bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifetime risk of cardiovascular-renal disease in type 2 diabetes: a population-based study in 473,399 individuals
Authors: Zhang Ruiqi , Mamza Jil Billy , Morris Tamsin , Godfrey George , Asselbergs Folkert W. , Denaxas Spiros , Hemingway Harry , Banerjee Amitava 
Published: February 2022

Abstract
Background
Cardiovascular and renal diseases (CVRD) are major causes of mortality in individuals with type 2 diabetes (T2D). Studies of lifetime risk have neither considered all CVRD together nor the relative contribution of major risk factors to combined disease burden.

Methods
In a population-based cohort study using national electronic health records, we studied 473,399 individuals with T2D in England 2007–2018. Lifetime risk of individual and combined major adverse renal cardiovascular events, MARCE (including CV death and CVRD: heart failure; chronic kidney disease; myocardial infarction; stroke or peripheral artery disease), were estimated, accounting for baseline CVRD status and competing risk of death. We calculated population attributable risk for individual CVRD components. Ideal cardiovascular health was defined by blood pressure, cholesterol, glucose, smoking, physical activity, diet, and body mass index (i.e. modifiable risk factors).

Results
In individuals with T2D, lifetime risk of MARCE was 80% in those free from CVRD and was 97%, 93%, 98%, 89% and 91% in individuals with heart failure, chronic kidney disease, myocardial infarction, stroke and peripheral arterial disease, respectively at baseline. Among CVRD-free individuals, lifetime risk of chronic kidney disease was highest (54%), followed by CV death (41%), heart failure (29%), stroke (20%), myocardial infarction (19%) and peripheral arterial disease (9%). In those with HF only, 75% of MARCE after index T2D can be attributed to HF after adjusting for age, gender, and comorbidities. Compared with those with > 1, < 3 and ≥3 modifiable health risk behaviours, achieving ideal cardiovascular health could reduce MARCE by approximately 41.5%, 23.6% and 17.2%, respectively, in the T2D population.

Conclusions
Four out of five individuals with T2D free from CVRD, and nearly all those with history of CVRD, will develop MARCE over their lifetime. Early preventive measures in T2D patients are clinical, public health and policy priorities.
Comparison between pressure support ventilation and T-piece in spontaneous breathing trials
Authors: Na Soo Jin , Ko Ryoung-Eun , Nam Jimyoung , Ko Myeong Gyun , Jeon Kyeongman 
Published: February 2022

Abstract
Background
Recent guidelines recommended conducting spontaneous breathing trial (SBT) with modest inspiratory pressure augmentation rather than T-piece or continuous positive airway pressure. However, it was based on few studies focused on the outcomes of extubation rather than the weaning process, despite the existence of various weaning situations in clinical practice. This study was designed to investigate the effects of SBT with pressure support ventilation (PSV) or T-piece on weaning outcomes.

Methods
All consecutive patients admitted to two medical intensive care units (ICUs) and those requiring mechanical ventilation (MV) for more than 24 h from November 1, 2017 to September 30, 2020 were prospectively registered. T-piece trial was used until March 2019, and then, pressure support of 8 cmH2O and 0 positive end-expiratory pressure were used for SBT since July 2019, after a 3-month transition period for the revised SBT protocol. The primary outcome of this study was successful weaning defined according to the WIND (Weaning according to a New Definition) definition and were compared between the T-piece group and PSV group. The association between the SBT method and weaning outcome was evaluated with logistic regression analysis.

Results
In this study, 787 eligible patients were divided into the T-piece (n = 473) and PSV (n = 314) groups after excluding patients for a 3-month transition period. Successful weaning was not different between the two groups (85.0% vs. 86.3%; p = 0.607). However, the PSV group had a higher proportion of short weaning (70.1% vs. 59.0%; p = 0.002) and lower proportion of difficult weaning (13.1% vs. 24.1%; p < 0.001) than the T-piece group. The proportion of prolonged weaning was similar between the two groups (16.9% vs. 16.9%; p = 0.990). After excluding patients who underwent tracheostomy before the SBTs, similar results were found. Reintubation rates at 48 h, 72 h, and 7 days following the planned extubation were not different between the PSV and T-piece groups. Moreover, no significant differences in intensive care unit and hospital mortality and length of stay were observed.

Conclusions
In critically ill medical patients, SBT using PSV was not associated with a higher rate of successful weaning compared with SBT using T-piece. However, PSV could shorten the weaning process without increasing the risk of reintubation.
Pneumothorax management: current state of practice in the UK
Authors: Hallifax Rob J. , Roberts Mark , Russell Nicky , Laskawiec-Szkonter Magda , Walker Steve P. , Maskell Nick A. , Rahman Najib M. 
Published: February 2022

Abstract
Background and objective
Spontaneous pneumothorax is a common pathology but optimal initial treatment regime is not well defined. Treatment options including conservative management, needle aspiration (NA) or insertion of a small-bore chest drain. Recent large randomised controlled trials may change the treatment paradigm: comparing conservative and ambulatory management to standard care, but current guidelines need to be updated. The aim of this study was to assess the current “state of play” in the management of pneumothorax in the UK.

Methods
Physicians and respiratory healthcare staff were invited to complete an online survey on the initial and subsequent management of pneumothorax.

Results
This study is the first survey of pneumothorax practice across the UK, which highlights variation in practice: 50% would manage a large primary pneumothorax with minimal symptoms conservatively, compared to only 3% if there were significant symptoms; 64% use suction if the pneumothorax had not resolved after > 2 days, 15% always clamp the chest drain prior to removal; whereas 30% never do. NICE guidance recommends the use of digital suction but this has not translated into widespread usage: only 23% use digital suction to check for resolution of air leak).

Conclusion
Whilst there has always been allowance for individual clinician preference in guidelines, there needs to be consensus on the optimum management strategy. The challenge the new guidelines face is to design a simple and pragmatic approach, using this new evidence base.
Targeting HNRNPU to overcome cisplatin resistance in bladder cancer
Authors: Shi Zhen-duo , Hao Lin , Han Xiao-xiao , Wu Zhuo-Xun , Pang Kun , Dong Yang , Qin Jia-xin , Wang Guang-yue , Zhang Xuan-ming , Xia Tian , Liang Qing , Zhao Yan , Li Rui , Zhang Shao-qi , Zhang Jun-hao , Chen Jian-gang , Wang Gong-cheng , Chen Zhe-Sheng , Han Cong-hui 
Published: February 2022

Abstract
Purpose
The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC.

Experimental design
The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity.

Results
Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1).

Conclusions
Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.
Causal systems mapping to promote healthy living for pandemic preparedness: a call to action for global public health
Authors: Pronk Nicolaas P. , Faghy Mark A. 
Published: February 2022

AbstractCOVID-19 has severely impacted population health and well-being globally. Acknowledging that COVID-19 will not be the world’s last pandemic, improving healthy living factors (i.e., physical activity, healthful nutrition, healthy weight), which are important in mitigating negative outcomes of future infectious disease pandemics, should be prioritized. Although well-documented, promoting healthy living factors remains challenged by a lack of scalability and sustainability due, in part, to a mismatch between intervention focus on individual behavior change as opposed to recognizing complex and multifactorial causes that prevent people from living healthy lifestyles and maintaining them long-term (such as political will, economic benefits, urban planning, etc.). To recognize this complexity in promoting healthy living, we propose the application of systems science methods for the creation of a comprehensive causal systems map of healthy living factors in the context of COVID-19 to inform future pandemic preparedness. Generating such a map would benefit researchers, practitioners, and policy makers in multi-sector collaborative efforts to improve public health preparedness in the context of future pandemics in a scalable, sustainable, and equitable manner. This effort should be facilitated by a trusted and widely respected governing body with global reach.
Neuroprotective effects of alisol A 24-acetate on cerebral ischaemia–reperfusion injury are mediated by regulating the PI3K/AKT pathway
Authors: Lu Taotao , Li Huihong , Zhou Yangjie , Wei Wei , Ding Linlin , Zhan Zengtu , Liu Weilin , Tao Jing , Xue Xiehua 
Published: February 2022

Abstract
Background
Neuroinflammation and apoptosis are involved in the pathogenesis of ischaemic stroke. Alisol A 24-acetate (24A) exerts a strong inhibitory effect on inflammation and cell apoptosis. The neuroprotective effect of 24A on global cerebral ischaemia/reperfusion (GCI/R) injury remains unclear.

Methods
GCI/R mice were used to investigate the neuroprotective effect of 24A. Modified neurological deficit scores, Morris water maze and object recognition tests were used to evaluate behaviours. Metabolism in brain regions was detected using magnetic resonance spectroscopy (MRS), and changes in microglia, astrocytes and neurons were detected. Inflammation and apoptosis were measured.

Results
The results showed that 24A suppressed neurological deficits scores and improved GCI/R induced cognitive dysfunction. It was also observed that 24A could alleviate neuroinflammation, which manifested as 24A inhibited microglia and astrocytes proliferation, downregulated the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) in the GCI/R mice brain. The apoptosis of neurons reduced, and dendritic spines of hippocampal neurons increased in the presence of 24A. In addition, 24A could up-regulate the expression of phosphorylated phosphoinositide 3-kinases (p-PI3K) and phosphorylated protein kinase B (p-AKT) in GCI/R mice brain, and all the morphological, neurological, and biochemical changes of 24A treatment were abolished by the application of PI3K/AKT pathway inhibitor LY294002.

Conclusions
Taken together, our study indicated that 24A alleviated GCI/R injury by inhibiting neuroinflammation and apoptosis through the regulation of the PI3K/AKT pathway.
Gas6 induces inflammation and reduces plaque burden but worsens behavior in a sex-dependent manner in the APP/PS1 model of Alzheimer’s disease
Authors: Owlett Laura D. , Karaahmet Berke , Le Linh , Belcher Elizabeth K. , Dionisio-Santos Dawling , Olschowka John A. , Elliott Michael R. , O’Banion M. Kerry 
Published: February 2022

Abstract
Background
Alzheimer’s disease is the leading cause of dementia worldwide. TAM receptor tyrosine kinases (Tyro3, Axl, MerTK) are known for their role in engagement of phagocytosis and modulation of inflammation, and recent evidence suggests a complex relationship between Axl, Mer, and microglial phagocytosis of amyloid plaques in AD. Gas6, the primary CNS TAM ligand, reduces neuroinflammation and improves outcomes in murine models of CNS disease. Therefore, we hypothesized that AAV-mediated overexpression of Gas6 would alleviate plaque pathology, reduce neuroinflammation, and improve behavior in the APP/PS1 model of Alzheimer’s disease.

Methods
Adeno-associated viral vectors were used to overexpress Gas6 in the APP/PS1 model of Alzheimer’s disease. Nine-month-old male and female APP/PS1 and nontransgenic littermates received bilateral stereotactic hippocampal injections of AAV-Gas6 or AAV-control, which expresses a non-functional Gas6 protein. One month after injections, mice underwent a battery of behavioral tasks to assess cognitive function and brains were processed for immunohistochemical and transcriptional analyses.

Results
Gas6 overexpression reduced plaque burden in male APP/PS1 mice. However, contrary to our hypothesis, Gas6 increased pro-inflammatory microglial gene expression and worsened contextual fear conditioning compared to control-treated mice. Gas6 overexpression appeared to have no effect on phagocytic mechanisms in vitro or in vivo as measured by CD68 immunohistochemistry, microglial methoxy-04 uptake, and primary microglial uptake of fluorescent fibrillar amyloid beta.

Conclusion
Our data describes a triad of worsened behavior, reduced plaque number, and an increase in proinflammatory signaling in a sex-specific manner. While Gas6 has historically induced anti-inflammatory signatures in the peripheral nervous system, our data suggest an alternative, proinflammatory role in the context of Alzheimer’s disease pathology.
Neurocognitive impact of Zika virus infection in adult rhesus macaques
Authors: Hsu Denise C. , Chumpolkulwong Kesara , Corley Michael J. , Hunsawong Taweewun , Inthawong Dutsadee , Schuetz Alexandra , Imerbsin Rawiwan , Silsorn Decha , Nadee Panupat , Sopanaporn Jumpol , Phuang-Ngern Yuwadee , Klungthong Chonticha , Reed Matthew , Fernandez Stefan , Ndhlovu Lishomwa C. , Paul Robert , Lugo-Roman Luis , Michael Nelson L. , Modjarrad Kayvon , Vasan Sandhya 
Published: February 2022

AbstractBackgroundZika virus (ZIKV) is a mosquito-transmitted flavivirus that affects many regions of the world. Infection, in utero, causes microcephaly and later developmental and neurologic impairments. The impact of ZIKV infection on neurocognition in adults has not been well described. The objective of the study was to assess the neurocognitive impact of ZIKV infection in adult rhesus macaques.MethodsNeurocognitive assessments were performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) via a touch screen and modified Brinkman Board before and after subcutaneous ZIKV inoculation. Immune activation markers were measured in the blood and cerebral spinal fluid (CSF) by multiplex assay and flow cytometry.ResultsAll animals (N = 8) had detectable ZIKV RNA in plasma at day 1 post-inoculation (PI) that peaked at day 2 PI (median 5.9, IQR 5.6–6.2 log10genome equivalents/mL). In all eight animals, ZIKV RNA became undetectable in plasma by day 14 PI, but persisted in lymphoid tissues. ZIKV RNA was not detected in the CSF supernatant at days 4, 8, 14 and 28 PI but was detected in the brain of 2 animals at days 8 and 28 PI. Elevations in markers of immune activation in the blood and CSF were accompanied by a reduction in accuracy and reaction speed on the CANTAB in the majority of animals.ConclusionsThe co-occurrence of systemic and CSF immune perturbations and neurocognitive impairment establishes this model as useful for studying the impact of neuroinflammation on neurobehavior in rhesus macaques, as it pertains to ZIKV infection and potentially other pathogens.
Intermediate-dose cytarabine is an effective therapy for adults with non-Langerhans cell histiocytosis
Authors: Liu Ting , Cai Hua-cong , Cai Hao , Chen Miao , Zhang Wei , Li Jian , Zhou Dao-bin , Cao Xin-xin 
Published: February 2022

Abstract
Background
Non-Langerhans cell histiocytosis, including Erdheim–Chester disease (ECD), Rosai–Dorfman disease (RDD), indeterminate cell histiocytosis (ICH), and unclassified histiocytosis, is a rare disorder lacking a standard treatment strategy. We report our experience using intermediate-dose cytarabine as the first or subsequent therapy in non-Langerhans cell histiocytosis.

Results
Nine ECD patients, 5 RDD patients, 1 ICH patient and 1 unclassified histiocytosis patient were enrolled. Intermediate-dose cytarabine therapy was administered as 0.5–1.0 g/m2 of intravenous cytarabine every 12 h for 3 days every 5 weeks. The median age at cytarabine initiation was 47.5 years (range 18–70 years). The median number of cycles of cytarabine administered was 5.5 (range 2–6). The overall response rate (ORR) was 87.5% in the overall cohort, including 12.5% with complete response and 75.0% with partial response. One patient experienced disease recurrence 19 months after cytarabine therapy. The median follow-up duration for the entire cohort was 15.5 months (range 6–68 months). The estimated 2-year progression-free survival and overall survival rates were 85.6% and 92.3%, respectively. The most common toxicity was haematological adverse events, including grade 4 neutropenia and grade 3–4 thrombocytopenia. No treatment-related deaths occurred.

Conclusions
Intermediate-dose cytarabine is an efficient treatment option for non-Langerhans cell histiocytosis patients, especially for those with CNS involvement.
A serological survey of Toxoplasma gondii in Polish pigs from organic farms, other housing systems and in pigs of different age groups
Authors: Puchalska Martyna , Wiśniewski Jan , Klich Daniel , Gołąb Elżbieta , Jańczak Dawid , Sokołowska Justyna , Urbańska Kaja , Anusz Krzysztof 
Published: February 2022

AbstractBackgroundThe consumption of raw or undercooked meat, especially pork, and offal containing infective tissue cysts is suspected to be a significant route of infection withToxoplasma gondii. Although the use of “animal-friendly pig production systems” ensuring direct contact with the natural environment offers ethical benefits, it limits the ability to ensure animal health; it may also increase the probability of infections by pathogens such asT. gondii, and thus their entry into the food chain. This study determines the seroprevalence ofT. gondiiin pigs from different housing systems and farms with different hygiene standards in Poland, as well as among pigs of different age groups from farms with high hygiene standards. In total 760 pig serum samples were examined for the presence of specific antibodies using the PrioCHECK®Toxoplasma Ab porcine commercial ELISA test (Prionics, Switzerland).ResultsTest results with PP ≥ 20% were regarded as positive, as indicated by the manufacturer. Antibodies toT. gondiiwere found in 193 of 760 (25.4%) tested sera. Regarding different housing systems, antibodies were found in 117 pigs: of these, 52.6% (61/116) were from organic farms, 40.9% (47/115) from farms with low hygiene standards, 5.4% (9/167) from farms with high hygiene standards and 0% (0/40) from a farm with a high level of biosecurity. Regarding age groups, antibodies were found in 76 animals on farms with high hygiene standards: 11.1% (7/63) were pigs younger than 3 months, 0% (0/60) aged 3–4 months, 12.3% (7/57) aged 5–6 months (final fattening stage) and 43.7% (62/142) were sows aged 9 months and older.ConclusionsAntibodies toT. gondiiwere most often found in pigs from organic and low-hygiene farms, as well as in pigs aged 9 months and older. Meat derived from seropositive animals can pose a potential source of infection for humans. As maternal antibodies toT. gondiican be present in the blood of piglets aged up to 3–4 months, serological examination is unjustified in piglets up to this age.
Identifying best practice for the supervision of mental health and psychosocial support in humanitarian emergencies: a Delphi study
Authors: Travers Áine , Abujaber Nadeen , McBride Kelly A , Tingsted Blum Pia , Wiedemann Nana , Vallières Frédérique 
Published: February 2022

Abstract
Background
Supportive supervision has been shown to improve worker resilience and wellbeing, which are particularly important in the context of humanitarian emergency settings. Despite its noted importance however, supervision remains an under-prioritised area in mental health and psychosocial support (MHPSS).

Method
The present study used a Delphi consensus-building methodology to examine levels of agreement among a diverse sample of MHPSS stakeholders (n = 48) on key ideas and concepts relating to supervision in humanitarian settings.

Results
The majority of statements presented showed a high degree of consensus, with some receiving almost universal agreement, such as the importance of using active listening skills in the supervisory context and the need for supervisors to have access to their own supervisory support. However, disagreement on several points remained. For example, participants disagreed about whether the qualities required to be an effective supervisor can be taught, or whether they are more innate and should be screened for when recruiting supervisors. Gender differences in responses were also analysed, with potential associations between gender and level of agreement emerging in relation to statements about power dynamics, remote supervision, and intervention quality enhancement.

Conclusions
The findings of the present study are discussed in terms of their implications for a forthcoming set of guidelines for supervision of MHPSS in humanitarian settings: The Integrated Model for Supervision (IMS).