bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depression and anxiety among pregnant mothers in the initial stage of the Coronavirus Disease (COVID-19) pandemic in the southwest of Iran
Authors: Maharlouei Najmeh , Keshavarz Pedram , Salemi Niloufar , Lankarani Kamran B. 
Published: June 2021

Abstract
‌Background
Women are at a higher risk for depression progression, especially during pregnancy. The current study purposed to investigate depression, anxiety, and stress levels of pregnant mothers in the initial stage of the COVID-19 infection in the southwest of Iran.

Methods
This cross-sectional study was conducted during March and April, 2020, in Shiraz, Iran. Pregnant mothers registered in maternity clinics affiliated with Shiraz University of Medical Sciences were included. An online self-administered checklist was used. It included socio-demographic, obstetric and medical histories, and the short form of the Depression Anxiety Stress Scales (DASS-21) to evaluate depression, anxiety, and stress. A p-value < 0.05 was considered significant.

Results
In total, 540 pregnant mothers answered the questionnaire. 83.5% had no comorbidity. Abnormal depression scores were significantly higher in those who had no insurance (OR = 2.5) and in those with poor self-rated health (SRH) (OR = 27.8). Pregnant mothers with lower SRH and two or more comorbidities had a higher chance of having an abnormal level of anxiety subscale (6.9, 3.7 times, retrospectively).

Conclusion
The results revealed that an abnormal level of depression was associated with SRH and medical insurance status. Moreover, the number of comorbidities and poor SRH significantly increased the chance of achieving abnormal anxiety levels in pregnant mothers during the COVID-19 pandemic.
Deciphering the temporal heterogeneity of cancer-associated fibroblast subpopulations in breast cancer
Authors: Venning Freja Albjerg , Zornhagen Kamilla Westarp , Wullkopf Lena , Sjölund Jonas , Rodriguez-Cupello Carmen , Kjellman Pontus , Morsing Mikkel , Hajkarim Morteza Chalabi , Won Kyoung Jae , Erler Janine Terra , Madsen Chris Denis 
Published: June 2021

Abstract
Background
Cancer-associated fibroblasts (CAFs) comprise a heterogeneous population of stromal cells within the tumour microenvironment. CAFs exhibit both tumour-promoting and tumour-suppressing functions, making them exciting targets for improving cancer treatments. Careful isolation, identification, and characterisation of CAF heterogeneity is thus necessary for ex vivo validation and future implementation of CAF-targeted strategies in cancer.

Methods
Murine 4T1 (metastatic) and 4T07 (poorly/non-metastatic) orthotopic triple negative breast cancer tumours were collected after 7, 14, or 21 days. The tumours were analysed via flow cytometry for the simultaneous expression of six CAF markers: alpha smooth muscle actin (αSMA), fibroblast activation protein alpha (FAPα), platelet derived growth factor receptor alpha and beta (PDGFRα and PDGFRβ), CD26/DPP4 and podoplanin (PDPN). All non-CAFs were excluded from the analysis using a lineage marker cocktail (CD24, CD31, CD45, CD49f, EpCAM, LYVE-1, and TER-119). In total 128 murine tumours and 12 healthy mammary fat pads were analysed.

Results
We have developed a multicolour flow cytometry strategy based on exclusion of non-CAFs and successfully employed this to explore the temporal heterogeneity of freshly isolated CAFs in the 4T1 and 4T07 mouse models of triple-negative breast cancer. Analysing 128 murine tumours, we identified 5–6 main CAF populations and numerous minor ones based on the analysis of αSMA, FAPα, PDGFRα, PDGFRβ, CD26, and PDPN. All markers showed temporal changes with a distinct switch from primarily PDGFRα+ fibroblasts in healthy mammary tissue to predominantly PDGFRβ+ CAFs in tumours. CD26+ CAFs emerged as a large novel subpopulation, only matched by FAPα+ CAFs in abundance.

Conclusion
We demonstrate that multiple subpopulations of CAFs co-exist in murine triple negative breast cancer, and that the abundance and dynamics for each marker differ depending on tumour type and time. Our results form the foundation needed to isolate and characterise specific CAF populations, and ultimately provide an opportunity to therapeutically target specific CAF subpopulations.
Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer
Authors: Zhang Hao , Dai Ziyu , Wu Wantao , Wang Zeyu , Zhang Nan , Zhang Liyang , Zeng Wen-Jing , Liu Zhixiong , Cheng Quan 
Published: June 2021

AbstractThe cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)/B7 and programmed death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) are two most representative immune checkpoint pathways, which negatively regulate T cell immune function during different phases of T-cell activation. Inhibitors targeting CTLA-4/B7 and PD1/PD-L1 pathways have revolutionized immunotherapies for numerous cancer types. Although the combined anti-CTLA-4/B7 and anti-PD1/PD-L1 therapy has demonstrated promising clinical efficacy, only a small percentage of patients receiving anti-CTLA-4/B7 or anti-PD1/PD-L1 therapy experienced prolonged survival. Regulation of the expression of PD-L1 and CTLA-4 significantly impacts the treatment effect. Understanding the in-depth mechanisms and interplays of PD-L1 and CTLA-4 could help identify patients with better immunotherapy responses and promote their clinical care. In this review, regulation of PD-L1 and CTLA-4 is discussed at the levels of DNA, RNA, and proteins, as well as indirect regulation of biomarkers, localization within the cell, and drugs. Specifically, some potential drugs have been developed to regulate PD-L1 and CTLA-4 expressions with high efficiency.
Podiatrists' views and experiences of using real time clinical gait analysis in the assessment and treatment of posterior tibial tendon dysfunction
Authors: Harradine Paul , Gates Lucy , Metcalf Cheryl , Bowen Catherine 
Published: June 2021

AbstractBackgroundReal time clinical gait analysis (RTCGA) is often incorporated as part of a general or lower limb musculoskeletal (MSK) adult patient assessment. However, it is not known if RTCGA is clinically effective as a useful outcome measure or aids in decision making. Whether there is a clinical worth in conducting RTCGA in adult MSK consultations remains controversial. The aim of this study was to provide unique insights into MSK podiatrists use and opinions of RTCGA, using Posterior Tibial Tendon Dysfunction (PTTD) as an exemplar adult condition.MethodsA qualitative approach was employed to explore MSK podiatrists' views and experiences of RTCGA when assessing or treating patients with PTTD. Semi‐structured interviews were conducted via Skype video calls which were transcribed using an orthographic transcription method. Thematic analysis was employed to identify key meanings and report patterns within the data.ResultsTwenty nine MSK podiatrists who used RTCGA in the assessment and treatment of PTTD participated in the study. Five themes were identified as 1) RTCGA Method; 2) Working with RTCGA; 3) RTCGA uses; 4) What could aid RTCGA; 5) How RTCGA skills are acquired. This is the first known study to explore this topic of relevance to clinicians and researchers alike. Clinical observations were not only kinematic, but also included patient perceived experiences such as pain and orthotic comfort with normative kinematic reference values not perceived as important to that management goal. The most common barefoot RTCGA observations performed were the rearfoot to leg angle, medial bulge, forefoot abduction and arch integrity. However, a high amount of variation in many gait observations was noted between participants. Documentation methods also varied with a four‐point scale system to grade motion and position most often employed and RTCGA was most often learnt through experience. The main barriers to performing RTCGA were clinical time and space restrictions.ConclusionFindings from this study have provided a view of how podiatry MSK clinicians utilise RTCGA within their practice. MSK podiatrists use RTCGA as both an outcome measure and as an aid in decision making. This implies a perceived worth in conducting RTCGA, however further work is recommended that focusses on development of a national guideline to RTCGA to be adopted.
Sleep disorders reveal distress among children and adolescents during the Covid-19 first wave: results of a large web-based Italian survey
Authors: Dondi Arianna , Fetta Anna , Lenzi Jacopo , Morigi Francesca , Candela Egidio , Rocca Alessandro , Cordelli Duccio Maria , Lanari Marcello 
Published: June 2021

Abstract
Background
Measures to contain the Covid-19 pandemic led to significant lifestyle changes for children and adolescents mainly related to the closure of schools and recreational activities, reduced social interaction, and increased family concerns.

Methods
A cross-sectional online survey of 78 questions investigating social determinants of health, mood changes, symptoms of anxiety, increase in sleep disorders and unusual repetitive movements was offered to parents living in Italy with children ≤18 years; including families of children with disabilities, autism spectrum disorders, chronic diseases, and specific learning disabilities. The survey was conducted on the Qualtrics platform 6 months after the beginning of the pandemic and distributed in hospitals and paediatricians’ waiting rooms as well as through social networks. The primary outcomes were the increase in sleep disorders among children and adolescents. Possible risk factors were investigated through multivariable regression.

Results
Six thousand two hundred ten volunteer parents responded to the questions concerning mood changes, sleep disorders and unusual repetitive movements, and were included in the present study. The majority were female (91.8%) and Italian (97.0%). 72.7% answered that their children had become more nervous, worried, or sad (80.2% in children with learning disabilities); 77.6% reported feelings of loneliness and 69.3% more difficulties in children falling asleep, 30.2% in staying asleep, and 18.7% an increase in nightmares and/or sleep terrors. Statistical analysis identified socioeconomic status, parent’s job loss, food insecurity, family attitude toward the pandemic, and children’s mood swing, feelings of loneliness, or missing outdoor activities, as major risk factors for sleep disorders.

Conclusion
The first Covid-19 lockdown impacted children’s and adolescents’ health through an increase in sleep disorders. In the following phases of the pandemic, this evidence may be useful to investigate and treat these disorders as well as make decisions about containment health policies concerning this age group.
Exploring intervention components in association with changes in preschool children’s vegetable intake: the BRA-study
Authors: Kristiansen Anne Lene , Himberg-Sundet Anne , Bjelland Mona , Lien Nanna , Holst René , Andersen Lene Frost 
Published: June 2021

Abstract
Objective
The present study aimed to explore kindergarten staffs’ perceived usefulness of intervention components in association with changes in children’s vegetable intake and vegetables served in the kindergarten. Assessment of the perceived usefulness of intervention components consisted of a paper-based questionnaire for the kindergarten staff assessing usefulness of posters, supplementary material and 1-day inspirational course. Children’s vegetable intake in the kindergarten was assessed by direct observation, while vegetables served was assessed by a 5-day weighted vegetable diary.

Results
Seventy-three kindergartens in two counties in Norway participated (response rate 15%) and parental consent was obtained for 633 children 3–5 years of age at baseline (response rate 39%). Mixed effect models indicated a tendency that posters were associated with increased child vegetable intake (P = 0.062). Surprisingly, a low degree of perceived usefulness of supplementary material was associated with the largest increase in child vegetable intake (P = 0.020). No significant associations between perceived usefulness of intervention components and vegetables served in the kindergarten were found. This study indicated a tendency that posters were associated with increased child vegetable intake; however, this may also be due to synergies between multiple intervention components.
Trial registration International Standard Randomized Controlled Trials ISRCTN51962956 (http://www.isrctn.com/ISRCTN51962956). Registered 21 June 2016 (retrospectively registered).
Whole gene analysis of a genotype G29P[6] human rotavirus strain identified in Central African Republic
Authors: Banga-Mingo Virginie , Esona Mathew D. , Betrapally Naga S. , Gautam Rashi , Jaimes Jose , Katz Eric , Waku-Kouomou Diane , Bowen Michael D. , Gouandjika-Vasilache Ionela 
Published: June 2021

Abstract
Objective
Rotavirus A (RVA) remains the main causative agent of gastroenteritis in young children and the young of many mammalian and avian species. In this study we describe a RVA strain detected from a 6-month-old child from Central African Republic (CAR).

Results
We report the 11 open reading frame sequences of a G29-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2 rotavirus strain, RVA/Human-wt/CAR/CAR91/2014/G29P[6]. Nine genes (VP1–VP3, VP6, NSP1–NSP5) shared 90–100% sequence similarities with genogroup 2 rotaviruses. Phylogenetically, backbone genes, except for VP3 and NSP4 genes, were linked with cognate gene sequences of human DS-1-like genogroup 2, hence their genetic origin. The VP3 and NSP4 genes, clustered genetically with both human and animal strains, an indication genetic reassortment human and animal RVA strains has taken place. The VP7 gene shared nucleotide (93–94%) and amino acid (95.5–96.7%) identities with Kenyan and Belgian human G29 strains, as well as to buffalo G29 strain from South Africa, while the VP4 gene most closely resembled P[6]-lineage I strains from Africa and Bangladesh (97%).
Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity
Authors: Sarn Nick , Thacker Stetson , Lee Hyunpil , Eng Charis 
Published: June 2021

Abstract
Background
Autism spectrum disorder (ASD) has a strong genetic etiology. Germline mutation in the tumor suppressor gene PTEN is one of the best described monogenic risk cases for ASD. Animal modeling of cell-specific Pten loss or mutation has provided insight into how disruptions to the function of PTEN affect neurodevelopment, neurobiology, and social behavior. As such, there is a growing need to understand more about how various aspects of PTEN activity and cell-compartment-specific functions, contribute to certain neurological or behavior phenotypes.

Methods
To understand more about the relationship between Pten localization and downstream effects on neurophenotypes, we generated the nuclear-predominant PtenY68H/+ mouse, which is identical to the genotype of some PTEN-ASD individuals. We subjected the PtenY68H/+ mouse to morphological and behavioral phenotyping, including the three-chamber sociability, open field, rotarod, and marble burying tests. We subsequently performed in vivo and in vitro cellular phenotyping and concluded the work with a transcriptomic survey of the PtenY68H/+ cortex, which profiled gene expression.

Results
We observe a significant increase in P-Akt downstream of canonical Pten signaling, macrocephaly, decreased sociability, decreased preference for novel social stimuli, increased repetitive behavior, and increased thigmotaxis in PtenY68H/+ six-week-old (P40) mice. In addition, we found significant microglial activation with increased expression of complement and neuroinflammatory proteins in vivo and in vitro accompanied by enhanced phagocytosis. These observations were subsequently validated with RNA-seq and qRT-PCR, which revealed overexpression of many genes involved in neuroinflammation and neuronal function, including oxytocin. Oxytocin transcript was fivefold overexpressed (P = 0.0018), and oxytocin protein was strongly overexpressed in the PtenY68H/+ hypothalamus.

Conclusions
The nuclear-predominant PtenY68H/+ model has clarified that Pten dysfunction links to microglial pathology and this associates with increased Akt signaling. We also demonstrate that Pten dysfunction associates with changes in the oxytocin system, an important connection between a prominent ASD risk gene and a potent neuroendocrine regulator of social behavior. These cellular and molecular pathologies may related to the observed changes in social behavior. Ultimately, the findings from this work may reveal important biomarkers and/or novel therapeutic modalities that could be explored in individuals with germline mutations in PTEN with ASD.
Influence of the densities and nutritional components of bacterial colonies on the culture-enriched gut bacterial community structure
Authors: Gu Yanrong , Yan Dong , Wu Minna , Li Min , Li Puze , Wang Jingjing , Chang Yahan , Yang Fan , Di Shaojun , Ni Shijun , Yang Mengjie , Liu Jieyu 
Published: June 2021

AbstractIsolating relevant microorganisms is still a substantial challenge that limits the use of bacteria in the maintenance of human health. To confirm which media and which bacterial colony densities can enrich certain kinds of bacteria, we selected eight common media and used them to enrich the gut microorganisms on agar plates. Then, we calculated the numbers of bacterial colonies and collected the bacterial culture mixtures from each kind of medium. Using the Illumina HiSeq platform, we analyzed the composition and diversity of the culture-enriched gut bacterial community. Our data suggested that medium supplemented with blood could increase the diversity of the bacterial community. In addition, beef powder and peptone could significantly change the culture-enriched bacterial community. A moderate density (100–150 colony-forming units per plate) was optimal for obtaining the highest diversity on the agar. Similarly, membrane transport was significantly enriched in the moderate-density group, which indicated a more active metabolism in this density range. Overall, these results reveal the optimal culture conditions, including the densities of colonies and nutritional components for various gut bacteria, that provide a novel strategy for isolating bacteria in a way that is targeted and avoids blinded and repetitive work.
Short-term health-related quality of life, physical function and psychological consequences of severe COVID-19
Authors: Carenzo Luca , Protti Alessandro , Dalla Corte Francesca , Aceto Romina , Iapichino Giacomo , Milani Angelo , Santini Alessandro , Chiurazzi Chiara , Ferrari Michele , Heffler Enrico , Angelini Claudio , Aghemo Alessio , Ciccarelli Michele , Chiti Arturo , Iwashyna Theodore J. , Herridge Margaret S. , Cecconi Maurizio ,   the Humanitas COVID-19 Task Force
Published: June 2021

Abstract
Background
Survivors of severe COVID-19 are at risk of impaired health-related quality of life (HRQoL) and persistent physical and psychological disability after ICU and hospital discharge. The subsequent social burden is a major concern. We aimed to assess the short-term HRQoL, physical function and prevalence of post-traumatic stress symptoms of invasively mechanically ventilated COVID-19 patients treated in our ICU.

Methods
Prospective, observational cohort study in a follow-up clinic. Patients completed a 6-min walking test (6MWT) to assess their cardio-pulmonary function around 2 months (early follow-up) from hospital discharge, the EQ-5D-5L questionnaire for quality of life assessment around 2 months and at 6 months from hospital discharge and an anonymous web-based Impact of Event Scale-Revised (IES-R) questionnaire for Post-Traumatic Stress symptoms at 2 months.

Results
47 patients attended our follow-up program, mean age 59 ± 10 years, median pre-morbid Clinical Frailty Scale (CFS) 2 [2–3]. The median distance walked in 6 min was 470 [406–516] m, 83 [67–99]% of the predicted value. Overall 1 out 3 patients and 4/18 (22%) among those with a good functional baseline prior to COVID-19 (CFS of 1 or 2) had lower (84%) than predicted 6MWT. EQ-5D-5L quality of life VAS was 80 [70–90] out of 100 at early follow-up with a slight improvement to 85 [77.5–90] at 6 months. Mobility, self-care and usual activities improved between the two timepoints, while pain/discomfort and depression/anxiety did not improve or got worse. The IES-R total score was greater than the threshold for concern of 1.6 in 27/41(66%) respondents.

Conclusions
Patients recovering from severe COVID-19 requiring invasive mechanical ventilation surviving hospital discharge present with early mild to moderate functional impairment, mildly reduced quality of life from hospital discharge with an overall improvement of mobility, self-care and the ability of performing usual activities, while a worsening of pain and depression/anxiety symptoms at 6 months and a large proportion of symptoms of post-traumatic distress soon after hospital discharge.
Tsunami evacuation times and routes to safe zones: a GIS-based approach to tsunami evacuation planning on the island of Stromboli, Italy
Authors: Bonilauri Emmie M. , Harris Andrew J. L. , Morin Julie , Ripepe Maurizio , Mangione Domenico , Lacanna Giorgio , Ciolli Stefano , Cusolito Maria , Deguy Pauline 
Published: June 2021

AbstractWhile a landslide at the volcanic island of Stromboli (Aeolian Islands, Italy) in December 2002 created a tsunami with a run-up of 10.9 m, two paroxysmal eruptions in the summer of 2019 caused a tsunami with an amplitude of 40 to 20 cm. All three events required rapid, spontaneous emergency evacuations of the beach zone as the time between tsunami generation and impact is around 4 min. These conditions thus require a special consideration of the issue of evacuation capabilities on the island in the event of a volcanogenic tsunami. The purpose of this paper is thus to (i) determine pedestrian evacuation times from high-risk coastal areas to safe zones, (ii) to assess building evacuation ease, and (iii) determine emergency evacuation plans (for buildings and coastal zones). For this purpose, we created a GIS-based risk analysis/mapping tool that also allowed macroscopic evacuation modelling. In our case, the high-risk zone to be evacuated involves an area extending to 10 m a.s.l. and involving 123 individual buildings over an area of 0.18 km2. The results show that 33% of the buildings can be evacuated in 4 min, and that a 10-min warning time is required for a complete and well-distributed evacuation whereby the population is evenly distributed between all evacuation exits to avoid the potential for congestion. Initial interviews of residents in the at-risk zone reveal a high level of awareness and a desire for personalized evacuation scenarios.