bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting specific abilities after disabling stroke: Development and validation of prognostic models
Authors: Visvanathan Akila , Graham Catriona , Dennis Martin , Lawton Julia , Doubal Fergus , Mead Gillian , Whiteley William 
Published: January 2021

Background Predicting specific abilities (e.g. walk and talk) to provide a functional profile six months after disabling stroke could help patients/families prepare for the consequences of stroke and facilitate involvement in treatment decision-making. Aim To develop new statistical models to predict specific abilities six months after stroke and test their performance in an independent cohort of patients with disabling stroke. Methods We developed models to predict six specific abilities (to be independent, walk, talk, eat normally, live without major anxiety/depression, and to live at home) using data from seven large multicenter stroke trials with multivariable logistic regression. We included 13,117 participants recruited within three days of hospital admission. We assessed model discrimination and derived optimal cut-off values using four statistical methods. We validated the models in an independent single-center cohort of patients ( n = 403) with disabling stroke. We assessed model discrimination and calibration and reported the performance of our models at the statistically derived cut-off values. Results All six models had good discrimination in external validation (AUC 0.78–0.84). Four models (predicting to walk, eat normally, live without major anxiety/depression, live at home) calibrated well. Models had sensitivities between 45.0 and 97.9% and specificities between 21.6 and 96.5%. Conclusions We have developed statistical models to predict specific abilities and demonstrated that these models perform reasonably well in an independent cohort of disabling stroke patients. To aid decision-making regarding treatments, further evaluation of our models is required.
Surgical treatment of pulmonary artery sarcoma: a report of 17 cases
Authors: Song Wu , Deng Long , Zhu Jiade , Zheng Shanshan , Wang Haiping , Song Yunhu , Liu Sheng 
Published: January 2021

Pulmonary artery sarcoma (PAS) is a rare and devastating disease. The diagnosis is often delayed, and optimal treatment remains unclear. The aim of this study is to report our experience in the surgical management of this disease. Between 2000 and 2018, 17 patients underwent operations for PAS at our center. The medical records were retrospectively reviewed to evaluate the clinical characteristics, operative findings, the postoperative outcomes, and the long‐term results. The mean age at operation was 46.0 ± 12.4 years (range, 26–79 years), and eight (47.1%) patients were male. Six patients underwent tumor resection alone, whereas the other 11 patients received pulmonary endarterectomy (PEA). There were two perioperative deaths. Follow‐up was completed for all patients with a mean duration of 23.5 ± 17.6 months (1–52 months). For all 17 patients, the median postoperative survival was 36 months, and estimated cumulative survival rates at 1, 2, 3, and 4 years were 60.0%, 51.4%, 42.9%, and 21.4%, respectively. The mean survival was 37.0 months after PEA and 14.6 months after tumor resection only (p = 0.046). Patients who had no pulmonary hypertension (PH) postoperatively were associated with improved median survival (48 vs. 5 months, p = 0.023). In conclusion, PAS is often mistaken for chronic pulmonary thromboembolism. The prognosis of this very infrequent disease remains poor. Early detection is essential for prompt and best surgical approach, superior to tumor resection alone, and PEA surgery with PH relieved can provide better chance of survival.
Plasma fibrinolysis, inflammatory markers, and postthrombotic syndrome: preliminary findings from the Kids-DOTT Biobank
Authors: Betensky Marisol , Amankwah Ernest K. , Brandal Stephanie , Everett Allen D. , Goldenberg Neil A. 
Published: January 2021

Abstract
Plasma levels of markers of coagulation and inflammation have been identified as prognostic factors for adult postthrombotic syndrome (PTS). We aimed to determine whether plasma fibrinolytic capacity and cytokine levels during the first 3 months after provoked deep venous thrombosis (DVT) are associated with risk of PTS in young patients. We analyzed plasma biospecimens (6 weeks and 3 months after provoked DVT) and clinical data from a National Heart, Lung, and Blood Institute–sponsored multinational trial of anticoagulation for provoked venous thromboembolism in patients younger than age 21 years (Kids-DOTT). Patients with a provoked extremity DVT who had plasma samples available at both 6-week and 3-month post-DVT time points and PTS assessment at 1 year were included. We measured plasma fibrinolytic capacity using the Clot Formation and Lysis (CloFAL) assay and plasma cytokine levels by multiplex immunoassay. Logistic regression analyses evaluated prognostic associations with PTS. Seventy-nine patients were included (median age, 12.8 years; range, 0.04-20.8 years). PTS developed in 34%. Complete veno-occlusion at 6 weeks after diagnosis of DVT (odds ratio [OR], 3.12; 95% confidence interval [CI], 0.81-11.94; P = .097), low fibrinolytic capacity in plasma at 3 months post-DVT (OR, 2.71; 95% CI, 0.92-7.97; P = .07), and elevated serum amyloid A at 3 months post-DVT (OR, 2.85; 95% CI, 0.98-8.34; P = .055) were identified as putative prognostic factors for development of PTS. In multivariable logistic regression analysis, these factors did not retain a statistically significant independent association with PTS, but these preliminary results warrant further investigation in an independent data set to definitively evaluate these findings and identify additional potential prognostic factors for the development of PTS after a provoked DVT in young patients.
Chinese herbal extract granules combined with 5-aminosalicylic acid for patients with moderately active ulcerative colitis: study protocol for a multicenter randomized double-blind placebo-controlled trial
Authors: Shen Zhaofeng , Zheng Kai , Zou Jiandong , Gu Peiqing , Xing Jing , Zhang Lu , Zhu Lei , Shen Hong 
Published: January 2021

Abstract
Background
Ulcerative colitis (UC) is an intestinal inflammatory disease characterized by inflammation of the colonic mucosa. With unknown pathogenesis, it has become a chronic lifetime disorder worldwide. In patients with moderately active UC, several therapies (e.g., aminosalicylates, corticosteroids, immunosuppressants, and biologics) are recommended for induction (or maintenance) of remission. Given the side effects and disease burden, it is difficult for most patients to achieve ideal treatment goals in clinical practice. Chinese herbal medicine (CHM), as a complementary therapy, has been widely used in the management of UC in China. Qing-Chang-Hua-Shi granule (QCHS) is a classical Chinese herbal formula. Our preliminary study suggested that the QCHS decoction has a significant effect on patients with moderately active UC. However, its effectiveness and safety has not been evaluated convincingly. Therefore, we designed this protocol to investigate the efficacy of QCHS granule for moderately active UC.

Methods
This is a multicenter, randomized, double-blind, placebo-controlled, superiority trial. A total of 120 patients with moderately active UC will be recruited from 10 hospitals in China. Each eligible participant will be randomly assigned to receive QCHS granule or placebo for 12 weeks. Both groups will be given basic treatment with mesalazine (4 g/day). The primary outcomes are the clinical response (remission) rate. The secondary outcomes are health-related quality of life, endoscopic response rate, mucosal healing rate, and inflammatory markers (e.g., fecal calprotectin and CRP). The whole study period will last 36 weeks, including 24 weeks follow-up time. According to the intention-to-treat principle, variables will be assessed at 2, 4, 6, 8, 10, and 12 weeks after study commencement.

Discussion
This is the first randomized controlled clinical study protocol regarding Chinese herbal extract granules in the management of moderately active UC. We aim to investigate the superiority of QCHS granules over placebo in terms of induction of remission. If the trial shows significant benefits of QCHS granules, it will help clinical practitioners, UC patients, and policymakers make more informed choices in the decision-making.

Trial registration
Chinese Clinical Trial Registry ChiCTR-IOR-14005554. Registered on 27 November 2014.
Clinical laboratory test-wide association scan of polygenic scores identifies biomarkers of complex disease
Authors: Dennis Jessica K. , Sealock Julia M. , Straub Peter , Lee Younga H. , Hucks Donald , Actkins Ky’Era , Faucon Annika , Feng Yen-Chen Anne , Ge Tian , Goleva Slavina B. , Niarchou Maria , Singh Kritika , Morley Theodore , Smoller Jordan W. , Ruderfer Douglas M. , Mosley Jonathan D. , Chen Guanhua , Davis Lea K. 
Published: January 2021

Abstract
Background
Clinical laboratory (lab) tests are used in clinical practice to diagnose, treat, and monitor disease conditions. Test results are stored in electronic health records (EHRs), and a growing number of EHRs are linked to patient DNA, offering unprecedented opportunities to query relationships between genetic risk for complex disease and quantitative physiological measurements collected on large populations.

Methods
A total of 3075 quantitative lab tests were extracted from Vanderbilt University Medical Center’s (VUMC) EHR system and cleaned for population-level analysis according to our QualityLab protocol. Lab values extracted from BioVU were compared with previous population studies using heritability and genetic correlation analyses. We then tested the hypothesis that polygenic risk scores for biomarkers and complex disease are associated with biomarkers of disease extracted from the EHR. In a proof of concept analyses, we focused on lipids and coronary artery disease (CAD). We cleaned lab traits extracted from the EHR performed lab-wide association scans (LabWAS) of the lipids and CAD polygenic risk scores across 315 heritable lab tests then replicated the pipeline and analyses in the Massachusetts General Brigham Biobank.

Results
Heritability estimates of lipid values (after cleaning with QualityLab) were comparable to previous reports and polygenic scores for lipids were strongly associated with their referent lipid in a LabWAS. LabWAS of the polygenic score for CAD recapitulated canonical heart disease biomarker profiles including decreased HDL, increased pre-medication LDL, triglycerides, blood glucose, and glycated hemoglobin (HgbA1C) in European and African descent populations. Notably, many of these associations remained even after adjusting for the presence of cardiovascular disease and were replicated in the MGBB.

Conclusions
Polygenic risk scores can be used to identify biomarkers of complex disease in large-scale EHR-based genomic analyses, providing new avenues for discovery of novel biomarkers and deeper understanding of disease trajectories in pre-symptomatic individuals. We present two methods and associated software, QualityLab and LabWAS, to clean and analyze EHR labs at scale and perform a Lab-Wide Association Scan.
Donor heart preservation with hypoxic-conditioned medium-derived from bone marrow mesenchymal stem cells improves cardiac function in a heart transplantation model
Authors: Zhou Pengyu , Liu Hao , Liu Ximao , Ling Xiao , Xiao Zezhou , Zhu Peng , Zhu Yufeng , Lu Jun , Zheng Shaoyi 
Published: January 2021

Abstract
Background
In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium (CdM) derived from BMSCs would improve post-transplant graft function.

Methods
Normoxic or hypoxic CdM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted; stored in cardioplegic solution supplemented with either a medium (vehicle), normoxic CdM (N-CdM), or hypoxic CdM (H-CdM); and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic and normoxic CdM.

Results
After heart transplantation, the donor heart preservation with normoxic CdM was associated with a shorter time to return of spontaneous contraction and left ventricular systolic diameter, lower histopathological scores, higher ejection fraction, and fractional shortening of the transplanted hearts. The cardioprotective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of plasma proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CdM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CdM compared with normoxic CdM. Furthermore, compared with vehicle and N-CdM groups, the protein levels of PI3K and p-Akt/Akt ratio in the transplanted hearts significantly increased in the H-CdM group. However, no significant difference was found in the phosphorylation of Smad2 and Smad3 for the donor hearts among the three groups.

Conclusions
Our results indicate that the cardioplegic solution-enriched with hypoxic CdM can be a novel and promising preservation solution for donor hearts.
Subconjunctival injection of mesenchymal stem cells for corneal failure due to limbal stem cell deficiency: state of the art
Authors: Galindo Sara , de la Mata Ana , López-Paniagua Marina , Herreras Jose M. , Pérez Inmaculada , Calonge Margarita , Nieto-Miguel Teresa 
Published: January 2021

AbstractMesenchymal stem cells (MSCs) have unique and beneficial properties and are currently used to treat a broad variety of diseases. These properties include the potential for differentiation into other cell types, secretion of different trophic factors that promote a regenerative microenvironment, anti-inflammatory actions, selective migration to damaged tissues, and non-immunogenicity. MSCs are effective for the treatment of ocular surface diseases such as dry eye, corneal burns, and limbal stem cell deficiency (LSCD), both in experimental models and in humans. LSCD is a pathological condition in which damage occurs to the limbal epithelial stem cells, or their niche, that are responsible for the continuous regeneration of the corneal epithelium. If LSCD is extensive and/or severe, it usually causes corneal epithelial defects, ulceration, and conjunctival overgrowth of the cornea. These changes can result in neovascularization and corneal opacity, severe inflammation, pain, and visual loss. The effectiveness of MSCs to reduce corneal opacity, neovascularization, and inflammation has been widely studied in different experimental models of LSCD and in some clinical trials; however, the methodological disparity used in the different studies makes it hard to compare outcomes among them. In this regard, the MSC route of administration used to treat LSCD and other ocular surface diseases is an important factor. It should be efficient, minimally invasive, and safe. So far, intravenous and intraperitoneal injections, topical administration, and MSC transplantation using carrier substrata like amniotic membrane (AM), fibrin, or synthetic biopolymers have been the most commonly used administration routes in experimental models. However, systemic administration carries the risk of potential side effects and transplantation requires surgical procedures that could complicate the process. Alternatively, subconjunctival injection is a minimally invasive and straightforward technique frequently used in ophthalmology. It enables performance of local treatments using high cell doses. In this review, we provide an overview of the current status of MSC administration by subconjunctival injection, analyzing the convenience, safety, and efficacy for treatment of corneal failure due to LSCD in different experimental models. We also provide a summary of the clinical trials that have been completed, are in progress, or being planned.
The underestimated role of the microphthalmia-associated transcription factor (MiTF) in normal and pathological haematopoiesis
Authors: Oppezzo Alessia , Rosselli Filippo 
Published: January 2021

AbstractHaematopoiesis, the process by which a restrained population of stem cells terminally differentiates into specific types of blood cells, depends on the tightly regulated temporospatial activity of several transcription factors (TFs). The deregulation of their activity or expression is a main cause of pathological haematopoiesis, leading to bone marrow failure (BMF), anaemia and leukaemia. TFs can be induced and/or activated by different stimuli, to which they respond by regulating the expression of genes and gene networks. Most TFs are highly pleiotropic; i.e., they are capable of influencing two or more apparently unrelated phenotypic traits, and the action of a single TF in a specific setting often depends on its interaction with other TFs and signalling pathway components. The microphthalmia-associated TF (MiTF) is a prototype TF in multiple situations. MiTF has been described extensively as a key regulator of melanocyte and melanoma development because it acts mainly as an oncogene.Mitf-mutated mice show a plethora of pleiotropic phenotypes, such as microphthalmia, deafness, abnormal pigmentation, retinal degeneration, reduced mast cell numbers and osteopetrosis, revealing a greater requirement for MiTF activity in cells and tissue. A growing amount of evidence has led to the delineation of key roles for MiTF in haematopoiesis and/or in cells of haematopoietic origin, including haematopoietic stem cells, mast cells, NK cells, basophiles, B cells and osteoclasts. This review summarizes several roles of MiTF in cells of the haematopoietic system and how MiTFs can impact BM development.
Cytokines in the colon, central nervous system and serum of irritable bowel syndrome rats
Authors: Chao Guanqun , Wang Zhaojun , Chen Xinli , Zhang Shuo 
Published: January 2021

Abstract
Objective
The aim of this study was to detect the expression of interleukin (IL)-1β and transforming growth factor (TGF)-β1 in the colonic tissue and serum of irritable bowel syndrome (IBS) rats, as well as the distribution and expression of corticotropin-releasing factor (CRF) in the spinal cord and brain of the visceral hypersensitivity rats, thus to ascertain the mechanism of visceral hypersensitivity signal conduction pathway.

Methods
The expression of IL-1β and TGF-β1 in the colonic tissue and serum of IBS rats was screened by the liquid chip technology and verified by RT-PCR technology. Then the quantitative analysis of CRF in the spinal cord and brain was achieved by the immunohistochemical method and computerized image system.

Result
The rat model with visceral hypersensitivity was successfully established. Among the screened indicators of IL-1β and TGF-β1 in colon tissue and serum, only the expression of IL-1β in the model group was up-regulated (P < 0.05). The immunohistochemical method showed that CRF was expressed in the spinal cord, hypothalamus, and the third ventricle. The positive index number of the model groups was higher than that of the control group (P < 0.01).

Conclusion
From the research, it can be inferred that IL-1β may participate in the pathogenesis mechanism of IBS via regulating the colon function. The increasing expression of CRF linked to stress in the spinal cord, hypothalamus and the third ventricle indicated that it might play an important role in the mechanisms of visceral hypersensitivity signal conduction pathway.
Indocyanine green fluorescence navigation for hepatocellular carcinoma with bile duct tumor thrombus: a case report
Authors: Matsumura Masaru , Seyama Yasuji , Ishida Hiroyuki , Nemoto Satoshi , Tani Keigo , Imamura Jun 
Published: January 2021

Abstract
Background
Bile duct tumor thrombus (BDTT) is one of the features of advanced hepatocellular carcinoma (HCC). In the resection of HCC with BDTT, it is important to detect the BDTT tip to decide the appropriate point of bile duct division. In this regard, the efficacy of indocyanine green (ICG) fluorescence navigation has been confirmed for the detection of HCC, whereas its utility for BDTT has not yet been reported. Herein, we describe our experience with right hepatectomy for HCC with BDTT using ICG fluorescence navigation.

Case presentation
A 72-year-old woman had experienced local recurrences of HCC after radiofrequency ablation, with BDTT reaching the confluence of the right anterior branch and posterior branch. Right hepatectomy was planned, and 2.5 mg of ICG was injected one day before surgery. After transection of the liver parenchyma, the right liver was connected with only the right hepatic duct. ICG fluorescence imaging visualized the tip of BDTT in the bile duct with clear contrast; the proximal side (hepatic side) of the right hepatic duct showed stronger fluorescence than the distal side (duodenal side). The bile duct was divided at the distal side of the BDTT border, and the tip of BDTT was recognized into the resected right hepatic duct without laceration. The patient had an uneventful postoperative course and currently lives without recurrences for 6 months.

Conclusions
ICG fluorescence navigation assisted in the precise resection of the bile duct in HCC with BDTT.