bluuebunny/crossref_metadata_2025_split huggingface dataset:
The experiences of patients with diabetes and strategies for their management during the first COVID-19 lockdown: a qualitative study
Authors: Vilafranca Cartagena Mireia , Tort-Nasarre Glòria , Romeu-Labayen Maria , Vidal-Alaball Josep 
Published: May 2022

Abstract
Background
During the pandemic, primary care systems prioritised attention to COVID-19 patients; chronically ill patients, such as people with Type 2 Diabetes were obliged to take more responsibility for their own care. We aimed to analyse the experiences of patients with Type 2 Diabetes Mellitus during the stay-at-home order that was in place during the first wave of the COVID-19 pandemic and identify the strategies and resources used in managing their care.

Method
We conducted a qualitative descriptive study. The participants were ten patients with type 2 Diabetes Mellitus who experienced strict lockdown during the first wave of the COVID-19 pandemic in Catalonia, Spain, selected using intentional sampling. We recorded semi-structured interviews with the participants and conducted thematic analysis.

Results
We identified 14 subthemes, which we then grouped into three overarching themes: 1) anxiety, fear, and vulnerability (anxiety, fear, vulnerability, rethinking life, loneliness, sadness), 2) insufficient diabetes monitoring by the health system (health care received, glycaemic control, view of treatment by health providers) and proactive self-care (changes in daily routine, diet, physical activity, medication, personal protective equipment & social distancing).

Conclusion
Despite the exceptional nature of the situation and the stress, worry, and changes in their daily lives, many respondents reported that they had successfully modified their lifestyles. Self-care was effective during confinement and was based on a process of adaptation using the resources available, without face-to-face contact with primary care health staff.

Relevance to clinical practice
These results can help to guide the design and implementation of self-care-focused strategies and also to explore new ways of empowering patients without access to health care personnel.
Experimental demonstration of tethered gene drive systems for confined population modification or suppression
Authors: Metzloff Matthew , Yang Emily , Dhole Sumit , Clark Andrew G. , Messer Philipp W. , Champer Jackson 
Published: May 2022

Abstract
Background
Homing gene drives hold great promise for the genetic control of natural populations. However, current homing systems are capable of spreading uncontrollably between populations connected by even marginal levels of migration. This could represent a substantial sociopolitical barrier to the testing or deployment of such drives and may generally be undesirable when the objective is only local population control, such as suppression of an invasive species outside of its native range. Tethered drive systems, in which a locally confined gene drive provides the CRISPR nuclease needed for a homing drive, could provide a solution to this problem, offering the power of a homing drive and confinement of the supporting drive.

Results
Here, we demonstrate the engineering of a tethered drive system in Drosophila, using a regionally confined CRISPR Toxin-Antidote Recessive Embryo (TARE) drive to support modification and suppression homing drives. Each drive was able to bias inheritance in its favor, and the TARE drive was shown to spread only when released above a threshold frequency in experimental cage populations. After the TARE drive had established in the population, it facilitated the spread of a subsequently released split homing modification drive (to all individuals in the cage) and of a homing suppression drive (to its equilibrium frequency).

Conclusions
Our results show that the tethered drive strategy is a viable and easily engineered option for providing confinement of homing drives to target populations.
The effectiveness of the Structured Health Intervention For Truckers (SHIFT): a cluster randomised controlled trial (RCT)
Authors: Clemes Stacy A. , Varela-Mato Veronica , Bodicoat Danielle H. , Brookes Cassandra L. , Chen Yu-Ling , Edwardson Charlotte L. , Gray Laura J. , Guest Amber J. , Johnson Vicki , Munir Fehmidah , Paine Nicola J. , Richardson Gerry , Ruettger Katharina , Sayyah Mohsen , Sherry Aron , Di Paola Ana Suazo , Troughton Jacqui , Yates Thomas , King James A. 
Published: May 2022

AbstractBackgroundLong distance heavy goods vehicle (HGV) drivers exhibit higher than nationally representative rates of obesity, and obesity-related co-morbidities, and are underserved in terms of health promotion initiatives. The purpose of this study was to evaluate the effectiveness of the multicomponent ‘Structured Health Intervention For Truckers’ (SHIFT), compared to usual care, at 6- and 16–18-month follow-up.MethodsWe conducted a two-arm cluster RCT in transport sites throughout the Midlands, UK. Outcome measures were assessed at baseline, at 6- and 16–18-month follow-up. Clusters were randomised (1:1) following baseline measurements to either the SHIFT arm or usual practice control arm. The 6-month SHIFT programme included a group-based interactive 6-h education and behaviour change session, health coach support and equipment provision (Fitbit® and resistance bands/balls to facilitate a ‘cab workout’). The primary outcome was device-assessed physical activity (mean steps/day) at 6 months. Secondary outcomes included the following: device-assessed sitting, physical activity intensity and sleep; cardiometabolic health, diet, mental wellbeing and work-related psychosocial variables. Data were analysed using mixed-effect linear regression models using a complete-case population.ResultsThree hundred eighty-two HGV drivers (mean ± SD age: 48.4 ± 9.4 years, BMI: 30.4 ± 5.1 kg/m2, 99% male) were recruited across 25 clusters (sites) and randomised into either the SHIFT (12 clusters,n = 183) or control (13 clusters,n = 199) arms. At 6 months, 209 (55%) participants provided primary outcome data. Significant differences in mean daily steps were found between groups, in favour of the SHIFT arm (adjusted mean difference: 1008 steps/day, 95% CI: 145–1871,p = 0.022). Favourable differences were also seen in the SHIFT group, relative to the control group, in time spent sitting (− 24 mins/day, 95% CI: − 43 to − 6), and moderate-to-vigorous physical activity (6 mins/day, 95% CI: 0.3–11). Differences were not maintained at 16–18 months. No differences were observed between groups in the other secondary outcomes at either follow-up.ConclusionsThe SHIFT programme led to a potentially clinically meaningful difference in daily steps, between trial arms, at 6 months. Whilst the longer-term impact is unclear, the programme offers potential to be incorporated into driver training courses to promote activity in this at-risk, underserved and hard-to-reach essential occupational group.Trial registrationISRCTN10483894 (date registered: 01/03/2017)
Genetic susceptibility, screen-based sedentary activities and incidence of coronary heart disease
Authors: Kim Youngwon , Yeung Shiu Lun Au , Sharp Stephen J. , Wang Mengyao , Jang Haeyoon , Luo Shan , Brage Soren , Wijndaele Katrien 
Published: May 2022

Abstract
Background
Whether the associations of time spent in screen-based sedentary activities with CHD vary by genetic susceptibility is currently unknown. The objective of this study was to examine the interplay of genetic susceptibility to CHD and two prevalent types of screen-based sedentary activities (television [TV] viewing and computer use) for CHD incidence.

Methods
This prospective cohort study included 373,026 individuals of European ancestry without prevalent CHD/stroke from UK Biobank data. Genetic susceptibility to CHD was assessed using weighted polygenic risk scores, calculated by summing the number of risk-increasing alleles among 300 single-nucleotide polymorphisms, multiplied by their corresponding effect estimates. TV viewing and computer use were assessed through touch-screen questionnaires. CHD incidence (n=9185) was adjudicated over a median 12.6-year follow-up.

Results
Compared with ≥4h/day of TV viewing, the hazard ratio of CHD was 0.84 (95% confidence interval [CI] 0.79–0.90) and 0.94 (0.90–0.99) for ≤1h/day and 2–3h/day of TV viewing, respectively, after adjusting for confounders including the genetic risk. CHD hazards were higher for medium and high genetic risk than for low genetic risk. Across all levels of genetic risk including high-genetic risk, ≤1h/day of TV viewing had lower CHD hazards, compared with ≥4h/day: no evidence of interaction between genetic risk and TV viewing (p value: 0.362). Estimates of the population attributable fraction (PAF) suggested that 10.9% (95% CI 6.1–15.3%) of CHD could be prevented if TV viewing time were reduced to ≤1h/day, assuming causality. The PAF values were relatively larger for medium-to-high genetic risk than for low genetic risk, although the CIs were wide and overlapping. No associations were observed for computer use.

Conclusions
Less TV viewing time was associated with lower CHD risk independently of genetic risk. Clinical trials targeted at individuals with high genetic susceptibility should consider reducing TV viewing as as a behavioural target for prevention of an early onset of cardiovascular events.
Exogenous leptin enhances markers of airway fibrosis in a mouse model of chronic allergic airways disease
Authors: Ihrie Mark D. , McQuade Victoria L. , Womble Jack T. , Hegde Akhil , McCravy Matthew S. , Lacuesta Cyrus Victor G. , Tighe Robert M. , Que Loretta G. , Walker Julia K. L. , Ingram Jennifer L. 
Published: May 2022

Abstract
Background
Asthma patients with comorbid obesity exhibit increased disease severity, in part, due to airway remodeling, which is also observed in mouse models of asthma and obesity. A mediator of remodeling that is increased in obesity is leptin. We hypothesized that in a mouse model of allergic airways disease, mice receiving exogenous leptin would display increased airway inflammation and fibrosis.

Methods
Five-week-old male and female C57BL/6J mice were challenged with intranasal house dust mite (HDM) allergen or saline 5 days per week for 6 weeks (n = 6–9 per sex, per group). Following each HDM exposure, mice received subcutaneous recombinant human leptin or saline. At 48 h after the final HDM challenge, lung mechanics were evaluated and the mice were sacrificed. Bronchoalveolar lavage was performed and differential cell counts were determined. Lung tissue was stained with Masson’s trichrome, periodic acid-Schiff, and hematoxylin and eosin stains. Mouse lung fibroblasts were cultured, and whole lung mRNA was isolated.

Results
Leptin did not affect mouse body weight, but HDM+leptin increased baseline blood glucose. In mixed-sex groups, leptin increased mouse lung fibroblast invasiveness and increased lung Col1a1 mRNA expression. Total lung resistance and tissue damping were increased with HDM+leptin treatment, but not leptin or HDM alone. Female mice exhibited enhanced airway responsiveness to methacholine with HDM+leptin treatment, while leptin alone decreased total respiratory system resistance in male mice.

Conclusions
In HDM-induced allergic airways disease, administration of exogenous leptin to mice enhanced lung resistance and increased markers of fibrosis, with differing effects between males and females.
COVID-19 double jeopardy: the overwhelming impact of the social determinants of health
Authors: Badalov Elizabeth , Blackler Liz , Scharf Amy E. , Matsoukas Konstantina , Chawla Sanjay , Voigt Louis P. , Kuflik Arthur 
Published: May 2022

Abstract
Background
The COVID-19 pandemic has strained healthcare systems by creating a tragic imbalance between needs and resources. Governments and healthcare organizations have adapted to this pronounced scarcity by applying allocation guidelines to facilitate life-or-death decision-making, reduce bias, and save as many lives as possible. However, we argue that in societies beset by longstanding inequities, these approaches fall short as mortality patterns for historically discriminated against communities have been disturbingly higher than in the general population.

Methods
We review attack and fatality rates; survey allocation protocols designed to deal with the extreme scarcity characteristic of the earliest phases of the pandemic; and highlight the larger ethical perspectives (Utilitarianism, non-Utilitarian Rawlsian justice) that might justify such allocation practices.

Results
The COVID-19 pandemic has dramatically amplified the dire effects of disparities with respect to the social determinants of health. Patients in historically marginalized groups not only have significantly poorer health prospects but also lower prospects of accessing high quality medical care and benefitting from it even when available. Thus, mortality among minority groups has ranged from 1.9 to 2.4 times greater than the rest of the population. Standard allocation schemas, that prioritize those most likely to benefit, perpetuate and may even exacerbate preexisting systemic injustices.

Conclusions
To be better prepared for the inevitable next pandemic, we must urgently begin the monumental project of addressing and reforming the structural inequities in US society that account for the strikingly disparate mortality rates we have witnessed over the course of the current pandemic.
Long-term surgical outcomes of gastric neuroendocrine carcinoma and mixed neuroendocrine-non-neuroendocrine neoplasms
Authors: Iwasaki Kenichi , Barroga Edward , Enomoto Masaya , Tsurui Kazushige , Shimoda Yota , Matsumoto Moe , Miyoshi Kenta , Ota Yoshihiro , Matsubayashi Jun , Nagakawa Yuichi 
Published: May 2022

Abstract
Background
Neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are extremely rare subtypes of gastric cancer. MiNEN is a mix of carcinomatous components and neuroendocrine neoplasm in the same lesion. NEC and MiNEN have a poor prognosis, are difficult to diagnose, and have no established treatment. Herein, we assessed the clinicopathological characteristics and long-term surgical outcomes of gastric NEC and MiNEN patients in our hospital.

Methods
We retrospectively assessed 1538 patients pathologically diagnosed with gastric cancer and who underwent curative surgical resection at our institution between January 1999 and October 2021. Of these patients, 25 (1.6%) were pathologically diagnosed with neuroendocrine neoplasms. From these 25 patients, we retrospectively analyzed the clinicopathological characteristics and surgical outcomes of 13 (0.8%) patients pathologically diagnosed with NEC or MiNEN.

Results
The NEC and MiNEN patients consisted of 11 men and 2 women [mean age, 74 (62–84) years]. The preoperative histological diagnoses were NEC (n = 4) and adenocarcinoma (n = 9). The final pathological diagnoses were large cell neuroendocrine carcinoma (LCNEC; n = 7) and MiNEN (n = 6). Total gastrectomy was the most common surgical procedure (9/13, 69.2%), followed by distal gastrectomy (3/13, 23.1%) and proximal gastrectomy (1/13, 7.7%). Immunohistochemical staining showed 8 CD56-positive patients. All 13 patients were positive for chromogranin A and synaptophysin. The mean Ki-67 value was 64.8 (0–95)%, and the mean mitotic score was 107.9 (0–400). Nine patients survived without recurrence postresection. The median postresection overall survival time was 68.7 (8.0–129) months. The 5-year survival rate was 0.75 ([95% CI] 0.408–0.912).

Conclusion
The surgical treatment outcomes of NEC and MiNEN patients were relatively favorable. Although evidence concerning the effectiveness of surgery alone is meager, radical resection as part of multidisciplinary treatment including chemotherapy can potentially improve prognosis.
Asperosaponin VI ameliorates the CMS-induced depressive-like behaviors by inducing a neuroprotective microglial phenotype in hippocampus via PPAR-γ pathway
Authors: Jiang Xue , Yi Saini , Liu Qin , Su Dapeng , Li Liangyuan , Xiao Chenghong , Zhang Jinqiang 
Published: May 2022

Abstract
Background
The natural compound asperosaponin VI has shown potential as an antidepressant, but how it works is unclear. Here, we explored its effects on mice exposed to chronic mild stress (CMS) and the underlying molecular pathways.

Methods
Mice were exposed to CMS for 3 weeks followed by asperosaponin VI (40 mg/kg) or imipramine (20 mg/kg) for another 3 weeks. Depression-like behaviors were assessed in the forced swimming test (FST), sucrose preference test (SPT), tail suspension test (TST). Microglial phenotypes were evaluated using immunofluorescence staining, real-time quantitative PCR and enzyme-linked immunosorbent assays in hippocampus of mice. In some experiments, stressed animals were treated with the PPAR-γ antagonist GW9662 to examine its involvement in the effects of asperosaponin VI. Blockade of PPAR-γ in asperosaponin VI-treated primary microglia in the presence of lipopolysaccharide (LPS) was executed synchronously. The nuclear transfer of PPAR-γ in microglia was detected by immunofluorescence staining in vitro and in vivo. A co-cultured model of neuron and microglia was used for evaluating the regulation of ASA VI on the microglia–neuron crosstalk molecules.

Results
Asperosaponin VI ameliorated depression-like behaviors of CMS mice based on SPT, TST and FST, and this was associated with a switch of hippocampal microglia from a pro-inflammatory (iNOS+-Iba1+) to neuroprotective (Arg-1+-Iba1+) phenotype. CMS reduced the expression levels of PPAR-γ and phosphorylated PPAR-γ in hippocampus, which asperosaponin VI partially reversed. GW9662 treatment prevented the nuclear transfer of PPAR-γ in asperosaponin VI-treated microglia and inhibited the induction of Arg-1+ microglia. Blockade of PPAR-γ signaling also abolished the ability of asperosaponin VI to suppress pro-inflammatory cytokines while elevating anti-inflammatory cytokines in the hippocampus of CMS mice. The asperosaponin VI also promoted interactions between hippocampal microglia and neurons by enhancing CX3CL1/CX3CR1 and CD200/CD200R, and preserved synaptic function based on PSD95, CamKII β and GluA levels, but not in the presence of GW9662. Blockade of PPAR-γ signaling also abolished the antidepressant effects of asperosaponin VI in the SPT, TST and FST.

Conclusion
CMS in mice induces a pro-inflammatory microglial phenotype that causes reduced crosstalk between microglia and neuron, inflammation and synaptic dysfunction in the hippocampus, ultimately leading to depression-like behaviors. Asperosaponin VI may ameliorate the effects of CMS by inducing microglia to adopt a PPAR-γ-dependent neuroprotective phenotype.
Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress
Authors: Liu Chen-Yue , Chen Jian-Bei , Liu Yue-Yun , Zhou Xue-Ming , Zhang Man , Jiang You-Ming , Ma Qing-Yu , Xue Zhe , Zhao Zong-Yao , Li Xiao-Juan , Chen Jia-Xu 
Published: May 2022

Abstract
Background
Many studies about depression have focused on the dysfunctional synaptic signaling in the hippocampus that drives the pathophysiology of depression. Radix Bupleuri has been used in China for over 2000 years to regulate liver-qi. Extracted from Radix Bupleuri, Saikosaponin D (SSD) is a pharmacologically active substance that has antidepressant effects. However, its underlying mechanism remains unknown.

Materials and methods
A chronic unpredictable mild stress (CUMS) paradigm was used as a rat model of depression. SD rats were randomly assigned to a normal control (NC) group or one exposed to a CUMS paradigm. Of the latter group, rats were assigned to four subgroups: no treatment (CUMS), fluoxetine-treated (FLU), high-dose and low-dose SSD-treated (SSDH and SSDL). SSD was orally administrated of 1.50 mg/kg and 0.75 mg/kg/days for three weeks in the SSDH and SSDL groups, respectively. Fluoxetine was administrated at a dose of 2.0 mg/kg/days. SSD’s antidepressant effects were assessed using the open field test, forced swim test, and sucrose preference test. Glutamate levels were quantified by ELISA. Western blot and immunochemical analyses were conducted to quantify proteins in the Homer protein homolog 1 (Homer1)-metabotropic glutamate receptor 5 (mGluR5) and mammalian target of rapamycin (mTOR) pathways in the hippocampal CA1 region. To measure related gene expression, RT-qPCR was employed.

Results
CUMS-exposed rats treated with SSD exhibited increases in food intake, body weight, and improvements in the time spent in the central are and total distance traveled in the OFT, and less pronounced pleasure-deprivation behaviors. SSD also decreased glutamate levels in CA1. In CA1 region of CUMS-exposed rats, SSD treatment increased mGluR5 expression while decreasing Homer1 expression. SSD also increased expressions of postsynaptic density protein 95 (PSD95) and synapsin I (SYP), and the ratios of p-mTOR/mTOR, p-p70S6k/p70S6k, and p-4E-BP1/4E-BP1 in the CA1 region in CUMS-exposed rats.

Conclusions
SSD treatment reduces glutamate levels in the CA1 region and promotes the expression of the synaptic proteins PSD-95 and SYP via the regulation of the Homer1-mGluR5 and downstream mTOR signaling pathways. These findings suggest that SSD could act as a natural neuroprotective agent in the prevention of depression.
Intensity matters: protocol for a randomized controlled trial exercise intervention for individuals with chronic stroke
Authors: Rodrigues Lynden , Moncion Kevin , Eng Janice J. , Noguchi Kenneth S. , Wiley Elise , de Las Heras Bernat , Sweet Shane N. , Fung Joyce , MacKay-Lyons Marilyn , Nelson Aimee J. , Medeiros Diogo , Crozier Jennifer , Thiel Alexander , Tang Ada , Roig Marc 
Published: May 2022

AbstractRationaleCardiovascular exercise is an effective method to improve cardiovascular health outcomes, but also promote neuroplasticity during stroke recovery. Moderate-intensity continuous cardiovascular training (MICT) is an integral part of stroke rehabilitation, yet it may remain a challenge to exercise at sufficiently high intensities to produce beneficial adaptations to neuroplasticity. High-intensity interval training (HIIT) could provide a viable alternative to achieve higher intensities of exercise by using shorter bouts of intense exercise interspersed with periods of recovery.Methods and designThis is a two-arm, parallel-group multi-site RCT conducted at the Jewish Rehabilitation Hospital (Laval, Québec, Canada) and McMaster University (Hamilton, Ontario, Canada). Eighty participants with chronic stroke will be recruited at both sites and will be randomly allocated into a HIIT or MICT individualized exercise program on a recumbent stepper, 3 days per week for 12 weeks. Outcomes will be assessed at baseline, at 12 weeks post-intervention, and at an 8-week follow-up.OutcomesThe primary outcome is corticospinal excitability, a neuroplasticity marker in brain motor networks, assessed with transcranial magnetic stimulation (TMS). We will also examine additional markers of neuroplasticity, measures of cardiovascular health, motor function, and psychosocial responses to training.DiscussionThis trial will contribute novel insights into the effectiveness of HIIT to promote neuroplasticity in individuals with chronic stroke.Trial registrationClinicalTrials.govNCT03614585. Registered on 3 August 2018
Transcriptomic perspectives of memory-like NK cells and aging
Authors: Wang Dandan , Malarkannan Subramaniam 
Published: May 2022

AbstractA recent study highlights the presence of a unique memory-like natural killer (NK) cell subset, which accumulates with aging and appears to associate withdisease severity in COVID-19 patients. While the clinical relevance of memory in NK cells is being debated, the molecular identity of this subset in the form of a single-cell transcriptome is essential to define their origin, longevity, functions, and disease relevance.