bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of an open-source, disposable, 3D-printed
in vitro
environmental exposure system for Transwell culture inserts
Authors: Chandiramohan Abiram , Dabaghi Mohammedhossein , Aguiar Jennifer A. , Tiessen Nicholas , Stewart Mary , Cao Quynh T. , Nguyen Jenny P. , Makhdami Nima , Cox Gerard , Doxey Andrew C. , Hirota Jeremy A. 
Published: December 2020

Accessible
in vitro
models recapitulating the human airway that are amenable to study whole cannabis smoke exposure are needed for immunological and toxicological studies that inform public health policy and recreational cannabis use. In the present study, we developed and validated a novel three-dimensional (3D)-printed
in vitro
exposure system (IVES) that can be directly applied to study the effect of cannabis smoke exposure on primary human bronchial epithelial cells.
Using commercially available design software and a 3D printer, we designed a four-chamber Transwell insert holder for exposures to whole smoke. COMSOL Multiphysics software was used to model gas distribution, concentration gradients, velocity profile and shear stress within IVES. Following simulations, primary human bronchial epithelial cells cultured at the air�liquid interface on Transwell inserts were exposed to whole cannabis smoke using a modified version of the Foltin puff procedure. Following 24 h, outcome measurements included cell morphology, epithelial barrier function, lactate dehydrogenase (LDH) levels, cytokine expression and gene expression.
Whole smoke delivered through IVES possesses velocity profiles consistent with uniform gas distribution across the four chambers and complete mixing. Airflow velocity ranged between 1.0 and 1.5 �m�s
-1
and generated low shear stresses (<<1 Pa). Human airway epithelial cells exposed to cannabis smoke using IVES showed changes in cell morphology and disruption of barrier function without significant cytotoxicity. Cannabis smoke elevated interleukin-1 family cytokines and elevated CYP1A1 and CYP1B1 expression relative to control, validating IVES smoke exposure impacts in human airway epithelial cells at a molecular level.
The growing legalisation of cannabis on a global scale must be paired with research related to potential health impacts of lung exposures. IVES represents an accessible, open-source, exposure system that can be used to model varying types of cannabis smoke exposures with human airway epithelial cells grown under air�liquid interface culture conditions.
Pleuroparenchymal fibroelastosis inMycobacterium aviumcomplex pulmonary disease: clinical characteristics and prognostic impact
Authors: Yamamoto Yuji , Tsujino Kazuyuki , Kuge Tomoki , Okabe Fukuko , Kawasaki Takahiro , Matsuki Takanori , Kagawa Hiroyuki , Miki Mari , Miki Keisuke , Mori Masahide , Kida Hiroshi 
Published: December 2020

The association betweenMycobacterium aviumcomplex pulmonary disease (MAC-PD) and pleuroparenchymal fibroelastosis (PPFE) has been reported previously, and interstitial pneumonia as a comorbidity is associated with a worse prognosis. However, no study has thoroughly reported on PPFE associated with MAC-PD. The present study investigated the prevalence, clinical characteristics, and prognostic impact of PPFE in patients with MAC-PD.A total of 224 patients, newly diagnosed with MAC-PD, were retrospectively reviewed. At the time of diagnosis, chest high-resolution computed tomography (HRCT), sputum examination, and clinical characteristics were collected. The extent of PPFE and MAC-PD was evaluated semi-quantitatively using HRCT scores. Risk factor analysis for clinical or radiological deterioration necessitating multidrug antimicrobial treatment within 3 years, and all-cause mortality within 5 years, from the initial diagnosis was performed based on the PPFE score.PPFE was observed in 59 out of 224 patients (26.3%). A higher PPFE score was a risk factor for dyspnoea, fatigue, and lower body mass index (BMI) (p<0.05). Although PPFE score did not correlate with clinical or radiological deterioration within 3 years (p=0.576), a higher PPFE score (adjusted OR 1.66, 95% CI 1.06–2.60, p=0.028) and lower BMI (adjusted OR 0.61, 95% CI 0.39–0.94, p=0.028) increased the risk of 5-year mortality.PPFE is a relatively common complication and an independent poor prognostic factor of MAC-PD. This study highlights the need for further studies investigating whether the presence of PPFE can be a clinical indicator for initiating treatment of MAC-PD.
Association between high psychological distress and poor oral health-related quality of life (OHQoL) in Japanese community-dwelling people: the Nagasaki Islands Study
Authors: Sekiguchi Ai , Kawashiri Shin-ya , Hayashida Hideaki , Nagaura Yuki , Nobusue Kenichi , Nonaka Fumiaki , Yamanashi Hirotomo , Kitamura Masayasu , Kawasaki Koji , Fukuda Hideki , Iwasaki Takahiro , Saito Toshiyuki , Maeda Takahiro 
Published: December 2020

Abstract
Background
We investigated the association between psychological distress and oral health status/oral health-related quality of life (OHQoL) in Japanese community-dwelling people.

Methods
We conducted a cross-sectional study using data from the Nagasaki Islands Study. A total of 1183 (455 men and 728 women) has been analyzed in this study. Psychological distress was measured using the Kessler Psychological Distress Scale (K6). Oral health status was measured by dental examination. The OHQoL was measured using the General Oral Health Assessment Index (GOHAI). We defined the total score of ≥5 points on the K6 as high psychological distress (high-K6 group).

Results
The multiple linear regression analysis to identify the GOHAI showed that gender, K6, the total number of teeth, the number of dental caries, and visiting a dental clinic within the past 6 months significantly associated with the GOHAI. Among all of these variables, high-K6 (≥ 5) was a substantial contributing factor of the GOHAI (β = − 0.23, 95% Cl − 2.31 to −1.41, p < 0.0001).

Conclusions
It is likely that the individual with high psychological distress was strongly related to poor OHQoL even in the general population.
PyClone-VI: scalable inference of clonal population structures using whole genome data
Authors: Gillis Sierra , Roth Andrew 
Published: December 2020

AbstractBackgroundAt diagnosis tumours are typically composed of a mixture of genomically distinct malignant cell populations. Bulk sequencing of tumour samples coupled with computational deconvolution can be used to identify these populations and study cancer evolution. Existing computational methods for populations deconvolution are slow and/or potentially inaccurate when applied to large datasets generated by whole genome sequencing data.ResultsWe describe PyClone-VI, a computationally efficient Bayesian statistical method for inferring the clonal population structure of cancers. We demonstrate the utility of the method by analyzing data from 1717 patients from PCAWG study and 100 patients from the TRACERx study.ConclusionsOur proposed method is 10–100× times faster than existing methods, while providing results which are as accurate. Software implementing our method is freely availablehttps://github.com/Roth-Lab/pyclone-vi.
Predictors of acute cardiovascular events following acute exacerbation period for patients with COPD: a nested case–control study
Authors: Hu Wei-ping , Lhamo Tsokyi , Zhang Feng-ying , Hang Jing-qing , Zuo Yi-hui , Hua Jian-lan , Li Shan-qun , Zhang Jing 
Published: December 2020

Abstract
Background
It has been noted that there is an increase in the incidence of acute cardiovascular events (CVEs) in patients with chronic obstructive pulmonary disease (COPD) during an acute exacerbation (AE), thereby causing increased inpatient mortality. Thus, we have tried to identify predictors of acute CVEs in patients with AECOPD via a nested case–control study.

Methods
A total of 496 cases hospitalized for AECOPD were included in this study, and followed-up for up to 6 months after discharge. Acute CVEs in the AE period were defined as a new or worsening acute coronary syndrome (ACS), arrhythmia, or left ventricular disfunction (LVD). Predictors of CVEs were selected from several variables, including baseline characteristics and treatments in the stable period as well as symptoms, laboratory tests, complications and treatments in the AE period.

Results
Thirty cases (6.05%) had acute CVEs, namely 2 had ACS, 13 had LVD and 19 experienced some form of arrhythmia. Four deaths were observed in the CVE group, with significantly increased death risk compared with the non-CVE group (P = 0.001, OR = 5.81). Moreover, patients who had CVEs were more prone to have re-exacerbation within 3 months. Multivariate analysis showed that previous LVD history (P = 0.004, OR = 5.06), 20% increase in heart rate (HR) (P = 0.003, OR = 10.19), electrolyte disturbance (P = 0.01, OR = 4.24) and diuretics (P = 0.002, OR = 6.37) were independent predictors of CVEs. In addition, usage of theophylline, fluoroquinolone and inhaled beta agonists in the AE period were not statistically associated with acute CVEs.

Conclusions
Our preliminary study indicates that patients hospitalized for AECOPD with previous LVD history or increased HR need close observation and diuretics should be cautiously used with regular electrolyte monitoring. These findings need to be confirmed in a large cohort.
Short-term use of “ECMELLA” in the context of fulminant eosinophilic myocarditis with cardiogenic shock
Authors: Bohné Mintje , Chung Da-Un , Tigges Eike , van der Schalk Hendrick , Waddell Daniela , Schenker Niklas , Willems Stephan , Klingel Karin , Kivelitz Dietmar , Bahlmann Edda 
Published: December 2020

Abstract
Background
Eosinophilic myocarditis (EM) is a rare form of myocarditis. Clinical presentation is various, includes cardiogenic shock and can often be fatal. Diagnosis is based on myocardial eosinophilic infiltration in endomyocardial biopsy. Mechanical circulatory support (MCS) is often required in patients suffering from severe cardiogenic shock. Among the available MCS options the “ECMELLA” concept, a combination of left ventricular venting by Impella® device and extracorporeal life support (ECLS) is possibly able to provide the necessary time frame for diagnostics and initiation of anti-inflammatory medication in patients with fulminant myocarditis.

Case presentation
We report a case of a 38‐year‐old woman who was presented to us in severe cardiogenic shock, quickly requiring hemodynamic support by an Impella CP® device. Further dramatic hemodynamic deterioration accompanied by multi-organ dysfunction required escalation of MCS via ECLS as veno‐arterial extracorporeal membrane oxygenation (VA-ECMO). After histopathological diagnosis of EM, our patient was put on immunosuppressive therapy with prednisolone. Recovery of both right and left ventricular function allowed explanation of VA-ECMO on day 4 and further hemodynamic improvement allowed removal of the Impella® device on day 9. The patient was discharged after 7 weeks with fully restored cardiac function and in a good neurological state.

Conclusions
In severe cardiac shock due to fulminant EM the ECMELLA concept as bridge-to-recovery seems to be a valid option to provide the required time for diagnostics and specific therapy.
Integrating expert opinions with clinical trial data to analyse low-powered subgroup analyses: a Bayesian analysis of the VeRDiCT trial
Authors: Thirard Russell , Ascione Raimondo , Blazeby Jane M. , Rogers Chris A. 
Published: December 2020

AbstractBackgroundTypically, subgroup analyses in clinical trials are conducted by comparing the intervention effect in each subgroup by means of an interaction test. However, trials are rarely, if ever, adequately powered for interaction tests, so clinically important interactions may go undetected. We discuss the application of Bayesian methods by using expert opinions alongside the trial data. We applied this methodology to the VeRDiCT trial investigating the effect of preoperative volume replacement therapy (VRT) versus no VRT (usual care) in diabetic patients undergoing cardiac surgery. Two subgroup effects were of clinical interest, a) preoperative renal failure and b) preoperative type of antidiabetic medication.MethodsClinical experts were identified within the VeRDiCT trial centre in the UK. A questionnaire was designed to elicit opinions on the impact of VRT on the primary outcome of time from surgery until medically fit for hospital discharge, in the different subgroups. Prior beliefs of the subgroup effect of VRT were elicited face-to-face using two unconditional and one conditional questions per subgroup analysis. The robustness of results to the ‘community of priors’ was assessed. The community of priors was built using the expert priors for the mean average treatment effect, the interaction effect or both in a Bayesian Cox proportional hazards model implemented in the STAN software in R.ResultsExpert opinions were obtained from 7 clinicians (6 cardiac surgeons and 1 cardiac anaesthetist). Participating experts believed VRT could reduce the length of recovery compared to usual care and the greatest benefit was expected in the subgroups with the more severe comorbidity. The Bayesian posterior estimates were more precise compared to the frequentist maximum likelihood estimate and were shifted toward the overall mean treatment effect.ConclusionsIn the VeRDiCT trial, the Bayesian analysis did not provide evidence of a difference in treatment effect across subgroups. However, this approach increased the precision of the estimated subgroup effects and produced more stable treatment effect point estimates than the frequentist approach. Trial methodologists are encouraged to prospectively consider Bayesian subgroup analyses when low-powered interaction tests are planned.Trial registrationISRCTN,ISRCTN02159606. Registered 29th October 2008.
Linkage of primary care prescribing records and pharmacy dispensing Records in the Salford Lung Study: application in asthma
Authors:   The Salford Lung Study Team, Tibble Holly , Lay-Flurrie James , Sheikh Aziz , Horne Rob , Mizani Mehrdad A. , Tsanas Athanasios 
Published: December 2020

Abstract
Background
Records of medication prescriptions can be used in conjunction with pharmacy dispensing records to investigate the incidence of adherence, which is defined as observing the treatment plans agreed between a patient and their clinician. Using prescribing records alone fails to identify primary non-adherence; medications not being collected from the dispensary. Using dispensing records alone means that cases of conditions that resolve and/or treatments that are discontinued will be unaccounted for. While using a linked prescribing and dispensing dataset to measure medication non-adherence is optimal, this linkage is not routinely conducted. Furthermore, without a unique common event identifier, linkage between these two datasets is not straightforward.

Methods
We undertook a secondary analysis of the Salford Lung Study dataset. A novel probabilistic record linkage methodology was developed matching asthma medication pharmacy dispensing records and primary care prescribing records, using semantic (meaning) and syntactic (structure) harmonization, domain knowledge integration, and natural language feature extraction. Cox survival analysis was conducted to assess factors associated with the time to medication dispensing after the prescription was written. Finally, we used a simplified record linkage algorithm in which only identical records were matched, for a naïve benchmarking to compare against the results of our proposed methodology.

Results
We matched 83% of pharmacy dispensing records to primary care prescribing records. Missing data were prevalent in the dispensing records which were not matched – approximately 60% for both medication strength and quantity. A naïve benchmarking approach, requiring perfect matching, identified one-quarter as many matching prescribing records as our methodology. Factors associated with delay (or failure) to collect the prescribed medication from a pharmacy included season, quantity of medication prescribed, previous dispensing history and class of medication. Our findings indicate that over 30% of prescriptions issued were not collected from a dispensary (primary non-adherence).

Conclusions
We have developed a probabilistic record linkage methodology matching a large percentage of pharmacy dispensing records with primary care prescribing records for asthma medications. This will allow researchers to link datasets in order to extract information about asthma medication non-adherence.
Experiences of managerial accountability in Ethiopia’s primary healthcare system: a qualitative study
Authors: Fetene Netsanet , Patel Akshar , Benyam Tibebu , Ayde Assefa , Desai Mayur M. , Curry Leslie , Linnander Erika 
Published: December 2020

AbstractBackgroundDespite calls for improved accountability in global health systems, and a set of clear and consistent theoretical accountability frameworks, empirical descriptions of how accountability is experienced and enacted in low- and middle- income country (LMIC) settings is limited. Therefore, we sought to characterize how managers at all levels of Ethiopia’s primary healthcare system experience accountability in their daily practice.MethodsWe conducted in-depth key informant interviews with 41 key stakeholders across 4 regions (Amhara, Oromia, Southern Nations Nationalities and Peoples, and Tigray) in the context of the Primary Healthcare Transformation Initiative (PTI). Consistent with the principles of grounded theory, our team used the constant comparative method to identify emergent themes related to concrete areas that could be targeted to allow an overall culture of accountability to flourish.ResultsEmergent themes were: development of a shared understanding of system-wide accountability, streamlining of managerial reporting lines, strengthening of medico-legal knowledge and systems, and development of mechanisms for bottom-up accountability.ConclusionsFindings may be valuable to policymakers seeking to create more effective national accountability frameworks; practitioners and development partners seeking to strengthen implementation of evidence-based accountability systems and practices; and researchers aiming to develop meaningful, practical measures of accountability in public health.
Monozygotic dichorionic-diamniotic pregnancies following single frozen-thawed blastocyst transfer: a retrospective case series
Authors: Li He , Shen Tingting , Sun Xiaoxi 
Published: December 2020

Abstract
Background
The primary aim of the study is to report cases of monozygotic dichorionic-diamniotic (DC-DA) pregnancies after single frozen-thawed blastocyst transfer.

Methods
This is a retrospective case series. All single frozen-thawed blastocyst transfer cycles performed between June 2013 and December 2018 at the Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China, were reviewed retrospectively. We included frozen embryo transfer (FET) cycles which clinical pregnancy was confirmed with multiple gestational sacs showed on ultrasonography at around 6 to 7 weeks of gestation. We then conducted an in-depth analysis to further exclude cases which contained newborns of different genders or natural FET cycles.

Results
Five thousand four hundred fifteen frozen-thawed single blastocyst transfer cycles were preformed between June 2013 and December 2018 at the Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China. Of these, fourteen women underwent a single blastocyst transfer and then achieved clinical pregnancy with an ultrasound diagnosis of multi-chorionic pregnancy. With one natural cycle FET excluded, we finally included thirteen single blastocyst transfer cycles performed in down-regulated controlled FET or hormone replacement FET, in which the possibility of concurrently spontaneous pregnancy was extremely small. These included 13 cases reveal the phenomenon of monozygotic DC-DA twinning after single blastocyst transfer, which challenges the classical theory that only monochorionic pregnancy could happen after 3 days of fertilization.

Conclusion
This case series suggest that single blastocyst transfer could result DC-DA pregnancies during IVF treatment.
“An unnecessary cut?” multilevel health systems analysis of drivers of caesarean sections rates in Italy: a systematic review
Authors: Laurita Longo Valentina , Odjidja Emmanuel Nene , Beia Thierry Kamba , Neri Manuela , Kielmann Karina , Gittardi Irene , Di Rosa Amanda Isabella , Boldrini Michela , Melis Gian Benedetto , Scambia Giovanni , Lanzone Antonio 
Published: December 2020

Abstract
Background
Improvements in medical technologies have seen over-medicalization of childbirth. Caesarean section (CS) is a lifesaving procedure proven effective in reducing maternal and perinatal mortality across the globe. However, as with any medical procedure, the CS intrinsically carries some risk to its beneficiaries. In recent years, CS rates have risen alarmingly in high-income countries. Many exceeding the World Health Organisation (WHO) recommendation of a 10 to 15% annual CS rate. While this situation poses an increased risk to women and their children, it also represents an excess human and financial burden on health systems. Therefore, from a health system perspective this study systematically summarizes existing evidence relevant to the factors driving the phenomenon of increasing CS rates using Italy as a case study.

Methods
Employing the WHO Health System Framework (WHOHSF), this systematic review used the PRISMA guidelines to report findings. PubMed, SCOPUS, MEDLINE, Cochrane Library and Google Scholar databases were searched up until April 1, 2020. Findings were organised through the six dimensions of the WHOHSF framework: service delivery, health workforce, health system information; medical products vaccine and technologies, financing; and leadership and governance.

Results
CS rates in Italy are affected by complex interactions among several stakeholder groups and contextual factors such as the hyper-medicalisation of delivery, differences in policy and practice across units and the national context, issues pertaining to the legal and social environment, and women’s attitudes towards pregnancy and childbirth.

Conclusion
Mitigating the high rates of CS will require a synergistic multi-stakeholder intervention. Specifically, with processes able to attract the official endorsement of policy makers, encourage concensus between regional authorities and local governments and guide the systematic compliance of delivery units with its clinical guidelines.