bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
Significance of Education for Sustainable Menstrual Hygiene Management Practices: A rapid review
Authors: Pednekar Sulochana , Some Shreya , Thakore Renuka , Rivankar Kajal 
Published: July 2022

Abstract
This paper highlights the crucial role of education in the menstrual hygiene management, growth and development of a country, gender equality and women’s empowerment, which are integral parts of the Sustainable Development Goals (SDGs). Half of the world’s population are women, and women have specific needs to manage the menstrual cycle during their lifetime. To manage the bleeding during the menstrual cycle, girls and women use different products, depending on their accessibility and affordability. They are a) disposable – one-time use products such as disposable pads, tampons, and b) reusable products – reusable products such as cloth, washable and reusable cloth pads, menstrual cups, and period panties. On average, women use 6–8 sanitary napkins per cycle and generate approximately 125 kg of menstrual waste during menstruating. The literature search revealed that there are limited studies related to the use of menstrual products and the impacts of these products on women’s health and the environment. A rapid review of the literature identified factors responsible for choosing a particular type of menstrual product, the perceptions of women using the products, and their implications on the health and environment. The study concluded with the need to study the type of menstrual products preferred by women using appropriate variables, address the issues of disposal systems, provide adolescent girls with adequate infrastructure, and provide access to affordable sanitary products and gender equity to manage their periods with dignity, suggesting further investigation in menstrual hygiene management.
Robust and predictive 2D/3D-QSAR models for predicting the activities of novel pleuromutilin derivatives as antibacterial agents
Authors: Wang Fangfang , Zhou Bo 
Published: July 2022

Abstract
In recent years, antibiotics have been widely used and even caused abuse, many kinds of bacteria are becoming more and more resistant to existing antibiotics. Drug resistance has become a major problem to be solved, therefore, development of novel antibiotics is imperative. Studies have proven that novel pleuromutilin derivatives would provide powerful means to solve the problem of medical infection of drug-resistant pathogens, thus, it is noteworthy to in-depth study this series of derivatives. Therefore, the antibacterial activity of a series of novel pleuromutilin derivatives were investigated by 2D-QSAR and 3D-QSAR modeling. The CoMFA and CoMSIA methods were conducted to build up the 3D-QSAR models. Satisfactory statistical parameters (R2cv=0.608, R2pred=0.8596 for S. aureus-25923/CoMFA, R2cv=0.780, R2pred=0.8030 for S. aureus-25923/CoMSIA; R2cv=0.588, R2pred=0.6062 for MRSE-51625/CoMFA, R2cv=0.571, R2pred=0.5998 for MRSE-51625/CoMSIA; R2cv=0.604, R2pred=0.8061 for MRSA-337371/CoMFA, R2cv=0.737, R2pred=0.8241 for MRSA-3373715/CoMSIA; R2cv=0.704, R2pred=0.7504 for S. dysgalactiae/CoMFA, R2cv=0.683, R2pred=0.7852 for S. dysgalactiae/CoMSIA; R2cv=0.708, R2pred=0.7663 for S. agalactiae/CoMFA, R2cv=0.734, R2pred=0.6692 for S. agalactiae/CoMSIA) were obtained. To validate the results of 3D-QSAR models, MLR method was used to develop the 2D-QSAR models, which would provide structural information for the ligand modification. All the results would be of great help for the design of new antibacterial agents.
Raising CPR to 50% by 2025 in Pakistan: An analysis of number of users and service delivery channels
Authors: Abdullah Mujahid , Bilal Faiq , Khan Romesa , Ahmed Azadeh , Khawaja Aamir Ashraf , Sultan Faisal , Khan Adnan Ahmad 
Published: July 2022

Abstract
Background Pakistan is the fifth most populous country in the world with a population growing at 2.4% annually. Despite considerable political will, including a national commitment that was endorsed by the President to raise contraceptive prevalence rate (CPR) to 50% by 2025, it has stagnated around 30-35%. Much of the dialogue on raising CPR is hypothetical and revolves around percentage point change rather than actual number of women that must be served. Methods DHS 2017-18 informs about the channels from which users avail their methods and disaggregates this information at the provincial level. Proportions of users from each of these channels were multiplied with Pakistan Census 2017 populations to arrive at the number of users. These users were compared with the total FP users and the number of women that availed any FP service in the past 12 months. Linear estimations of population were applied to calculate population numbers in 2025. Results National target of 50% CPR by 2025 translates into a population of 20.02 million users. Currently 11.26 million MWRA use any method, 8.22 million use a modern method and 4.94 million availed their method in the past 12 months. Of these 2.7 million did so from social marketing outlets, 0.76 million from public sector outreach (LHW), 0.55 million from private and 0.88 million from public sector facilities. However, arriving at CPR target means expanding annual service delivery from 4.94 to 13.7 million users. Since social marketing and LHW outreach may have become saturated, only health facilities are the likely channels for such an expansion. Conclusions We demonstrate triangulation of survey with census as a simple policy analysis tool that can help decision makers estimate the quantum of services they must provide. Such an analysis also allows an understanding of utilization patterns of each of these channels. In Pakistan’s context, under-utilization of funds and existing facilities suggest that increased funding or more providers will be unlikely helpful. The most effective policy changes that will likely help include adding outreach to support existing public and private sector facilities while ensuring that procurement of commodities is prioritized.
Uretero-neocystostomy: a retrospective comparison of open, laparoscopic and robotic techniques
Authors: Ramesmayer Christian , Pallauf Maximilian , Gruber Ricarda , Kunit Thomas , Oswald David , Lusuardi Lukas , Mitterberger Michael 
Published: July 2022

Abstract
BACKGROUND: Uretero-neocystostomy (UNC) is the gold-standard for distal-ureter repair. Whether the surgery should be conducted minimally invasive (laparoscopic (LAP), robotic RAL)) or open remains unanswered by the literature.METHODS: Retrospective analysis of surgical outcome of patients treated with UNC for distal ureteral stenosis (January 2012-March 2021). Patient demographics, estimated blood loss (EBL), surgical technique, operative time, complications and length of hospital stay (LOS) were recorded. During the follow-up period, patient underwent renal ultrasound and kidney function tests. Success was defined as relieve of symptoms or no findings of obstruction needing urine drainage. RESULTS: 57 patients were included (6 RAL, 25 LAP, 26 open). The different cohorts were similar of age, gender, American Society of Anesthesiologists (ASA) score, body-mass index and history of prior treatment of the ureter. No intraoperative complications were detected in all groups. There was no conversion to open surgery in the RAL group, whereas one was found in the LAP arm. Six patients had a recurrent stricture, but with no significant difference between the cohorts. EBL was not different between the groups. LOS was significantly lower in the RAL group compared to LAP and open (7 vs. 9. vs. 13 days, p=0.030), despite significantly longer operating times (164.5 vs. 193.1 vs. 125.5 minutes, p=0.007). CONCLUSIONS: RAL UNC is a feasible and safe surgical method and provides similar results in terms of success rates in comparison to LAP and open approach. A shorter LOS could be detected. Further prospective studies need to be done.