bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Incorporating the Air–Lake Interaction on Quantitative Precipitation Forecasts over Southern Ontario, Canada
Authors: Cao Zuohao , Bélair Stéphane , Zhang Da-Lin 
Published: June 2022

Abstract
A short-range regional, two-way coupled atmosphere–ocean–ice model has been recently developed in an attempt to improve, among other things, quantitative precipitation forecasts (QPFs) over southern Ontario, Canada, by incorporating air–lake interaction over the Great Lakes region. Here, we attempt to 1) assess the impact of the air–lake coupling on daily QPFs, as verified against the Canadian Precipitation Analysis and independent observations, over southern Ontario during the period of June 2016–May 2017; and 2) diagnose major physical processes governing the QPF differences between the coupled and uncoupled models by relating precipitation to those processes at the air–water interface and above. Results indicate that the coupled model tends to reduce the area-averaged and monthly averaged daily QPF biases and standard deviations in 5 months of October, November, and December 2016, and April and May 2017, but increase and deteriorate precipitation biases during the summer months. Most of the deteriorations occur during the daytime, while improvements are observed during the nighttime (in 7 of 12 months). During the daytime, slight improvements appear in 2 months. A further diagnosis indicates that the daily QPF differences between the two models are highly correlated with the differences of their sensible and latent heat fluxes. The maximum (minimum) difference of sensible (latent) heat flux in August 2016 (December 2016) is in phase with the maximum (minimum) difference of the two-model daily QPFs. The daily QPF differences in the other months are also controlled by the differences of vertically integrated water vapor flux convergence, and surface temperature.
Imaging the inflammatory phenotype in migraine
Authors: Christensen Rune Häckert , Gollion Cédric , Amin Faisal Mohammad , Moskowitz Michael A. , Hadjikhani Nouchine , Ashina Messoud 
Published: June 2022

AbstractSeveral preclinical and clinical lines of evidence suggest a role of neuroinflammation in migraine. Neuroimaging offers the possibility to investigate and localize neuroinflammationin vivoin patients with migraine, and to characterize specific inflammatory constituents, such as vascular permeability, and macrophage or microglia activity. Despite all imaging data accumulated on neuroinflammation across the past three decades, an overview of the imaging evidence of neuroinflammation in migraine is still missing.We conducted a systematic review in the Pubmed and Embase databases to evaluate existing imaging data on inflammation in migraine, and to identify gaps in the literature. We included 20 studies investigating migraine without aura (N= 4), migraine with aura (N= 8), both migraine with and without aura (N= 3), or hemiplegic migraine (N= 5).In migraine without aura, macrophage activation was not evident. In migraine with aura, imaging evidence suggested microglial and parameningeal inflammatory activity. Increased vascular permeability was mostly found in hemiplegic migraine, and was atypical in migraine with and without aura. Based on the weight of existing and emerging data, we show that most studies have concentrated on demonstrating increased vascular permeability as a marker of neuroinflammation, with tools that may not have been optimal. In the future, novel, more sensitive techniques, as well as imaging tracers delineating specific inflammatory pathways may further bridge the gap between preclinical and clinical findings.
A randomized placebo-controlled double-blind study of dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery
Authors: Wu Yu , Miao Yuhua , Chen Xuzhen , Wan Xiaojian 
Published: June 2022

Abstract
Background
Postoperative sleep disorder is common and may cause aggravated postoperative pain, delirium, and poor prognosis. We accessed the effect of intraoperative intravenous dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery.

Methods
This single-center, double-blind, placebo-controlled randomized clinical trial enrolled a total of 110 participants aged 18 years to 65 years who were scheduled to receive endoscopic sinus surgery. Placebo (normal saline) or dexmedetomidine infusion (load dose 0.5 μg kg−1 over 10 min, followed by maintenance dose 0.2 ug kg−1 h−1) during surgery. The primary outcome was postoperative sleep quality. Secondary outcomes were postoperative Ramsay sedation scores, Visual Analog Scale (VAS) scores, serum cortisol, 5-hydroxytryptamine (5-HT) and hypocretin, delirium, and postoperative nausea and vomiting (PONV).

Results
Among enrolled 110 patients, 55 were randomized to administer intraoperative dexmedetomidine and placebo. In total, 14 patients (7 in each group) were excluded because of protocol deviations, and 96 patients (48 in each group) were included in the per-protocol analysis. The dexmedetomidine group had a significantly higher sleep efficiency index(SEI) (66.85[3.00] vs 65.38[3.58]), the ratio of rapid eye movement sleep to total sleep(REM)(13.63[1.45] vs 12.38[2.11]) and lower arousal index (AI) (7.20[1.00] vs 8.07[1.29]), higher Ramsay sedation score at post-operation 1 h, 12 h point, lower VAS scores at post-operation 1 h, 12 h, 24 h point, lower cortisol, higher 5-HT and hypocretin in serum than the placebo group.

Conclusion
In this randomized clinical trial, dexmedetomidine can improve the sleep quality of patients undergoing endoscopic sinus surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative sleep quality in patients with endoscopic sinus surgery.

Trial registration
The study was approved by the Bethune International Peace Hospital Ethics Committee (2021-KY-129) and registered in the Chinese Clinical Trial Registry (www.chictr.org.cn/index.aspx, 28/09/2021).
Plasma repressor element 1-silencing transcription factor levels are decreased in patients with Alzheimer's disease
Authors: Wei Mingqing , Ni Jingnian , Shi Jing , Li Ting , Xu Xiaoqing , Li Chenmeng , Qin Bin , Fan Dongsheng , Xie Hengge , Wang Zhong , Wang Yongyan , Lu Tao , Tian Jinzhou 
Published: June 2022

Abstract
Background
Repressor element 1-silencing transcription (REST)/neuron-restrictive silencer factor is considered a new therapeutic target for neurodegenerative disorders such as Alzheimer’s disease (AD). However, the relationship between AD and REST remains unclear. This study aimed to 1) examine plasma REST levels and REST gene levels in AD patients and 2) further explore the pathological relationships between REST protein levels and cognitive decline in clinical conditions, including medial temporal lobe atrophy.

Methods
Participants (n = 252, mean age 68.95 ± 8.78 years) were recruited in Beijing, China, and then divided into a normal cognition (NC) group (n = 89), an amnestic mild cognitive impairment (aMCI) group (n = 79), and an AD dementia group (n = 84) according to diagnostic criteria. All participants underwent neuropsychological assessments, laboratory tests, and neuroimaging scans (magnetic resonance imaging) at baseline. Plasma REST protein levels and the distribution of REST single nucleotide polymorphisms (SNPs) were compared among the three groups. Correlations between cognitive function, neuro-imaging results, and REST levels were determined by a multivariate linear regression analysis.

Results
The plasma REST levels in both the NC group (430.30 ± 303.43)pg/ml and aMCI group (414.27 ± 263.39)pg/ml were significantly higher than that in the AD dementia group (NC vs AD dementia group, p = 0.034; aMCI vs AD dementia group, p = 0.033). There was no significant difference between the NC and aMCI groups (p = 0.948). No significant difference was found among the three groups regarding the genotype distribution (rs2227902 and rs3976529 SNPs) of the REST gene. The REST level was correlated with the left medial temporal lobe atrophy index (r = 0.306, p = 0.023). After 6 months of follow-up, the REST level in the NC group was positively correlated with the change in the Mini-Mental State Examination score (r = 0.289, p = 0.02).

Conclusion
The plasma REST protein level is decreased in AD dementia patients, which is associated with memory impairment and left temporal lobe atrophy and may have potential value for clinical diagnosis of AD dementia.
Birth prevalence of neural tube defects in eastern Africa: a systematic review and meta-analysis
Authors: Ssentongo Paddy , Heilbrunn Emily S. , Ssentongo Anna E. , Ssenyonga Lydia V. N. , Lekoubou Alain 
Published: June 2022

Abstract
Background
Neural tube defects (NTDs) are associated with high rates of neonatal mortality and morbidity worldwide. The promotion of folic acid fortification and supplementation in pregnant women by the Food and Drug Administration significantly decreased the incidence of NTDs in the United States. This practice is not widely adopted in Eastern Africa countries. We hypothesized that these countries experience a higher burden of NTDs than countries that promote the use of folic acid. We aimed to estimate the birth prevalence of NTDs in the United Nations (UN) Eastern African region.

Methods
PubMed (Medline), Embase, and Cochrane Library databases were systematically searched from inception to December 17, 2021. We included randomized controlled trials or observational studies that reported the prevalence estimates of NTDs in Eastern Africa. Random effects model was used to pool the effect estimates. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess the certainty of the evidence. Outcome measures were overall and specific (spina bifida, anencephaly, encephalocele) rates of NTDs per 10,000 births, including live and stillborn cases.

Results
The meta-analysis included 20 studies consisting of 752,936 individuals. The pooled prevalence of all NTDs per 10,000 births in Eastern Africa was 33.30 (95% CI: 21.58 to 51.34). Between-study heterogeneity was high (I2 = 97%, p < 0.0001), The rate was highest in Ethiopia (60 per 10,000). Birth prevalence of spina bifida (20 per 10,000) was higher than anencephaly (9 per 10,000) and encephalocele (2.33 per 10,000). No studies on NTDs were identified in 70% of the UN Eastern Africa region. Birth prevalence increased by 4% per year from 1983 to 2018. The level of evidence as qualified with GRADE was moderate.

Conclusion
The birth prevalence of NTDs in the United Nations region of Eastern Africa is 5 times as high as observed in Western countries with mandatory folic acid supplementation in place. Therefore, mandatory folic acid supplementation of stable foods may decrease the risk of NTDs in Eastern Africa.
Reflections on workplace adjustments for pregnant employees: a qualitative study of the experiences of pregnant employees and their managers
Authors: Andersen Dorte Raaby , Momsen Anne-Mette Hedeager , Pedersen Pernille , Maimburg Rikke Damkjær 
Published: June 2022

Abstract
Background
The European Union directive requires employers to assess and ensure safety measures for pregnant women in the workplace. Despite this, the rate of sick leave among pregnant Scandinavian women is relatively high. This study aims to provide insight into how pregnant employees and their managers experience and address pregnancy at the workplace, to identify preconditions for successful workplace adjustments for pregnant women.

Methods
We carried out a qualitative study that involved semi-structured interviews with seventeen participants: eight pregnant women and nine managers from occupations whose employees demonstrate an increased likelihood of taking sick leave during pregnancy. The interviews were thematically coded and organized into main themes and subthemes.

Results
Based on semi-structured interviews with the seventeen participants (eight pregnant employees and nine managers), we identified preconditions for successful workplace adjustments. According to the pregnant employees, these included, “The managers' concern, understanding, and acknowledgment,” “support and acceptance from colleagues,” and “pregnant employees’ acceptance of their need for adjustments.” According to the managers, the preconditions for successful workplace adjustments included “an open and honest dialogue” and “a systematic approach.”

Conclusion
Implementing workplace adjustments for pregnant employees is a complex process that comprises various initiatives, and their success may depend on several factors. This study’s findings suggest that the success of workplace interventions depends on 1) management, colleagues, and the pregnant employee recognizing and accepting pregnant women’s needs, 2) an organizational culture that supports women and pregnancy without compromising the occupational health of other employees, and 3) professional guidance that supports both women and managers when dealing with pregnancy-related concerns. We suggest that this study’s findings may be used to improve the implementation of workplace adjustments for pregnant women.
Sex-dependent influence of maternal predictors on fetal anthropometry in pregnancies with gestational diabetes mellitus
Authors: Antoniou Maria-Christina , Gilbert Leah , Gross Justine , Rossel Jean-Benoît , Fumeaux Céline Julie Fischer , Vial Yvan , Puder Jardena Jacqueline 
Published: June 2022

Abstract
Background
Third trimester fetal anthropometric parameters are known to predict neonatal complications. A better understanding of predictors of adverse fetal parameters might help to personalize the use and frequency of fetal ultrasound. The objectives of this study were:
(a) to evaluate the utility of maternal sociodemographic, anthropometric and metabolic predictors to predict 3rd trimester fetal anthropometric parameters in women with gestational diabetes mellitus (GDM),
(b) to assess whether the impact of these maternal predictors is fetal sex-dependent, and
(c) to provide a risk stratification for markers of fetal overgrowth (fetal weight centile (FWC) and fetal abdominal circumference centile (FACC) depending on prepregnancy BMI and gestational weight gain (GWG) until the 1st GDM visit.

Methods
This prospective study included 189 women with GDM. Maternal predictors were age, ethnicity, prepregnancy BMI, GWG and excessive weight gain until the 1st GDM visit, fasting, 1-hour and 2-hour blood glucose oral glucose tolerance test values, HbA1c at the 1st visit and medical treatment requirement. Fetal outcomes included FWC, FWC >90% and <10%, FACC, FACC >90% and <10%, at 29 0/7 to 35 6/7 weeks of gestational age. We performed univariate and multivariate regression analyses and probability analyses.

Results
In multivariate analyses, prepregnancy BMI was associated with FWC, FWC > 90% and FACC. GWG until the 1st GDM visit was associated with FWC, FACC and FACC > 90% (all p ≤ 0.045). Other maternal parameters were not significantly associated with fetal anthropometry in multivariate analyses (all p ≥ 0.054). In female fetuses, only GWG was associated with FACC (p= 0.044). However, in male fetuses, prepregnancy BMI was associated with FWC, FWC > 90% and FACC and GWG with FWC in multivariate analyses (all p ≤ 0.030). In women with a prepregnancy BMI of ≥ 25 kg/m2 and a GWG until the 1st GDM visit ≥ 10.3 kg (mean GWG), the risk for FWC > 90% and FACC > 90% was 5.3 and 4 times higher than in their counterparts.

Conclusions
A personalized fetal ultrasound surveillance guided by fetal sex, prepregnancy BMI and GWG may be beneficial in reducing adverse fetal and neonatal outcomes.
Efficacy of osimertinib in epidermal growth factor receptor-mutated non-small-cell lung cancer patients with pleural effusion
Authors: Nokihara Hiroshi , Ogino Hirokazu , Mitsuhashi Atsushi , Kondo Kensuke , Ogawa Ei , Ozaki Ryohiko , Yabuki Yohei , Yoneda Hiroto , Otsuka Kenji , Nishioka Yasuhiko 
Published: June 2022

Abstract
Background
Osimertinib is a standard first-line treatment for advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Although malignant pleural effusion (PE) is a common clinical problem in NSCLC, information about the efficacy of osimertinib in patients with PE is limited, especially regarding its efficacy in EGFR T790M-negative patients with PE remains unclear.

Methods
We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who were treated with osimertinib in our institution between May 2016 and December 2020.

Results
A total of 63 patients with EGFR mutated NSCLC were treated with osimertinib; 33 (12 with PE) had no EGFR T790M mutation, while 30 (12 with PE) had EGFR T790M mutation. In EGFR T790M-negative NSCLC, the progression-free survival (PFS) of the patients with PE was comparable to that of the patients without PE (median PFS 19.8 vs. 19.8 months, p = 0.693). In EGFR T790M- positive NSCLC, the PFS and overall survival (OS) of the patients with PE were significantly shorter than those of the patients without PE (median PFS 16.8 vs. 8.3 months, p = 0.003; median OS 44.9 vs. 14.2 months, p = 0.007). In the multivariate analysis, the presence of PE was independently associated with shorter PFS and OS in EGFR T790M-positive NSCLC patients, but not EGFR T790M-negative patients.

Conclusions
These data suggest the efficacy of osimertinib may differ between EGFR T790M-positive and -negative NSCLC patients with PE.
A two-center pilot study on the effects of clinical ethics support on coercive measures in psychiatry
Authors: Stoll Julia , Westermair Anna Lisa , Kübler Ulrike , Reisch Thomas , Cattapan Katja , Bridler René , Maier Robert , Trachsel Manuel 
Published: June 2022

Abstract
Background
The use of formal coercion such as seclusion, mechanical restraint, and forced medication is one of the most challenging and complex issues in mental health care, on the clinical, the legal, and the ethical level. Clinical ethics support aims at assisting healthcare practitioners in determining the morally most justifiable course of action in these situations. However, the effectiveness of clinical ethics support has hardly been studied so far.

Methods
Monthly moral case deliberation (MCD) was implemented in two acute wards of two different psychiatric hospitals in Switzerland. Frequency and intensity of coercion was measured on ward level (npatients = 405), and the Moral Attentiveness Scale, Knowledge on Coercion Scale, and Staff Attitudes towards Coercion Scale were applied on healthcare practitioner level (nHP = 46). Pre-post-comparisons were conducted using multi-level modeling where appropriate.

Results
After implementation of MCD, formal coercion was less frequent (particularly seclusion, small effect size; 9.6 vs. 16.7%, p = .034, Cramér’s V = .105) and less intense (particularly mechanical restraint, large effect size; 86.8 ± 45.3 vs. 14.5 ± 12.1 h, exact p = .019, r = -.74), and approval for coercive measures among healthcare practitioners was lower when controlling for the number of MCD sessions attended.

Conclusions
Clinical ethics support such as MCD may be a hitherto underutilized service for the reduction of coercion, complementing existing strategies and programs. Implementing clinical ethics support may help improve quality of care for persons suffering from severe mental illness.
I (Don’t) want to consume counterfeit medicines: exploratory study on the antecedents of consumer attitudes toward counterfeit medicines
Authors: Ofori-Parku Sylvester Senyo , Park Sung Eun 
Published: June 2022

Abstract
Background
Substandard and falsified medicine (SFM) sales (an estimated > $200 billion) has become one of the worlds’ fastest growing criminal enterprises. It presents an enormous public health and safety challenge. While the developed world is not precluded from this challenge, studies focus on low-income countries. They emphasize supply chain processes, technological, and legal mechanisms, paying less attention to consumer judgment and decision-making aspects.

Methods
With attention to the demand side of the counterfeit medicines challenge, this survey of U.S. consumers (n = 427) sheds light on some of the social, psychological, and normative factors that underlie consumers’ attitudes, risk perceptions, and purchase intentions.

Results
Consumers who (a) self-report that they know about the problem, (b) are older, (c) view counterfeit medicine consumption as ethical, and (d) think their significant others would approve of them using such products are more inclined to perceive lower risks and have favorable purchase intentions. Risk averseness is also inversely related to the predicted outcomes.
Perceived benefit of SFMs is a factor but has no effect when risk perception and aversion, attitudes, and subjective norms are factored into the model that predicts purchase intentions.

Conclusion
The results of this study indicate that consumer knowledge (albeit in an unexpected direction), people’s expectations about what will impress their significant others, their ethical judgments about selling and consuming counterfeits, and their risk-aversion are associated with their decision-making about counterfeit medicines. The study offers insights into a demand-side approach to addressing SFM consumption in the U.S. Implications for public health, consumer safety, and brand advocacy education are discussed.
Protocol paper: a multi-center, double-blinded, randomized, 6-month, placebo-controlled study followed by 12-month open label extension to evaluate the safety and efficacy of Saracatinib in Fibrodysplasia Ossificans Progressiva (STOPFOP)
Authors: Smilde Bernard J. , Stockklausner Clemens , Keen Richard , Whittaker Andrew , Bullock Alex N. , von Delft Annette , van Schoor Natasja M. , Yu Paul B. , Eekhoff E. Marelise W. 
Published: June 2022

Abstract
Background
Fibrodysplasia Ossificans Progressiva (FOP) is a genetic, progressive and devastating disease characterized by severe heterotopic ossification (HO), loss of mobility and early death. There are no FDA approved medications. The STOPFOP team identified AZD0530 (saracatinib) as a potent inhibitor of the ALK2/ACVR1-kinase which is the causative gene for this rare bone disease. AZD0530 was proven to prevent HO formation in FOP mouse models. The STOPFOP trial investigates the repositioning of AZD0530, originally developed for ovarian cancer treatment, to treat patients with FOP.

Methods
The STOPFOP trial is a phase 2a study. It is designed as a European, multicentre, 6-month double blind randomized controlled trial of AZD0530 versus placebo, followed by a 12-month trial comparing open-label extended AZD0530 treatment with natural history data as a control. Enrollment will include 20 FOP patients, aged 18–65 years, with the classic FOP mutation (ALK2 R206H). The primary endpoint is objective change in heterotopic bone volume measured by low-dose whole-body computer tomography (CT) in the RCT phase. Secondary endpoints include 18F NaF PET activity and patient reported outcome measures.

Discussion
Clinical trials in rare diseases with limited study populations pose unique challenges. An ideal solution for limiting risks in early clinical studies is drug repositioning – using existing clinical molecules for new disease indications. Using existing assets may also allow a more fluid transition into clinical practice.
With positive study outcome, AZD0530 may provide a therapy for FOP that can be rapidly progressed due to the availability of existing safety data from 28 registered clinical trials with AZD0530 involving over 600 patients.

Trial registration
EudraCT, 2019–003324-20. Registered 16 October 2019, https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-003324-20/NL. Clinicaltrials.gov, NCT04307953. Registered 13 March 2020.