bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disseminated Talaromyces marneffei infection presenting as multiple intestinal perforations and diffuse hepatic granulomatous inflammation in an infant with STAT3 mutation: a case report
Authors: Pan Mianluan , Qiu Ye , Zeng Wen , Tang Shudan , Wei Xuan , Zhang Jianquan 
Published: June 2020

Abstract
Background
Talaromyces marneffei is a highly pathogenic fungus that can cause life-threatening fatal systemic mycosis. Disseminated Talaromycosis marneffei affects multiple organs, including the lungs, skin, and reticuloendothelial system. However, T. marneffei infection has rarely been reported in human immunodeficiency virus (HIV)-negative infants with multiple intestinal perforations and diffuse hepatic granulomatous inflammation.

Case presentation
We present the case of an HIV-negative 37-month-old boy who has had recurrent pneumonia since infancy and was infected with disseminated Talaromycosis. Contrast-enhanced computed tomography of the whole abdomen showed hepatomegaly and intestinal wall thickening in the ascending colon and cecum with mesenteric lymphadenopathy. Colonoscopy showed a cobblestone pattern with erosion, ulcer, polypoid lesions, and lumen deformation ranging from the colon to the cecum. T. marneffei was isolated from the mucous membrane of the colon, liver, and bone marrow. After antifungal treatment and surgery, his clinical symptoms significantly improved. Whole-exome sequencing using the peripheral blood of the patient and his parents’ revealed a heterozygous missense mutation in exon 17 of the STAT3 gene (c.1673G>A, p.G558D).

Conclusions
In T. marneffei infection-endemic areas, endoscopic examination, culture, or histopathology from the intestine tissue should be performed in disseminated Talaromycosis patients with gastrointestinal symptoms. Timely and systemic antifungal therapy could improve the prognosis. Immunodeficiency typically should be considered in HIV-negative infants with opportunistic infections.
Total DNA methylation as a biomarker of DNA damage and tumor malignancy in intracranial meningiomas
Authors: Barciszewska Anna-Maria 
Published: June 2020

AbstractBackgroundMeningiomas are the most common primary intracranial tumors in adults. They are initially detected with neuroimaging techniques, but definite histological diagnosis requires tumor surgery to collect tumor tissue. Gross total resection is an optimal and final treatment for the majority of patients, followed by radiotherapy in malignant or refractory cases. However, there are a lot of uncertainties about i.a. the need for intervention in incidental cases, estimation of growth kinetics, risk of malignant transformation, or response to radiotherapy. Therefore a new diagnostic approach is needed. It has already been shown that epigenetics plays a crucial role in cancer biology, development, and progression. DNA methylation, the presence of 5-methylcytosine in DNA, is one of the main elements of a broad epigenetic program in a eukaryotic cell, with superior regulatory significance. Therefore, we decided to look at meningioma through changes of 5-methylcytosine.MethodsWe performed an analysis of the total amount of 5-methylcytosine in DNA isolated from intracranial meningioma tissues and peripheral blood samples of the same patients. The separation and identification of radioactively labeled nucleotides were performed using thin-layer chromatography.ResultsWe found that the 5-methylcytosine level in DNA from intracranial meningiomas is inversely proportional to the malignancy grade. The higher the tumor WHO grade is, the lower the total DNA methylation. The amount of 5-methylcytosine in tumor tissue and peripheral blood is almost identical.ConclusionsWe conclude that the total DNA methylation can be a useful marker for brain meningioma detection, differentiation, and monitoring. It correlates with tumor WHO grade, and the 5-methylcytosine level in peripheral blood reflects that in tumor tissue. Therefore it’s applicable for liquid biopsy.Our study creates a scope for further research on epigenetic mechanisms in neurooncology and can lead to the development of new diagnostic methods in clinical practice.
Low gestational age is associated with less anastomotic complications after open primary repair of esophageal atresia with tracheoesophageal fistula
Authors: Dingemann Carmen , Brendel Julia , Wenskus Julia , Pirr Sabine , Schukfeh Nagoud , Ure Benno , Reinshagen Konrad 
Published: June 2020

AbstractBackgroundThe aim of this study was to evaluate anastomotic complications after primary one-staged esophageal atresia (EA) repair relating to the patients` gestational age (GA).MethodsRetrospective data analyses of patients who underwent closure of tracheoesophageal fistula (TEF) and primary esophageal anastomosis from 01/2007 to 12/2018 in two pediatric surgical centers. Exclusion of EA other than Gross type C, long-gap EA, minimal invasive or staged approach. Postoperative complications during the first year of life were assessed. Associated malformations, the incidence of infant respiratory distress syndrome (IRDS) and intraventricular bleeding were analyzed.ResultsInclusion of 75 patients who underwent primary EA repair. Low GA was associated with significantly lower incidence of anastomotic complications (p = 0.019,r = 0.596, 95% CI 0.10–0.85). Incidence of anastomotic leakage (0% vs. 5.5%;p = 0.0416), recurrent TEF (0% vs. 5.5%;p = 0.0416) und anastomotic stricture (0% vs. 14.5%;p = 0.0019) was significantly lower in patients < 34 gestational weeks. Incidence of IRDS (55% vs. 0%;p < 0.0001) and intraventricular bleeding (25% vs. 3.6%;p = 0.0299) was significantly higher in patients < 34 gestational weeks.ConclusionsDespite prematurity-related morbidity, low GA did not adversely affect surgical outcome after primary EA repair. Low GA was even associated with a better anastomotic outcome indicating feasibility and safety of primary esophageal reconstruction.
Over 20 years of chronic patellar ligament rupture with severe knee osteoarthritis for Total knee Arthroplasty: a case report
Authors: Zhang Xuejun , Li Yun , Chen Jianfeng , Yan Chao , Tan Xiaoyi , Liu Huafang 
Published: June 2020

AbstractBackgroundExtensor apparatus rupture is a severe complication after knee arthroplasty, but there have not been many reports on how to perform knee arthroplasty after chronic patellar ligament rupture. We reported a case of total knee arthroplasty (TKA) in a patient with severe osteoarthritis (OA) complicated by chronic patellar ligament rupture.Case presentationIn this case, a 67-year-old male patient suffered from patellar ligament rupture due to trauma more than 20 years ago and did not undergo any formal treatment. Physical examination revealed a small amount of fluid and extension lag, and the patella was displaced upward by approximately 5.5 cm. The quadriceps were atrophic and weak. There was significant tenderness on the medial side of the left knee joint. Passive motion of the left knee joint ranged from full extension to 120° of flexion with discomfort during excessive flexion. Active flexion of the knee joint to 120°, and extensor lag was approximately 90°. We reconstructed the extensor apparatus through a quadriceps tendon V-Y quadricepsplasty and Krackow suture technique of the patellar ligament, and osteoarthritis was resolved with TKA. The visual analogue scale (VAS) score decreased from 5 points to 1 point after surgery. Six weeks later, the patient was able to walk normally without a walking stick, and the knee joint could stretch actively to approximately 30°. However, he had obvious extension lag. This problem improved 10 months after surgery. The AKS score increased from 35 to 95 10 months after surgery. The HSS score increased from 43 to 93.ConclusionsTKA and ligament reconstruction are options for the treatment of knee OA with chronic patellar ligament rupture. V-Y lengthening of the quadriceps femoris tendon after the Krackow suture technique of the patellar ligament with transpatellar tunnels may be a reasonable choice during TKA.
Association between serum vitamin D and uric acid in the eastern Chinese population: a population-based cross-sectional study
Authors: Chen Yingchao , Cheng Jing , Chen Yi , Wang Ningjian , Xia Fangzhen , Chen Chi , Han Bing , Lu Yingli 
Published: June 2020

Abstract
Background
Uric acid (UA) is the end product of purine metabolism, which is thought to be related to many human diseases, such as nephrolithiasis, gout, cardiovascular disease (CVD), type 2 diabetes mellitus, metabolic syndrome. However, the relationship between serum UA (SUA) and 25(OH) D is still unclear in the eastern Chinese population.

Methods
We did a population-based observational investigation, which included 12,770 residents living in eastern China. Ultimately, data from 9220 subjects were analyzed. Serum 25(OH) D, SUA, fasting plasma glucose (FPG), fasting insulin, HbA1c and other metabolic parameters were tested. Waist circumference (WC), weight and height were also measured. Questionnaires were collected from these subjects for information on smoking and drinking status.

Results
We enrolled 9220 Chinese adults, including 3681 males (age 55.57 ± 13.23 years) and 5539 females (age 54.31 ± 12.83 years). The levels of SUA were 352.07 ± 79.25 nmol/L and 269.29 ± 64.68 nmol/L in males and females, respectively. The proportion of adults with hyperuricemia (HUA) was 12.26% in the total population. Levels of SUA were positively associated with 25(OH) D, and the incidence of HUA increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001).

Conclusions
SUA was positively associated with 25(OH) D in the eastern Chinese population. Higher levels of serum 25(OH) D may be a potential predictor of HUA.
Feikang granules ameliorate pulmonary inflammation in the rat model of chronic obstructive pulmonary disease via TLR2/4-mediated NF-κB pathway
Authors: Yang Liuliu , Wen Minyong , Liu Xiaohong , Wang Kai , Wang Yong 
Published: June 2020

Abstract
Purpose
Several reports have shown that traditional Chinese medicine could be an alternative therapeutic approach for COPD patients, but the mechanism remains unknown. The present study aimed to examine the effects of Feikang granules in a COPD model rat and investigate the possible mechanisms via Toll-like receptor (TLR)/ nuclear factor kappa B (NF-κB) signaling.

Methods
The COPD model rats were treated with Feikang granules, dexamethasone, or normal saline. The pulmonary function; lung tissue histology; levels of inflammatory cytokines; mRNA levels of TNFα, IL-6, TLR4, and TLR2; and protein levels of TLR4, TLR2, p-IκB, IκB and P65 in lung tissues were evaluated.

Results
The present study confirmed that the pro-inflammatory cytokines, TNF-α, IL-1β, IL-6, and IL-17 levels were elevated and the pulmonary function and morphology are altered in COPD model rats. The TLR2 and TLR4 -mediated NF-kB signaling pathway plays a role in the mechanism of action. Feikang granules, a type of Chinese herbal medicine, significantly reduced LPS induced inflammatory cytokines release from lung tissue and alveolar macrophage in a dose-dependent manner. These medical herbs also prevented TLR2/4 and IκB downregulation and reversed the p-IκB and NF-κB p65 upregulation of the lung tissue in the COPD rats. Feikang granules were also found to protect against pulmonary dysfunction and pathological changes in the COPD rats.

Conclusion
The Chinese herbal medicine formula Feikang granules prevent pulmonary inflammation and improve pulmonary function, suggesting that Feikang granules may be an effective treatment for chronic pulmonary diseases, such as COPD.
Control of unreasonable growth of medical expenses in public hospitals in Shanghai, China: a multi-agent system model
Authors: Yu Wenya , Liu Xiang , Zhao Fangjie , Li Meina , Zhang Lulu 
Published: June 2020

Abstract
Background
This study aims to establish a multi-agent system model to provide accurate suggestions for the policy proposal of controlling the unreasonable growth of medical expenses charged by public hospitals in China.

Methods
A multi-agent system model was employed in this study. Agents of this model were divided into patients, doctors, medical institutions, the government, and medical insurance agencies. The model was composed of two subsystems: the disease and medical-seeking subsystem, and the medical expenses subsystem. Policy intervention experiments were conducted on patients’ medical-seeking preferences, doctors’ public welfare behaviors, and the government’s financial investment.

Results
At present, medical expenses in China are unreasonable and keep increasing, and the proportion of medicine and physical examination expenses to total medical expenses for public hospitals is unreasonable. Intervention experiments suggested that expanding the promotion and application of the community first-visit system could rationalize patients’ medical-seeking preferences, increasing doctors’ incomes and reducing workload could significantly restrict doctors’ over-prescription behaviors. Also, improving the government’s financial investment could guide public hospitals to strengthen their commitment to public welfare responsibilities. These interventions could decrease the unreasonable growth of medical expenses of public hospitals. The combined intervention effects on suppliers, demanders, and the government were better than the effect of these agents independently.

Conclusions
The main reasons for the unreasonable increase in patient medical expenses at public hospitals could be attributed to patients’ unreasonable medical-seeking preferences, doctors’ weak public welfare incentives, and the government’s inadequate financial investment. Policy-makers should consider proposals to restrict and guide the behaviors of suppliers, demanders, and the government, simultaneously. The government should consider the feasibility, response speed, and implementation cost of policies as well.
The challenges of colposcopy for cervical cancer screening in LMICs and solutions by artificial intelligence
Authors: Xue Peng , Ng Man Tat Alexander , Qiao Youlin 
Published: June 2020

AbstractBackgroundThe World Health Organization (WHO) called for global action towards the elimination of cervical cancer. One of the main strategies is to screen 70% of women at the age between 35 and 45 years and 90% of women managed appropriately by 2030. So far, approximately 85% of cervical cancers occur in low- and middle-income countries (LMICs). The colposcopy-guided biopsy is crucial for detecting cervical intraepithelial neoplasia (CIN) and becomes the main bottleneck limiting screening performance. Unprecedented advances in artificial intelligence (AI) enable the synergy of deep learning and digital colposcopy, which offers opportunities for automatic image-based diagnosis. To this end, we discuss the main challenges of traditional colposcopy and the solutions applying AI-guided digital colposcopy as an auxiliary diagnostic tool in low- and middle- income countries (LMICs).Main bodyExisting challenges for the application of colposcopy in LMICs include strong dependence on the subjective experience of operators, substantial inter- and intra-operator variabilities, shortage of experienced colposcopists, consummate colposcopy training courses, and uniform diagnostic standard and strict quality control that are hard to be followed by colposcopists with limited diagnostic ability, resulting in discrepant reporting and documentation of colposcopy impressions. Organized colposcopy training courses should be viewed as an effective way to enhance the diagnostic ability of colposcopists, but implementing these courses in practice may not always be feasible to improve the overall diagnostic performance in a short period of time. Fortunately, AI has the potential to address colposcopic bottleneck, which could assist colposcopists in colposcopy imaging judgment, detection of underlying CINs, and guidance of biopsy sites. The automated workflow of colposcopy examination could create a novel cervical cancer screening model, reduce potentially false negatives and false positives, and improve the accuracy of colposcopy diagnosis and cervical biopsy.ConclusionWe believe that a practical and accurate AI-guided digital colposcopy has the potential to strengthen the diagnostic ability in guiding cervical biopsy, thereby improves cervical cancer screening performance in LMICs and accelerates the process of global cervical cancer elimination eventually.
Linagliptin, when compared to placebo, improves CD34+ve endothelial progenitor cells in type 2 diabetes subjects with chronic kidney disease taking metformin and/or insulin: a randomized controlled trial
Authors: Awal Hassan B. , Nandula Seshagiri Rao , Domingues Cleyton C. , Dore Fiona J. , Kundu Nabanita , Brichacek Beda , Fakhri Mona , Elzarki Adrian , Ahmadi Neeki , Safai Shauna , Fosso Magan , Amdur Richard L. , Sen Sabyasachi 
Published: June 2020

Abstract
Background
Endothelial Progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) leading to poor regeneration of endothelium and renal perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP4 inhibitors such as linagliptin (LG) on CVD risk, in patients with T2DM with established CKD has not been established. Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD) population.

Methods
31 subjects taking metformin and/or Insulin were enrolled in this 12 weeks, double blind, randomized placebo matched trial, with 5 mg LG compared to placebo. Type 2 diabetes subjects (30–70 years old), HbA1c of 6.5–10%, CKD Stage 1–3 were included. CD34+ cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, biochemistry, resting energy expenditure and body composition were measured. Data were collected at week 0, 6 and 12. A mixed model regression analysis was done with p value < 0.05 considered significant.

Results
A double positive CD34/CD184 cell count had a statistically significant increase (p < 0.02) as determined by flow cytometry in LG group where CD184 is SDF1a cell surface receptor. Though mRNA differences in CD34+ve was more pronounced CD34- cell mRNA analysis showed increase in antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and prominent endothelial markers (PECAM1, VEGF-A, vWF and NOS3). Arterial stiffness measures such as augmentation Index (AI) (p < 0.04) and pulse wave analysis (PWV) were improved (reduced in stiffness) in LG group. A reduction in LDL: HDL ratio was noted in treatment group (p < 0.04). Urinary exosome protein examining podocyte health (podocalyxin, Wilms tumor and nephrin) showed reduction or improvement.

Conclusions
In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34 + progenitor cells with a concomitant improvement in vascular and renal parameters at 12 weeks.
Trial Registration Number NCT02467478 Date of Registration: 06/08/2015
Applied systems thinking: a viable approach to identify leverage points for accelerating progress towards ending neglected tropical diseases
Authors: Glenn Jeffrey , Kamara Kimberly , Umar Zaiyanatu Abubakar , Chahine Teresa , Daulaire Nils , Bossert Thomas 
Published: June 2020

Abstract
Background
Systems thinking is a conceptual approach that can assist stakeholders in understanding complexity and making progress on persistent public health challenges. Neglected tropical diseases (NTDs), a complex global health problem, are responsible for a large disease burden among impoverished populations around the world. This aim of this study was to better discern the many complexities of the global NTD system in order to identify and act on leverage points to catalyse progress towards ending NTDs.

Methods
Existing frameworks for systems change were adapted to form the conceptual framework for the study. Using a semi-structured interview guide, key informant interviews were conducted with NTD stakeholders at the global level and at the country level in Nigeria. The interview data were coded and analysed to create causal loop diagrams that resulted in a qualitative model of the global NTD system.

Results
The complete qualitative model is discussed and presented visually as six separate sub-components that highlight key forces and feedback loops within the global NTD system.

Conclusions
We identified five leverage points for NTD system change, namely (1) clarify the potential for and assess realistic progress towards NTD elimination, (2) increase support for interventions besides drug delivery, (3) reduce dependency on international donors, (4) create a less insular culture within the global NTD community, and (5) systemically address the issue of health worker incentives. The specific findings for NTDs raise a number of uncomfortable questions that have not been addressed, at least in part, because it is easier to continue focusing on ‘quick win’ solutions. The study provides a model of a systems thinking approach that can be applied to other complex global health and development challenges in order to understand complexity and identify leverage points for system change.
Key factors for national spread and scale-up of an eConsult innovation
Authors: Moroz Isabella , Archibald Douglas , Breton Mylaine , Cote-Boileau Elizabeth , Crowe Lois , Horsley Tanya , Hyseni Lirjie , Johar Gina , Keely Erin , Burns Katharina Kovacs , Kuziemsky Craig , Laplante Jim , Mihan Ariana , Oppenheimer Luis , Sturge Don , Tuot Delphine S. , Liddy Clare 
Published: June 2020

Abstract
Background
Expanding healthcare innovations from the local to national level is a complex pursuit requiring careful assessment of all relevant factors. In this study (a component of a larger eConsult programme of research), we aimed to identify the key factors involved in the spread and scale-up of a successful regional eConsult model across Canada.

Methods
We conducted a constant comparative thematic analysis of stakeholder discussions captured during a full-day National eConsult Forum meeting held in Ottawa, Canada, on 11 December 2017. Sixty-four participants attended, representing provincial and territorial governments, national organisations, healthcare providers, researchers and patients. Proceedings were recorded, transcribed and underwent qualitative analysis using the Framework for Applied Policy Research.

Results
This study identified four main themes that were critical to support the intentional efforts to spread and scale-up eConsult across Canada, namely (1) identifying population care needs and access problems, (2) engaging stakeholders who were willing to roll up their sleeves and take action, (3) building on current strategies and policies, and (4) measuring and communicating outcomes.

Conclusions
Efforts to promote innovation in healthcare are more likely to succeed if they are based on an understanding of the forces that drive the spread and scale-up of innovation. Further research is needed to develop and strengthen the conceptual and applied foundations of the spread and scale-up of healthcare innovations, especially in the context of emergent learning health systems across Canada and beyond.