bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients with premature coronary artery disease: a retrospective cohort study
Authors: Wu Zhenguo , Liu Li , Wang Weiwei , Cui Huiliang , Zhang Yerui , Xu Jiechang , Zhang Wencheng , Zheng Tengfei , Yang Jianmin 
Published: July 2022

Abstract
Background
Premature coronary artery disease (PCAD) has become more common in recent years and is often associated with poor outcomes. Triglyceride-glucose (TyG) index is a simple and reliable surrogate for insulin resistance (IR) and is an independent predictor of cardiovascular prognosis. However, the prognostic value of the TyG index in patients with PCAD remains uncertain. Thus, this study aimed to investigate the prognostic value and predictive performance of the TyG index in patients with PCAD.

Methods
A total of 526 young subjects (male < 45 years, female < 55 years) with angiographically proven CAD from January 2013 to December 2018 were included consecutively in this study. Their clinical and laboratory parameters were collected, and the TyG index was calculated as $$\mathrm{Ln}[\mathrm{fasting triglyceride }(\mathrm{TG}) (\mathrm{mg}/\mathrm{dL})\times \mathrm{fasting plasma glucose }(\mathrm{FPG}) (\mathrm{mg}/\mathrm{dL})/2]$$

Ln
[

fasting
triglyceride

(
TG
)
(
mg
/
dL
)
×

fasting
plasma
glucose

(
FPG
)
(
mg
/
dL
)
/
2
]

. The follow-up time after discharge was 40–112 months (median, 68 months; interquartile range, 49‒83 months). The primary endpoint was the occurrence of the major adverse cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction (MI), coronary artery revascularization, and non-fatal stroke.

Results
The TyG index was significantly associated with traditional cardiovascular risk factors and the Gensini score (GS). Kaplan–Meier survival (MACE-free) curves by tertiles of the TyG index showed statistically significant differences (log-rank test, p = 0.001). In the fully adjusted Cox regression model, the Hazard ratio (95% CI) of MACE was 2.17 (1.15–4.06) in tertile 3 and 1.45 (1.11–1.91) for per SD increase in the TyG index. Time-dependent ROC analyses of the TyG for prediction of MACE showed the area under the curves (AUC) reached 0.631 at 3 years, 0.643 at 6 years, and 0.710 at 9 years. Furthermore, adding TyG index to existing risk prediction model could improve outcome prediction [C-statistic increased from 0.715 to 0.719, p = 0.007; continuous net reclassification improvement (NRI) = 0.101, p = 0.362; integrated discrimination improvement (IDI) = 0.011, p = 0.017].

Conclusion
The TyG index is an independent predictor of MACE in patients with PCAD, suggesting that the TyG index has important clinical implications for risk stratification and early intervention of PCAD.
The development of task sharing policy and guidelines in Kenya
Authors: Kinuthia Rosemary , Verani Andre , Gross Jessica , Kiriinya Rose , Hepburn Kenneth , Kioko Jackson , Langat Agnes , Katana Abraham , Waudo Agnes , Rogers Martha 
Published: July 2022

Abstract
Background
The global critical shortage of health workers prevents expansion of healthcare services and universal health coverage. Like most countries in sub-Saharan Africa, Kenya’s healthcare workforce density of 13.8 health workers per 10,000 population falls below the World Health Organization (WHO) recommendation of at least 44.5 doctors, nurses, and midwives per 10,000 population. In response to the health worker shortage, the WHO recommends task sharing, a strategy that can increase access to quality health services. To improve the utilization of human and financial health resources in Kenya for HIV and other essential health services, the Kenya Ministry of Health (MOH) in collaboration with various institutions developed national task sharing policy and guidelines (TSP). To advance task sharing, this article describes the process of developing, adopting, and implementing the Kenya TSP.

Case presentation
The development and approval of Kenya’s TSP occurred from February 2015 to May 2017. The U.S. Centers for Disease Control and Prevention (CDC) allocated funding to Emory University through the United States President’s Emergency Plan for AIDS Relief (PEPFAR) Advancing Children’s Treatment initiative. After obtaining support from leadership in Kenya’s MOH and health professional institutions, the TSP team conducted a desk review of policies, guidelines, scopes of practice, task analyses, grey literature, and peer-reviewed research. Subsequently, a Policy Advisory Committee was established to guide the process and worked collaboratively to form technical working groups that arrived at consensus and drafted the policy. The collaborative, multidisciplinary process led to the identification of gaps in service delivery resulting from health workforce shortages. This facilitated the development of the Kenya TSP, which provides a general orientation of task sharing in Kenya. The guidelines list priority tasks for sharing by various cadres as informed by evidence, such as HIV testing and counseling tasks. The TSP documents were disseminated to all county healthcare facilities in Kenya, yet implementation was stopped by order of the judiciary in 2019 after a legal challenge from an association of medical laboratorians.

Conclusions
Task sharing may increase access to healthcare services in resource-limited settings. To advance task sharing, TSP and clinical practice could be harmonized, and necessary adjustments made to other policies that regulate practice (e.g., scopes of practice). Revisions to pre-service training curricula could be conducted to ensure health professionals have the requisite competencies to perform shared tasks. Monitoring and evaluation can help ensure that task sharing is implemented appropriately to ensure quality outcomes.
Cost–benefit analysis of kidney transplant in patients with chronic kidney disease: a case study in Iran
Authors: Abdi Farzaneh , Alinia Cyrus , Taghizadeh Afshari Ali , Yusefzadeh Hasan 
Published: July 2022

Abstract
Background
Chronic kidney disease (CKD) is a health problem due to its increasing prevalence and imposes a significant economic burden on the health system. This study aimed to analyze the cost–benefit of kidney transplantation through the valuation of patients with ESRD for a kidney transplant and its costs to help decide this regard.

Material and methods
This study was a descriptive-analytical and cross-sectional economic evaluation study of health interventions performed in Imam Khomeini Hospital in Urmia from the patient’s perspective. The records of kidney recipients were used to calculate the direct costs of kidney transplantation based on the government tariff rate in 2021. The willingness to pay for kidney transplantation (benefit) was measured through a questionnaire and with a contingent valuation method from 266 samples of patients with ESRD. The questionnaire designed by the researchers had four scenarios with different chances for kidney transplant success. Validation and test–retest methods were used to check the validity and reliability of the questionnaire. Stata software was used to estimate the regression of the factors affecting the willingness to pay and the kidney transplant demand function.

Results
The average cost of a kidney transplant was $877.4. The average willingness to pay for a kidney transplant for four scenarios was estimated at $4733. The mean cost–benefit ratio (BCR) and net present value (NPV) for the four kidney transplant scenarios were 5.39 and $3855. The variables of employment status, awareness of kidney function, number of years with ESRD, insurance coverage, and patients’ income significantly affected their willingness to pay. However, the effect of other variables was not significant. The absolute value of price elasticity of kidney transplant demand was also equal to 2.13.

Conclusion
According to the cost–benefit analysis indexes, the study results showed that a kidney transplant has a net positive benefit for all levels of its probability of success, so the willingness to pay or valuation of patients is about five times the cost of a kidney transplant. Also, the demand for kidney transplantation shows the high sensitivity of the demand for this service to the price. Therefore, preparations for kidney transplantation in patients with ESRD should be considered in situations where the price and cost of transplantation change. The results can help health policy-makers decide to allocate financial resources more efficiently.
Dose escalation based on 18F-FDG PET/CT response in definitive chemoradiotherapy of locally advanced esophageal squamous cell carcinoma: a phase III, open-label, randomized, controlled trial (ESO-Shanghai 12)
Authors: Zhu Hongcheng , Liu Qiufang , Xu Hao , Mo Miao , Wang Zezhou , Lu Kui , Zhou Jialiang , Chen Junqiang , Zheng Xiangpeng , Ye Jinjun , Ge Xiaolin , Luo Honglei , Liu Qi , Deng Jiaying , Ai Dashan , Hao Shengnan , Zhang Junhua , Tseng I Hsuan , Song Shaoli , Chen Yun , Zhao Kuaile 
Published: July 2022

Abstract
Introduction
Definitive chemoradiotherapy has established the standard non-surgical treatment for locally advanced esophageal cancer. The standard dose of 50–50.4 Gy has been established decades ago and been confirmed in modern trials. The theorical advantage of better local control and technical advances for less toxicity have encouraged clinicians for dose escalation investigation. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) have the potential to tailor therapy for esophageal patients not showing response to CRT and pioneers the PET-based dose escalation.

Methods and analysis
The ESO-Shanghai 12 trial is a prospective multicenter randomized phase 3 study in which patients are randomized to either 61.2 Gy or 50.4 Gy of radiation dose by PET response. Both groups undergo concurrent chemoradiotherapy with paclitaxel/cisplatin regimen for 2 cycles followed by consolidation chemotherapy for 2 cycles. Patients with histologically confirmed ESCC [T1N1-3M0, T2-4NxM0, TxNxM1 (Supraclavicular lymph node metastasis only), (AJCC Cancer Staging Manual, 8th Edition)] and without any prior treatment of chemotherapy, radiotherapy or surgery against esophageal cancer will be eligible. The primary endpoints included overall survival in PET/CT non-responders (SUVmax > 4.0) and overall survival in total population. Patients will be stratified by standardized uptake volume, gross tumor volume and tumor location. The enrollment could be ended, when the number of PET/CT non-responder reached 132 and the total population reached 646 for randomization.

Ethics and dissemination
This trial has been approved by the Fudan University Shanghai Cancer Center Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations.
Trial registration The trial was initiated in 2018 and is currently recruiting patients. Trial registration number NCT03790553.
Lifecycle management of orphan drugs approved in Japan
Authors: Seki Kiyoshi , Suzuki Hiroshi , Abe Seiji , Saotome Chikako 
Published: July 2022

Abstract
Background
The development of orphan drugs (ODs) is challenging from both development and business perspectives because of their small patient populations. To overcome such business challenges, lifecycle management (LCM), which maximizes profits by increasing sales and extending product lifetimes, is important to overcome the business challenges arising from their small patient populations. To clarify the activities of the LCM of ODs, we investigated additional indications that contribute to market expansion and marketing exclusivity using the patent extension and re-examination system of ODs approved in Japan between 2004 and 2019.

Results
The 203 ODs consisting of 173 active ingredients were approved in Japan between 2004 and 2019. Sixty-eight (39%) of the 173 active ingredients have additional indications, of which 57 have at least one non-OD indication. Three-fourths of the 203 ODs had patent rights, and most of them included substance or use claims. Although the re-examination period for most ODs was 10 years after the approval, most patents had a longer duration than the re-examination period.

Conclusions
Pharmaceutical companies were actively adding non-OD indications and were emphasizing the use of patent rights by registering extensions of substance or use patents for exclusive marketing periods. These results indicate that LCM through the addition of indications and registration of patent extensions is carried out as a strategy for many ODs in Japan, similar to the LCM of general non-ODs.
Use of the bibliometric in rare diseases: taking Wilson disease personally
Authors: Chen Lin , Lou Zhuoqi , Fang Yangxin , Pan Liya , Zhao Jianhua , Zeng Yifan , Wang Ying , Wang Nan , Ruan Bing 
Published: July 2022

Abstract
Background
Bibliometric have been widely applied to the evaluation of academic productivity. However, those of individuals or institutions on a specific disease have not been explored. The aim of the present study is to conduct a bibliometric analysis of particular rare disease and investigate whether those doctors and hospitals with higher index screened by this method specialize in this disease.

Methods
A representative rare disease, Wilson disease (WD), was searched on Clarivate Analytics’ Web of Science and Elsevier’s Scopus, which was published in English between 1 January 2001 and 31 December 2020. Clinical authors and medical institutions with the most papers were screened, and their total number of publications and citations, h-index and g-index were computed and then ranked by h-index.

Results
A total of 6856 and 6193 papers and 200 and 160 authors were got from WoS and Scopus, respectively. Scopus provided 160 institutions. The above bibliometric indices were calculated in 100 researchers and 80 institutions, and top 30 authors (Top-30a) and top 20 institutions (Top-20i) of them based on the h-index were listed in the tables. Top-30a came from seven specialties and 13 countries whose median (interquartile range) h-index was 14 (12–19.5) (range 10–28) which was located between associate and full professors in some other disciplines. Top-20i was distributed in 13 countries whose mean ± standard deviation of the h-index was 15 ± 4.9 (range 10–27).

Conclusions
The related specialists and medical institutions of WD screened by specific disease bibliometric analysis are eminent and credible and benefit WD patients to obtain reliable medical treatment. This model may be suitable for other rare diseases.
Estimating the risk of environmental contamination by forest users in African Swine Fever endemic areas
Authors: Gervasi Vincenzo , Marcon Andrea , Guberti Vittorio 
Published: July 2022

Abstract
Background
African Swine Fever (ASF) is a highly lethal viral disease caused by the African Swine Fever Virus (ASFV), the only virus of the Asfaviridae family, which affects different species of wild and domestic suids, and for which no vaccination or effective medical treatment is currently available. The virus can survive for long periods in the environment, and humans can unintentionally act as vectors through infected fomites, a risk that is linked to the ASF introduction into pig farms. We ran a simulation study, in which we reconstructed the probability process leading to the different forms of human-mediated ASF contamination in ASF endemic areas. We compared the infection risks related to different types of human forest activities and produced estimates of the minimum expected number of human-induced contamination events occurring annually at the scale of some European countries.

Results
When analysed on a short temporal scale and in a relatively small spatial context, ASF environmental contamination appeared as a rather unlikely event for most of the simulated forest uses, with contamination probabilities often lower than 0.1%. When scaling up the contamination process to a whole year and to large geographic areas, though, the accumulation of the same forest activities, repeated several times per month within the same patch of forest, produced the expectation that thousands of contamination events would occur each year, with potentially relevant epidemiological consequences. Wild boar supplemental feeding and forest logging emerged as the riskiest activities in terms of contamination probabilities, but risk was highly influenced by the frequency and intensity of the different types of forest use.

Conclusions
The risk of human-mediated ASF environmental contamination should not be disregarded when planning management actions to reduce ASF circulation and prevent its breach into the pig farming system. Supplemental feeding should be strongly reduced or avoided in ASF affected areas. Wild boar hunting, which is often employed as an active management tool in ASF affected areas, should be seen as both a tool for controlling wild boar density and as a potential risk for further contamination. It is essential to implement and enforce strict biosecurity measures for all forest-based human activities in ASF endemic areas.
Neurological vertigo in the emergency room in pediatric and adult age: systematic literature review and proposal for a diagnostic algorithm
Authors: Pellegrino Noemi , Di Stefano Vincenzo , Rotondo Eleonora , Graziosi Alessandro , Rispoli Marianna Gabriella , Torrente Angelo , Lupica Antonino , Brighina Filippo , Raucci Umberto , Parisi Pasquale 
Published: July 2022

AbstractNeurological vertigo is a common symptom in children and adults presenting to the emergency department (ED) and its evaluation may be challenging, requiring often the intervention of different medical specialties. When vertigo is associated with other specific symptoms or signs, a differential diagnosis may be easier. Conversely, if the patient exhibits isolated vertigo, the diagnostic approach becomes complex and only through a detailed history, a complete physical examination and specific tests the clinician can reach the correct diagnosis. Approach to vertigo in ED is considerably different in children and adults due to the differences in incidence and prevalence of the various causes. The aim of this systematic review is to describe the etiopathologies of neurological vertigo in childhood and adulthood, highlighting the characteristics and the investigations that may lead clinicians to a proper diagnosis. Finally, this review aims to develop an algorithm that could represent a valid diagnostic support for emergency physicians in approaching patients with isolated vertigo, both in pediatric and adult age.
Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas
Authors: Lee Sanghoon , Osmanbeyoglu Hatice Ulku 
Published: July 2022

Abstract
Background
Invasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored.

Methods
Here, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq) dataset.

Results
We identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC.

Conclusions
This study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis.
Interdisciplinary intervention (GAIN) for adults with post-concussion symptoms: a study protocol for a stepped-wedge cluster randomised trial
Authors: Næss-Schmidt Erhard Trillingsgaard , Thastum Mille Møller , Stabel Henriette Holm , Odgaard Lene , Pedersen Asger Roer , Rask Charlotte Ulrikka , Silverberg Noah D. , Schröder Andreas , Nielsen Jørgen Feldbæk 
Published: July 2022

AbstractBackgroundPersistent post-concussion symptoms (PCS) are associated with prolonged disability, reduced health-related quality of life and reduced workability. At present, no strong evidence for treatments for people with persistent PCS exists. Our research group developed a novel intervention, “Get going After concussIoN (GAIN)”, that incorporates multiple evidence-based strategies including prescribed exercise, cognitive behavioural therapy, and gradual return to activity advice. In a previous randomised trial, GAIN provided in a hospital setting was effective in reducing symptoms in 15–30-year-olds with PCS 2–6 months post-injury. In the current study, we describe the protocol for a trial designed to test the effectiveness of GAIN in a larger municipality setting. Additionally, we test the intervention within a broader age group and evaluate a broader range of outcomes. The primary hypothesis is that participants allocated to enhanced usual care plus GAIN report a higher reduction in PCS 3 months post-intervention compared to participants allocated to enhanced usual care only.MethodsThe study is a stepped-wedge cluster-randomised trial with five clusters. The 8-week interdisciplinary GAIN program will be rolled out to clusters in 3-month intervals. Power calculation yield at least 180 participants to be enrolled. Primary outcome is mean change in PCS measured by the Rivermead Post-Concussion Symptoms Questionnaire from enrolment to 3 months after end of treatment. Secondary outcomes include participation in and satisfaction with everyday activities, labour market attachment and other behavioural measures. Self-reported outcomes are measured at baseline, by end of treatment and at 3, 6, and 18 months after end of treatment. Registry-based outcomes are measured up to 36 months after concussion.DiscussionThe trial will provide important information concerning the effectiveness of the GAIN intervention in a municipality setting. Furthermore, it will provide knowledge of possible barriers and facilitators that may be relevant for future implementation of GAIN in different settings.Trial registrationThe current GAIN trial is registered in ClinicalTrials.gov (study identifier:NCT04798885) on 20 October 2020.