bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylmalonic and propionic acidemia among hospitalized pediatric patients: a nationwide report
Authors: Jiang Yi-Zhou , Shi Yu , Shi Ying , Gan Lan-Xia , Kong Yuan-Yuan , Zhu Zhi-Jun , Wang Hai-Bo , Sun Li-Ying 
Published: December 2019

Abstract
Background
Methylmalonic acidemia (MMA) and propionic acidemia (PA) are two kinds of diseases caused by inborn errors of metabolism. So far, the epidemiological data on them are limited in China. The aim of our study is to investigate the proportion and characteristics of hospitalized pediatric patients with MMA and PA in China.

Methods
The data in this study were obtained from the Hospital Quality Monitoring System, a national inpatient database in China, with information on the patients hospitalized during the period from 2013 to 2017. We identified the data related to the patients who were under 18 years old and were diagnosed with MMA/PA, and extracted the information on demographic characteristics, hospital location, total cost and other related clinical presentations from the data.

Results
Among all hospitalized pediatric patients with liver diseases, there were increasing trends in the proportion of individuals diagnosed with MMA or PA during the period from 2013 (0.76% for MMA; 0.13% for PA) to 2017 (1.61% for MMA; 0.32% for PA). For both MMA and PA, children under 2-year-old accounted for the highest proportion. The median of total cost per hospitalization was relatively high (RMB 7388.53 for MMA; RMB 4999.66 for PA). Moreover, most patients hospitalized in tertiary class A hospitals (MMA: 80.96%, PA: 76.21%); and a majority of pediatric patients admitted in the hospitals in Shanghai and Beijing are from outside districts. Manifestations of nervous system-related symptoms, and metabolic acidosis or anemia in laboratory findings were more common during hospitalization.

Conclusions
The study is the first nationwide one in providing epidemiological and clinical information on hospitalized pediatric patients with MMA/PA. An increasing hospitalization with various presentations and a heavy financial burden were observed. In addition, geographically, the medical resources in China have been unevenly distributed.
Dua Ti Dawa Ti: understanding psychological distress in the ten districts of the Kashmir Valley and community mental health service needs
Authors: Housen Tambri , Ara Shabnum , Shah Akmal , Shah Showkat , Lenglet Annick , Pintaldi Giovanni 
Published: December 2019

Abstract
Background
An extensive body of research exists looking at the level of psychological distress in populations affected by political conflict. Recommended response to psychological distress in humanitarian crises is still based on frameworks for interventions developed in western/European contexts including psychological first aid, counselling and group therapy. While there is growing, but limited, evidence that culturally modified interventions can lead to reduction in symptoms of psychological distress in conflict affected populations, there is a need to understand mental health help-seeking behaviour and mental health service needs from the perspective of affected communities.

Methods
This study employed a qualitative exploratory research design based on principles of grounded theory. A combination of convenience and snowball sampling was used to recruit 186 adults from the general population to 20 focus group discussions; 95 men, median age 40 years, interquartile range (IQR): 27–48 years and 91 women, median age 40 years IQR: 32–50 years. Trained Kashmiri facilitators used a semi-structured interview guide to ascertain community perceptions on mental illness, help-seeking and service needs from the perspective of communities in the Kashmir Valley. Content analysis of transcripts resulted in the identification of seven overarching themes.

Results
Common locally recognized symptoms of psychological distress were synonymous with symptoms listed in the Hopkins Symptoms Checklist (HSCL-25) and the Harvard Trauma Questionnaire (HTQ). Protracted political insecurity was highlighted as a major perceived cause of psychological distress in communities. Mental health help-seeking included traditional/spiritual healers in combination with practitioners of western medicine, with access highlighted as the main barrier. Divergent views were expressed on the effectiveness of treatment received. Participants’ expressed the need for investment in mental health literacy to improve the community’s capacity to recognize and support those suffering from psychological distress.

Conclusions
Our findings demonstrate the universality of symptoms of psychological distress whilst simultaneously highlighting the importance of recognizing the cultural, spiritual and contextual framework within which psychological distress is understood and manifest. Co-constructed models of community based mental health services are needed.
Recommended care and care adherence following a diagnosis of Lynch syndrome: a mixed-methods study
Authors: Mittendorf Kathleen F. , Hunter Jessica Ezzell , Schneider Jennifer L. , Shuster Elizabeth , Rope Alan F. , Zepp Jamilyn , Gilmore Marian J. , Muessig Kristin R. , Davis James V. , Kauffman Tia L. , Bergen Kellene M. , Wiesner Georgia L. , Acheson Louise S. , Peterson Susan K. , Syngal Sapna , Reiss Jacob A. , Goddard Katrina A. B. 
Published: December 2019

Abstract
Background
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. This study assesses trends in diagnosis of LS and adherence to recommended LS-related care in a large integrated healthcare organization (~ 575,000 members).

Methods
Electronic medical record (EMR) data (1999–2015) were examined to identify patients with a diagnosis of LS. We examined their LS-associated care recommendations and adherence to these recommendations. Qualitative patient and provider interviews were conducted with the aim of identifying opportunities for improved care delivery.

Results
We identified 74 patients with a diagnosis of LS; 64% were diagnosed with a LS-related malignancy prior to their diagnosis of LS. The time to LS diagnosis following development of a LS-related cancer decreased over time: before 2009 11% of individuals received a diagnosis of LS within 1 year of developing a LS-related cancer compared to 83% after 2009 (p < 0.0001). Colonoscopy recommendations were documented in the EMR for almost all patients with LS (96%). Documentation of other recommendations for cancer surveillance was less commonly found. Overall, patient adherence to colonoscopy was high (M = 81.5%; SD = 32.7%), and adherence to other recommendations varied. To improve care coordination, patients and providers suggested providing automated reminder prompts for LS-related surveillance, adding a LS-specific diagnosis code, and providing guidelines for LS-related surveillance in the EMR.

Conclusions
We identified fewer than expected patients with LS in our large care system, indicating that there is still a diagnostic care gap. However, patients with LS were likely to receive and follow CRC surveillance recommendations. Recommendations for and adherence to extracolonic surveillance were variable. Improved care coordination and clearer documentation of the LS diagnosis is needed.
Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review
Authors: Li Claire H. , Karantza Vassiliki , Aktan Gursel , Lala Mallika 
Published: December 2019

AbstractBackgroundMetastatic triple-negative breast cancer (mTNBC), an aggressive histological subtype, has poor prognosis. Chemotherapy remains standard of care for mTNBC, although no agent has been specifically approved for this breast cancer subtype. Instead, chemotherapies approved for metastatic breast cancer (MBC) are used for mTNBC (National Comprehensive Cancer Network Guidelines [NCCN] v1.2019). Atezolizumab in combination with nab-paclitaxel was recently approved for programmed death-ligand 1 (PD-L1)–positive locally advanced or metastatic TNBC. Published historical data were reviewed to characterize the efficacy of NCCN-recommended (v1.2016) agents as first-line (1L) and second-line or later (2L+) treatment for patients with locally recurrent inoperable or metastatic TNBC (collectively termed mTNBC herein).MethodsA systematic literature review was performed, examining clinical efficacy of therapies for mTNBC based on NCCN v1.2016 guideline recommendations. Data from 13 studies, either published retrospective mTNBC subgroup analyses based on phase III trials in MBC or phase II trials in mTNBC, were included.ResultsA meta-analysis of mTNBC subgroups from three phase III trials in 1L MBC reported pooled objective response rate (ORR) of 23%, median overall survival (OS) of 17.5 months, and median progression-free survival (PFS) of 5.4 months with single-agent chemotherapy. In two subgroup analyses from a phase III study and a phase II trial (n = 40 each), median duration of response (DOR) to 1L chemotherapy for mTNBC was 4.4–6.6 months; therefore, responses were not durable. A meta-analysis of seven cohorts showed the pooled ORR for 2L+ chemotherapy was 11% (95% CI, 9–14%). Median DOR to 2L+ chemotherapy in mTNBC was also limited (4.2–5.9 months) per two subgroup analyses from a phase III study. No combination chemotherapy regimens recommended by NCCN v1.2016 for treatment of MBC showed superior OS to single agents.ConclusionsChemotherapies have limited effectiveness and are associated with unfavorable toxicity profiles, highlighting a considerable unmet medical need for improved therapeutic options in mTNBC. In addition to the recently approved combination of atezolizumab and nab-paclitaxel for PD-L1–positive mTNBC, new treatments resulting in durable clinical responses, prolonged survival, and manageable safety profile would greatly benefit patients with mTNBC.
Guidelines for benchmarking of optimization-based approaches for fitting mathematical models
Authors: Kreutz Clemens 
Published: December 2019

AbstractInsufficient performance of optimization-based approaches for the fitting of mathematical models is still a major bottleneck in systems biology. In this article, the reasons and methodological challenges are summarized as well as their impact in benchmark studies. Important aspects for achieving an increased level of evidence for benchmark results are discussed. Based on general guidelines for benchmarking in computational biology, a collection of tailored guidelines is presented for performing informative and unbiased benchmarking of optimization-based fitting approaches. Comprehensive benchmark studies based on these recommendations are urgently required for the establishment of a robust and reliable methodology for the systems biology community.
CTCF modulates allele-specific sub-TAD organization and imprinted gene activity at the mouse Dlk1-Dio3 and Igf2-H19 domains
Authors: Llères David , Moindrot Benoît , Pathak Rakesh , Piras Vincent , Matelot Mélody , Pignard Benoît , Marchand Alice , Poncelet Mallory , Perrin Aurélien , Tellier Virgile , Feil Robert , Noordermeer Daan 
Published: December 2019

AbstractBackgroundGenomic imprinting is essential for mammalian development and provides a unique paradigm to explore intra-cellular differences in chromatin configuration. So far, the detailed allele-specific chromatin organization of imprinted gene domains has mostly been lacking. Here, we explored the chromatin structure of the two conserved imprinted domains controlled by paternal DNA methylation imprints—theIgf2-H19andDlk1-Dio3domains—and assessed the involvement of the insulator protein CTCF in mouse cells.ResultsBoth imprinted domains are located within overarching topologically associating domains (TADs) that are similar on both parental chromosomes. At each domain, a single differentially methylated region is bound by CTCF on the maternal chromosome only, in addition to multiple instances of bi-allelic CTCF binding. Combinations of allelic 4C-seq and DNA-FISH revealed that bi-allelic CTCF binding alone, on the paternal chromosome, correlates with a first level of sub-TAD structure. On the maternal chromosome, additional CTCF binding at the differentially methylated region adds a further layer of sub-TAD organization, which essentially hijacks the existing paternal-specific sub-TAD organization. Perturbation of maternal-specific CTCF binding site at theDlk1-Dio3locus, using genome editing, results in perturbed sub-TAD organization and bi-allelicDlk1activation during differentiation.ConclusionsMaternal allele-specific CTCF binding at the imprintedIgf2-H19and theDlk1-Dio3domains adds an additional layer of sub-TAD organization, on top of an existing three-dimensional configuration and prior to imprinted activation of protein-coding genes. We speculate that this allele-specific sub-TAD organization provides an instructive or permissive context for imprinted gene activation during development.
Curing hemophilia A by NHEJ-mediated ectopic F8 insertion in the mouse
Authors: Zhang Jian-Ping , Cheng Xin-Xin , Zhao Mei , Li Guo-Hua , Xu Jing , Zhang Feng , Yin Meng-Di , Meng Fei-Ying , Dai Xin-Yue , Fu Ya-Wen , Yang Zhi-Xue , Arakaki Cameron , Su Ruijun Jeanna , Wen Wei , Wang Wen-Tian , Chen Wanqiu , Choi Hannah , Wang Charles , Gao Guangping , Zhang Lei , Cheng Tao , Zhang Xiao-Bing 
Published: December 2019

Abstract
Background
Hemophilia A, a bleeding disorder resulting from F8 mutations, can only be cured by gene therapy. A promising strategy is CRISPR-Cas9-mediated precise insertion of F8 in hepatocytes at highly expressed gene loci, such as albumin (Alb). Unfortunately, the precise in vivo integration efficiency of a long insert is very low (~ 0.1%).

Results
We report that the use of a double-cut donor leads to a 10- to 20-fold increase in liver editing efficiency, thereby completely reconstituting serum F8 activity in a mouse model of hemophilia A after hydrodynamic injection of Cas9-sgAlb and B domain-deleted (BDD) F8 donor plasmids. We find that the integration of a double-cut donor at the Alb locus in mouse liver is mainly through non-homologous end joining (NHEJ)-mediated knock-in. We then target BDDF8 to multiple sites on introns 11 and 13 and find that NHEJ-mediated insertion of BDDF8 restores hemostasis. Finally, using 3 AAV8 vectors to deliver genome editing components, including Cas9, sgRNA, and BDDF8 donor, we observe the same therapeutic effects. A follow-up of 100 mice over 1 year shows no adverse effects.

Conclusions
These findings lay the foundation for curing hemophilia A by NHEJ knock-in of BDDF8 at Alb introns after AAV-mediated delivery of editing components.
Reduction of the long-term use of proton pump inhibitors by a patient-oriented electronic decision support tool (arriba-PPI): study protocol for a randomized controlled trial
Authors: Rieckert Anja , Becker Annette , Donner-Banzhof Norbert , Viniol Annika , Bücker Bettina , Wilm Stefan , Sönnichsen Andreas , Barzel Anne 
Published: December 2019

Abstract
Background
Proton pump inhibitors (PPIs) are increasingly being prescribed, although long-term use is associated with multiple side effects. Therefore, an electronic decision support tool with the aim of reducing the long-term use of PPIs in a shared decision-making process between general practitioners (GPs) and their patients has been developed. The developed tool is a module that can be added to the so-called arriba decision support tool, which is already used by GPs in Germany in routine care. In this large-scale cluster-randomized controlled trial we evaluate the effectiveness of this arriba-PPI tool.

Methods
The arriba-PPI tool is an electronic decision support system that supports shared decision-making and evidence-based decisions around the long-term use of PPIs at the point of care. The tool will be evaluated in a cluster-randomized controlled trial involving 210 GP practices and 3150 patients in Germany. GP practices will be asked to recruit 20 patients aged ≥ 18 years regularly taking PPIs for ≥ 6 months. After completion of patient recruitment, each GP practice with enrolled patients will be cluster-randomized. Intervention GP practices will get access to the software arriba-PPI, whereas control GPs will treat their patients as usual. After an observation period of six months, GP practices will be compared regarding the reduction of cumulated defined daily doses of PPI prescriptions per patient.

Discussion
Our principal hypothesis is that the application of the arriba-PPI tool can reduce PPI prescribing in primary care by at least 15% compared to conventional strategies used by GPs. A positive result implies the implementation of the arriba-PPI tool in routine care.

Trial registration
German Clinical Trials Register, DRKS00016364. Registered on 31 January 2019.
Multicenter randomized study on the comparison between electronic and traditional chest drainage systems
Authors: Marulli Giuseppe , Comacchio Giovanni M. , Nosotti Mario , Rosso Lorenzo , Mendogni Paolo , Natale Giuseppe , Andriolo Luigi , Imbriglio Giovanna , Larocca Valentina , Brascia Debora , Rea Federico 
Published: December 2019

Abstract
Background
In patients submitted to major pulmonary resection, the postoperative length of stay is mainly influenced by the duration of air leaks and chest tube removal. The measurement of air leaks largely relies on traditional chest drainage systems which are prone to subjective interpretation. Difficulty in differentiating between active air leaks and bubbles due to a pleural space effect may also lead to tentative drain clamping and prolonged time for chest drain removal. New digital systems allow continuous monitoring of air leaks, identifying subtle leakage that may be not visible during daily patient evaluation. Moreover, an objective assessment of air leaks may lead to a reduced interobserver variability and to an optimized timing for chest tube removal.

Methods
This study is a prospective randomized, interventional, multicenter trial designed to compare an electronic chest drainage system (Drentech™ Palm Evo) with a traditional system (Drentech™ Compact) in a cohort of patients undergoing pulmonary lobectomy through a standard three-port video-assisted thoracic surgery approach for both benign and malignant disease. The study will enroll 382 patients in three Italian centers. The duration of chest drainage and the length of hospital stay will be evaluated in the two groups. Moreover, the study will evaluate whether the use of a digital chest system compared with a traditional system reduces the interobserver variability. Finally, it will evaluate whether the digital drain system may help in distinguishing an active air leak from a pleural space effect, by the digital assessment of intrapleural differential pressure, and in identifying potential predictors of prolonged air leaks.

Discussion
To date, few studies have been performed to evaluate the clinical impact of digital drainage systems. The proposed prospective randomized trial will provide new knowledge to this research area by investigating and comparing the difference between digital and traditional chest drain systems. In particular, the objectives of this project are to evaluate the feasibility and usefulness of digital chest drainages and to provide new tools to identify patients at higher risk of developing prolonged air leaks.

Trial registration
ClinicalTrials.gov, NCT03536130. Retrospectively registered on 24 May 2018.
Determining the effects of exercise after smoking cessation therapy completion on continuous abstinence from smoking: Japanese study protocol
Authors: Ozaki Yuka , Komiyama Maki , Ueshima Kenji , Iso Hiroyasu , Sakata Satoko , Morino Ayumi , Takahara Mitsuyoshi , Noguchi Satoshi , Kuwabara Yoshihiro , Takahashi Yuko , Hasegawa Koji 
Published: December 2019

AbstractBackgroundDespite a steady world-wide decline over recent decades, rates of smoking remain high in developed countries. In Japan, 30% of men and 10% of women are smokers. Based on these rates, 18.8 million (14.06 million men and 4.74 million women) in Japan are smokers. The rate of success for smoking cessation has recently improved due to the widespread availability of drug therapy; however, the success rate for quitting smoking one year after beginning therapy is only around 50%. Previous studies have demonstrated that exercise can relieve mental stress during continuous abstinence from smoking and curb smoking resumption. To date, no large-scale, randomized controlled trials have examined the effects of exercise on smoking cessation. The present study aims to determine the effects of exercise instruction on continuous abstinence from smoking after completion of smoking cessation therapy.MethodsThis is a multicenter, prospective, parallel-group, randomized controlled trial in Japan. We will enroll 300 individuals visiting a smoking cessation clinic (over 3 months) who have abstained from smoking in the second month after their initial visit as potential participants. Participants will not habitually exercise and will need to consent to participate. Participants will be randomly assigned to the exercise intervention group or control group. The intervention group will receive instruction on exercises that can be incorporated into their daily lives. The control group will be followed during the standard smoking cessation support program. The primary endpoint will be the continuous abstinence rate, and secondary endpoints will be weight, blood pressure, exhaled carbon monoxide concentration, psychological state, and blood test results. These indices will be compared between the intervention and control groups, with follow-up periods of 9 months in both groups.DiscussionBy examining the effects of exercise instruction after completion of 12-week smoking cessation therapy, this study should yield quality information that can be used to develop protocols to improve the continuous abstinence rate and inhibit weight gain after smoking cessation therapy.Trial registrationUMIN Clinical Trials Registry,UMIN000014615. Registered on 1 October 2014.
Reporting quality and adherence of randomized controlled trials about statins and/or fibrates for diabetic retinopathy to the CONSORT checklist
Authors: Mozetic Vânia , Leonel Letícia , Leite Pacheco Rafael , de Oliveira Cruz Latorraca Carolina , Guimarães Taís , Logullo Patricia , Riera Rachel 
Published: December 2019

Abstract
Background
A considerable amount of randomized controlled trials (RCTs) have been published on statins and/or fibrates for diabetic retinopathy, a clinical condition associated with high social and economic burden. Adherence to the CONSORT statement items is imperative to ensure transparency and reproducibility in clinical research. The aim of this study is to assess the reporting quality and the adherence to CONSORT of RCTs assessing statins and/or fibrates for diabetic retinopathy.

Methods
We conducted a critical appraisal study at Discipline of Evidence-based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp). A sensitive literature search was performed to identify all relevant RCTs, with no time or language limits. Two authors independently evaluated the reporting quality of the selected RCTs using the CONSORT statement as a standard.

Results
Thirteen reports of RCTs were included in this study. The adherence of the reports to CONSORT items ranged from 24% to 68%. The median score was 11 (interquartile range (IQR) 8 to 13). When analyzed separately, the methods sections of the reports had a median of three items (IQR 2 to 4) judged adherent to the methods items of CONSORT (items 3 to 12). The most underreported items were those related to trial design, title and abstract, allocation concealment, implementation of the randomization sequence, and blinding. Other important items, such as the one related to the description of the inclusion criteria, also had low adherence.

Conclusions
The overall adherence to the CONSORT checklist items was poor, especially in the items related to the methods section. RCT reports on statins and/or fibrates for diabetic retinopathy must be optimized to avoid reporting biases and to improve transparency and reproducibility.