bluuebunny/crossref_metadata_2025 huggingface dataset:
INCIDENCE OF DRUG ADDICTION AND ALCOHOLISM IN THE RUSSIAN FEDERATION IN THE FIRST TWO DECADES OF THE XXI CENTURY. DYNAMICS AND MAIN TRENDS
Authors:   Bekhterev Psychoneurological Research Institute, St. Petersburg, Russia, Semenova N.V. , Vishnyakov N.I. ,   I.P. Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia, Kurkova E.S. ,   Bekhterev Psychoneurological Research Institute, St. Petersburg, Russia,   City Narcological Hospital, St. Petersburg, Russia, Skripov V.S. ,   Bekhterev Psychoneurological Research Institute, St. Petersburg, Russia,   I.P. Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia, Esina K.M. ,   Bekhterev Psychoneurological Research Institute, St. Petersburg, Russia, Tominina E.V. ,   Kirov Regional Narcological Dispensary, Kirov, Russia, Kulakov D.D. ,   Kirov Regional Narcological Dispensary, Kirov, Russia
Published: November 2022

Substance use disorders, despite their steady decline over the first 20 years of the 21st century, still remain one of the most important medical and social problems of modern times. Significant changes have been made both in the detection of substance use disorders and in the structure of the consumption of psychoactive substances. Purpose. To analyze dynamics in incidence of alcoholism and drug addiction in the Russian Federation as a whole and in the federal districts as well as to evaluate changes in the pattern of mental and behavioral disorders associated with psychoactive substance use. Material and methods. A retrospective analysis of the incidence of alcoholism and drug addiction, as well as the use of psychoactive substances with harmful consequences, was carried out in dynamics over the period from 2000 to 2020. Information for the analysis was obtained from the forms of the federal state statistical observation No. 11 "Information on the incidence of substance use disorders" for the indicated years. Information about the population size was obtained from the collections of the Federal State Statistics Service. Evaluation of relative values, including extensive and intensive coefficients, was carried out. Results. In general, in Russia, incidence of substance use disorders decreased 3.8 times from 2000 to 2020. However, some federal districts show deviations from certain trends observed in the Russian Federation. There has been a steady downward trend in the detection rate of alcoholism since 2003, which is accounted for by the anti-alcohol campaign launched at that time. Since 2000, there has been a sharp decline in drug addiction due to decreased number of opiate users. During the period under study, a number of bursts of growth in the drug addiction detection rate has been registered, associated with the appearance of desomorphine in 2005, and “designer” drugs and psychostimulants later on.
GPU Based Similarity Metrics Computation and Machine Learning Approaches for String Similarity Evaluation in Large Datasets
Authors: Baloi Aurel , Belean Bogdan , Turcu Flaviu , Peptenatu Daniel
Published: November 2022

The digital era brings up on one hand massive amounts of available data, and on the other hand the need of parallel computing architectures for efficient data processing. String similarity evaluation is a processing task applied on large data volumes, commonly performed by various applications such as search engines, bio-medical data analysis and even software tools for defending against viruses, spyware, or spam. String similarities are also evaluated in musical industry for matching playlist records with repertory records composed of song titles, performer artists and producers names, aiming to assure copyright protection of massmedia broadcast materials. Thus, the present paper proposes a GPU based approach for parallel implementation of the Jaro-Winkler string similarity metric computation. Further on, a thresholding-based algorithm is also implemented using GPU for matching records over large datasets. The global GPU RAM memory is used to store multiple string lines as raw data. In the case of a single string, its comparisons with the raw data are performed using the maximum number of available GPU threads and the stride operations. Moreover, based on the computed similarity metrics, an adaptive neural network approach guided by a novelty detection classifier together with a naive neural network implementation are proposed to increase the accuracy of the records matching procedure. Timing considerations and the computational complexity are detailed for the proposed approaches compared with state-of-the-art CPU and GPU approaches. A speed-up factor of 21.6 was obtained for the GPU based JaroWinkler implementation compared with the general purpose processor one, whereas improved accuracy for the records matching procedure was delivered using machine learning approaches.
The Cross-talk, Genetic Alteration, Molecular Functions, and Cluster Relevance of the Major Types of Regulated Cell Death in Bladder Cancer
Authors: Zhang Zhihong , Li Jingxian , Qi Yuanjiong , Liu Yang , Liu Xun , Li Shuai , Shi Jianxi , Gao Chao , Li Bo , Zhang Changwen , Du E
Published: November 2022

The dysfunction of regulated cell death (RCD) could cause human diseases such as cancer, neurodegeneration, autoimmune diseases, and infectious diseases. Recent studies have indicated that RCD has closely functional interaction. Our study aimed to explore the cross-talk, genetic alteration, functions, mechanism, and cluster relevance of the several major types of RCD, including apoptosis, ferroptosis, pyroptosis, necroptosis, autophagy-dependent cell death, in bladder cancer (BLCA). Through analyzing the public database, we found that the genes representing these five RCD types showed complex cross-talk in mRNA, protein levels, somatic mutation, and DNA copy number in BLCA. The mRNA expression of regulated cell death genes (RCDGs) was affected by DNA copy number, somatic mutation, DNA methylation, and RNA modification. Several RCDGs were essential for cell viability, and the expression of RCDGs was correlated with radiotherapeutic sensitivity and IC50 of chemotherapy drugs. Based on the expression of RCDGs, the BLCA patients were divided into two clusters. We found multiple immune-related pathways significantly enriched in cluster1/cluster2. In addition, the patients' prognosis, immune therapy response, and drug sensitivity in these two clusters were significantly different. Through the comparison between the RCD clusters and consensus cluster, we found that RCD cluster1 mainly correlated with the basal squamous cluster, and the RCD cluster2 mainly correlated with the luminal cluster. Through the weighted gene co-expression network analysis (WGCNA), we identified the high correlation RCDGs with cluster1/cluster2. We found that most cluster1-RCDGs were correlated with poor prognosis for patients, and most prognosis-protection genes correlated with cluster2. Besides, the expression of these prognosis-related RCDGs showed different distribution patterns in basal/luminal subtypes. In summary, our study conducted a comprehensive analysis of RCDGs in BLCA, which provided the foundation for subsequent experiments and therapeutic options.
Experience-dependent phosphoproteomic changes in hippocampus and neocortex correlate with the abundance of spindle oscillations during the transition between SWS and REM sleep
Authors: Souza Annie C. , Golbert Daiane C. F. , Cassoli Juliana S. , Sánchez-Gendriz Ignacio , Lima Vinícius V. F. , Cini Felipe A. , Martins-de-Souza Daniel , Ribeiro Sidarta
Published: November 2022

The role of sleep on memory consolidation is thought to involve experience-dependent changes in spindle oscillations and protein phosphorylation, but how these phenomena are related remains poorly understood. To gain insight into this relationship, we used electrophysiological recordings and quantitative phosphoproteomic analysis to assess spindle oscillations and phosphoprotein levels in the hippocampus (HP) and primary somatosensory cortex (S1) of adult male rats recorded across the sleep cycle. Animals were surgically implanted with multielectrode probes and after recovery were exposed or unexposed to novel objects (+ and – groups, respectively). HP and S1 samples were obtained after periods rich in either slow-wave sleep (SWS) or rapid-eye-movement sleep. Bottom-up shotgun mass spectrometry in a two-dimensional liquid chromatography-tandem mass spectrometry setup (MSE mode with label-free quantification) showed that the proteomes differed in the numbers of phosphoproteins identified by phosphoryl modification STY tags, with a total of 337 validated phosphoproteins identified in S1 and 198 in the HP. A comparison of the phosphoproteomic profiles of the treatments and regions (SWS+ versus SWS-, REM+ versus REM-, REM+ versus SWS+ and REM- versus SWS-), using clustering analysis of the significantly identified phosphoproteins, found that 51 phosphoproteins from S1 were sufficient to separate the four experimental conditions, while 37 phosphoproteins from the HP could only partially separate the groups. Fold change analysis identified 90 significantly modulated phosphoproteins related to synaptic function, actin-microtubule regulation, DNA-RNA binding, proteases-phosphatases-kinases and other regulatory functions, including CaMKII and MAPK. In both the HP and S1, nearly one third of the clustering-relevant phosphoproteins had levels significantly correlated with the abundance of spindle oscillations pooled across the transition from SWS to REM. In S1, phosphorylated Reelin was upregulated during REM compared to SWS, in proportion to the number of spindle oscillations during the transition from SWS to REM. In the HP, a voltage-gated calcium channel subunit (Cacna2d1) was down-regulated during REM+ compared to SWS+, in proportion to spindle counts. Since spindles facilitate calcium entry through the opening of voltage-dependent calcium channels, Cacna2d1 down-regulation may lead to a hippocampus-specific, REM-dependent downregulation of synaptic plasticity after exposure to novel objects. The results point to major experience-dependent differences between HP and S1 in phosphoproteomic regulation across the sleep cycle, with potential implications for memory corticalization.
Risk Assessment of Human Monkeypox Infections for Vaccine Prioritization
Authors: Zucker Roy , Lavie Gil , Sagy Yael Wolff , Arieh Noa Gur , Markovits Hila , Abu-Ahmad Weissam , Battat Erez , Ramot Noga , Beckenstein Tanya , Carmeli Guy , Mark-Amir Avner , Wagner-Kolasko Gal , Edry Amos , Duskin-Bitan Hadar , Yaron Shlomit , Peretz Alon , Netzer Doron , Arbel Ronen
Published: November 2022

Background
The global supply of vaccines against monkeypox virus infection (MPXVi) is significantly lower than demand. Evidence-based vaccine prioritization criteria, based on risk assessment, are essential for fair vaccine distribution. Our objective was to identify the characteristics of individuals at the highest risk for MPXVi.
Methods
This population-based cohort study included all Clalit Health Services (CHS) subjects assumed to be at risk for MPXVi, based on known characteristics of infected subjects worldwide and insights of LGBTQ+ -specialized CHS clinicians. Cox hazards models were used to identify risk factors for MPXVi in the study cohort. The study commenced on June 6, 2022, the date of the first known MPXVi in CHS patients, until July 31, 2022, when the MPXV vaccination campaign started.
Results
8,088 individuals (0.18% of the CHS total population) were identified according to the study inclusion criteria. Of those, 69 (0.85%) were infected during the study period. Risk factors for MPXVi were birth in 1980 or later, history of syphilis, HIV-PrEP use, PDE5 inhibitors use, recent STIs, and registeration to primary healthcare clinics in the Tel-Aviv district. No infections were observed in individuals with none of the factors. Individuals with 3+ risk factors had a 20-fold higher risk for MPXVi compared to those with 0-2, with 85.5% sensitivity and 77.8% specificity.
Conclusions
Counting the number of validated risk factors per individual seems to provide a robust, simple risk score for MPXVi. Weighting individuals’ risk levels against vaccine availability can assist health systems in the equitable prioritization of vaccine allocation.
Large and fast excitatory transcriptomic neuron types in human cortex preferentially express genes of intelligence and HARs.
Authors: Driessens Stan , Driessens Stan , Heyer Djai , Pieterse Isabel , Wilbers René , Mertens Eline , Waleboer Femke , Heistek Tim , Coenen Loet , Idema Sander , Hamer Philip de Witt , Noske David , de Kock Christiaan , Lee Brian , Smith Kimberly , Ting Jonathan , Lein Ed S. , Mansvelder Huibert , Goriounova Natalia
Published: November 2022

Human intelligence is a highly heritable trait, and GWAS have yielded numerous associated genes. These genes overlap with human accelerated regions (HARs) implicated in human brain evolution and might act on the same biological processes. Here, we investigated whether genes associated with human cognition and HAR genes are similarly expressed in adult human cortical neurons and brain areas of cognition, and how their expression relates to neuronal function and structure. We find that these gene sets are preferentially expressed in L3 excitatory neurons in middle temporal gyrus (MTG). Furthermore, neurons with higher expression had larger dendrites and faster action potential kinetics, properties previously linked to intelligence. Finally, we identify a subset of genes associated with dendritic length, with predominantly synaptic functions and high abundance of HARs. Our results indicate that mechanisms underlying human brain evolution and interindividual differences in intelligence might share genetic origin and manifest in specific neuronal types.
The experience of being a caregiver of patients with digestive cancer, from patients and caregivers' perception: a mixed study.
Authors: GRIVEL Charlotte , NIZET Pierre , MARTIN Manon , PECOUT Solange , LEPEINTRE Aurélie , TOUCHEFEU Yann , PROT-LABARTHE Sonia , EVIN Adrien , HUON Jean François
Published: November 2022

Objective
To explore the experience of caregivers of patients with digestive cancer and to compare the perspectives of patients and caregivers.
Methods
Caregiver-patient dyads were enrolled in this mixed-methods study. The Caregiver Reaction Assessment (CRA) and the Supportive Care Needs Survey for Partners and Caregivers (SCNS-PC) questionnaires were distributed to caregivers. Semi-structured interviews with the dyads were conducted.
Results
Thirty-two caregivers completed the questionnaires. Responses showed high self-esteem, schedule burden, and a need for care and information services. Ten dyads participated in the interviews. Three themes emerged from the caregiver’s interviews: illness is an upheaval; loneliness and helplessness are experienced; caring is a natural role with positive outcomes. Four themes emerged from patient's interviews: the caregiver naturally assumes the role and gets closer; he is the patient's anchor; his life is disrupted; anxiety and guilt accompany the desire to protect him. In comparing patient and caregiver data, we identified many similarities. The main theme of disagreement was their relationship.
Conclusions
Caregiver care does not appear to be optimal, particularly in terms of their need for information. Even though the patients have a fairly good representation of their caregiver’s experience, their opinion and their communication still need to be considered.
Outcomes after first IVF/ICSI attempts (fresh and frozen) differ between overweight and obese patients
Authors: Pretalli Jean-Baptiste , Pithois Alixane , Tio Grégory , Frontczak-Franck Sophie , Briet Maïté , Mauppin Camille , Roux Christophe
Published: November 2022

Background
Women with high body mass index (BMI) may have reduced natural fecundity and compromised In vitro fertilization outcomes. However, data are discordant.. Our objective was to evaluate the relationship between BMI and outcomes of IVF and/or ICSI, for the first fresh embryo transfers, and for complete (fresh and frozen) cycles.
Methods
We included 1912 consecutive cycles; 1286 (67.3%) first fresh embryo transfers and 626 (32.7%) frozen embryo transfers, all performed between 01/01/2013 and 12/31/2018 in the Department of Reproductive Medicine and Biology - Cryobiology of the University Hospital of Besançon (France). The study population comprised infertile women undergoing IVF/ICSI treatment divided into 3 groups :obese, overweight and normal BMI.
Results
The cumulative live birth rate (after fresh and frozen cycles) was lower in overweight women compared to those with normal BMI (respectively 110/421 (26.1%) vs 406/1273 (31.9%), p = 0.025), while there was no significant difference between obese (58/214 (27.1%)) and normal BMI women. The cumulative clinical pregnancy rate was lower for overweight women compared to normal BMI (respectively 128/421 (30.4%) and 467/1277 (36.6%), p = 0.021), but did not differ between obese (66/214 (30.8%)) and normal BMI women.
Conclusion
Our results raise questions about the optimal management of women undergoing IVF/ICSI. They highlight complexity of management for women with high BMI. Further research is warranted to clarify the exact contribution of overweight and obesity to outcomes. Pending further research, we might consider overweight to be as impairing as obesity in this setting.
Label-free adaptive optics single-molecule localization microscopy for whole animals
Authors: Choi Wonshik , Park Sanghyeon , Jo Yonghyeon , Kang Minsu , Hong Jin Hee , Ko Sangyoon , Kim Suhyun , Park Sangjun , Park Hae-Chul , Shim Sang-Hee
Published: November 2022

The specimen-induced aberration has been a major factor limiting the imaging depth of single-molecule localization microscopy (SMLM). Here, we report the application of label-free wavefront sensing adaptive optics to SMLM for deep-tissue super-resolution imaging. The proposed system measures complex tissue aberrations from intrinsic reflectance rather than fluorescence emission and physically corrects the wavefront distortion more than three-fold stronger than the previous limit. This enables us to resolve sub-diffraction morphologies of cilia and oligodendrocytes in whole intact zebrafish as well as dendritic spines in thick mouse brain tissues at the depth of up to 102 µm with localization number enhancement by up to 37 times and localization precision comparable to aberration-free samples. The proposed approach can expand the application range of SMLM to intact animals that cause the loss of localization points owing to severe tissue aberrations.
Renewable and non-renewable energy consumption, economic growth and Ecological footprint relationship in the top Russian energy importers: A panel data analysis
Authors: Öncel Abidin , Kabasakal Ali , Kutlar Aziz , Acar Samet
Published: November 2022

This study examines the relationship between renewable and non-renewable energy consumption, economic growth, and EF for the top 14 Russian energy importing countries in the 2000-2018 period. Through PVAR analysis, this study calculates the long-term correlation between variables using a VEC model. The VAR approach addresses the endogeneity issue by including endogenous interactions between the variables in the model. Additionally, the impulse response functions and the influence of various variables on certain lags are evaluated. Cointegration between variables was evaluated using DOLS and FMOLS panel analysis to evaluate the long-term link further. Our findings demonstrate that there is a cointegration relationship between all series. According to the impulse response analysis results, an energy shock from Russia will negatively affect the countries' economic growth and decrease the EF. Increasing both PEC and REC domestically increases EF, but the effect of REC on EF seems to be a little less. According to DOLS findings, a 10 percent increase in LNFUELS increases the elasticity of LNPGDP by 0.61%.In contrast, FMOLS findings indicate a 10% increase in the EF or LNFUELS, increasing the elasticity of LNPGDP by 1%. Although the direction of the relationship is positive when EF is considered the dependent variable, while the PEC elasticity coefficient was 0.030 in the DOLS model, it was found to be 0.023 in the FMOLS model. The elasticity value of the LNPGDP variable was found to be 0.69 in the FMOLS model.
JEL CODES: O13; O44; C59, Q56
Chronological measurement of effector CD8 T cell activity using a bioluminescence-based cell viability assay
Authors: Hayashi Ryota , Nakatani Hayato , Kawahata Hinami , Fujie Ryonosuke , Kurowarabe Kaoru , Hayasaka Haruko
Published: November 2022

Background
Although cell-mediated cytotoxicity has been evaluated with various protocols, methods for monitoring cytotoxicity in a time series have not been established. This work describes a method for evaluating cytotoxicity using a real-time luminometer.
Materials & Methods
The efficiency of effector CD8 T cell expansion from melanoma-bearing splenocytes was analyzed. The effect of CD8 T cells on the viability of luciferase-expressing target cells was measured by bioluminescence.
Results
Melanoma-specific effector CD8 T cells were differentiated by in vitro coculture. The melanoma cell growth was significantly inhibited in the presence of in vitro expanded activated T cells inthe bioluminescence-basedtime-lapse analysis.
Conclusion
The bioluminescence-based assay is a useful method for monitoring the time course of cell viability of target tumor cells.
Audiological benefit, quality of life, and factors associated with functional gain in elderly hearing aid users in a developing country between 2017 and 2020: A pre- post-study
Authors: Peñaranda Daniel , Pérez-Herrera Lucia C. , Moreno-López Sergio , Noguera Lucia , Hernández Diana , Martínez Daniel , Peñaranda Augusto
Published: November 2022

Background: Sensorineural hearing loss (SNHL) is the most common auditory deficit in older adults and may lead to quality-of-life deterioration. However, few studies have been performed in low/middle-income countries, particularly in Latin America. This study aimed to assess the audiological benefit, quality of life, and factors associated with functional gain in elderly hearing aid users in the Fundación Santa Fe de Bogotá and UNIMEQ-ORL, two otology referral centers in Colombia.
Design: Pre-post study that included hearing aid users at the otology consult of the Fundación Santa Fe de Bogotá and UNIMEQ-ORL between June 2017 and December 2020. Glasgow Benefit Inventory (GIB) and Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaires were applied. Audiometric (0,5kHz to 4kHz) and logoaudiometric results were collected.
Results: A total of 75 participants (132 ears) were included. The mean age was 70.73 years (SD: 12.66). The median hearing aid use in years was 0.71 (IQR: 0.64-0.90). Mean change in logoaudiometry was -26.53dB (95%CI: -28.09, -24.97; p<0.001), in functional gain was -21.75dB (-23.81, -19.68; p<0.001). The mean changes in the APHAB domains were Ease of Communication: -37.85 (95%CI: -43.01; -32.7), Background Noise: -3.51 (-6.06; -0.95), and Aversiveness of Sounds: -6.9 (-2.04; 11.77). The GBI assessment of quality of life showed improvement in 100% of the population after the use of hearing aids. The number of years of hearing aids use was associated with functional gain.
Conclusion: The number of years of hearing aids use may impact on the functional gain in these populations. A significant clinical benefit was found in terms of quality of life, communication, and reverberation related to the use of hearing aids. Access to hearing aids should be granted, and public health strategies are needed to grant the access to hearing rehabilitation in these populations.
Trial registration: Fundación Santa Fe de Bogotá (Protocol Number: CCEI-12666-2020)
Ultra-compacted single self-amplifying RNA molecules as quintessential vaccines
Authors: Herrero Jorge Moreno , Stahl Theo , Erbar Stephanie , Maxeiner Konrad , Schlegel Anne , Bacic Tijana , Cavalcanti Leide , Schroer Martin , Svergun Dmitri , Sahin Ugur , Haas Heinrich
Published: November 2022

We introduce aqueous phases comprising single, highly compacted self-amplifying messenger RNA (saRNA) molecules, that are suitable for prophylactic and therapeutic application, specifically for vaccination against infectious diseases. The formulations are formed in the presence of the positively charged polymer polyethylenimine (PEI), which leads to condensation of the single saRNA molecules into a globular organization with high packing density, low mass fraction of polymer, and, consequently, very small size. In this format, they display improved biological activity in comparison to previously described saRNA/PEI nanoparticlulate formulations, both in vitro and in vivo. Application of the ultra-compacted single saRNA formulation for vaccination, via intramuscular route, results in relevant titers for practical use at lower doses compared to the nanoparticle formulations. These novel saRNA vaccine products can be obtained by straight-forward manufacturing routes, and they can be readily frozen or lyophilized. With these characteristics they can be particularly of interest for future vaccine products even for application under challenging conditions, where requirements such as high activity, good thermostability, low cost of goods, and facilitated logistics need to be fulfilled at the same time.
One-Sentence Summary: single saRNA molecules, condensed into an unusually compact globular organization with very small size by an oppositely charged polyelectrolyte (polyethylenimine), are applicable as vaccines, which induce very strong immunological responses at very low doses.
Adsorption and degradation of neonicotinoid insecticides in agricultural soils
Authors: Li Yang , Li Yadong , Bi Guihong , Ward Timothy , Li Lin
Published: November 2022

The adsorption and degradation of seven commercially available neonicotinoid insecticides in four types of agricultural soils from three states (Mississippi, Arkansas, and Tennessee) in the United States were studied. The adsorptions of all the neonicotinoids fit a linear isotherm. The adsorption distribution coefficients (Kd) were found to be below 2.0 L/kg for all the neonicotinoids in all the soils in Mississippi and Arkansas. Only in the Tennessee soil, the Kd ranged from 0.96 to 4.21 L/kg. These low values indicate a low affinity and high mobility of these insecticides in the soils. The soil organic carbon-water partitioning coefficient Koc ranged from 349 to 2569 L/kg. These Kd values showed strong positive correlations with organic carbon content of the soils. The calculated Gibbs energy change (ΔG) of these insecticides in all the soils ranged from − 14.6 to -19.5 kJ/mol, indicating that physical process was dominant in the adsorptions. The degradations of all these neonicotinoids in the soils followed a first-order kinetics with half-lives ranging from 33 to 305 d. The order of the insecticides with decreasing degradation rate is: clothianidin > thiamethoxam > imidacloprid > acetamiprid > dinotefuran > thiacloprid > nitenpyram. The moisture content, clay content, and cation exchange capacity showed positive effects on the degradation rate of all the neonicotinoids. The Groundwater Ubiquity Score (GUS) calculated from the adsorption distribution coefficient, organic content, and half-life indicates that, except for thiacloprid, all the neonicotinoids in all the soils are possible leachers, having potentials to permeate into and through groundwater zones.
Sex influences Blood Pressure but not Blood Pressure Variability in response to Dietary Sodium and Potassium in Salt-Resistant Adults
Authors: Ramos-Gonzalez Macarena , Smiljanec Katarina , Mbakwe Alexis , Lobene Andrea , Pohlig Ryan , Farquhar William , Lennon Shannon
Published: November 2022

Dietary sodium and potassium have been shown to affect blood pressure (BP) but their influence on BP variability (BPV) is less studied as is the influence of sex. The aim of this study was to compare 24-h BP and short-term BPV in response to varying dietary levels of sodium and potassium in healthy non-obese normotensive salt-resistant adults. We hypothesized that high sodium would increase short-term BP and BPV while the addition of high potassium would counteract this increase. Furthermore, we hypothesized that women would experience greater increases in BPV under high sodium conditions compared to men while potassium would attenuate this response. Thirty-seven subjects (17M/20W; 27 ± 5 years old; BMI 24.3 ± 3 kg/m2) completed seven days each of the following randomized diets: moderate potassium/low sodium (MK/LS), moderate potassium/high sodium (MK/HS) and high potassium/high sodium (HK/HS). BP and short-term BPV were assessed using 24-h ambulatory BP monitoring starting on day 6. BPV was calculated using the average real variability (ARV) index. Twenty-four hour, daytime, and nighttime systolic BP (SBP) were lower in women compared to men regardless of diet. However, 24-h and daytime SBP were lowered in women on the HK/HS diet compared to the MK/HS diet. There were no significant effects of diet or sex for 24-h, daytime or nighttime SBP ARV. However, men exhibited a higher 24-DBP ARV than women regardless of diet. In conclusion, a high potassium diet lowered BP under high sodium conditions in women alone while men exhibited higher short-term BPV that was not influenced by diet.
Antioxidant combination inhibits angiogenesis in diabetic retinopathy by targeting VEGF/PI3K/AKT signaling
Authors: Zhang Bei , Zhou Dong , Jiang Yi , Liu Zhinan , Zhang Jun , Xie Keren , Deng Guohua
Published: November 2022

Background: Angiogenesis is one of the main hallmarks of diabetic retinopathy (DR), and antioxidants have shown some therapeutic effects in DR.
Objective: To investigate the effect and mechanism of action of antioxidant combination on angiogenesis in the process of DR.
Methods: Human retinal microvascular endothelial cells (HRMECs) were exposed to high-glucose (HG) and then treated with antioxidants: N-acetylcysteine (NAC) and/or taurine (TAU). HRMECs were assayed for proliferation, migration, apoptosis, and angiogenic capacity. A rat model of DR was induced using streptozotocin (STZ). HE staining was used to observe the retinal thickness of rats. apoptosis was detected by TUNEL assay. protein expression in VEGF/PI3K/AKT pathway was detected by Western blot.
Results: HRMECs showed enhanced cell proliferation and migration and reduced apoptosis after exposure to HG, whereas antioxidant treatment attenuated the survival of HRMECs. In addition, the total retinal thickness of DR model rats was very thin, and antioxidant treatment, especially their combined application, significantly thickened their retinas and greatly reduced the level of apoptosis. western blot assays showed that antioxidants may act by inhibiting the activation of VEGF/PI3K/AKT pathway.
Conclusion: Antioxidants may inhibit angiogenesis by inhibiting VEGF/PI3K/AKT signaling, thereby improving the extent of DR.
Information Use, Seeking Behaviors, and Barriers to Evidence-Based Information at a Large Teaching Hospital in the UK
Authors: Lagojda Lukasz , O'Connell Bridget , Brown Anna , Dekker Natasha S. den
Published: November 2022

Background: In order to better understand the needs of service users, this study explored
the information use and the factors affecting access to evidence-based information by clinicians
in a primary care setting.
Methods: An online survey was distributed to all staff
via SurveyMonkey®. Data were curated in Microsoft Excel and managed using SPSS v26.
Graphs were generated using GraphPad PRIMS.
Results: Ninety-three per cent of the surveyed
clinicians used evidence-based information in practice, primarily for patient care and
education. Clinicians employed a range of seeking behaviors to retrieve this information,
which varied based on how often this information was needed. The barriers to evidencebased
information varied between clinical professions but ‘time’ was the most consistent
factor. The belief of evidence-based practice being not part of the job role was the overwhelming
factor for not using evidence-based information.
Conclusions: The findings of this
study are consistent with previous reports describing significant impact of time and access to
IT resources on whether search for evidence-based information and provided us with useful
insights for improving our services.
‘We could easily get HIV infection here': the voice of incarcerated young people in Malawi's semi-urban prisons
Authors: Nkambule Ellen , Herce Michael , Wella Kondwani , Mbakaya Balwani Chingatichifwe
Published: November 2022

Introduction: People incarcerated in Malawi's detention facilities face a lot of problems. The most common challenges are overcrowding, poor sanitation, and lack of access to basic needs such as adequate food, bedding, clothing, security, and health care. In addition, young people are vulnerable to sexual abuse.
Methods: A qualitative approach using an exploratory study design was used to explore the experiences of incarcerated young people in semi-urban prisons. Ethical approval for the study was obtained from Malawi’s National Health Science Research Committee. Two focus group discussions (FGD) were conducted; involving six young incarcerated people aged 18 in each group. Focused groups followed a semi-structured interview guide; data was analyzed using thematic analysis.
Results: The following four themes emerged from the data: prisoner-on-prisoner sexual violence; the need for communication regarding sexual violence; trauma associated with incarceration; and youth surviving prison life. The young incarcerated people reported being given incentives such as extra food and adequate sleeping space in exchange for sexual favours with adult incarcerated people or individuals with leadership roles. The sexually abused victims have had some difficulties in reporting the incidences due to a non-existent reporting system for such matters to prison authorities.
Conclusions: This study reveals that the prison environment in Malawi is unsafe, particularly for young incarcerated people who are at an increased risk of being victims of sexual violence. The young people reported being more likely to be sexually abused when accommodated together with adult prisoners. Unfortunately, the perpetrators of sexual abuse are typically incarcerated adults in supervisory roles. Therefore, young people need special protection in prisons. We recommend that the youths should be separated from adults according to the United Nations Office on Drugs and Crime (UNODC) recommendations. The correction officers should prevent the young inmates from having sight or physical contact with adult incarcerated people while in housing units. We further recommend that prisons establish systems where abused inmates can report abuse without fear of retribution.
USP18 is an essential regulator of muscle cell differentiation and maturation
Authors: Olie Cyriel , Pinto-Fernández Adán , Damianou Andreas , Vendrell Iolanda , Mei Hailiang , Hamer Bianca den , Wal Erik van der , de Greef Jessica , raz vered , Kessler Benedikt
Published: November 2022

Muscle degeneration, a key feature in a wide range of human pathologies, is typified by impaired proteastasis, in which the ubiquitin proteasomal system in particular plays an important role. Yet, little is known about the function of deubiquitinating enzymes (DUBs) in muscle cell biology. We performed a genetic screen to identify DUBs regulators of muscle cell differentiation. Surprisingly, we observed that USP18-depletion induced differentiation and reduced proliferation of muscle cells. USP18 enzymatic function typically attenuates the immune response by removing ISG15, but in muscle cells, we found that USP18 regulates differentiation independent of ISG15 and the IFN-1 pathway. USP18 accumulation in muscle cell nuclei was concomitant with reduced expression of the cell-cycle gene network and altered transcription-regulated gene networks, including myogenic transcription factors. Additionally, USP18-depletion altered calcium channel gene networks, which was in line with reduced calcium flux in myotubes. Reduced sarcomeric genes were linked to reduced contractile force in an engineered muscle model. Our results revealed nuclear USP18 as a critical regulator of differentiation initiation and differentiation maintenance, independent of the IFN-1 pathway.
Effects of Repetitive Functional Magnetic Stimulation in the sacral nerve in patients with neurogenic detrusor overactivity after suprasacral spinal cord injury: a study protocol for a randomized controlled trial
Authors: Li Jiyang , Wang Jianxiong , Hu Yue , Jian Rui , Zhao Yulu , Li Dan , Wan Tenggang , Jike Wuga , Xu Fangyuan , Huang Maomao
Published: November 2022

Background

Neurogenic detrusor overactivity (NDO) is a serious and common complication after spinal cord injury, affecting patients' quality of life. Therefore we developed this research protocol to evaluate the efficacy of repetitive functional magnetic stimulation (rFMS) in the sacral nerve in patients with neurogenic detrusor overactivity (NDO) after suprasacral spinal cord injury (SCI) and provide more options for rFMS in treating NDO after suprasacral SCI.

Methods

This study is a single-center, randomized, parallel-group clinical trial. The sample size is 62, including 31 patients and 31 controls who will receive magnetic stimulation. We will recruit the patients with NDO after suprasacral SCI in the Rehabilitation Department of the Affiliated Hospital of Southwest Medical University from September 2022 to August 2023. They will be assigned to the rFMS group and the sham stimulation group randomly. The rFMS group will receive real rFMS treatment of the sacral nerve (100% stimulation intensity, 5 Hz, twenty minutes each time, five times a week), and the sham group will receive sham stimulation. Both groups will receive similar treatment strategies, including medication, standard urine management, acupuncture treatment, and health evangelism. The bladder capacity, maximum detrusor pressure (Pdet) and pudendal nerve electromyography will be evaluated at baseline, 8th week of treatment. The residual volume of the bladder and bladder diary will be recorded once a week during 8 weeks of treatments. SCI-QOL and NBSS will be evaluated at baseline, the 4th and 8th week of treatment. In addition, the above assessments will be followed up at 8 weeks after the end of treatment.

Discussion

It is expected that the bladder function, symptoms and quality of life might be significantly improved after rFMS of the sacral nerve.
Trial registration: The China Clinical Trials Registry has approved this study, registration number: ChiCTR2100045148.
Primary central nervous system lymphoma in children - a rare but serious disease with good prognosis from a single center in China
Authors: Duan Yanlong , Gao Huixia , Zhou Chunju , Jin Ling , Yang Jing , Huang Shuang , Zhang Ningning , Zhang Meng , Yang Xueliang , Zhang Yonghong , Wang Tianyou
Published: November 2022

Objective:To discuss the clinical efficacy of systemic chemotherapy based on HD-MTX combined with IT therapy in children with PCNSL, and to increase the understanding of the treatment of children with PCNSL.
Methods: We reviewed the clinical data, treatment regimens and survival status of 12 children diagnosed with PCNSL in Beijing Children's Hospital, Capital Medical University, during the past 10 years. We retrospectively reported information on PCNSL in children from Eastern countries.
Results:Twelve patients among 1500 with non-Hodgkin lymphoma (NHL) were diagnosed with PCNSL in Beijing Children’s Hospital in the past ten years. The male: female ratio was 4:1, and the median age was 5.9 yr (2.3-13.9 yr). The primary sites were ventricle, cerebellum, spinal cord, and spinal canal, each of which was represented by one case; the remaining eight cases were all in multiple areas. Their pathologic diagnoses were lymphoblastic lymphoma in six cases, Burkitt lymphoma in three, anaplasticlarge cell lymphoma (ALCL) in two and diffuse large B-cell lymphoma (DLBCL) in one. All patients received a high-dose methotrexate (HD-MTX)-based induction chemotherapy regimen combined with intrathecal (IT) chemotherapy (methotrexate, cytarabine, dexamethasone) that was administered 10 to 26 times (median 16 times). None of the patients had RT as a first-line treatment. As the understanding of this disease has been updated, patients with invasive mature B-cell origin are no longer receiving rituximab chemotherapy, and the duration of maintenance therapy is gradually shortening. No patient had recurrence or treatment-related mortality.
Conclusions: PCNSL is a rare childhood disease that can be successfully treated with HD-MTX-based systemic chemotherapy combined with IT chemotherapy rather than craniospinal RT.
A longitudinal study of children with COVID-19 in outpatient centers in terms of clinical manifestations, hospitalization, antibiotic prescription, and the number of COVID-19 times
Authors: Hosseininasab Ali , Alidousti Katayoun , Jafari Maedeh , Ebrahimpour Maryam
Published: November 2022

Background:A few months after the first description of COVID-19 in China, there was evidence that this serious problem was increasing worldwide. The SARS-CoV-2 virus has several subtypes with different characteristics. The disease is mild in children, and patients with this infection are generally not expected to receive antibiotics. This study aimed to focus on the number of times a person gets sick with COVID-19 and the use of antibiotics due to secondary bacterial infections in outpatient children.Methods:From February 2020 to August 2022, children aged <15 years diagnosed with SARS-CoV-2 infection were studied regarding clinical manifestations, need for hospitalization, antibiotic prescription, and the number of COVID-19 infection times.Results:Of 2448 children with the final diagnosis of COVID-19, 65% were boys, 192 people (7.84%) were infected with COVID-19 twice, 35 (1.43%) three times, 7 (0.29%) four times, and 2 (0.14%) five times, and 143 (5.84%) needed hospitalization. The prevalence of antibiotic use was 17.73% (n = 434); Acute bacterial sinusitis (12.21%) and middle ear infection (8.52%) were the most common known reasons for an antibiotic prescription, respectively.Conclusions:Several subtypes of SARS-CoV-2 have different clinical behaviors in the age group of children. A person may be infected with COVID-19 several times. The use of antibiotics in outpatients is insignificant and mostly limited to acute sinusitis and middle ear infection.
Narrow bandwidth, low-emittance positron beams from a laser-wakefield accelerator
Authors: Streeter Matthew , Colgan Cary , Cavanagh Niall , Los Eva , Antoine Andre , Audet Thomas , Balcazar Mario , Calvin Luke , Cardarelli Jason , Ahmed Hamad , Kettle Brendan , Ma Yong , Mangles Stuart , Najmudin Zulfikar , Rajeev Paramel Pattathil , Symes Dan , Thomas Alexander , Sarri G
Published: November 2022

Laser-wakefield accelerated electron beams have been demonstrated to be a viable alternative to those produced by radio-frequency systems, with unique characteristics including intrinsic femtosecond-scale duration and micron-scale source size. In addition, they present the practical advantage of a generally compact and cost-effective setup inherently synchronsed with a high-power laser. The rapid progress experienced by these accelerators is now posing the question as to whether they could be included in the design of the next generation of electron-positron colliders. However, the asymmetry of the accelerating wake-fields presents challenging complications on positron acceleration. Despite considerable numerical work on positron wakefield acceleration, this area of research has thus far experienced limited experimental progress due to the lack of positron beams suitable to seed a plasma accelerator.
Here, we experimentally demonstrate that moderate power lasers ($\approx$ 100 TW peak power) can generate ultra-relativistic positron beams with sufficient spectral and spatial quality to be injected in a plasma accelerator. Our results indicate, in agreement with numerical simulations, selection and transport of positron beamlets with a 5\% bandwidth around 600 MeV, with femtosecond-scale duration and micron-scale normalised emittance. It is proposed that beams with these characteristics are readily suited for experimental studies of positron acceleration in a plasma wakefield.
Gallium-68 labelled RGD PET/CT imaging of endothelial activation in COVID-19 patients
Authors: Genugten Evelien A.J. van , Lith Theresa J. van , Heuvel Frederik M.A. van den , Steenis Josee van , Heggeler Romy M. ten , Brink Monique , Rodwell Laura , Lobeek Daphne , Have Wanda Hagmolen of ten , de Veerdonk Frank L. van , Netea Mihai G. , Prokop Mathias , Nijveldt Robin , Tuladhar Anil M. , Aarntzen Erik H.J.G.
Published: November 2022

In coronavirus disease 2019 (COVID-19), endothelial cells play a central role and inadequate response is associated with vascular complications. PET imaging with gallium-68 labelled RGD-peptide (68Ga-RGD) targets αvβ3 integrin expression which allows quantification of endothelial activation. In this single-center, prospective observational study, we included ten hospitalized patients with COVID-19 between October 2020 and January 2021. Patients underwent 68Ga-RGD PET/CT followed by iodine mapping of lung parenchyma. CT-based segmentation of lung parenchyma, carotid arteries and myocardium was used to quantify tracer uptake by calculating standardized uptake values (SUV). Five non-COVID-19 patients were used as reference. The study population was 68.5 (IQR 52.0-74.5) years old, with median oxygen need of 3 l/min (IQR 0.9-4.0). 68Ga-RGD uptake quantified as SUV ± SD was increased in lungs (0.99 ± 0.32 versus 0.45 ± 0.18, p < 0.01) and myocardium (3.44 ± 1.59 versus 0.65 ± 0.22, p < 0.01) of COVID-19 patients compared to reference but not in the carotid arteries. Iodine maps showed local variations in parenchymal perfusion but no correlation with SUV. In conclusion, using 68Ga-RGD PET/CT in COVID-19 patients admitted with respiratory symptoms, we demonstrated increased endothelial activation in the lung parenchyma and myocardium. Our findings indicate the involvement of increased and localized endothelial cell activation in the cardiopulmonary system in COVID-19 patients.
Trail registration
NCT04596943
Siting central venous catheters precisely by means of the ECG method - A Reliability Study
Authors: Schummer Wolfram
Published: November 2022

Introduction: For central venous catheters (CVC) to function properly, optimal tip location is of utmost importance.
One technique to verify CVC position is the ECG method. Nowadays, the ECG method is applied using the maximum P-wave amplitude (P-max).
The hypothesis is that a method believed to be precise in assessing CVC position can provide the same results for CVC tip positions regardless of their respective insertion sites.
Methods: Only critically ill patients with multiple organ dysfunction were eligible for the study. Another condition was a prerequisite for reliable illustration of the results, i.e. at least two central venous lines had to be in place. All catheters were placed using the ECG method with the CVC tip at P-max. In all patients, a chest X-ray was performed within 24 hours of line insertion to assess the CVC positions.
Results: Between January 2018 and December 2020, 51 critically ill patients with more than one CVC concurrently in place were deemed eligible and were included in the study. The distance between the inserted CVC tips was measured using the picture archiving and communication system (PACS). Across 51 patients, the mean difference between the two central lines inserted was 0.31 cm. The median was 0.00 cm, indicating that more than half of the sample exhibited no difference in positioning.
Conclusion: The ECG method of placing the CVC tip at P-max is a stable and reliable bedside method for positioning CVCs as the results for double CVCs impressively underline and it already works during the access procedure. However, the results demand confirmation in further studies.