bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy, safety, and cost-effectiveness analysis of adjuvant herbal medicine treatment, Palmijihwang-hwan, for chronic low back pain: a study protocol for randomized, controlled, assessor-blinded, multicenter clinical trial
Authors: Sung Won-Suk , Jeon Sae-Rom , Hong Ye-Jin , Kim Tae-Hun , Shin Seungwon , Lee Hyun-Jong , Seo Byung-Kwan , Park Yeon-Cheol , Kim Eun-Jung , Nam Dong-Woo 
Published: December 2019

Abstract
Background
Low back pain is a common symptom and continuous or recurrent pain results in chronic low back pain (CLBP). While many patients with CLBP have tried various treatments, complementary and alternative medicine including acupuncture and herbal medicine is one of the commonly used treatments. Palmijihwang-hwan is a herbal medicine used frequently in clinical practice but there has been no report of the efficacy, safety, or cost-effectiveness analysis of Palmijihwang-hwan for CLBP.

Methods
This study is a randomized, assessor-blinded, multicenter, clinical trial with two parallel groups. Four Korean medicine hospitals will recruit 84 participants and randomly allocate them into the control or treatment group in a 1:1 ratio. The control group will receive acupuncture treatment at 11 local and 4 distal acupuncture points for 20 min twice a week for 6 weeks. The treatment group will receive the same acupuncture treatment as the control group and also take Palmijihwang-hwan for 6 weeks. The primary outcome will be the change in visual analog scale (VAS) score between baseline (visit 1) and completion of the intervention (visit 12), and secondary outcomes will be pain-related clinical relevance (minimal clinical important difference or the proportion of the participants who decrease more than 30, or 50% on VAS), disability (Roland and Morris Disability Questionnaire), quality of life (EuroQol-5D), global assessment (Patient Global Impression of Change), and economic analysis (cost-effectiveness and cost-utility analysis). Additionally, safety will be assessed.

Discussion
The results of our study will provide the clinical evidence about the efficacy, safety, and cost-effectiveness analysis of Palmijihwang-hwan for CLBP. There will be a chance to provide multiple subdivided influence of this treatment with various outcome measures, but lack of placebo is our limitation.

Trial registration
Clinical Research Information Service, KCT0002998. Registered on 12 July 2018.
Two interventions to treat pain disorders and post-traumatic symptoms among Syrian refugees: protocol for a randomized controlled trial
Authors: Hasha Wegdan , Fadnes Lars T. , Igland Jannicke , Vårdal Rolf , Giusti Line Merete , Strømme Elisabeth Marie , Haj-Younes Jasmin , Heltne Unni , Kumar Bernadette N. , Diaz Esperanza 
Published: December 2019

Abstract
Background
There is a high prevalence of pain and post-traumatic symptoms among refugees and feasible interventions to manage these are needed. However, knowledge about the effect of physiotherapy and psychological group interventions among refugees is scarce. Our aim is to determine whether two different interventions, the Physiotherapy Activity and Awareness Intervention (PAAI) and Teaching Recovery Techniques (TRT), reduce pain and post-traumatic symptoms among refugees from Syria living in Norway.

Methods/design
Syrian adults with either pain disorders or post-traumatic symptoms, or both, will be recruited to this randomized control trial. The trial will include two separate interventions: participants with dominating pain symptoms will be assigned to the PAAI; and those with a predominance of post-traumatic symptoms will be assigned to the TRT intervention. Participants will be randomized to either the immediate intervention group or the delayed intervention group, for each of the interventions (PAAI and TRT). A minimum of 68 participants will be recruited for the PAAI and 78 participants for TRT, in order to detect clinically and statistically significant symptom improvement, assuming 25–30% attrition after recruitment. The main outcomes for the analyses will be pain intensity measured by the Brief Pain Inventory questionnaire and the scores of the Impact of Events Scale — Revised. The effect will be evaluated at the end of interventions lasting 8 weeks (PAAI) and 6 weeks (TRT) using the same instruments after the end of the intervention, and again 4–6 weeks later. Additionally, a qualitative evaluation will be conducted through an embedded process evaluation and personal interviews with participants after each of the interventions is finished.

Discussion
Our study will determine the feasibility of the implementation of two different interventions and the effect of these interventions among refugees from Syria with pain disorders and/or post-traumatic symptoms.

Trial registration
Clinical Trials.gov, NCT03951909. Retrospectively registered on 19 February 2019.
Age-specific diabetes risk by the number of metabolic syndrome components: a Korean nationwide cohort study
Authors: Lee Min-Kyung , Han Kyungdo , Kwon Hyuk-Sang 
Published: December 2019

Abstract
Background
Metabolic syndrome is associated with an increased risk of diabetes. This study investigated the associations between the number of metabolic syndrome components and diabetes risk by age, sex and BMI.

Methods
Data for 19,475,643 participants ≥ 20 years old with no history of diabetes were obtained between 2009 and 2012 and were accessed using the South Korean National Health Insurance Service. Metabolic syndrome was defined according to the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III. We assessed the risk of diabetes according to the number of metabolic syndrome components after stratifying the study participants into groups by age (20–39, 46–64, ≥ 65 years), sex, and BMI (below or above 25).

Results
During an average of 5.13 years of follow-up, the incidence rates of diabetes increased with the number of metabolic syndrome components. Age and BMI gradually increased with the number of metabolic syndrome components. The multivariable-adjusted hazard ratios (HRs) for incident diabetes were 1.401, 1.862, 2.47, 3.164 and 4.501 for participants with one through five components, respectively, compared with those without metabolic syndrome components. The risk of diabetes was 1.79-, 2.18-, and 3.05-times higher for participants ≥ 65 years; 2.57-, 3.45-, and 5.18-times higher for participants 40–64 years; and 2.55-, 3.89-, and 6.31-times higher for participants 20–39 years of age with three through five components, respectively, compared to those with no components. There was no difference in the risk of diabetes between men and women. The HRs were 5.63 for participants with a BMI ≥ 25 and 3.98 for those with a BMI < 25 among individuals with five components.

Conclusions
The risk of diabetes was more strongly associated with the number of metabolic syndrome components among younger adults. In addition, the risk of diabetes across the number of metabolic syndrome components was greater in participants with a BMI ≥ 25.
Plasma amyloid assay as a pre-screening tool for amyloid positron emission tomography imaging in early stage Alzheimer’s disease
Authors: Lin Szu-Ying , Lin Kun-Ju , Lin Po-Chen , Huang Chin-Chang , Chang Chiung-Chih , Lee Yi-Chung , Hsiao Ing-Tsung , Yen Tzu-Chen , Huang Wen-Sheng , Yang Bang-Hung , Wang Pei-Ning 
Published: December 2019

Abstract
Introduction
Due to the high cost and high failure rate of ascertaining amyloid positron emission tomography positivity (PET+) in patients with earlier stage Alzheimer’s disease (AD), an effective pre-screening tool for amyloid PET scans is needed.

Methods
Patients with mild cognitive impairment (n = 33, 24.2% PET+, 42% females, age 74.4 ± 7.5, MMSE 26.8 ± 1.9) and mild dementia (n = 19, 63.6% PET+, 36.3% females, age 73.0 ± 9.3, MMSE 22.6 ± 2.0) were recruited. Amyloid PET imaging, Apolipoprotein E (APOE) genotyping, and plasma amyloid β (Aβ)1–40, Aβ1–42, and total tau protein quantification by immunomagnetic reduction (IMR) method were performed. Receiver operating characteristics (ROC) analysis and Youden’s index were performed to identify possible cut-off points, clinical sensitivities/specificities, and areas under the curve (AUCs).

Results
Amyloid PET+ participants had lower plasma Aβ1–42 levels than amyloid PET-negative (PET−) subjects. APOE ε4 carriers had higher plasma Aβ1–42 than non-carriers. We developed an algorithm involving the combination of plasma Aβ1–42 and APOE genotyping. The success rate for detecting amyloid PET+ patients effectively increased from 42.3 to 70.4% among clinically suspected MCI and mild dementia patients.

Conclusions
Our results demonstrate the possibility of utilizing APOE genotypes in combination with plasma Aβ1–42 levels as a pre-screening tool for predicting the positivity of amyloid PET findings in early stage dementia patients.
High occurrence of transportation and logistics occupations among vascular dementia patients: an observational study
Authors: van Loenhoud A. C. , de Boer C. , Wols K. , Pijnenburg Y. A. , Lemstra A. W. , Bouwman F. H. , Prins N. D. , Scheltens P. , Ossenkoppele R. , van der Flier W. M. 
Published: December 2019

Abstract
Background
Growing evidence suggests a role of occupation in the emergence and manifestation of dementia. Occupations are often defined by complexity level, although working environments and activities differ in several other important ways. We aimed to capture the multi-faceted nature of occupation through its measurement as a qualitative (instead of a quantitative) variable and explored its relationship with different types of dementia.

Methods
We collected occupational information of 2121 dementia patients with various suspected etiologies from the Amsterdam Dementia Cohort (age 67 ± 8, 57% male; MMSE 21 ± 5). Our final sample included individuals with Alzheimer’s disease (AD) dementia (n = 1467), frontotemporal dementia (n = 281), vascular dementia (n = 98), Lewy body disease (n = 174), and progressive supranuclear palsy/corticobasal degeneration (n = 101). Within the AD group, we used neuropsychological data to further characterize patients by clinical phenotypes. All participants were categorized into 1 of 11 occupational classes, across which we evaluated the distribution of dementia (sub)types with χ2 analyses. We gained further insight into occupation-dementia relationships through post hoc logistic regressions that included various demographic and health characteristics as explanatory variables.

Results
There were significant differences in the distribution of dementia types across occupation groups (χ2 = 85.87, p < .001). Vascular dementia was relatively common in the Transportation/Logistics sector, and higher vascular risk factors partly explained this relationship. AD occurred less in Transportation/Logistics and more in Health Care/Welfare occupations, which related to a higher/lower percentage of males. We found no relationships between occupational classes and clinical phenotypes of AD (χ2 = 53.65, n.s.).

Conclusions
Relationships between occupation and dementia seem to exist beyond the complexity level, which offers new opportunities for disease prevention and improvement of occupational health policy.
Gallbladder hemorrhage during orally administered edoxaban therapy: a case report
Authors: Itagaki Hideya , Katuhiko Suzuki 
Published: December 2019

Abstract
Background
Edoxaban is an orally administered anticoagulant treatment that is used in patients with cerebral infarction, venous thrombosis, or other conditions, with a reported incidence of gastrointestinal hemorrhage at approximately 1%. We encountered the rare case of a patient who developed a gallbladder hemorrhage after the administration of edoxaban.

Case presentation
An 86-year-old Japanese woman visited our gastrointestinal department due to the chief complaint of melena lasting for a week. Her medical history included hypertension and embolic cerebral infarction, and she was taking orally administered carvedilol (5 mg/day) and edoxaban (30 mg/day). Her palpebral conjunctiva was pale during a physical examination, indicating the possibility of anemia. Her blood test results confirmed severe anemia with red blood cells at 1.7 × 106/μL and hemoglobin at 4.7 g/dL. An upper gastrointestinal endoscopy revealed bile and fresh blood on the duodenal bulb and in more distal regions; hemobilia was suspected. A computed tomography scan on the ninth hospitalization day confirmed the hemobilia with a gallbladder fundus high-density signal. She was discharged on the 30th day of hospitalization with only fluid therapy and no progression of anemia. Moreover, she underwent a laparoscopic cholecystectomy 1 month after discharge, but the pathologist did not identify false aneurysms or neoplastic lesions. She has not been shown to develop anemia for 5 months after surgery.

Conclusions
Our case suggests that gallbladder hemorrhage needs to be considered a possible complication for patients on direct oral anticoagulants.
Economic burden of vertigo: a systematic review
Authors: Kovacs Eva , Wang Xiaoting , Grill Eva 
Published: December 2019

Abstract
Background
Vertigo, a highly prevalent disease, imposes a rising burden on the health care system, exacerbated by the ageing of the population; and further, contributes to a wide span of indirect burden due to reduced capacity to work or need of assistance in activities of daily living. The aim of this review was to summarise the evidence on the economic burden of vertigo.

Methods
All original studies published between 2008 and 2018 about the economic evaluation of peripheral or central vestibular vertigo in developed countries were considered eligible, unrestricted to setting, health care provider, or study type.

Results
The electronic search in three databases identified 154 studies from which 16 qualified for inclusion. All studies presented partial economic evaluation referring to a variety of vestibular vertigo including unspecified vertigo. Nine studies presented monetised cost results and seven studies reported health care utilization. Direct costs derived mainly from repeated and not well-targeted consultations at all levels of health care, excessive use of diagnostic imaging, and/or of emergency care. Considerable societal burden was caused by decreased productivity, mainly due to work absenteeism.

Conclusion
To the best of our knowledge, this is the first systematic review of the existing evidence of the economic burden of vertigo. The lack of conclusive evidence revealed apparent targets of future research. First, studies of diagnostics and therapies for vestibular disease should include cost-effectiveness considerations. Population-based studies of health services utilization should include simple vestibular assessments to get more reliable estimates of the burden of disease and associated costs on the level of the general population. Further, clinical and population-based registries that include patients with vestibular disease, should consider collecting long-term data of societal burden. Primary data collection should increasingly include assessment of health care utilization e.g. by linking their diagnoses and outcomes to routine data from health insurances.
Building a Group-Based Opioid Treatment (GBOT) blueprint: a qualitative study delineating GBOT implementation
Authors: Sokol Randi , Albanese Mark , Chew Aaronson , Early Jessica , Grossman Ellie , Roll David , Sawin Greg , Wu Dominic J. , Schuman-Olivier Zev 
Published: December 2019

AbstractBackgroundGroup-Based Opioid Treatment (GBOT) has recently emerged as a mechanism for treating patients with opioid use disorder (OUD) in the outpatient setting. However, the more practical “how to” components of successfully delivering GBOT has received little attention in the medical literature, potentially limiting its widespread implementation and utilization. Building on a previous case series, this paper delineates the key components to implementing GBOT by asking: (a) What are thecorecomponents to GBOT implementation, and how are they defined? (b) What are themalleablecomponents to GBOT implementation, and what conceptual framework should providers use in determining how to apply these components for effective delivery in their unique clinical environment?MethodsTo create a blueprint delineating GBOT implementation, we integrated findings from a previously conducted and separately published systematic review of existing GBOT studies, conducted additional literature review, reviewed best practice recommendations and policies related to GBOT and organizational frameworks for implementing health systems change. We triangulated this data with a qualitative thematic analysis from 5 individual interviews and 2 focus groups representing leaders from 5 different GBOT programs across our institution to identify the key components to GBOT implementation, distinguish “core” and “malleable” components, and provide a conceptual framework for considering various options for implementing the malleable components.ResultsWe identified 6 core components to GBOT implementation that optimize clinical outcomes, comply with mandatory policies and regulations, ensure patient and staff safety, and promote sustainability in delivery. These included consistent group expectations, team-based approach to care, safe and confidential space, billing compliance, regular monitoring, and regular patient participation. We identified 14 malleable components and developed a novel conceptual framework that providers can apply when deciding how to employ each malleable component that considers empirical, theoretical and practical dimensions.ConclusionWhile further research on the effectiveness of GBOT and its individual implementation components is needed, the blueprint outlined here provides an initial framework to help office-based opioid treatment sites implement a successful GBOT approach and hence potentially serve as future study sites to establish efficacy of the model. This blueprint can also be used to continuously monitor how components of GBOT influence treatment outcomes, providing an empirical framework for the ongoing process of refining implementation strategies.
Total hip arthroplasty for intertrochanteric fracture fixation failure
Authors: Liu Liyun , Sun Yongqiang , Wang Linlin , Gao Qiankun , Li Ang , Wang Jialin , Gao Yanzheng 
Published: December 2019

AbstractBackgroundIntertrochanteric fracture is a common fracture suffered by elderly patients. Total hip arthroplasty (THA) is regarded as a salvage operation to restore hip joint function after fixation failure, which remains somewhat controversial due to some clinical potential issues.Methods18 elderly patients (average age 70.3 years) each with intertrochanteric fracture fixation failure treated with THA between September 2013 and October 2016 were retrospectively analyzed. Internal fixation treatments involved 5 patients who had received proximal femoral nail anti-rotation, 7 who received locking proximal femur plates and 6 who received dynamic hip screws. All patients were treated with THA using biological acetabular prosthesis and hip arthroplasty (HA) coating skillet femoral prosthesis, with the greater trochanter fixed using wire or steel when necessary. Patients’ Harris scores pre- and post-treatment, SF-36 Health Questionnaire score and digital radiology (DR) were used for joint prostheses initial stability and survival evaluation.Results15 patients completed follow-up periods ranging between 19 and 54 months (mean 26.2 months; 1 patient died from a pulmonary embolism, 1 patient died from pulmonary heart disease 1 year after surgery and 1 patient withdrew for personal reasons). There were no joint infections, periprosthetic fractures or dislocations. The average Harris score increased significantly, from 32.68 ± 12.04 points before surgery to 91.08 ± 5.9 points at 24 months post-treatment. SF-36 scores were significantly increased.ConclusionTHA as salvage treatment for failed internal fixation of intertrochanteric femoral fractures in elderly patients significantly reduced hip pain and restored joint function, and early clinical outcomes were satisfactory.
HIF1/2-exerted control over glycolytic gene expression is not functionally relevant for glycolysis in human leukemic stem/progenitor cells
Authors: Wierenga Albertus T. J. , Cunningham Alan , Erdem Ayşegül , Lopera Nuria Vilaplana , Brouwers-Vos Annet Z. , Pruis Maurien , Mulder André B. , Günther Ulrich L. , Martens Joost H. A. , Vellenga Edo , Schuringa Jan Jacob 
Published: December 2019

Abstract
Background
Hypoxia-inducible factors (HIF)1 and 2 are transcription factors that regulate the homeostatic response to low oxygen conditions. Since data related to the importance of HIF1 and 2 in hematopoietic stem and progenitors is conflicting, we investigated the chromatin binding profiles of HIF1 and HIF2 and linked that to transcriptional networks and the cellular metabolic state.

Methods
Genome-wide ChIPseq and ChIP-PCR experiments were performed to identify HIF1 and HIF2 binding sites in human acute myeloid leukemia (AML) cells and healthy CD34+ hematopoietic stem/progenitor cells. Transcriptome studies were performed to identify gene expression changes induced by hypoxia or by overexpression of oxygen-insensitive HIF1 and HIF2 mutants. Metabolism studies were performed by 1D-NMR, and glucose consumption and lactate production levels were determined by spectrophotometric enzyme assays. CRISPR-CAS9-mediated HIF1, HIF2, and ARNT−/− lines were generated to study the functional consequences upon loss of HIF signaling, in vitro and in vivo upon transplantation of knockout lines in xenograft mice.

Results
Genome-wide ChIP-seq and transcriptome studies revealed that overlapping HIF1- and HIF2-controlled loci were highly enriched for various processes including metabolism, particularly glucose metabolism, but also for chromatin organization, cellular response to stress and G protein-coupled receptor signaling. ChIP-qPCR validation studies confirmed that glycolysis-related genes but not genes related to the TCA cycle or glutaminolysis were controlled by both HIF1 and HIF2 in leukemic cell lines and primary AMLs, while in healthy human CD34+ cells these loci were predominantly controlled by HIF1 and not HIF2. However, and in contrast to our initial hypotheses, CRISPR/Cas9-mediated knockout of HIF signaling did not affect growth, internal metabolite concentrations, glucose consumption or lactate production under hypoxia, not even in vivo upon transplantation of knockout cells into xenograft mice.

Conclusion
These data indicate that, while HIFs exert control over glycolysis but not OxPHOS gene expression in human leukemic cells, this is not critically important for their metabolic state. In contrast, inhibition of BCR-ABL did impact on glucose consumption and lactate production regardless of the presence of HIFs. These data indicate that oncogene-mediated control over glycolysis can occur independently of hypoxic signaling modules.
Selection and screening strategies in directed evolution to improve protein stability
Authors: Ren Chang , Wen Xin , Mencius Jun , Quan Shu 
Published: December 2019

AbstractProtein stability is not only fundamental for experimental, industrial, and therapeutic applications, but is also the baseline for evolving novel protein functions. For decades, stability engineering armed with directed evolution has continued its rapid development and inevitably poses challenges. Generally, in directed evolution, establishing a reliable link between a genotype and any interpretable phenotype is more challenging than diversifying genetic libraries. Consequently, we set forth in a small picture to emphasize the screening or selection techniques in protein stability-directed evolution to secure the link. For a more systematic review, two main branches of these techniques, namely cellular or cell-free display and stability biosensors, are expounded with informative examples.