bluuebunny/crossref_metadata_2025 huggingface dataset:
Working memory dysfunction in fibromyalgia is associated with genotypes of the catechol- O-methyltransferase gene: An event-related potential study
Authors: Ferrera David , Gómez-Equer Francisco , Peláez Irene , Barjola Paloma , Fernandes-Magalhaes Roberto , Carpio Alberto , De Lahoz María E. , Martín-Buro María Carmen , Mercado Francisco
Published: July 2022

Recent findings have associated different COMT genotypes with working memory capacity in patients with fibromyalgia. Although it is thought that the COMT gene may influence neural correlates (P2 and P3 ERP components) underlying working memory impairment in this chronic pain syndrome, it has not yet been explored. Therefore, the aim of the present research was to investigate the potential effect of the COMT gene in fibromyalgia patients on ERP working memory indices (P2 and P3 components). For this purpose, 102 participants (51 patients and 51 healthy control participants) took part in the experiment. Event-related potentials and behavioural responses were recorded while participants performed a spatial n-back task. Participants had to decide if the stimulus coincided or not in the same location as the one presented one (1-back condition) or two (2-back condition) trials before. Genotypes of the COMT gene were determined through a saliva sample from all participants. Present results significantly showed lower working memory performance (p < 0.05) in patients with fibromyalgia as compared to control participants (higher rate of errors and slower reaction times). At neural level, we found that patients exhibited enhanced frontocentral and parieto-occipital P2 amplitudes compared to control participants (p < 0.05). Interestingly, we also observed that only fibromyalgia patients carrying the Val/Val genotype of the COMT gene showed higher frontocentral P2 amplitudes than control participants (p < 0.05). Current results (behavioural outcomes and P2 amplitudes) confirmed the presence of an alteration in working memory functioning in fibromyalgia. The enhancement of frontocentral P2 could be reflecting that these patients would manifest an inefficient way of activating executive attention processes, in carriers of the Val/Val genotype of COMT. To our knowledge, the present findings are the first linking neural indices of working memory dysfunctions and COMT genotypes in fibromyalgia. Applying a subgroup of patient’s strategy based on this genetic marker could be useful to establish more tailored therapeutical approaches.
Learning experiences of first year graduate entry nursing students: a longitudinal case study
Authors: Winnington Rhona , Shannon Kay , Turner Rosemary , Jarden Rebecca , McClunie-Trust Patricia , Jones Virginia , Merrick Eamon , Donaldson Andrea , Macdiarmid Rachel
Published: July 2022

Background: Graduate entry nursing programmes provide students with an accelerated pathway to becoming a registered nurse. Motivations for study, together with commonly shared characteristics of students enrolling in such programmes is becoming well documented, however, their experiences of studying for a professional qualification in this manner is less understood. As a means of maintaining the relevance of these fast-tracked programmes in the future, an understanding of graduate entry nursing students’ experiences of academic teaching and clinical placements is imperative. Objective: To explore the academic and clinical experiences of students enrolled in the first year of a graduate entry nursing programme.Methods: A longitudinal case study approach was taken based on Yin. Here we report the experiences of nine students enrolled in a graduate entry nursing programme during 2020. Semi-structured interviews were used for data collection and analysed using Braun and Clarke’s thematic analysis. Findings: Three overarching themes were developed - affirmation nursing was the correct career choice, reflections on expectations of a graduate entry nursing programme and the reality of nursing when exposed to clinical placements. Conclusion: This study highlights the experiences of first year graduate entry nursing students, with many experiencing affirmation that their altruistic career visions came to fruition. The findings indicate that many students are flexible and adaptable in their approach to study as a means of meeting the challenges of the programme, all of which are key characteristics for a registered nurse; with the maturing of emotional intelligence providing preparation for their second year of study.
Randomized clinical trial with fractional CO2 laser and Clobetasol in the treatment of Vulvar Lichen Sclerosus: A clinic study of feasibility
Authors: Salgado Hakayna , Drumond Denise , Pannain Gabriel , Costa Louise Gracielle e , Sampaio Fernanda , Leite Isabel
Published: July 2022

Objectives: The main objective of the study was to describe and compare the feasibility of using fractional CO2 laser to the usual treatment with Clobetasol. Randomized clinical trial brought together 20 women from a Brazilian university hospital, 9 of them were submitted to Clobetasol treatment and 11 to laser therapy. Sociodemographic data were obtained and quality of life parameters, vulvar anatomy, self-perception and histopathological analysis of vulvar biopsies were evaluated. Evaluations were made before the beginning of the treatment, during its implementation, right after its completion (3 months), and 12 months after. The SPSS 14.0 program was used, obtaining descriptive measurements. The level of significance adopted was 5%. Results: The clinical/anatomical characteristics of the vulva did not differ between the treatment groups, as much before as after its performance. There was no statistically significant difference between the treatments performed regarding the impact on the life quality of the patients. A higher satisfaction degree with the treatment was obtained with the patients in the Laser group in the third month of evaluation. Laser therapy also revealed a higher occurrence of telangiectasia after treatment completion. Fractional CO2 laser has proven to be well accepted and is a promising therapeutic option.
An AGS-associated mutation in ADAR1 catalytic domain causes early-onset and MDA5- dependent encephalopathy with IFN pathway activation in the brain
Authors: Guo Xinfeng , Steinman Richard A. , Sheng Yi , Chao Guodong , Wiley Clayton A. , Wang Qingde
Published: July 2022

Background:Aicardi-Goutières syndrome (AGS) is a severe autoimmune disease characterized by inflammatory encephalopathy with an elevated Type 1 interferon-stimulated gene (ISG) expression signature in the brain. It is featured by early-onset encephalopathy and progressive loss of intellectual abilities and motor control. Gene mutations in 7 protein-coding genes were found to be associated with AGS. However, the causative role of these mutations in the early-onset neuropathogenesis has not been demonstrated in animal models, and the mechanism of neurodegeneration of AGS remains ambiguous.Methods:Via CRISPR/Cas-9 technology, we established a mutant mouse model in which a genetic mutation found in AGS patients at the ADAR1 coding gene loci was introduced into mouse genome. A mouse model carrying double gene mutations encoding ADAR1 and MDA-5 was prepared through breeding strategy. Phenotype, gene expression, RNA sequencing, innate immune pathway activation, and pathologic studies including RNA in situ hybridization (ISH) and immunohistochemistry (IHC) were used for characterization of the mouse models to determine the disease mechanisms.Results:We established a mouse model bearing a mutation in the catalytic domain of ADAR1, the D1113H mutation found in AGS patients. With this mouse model, we demonstrated a causative role of this mutation for the early-onset brain injuries in AGS and determined the signaling pathway underlying the neuropathogenesis. First, this mutation altered RNA editing profile in neural transcripts and led to robust IFN stimulated gene (ISG) expression in the brain. By in situ hybridization, the brain of mutant mice showed an unusual multifocal increased expression of ISGs that was cell-type dependent. An early onset astrocytosis and microgliosis, and later stage calcification in the deep white matter areas were observed in the mutant mice. Brain ISG activation and neuroglial reaction were completely prevented in the D1113H ADAR1 mutant mice by blocking RNA-sensing through deletion of the cytosolic RNA receptor MDA-5.Conclusions:The D1113H ADAR1 mutation causes RNA editing alteration in the brain, activating MDA5-dependent RNA sensing pathway activation and ISG expression, leading to the early-onset brain pathogenesis of AGS.
Genetic diversity of human papillomavirus (HPV) as specified by the detection method, gender, and year of sampling: a retrospective cross-sectional study
Authors: Finan Ramzi R. , Chemaitelly Hiam , Racoubian Eddie , Aimagambetova Gulzhanat , Almawi Wassim
Published: July 2022

Purpose.
This study assesses HPV prevalence and genotype distribution in Lebanon, and to identify differentials in HPV infection, infection with multiple genotypes, and with high-risk genotypes, by sex, age, and year of data collection.
Methods.
Study participants comprised 1,042 female and 160 male participants between 2006–2018. HPV genotyping was done by PCR and hybridization (2006–2013) or real-time PCR (2013 onwards). Diversity of HPV genotypes across gender, age groups, and years of data collection was tested by applying Shannon Diversity Index.
Results.
The overall HPV prevalence was 44.8% among study participants, and 3-fold higher in women than men. Single HPV infection was seen in two-third of HPV-positive participants. Women were less likely to be infected with multiple HPV strains, but more likely to be infected with high-risk or mixed risk HPV genotypes. HPV16 (11.0%, 9.8%) and HPV53 (8.5%, 4.9%) were the most prevalent high-risk HPV genotypes in women and men, respectively, while HPV18 prevalence was 4.9% in men and 3.1% in women, while HPV59 prevalence was 6.6% in men and 2.1% in women. Samples collected post-2011 from women showed twice higher odds of HPV infection than those collected earlier and were 3-fold more likely to be infected with multiple HPV strains, and twice more likely to be infected with high-risk genotypes compared to those tested earlier. Women scored higher on Shannon index indicating high diversity in HPV types and frequency, with trend of increased diversity over time. While the odds of HPV infection remained associated with sex and temporal trend in multivariable analysis, odds of having high-risk genotypes was mainly associated with infection with multiple HPV strains.
Conclusion.
Our study showed high diversity in HPV genotypes and an increasing trend of infection with multiple and high-risk genotypes in recent years. Findings underscore the need for effective screening/surveillance and HPV vaccination programs.
Selection and Performance of AM Superalloys for High-Speed Flight Environments
Authors: James William Sean , Ganguly Supriyo , Pardal Goncalo
Published: July 2022

In developing the Wire + Arc Additive Manufacturing (WAAM) process for the manufacture of components used in high-speed flight environments, a selection process for suitable alloys was devised. Using elevated temperature material properties from literature sources, creep-resistant alloys were down selected based on the requirement for service in a high temperature, high stress environment and the need for an alloy suitable for additive manufacturing using a wire-arc process. Down selected alloys Inconel 718 (IN718), Rene 41 (RE41), Haynes 188 (H188) and Inconel 625 (IN625) were deposited by a plasma transferred arc WAAM process in an oxygen-controlled environment. The structures were built then underwent mechanical testing. The performance of as deposited material was then compared against wrought alloy data from literature. Tensile testing at room temperature revealed a correlation with similarly strengthened IN718 & RE41, but no correlation with solution strengthened H188 and IN625. Results revealed that the AM material did not meet the wrought strength and with performance varying depending on each alloy’s strengthening mechanism. Results illustrate the need for further processing to return the mechanical performance to wrought values.
Fast in vivo assay of creatine kinase in human brain by 31P magnetic resonance fingerprinting
Authors: Widmaier Mark , Lim Song-I , Wenz Daniel , Xin Lijing
Published: July 2022

A new and efficient magnetisation transfer 31P magnetic resonance fingerprinting (MT-31P-MRF) approach is introduced to measure the creatine kinase metabolic rate kCK between phosphocreatine (PCr) and adenosine triphosphate (ATP) in human brain. The MRF framework is extended to overcome challenges in conventional 31P measurement methods in the human brain in vivo by reducing specific absorption rate deposition, incorporating system imperfection into a model, and testing a range of values for each parameter to arrive at their estimation. To compute complex high-dimensional datasets, we propose a nested iteration interpolation method (NIIM). As the number of parameters to estimate increases, the size of the dictionary grows exponentially. NIIM can reduce the computational load by breaking dictionary matching into subsolutions of linear computational order. The MT-31P-MRF combined with the NIIM provides T1PCr , T 1ATP , and kCK estimates in good agreement with those obtained by the exchange kinetics by band inversion transfer (EBIT) method and literature values. Furthermore, the test-retest reproducibility results showed that the MT-31P-MRF achieves less than 10% of the coefficient of variation for T1PCr , T 1ATP , and kCK measurements in 4 min 15 s, which is more than four times faster than the EBIT method. We conclude that MT-31P-MRF in combination with the NIIM is a fast, accurate and reproducible approach for in vivo kCK assays in the human brain, which enables the potential for investigating energy metabolism in a clinical setting.
Immune cell density differences in normal breast lobules of BRCA1/2 mutation carriers, women with benign breast disease and healthy research volunteers
Authors: Ogony Joshua , Hoskin Tanya L , Stallings-Mann Melody , Winham Stacey , Brahmbhatt Rushin , Arshad Muhammad Asad , Kannan Nagarajan , Peña Alvaro , Allers Teresa , Brown Alyssa , Sherman Mark E , Visscher Daniel W , Knutson Keith L. , Radisky Derek C , Degnim Amy
Published: July 2022

Purpose
Breast cancer risk is elevated in pathogenic germline BRCA 1/2 mutation carriers due to compromised DNA quality control and elevated mutagenic load. We hypothesized that if immunosurveillance promotes tumor suppression, then normal breast lobules from BRCA carriers may demonstrate higher immune cell densities.
Methods
We assessed immune cell composition in normal breast lobules from age-matched women with progressively increased breast cancer risk, including 1) 19 women who donated normal breast tissue to the Komen Tissue Bank (KTB) at Indiana University Simon Cancer Center, 2) 15 women with biopsy-identified benign breast disease (BBD), and 3) 19 prophylactic mastectomies from women with germline mutations in BRCA1/2 genes. We performed immunohistochemical stains and analysis to quantitate immune cell densities from digital images in up to 10 representative lobules per sample. Median cell counts per mm2 were compared between groups using Wilcoxon rank-sum tests.
Results
Compared to BBD tissues, normal breast lobules from BRCA carriers had significantly higher densities of CD8 + cells (median 354.4 vs 200.0 cells/mm2, p = 0.01). Compared to KTB normal donor breast tissues, normal breast lobules from BRCA carriers also had significantly higher densities of CD4+ (median 116.3 vs 17.7 cells/mm2), CD8+ (354.4 vs 150.9 cells/mm2), CD11c+ (3.5% vs 0.4% pixels positive), and CD68+ (237.5 vs 57.8 cells/mm2) immune cells (each p < 0.001).
Conclusions
These preliminary analyses show that normal/benign breast lobules of BRCA mutation carriers contain increased immune cells compared with BBD and normal donated tissues. Future studies will be helpful to define relationships of mutations and immune responses.
Less is more: learning predictability in reversible steganography
Authors: Chang Ching-Chun , Wang Xu , Chen Sisheng , Kiya Hitoshi , Echizen Isao
Published: July 2022

Artificial neural networks have advanced the frontiers of reversible steganography. The core strength of neural networks is the ability to render accurate predictions for a bewildering variety of data. Residual modulation is recognised as the most advanced reversible steganographic algorithm for digital images. The pivot of this algorithm is predictive analytics in which pixel intensities are predicted given some pixel-wise contextual information. This task can be perceived as a low-level vision problem and hence neural networks for addressing a similar class of problems can be deployed. On top of the prior art, this paper analyses predictability and endows the predictive analytics module with the option to abstain when encountering a high level of uncertainty. Predictability analysis can be formulated as a pixel-level binary classification problem and tackled by both supervised and unsupervised learning. In contrast to conventional statistical analysers, a learning machine can automatically acquire some statistical principles regarding image patterns and simultaneously adapt to a specific predictor. Selective prediction induces fewer and yet predictable pixels designated to carry the payload, which in turn leads to better capacity–imperceptibility performance, reflecting the ‘less is more’ philosophy. Experimental results show that steganographic performance can be remarkably improved by adaptively filtering out the unpredictable pixels with the learning-based predictability analysers.
Evaluation of GeneXpert® in Brazil Through a Historical and Epidemiological Approach
Authors: Iúdice Tirça Naiara da Silva , Conceição Marília Lima da , de Brito Artemir Coelho , de Souza Nicole Menezes , Mesquita Cristal Ribeiro , Guimarães Ricardo José de Paula Souza e , Furlaneto Ismari Perini , Saboia Alessandra de Souza , Lourenço Maria Cristina da Silva , Lima Karla Valéria Batista , Conceição Emilyn Costa
Published: July 2022

Background: The Rapid Molecular Test (RMT) Gene Xpert is widely used as a control strategies and surveillance for tuberculosis (TB). In the region of the Americas TB incidence is slowly increasing, owing to an upward trend in Brazil, which is among the high TB burden countries (HBCs) ranking the 19th position. In this context, we aimed to: (i) describe the implementation and history of RMT-TB (Xpert® MTB/RIF and Xpert® MTB/RIF Ultra) in Brazil; (ii) to evaluate the national RMT-laboratory distribution and TB and RIF detection by RMT-TB equipment (by year, by federal units and by region); and (iii) to correlate these data the Brazilian TB incidence. Methods: For this, we collected the quantitative data of Xpert® MTB/RIF and Xpert® MTB/RIF Ultra assays, performed in the pulmonary TB investigation from 2014 to 2020, provided by the Brazilian Ministry of Health. A spatial visualization using ArcGIS software was performed. Results: The Southeast region allocated about double RMT-laboratories from 39.4% - 45.9% of the total value over five which is the number of regions. Regarding the federal units, the São Paulo state allocated alone from 20.2% to 34.1% (5.0 to 8.5 times the value) of RMT-laboratories depending on the year observed. There were significant differences (p < 0.0001) in the frequency of RMT-laboratory in all years of the historical series. There was an unequal distribution of RMT-laboratory between Brazilian regions and federal units. Conclusions: This alerts for the surveillance of rapid molecular detection of TB in different parts of the country, with the possibility of improving the distribution of tests in areas of higher incidence to achieve the disease control recommended by national and worldwide authorities.
Sex Differences in cognitive impairment and clinical correlates in Chinese patients with subthreshold depression
Authors: Lv Qinyu , Li Xin , Zhang Yao , Lu Daofeng , Lu Jiajing , Xie Qingfang , Li Hong , Wu Yiming , Wang Chongze , Yi Zhenghui
Published: July 2022

Objective: Subthreshold depression (SD) is a global mental health problem given its high prevalence, comorbidity, functional impairment, and associated with increased service utilization. However, currently little is known about gender differences in SD in cognitive impairment with clinical correlates. The aim of this study was tantamount to explore sex differences in subjective cognitive impairment and clinical associated risk factors in Chinese patients with SD.Methods: A total of 126 SD patients (males/females=40/86, aged 18-45 years) were included in this cross-sectional observational study. The general information, psychological assessments and psychiatric symptom assessments were collected online. The Patient Health Questionnaire-9 (PHQ-9) was used for depressive symptoms, Generalized Anxiety Disorder-7 (GAD-7) was used for anxiety symptoms, Perceived Deficits Questionnaire-Depression (PDQ-D) was used for the cognitive symptoms. Alexithymia was assessed with 20-item Toronto Alexithymia Scale (TAS-20), including 3 subdomains: Factor 1 (F1) evaluated difficulty identifying feelings; Factor 2 (F2) evaluated difficulty describing feelings to others; Factor 3 (F3) evaluated externally oriented thinking. A multivariate analysis of covariance and regression models were used.Results: Our results showed that female patients had significantly higher PDQ-D-20 total score than male patients. However, there were no significant sex differences in the mean TAS-20 and subdomain score. Notably, F2 contributed to cognitive impairment in men, whereas both PHQ-9 aggregate score and F2 contributed to cognitive impairment in women.Conclusion: These findings revealed significant sex differences in cognitive impairments and clinical correlates in SD, which deserves a follow-up study of SD in the future.
Spherical cap model of epidural hematomas
Authors: Chen Chien-Hua , Liao Chun-Chih , Liao Heng-Chun , Jaw Fu-Shan , Xiao Furen
Published: July 2022

Epidural hematomas (EDHs), which have a characteristic biconvex shape, are a type of post-traumatic intracranial mass. EDHs and other types of intracranial hematomas are often diagnosed with computed tomography (CT). Based on our half sphere model of the supratentorial brain parenchyma, we modeled the geometry of EDHs with two spherical caps. Applying the relationship between the sphere radius, spherical cap height, and base circle radius, we derived formulas for the shape of an EDH, relating its largest diameter and location to the other two diameters. We also estimated EDH volumes using the spherical cap volume and conventional ABC formulas. We then constructed a lookup table accordingly. Our model was verified using EDH diameter measurements in 14 CT image sets from previously reported patients. With our model, the number of parameters needed for EDH volume estimation was reduced from three to one, accelerating clinical decision-making for critically injured patients.
Differentiation Value of Left Atrial Dysfunction in Reperfused Chronic Myocardial Infarction
Authors: Zhang He , Liu Ting
Published: July 2022

Evaluation of left atrial dysfunction is of great value to assess reperfused chronic myocardial infarction. LA volumetric and strain parameters can be of great help to estimate left atrial function. However, limited data are accessed on its prognostic value in reperfused chronic myocardial infarction.Purpose: In order to evaluate the relationship between LA volumetric and strain parameters in patients with chronic myocardial infarction. Materials and methods: In this retrospective study, recruited people(included from April in 2017 to the June in 2021) experience cardiovascular MRI. The relationship between LA volumetric and strain parameters and chronic myocardial infarction was evaluated by linear regression. Results: 83 patients with chronic myocardial infarction(mean age±standard deviation, 58.16 years±9.58; 69men) were included. LATEF was weakly correlated with LAVmin(Pearson correlation coefficient r=-0.674, P＜0.001), Booster longitudinal strain(r=0.577, P＜0.001), GLSRa(r=-0.567, P＜0.001), Total longitudinal strain(r=0.574, P＜0.001). Better passive radial strain is correlated to a lower rate of chronic myocardial infarction(hazard ratio, 0.789[0.699,0.892]; P＜0.001) after adjusting for multiple clinical and CMR-based variables. Conclusion: Left atrial volumetric parameters, strain and strain rate can be of great value in reperfused chronic myocardial infarction.
Anatomical basis for the trigeminal autonomic cephalalgia-like response produced by formalin injection into the facial cheek in rats
Authors: Wang Ming R. , Tseng Ching J. , Kuo Jon S.
Published: July 2022

Trigeminal autonomic cephalalgias (TACs) comprise cluster headaches and are characterized 19 by unilateral neuralgiform headache attacks associated with autonomic responses and somatic 2 20 responses. An animal model for evaluating the anatomical basis of the TAC-like response is 21 not currently available. Twenty-five rats weighing 550-650 g were anaesthetized with 22 urethane. The TAC-like response was produced either by subcutaneous injection of formalin 23 into the unilateral facial cheek or by electrical stimulation of the unilateral intact trigeminal 24 nerve. The induced TAC-like response, which included ipsilateral common carotid arterial 25 flow (iCCAF) and other autonomic responses, was studied in intact nerves or after cutting 26 either the ipsilateral trigeminal nerve or the ipsilateral facial nerve. The formalin injections 27 produced concentration-dependent iCCAF increases accompanied by ipsilateral autonomic 28 responses of rhinitis-like nasal congestion, nasal mucus, meiosis, lacrimation, red eye, and 29 eyelid oedema. The formalin (5% or 10%, 0.5 cc)-induced responses were nearly abolished 30 by sectioning of either the facial or trigeminal nerve. The electrical stimulation (15 V, 60 Hz, 31 and 0.4 ms) of the intact trigeminal nerve or its ophthalmo-maxillary branch also produced 32 stimulation strength-dependent iCCAF increases as well as autonomic responses; however, 33 the electrical stimulation-induced iCCAF increases and other autonomic responses could still 34 be induced by electrical stimulation of the central but not the peripheral end of the 35 ophthalmo-maxillary branch (n = 8) or the trigeminal nerve (n = 2). Thus, an animal model 36 for inducing the TAC-like response by subcutaneous formalin injection into the rat facial 37 cheek was established. The TAC-like response could be sequentially mediated via the 38 afferent trigeminal nerve, trigeminal nucleus, dorsal facial nucleus, and efferent facial nerve.
Association of depressive disorders and dementia with mortality among older people with hip fracture
Authors: Olofsson Erika , Gustafson Yngve , Mukka Sebastian , Tengman Eva , Lindgren Lenita , Olofsson Birgitta
Published: July 2022

Background: Hip fracture (HF) is a significant cause of mortality among older people. Almost half of the patients with HF have dementia, which increases the mortality risk further. Cognitive impairment is associated with depressive disorders (DDs) and both dementia and DDs are independent risk factors for poor outcome after HF. However, most studies that evaluate mortality risk after HF separate these conditions.Aims: To investigate whether dementia with depressive disorders (DwD) affects the mortality risk at 12, 24, and 36 months after HF among older people.Methods: Patients with acute HF (n = 404) were included in this retrospective analysis of two randomized controlled trials performed in orthopedic and geriatric departments. Depressive symptoms were assessed using the Geriatric Depression Scale and cognitive function was assessed using the Mini-Mental State Examination. A consultant geriatrician made final depressive disorder and dementia diagnoses using the Diagnostic and Statistical Manual of Mental Disorders criteria, with support from assessments and medical records. The 12-, 24- and 36-month mortality after HF was analyzed using logistic regression models adjusted for covariates.Results: In analyses adjusted for age, sex, comorbidity, pre-fracture walking ability, and fracture type, patients with DwD had increased mortality risks at 12 [odds ratio (OR) 4.67, 95% confidence interval (CI) 1.75–12.51], 24 (OR 3.61, 95% CI 1.71–7.60), and 36 (OR 4.53, 95% CI 2.24–9.14) months. Similar results were obtained for patients with dementia, but not depressive disorders, alone.Conclusion: DwD is an important risk factor for increased mortality at 12, 24, and 36 months after HF among older people. Routinely assessments after HF for cognitive- and depressive disorders could identify patients at risk for increased mortality, and enable early interventions.Trial registration: RCT1: was not registered, since it was not mandatory when the data was collected. RCT2: International Standard Randomized Controlled Trial Number Register, trial registration number: ISRCTN15738119, registration date: 16/06/2008.
New Method of Metrological Evaluation of Industrial Rolling
Authors: Wrzochal Mateusz
Published: July 2022

The paper contains a description of a new method of evaluation of the indications of industrial rolling bearing vibration measurement systems. By using an additional vibration sensor, this method enables verification of the correct value of the tested bearing’s measured quantity by creating a new reference point instead of the bearing acting as the reference point itself. The presented measurement method was used for three measurement systems of different designs to select the most accurate system. The presented method also makes it possible to detect a defective measurement chain.
Optimal design of DVA-beam system by simultaneously optimizing DVA position, mass, damping and stiffness using Particle Swarm optimization
Authors: Song Jie , Zeng Xin , Hua Hongliang , Qiu Ming
Published: July 2022

Using Dynamic Vibration Absorber (DVA) to suppress the vibration of slender structure is promising for its reliable, efficiency and low cost. The main purpose of this study is to suppress the beam vibration by simultaneously optimizing DVA position, mass, damping and stiffness of a DVA-beam system. The motion equations of the DVA-beam system are derived first using the Rayleigh-Ritz method and Lagrange’s equation. Then the Particle Swarm Optimization is then applied to seek the DVA optimal parameters. In which the objective is to minimize the RMS value of the beam tip deflection in a specific time domain. The PSO performance is investigated in three kinds of beam load conditions, that is free vibration, beam subjected to pulse excitation and harmonic excitation. It is observed that in these optimizations the objective function converges quickly. Based on the optimal DVA parameters, the dynamic responses of the optimal DVA-beam system are analyzed and compared with those of bare beam. The results demonstrate that the optimal designed DVA can effectively suppress the beam vibration.
Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions
Authors: Reemst Kitty , Kracht Laura , Kotah Janssen , Rahimian Reza , Irsen Astrid Anne Sophie van , Sotomayor Gonzalo Congains , Verboon Laura Nathalie , Brouwer Nieske , Simard Sophie , Turecki Gustavo , Mechawar Naguib , Kooistra Susanne M. , Eggen Bart , Korosi Aniko
Published: July 2022

Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS induced by limited bedding and nesting material during the first week of life (postnatal days [P]2–9) on microglial i) morphology; ii) hippocampal gene expression; and iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, synaptosomes from ELS-exposed mice were phagocytosed less by age-matched microglia. At P200, but not P9, ELS microglia showed reduced synaptosome phagocytic capacity when compared to CTRL microglia. Lastly, we confirmed the ELS-induced increased expression of the phagocytosis-related gene GAS6 that we observed in mice, in the dentate gyrus of individuals with a history of child abuse using in situ hybridization. These findings reveal persistent effects of ELS on microglial function and suggest that altered microglial phagocytic capacity is a key contributor to ELS-induced phenotypes.
Maternal and infant NR3C1 and SLC6A4 epigenetic signatures of the COVID-19 pandemic lockdown: When timing matters
Authors: Provenzi Livio , Nazzari Sarah , Grumi Serena , Mambretti Fabiana , Villa Marco , Giorda Roberto
Published: July 2022

Stress exposure during pregnancy is critically linked with maternal mental health and child development. The effects might involve altered patterns of DNA methylation in specific stress-related genes (i.e., glucocorticoid receptor gene, NR3C1, and serotonin transporter gene, SLC6A4) and might be moderated by the gestational timing of stress exposure. In this study, we report on NR3C1 and SLC6A4 methylation status in Italian mothers and infants who were exposed to the COVID-19 pandemic lockdown during different trimesters of pregnancy. From May 2020 to February 2021, 283 mother-infant dyads were enrolled at delivery. Within 24 hours from delivery, buccal cells were collected to assess NR3C1 (44 CpG sites) and SLC6A4 (13 CpG sites) methylation status. Principal component (PC) analyses were used to reduce methylation data dimension to one PC per maternal and infant gene methylation. Mother-infant dyads were split into three groups based on the pregnancy trimester (first, second, third) during which they were exposed to the COVID-19 lockdown. Mothers and infants who were exposed to the lockdown during the first trimester of pregnancy had lower NR3C1 and SLC6A4 methylation when compared to counterparts exposed during the second or third trimesters. The effect remained significant after controlling for confounders. Women who were pregnant during the pandemic and their infants might present altered epigenetic biomarkers of stress-related genes. As these epigenetic marks have been previously linked with heightened risk of maternal psychiatric problems and less-than-optimal child development, mothers and infants should be adequately monitored for psychological health during and after the pandemic.
Effects of coastal shellfish farming and hypoxic stress on DMS production
Authors: Zhang Shenghui , Sun Jing , Zhang Xiaoli , Yao Cheng , Zhao Miao , Zhao Wanyu , Zhang Honghai , Yang Gui-Peng , Zhao Jianmin
Published: July 2022

Dimethylsulfide (DMS) plays an important role in the sulfur biogeochemical cycle and cloud formation on Earth. In the past few decades, coastal shellfish breeding facilities have developed rapidly and the number of hypoxic environments has increased rapidly in shallow coastal areas. However, the effects of hypoxia and marine animal feeding on DMS production remain controversial. The Yantai offshore area is an important shellfish breeding area where hypoxia occurs frequently in the bottom seawater during the summer. In this study, we found that particle dimethylsulfoniopropionate (DMSPp) and attached bacteria play dominated roles in DMS production and average DMS concentration in coastal shellfish farming region was 38.84% higher than that in non-shellfish farming region during the breeding period. Different from the zooplankton “sloppy feeding”, the shellfish “filter-feeding” first repackages the phytoplanktonic DMSP into fecal DMSP, and then degrades DMSPp into DMS by attracting attached bacteria. Based on field investigations and hypoxia simulation experiment, we found that hypoxic stress had no significant effect on the production or consumption of DMS in seawater and the decline rates of DMS at the sediment-water interface between the oxic and hypoxic groups were nearly identical. Therefore, no significant difference in average DMS concentration was observed between the mild hypoxic area and the other sea areas during the summer. Meanwhile, although the DMSP-degrading bacteria presented different responses to hypoxia, little difference was observed in the entire microbial community structure or the DMSP catabolizing genes.
Owner-rated hyperactivity/impulsivity is associated with sleep efficiency in family dogs. A non-invasive EEG study
Authors: Carreiro Cecília , Reicher Vivien , Kis Anna , Gácsi Márta
Published: July 2022

Subjective sleep disturbances are reported by humans with attention-deficit/hyperactivity disorder (ADHD). However, no consistent objective findings related to sleep disturbances led to sleep problems removal from ADHD diagnostic criteria. As a model for human ADHD with questionnaires validated for this purpose, dogs have been used also because their sleep physiology can be measured by non-invasive methods similarly to humans. We recorded spontaneous sleep EEG in family dogs during a laboratory session. We analyzed the association of sleep macrostructure and deep sleep (NREM) slow-wave activity (SWA) with a validated owner-rated ADHD questionnaire, assessing inattention (IA), hyperactivity/impulsivity (H/I) and total (T) scores. Higher H/I and T were associated with lower sleep efficiency and longer time awake after initial drowsiness and NREM. IA showed no associations with sleep variables. Further, no association was found between ADHD scores and SWA. Our results are in line with human studies in which poor sleep quality reported by ADHD subjects is associated with some objective EEG macrostructural parameters. This suggests that dogs’ H/I natural variation is useful to gain a deeper insight of ADHD neural mechanisms.
Vaccination strategies in structured populations under partial immunity and reinfection
Authors: Rodriguez-Maroto Gabriel , Atienza-Diez Iker , Ares Saúl , Manrubia Susanna
Published: July 2022

Optimal protocols of vaccine administration to minimize the effects of infectiousdiseases depend on a number of variables that admit different degrees of control.Examples include the characteristics of the disease and how it impacts on differentgroups of individuals as a function of sex, age or socioeconomic status, its transmissionmode, or the demographic structure of the affected population. Here we introduce acompartmental model of infection propagation with vaccination and reinfection andanalyse the effect that variations on the rates of these two processes have on theprogression of the disease and on the number of fatalities. The population is split intotwo groups to highlight the overall effects on disease caused by different relationshipsbetween vaccine administration and various demographic structures. As a practicalexample, we study COVID-19 dynamics in various countries using real demographicdata. The model can be easily applied to any other disease and demographic structurethrough a suitable estimation of parameter values. Two main conclusions stand out.First, the higher the fraction of reinfected individuals, the higher the likelihood that thedisease becomes quasi-endemic. Second, optimal vaccine roll-out depends ondemographic structure and disease fatality, so there is no unique vaccination protocol,valid for all countries, that minimizes the effects of a specific disease. Simulations of thegeneral model can be carried out at this interactive webpage [1].
Emergence of synchronized rotations in dense active
matter with disorder
Authors: Vahabli Danial , Vicsek Tamas
Published: July 2022

We consider the rich variety of collective motion patterns emerging when aligning active particles move in the presence of randomly distributed obstacles - representing quenched noise in two dimensions. In order to get insight into the involved complex flows and the transitions between them we use a simple model allowing the observation and analysis of behaviours that are less straightforwardly accessible by experiments or analytic calculations. We find a series of symmetry braking states in spite of the applied disorder being isotropic. In particular, as the level of perturbations is increased, the system of self-propelled particles changes its collective motion patterns from i) directed (polar) flow ii) through a mixed state of locally directed or locally rotating flow to iii) a novel, globally synchronized rotating state thereby the system violating overall chiral symmetry. Finally, this phase crosses over to a state in which iv) clusters of locally synchronized rotations are observed. The way of change from polar flow to overall synchronization can be interpreted as indicating a non-reciprocal phase transition. Our simulations suggest that, when both present, quenched rather than shot noise dominates the behaviours.
WF-OCTA for detecting diabetic retinopathy and evaluating the effect of photocoagulation on posterior vitreous detachment
Authors: Gong Yi , Hu Liying , Wang Linni , Shao Yan , Li Xiaorong
Published: July 2022

Purpose: To assess the clinical usefulness of widefield swept source optical coherence tomography angiography (WF SS-OCTA) for detecting microvasculature lesions in diabetic retinopathy (DR) by comparing with ultra-widefield (UWF) fluorescein angiography (FA). And investigate the effect of panretinal photocoagulation (PRP) on posterior vitreous detachment (PVD) status.Methods: DR patients underwent WF SS-OCTA with 12×12mm scan pattern of five visual fixations at baseline and at least 3-month visit after PRP treatment. Patients with no contraindications were imaged with UWF FA within a week. Images were evaluated in two methods for the areas of visible field of view (FOV), non-perfused area (NPA), presence of neovascularization of disc (NVD), neovascularization elsewhere (NVE) and PVD status.Results: 44 eyes of 28 patients with DR initially treated with PRP were enrolled. The FOV of UWFFA were significantly wider than WF-OCTA. There was a good consistency for quantitative measurement of NPAs between two methods. NPAs more than 5DA outside the panoramic OCTA imaging area were detected in 1 eye with NPDR (8.3%) and 10 eyes with PDR (47.8%). WF-OCTA had high detection for NVDs and NVEs with a low rate of false positives. After PRP treatment, no eyes showed progression in PVD stages around the macula, optical disc and NVEs at short follow-up.Conclusion: WF SS-OCTA is clinically useful for evaluating NPAs and NVs in DR. PRP treatment cannot induce PVD development in a short time.
Design, synthesis, in vitro, and in silico biological evaluations of new coumarin-indole hybrids as anti-α-glucosidase agents
Authors: Niri Davood Rezapour , Sayahi Mohammad Hosein , Behrouz Somayeh , Moazzam Ali , Mojtabavi Somayeh , Faramarzi Mohammad Ali , Larijani Bagher , Rastegar Hossein , Mohammadi-Khanaposhtani Maryam , Mahdavi Mohammad
Published: July 2022

Background
A new series of coumarin-indole hybrids was designed and synthesized as novel anti-diabetic agents through inhibition of α-glucosidase, which is an important anti-diabetic target. The title hybrids were designed based on hybridization of two active pharmacophors against α-glucosidase: coumarin and indole.
Methods
The thirteen various derivatives 4a-m were synthesized, purified, and fully characterized. These compounds were evaluated against α-glucosidase in vitro and in silico. In silico pharmacokinetic study of the most potent compounds was also performed.
Results
Most of the title compounds exhibited high anti-α-glucosidase activity in comparison to standard drug acarbose. In particular, the phenoxy derivative 4d namely 3-((1H-indol-3-yl)(3-phenoxyphenyl)methyl)-4-hydroxy-2H-chromen-2-one showed promising activity. This compound is a competitive inhibitor into α-glucosidase and showed the lowest binding energy at α-glucosidase active site in comparison to other potent newly synthesized compounds and acarbose.
Conclusion
Compound 4d can be a lead compound for further structural development to obtain an effective and potent α-glucosidase inhibitor.
The Role of E3 ubiquitin Ligase WWP2 and the Regulation of PARP1 by Ubiquitinated Degradation in Apoptosis of Acute Lymphoblastic Leukemia
Authors: Zhang Lijun , Lu Xinxin , Huang Xinyue , Xu Haiqi , Lu Saien , You Shilong , xu jiaqi , Zhan Qianru , Dong Chao , Zhang Ning , Zhang Ying , Cao Liu , Zhang Naijin
Published: July 2022

Acute lymphoblastic leukemia (ALL) has been huge threaten for people health and finding effective target therapy is urgent and important. WWP2, as one of E3 ubiquitin ligase, is involved in many biological processes by specifically binding to substrates. PARP1 plays a role in cell apoptosis and is considered as a therapeutic target of certain cancers. In this study, we firstly tested WWP2 expression in patients and normal people and analyzed the relationship with clinicopathologic factors. We demonstrated WWP2 was involved in ALL apoptosis and knockout WWP2 alleviated ALL apoptosis induced by Dox in vitro and vivo. WWP2 negatively regulated and interacted with PARP1 in vitro and vivo and WWP2 mechanically degraded PARP1 through polyubiquitin-proteasome pathway. These findings suggested WWP2 played a role in ALL apoptosis and displayed a regulatory pathway of PARP1, which provide a new potential therapeutic target for the treatment of ALL.
Evidence of High-Risk Human Papillomavirus in Prostate cancer: A UK based study
Authors: Ahmed M. Yahya , Salman Nadia Aziz , Sandhu Sarbjinder , Seddon Alan M. , Ashrafi G. Hossein
Published: July 2022

Human papillomavirus (HPV) infection is one of the sexually transmitted diseases (STDs) which have been implicated in the etiology of multiple cancers. To date, several studies have been conducted to evaluate the incidence of High-Risk (HR) HPV in prostate cancer (PCa) which have generated widely conflicting data. Hence, this leaves a lack of awareness on the causal role of persistent HPV infection in the development of PCa. Although this has been investigated in a handful of countries, to the best of our knowledge, no prior studies have been conducted in the UK. In this study, polymerase chain reaction (PCR) and Sanger sequencing were implemented to analyze a total of 49 fresh prostate specimens (35 benign and 14 malignant specimens) for the presence of viral DNA of 12 HR-HPV types. Data obtained confirmed the presence of HR-HPV in 32.7% of analyzed benign and malignant prostate tissues with HPV 35 being identified as the most frequent type. Moreover, using Immunohistochemistry (IHC), we have confirmed the expression of HPV protein in prostate tissues positive for HPV DNA. This observation, the first in the UK, suggests that HPV may have a possible etiological role in prostate cancer development.