North Atlantic. Thematically, papers on remote sensing of ocean fronts dominate, with special attention to the development of new advanced front-detection algorithms applied to satellite data on sea surface temperature and chlorophyll. Numerous papers on marine fronts in the China Seas present important results that have to be considered by international researchers. Overall, this review emphasizes the significant contributions made by Chinese oceanographers, particularly to the frontal oceanography of the China Seas.
Clinical Characteristics of 427 Unvaccinated Chinese Adult Patients with Maintenance Hemodialysis infected with SARS-CoV-2 Omicron subvariant BA.5.2
Authors: Ha Xiaowen , Zhao Zhigang , Zhao Tiantian , muhetaer gulimire , Wang Xiaoyu , Bao Aihong , Duan Yanya , Zhuang Jing , Song Xue , Zhou Yipeng , Zhang Qingqing , Wu Jianhua , Fan Min , Zhang Li , Tian Xuefei , Jiang Hong
Published: July 2023

To analyze the clinical characteristics and outcomes of unvaccinated adult patients on maintenance hemodialysis infected with SARS-CoV-2 Omicron subvariant BA.5.2.The clinical data of 427 maintenance hemodialysis patients infected with SARS-CoV-2 Omicron subvariant BA.5.2 in our hospital were retrospectively collected. The patients were grouped according to the severity of the disease and compared. The clinical outcome and two-month follow-up were analyzed.These results suggest that CRP level, procalcitonin level, and bicarbonate concentration are related to the severity of disease caused by SARS-CoV-2 omicron BA.5.2 infection in unimmunized MHD patients. In addition, the co-bacterial infection may be an important cause of severe illness. Therefore, strengthen the treatment of critically ill patients, and actively and effectively control infection and secondary infection; Effective vaccination is the key to improving clinical outcomes to prevent the conversion of ordinary patients to severe and critical cases. Fever, age, ORF1ab gene value, and arterial oxygen partial pressure may be independent risk factors for disease severity in COVID-19 patients.
Molecular Bonding Regulated Defect Passivation for Modulating Efficiency and Stability of Methylammonium Free Inverted Perovskite Solar Cells
Authors: Shirai yasuhiro , Yanagida Masatoshi , Lyalin Andrey , Taketsugu Tetsuya , Miyano Kenjiro , KHADKA DHRUBA
Published: July 2023

Molecular passivation is a prominent approach for improving the power conversion efficiency and operation stability of perovskite solar cells. Herein, diammonium iodide functional molecules with an aryl or alkyl core are introduced on 3D-perovskite, and its interfacial passivation effect is explored. It showed that piperazine dihydriodide (PZDI) with alkyl core-electron rich -NH terminal is propitious to mitigate surface and bulk defects and modify surface chemistry or interfacial energy band leading to increase carrier extraction. Benefiting from superior PZDI passivation, the device efficiency has been scaled to 23.17% (area ~1 cm2) with superior operational device stability. We also achieved a certified efficiency of ~21.50% (area ~1.024 cm2). The theoretical calculation suggests that PZDI entangles onto the film’s surface with -NH2I anchor, and reinforces the adhesion. Device analysis corroborates that a stronger bonding interaction attenuates the defect densities in the perovskite film and suppresses ion migration, which is supported by the first-principle calculations. This work demonstrated that the bifunctional molecules with stronger surface adsorption play a crucial role in triggering defect mitigation, which paves the way for the design of bonding-regulated molecular passivation for enhancing device performance and stability.
Angiogenic and inflammatory responses in human induced microglia-like (iMG) cells from patients with Moyamoya disease
Authors: Shirozu Noritoshi , Ohgidani Masahiro , Hata Nobuhiro , Tanaka Shunya , Inamine Shogo , Sagata Noriaki , Kimura Tetsuaki , Inoue Ituro , Arimura Koichi , Nakamizo Akira , Nishimura Ataru , Maehara Naoki , Takagishi Soh , Iwaki Katsuma , Nakao Tomohiro , Masuda Keiji , Sakai Yasunari , Mizoguchi Masahiro , Yoshimoto Koji , Kato Takahiro A.
Published: July 2023

Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells.
We recruited 25 adult patients with MMD and 24 healthy volunteers. Patients with MMD were subdivided into progressive (N = 7) or stable (N = 18) group whether novel symptoms or radiographic advancement of Suzuki stage within 1 year was observed or not. We produced 3 types of iMG cells; resting, M1-, and M2-induced cells from monocytes, then RNA sequencing followed by GO and KEGG pathway enrichment analysis and qPCR assay were performed.
RNA sequencing of M2-induced iMG cells revealed that 600 genes were significantly upregulated (338) or downregulated (262) in patients with MMD. Inflammation and immune-related factors and angiogenesis-related factors were specifically associated with MMD in GO analysis. qPCR for MMP9, VEGFA, and TGFB1 expression validated these findings. This study is the first to demonstrate that M2 microglia are involved in the angiogenic process of MMD. The iMG technique provides a promising approach to explore the bioactivity of microglia in cerebrovascular diseases.
Mitochondrial Magnesium is the cationic rheostat for MCU-mediated mitochondrial Ca2+ uptake
Authors: Shanmughapriya Santhanam , Ponnusamy Thiruvelselvan , Velusamy Prema , Kumar Amrendra , Morris Daniel , Zhang Xueqian , Ning Gang , Klinger Marianne , Copper Jean , Rajan Sudarsan , Cheung Joseph , Kalimuthusamy Natarajaseenivasan , Mnatsakanyan Nelli
Published: July 2023

Calcium (Ca2+) uptake by mitochondria is essential in regulating bioenergetics, cell death, and cytosolic Ca2+ transients. Mitochondrial Calcium Uniporter (MCU) mediates the mitochondrial Ca2+ uptake. MCU is a hetero-oligomeric complex with a pore-forming component and accessory proteins required for channel activity. Though MCU regulation by MICUs is unequivocally established, there needs to be more knowledge of whether divalent cations regulate MCU. Here we set out to understand the mitochondrial matrix Mg2+-dependent regulation of MCU activity. We showed Mrs2 as the authentic mammalian mitochondrial Mg2+ channel using the planar lipid bilayer recordings. Using a liver-specific Mrs2 KO mouse model, we showed that decreased matrix [Mg2+] is associated with increased MCU activity and matrix Ca2+ overload. The disruption of Mg2+-dependent MCU regulation significantly prompted mitochondrial permeability transition pore opening-mediated cell death during tissue IR injury. Our findings support a critical role for mMg2+ in regulating MCU activity and attenuating mCa2+ overload.
Associations between 47 anthropometric markers derived from a body scanner and relative fat-free mass in a population-based study
Authors: Dietzmann Maximilian , Radke Dörte , Markus Marcello RP , Wiese Mats , Völzke Henry , Felix Stephan B. , Dörr Marcus , Bahls Martin , Ittermann Till
Published: July 2023

Background
Low relative fat free mass (FFM) is associated with an increased risk of chronic diseases and mortality. However, FFM assessment in clinical routine is time consuming and currently not being done.
Objective
Our aim was to identify easily accessible anthropometric markers assessed by a 3D optical body-scanner, which showed strong associations with FFM derived by either bioelectrical impedance analysis (BIA) or air displacement plethysmography (ADP).
Material And Methods
We analyzed data of 1,593 individuals (784 women; 49.2%, age range 28–88 years) enrolled in the population-based Study of Health in Pomerania (SHIP-TREND 1). Forty-seven anthropometric markers were derived from a body scanner. FFM was assessed by BIA and ADP. Anthropometric measurements were associated with FFM by sex-stratified linear regression models adjusted for body height and age. Anthropometric markers were ranked according to the coefficient of determination (R2) derived from these regression models.
Results
Circumferences of high hip, belly, middle hip, waist and high waist showed the strongest inverse associations with FFM. These relations were stronger in females than in males. Associations of anthropometric markers with FFM measured by ADP were greater compared to FFM assessment by BIA. Manually measured waist and hip circumference showed slightly weaker associations with the FFM compared to automated measurements.
Conclusion
Single anthropometric body scanner measures were more strongly associated with FFM assessed by ADP compared to FFM determined by BIA. Body scanner circumferences showed stronger associations with FFM than manual measurements. The detected anthropometrics could be helpful in assessing FFM in clinical routine.
Eco-friendly and practical plastic food-packaging alternatives of all-biomass-derived nanocomposite films
Authors: Chi Zhe , Ding Yuanyuan , Zhang Peng , Zhang Fenglong , Zhong Bocun , Yang Tenglin , Ding Xiang , Liu Chenguang
Published: July 2023

Approximately 60% of plastic pollution originates from the food and beverage packaging. Complete degradation of the bio-based plastic packaging presently available, relies on garbage sorting, recycling, and composting. Herein, we showcase that naturally-degradable bioplastics as food packaging alternatives can be accomplished with all-biomass nanocomposite encompassing pullulan, nanocellulose (NC) and/or hydrophobic lignin (HBL) using simple approaches. NC and HBL were derived from corn stalk using a recyclable eco-friendly deep eutectic solvent (DES). Optimal dispersion of NC in pullulan through high-pressure homogenization produced a pullulan-NC (PNC) bio-nanocomposite film with mechanical strength enhanced to 76.6 ± 1.9 MPa. Single PNC film could serve as food inner-packaging; while it collaborated with kraft paper wrapping to compensate its inadequate water resistance, performing as packaging for dry powders, biscuits, and oil. Remarkably, a sandwich-like film, created by hot-pressing two outer layers of HBL-NC (LNC) films and one PNC film layer, exhibited desirable mechanical strength and water resistance. Varying the number of LNC and PNC layers achieved diverse composite films as food outer-packaging, including preserving and shopping bags, disposable cups and straws. Significantly, all these films are biosafe and readily degraded in nature without counting on composting or recycling, underlining their prospects in future industrialization and sustainability.
Developing Public Health Surveillance Dashboards: A Scoping Review on the Design Principles
Authors: Rabiei Reza , Bastani Peivand , Ahmadi Hossein , Dehghan Shirin , Almasi Sohrab
Published: July 2023

Background
Public health dashboards facilitate the monitoring and prediction of disease outbreaks by continuously monitoring the health status of the community. This study aimed to identify design principles and determinants for developing public health surveillance dashboards.
Methodology
This scoping review is based on Arksey and O'Malley's framework as included in JBI guidance. Four databases were used to review and present the proposed principles of designing public health dashboards: IEEE, PubMed, Web of Science, and Scopus. We considered articles published between 2010 and 2022. The final search of articles was done on November 30, 2022. Only articles in English language were included. Qualitative synthesis and trend analysis was conducted.
Results
Findings from sixty-seven articles out of 543 retrieved articles which were eligible for analysis, indicate that most of the dashboards designed from 2020 onwards were at the national level for managing and monitoring COVID-19. Design principles for the public health dashboard were presented in five groups, i.e., considering aim and target users, appropriate content, interface, data analysis and presentation types, and infrastructure.
Conclusion
Effective and efficient use of dashboards in public health surveillance requires putting the design principles into practice to improve the functionality of these systems in monitoring and decision making. Taking requirements of users into account, developing a robust infrastructure for improving data accessibility, developing and applying Key Performance Indicators (KPIs) for data processing and reporting purposes, and designing interactive and intuitive interfaces are key for successful design and development.
Group-to-group Recommendation with Neural Graph Matching
Authors: Wang Chunchen , Wang Wei , Yang Cheng , Shi Chuan , Xie Ruobing , Lu Yuanfu , Yang Haili , Zhang Xu
Published: July 2023

Nowadays, with the development of recommender systems, an emerging recommendation scenario called group-to-group recommendation has played a vital role in information acquisition for users. The new recommendation scenario seeks to recommend a group of related items to users with similar interests.
To some extent, it alleviates the problem of point-to-point recommendations getting trapped in an information cocoon due to an over-reliance on user behaviors. For the new recommendation scenario, the existing recommendation methods cannot model the complex interactions between user groups and item groups, thus affecting the accuracy of the group-to-group recommendation.
In this paper, we propose a group-to-group recommendation method, which abstracts user groups and item groups into graphs and calculates the similarity between two graphs based on graph matching, dubbed as GMRec.
Specifically, we construct the graph of user groups and item groups and then calculate the graph similarity scores between user groups and item groups from two perspectives of feature matching and structure matching.
Experimental results show that our model achieves higher accuracy than state-of-the-art models on three industrial datasets with different group sizes, with a maximum improvement of 8.2\%.
Inhibiting tau-induced elevated nSMase2 activity and ceramides is therapeutic in murine Alzheimer’s disease
Authors: Tallon Carolyn , Bell Benjamin J , Malvankar Medhinee M , Deme Pragney , Nogueras-Ortiz Carlos , Eren Erden , Thomas Ajit G , Hollinger Kristen R , Pal Arindom , Mustapic Maja , Huang Meixiang , Coleman Kaleem , Joe Tawnjerae R , Rais Rana , Haughey Norman J , Kapogiannis Dimitrios , Slusher Barbara S
Published: July 2023

Background Cognitive decline in Alzheimer’s disease (AD) is associated with prion-like tau propagation between neurons along synaptically connected networks, in part via extracellular vesicles (EV). EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2(nSMase2)-mediated cleavage of sphingomyelin. We report, for the first time, that tau expression triggers an elevation in brain ceramides and nSMase2 activity.Methods To determine the therapeutic benefit of inhibiting this elevation, we evaluated the efficacy of PDDC, the first potent, selective, orally bioavailable, and brain-penetrable nSMase2 inhibitor, in the PS19 tau transgenic AD murine model. Changes in brain ceramide and sphingomyelin levels, Tau content, histopathology, and nSMase2 target engagement were monitored, as well as changes in the number of brain-derived EVs in plasma and their Tau content. Additionally, we evaluated the ability of PDDC to impede tau propagation in a murine model where an adeno-associated virus(AAV) encoding for P301L/S320F double mutant human tau was stereotaxically-injected unilaterally into the hippocampus and the contralateral transfer to the dentate gyrus was monitored.Results Similar to human AD, PS19 mice exhibited increased brain ceramides and nSMase2 activity; both were completely normalized by PDDC treatment. PS19 mice exhibited elevated tau immunostaining, thinning of hippocampal neuronal cell layers, increased mossy fiber synaptophysin immunostaining, and glial activation, all pathologic features of human AD. PDDC treatment significantly attenuated these aberrant changes. Mouse plasma isolated from PDDC-treated PS19 mice exhibited reduced levels of neuron- and microglia-derived EVs, the former carrying lower phosphorylated Tau(pTau) levels, compared to untreated mice. In the AAV tau propagation model, PDDC normalized the tau-induced increase in brain ceramides and significantly decreased tau spreading to the contralateral side.Conclusions PDDC is a first-in-class therapeutic candidate that normalizes elevated brain ceramides and nSMase2 activity leading to the slowing of tau spread in AD mice.
Differences in the absolute muscle strength and power of children and adolescents with overweight or obesity. A systematic review
Authors: ALANIZ-ARCOS José Luis , ORTIZ-CORNEJO Ma. Elena , LARIOS-TINOCO José Omar , KLÜNDER-KLÜNDER Miguel , Physical Karla VIDAL-MITZI. , GUTIÉRREZ-CAMACHO Claudia
Published: July 2023

This study aimed to describe absolute muscle strength and power in children and adolescents with obesity, overweight and normal weight, and the assessment tests and tools used. We retrieved observational studies from MEDLINE (PubMed), TripDataBase, Epistemonikos, EBSCO essentials, NICE, SCOPUS, and LILACs up to February 2023. In addition, we recovered data from studies with at least three comparison groups (obesity, overweight, normal weight) and with a description of the absolute muscle strength and power and the assessment tests and instruments used. The methodologic quality of the studies was assessed with the Joanna Briggs checklist, and the review was carried out using the PRISMA 2020 methodology. Eleven studies with 13, 451 participants aged 6 to 18 were included; upper limb absolute muscle strength was higher in overweight and obese compared to normal weight, but not when loading their body weight. In addition, lower limb absolute muscle strength was significantly lower in obese participants than in normal weight, regardless of age and gender. The most used tools to measure the absolute muscle strength of the upper limbs were the grip dynamometers and push-up exercises. In contrast, different jump tests were used to measure the power of the lower limbs. There are great differences in muscle strength and power between overweight or obese children and adolescents and those with normal weight. Therefore, it is recommended to use validated tests, preferably that assess strength through the load of the patient's body weight, either of the upper or lower limbs, for greater evaluation objectivity that facilitates the management of these children and adolescents.
Efficacy of Cytoreductive Surgery for Metastatic Upper Tract Urothelial Carcinoma: A Surveillance, Epidemiology and End Results (SEER) study of 508 patients
Authors: Hu Haopu , Lai Shicong , Wang Mingrui , Tang Xinwei , Lai Chin-hui , Wang Qi , Xu Kexin , Xu Tao , Hu Hao
Published: July 2023

Objective
To explore the role of cytoreductive surgery (CRS) in patients with metastatic upper tract urothelial carcinoma (mUTUC) receiving different types of adjuvant therapy.
Material and Methods
Data from 9,436 anonimized records was abstracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2008–2018. Of these, 508 individuals had received adjuvant therapy subsequent to being diagnosed with mUTUC. These patients had all been treated with adjuvant therapies such as chemotherapy and/or radiotherapy. Patients were stratified into either a non-surgical or surgical group based on CRS status before adjuvant therapeutics commenced. Kaplan-Meier curves were used to compare OS and CSS. Cox’s proportional hazard models were then used to analyze prognostic factors related to OS and CSS.
Results
Of the 508 cases, 36.8% (n = 187) had received CRS with adjuvant treatments. The remaining 63.2% (n = 321) received either chemotherapy and/or radiotherapy alone. Kaplan-Meier curves showed that 11.6% had 3-yr OS (95%CI 7.1–17.3) for CRS with adjuvant treatment and 4.9% (95%CI 2.7–8.0) for adjuvant treatment alone (p = 0.001). The 3-yr CSS was 14.9% for CRS plus adjuvant treatment (95%CI 9.4–21.7) and 6.0% (95%CI 3.4–9.8) for adjuvant treatments alone (p = 0.003). Under multivariate regression analysis, primary ureter site OS had a hazard ratio (HR) of 0.74 (95%CI 0.58–0.95, p = 0.019) and a CSS HR of 0.72 (95%CI 0.56–0.94, p = 0.014). The CRS OS HR was 0.79 (95%CI 0.65–0.95, p = 0.015) and the CSS HR was 0.75 (95%CI 0.61–0.92, p = 0.006). Additionally, chemotherapy had an OS HR of 0.46 (95%CI 0.33–0.0.65, p < 0.001) and a CSS HR of (0.44, 95%CI 0.31–0.63, p < 0.001). Bones and liver metastases were also indicative of poorer prognosis. Validation was conducted through subgroup analysis which suggested CRS was effective only for patients who received chemotherapy or combined chemo-radiotherapy but not for radiotherapy alone.
Conclusions
CRS provided significantly increased OS and CCS for mUTUC patients who received chemotherapy or combined chemo-radiotherapy in this study. In addition, the primary tumor and metastatic sites were related to improved patient survival although this was a small, relatively homogeneous sample therefore further research is required.
The Earliest Baltic Amber in Western Europe
Authors: Murillo-Barroso Mercedes , Cólliga Araceli Martín , Martinon-Torres Marcos
Published: July 2023

The expansion of Baltic amber through Europe has traditionally been associated to the spread of the Bell Beaker culture during the 3rd millennium BC. In Iberia, this phenomenon is particularly noticeable in the southern half. Here we present an amber bead recovered in a Late Neolithic funerary cave (3634 − 3363 2σ cal BC) from northeastern Iberia where more than 12 individuals had been buried. Fourier Transform Infrared Spectroscopy (FTIR) results of four samples revealed their complete resemblance with Baltic succinite reference spectra. Despite being a single bead, this finding provides the earliest evidence of the arrival of Baltic amber to the Mediterranean and Western Europe, before the Bell Beaker phenomenon and more than a millennium earlier than traditionally thought.
Sociodemographic disadvantage in the burden of stress and academic performance in medical school: implications for diversity in medicine
Authors: Eames Danielle , MS Shelby Thomas , Norman Kaden , Simanton Edward , Weisman Anne
Published: July 2023

Background
Nontraditional students bring to medicine inherent characteristics and perspectives that enrich the learning environment and contribute to expanding diversity in medicine. However, research has shown that these students, by virtue of their sociodemographic backgrounds, face unique challenges in medical education, which ultimately place them at a disadvantage compared to traditional medical students. The purpose of this study is to explore relationships between sociodemographic factors, stress, and academic performance, in the context of student outcomes that may influence diversity in medicine.
Methods
Perceived Stress Scale-4 surveys collected at four educational milestones and exam performance data on 358 of 360 students were utilized for the purposes of this retrospective observational cohort study. Using independent samples t-test, mean stress and academic performance were compared between groups based on generational status, underrepresented in medicine (URM) status, socioeconomic status, and age at matriculation. Results were considered significant where (P < .05).
Results
First-generation college students had significantly higher stress at the end of third year clerkships (mean 7.8 vs. 6.8, P= .03). URM students had significantly lower pre-clinical exam scores (mean 81.37 vs. 83.07, P = .02). Students who were 30 years of age or older at matriculation had significantly lower exam scores on all academic performance measures.
Conclusion
Expanding the sociodemographic diversity among physicians, and by extension, medical students, has long been recognized as an important avenue to address healthcare inequities for marginalized populations in the US. Results from our study suggest that aspects of medical education undermine the success of URM and older medical students, and thwart well-being in first-generation medical students. Residency program directors continue to use USMLE test scores as a primary metric to screen applicants. Therefore, poor performance on these exams has profound consequences on career trajectory which, in turn, may be impeding progress towards increasing diversity in medicine. Stress, depression, burnout, the learning environment, and academic performance are intimately related. A deeper understanding of the interplay between sociodemographic characteristics and success in medical school, both psychosocially and academically, is prudent to achieve diversity in medicine and, ultimately, health equity.
COVID-19 vaccination acceptance and hesitancy in health and care workers and the general population: a systematic review and policy recommendations
Authors: Silva Alessandra Pereira Pereira , Castaneda Luciana , de Oliveira Ana Paula Cavalcante , Fronteira Inês , Craveiro Isabel , Maia Leila Senna , Chança Raphael , Boniol Mathieu , Ferrinho Paulo , Poz Mario Roberto Dal
Published: July 2023

Introduction: The COVID-19 pandemic challenged the scientific community to find and develop a vaccine to fight the disease. However, and despite the vaccines developed thus far, problems with achieving high vaccine coverages have emerged, even among high-risk groups such as health and care workers (HCW). The lack of experience with such extensive vaccination created knowledge gaps in health policy and multisector decisions worldwide.
Objective: This systematic review aims to examine factors that influence HCW's adherence to COVID-19 vaccination and national policies to vaccinate the HCW and other target groups.
Methods: Searches were performed in the PubMed, Embase, Scopus, CINAHL, Web of Science, Lilacs, and WHO databases, besides Google Scholar for grey literature. The eligibility criterion for inclusion was being a member of the HCW. Vaccination was the target intervention, and the COVID-19 pandemic was the context. Qualitative synthesis used a meta-aggregation approach.
Results: Nineteen articles were included in the review, with study samples varying from 48 to 5,708 participants. Most of the evidence came from cross-sectional and qualitative studies. The main findings were related to vaccine hesitancy rather than acceptance. Factors associated with HCW vaccine hesitancy included subjective feelings such as safety concerns, related to rapid vaccine development, and insufficient testing. Non-adherence to vaccination by HCW can contribute to vaccine hesitancy in the general population. Countries have adopted few public policies to address this problem, and the main concern is whether to enforce vaccination and the extent to which measures are legal. Conclusion: Despite the large number of studies identified in the review, the quality of the evidence base remains weak. Skepticism, mistrust, and hesitancy toward vaccination are global issues that can jeopardize vaccination coverage. Governments need guidance to develop gender-specific policies to inform HCW and the public about the need to adhere to vaccination in the current and future pandemic scenarios.
Spatiotemporal evolution and inter-patient heterogeneity in primary and recurrent/metastatic head and neck squamous cell carcinoma
Authors: Kong Anthony , Bresadola Luisa , Weber David , Ritzel Christoph , Löwer Martin , Bukur Valesca , Akilli-Öztürk Özlem , Becker Julia , Schrörs Barbara , Vascotto Fulvia , Sahin Ugur , Mehanna Hisham
Published: July 2023

Head and neck cancer squamous cell carcinomas (HNSCCs) are heterogeneous in terms of origin and aetiology. In addition, there is uncertainty about the spatiotemporal genetic evolution from initial diagnosis to recurrence/metastasis (R/M) after primary treatments and further disease progression following systemic treatment. Changes in the genetic profile have implications on the selection of appropriate treatments for patients, especially in the era of targeted therapies and immunotherapies. Here, we analysed a cohort of 11 HNSCC patients with metachronous R/M, among whom nine had paired primary and R/M samples suitable for next-generation sequencing (multiple R/M samples collected at different time points were available for some of the patients). At the genomic level, the R/M samples shared a fraction of the somatic single nucleotide variants (SNVs) with the index primary tumours, but they also acquired many additional mutations, while losing only a few others. A similar behaviour was also observed when examining the changes of mutational signatures between primary and R/M samples. Overall, R/M appeared thus more genetically diverse than the respective primary tumours. The transcriptomic analysis showed that R/M samples had lower immune cell infiltration and several genes related to immune response were significantly downregulated compared to the primary samples. Our results underline the importance of analysing multiple samples per patient to obtain a more complete picture of the patient’s tumour and advocates a re-biopsy in the event of R/M and treatment failure, in order to select the most appropriate therapeutic strategy.
Smoke Exposure, Hemoglobin Levels, and the Risk of Anemia in Urban Informal Settlement in Southern Ghana
Authors: Appiah-Dwomoh Cyril , Tettey Prudence , Akyeampong Enoch , Amegbor Prince , Okello Gabriel , Botwe Paul , Quansah Reginald
Published: July 2023

Background: Even though there is evidence connecting smoke and its components to anemia, none of these studies were conducted on populations living in urban informal settlements. This study investigated the risks of anemia/HB levels in an informal settlement in Accra, Ghana. Smoke exposure was looked at from a variety of sources, including those in homes, neighborhoods, and places of work.
Methods: A questionnaire was administered during an interview to gather data on source of smoke exposure in the household, in the neighbourhood, and the workplace. A phlebotomist collected blood samples from the participants to assess their anaemia status.
Results
The population (n=329) had a high prevalence of anemia, with 49.1% of people fitting the WHO's definition of anemia, while the average hemoglobin level was 12.6±2.1g/dL. Anemia was associated with the number of different types of waste burntsimultaneously [(1 or 2: prevalence ratio (PR): 95% confidence interval (CI), 1.14, 0.99-1.28: 3+: 1.16, 1.01-1.63, p-for-trend=0.0082)], fuel stacking [(mixed stacking: 1.27, 1.07-1.20: dirty stacking:1.65, 1.19-2.25, p-for-trend=0.0062)], and involvement in fish smoking (1.22, 0.99-1.06). Reduced HB levels were associated with the number of different types of waste burnt simultaneously [(1 or 2: regression coefficient (β): 95% confidence interval (CI), -0.01, -0.97- -0.99: 3+: -0.14, -0.77- -0.05)], current smoker [(yes, almost daily: -1.40, -2.01- -0.79: yes, at least once a month: -1.14, -1.79—0.48)], SHS (yes, almost daily: -0.77, -1.30- -0.21), fuel stacking [(mixed stacking-0.93, -1.33--0.21: dirty stacking-1.04, -1.60- -0.48)], any smoke exposure indicator in the neighbourhood (-0.84, -1.43- -0.25), living close to a major road (-0.62, -1.09- -0.49), and fish smoking (-0.41,-0.93- -0.12).
Conclusion
Adult populations living in informal settlements may be at risk of anemia following exposure to smoke. Governments in developing nations should put in place pragmatic measures to control smoke emissions in informal settlements to protect human health and well-being.
Substrate promiscuity of Dicer toward precursors of the let-7 family and their 3'-end modifications
Authors: Dadhwal Gunjan , Samy Hebatallah , Bouvette Jonathan , El-Azzouzi Fatima , Dagenais Pierre , Legault Pascale
Published: July 2023

The human let-7 miRNA family consists of thirteen members that play critical roles in many biological processes, including development timing and tumor suppression, and their levels are disrupted in several diseases. Dicer is the endoribonuclease responsible for processing the precursor miRNA (pre-miRNA) to yield the mature miRNA, and thereby plays a crucial role in controlling the cellular levels of let-7 miRNAs. It is well established that the sequence and structural features of pre-miRNA hairpins such as the 5'-phosphate, the apical loop, and the 2-nt 3'-overhang are important for the processing activity of Dicer. Exceptionally, nine precursors of the let-7 family (pre-let-7) contain a 1-nt 3'-overhang and get mono-uridylated in vivo, presumably to allow efficient processing by Dicer. Pre-let-7 are also oligo-uridylated in vivo to promote their degradation and likely prevent their efficient processing by Dicer. In this study, we systematically investigated the impact of sequence and structural features of all human let-7 pre-miRNAs, including their 3'-end modifications, on Dicer binding and processing. Through the combination of SHAPE structural probing, in vitro binding and kinetic studies using purified human Dicer, we show that despite structural discrepancies among pre-let-7 RNAs, Dicer exhibits remarkable promiscuity in binding and cleaving these substrates. Moreover, the 1- or 2-nt 3'-overhang, 3'mono-uridylation and 3'-oligo-uridylation of pre-let-7 substrates appear to have little effect on Dicer binding and cleavage rate. Thus, this study extends current knowledge regarding the broad specificity of Dicer and provides novel insight regarding the effect of 3'-modifications on binding and cleavage by Dicer.