bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of Genetically Predicted Lp(a) (Lipoprotein [a]) and ApoB Levels for Cardiovascular Risk Assessment
Authors: Wu Haoyu , Luan Jian’an , Forgetta Vincenzo , Engert James C. , Thanassoulis George , Mooser Vincent , Wareham Nicholas J. , Langenberg Claudia , Richards J. Brent 
Published: August 2021

Background:
Current lipid guidelines suggest measurement of Lp(a) (lipoprotein[a]) and ApoB (apolipoprotein B) for atherosclerotic cardiovascular disease risk assessment. Polygenic risk scores (PRSs) for Lp(a) and ApoB may identify individuals unlikely to have elevated Lp(a) or ApoB and thus reduce such suggested testing.

Methods:
PRSs were developed using least absolute shrinkage and selection operator regression among 273 222 and 356 958 UK Biobank participants of white British ancestry for Lp(a) and ApoB, respectively, and validated in separate sets of 60 771 UK Biobank and 15 050 European Prospective Investigation into Cancer and Nutrition-Norfolk participants. We then assessed the proportion of participants who, based on these PRSs, were unlikely to benefit from Lp(a) or ApoB measurements, according to current lipid guidelines.

Results:
In the UK Biobank and European Prospective Investigation into Cancer and Nutrition-Norfolk cohorts, the area under the receiver operating curve for the PRS-predicted Lp(a) and ApoB to identify individuals with elevated Lp(a) and ApoB was at least 0.91 (95% CI, 0.90–0.92) and 0.74 (95% CI, 0.73–0.75), respectively. The Lp(a) PRS and measured Lp(a) showed comparable association with atherosclerotic cardiovascular disease incidence, whereas the ApoB PRS was in general less predictive of atherosclerotic cardiovascular disease risk than measured ApoB. In the context of the European Society of Cardiology/European Atherosclerosis Society lipid guidelines, at a 95% sensitivity to identify individuals with elevated Lp(a) and ApoB levels, at least 54% of Lp(a) and 24% of ApoB testing could be reduced by prescreening with a PRS while maintaining a low false-negative rate.

Conclusions:
A substantial proportion of suggested testing for elevated Lp(a) and a modest proportion of testing for elevated ApoB could potentially be reduced by prescreening individuals with PRSs.
Altered synthesis of genes associated with short-chain fatty acids in the gut of patients with atrial fibrillation
Authors: Zhang Jing , Zuo Kun , Fang Chen , Yin Xiandong , Liu Xiaoqing , Zhong Jiuchang , Li Kuibao , Li Jing , Xu Li , Yang Xinchun 
Published: August 2021

Abstract
Background
The gut microbiota provides health benefits in humans by producing short-chain fatty acids (SCFAs), whose deficiency causes multiple disorders and inflammatory diseases. However, gut bacteria producing SCFAs in patients with atrial fibrillation (AF), an arrhythmia with increasing prevalence, have not been reported. To investigate major gut microbial organisms related to SCFA synthesis, SCFAs-associated KEGG orthologues (KOs), enzymatic genes, and potential producers were examined according to metagenomic data-mining in a northern Chinese cohort comprising 50 non-AF control and 50 AF patients.

Results
Compared with non-AF controls, individuals with AF had marked differences in microbial genes involved in SCFA-related synthesis, including 125 KOs and 5 SCFAs-related enzymatic genes. Furthermore, there were 10 species that harbored SCFA-synthesis related enzymatic genes, and were markedly decreased in the gut of AF patients. Notably, discriminative features about SCFA-synthesis related function, including 8 KOs (K01752, K01738, K00175, K03737, K01006, K01653, K01647 and K15023), 4 genes (menI, tesB, yciA and CO dehydrogenase acetyl-CoA synthase complex) and 2 species (Coprococcus catus and Firmicutes bacterium CAG:103), were selected as key factors based on LASSO analysis. Furthermore, PLS-SEM analysis showed that 72.8 and 91.14 % of the overall effects on gut microbiota diversity and key species on AF, respectively, were mediated by the key KOs. Meanwhile, 46.31 % of the total effects of SCFA-synthesis related function on left atrial enlargement was mediated by hsCRP. Upon incorporation of clinical properties in AF, the KO score was still significantly associated with AF incidence (OR = 0.004, P = 0.001).

Conclusions
The current study revealed that dysbiotic gut microbiota in AF is coupled with disrupted SCFA-synthesis related genes, characterized by decreased abundances of KEGG orthologues, synthesis enzymatic genes and harboring species.
Investigator initiated trials versus industry sponsored trials - translation of randomized controlled trials into clinical practice (IMPACT)
Authors: Blümle Anette , Wollmann Katharina , Bischoff Karin , Kapp Philipp , Lohner Szimonetta , Nury Edris , Nitschke Kai , Zähringer Jasmin , Rücker Gerta , Schumacher Martin 
Published: August 2021

Abstract
Background
Healthcare decisions are ideally based on clinical trial results, published in study registries, as journal articles or summarized in secondary research articles. In this research project, we investigated the impact of academically and commercially sponsored clinical trials on medical practice by measuring the proportion of trials published and cited by systematic reviews and clinical guidelines.

Methods
We examined 691 multicenter, randomized controlled trials that started in 2005 or later and were completed by the end of 2016. To determine whether sponsorship/funding and place of conduct influence a trial’s impact, we created four sub-cohorts of investigator initiated trials (IITs) and industry sponsored trials (ISTs): 120 IITs and 171 ISTs with German contribution compared to 200 IITs and 200 ISTs without German contribution. We balanced the groups for study phase and place of conduct. German IITs were funded by the German Research Foundation (DFG), the Federal Ministry of Education and Research (BMBF), or by another non-commercial research organization. All other trials were drawn from the German Clinical Trials Register or ClinicalTrials.gov. We investigated, to what extent study characteristics were associated with publication and impact using multivariable logistic regressions.

Results
For 80% of the 691 trials, results were published as result articles in a medical journal and/or study registry, 52% were cited by a systematic review, and 26% reached impact in a clinical guideline. Drug trials and larger trials were associated with a higher probability to be published and to have an impact than non-drug trials and smaller trials. Results of IITs were more often published as a journal article while results of ISTs were more often published in study registries. International ISTs less often gained impact by inclusion in systematic reviews or guidelines than IITs.

Conclusion
An encouraging high proportion of the clinical trials were published, and a considerable proportion gained impact on clinical practice. However, there is still room for improvement. For publishing study results, study registries have become an alternative or complement to journal articles, especially for ISTs. IITs funded by governmental bodies in Germany reached an impact that is comparable to international IITs and ISTs.
Assessing multiple sclerosis-related quality of life among Iranian patients using the MSQOL-54 tool: a cross-sectional study
Authors: Ziaie Shadi , Namazi Niloofar , Afzal Golnaz , Barati Saghar , Mohebbi Rezvaneh , Mir Mahshad , Esmaily Hadi , Mehralian Gholamhossein 
Published: August 2021

Abstract
Background
Multiple sclerosis (MS) is a chronic autoimmune disease and is one of the most costly medical conditions that imposed families with catastrophic health expenditures. There is an increasing trend in using alternative medicines including, dietary supplements, herbs, vitamins, and minerals. To date, the association between dietary as well as herbal supplements and QoL in MS patients is under researched; thus, this study aimed to assess the association between the self-reported supplement used and QoL between MS patients.

Methods
This cross-sectional study was conducted on patients with MS referring to Shahid Kazemi Pharmacy, based in the city of Tehran, Iran, as a national pharmacy providing specialized pharmaceutical products and pharmaceutical care to patients. The Multiple Sclerosis Quality of Life-54 (MSQoL-54) tools was performed to evaluate MS patients QoL.

Results
A total number of 382 patients with MS participated in this study. They include 89 (23.3%) men and 293 (76.7%) women, aged 40 ± 10.9 years old. The overall score of the MSQoL-54 questionnaire was 41.58 out of 100. Physical health composite (PHC) and mental health composite (MHC) were 69.60 and 62.99 from 100, respectively. This study revealed that 76.4% of patients used at least one vitamin daily; 92.4% of patients do not receive any herbal product. Vitamin D is the most widely used supplement, followed by calcium, while vitamin C is the least consumed. No correlation was observed regarding supplement use and overall QoL, PHC, or MHC. There were no significant differences between QoL’s dimensions score in patients who used supplements. The results showed that increasing the number of supplements used did not relate to overall QoL, PHC, or MHC. In addition, there was not any correlation between the duration used of supplements and QoL’s dimensions score in MS patients (p-value> 0.05).

Conclusions
The dietary supplement appears to be popular among MS patients. The study results showed that the number of supplementations and their long-term use in patients with MS were not associated with higher QoL. Similarly, the herbal supplements have failed to improve QoL.
Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma
Authors: Amano Takahiro , Iijima Hideki , Shinzaki Shinichiro , Tashiro Taku , Iwatani Shuko , Tani Mizuki , Otake Yuriko , Yoshihara Takeo , Sugimoto Aya , Egawa Satoshi , Yamaguchi Shinjiro , Kinoshita Kazuo , Araki Manabu , Hirao Motohiro , Sakakibara Yuko , Hiyama Satoshi , Ogawa Hiroyuki , Nagaike Koji , Murata Jun , Komori Masato , Okuda Yorihide , Kizu Takashi , Tsujii Yoshiki , Hayashi Yoshito , Inoue Takahiro , Takahashi Hidekazu , Mizushima Tsunekazu , Morii Eiichi , Takehara Tetsuo 
Published: August 2021

Abstract
Background
The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA.

Methods
This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins.

Results
A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30–0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression.

Conclusion
Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.
Protocol of the Snuggle Bug/Acurrucadito Study: a longitudinal study investigating the influences of sleep-wake patterns and gut microbiome development in infancy on rapid weight gain, an early risk factor for obesity
Authors: Petrov Megan E. , Jiao Nana , Panchanathan Sarada S. , Reifsnider Elizabeth , Coonrod Dean V. , Liu Li , Krajmalnik-Brown Rosa , Gu Haiwei , Davidson Laurie A. , Chapkin Robert S. , Whisner Corrie M. 
Published: August 2021

Abstract
Background
Overweight, obesity, and associated comorbidities are a pressing global issue among children of all ages, particularly among low-income populations. Rapid weight gain (RWG) in the first 6 months of infancy contributes to childhood obesity. Suboptimal sleep-wake patterns and gut microbiota (GM) have also been associated with childhood obesity, but little is known about their influences on early infant RWG. Sleep may alter the GM and infant metabolism, and ultimately impact obesity; however, data on the interaction between sleep-wake patterns and GM development on infant growth are scarce. In this study, we aim to investigate associations of infant sleep-wake patterns and GM development with RWG at 6 months and weight gain at 12 months. We also aim to evaluate whether temporal interactions exist between infant sleep-wake patterns and GM, and if these relations influence RWG.

Methods
The Snuggle Bug/ Acurrucadito study is an observational, longitudinal study investigating whether 24-h, actigraphy-assessed, sleep-wake patterns and GM development are associated with RWG among infants in their first year. Based on the Ecological Model of Growth, we propose a novel conceptual framework to incorporate sleep-wake patterns and the GM as metabolic contributors for RWG in the context of maternal-infant interactions, and familial and socio-physical environments. In total, 192 mother-infant pairs will be recruited, and sleep-wake patterns and GM development assessed at 3 and 8 weeks, and 3, 6, 9, and 12 months postpartum. Covariates including maternal and child characteristics, family and environmental factors, feeding practices and dietary intake of infants and mothers, and stool-derived metabolome and exfoliome data will be assessed. The study will apply machine learning techniques combined with logistic time-varying effect models to capture infant growth and aid in elucidating the dynamic associations between study variables and RWG.

Discussion
Repeated, valid, and objective assessment at clinically and developmentally meaningful intervals will provide robust measures of longitudinal sleep, GM, and growth. Project findings will provide evidence for future interventions to prevent RWG in infancy and subsequent obesity. The work also may spur the development of evidence-based guidelines to address modifiable factors that influence sleep-wake and GM development and prevent childhood obesity.
Neonatal rebound hyperkalemia associated with ritodrine alone: a case report
Authors: Osumi Keita , Suga Kenichi , Suzue Masashi , Nakagawa Ryuji , Kagami Shoji 
Published: August 2021

Abstract
Background
Betamimetics have been used for tocolysis extensively in the past, and one of them, ritodrine is widely used in Japan. Various adverse events have been reported for this agent, including newborn hypoglycemia and hypokalemia, as well as maternal hypokalemia and rebound hyperkalemia; however, cases of neonatal rebound hyperkalemia are not described in the literature.

Case presentation
A male infant born at 36 weeks of gestation by cesarean section at a local maternity clinic suddenly entered cardiopulmonary arrest with ventricular tachycardia and fibrillation due to hyperkalemia (K+, 8.7 mmol/L). No monitoring, examination of blood electrolyte levels, or infusions had been performed prior to this event. Maternal infusion of ritodrine (maximum dose, 170 μg/min) had been performed for 7 weeks prior to cesarean section. After resuscitation combined with calcium gluconate, the infant died at 4 months old due to serious respiratory failure accompanied by acute lung injury following shock. No cause of hyperkalemia other than rebound hyperkalemia associated with ritodrine was identified.

Conclusions
This case report serves as a warning regarding the potential risk of neonatal rebound hyperkalemia in association with maternal long-term ritodrine administration.
Multiple anatomic sites of infarction in a pediatric patient with M. pneumoniae infection, a case report
Authors: Hahn Devon W. , Atkinson Claire E. , Le Matthew 
Published: August 2021

Abstract
Background
Although M. pneumoniae (M. pneumoniae) infections have been associated with various extrapulmonary manifestations, there have been very few documented cases of thrombotic events in pediatrics, and none to our knowledge with such extensive involvement as the patient described here. We aim to contribute to the urgency of discovering the mechanism of the coagulopathy associated with M. pneumoniae infections.

Case presentation
This 10-year-old boy was admitted after 2 weeks of fever, sore throat, worsening cough, and progressive neck and back pain. During hospitalization, he developed clots in several different organs: bilateral pulmonary emboli, cardiac vegetations, multiple splenic infarcts, and deep venous thromboses in three of four extremities. He was treated with long-term antibiotics and anticoagulation, and fully recovered.

Conclusions
This is the first case known to us of a child with an extensive number of thrombotic events in multiple anatomic sites associated with M. pneumoniae infection. The mechanism by which M. pneumoniae infection is related to thrombotic events is not fully understood, but there is evidence that the interplay between the coagulation pathways and the complement cascade may be significant. This patient underwent extensive investigation, and was found to have significant coagulopathy, but minimal complement abnormalities. By better understanding the mechanisms involved in complications of M. pneumoniae infection, the clinician can more effectively investigate the progression of this disease saving time, money, morbidity, and mortality.
“This course is like a compass to us” – a qualitative study on newly settled migrants’ perceptions of civic and health orientation in Sweden
Authors: Al-Adhami Maissa , Hjelm Katarina , Wångdahl Josefin , Larsson Elin C. 
Published: August 2021

Abstract
Background
Migrants face structural, socio-political barriers in their resettlement processes that negatively affect their health. Migration also adversely impacts resources such as social capital and health literacy that are of importance for health and integration into society. Hence, there is a need for health promotion in the early post-migration phase. In Sweden, newly settled refugee migrants who have received a residence permit are offered an Introduction programme including a civic orientation course. The program is intended to facilitate access to the labour market and promote integration. The aim of the study was to explore participants’ perceptions and experiences of a civic orientation course with added health communication.

Methods
We performed six focus group discussions: two in Arabic, two in Farsi and two in Somali. The discussions were facilitated by native speaking moderators. Participants were 32 men and women recruited from civic orientation classes in the county of Stockholm. We used an interview guide with semi-structured questions. The data were analysed using a method for content analysis for focus group discussions.

Results
Three main categories were identified: (1) ‘The course gives valuable information but needs adjustments’, which includes that the civic and health orientation is needed earlier, during the asylum phase, and that planning and course content need adjustments. (2) ‘The health communication inspired participants to focus on their health’, which includes that the health communication was useful and inspired uptake of healthier habits. (3) ‘Participation in the course promoted independence and self-confidence’, which includes that the course gave insights into society and values in Sweden, and promoted independence and new social contacts.

Conclusion
This study adds knowledge about the users’ perspectives on the potential of civic orientation to promote the health and integration of newly settled migrants, describing ways in which civic orientation with added health communication promoted health and empowerment. However, the content and delivery of the course need adjustment to better fit the migrants’ life situations and varying pre-existing knowledge.
Delayed positive COVID19 nasopharyngeal test, a case study with clinical and pathological correlation
Authors: Zhang Lei , Vunnamadala Syam P. , Yagi Shigeo , Meraj Riffat , Carbone Michele 
Published: August 2021

Abstract
Background
There are various reasons for delayed positive nasopharyngeal PCR tests for coronavirus disease 2019 (COVID19) in not only asymptomatic but also severely diseased patients. The pathophysiological attributes are not known. We explore this possibility through a case report.

Case presentation
A 64-year-old male with history of pulmonary fungal infection, asthma and chronic pulmonary obstructive disease (COPD), diabetes, coronary artery disease presented with shortness of breath, fever and chest image of ground opacity, reticular interstitial thickening, highly suspicious for COVID19. However, nasopharyngeal swab tests were discordantly negative for four times in two weeks, and IgG antibody for COVID19 was also negative. However, serum IgE level was elevated. No other pathogens are identified. His symptoms deteriorated despite corticosteroid, antibiotics and bronchodilator treatment. Bronchoalveolar lavage (BAL) and open lung wedge biopsy were performed for etiology diagnosis. They demonstrated COVID19 viral RNA positive fibrosing organizing pneumonia with respiratory tract damage characterized by suspicious viral cytopathic effect, mixed neutrophilic, lymphoplasmacytic, histiocytic and eosinophilic inflammation and fibrosis besides expected asthma and COPD change. One week later, repeated COVID19 nasopharyngeal tests on day 40 and day 49 became positive.

Conclusion
Our case and literature review indicate that allergic asthma and associated high IgE level together with corticosteroid inhalation might contribute to the delayed positive nasopharyngeal swab in upper airway; COPD related chronic airways obstruction and the addition of fibrosis induced ventilator dependence and poor prognosis in COVID19 pneumonia, and should be therapeutically targeted besides antiviral therapy.