Miracle-dz/UniFAR-FTUs huggingface dataset:
A patient with biliary colic and intestinal obstruction

A 38-year-old Caucasian male patient was referred to our emergency department with typical biliary colic. Medical and family history were unremarkable. Physical examination revealed a non-feverish mildly ill patient, with normal bowel sounds. In addition a remarkably ‘freckled’ skin was found, especially on periorbital and perioral skin and buccal mucosa (figure 1). Apart from abnormal liver enzymes (bilirubin 1.35 mg/dl, gamma-glutamyltransferase 1049 IU/l and alanine aminotransferase 286 IU/l) laboratory tests were normal. Abdominal ultrasonography showed dilated intra- and extrahepatic bile ducts and cholecystolithiasis but no signs of choledocholithiasis. An endoscopic retrograde cholangiopancreatography was performed because of presumed choledocholithiasis, but common bile duct cannulation was unsuccessful because of a large polypoid mass at its insertion (figure 2). During endoscopy multiple smaller polyps were seen in duodenum and stomach. Following endoscopic retrograde cholangiopancreatography …
Impact of azathioprine and tumour necrosis factor antagonists on the need for surgery in newly diagnosed Crohn's disease

Objective The aim of the study was to assess whether azathioprine and antitumour necrosis factor (TNF) treatment decrease the long-term need for surgery in patients with Crohn's disease. Methods This was an observational study of a referral centre cohort. The cumulative incidence of the first Crohn's disease-related major abdominal surgery was estimated using the Kaplan–Meier method, and independent predictors of surgery were identified using Cox proportional hazards regression with propensity scores adjustment. Receiver operating characteristic (ROC) analysis was used to identify optimal cut-offs for duration of maintenance treatments. The electronic charts of 296 incident cases of Crohn's disease from Nancy University Hospital, France, diagnosed between 2000 and 2008, were reviewed through January 2010. Results The median follow-up time per patient was 57 months. Seventy-six patients (26%) underwent at least one major abdominal surgical procedure. The cumulative probabilities of the first Crohn's disease-related major abdominal surgery were 6.5, 25.9 and 44.3 at 1, 5 and 9 years, respectively. In the ROC analysis, the duration of anti-TNF and azathioprine treatment had significant cut-off values (≤475 days ∼16 months and ≤45 days ∼1.5 months, respectively) with positive likelihood ratios (PLRs) of 1.52 (p<0.0001) and 1.51 (p=0.003) for the first Crohn's disease-related major abdominal surgery. Using multivariate Cox proportional hazards regression analysis (after propensity score adjustment), independent positive predictors of major abdominal surgery were stricturing (HR=12.01; 95% CI 5.97 to 24.17) or penetrating (HR=10.77; 95% CI 4.87 to 23.80) disease behaviour at diagnosis, duration of anti-TNF treatment of <16 months (HR=3.86; 95% CI 1.77 to 8.45) and duration of azathioprine treatment of <1.5 months (HR=2.00; 95% CI 1.20 to 3.34). Conclusions Non-complicated inflammatory disease behaviour and long-term anti-TNF treatment are associated with a lower risk for surgery whereas azathioprine only modestly lowers this risk.
Thromboembolic risk among Danish children and adults with inflammatory bowel diseases: a population-based nationwide study

Background Recommendations for venous thromboembolism (VTE) prophylaxis in patients with inflammatory bowel disease (IBD) can be refined by incorporating patient-specific risk factors. Objectives To determine the risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) in children and adults with Crohn's disease and ulcerative colitis and evaluate whether this risk varies by age and/or presence of other risk factors. Methods We performed a cohort study using Danish administrative data. Incidence rates of DVT and PE were calculated among patients with IBD and an age- and gender-matched comparison population and compared using Cox proportional hazards regression. We performed additional analyses stratifying by age, gender and disease type and restricting outcomes to unprovoked events (occurring without known malignancy, surgery, fracture/trauma or pregnancy). We next performed a nested case–control study to adjust for additional co-morbidities (congestive heart failure, diabetes, myocardial infarction and stroke) and the use of hormone replacement and antipsychotic medications. Results The study included 49 799 patients with IBD (14 211 Crohn's disease, 35 229 ulcerative colitis) and 477 504 members of the general population. VTE risk was elevated in patients with IBD (HR=2.0 (95% CI 1.8 to 2.1) for total events, HR=1.6 (95% CI 1.5 to 1.8) for unprovoked events). Although the incidence of VTE increased with age, the RR was higher in younger patients. Among those ≤20 years old, HRs were 6.0 (95% CI 2.5 to 14.7) for DVT and 6.4 (95% CI 2.0 to 20.3) for PE. After further adjusting for co-morbidity and medication use in the case-control analysis, ORs for all events remained in the 1.5–1.8 range. Discussion Patients with IBD have twice the incidence of PE or DVT as does the general population. This risk persisted after taking into account other VTE risk factors. Relative risks were particularly high at young ages, though actual incidence increased with age. These findings can further inform risk–benefit analysis of VTE prophylaxis.
Breaking down haem attenuates acute pancreatitis: a new treatment option?

The premature intracellular activation of digestive proteases can result in autodigestion of the pancreas and has long been regarded as the initial and a rate-limiting step in the development of acute pancreatitis.1 Recent evidence suggests, however, that inflammatory cells infiltrating the pancreas—rather than the extent of initial protease activation—determines the ultimate severity of acute pancreatitis.2 3 All attempts to target the inflammatory response of acute pancreatitis therapeutically have unfortunately been unsuccessful. One reason for this failure may lie in the type of inflammatory cells that were targeted.4 Macrophages orchestrate both the initiation and the resolution of inflammation and would therefore be an interesting therapeutic target for modulating the inflammatory response in acute pancreatitis. Selective depletion of the proinflammatory M1 macrophages has been found to reduce the severity in acute pancreatitis.5 Nature has provided a potent protective strategy to counter an overwhelming inflammatory response. Haemoxygenase-1 (HO-1) is an inducible isoform of the initial and rate-controlling enzyme used in the degradation of haem into iron, carbon monoxide and biliverdin. The latter is subsequently converted to bilirubin.6 HO-1 is expressed in various inflammatory cells including macrophages and has recently gained considerable attention for exerting …
Ribosomes in platelets protect the messenger.

In this issue of Blood , [Mills et al][1] comprehensively examine ribosome-bound messenger RNAs (mRNAs) in resting and activated platelets and describe a role for the ribosome rescue factor Pelota (PELO) in regulating mRNA decay in platelets (see figure). [1][2] ! [Figure][3] Ribosome
Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique

Background Oesophageal intraluminal impedance is currently used for assessment of reflux in gastro-oesophageal reflux disease (GORD). Oesophageal mucosa integrity may have a key role in heartburn perception in non-erosive reflux disease (NERD). Severe erosive oesophagitis is associated with low impedance baseline. We hypothesised that impedance baseline measurements could be used to evaluate changes in oesophageal mucosa integrity in man. Methods We measured oesophageal impedance baseline before, during and after acid perfusion in rabbits and healthy subjects. Transepithelial resistance (TER) was determined and dilated intercellular spaces (DIS) were assessed in isolated rabbit oesophageal mucosa. Impedance baseline was measured retrospectively at different levels of the oesophagus in impedance-pH recordings from asymptomatic volunteers and patients with GORD. Results In healthy subjects and rabbits, impedance baseline dropped dramatically during perfusion of control solution (pH 7.2) but after perfusion, impedance recovered. In rabbits, after perfusion with saline pH 1.5 and 1.0 impedance values remained a 39.1±7.0% and 63.9±6.5% (p<0.05) lower respectively. There was a positive correlation between in vivo basal impedance and in vitro TER values (r=0.72, p=0.0021). Tissue showed no erosions but both acidic solutions induced DIS. In healthy subjects, after perfusion with saline pH 2.0 and 1.0 the impedance baseline remained lower a 21.9±6.5% and 52.7±5.0%, (p<0.0001) respectively. Patients with GORD have a lower impedance baseline than healthy volunteers at the distal oesophagus. Conclusions Impedance baseline measurements might be used to evaluate the status of the oesophageal mucosa and to study the role of the impaired mucosal integrity in acid-induced heartburn in healthy volunteers and in patients with GORD.
Grazing of heterotrophic flagellates on viruses is driven by feeding behaviour.

The trophic interactions between viruses, bacteria and protists play a crucial role in structuring microbial communities and regulating nutrient and organic matter flux. Here, we show that the impact on viral density by heterotrophic flagellates is related to their feeding behaviour (feeding on sedimented particles - Thaumatomonas coloniensis, filter feeding of suspended particles - Salpingoeca sp., and actively searching raptorial feeding - Goniomonas truncata). Phage MS2 was co-incubated with flagellates and the natural bacterial and viral community originating from the same groundwater habitats where the flagellates were isolated. Three complementary assays, i.e. flow cytometry, qPCR and plaque assay, were used for enumeration of total viruses, total MS2 phages, and free and infectious MS2, respectively, to provide insights into the grazing mechanisms of the flagellates on viruses. Phage MS2 was actively removed by the suspension feeders T. coloniensis and Salpingoeca sp. in contrast with the actively raptoriale grazer G. truncata. The decline of viral titre was demonstrated to be caused by ingestion rather than random absorption by both qPCR and locating protein fluorescently labelled MS2 inside the flagellates. Further, we indicate that phages can be used as a minor carbon source for flagellates. Collectively, these data demonstrate that eliminating viruses can be an important function of protists in microbial food webs, carbon cycling and potentially water quality control.
A unified algorithm for estimation and scheduling in data path synthesis

A unified algorithm is presented to solve the problem of estimation and scheduling for performance constrained data path synthesis. The algorithm achieves superior results by first computing a lower bound on the number of functional units required to satisfy the performance constraint T, and then scheduling the operations into the best control steps using the lower bound algorithm. The lower bound not only greatly reduces the size of the solution space, but also provides a means to measure the proximity of the final solution to an optimal one. Our unified algorithm can also be incorporated in a branch-and-bound algorithm to solve the scheduling problem optimally. Experiments indicate that our scheduling algorithm can produce results very close to the lower bound. For all of the test cases the difference between our upper and lower bounds is not greater than one. <<ETX>>
Biogeographical distribution of denitrifying anaerobic methane oxidizing bacteria in Chinese wetland ecosystems.

The discovery of denitrifying anaerobic methane oxidation with nitrite as electron acceptor mediated by 'Candidatus Methylomirabilis oxyfera' connected the biogeochemical carbon and nitrogen cycle in a new way. However, it is important to have a comprehensive understanding about the distribution of M. oxyfera-like bacteria in the terrestrial realm, especially the wetland ecosystems that are known as the largest natural source of atmospheric methane. Here, our molecular evidence demonstrated that a wide geographical distribution of M. oxyfera-like bacteria at oxic/anoxic interfaces of various wetlands (n = 91) over the Chinese territory. Intriguingly, the M. oxyfera-like bacteria were detected in some extreme environments, indicating that M. oxyfera-like bacteria occupied a wide range of habitats. Quantitative polymerase chain reaction estimated that the abundance of M. oxyfera-like bacteria ranged from 2.2 × 10(3) to 2.3 × 10(7) copies g(-1) dry soil, and up to around 0.62% of the total number of bacteria. Moreover, the M. oxyfera-like bacteria showed high biodiversity in wetland ecosystems based on the analysis of 462 pmoA and 287 16S rRNA gene sequences. The current study revealed the widespread distribution and biogeography of M. oxyfera-like bacteria in the terrestrial system.
CD27 marks murine embryonic hematopoietic stem cells and type II prehematopoietic stem cells.

To the editor: Cell surface markers of adult hematopoietic stem cells (HSCs) are well established, but fewer markers are available for embryonic HSCs and their immediate precursors (pre-HSCs). HSCs differentiate from hemogenic endothelial cells in the major arteries of the embryo [dorsal aorta,
Evaluation of Right Ventricular Function in Patients With Complete Right Bundle-branch Block Using Total Cardiac Performance Index (TEI Index)

Background.We aimed to assess right ventricular (RV) function in patients with complete right bundle branch block (CRBBB) using noninvasive techniques.Methods. The studied subjects were 29 consecutive patients with CRBBB aged over 40 years (mean: 66 years). Six patients had hypertension; the other 23 patients had no cardiovascular disorders. Twenty age-matched healthy subjects (mean: 68 years) served as the controls. The RV volumes at end-diastole (RVEDV) and end-systole were measured via apical four-chamber view, and the RV ejection fraction (RVEF) was calculated. The isovolumic contraction (ICT) and relaxation times (IRT) and the ejection time (RVET) were measured using the recordings of RV inflow or outflow velocities and the electrocardiogram. The total cardiac performance index (TEI index) was calculated as (ICT + IRT) / RVET.Results. The patients with CRBBB were divided into two groups based on the mean + 2 standard deviations of RV TEI index (=0.40) in the controls: the low value group (23 patients with TEI indexConclusions.RV dysfunction or arrhythmic events may occur in some patients with CRBBB, and the TEI index may be useful for the detection and evaluation of these patients.
Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B

BACKGROUND The effect of hepatitis delta virus (HDV) infection on the clinical course of cirrhosis type B is poorly defined. AIMS To investigate the impact of HDV status on morbidity and mortality in cirrhosis type B. PATIENTS/METHODS Retrospective cohort study of 200 Western European patients with compensated cirrhosis type B followed for a median period of 6.6 years. RESULTS At diagnosis, 20% of patients had antibodies to HDV (anti-HDV); median age was lower in anti-HDV positive cirrhotics (34 v 48 years respectively). Kaplan-Meier five year probability of hepatocellular carcinoma (HCC) was 6, 10, and 9% in anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 22, 16, and 19% and for survival they were 92, 89, and 83% respectively. Cox regression analysis identified age, albumin concentration, γ-globulin concentration, and HDV status as significant independent prognostic variables. After adjustment for clinical and serological differences at baseline, the risk (95% confidence interval) for HCC, decompensation, and mortality was increased by a factor of 3.2 (1.0 to 10), 2.2 (0.8 to 5.7), and 2.0 (0.7 to 5.7) respectively in anti-HDV positive relative to HDV negative cirrhotic patients. The adjusted estimated five year risk for HCC was 13, 4, and 2% for anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 18, 8, and 14% and for survival 90, 95, and 93% respectively. CONCLUSIONS HDV infection increases the risk for HCC threefold and for mortality twofold in patients with cirrhosis type B.
Oxygen and the activity and distribution of marine Thaumarchaeota.

Ammonia-oxidizing Archaea, or Thaumarchaeota (Spang et al., 2010), are an abundant and widespread group of prokaryotes. They are particularly abundant in the mesopelagic zone of the open ocean (Karner et al., 2001) and in oxygen minimum zones (OMZs: Ulloa et al., 2012; Tolar et al., 2013; Peng et al., 2016), where they persist at oxygen concentrations that are at the limit of analytical detection. They perform an important geochemical process: the oxidation of ammonia to nitrite using molecular oxygen as an electron acceptor, the first step in the two-step process of nitrification. They also produce nitrous oxide, an ozone-destroying greenhouse gas, as a byproduct of their metabolism (Santoro et al., 2010; Santoro et al., 2011; Peng et al., 2016). They have proven difficult to isolate into pure culture and most of our knowledge of their ecophysiology stems from experiments with environmental samples or from work with the original isolate, Nitrosopumilus maritimus strain SCM1.
Emission Standards : The Case for Gasoline and Diesel Cars

Passenger transport affects climate through various mechanisms involving both long-lived and short-lived climate forcers. Because diesel cars generally emit less CO2 than gasoline cars, CO2 emission taxes for vehicle registrations and fuels enhance the consumer preference for diesel cars over gasoline cars. However, with the non-CO2 components, which have been changed and will be changed under the previous and upcoming vehicle emission standards, what does the shift from gasoline to diesel cars mean for the climate mitigation? By using a simple climate model, we demonstrate that, under the earlier emissions standards (EURO 3 and 4), a diesel car causes a larger warming up to a decade after the emissions than a similar gasoline car due to the higher emissions of black carbon and NOX (enhancing the O3 production). Beyond a decade, the warming caused by a diesel car becomes, however, weaker because of the lower CO2 emissions. As the latter emissions standards (EURO 5 and 6) are phased in, the short-term warming due to a diesel car becomes smaller primarily due to the lower black carbon emissions. Thus, although results are subject to restrictive assumptions and uncertainties, the switch from gasoline to diesel cars encouraged by CO2 taxes does not contradict with the climate mitigation focusing on long-term consequences.
Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma.

Daratumumab plus pomalidomide and dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary end point. Overall response rate (ORR) and minimal residual disease (MRD) by next-generation sequencing were secondary end points. Patients (N = 103) received a median (range) of 4 (1-13) prior therapies; 76% received ≥3 prior therapies. The safety profile of daratumumab plus pom-dex was similar to that of pom-dex alone, with the exception of daratumumab-specific infusion-related reactions (50%) and a higher incidence of neutropenia, although without an increase in infection rate. Common grade ≥3 adverse events were neutropenia (78%), anemia (28%), and leukopenia (24%). ORR was 60% and was generally consistent across subgroups (58% in double-refractory patients). Among patients with a complete response or better, 29% were MRD negative at a threshold of 10-5 Among the 62 responders, median duration of response was not estimable (NE; 95% confidence interval [CI], 13.6-NE). At a median follow-up of 13.1 months, the median progression-free survival was 8.8 (95% CI, 4.6-15.4) months and median overall survival was 17.5 (95% CI, 13.3-NE) months. The estimated 12-month survival rate was 66% (95% CI, 55.6-74.8). Aside from increased neutropenia, the safety profile of daratumumab plus pom-dex was consistent with that of the individual therapies. Deep, durable responses were observed in heavily treated patients. The study was registered at www.clinicaltrials. gov as #NCT01998971.
Pathology of Tumors of the Nervous System.

There is no reason why this, the second edition of the most definitive contemporary treatise on nervous system tumors written in English, will not have the same welcome reception it earned at its debut five years ago. The book is a wholly representative statement of modern British work in the field, comparable to its companion volume on neuropathology by the late Professor Greenfield and his collaborators. For those few readers not familiar with the first edition, it may be stated briefly that the book contains ample descriptions of all the commonly recognized neoplasms of the nervous system, including those of developmental and of secondarily invasive origin as well as the primary tumors of meningeal, vascular, and neuroectodermal derivation. The biological characteristics of the respective tumors are given adequate consideration, and the classification employed by the authors, a modified but not overly simplified version of the cytogenetic schema of Bailey and
Visceral perception: inflammatory and non-inflammatory mediators

Visceral hypersensitivity is currently the most widely accepted mechanism responsible for abdominal pain. Inflammatory mediators are known to sensitise primary afferents and to recruit silent nociceptors. Recent evidence suggests that non-inflammatory mediators also have the potential to trigger visceral pain. This sequence of events may constitute part of an alerting system which prompts the central nervous system to correct gastrointestinal responses to ingestion.
Distribution of Glycosaminoglycans in an Early Osteoarthritis-like Lesion in the Mandibular Condylar Cartilage of Senescence-Accelerated Mice

The purpose of this study was to determine the immunolocalization of glycosaminoglycans (GAGs) in the mandibular condylar cartilage of senescence-accelerated mice (SAM) with early osteoarthritis (OA). The cartilages in the mandibular condyles and in the proximal tibial epiphyses from two 10-month-old SAM strains, SAMP8 and SAMR1 (a control), were examined for the immunolocalization of chondroitin-4-sulphate (C4S) and keratan sulphate (KS). Morphologically, the mandibular condylar cartilage was disrupted with clefts in SAMP8 but not in SAMR1. C4S was distributed throughout the two cartilages. In contrast, KS was located in extracellular regions in the fibrous and proliferative cell layers of mandibular cartilage and in the lower maturative cell layer of epiphyseal cartilage. The two GAGs, particularly KS, were intensely immunostained around the clefts. These results suggest that C4S and KS could play differential roles in the structural function of articular cartilage and their functions might be involved in early mandibular OA lesions.