Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal neuroimaging following combat concussion: sub-acute, 1 year and 5 years post-injury

Abstract Questions remain regarding the long-term impact of combat concussive blast exposure. While efforts have begun to highlight the clinical impact, less is known about neuroimaging trajectories that may inform underlying pathophysiological changes post-injury. Through collaborative efforts in combat, following medical evacuation, and at universities in the USA, this study followed service members both with and without blast concussion from the sub-acute to 1-year and 5-year outcomes with quantitative neuroimaging. The following two primary and two exploratory groups were examined: combat-deployed controls without blast exposure history ‘non-blast control’ and concussive blast patients (primary) and combat concussion arising not from blast ‘non-blast concussion’ and combat-deployed controls with blast exposure history ‘blast control’ (exploratory). A total of 575 subjects were prospectively enrolled and imaged; 347 subjects completed further neuroimaging examination at 1 year and 342 subjects completed further neuroimaging examination at 5 years post-injury. At each time point, MRI scans were completed that included high-resolution structural as well as diffusion tensor imaging acquisitions processed for quantitative volumetric and diffusion tensor imaging changes. Longitudinal evaluation of the number of abnormal diffusion tensor imaging and volumetric regions in patients with blast concussion revealed distinct trends by imaging modality. While the presence of abnormal volumetric regions remained quite stable comparing our two primary groups of non-blast control to blast concussion, the diffusion tensor imaging abnormalities were observed to have varying trajectories. Most striking was the fractional anisotropy ‘U-shaped’ curve observed for a proportion of those that, if we had only followed them to 1 year, would look like trajectories of recovery. However, by continuing the follow-up to 5 years in these very same patients, a secondary increase in the number of reduced fractional anisotropy regions was identified. Comparing non-blast controls to blast concussion at each time point revealed significant differences in the number of regions with reduced fractional anisotropy at both the sub-acute and 5-year time points, which held after adjustment for age, education, gender, scanner and subsequent head injury exposure followed by correction for multiple comparisons. The secondary increase identified in patients with blast concussion may be the earliest indications of microstructural changes underlying the ‘accelerated brain aging’ theory recently reported from chronic, cross-sectional studies of veterans following brain injury. These varying trajectories also inform potential prognostic neuroimaging biomarkers of progression and recovery.
The effect of anticoagulant choice on venous thromboembolism recurrence and bleeding in sickle cell disease

Patients with sickle cell disease (SCD) experience accelerated morbidity and mortality. Venous thromboembolism (VTE), a risk factor for early mortality in SCD, occurs in 11-12% of patients with SCD by the age of 40. While indefinite anticoagulation is indicated in the SCD population, there is limited understanding of comparative efficacy and hemorrhagic risk of individual anticoagulation agents in this population. We reviewed the use of anticoagulation for treatment of VTE in patients with SCD at our institution to begin to address these questions. A retrospective chart review of all patients with SCD 18 years of age and older (currently alive or deceased) who received care at Boston Medical Center/Boston University between 2003 and 2018 was performed. VTE was defined as deep venous thrombosis (DVT) diagnosed by duplex ultrasound or pulmonary embolism (PE) diagnosed by either ventilation-perfusion scanning or computed tomography angiography. The primary efficacy outcome was the number of VTE events which occurred while the patient was receiving anticoagulation. The primary safety outcome was major bleeding as defined by the International Society on Thrombosis and Hemostasis 2005 guidelines. The medical records of 233 patients with SCD were reviewed; VTE was identified in 55 (23.6%) patients. Sixty-five percent were female. In these 55 patients, a total of 94 VTE events occurred. Fifteen (16.0%) were catheter-associated upper extremity DVTs. For the first event, initial outpatient treatment consisted of warfarin in 56%, low-molecular-weight heparin (LMWH) in 18.2%, rivaroxaban in 9.1%, apixaban in 5.5%, and fondaparinux in 3.6%. The median length of treatment was 7.3 (median: 6, IQR: 3-12) months. Recurrent VTEs occurred in 27 (49%) patients with a total of 39 recurrent events. Among the recurrent events, thirteen (33.0%) were treatment failures occurring during anticoagulation therapy (see Table 1): 7 of 37 (18.9%) on warfarin, 2 of 20 (10.0%) on LMWH, and 4 of 15 (26.7%) on rivaroxaban. Death from recurrent VTE occurred in two patients; one occurred while a patient was therapeutic on warfarin. Major bleeding occurred in two patients (3.6%); in both cases, this was intracranial hemorrhage while on warfarin. In this retrospective study, there was a high rate of VTE recurrence despite anticoagulation in patients with SCD. Treatment failure was highest with warfarin and rivaroxaban, although adherence was difficult to assess. Risk of hemorrhage and death appears higher in those prescribed warfarin. These data affirm the need for long-term anticoagulation in most patients with SCD with a VTE and support the use of direct oral anticoagulants as a first-line agent. Sloan: Abbvie: Other: Endpoint Review Committee; Stemline: Consultancy; Merck: Other: endpoint review commitee.
An insight into the brain of patients with type-2 diabetes mellitus and impaired glucose tolerance using multi-modal magnetic resonance image processing

The purpose of this thesis was to investigate brain anatomy and physiology of subjects with impaired glucose tolerance (IGT - 12 subjects), type-2 diabetes (T2DM - 17 subjects) and normoglycemia (16 subjects) using multi-modal magnetic resonance imaging (MRI) at 3T. Perfusion imaging using quantitative STAR labeling of arterial regions (QUASAR) arterial spin labeling (ASL) was the core dataset. Optimization of the post-processing methodology for this sequence was performed and the outcome was used for hemodynamic analysis of the cohort. Typical perfusion-related parameters, along with novel hemodynamic features were quantified. High-resolution structural, angiographic and carotid flow scans were also acquired and processed. Functional acquisitions were repeated following a vasodilating stimulus. Differences between the groups were examined using statistical analysis and a machine-learning framework. Hemodynamic parameters differing between the groups emerged from both baseline and post-stimulus scans for T2DM and mainly from the post-stimulus scan for IGT. It was demonstrated that quantification of not-typically determined hemodynamic features could lead to optimal group-separation. Such features captured the pattern of delayed delivery of the blood to the arterial and tissue compartments of the hyperglycemic groups. Alterations in gray and white matter, cerebral vasculature and carotid blood flow were detected for the T2DM group. The IGT cohort was structurally similar to the healthy cohort but demonstrated functional similarities to T2DM. When combining all extracted MRI metrics, features driving optimal separation between different glycemic conditions emerged mainly from the QUASAR scan. The only highly discriminant non-QUASAR feature, when comparing T2DM to healthy subjects, emerged from the cerebral angiogram. In this thesis, it was demonstrated that MRI-derived features could lead to potentially optimal differentiation between normoglycemia and hyperglycemia. More importantly, it was shown that an impaired cerebral hemodynamic pattern exists in both IGT and T2DM and that the IGT group exhibits functional alterations similar to the T2DM group.
Identification of a four-long non-coding RNA signature in predicting breast cancer survival

Long non-coding RNAs (lncRNAs) serve key roles in tumorigenesis and are differentially expressed in cancer. Using bioinformatics and statistical methods, the present study aimed to identify an lncRNA signature to predict breast cancer survival. The gene expression data of 768 patients with breast cancer were downloaded from The Cancer Genome Atlas database, and Cox regression, Kaplan-Meier and receiver operating characteristic (ROC) analyses were performed to construct and validate a predictive model. Gene Ontology term enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were employed to predict the functions of the indicated lncRNAs. A signature consisting of four lncRNAs, including PVT1, MAPT-AS1, LINC00667 and LINC00938, was identified, and patients were subsequently divided into high- and low-risk groups according to the median risk score. Kaplan-Meier analysis confirmed that patients in the high-risk group exhibited significantly poorer overall survival rate in both the training (P=0.0151) and the validation set (P=0.0016); furthermore, ROC analysis confirmed that the model could predict patient survival with a certain sensitivity and specificity. In conclusion, the four-lncRNA signature presents a potential prognostic biomarker for breast cancer that may be relevant for clinical application.
Cancer stem cells in neuroblastoma therapy resistance

Neuroblastoma (NB) is the most common cancer of infancy and accounts for nearly one tenth of pediatric cancer deaths. This mortality rate has been attributed to the > 50% frequency of relapse despite intensive, multimodal clinical therapy in patients with progressive NB. Given the disease’s heterogeneity and developed resistance, attaining a cure after relapse of progressive NB is highly challenging. A rapid decrease in the timeline between successive recurrences is likely due to the ongoing acquisition of genetic rearrangements in undifferentiated NB-cancer stem cells (CSCs). In this review, we present the current understanding of NB-CSCs, their intrinsic role in tumorigenesis, their function in disease progression, and their influence on acquired therapy resistance and tumor evolution. In particular, this review focus on the intrinsic involvement of stem cells and signaling in the genesis of NB, the function of pre-existing CSCs in NB progression and therapy response, the formation and influence of induced CSCs (iCSCs) in drug resistance and tumor evolution, and the development of a CSC-targeted therapeutic approach.
Comparison of AIMS65 and rockall scoring systems for predicting mortality in patients with upper gastrointestinal system hemorrhage

Aim: Acute upper gastrointestinal system hemorrhage is a common and life-threatening condition, and its mortality may reach 10% despite developing medical facilities. In this study, we aimed to compare the efficacy of the AIMS65 risk scoring and Rockall scoring in the non-variceal upper gastrointestinal hemorrhage patients and investigate the relationship between C-reactive protein/albumin ratio and these scoring systems. Materials and Methods: Forty-two inpatients diagnosed with upper gastrointestinal system hemorrhage in our hospital’s Internal Medicine Department between January 2018 and July 2018 included to study. For each patient, AIMS65 scoring according to the first evaluation results in the emergency department and Rockall scoring after the endoscopy were performed. Results: Mortality was observed in 2 (4.8%) patients. Both scoring systems were not statistically significant in determining the need for transfusion and predicting the hospitalization duration. The mean C-reactive protein/albumin ratio of the patients was found to be 0.94 (0.48-77.83), and C-reactive protein/albumin levels were higher in patients with high AIMS65 score (p=0.005). Conclusion: Upper gastrointestinal hemorrhage is a common emergency problem, and it constitutes 80% of all gastrointestinal system hemorrhages. In our study, the C-reactive protein/albumin ratio was consistent with the AIMS65 score and suggested that it could be a parameter that could be used in patients with upper gastrointestinal system hemorrhage, but more extensive studies are needed on this subject.
Clinical report and multidisciplinary team discussion of two fatal cases of severe acute pancreatitis

Severe acute pancreatitis (SAP) develops in 20% of patients with acute pancreatitis (AP). Patients with SAP are at a higher risk of systemic and local complications and often need invasive interventions. In order to assess the importance of multidisciplinary collaboration mode in the diagnosis and treatment of SAP, an international multidisciplinary discussion was held for two patients, who died of SAP. Through the multidisciplinary discussion, the recent relevant literature was reviewed and the experiences and lessons from these two cases were summarized.
Ten year outcomes of hypofractionated salvage post prostatectomy radiotherapy

Poster: "2019 ASM / R-0109 / Ten year outcomes of hypofractionated salvage post prostatectomy radiotherapy" by: "S. Chin, A. Fatimilehin, R. Walshaw, H. Mistry, T. Elliot, J. Logue, J. Wylie, A. Choudhury; Manchester/UK"
A Review of the Presentation of Overdiagnosis in Cancer Screening Patient Decision Aids

Introduction. Patient decision aid (PDA) certification standards recommend including the positive and negative features of each option of the decision. This review describes the inclusion of concepts related to overdiagnosis and overtreatment, negative features often ambiguously defined, in cancer screening PDAs. Methods. Our process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We reviewed 1) current systematic reviews of decision aids, 2) the Ottawa Hospital Research Institute Decision Aid Library Inventory, and 3) a web-based, gray literature search. Two independent reviewers identified and evaluated PDAs using content analysis. Reviewers coded whether overdiagnosis/overtreatment was described as 1) detecting cancer that would not lead to death, 2) detecting cancer that would not cause symptoms, and/or 3) a potential harm or consequence of screening. Coding discrepancies were resolved through consensus. Results. A total of 904 records (e.g., articles, PDAs) were reviewed and 85 PDAs were identified: prostate (n = 36), breast (n = 26), lung (n = 10), colorectal (n = 10), and other (n = 3). Sixty-seven PDAs included concepts related to overdiagnosis/overtreatment; 57 (67.1%) used a term other than overdiagnosis/overtreatment, 23 (27.1%) used the specific term “overdiagnosis,” and 13 (15.3%) used “overtreatment. ” PDAs described overdiagnosis/overtreatment as a potential harm or consequence of screening (n = 62) and/or a detection of a cancer that would not cause symptoms (n = 49). Thirty-six described overdiagnosis as the detection of a cancer that would not result in death. Twenty PDAs described the probabilities associated with overdiagnosis/overtreatment. Conclusions. Over three quarters of cancer screening PDAs addressed concepts related to overdiagnosis/overtreatment, yet terminology was inconsistent and few included probability estimates. Consistent terminology and minimum standards to describe overdiagnosis/overtreatment would help guide the design and certification of cancer screening PDAs.
Exploring the role of dimethylarginine dimethylaminohydrolase-mediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning in rats

Objective(s): Reperfusion of ischaemic myocardium results in reduced nitric oxide (NO) biosynthesis by endothelial nitric oxide synthase (eNOS) leading to endothelial dysfunction and subsequent tissue damage. Impaired NO biosynthesis may be partly due to increased levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of eNOS. As dimethylarginine dimethylaminohydrolase (DDAH) is a key enzyme responsible for degradation of ADMA, the present study was designed to explore the role of DDAH/ADMA/NO pathway in cardio-protective mechanism of ischaemic postconditioning. Materials and Methods: Isolated rat hearts were subjected to myocardial ischaemia for 30 min followed by reperfusion for 2 hours in control group. Myocardial injury was assessed by measurement of infarct size, left ventricular developed pressure (LVDP), lactate dehydrogenase (LDH) and creatine kinase (CK) enzymes in coronary effluents. The reperfused hearts were homogenised and tissue concentration of nitrite, ADMA level and DDAH enzyme activity was determined. Results: A significant increase in infarct size, LDH, CK release in coronary effluents and ADMA level in myocardial tissue was observed in control group. The increase in tissue ADMA coincided with reductions of NO tissue concentrations and DDAH activity. Ischaemic postconditioning significantly attenuated ischaemia-reperfusion induced myocardial injury manifested in the terms of decreased infarct size, LDH, CK, tissue ADMA along with increase in NO levels and DDAH enzyme activity. Pretreatment with L-Homocysteine (300 µM), a competitive inhibitor of DDAH, and L-NG-nitroarginine methyl ester (L-NAME; 100 µM), an inhibitor of eNOS, completely abolished ischaemic postconditioning-induced myocardial protection. Conclusion: Enhancing DDAH activity by postconditioning may be a novel target to reduce ADMA level and increase NO bioavailability to prevent myocardial ischaemia-reperfusion injury.
Southern African HIV Clinicians Society guideline for the prevention, diagnosis and management of cryptococcal disease among HIV-infected persons: 2019 update

Read online: Scan this QR code with your smart phone or mobile device to read online. Authors: Nelesh P. Govender 1,2,3 Graeme Meintjes4,5 Phetho Mangena6 Jeremy Nel7 Samantha Potgieter8 Denasha Reddy9 Helena Rabie10 Douglas Wilson11,12 John Black13 David Boulware14 Tom Boyles15,16 Tom Chiller17 Halima Dawood18,19 Sipho Dlamini20 Thomas S. Harrison21 Prudence Ive16,22 Joseph Jarvis23 Alan Karstaedt16,24 Matamela C. Madua25 Colin Menezes9,16 Mahomed-Yunus S. Moosa26 Zaaheera Motlekar27 Amir Shroufi17 Sarah Lynn Stacey16,28 Merika Tsitsi9,16 Gilles van Cutsem29,30 Ebrahim Variava16,31 Michelle Venter9,16 Rachel Wake1,21
Chronic asthma in adults

There are around 5.4 million people in the UK with asthma. Poorly controlled asthma places a particular burden on the NHS, and diminishes patients’ quality of life. More significantly, there are an estimated 1400 deaths from asthma each year in the UK, many of which are preventable. This is unacceptably high for a treatable condition. General practice carries much of the responsibility for diagnosis and management of asthma, and there is potential to improve the mortality and morbidity rates from asthma by improving knowledge transfer between GPs and their patients and the use of guidelines on compliance with agreed treatment paths. There are three separate sets of guidelines for the diagnosis and treatment of asthma: The British Thoracic Society and Scottish Intercollegiate Guidelines Network guidelines, The National Institute for Health and Care Excellence guidelines, and Global Initiative for Asthma guidelines. These will be reviewed throughout this article.
Bloodstream infection by Acinetobacter radioresistens: the first case report in Brazil

This report is the description of the first case in Brazil of community-acquired bloodstream infection caused by Acinetobacter radioresistens. A 73-year-old male patient with Alzheimer’s and Parkinson’s disease was hospitalized and diagnosed with pneumonia at a general hospital. MacConkey agar pure culture was obtained from blood cultures. Conventional tests identified the isolate as Acinetobacter baumannii complex. However, the matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) technique identified it as Acinetobacter radioresistens. The isolate was sensitive to all antibiotics tested by the disk diffusion method, including carbapenem. However, bla oxa-23 gene was detected by the polymerase chain reaction (PCR) assay. Acinetobacter radioresistens can be considered an important agent of opportunistic infections in immunocompromised patients, a potential disseminator of resistance genes.
Greater IL-6, D-dimer, and ICAM-1 Levels Are Associated With Lower Small HDL Particle Concentration in the Multicenter AIDS Cohort Study

In HIV-infected men, both untreated and on antiretroviral therapy, and in HIV-uninfected men, greater interleukin-6 (IL-6), D-dimer, and intercellular adhesion molecule-1 (ICAM-1) levels are associated with lower small HDL particle number (HDL-P), and greater IL-6 and ICAM-1 levels are associated with lower total HDL-P.
De-escalating management of primary and locally recurrent breast cancer

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Sensitive Biomarker Analysis of Xue-Fu-Zhu-Yu Capsule for Patients with Qi Stagnation and Blood Stasis Pattern: A Nested Case-Control Study

Objectives To identify the sensitive biomarker to predict the effectiveness of Xue-Fu-Zhu-Yu capsules (XFZYC). Methods This nested case-control study included 5 patients with response to XFZYC in the treatment group, 5 patients with no response to XFZYC also in the treatment group, and 5 patients in the control group treated with placebo who participated in the previous RCT. The mRNAs, miRNAs, lncRNAs, and circRNAs were sequenced by next-generation sequencing and differential-expressed (DE) RNAs were identified if p value ≤ 0.05 and fold change ≥2, bioinformatics analysis was conducted in terms of function annotations and signaling pathways, and then sensitive biomarker was analyzed based on real-time PCR. Results The distributions of clinical characteristics between the selected participants from treatment group and placebo group were well balanced. A total of 1156 DE RNAs, 388 miRNAs, 1954 lncRNAs, and 560 circRNAs were identified, which was associated the mechanism of XFZYC and composed the targeted potential biomarkers for further real-time PCR. The DE RNAs were enriched in KEGG pathways pertaining to pathogenesis of Qi Stagnation and Blood Stasis- (QS & BS-) & associated diseases such as coronary heart disease and digestive diseases. The expression level of FZD8 was significantly higher in response patients than that in nonresponse patients (p = 0.041) and circRNA_13799 significantly lower in response patients than that in nonresponse patients (p = 0.040) based on real-time PCR. Patients with higher expression level of FZD8 with 75% stratification have significantly higher reduction in the questionnaire score (p = 0.010), and the area under the curve (AUC) was 0.765 (95%CI = 0.593–0.936; p = 0.014). Conclusions FZD8 might perform the sensitive biomarker for predicting the effectiveness of XFZYC. However, further prospective cohort study was warranted to confirm the exact specificity and sensitivity of this biomarker.