Miracle-dz/UniFAR-FTUs huggingface dataset:
Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults.

Transitioning CD19-directed chimeric antigen receptor (CAR) T cells from early-phase trials in relapsed patients to a viable therapeutic approach with predictable efficacy and low toxicity for broad application among patients with high unmet need is currently complicated by product heterogeneity resulting from transduction of undefined T-cell mixtures, variability of transgene expression, and terminal differentiation of cells at the end of culture. A phase 1 trial of 45 children and young adults with relapsed or refractory B-lineage acute lymphoblastic leukemia was conducted using a CD19 CAR product of defined CD4/CD8 composition, uniform CAR expression, and limited effector differentiation. Products meeting all defined specifications occurred in 93% of enrolled patients. The maximum tolerated dose was 106 CAR T cells per kg, and there were no deaths or instances of cerebral edema attributable to product toxicity. The overall intent-to-treat minimal residual disease-negative (MRD-) remission rate for this phase 1 study was 89%. The MRD- remission rate was 93% in patients who received a CAR T-cell product and 100% in the subset of patients who received fludarabine and cyclophosphamide lymphodepletion. Twenty-three percent of patients developed reversible severe cytokine release syndrome and/or reversible severe neurotoxicity. These data demonstrate that manufacturing a defined-composition CD19 CAR T cell identifies an optimal cell dose with highly potent antitumor activity and a tolerable adverse effect profile in a cohort of patients with an otherwise poor prognosis. This trial was registered at www.clinicaltrials. gov as #NCT02028455.
Gastric emptying of a liquid nutrient meal in the critically ill: relationship between scintigraphic and carbon breath test measurement

Objective It is assumed that delayed gastric emptying (GE) occurs frequently in critical illness; however, the prevalence of slow GE has not previously been assessed using scintigraphy. Furthermore, breath tests could potentially provide a convenient method of quantifying GE, but have not been validated in this setting. The aims of this study were to (i) determine the prevalence of delayed GE in unselected, critically ill patients and (ii) evaluate the relationships between GE as measured by scintigraphy and carbon breath test. Design Prospective observational study. Setting Mixed medical/surgical intensive care unit. Patients 25 unselected, mechanically ventilated patients (age 66 years (49–72); and 14 healthy subjects (age 62 years (19–84)). Interventions GE was measured using scintigraphy and 14C-breath test. A test meal of 100 ml Ensure (standard liquid feed) labelled with 14C octanoic acid and 99mTechnetium sulphur colloid was placed in the stomach via a nasogastric tube. Main outcome measures Gastric ‘meal’ retention (scintigraphy) at 60, 120, 180 and 240 min, breath test t50 (BTt50), and GE coefficient were determined. Results Of the 24 patients with scintigraphic data, GE was delayed at 120 min in 12 (50%). Breath tests correlated well with scintigraphy in both patients and healthy subjects (% retention at 120 min vs BTt50; r2=0.57 healthy; r2=0.56 patients; p≤0.002 for both). Conclusions GE of liquid nutrient is delayed in approximately 50% of critically ill patients. Breath tests correlate well with scintigraphy and are a valid method of GE measurement in this group.
Understanding commuting to accompany work organisations' and employees' behaviour change

Commuting is a key domain for promoting sustainability but changing transportation habits to adopt more sustainable transportation modes is a hard challenge. Our approach is based on the idea of accompanying behaviour change by first understanding the context in which behaviours occur and then designing an appropriate intervention considering its practicability and acceptability. This paper illustrates key elements of reflection from a study on commuting that we have conducted in a workplace and that is informing our ongoing design of technology in support of behaviour change for the three stakeholders of commuting, commuters, work organisations and public administrators.
Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit

Objective To describe the patient characteristics, diagnoses and clinical outcomes of patients presenting with acute upper gastrointestinal bleeding (AUGIB) in the 2007 UK Audit. Design Multi-centre survey. Setting All UK hospitals admitting patients with AUGIB. Participants All adults (>16 years) presenting in or to UK hospitals with AUGIB between 1 May and 30 June 2007. Results Data on 6750 patients (median age 68 years) was collected from 208 participating hospitals. New admissions (n=5550) were younger (median age 65 years) than inpatients (n=1107, median age 71 years), with less co-morbidity (any co-morbidity 46% vs 71%, respectively). At presentation 9% (599/6750) had known cirrhosis, 26% a history of alcohol excess, 11% were taking non-steroidal anti-inflammatory drugs and 28% aspirin. Peptic ulcer disease accounted for 36% of AUGIB and bleeding varices 11%. In 13% there was evidence of further bleeding after the first endoscopy. 1.9% underwent surgery and 1.2% interventional radiology for AUGIB. Median length of stay was 5 days. Overall mortality in hospital was 10% (675/6750, 95% CI 9.3 to 10.7), 7% in new admissions and 26% among inpatients. Mortality was highest in those with variceal bleeding (15%) and with malignancy (17%). Conclusions AUGIB continues to result in substantial mortality although it appears to be lower than in 1993. Mortality is particularly high among inpatients and those bleeding from varices or upper gastrointestinal malignancy. Surgical or radiological interventions are little used currently.
Interaction of Aspergillus fumigatus conidia with Acanthamoeba castellanii parallels macrophage-fungus interactions.

Aspergillus fumigatus and free-living amoebae are common inhabitants of soil. Mechanisms of A. fumigatus to circumvent the amoeba's digestion may facilitate overcoming the vertebrate macrophage defence mechanisms. We performed co-culture experiments using A. fumigatus conidia and the amoeba Acanthamoeba castellanii. Approximately 25% of the amoebae ingested A. fumigatus conidia after 1 h of contact. During intra-amoebal passage, part of the ingested conidia was able to escape the food vacuole and to germinate inside the cytoplasm of A. castellanii. Fungal release into the extra-protozoan environment by exocytosis of conidia or by germination was observed with light and transmission electron microscopy. These processes resulted in structural changes in A. castellanii, leading to amoebal permeabilization without cell lysis. In conclusion, A. castellanii internalizes A. fumigatus conidia, resulting in fungal intracellular germination and subsequent amoebal death. As such, this interaction highly resembles that of A. fumigatus with mammalian and avian macrophages. This suggests that A. fumigatus virulence mechanisms to evade macrophage killing may be acquired by co-evolutionary interactions among A. fumigatus and environmental amoebae.
FLIN: Enabling Fairness and Enhancing Performance in Modern NVMe Solid State Drives

Modern solid-state drives (SSDs) use new host–interface protocols, such as NVMe, to provide applications with fast access to storage. These new protocols make use of a concept known as the multi-queue SSD (MQ-SSD), where the SSD has direct access to the application-level I/O request queues. This removes most of the OS software stack that was used in older protocols to control how and when the I/O requests were dispatched to storage devices. Unfortunately, while the elimination of the OS software stack leads to a significant performance improvement, we show in this paper that it introduces a new problem: unfairness. This is because the elimination of the OS software stack eliminates the mechanisms that were used to provide fairness among applications in older SSDs. To study application-level unfairness, we perform experiments using four real state-of-the-art MQ-SSDs. We demonstrate that the lack of fair scheduling mechanisms leads to high unfairness among concurrently-executing applications due to the interference among them. For instance, when one of these applications issues many more I/O requests than others, the other applications are slowed down significantly. We perform a comprehensive analysis of interference in real MQ-SSDs, and find four major interference sources: (1) the intensity of requests sent by each application, (2) differences in request access patterns, (3) the ratio of reads to writes, and (4) garbage collection. To alleviate unfairness in MQ-SSDs, we propose the Flash-Level INterference-aware scheduler (FLIN). FLIN is a lightweight I/O request scheduling mechanism that provides fairness among requests from different applications. FLIN uses a three-stage scheduling algorithm that protects against all four major sources of interference, while respecting the application-level priorities assigned by the host. FLIN is implemented fully within the SSD controller firmware, requiring no new hardware, and has negligible (<0.06%) storage cost. Compared to a state-of-the-art I/O scheduler, FLIN improves the fairness and performance of a wide range of enterprise and datacenter storage workloads, with an average improvement of 70% and 47%, respectively.
Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats

Background and aim Hepatic stellate cells (HSCs) are key participants in liver fibrosis development. 1,25(OH)2D3, the active form of vitamin D, has antiproliferative properties and antifibrotic potential, as well as a role in extracellular matrix and matrix metalloproteinase (MMP) regulation in renal and lung fibrosis. Little is known about the role of 1,25(OH)2D3 in liver and its involvement in liver fibrosis. Therefore, we investigated the antiproliferative and antifibrotic effects of 1,25(OH)2D3 in primary cultured HSCs and in a rat model of liver fibrosis induced by thioacetamide (TAA). Methods Primary HSCs were isolated from rats' livers and treated with 1,25(OH)2D3. Proliferation was examined by bromodeoxyuridine. Vitamin D receptor (VDR) expression and several fibrotic markers were detected by western blot analysis and real-time PCR. Collagen Iα1 and MMP-9 promoter activity were measured by luciferase assay. MMP-9 enzymatic activity was investigated by zymography. VDR silencing was performed by sh-RNA. An in vivo study was performed on TAA-induced liver fibrosis model in rats treated with or without 1,25(OH)2D3. The fibrotic score and collagen deposition were determined by Masson and by Sirius red staining. Results While VDR was highly expressed in quiescent HSCs, its expression decreased up to 40% during activation. Addition of 1,25(OH)2D3 to activated HSCs stimulated VDR expression. 1,25(OH)2D3 suppressed HSC proliferation and cyclin D1 expression by ∼50% and tissue inhibitor of metalloproteinase 1 (TIMP-1) by 60% and led to a 40% downregulation of collagen Iα1 expression. Moreover, 1,25(OH)2D3 increased MMP-9 activity by 30%. Silencing VDR by sh-RNA demonstrated that suppression of cyclin D1 and collagen Iα1 protein expression was VDR dependent. Treatment with 1,25(OH)2D3 significantly reduced extracellular matrix deposition and lowered the fibrotic score in TAA-induced liver fibrosis. Conclusion 1,25(OH)2D3 has antiproliferative and antifibrotic effects on liver fibrosis in in vitro and in vivo models and may be considered as having potential therapeutic value.
Rede e apoio social familiar no seguimento do recém-nascido pré-termo e baixo peso ao nascer

One of the connected aspects to the occurred of the preterm (PT) newborn and of low birth weight (LBW) is relative to the period after the discharge from hospital. This study aims to identify the social net and the social support of families where children were born prematurely and were hospitalized in the Neonatal Intensive Care Unit (NICU), from the utilization of the genogram and ecomap instruments with families from Cascavel city. It is a descriptive study, with qualitative approach; w e carry out the following of six families that had the PT/LBW children in the NICU by family’s appointments during the hospitalization and of seven home visits after child discharge in the three first months after hospital discharge. The facts were grouped about three subjects: The social net as the member of the PT and BPN segment in the family context; the social support in the experiences of the families with babies PT and BPN; the vulnerability and the context of the net and of the social support. It emerged an assembly of actors and settings that they are part of the net connection to the families in their routine. The action of the nursing earns more sense with the knowledge of the net that provides integration between practical knowledge and technical knowledge. Descriptors: Newborn ; Child care; Social support ; Community Health Nursing .
Targeted therapies in 54 patients with Erdheim-Chester disease, including follow-up after interruption (the LOVE study).

Short title: Targeted therapies in ECD Fleur Cohen-Aubart 1,2 , MD, PhD, Jean-François Emile 3 , MD, PhD, Fabrice Carrat 2,4 , MD, PhD, Frédéric Charlotte 2,5 , MD, PhD, Neila Benameur 6 , PharmD, Jean Donadieu 7 , MD, PhD, Philippe Maksud 8 , MD, PhD, Ahmed Idbaih 9 , MD, PhD, Stéphane Barete 10 , MD, PhD, Khê Hoang-Xuan 9 , MD, PhD, Zahir Amoura 1,2 , MD, MSc and Julien Haroche 1,2 , MD, PhD 1. AP-HP, Internal Medicine Department 2, Pitié-Salpêtrière Hospital, French National Centre for Rare Systemic Diseases, Paris-75013, France 2. Paris VI University, UPMC, Sorbonne Universités, Paris-75013, France 3. EA4340, Versailles University, & AP-HP, Ambroise Paré Hospital, Pathology Department, Boulogne, France 4. INSERM U1136, Pierre-Louis Institute Epidemiology and Public Health, Paris-75012, France and AP-HP, Public Health Department, Saint-Antoine Hospital, Paris-75012, France 5. AP-HP, Pathology Department, Pitié-Salpêtrière Hospital, Paris-75013, France 6. AP-HP, Pharmacy Department, Pitié-Salpêtrière Hospital, Paris-75013, France 7. AP-HP, Haematology Department, Trousseau Hospital, Paris-75012, France 8. AP-HP, Nuclear Medicine Department, Pitié-Salpêtrière Hospital, Paris-75013, France 9. AP-HP, Neurology Department, Pitié-Salpêtrière Hospital, Paris-75013, France 10. AP-HP, Dermatology Unit, Pitié-Salpêtrière Hospital, Paris-75013, France
The detection of magnetotactic bacteria in deep sea sediments from the east Pacific Manganese Nodule Province.

Magnetotactic bacteria (MTB) are distributed ubiquitously in sediments from coastal environments to the deep sea. The Pacific Manganese Nodule Province contains numerous polymetallic nodules mainly composed of manganese, iron, cobalt, copper and nickel. In the present study we used Illumina MiSeq sequencing technology to assess the communities of putative MTB in deep sea surface sediments at nine stations in the east Pacific Manganese Nodule Province. A total of 402 sequence reads from MTB were classified into six operational taxonomic units (OTUs). Among these, OTU113 and OTU759 were affiliated with the genus Magnetospira, OTU2224 and OTU2794 were affiliated with the genus Magnetococcus and Magnetovibrio, respectively, OTU3017 had no known genus affiliation, and OTU2556 was most similar to Candidatus Magnetananas. Interestingly, OTU759 was widely distributed, occurring at all study sites. Magnetism measurements revealed that all sediments were dominated by low coercivity, non-interacting single domain magnetic minerals. Transmission electron microscopy confirmed that the magnetic minerals were magnetosomes. Our data suggest that diverse putative MTB are widely distributed in deep sea surface sediments from the east Pacific Manganese Nodule Province.
A Tailored Intervention for Mammography Among Low-Income African-American Women

Abstract This report describes a tailored intervention to increase compliance regarding mammography and the stage of its adoption among low-income African-American women aged 45 to 64 years. Two randomly assigned groups received either an in-person tailored intervention or routine care. The intervention was targeted toward perceived risk of breast cancer and perceived benefits of and barriers to breast cancer screening. Participants accrued from a community service center were followed for one year to identify the effect of the intervention on adoption of mammography.
Association of circulating TNF‐α and IL‐6 with ageing and parkinsonism

Introduction ‐ We propose that the increase in TNF‐α and IL‐6 in the brain in idiopathic parkinsonism is in response to a peripheral immune/ inflammatory process, so ubiquitous as to be responsible for the resemblance between ageing and parkinsonism. Methods ‐ Circulating cytokine was measured in 78 subjects with idiopathic parkinsonism and 140 without, aged 30 to 90 years, all obeying inclusion/exclusion criteria. Results ‐ Serum TNF‐α increased (P<0.0001) by 1.37 (95% CI 0.75, 2.00) %‐y‐1, IL‐6 by 2.63 (1.75, 3.52) (P<0.0005). TNF‐α appeared elevated in parkinsonians whose postural and psychomotor responses were abnormal, being suppressed where they were normal: trends which contrasted with those in controls (P=0.015 and 0.05, respectively). Parkinsonism appeared (P=0.08) to have an effect on IL‐6, equivalent to that of >10 years of ageing (28(‐3, 69)%), but was not immediately related to between‐subject differences in performance. Conclusion ‐Ageing and pathogenetic insult may be confounded, age being a progression, not a risk, factor.
GERIATRIC KNOWLEDGE AND EDUCATIONAL NEEDS AMONG RURAL HEALTH CARE PROFESSIONALS

Geriatrics has only recently been incorporated into the health science curriculum and, consequently, students continue to graduate with little or no formal training in this area. A survey of 84 rural health care professionals was conducted to determine their geriatric knowledge, their educational needs, and their preferred venue for continuing education. A variety of health care professions was represented in the sample, with the greatest representation from physicians (44%), pharmacists (15%), and nurses (14%). Approximately 39% of the sample reported above average knowledge in geriatrics and 64% indicated that they were interested in learning more about geriatrics. The three most common geriatric areas respondents were interested in included Alzheimer's disease/dementia, medication use/polypharmacy, and adverse medication events. The most preferred training materials included videotapes and CD-ROM courses, and preferred venues of educational activities were in the community or region. An interdisciplinary approach to geriatric care is the preferred method of care. In order to provide better care to the aging population, continuing medical educational opportunities in geriatrics for practicing health care professionals in rural areas need to increase and the curriculum of all health care professional students should include a sufficient geriatric component.
Hacking the stem cell niche.

In this issue of Blood , Stoddart et al think outside of the stem cell “box” to identify a therapeutically tractable pathway in del(5q) myelodysplastic syndrome (MDS), through blocking pathologically activated Wnt signaling arising within the stem cell niche. 1
Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial.

Primary chronic cold agglutinin disease (CAD) is a well-defined clinicopathologic entity in which a bone marrow clonal B-cell lymphoproliferation results in autoimmune hemolytic anemia and cold-induced circulatory symptoms. Rituximab monotherapy and fludarabine-rituximab in combination are documented treatment options. In a prospective, nonrandomized multicenter trial, 45 eligible patients received rituximab 375 mg/m2 day 1 and bendamustine 90 mg/m2 days 1 and 2 for 4 cycles at a 28-day interval. Thirty-two patients (71%) responded; 18 (40%) achieved complete response (CR) and 14 (31%) partial response (PR). Among 14 patients previously treated with rituximab or fludarabine-rituximab, 7 (50%) responded to bendamustine-rituximab (3 CR and 4 PR). Hemoglobin levels increased by a median of 4.4 g/dL in the complete responders, 3.9 g/dL in those achieving PR, and 3.7 g/dL in the whole cohort. The 10th percentile of response duration was not reached after 32 months. Grade 3-4 neutropenia occurred in 15 patients (33%), but only 5 (11%) experienced infection with or without neutropenia. Thirteen patients (29%) had their dose of bendamustine reduced. In conclusion, bendamustine-rituximab combination therapy is highly efficient, sufficiently safe, and may be considered in first line for patients with CAD requiring therapy. The trial was registered at www.clinicaltrials. gov as #NCT02689986.
Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th1 or Th0 profile dominated by interferon gamma.

Coeliac disease is precipitated in susceptible subjects by ingestion of wheat gluten or gluten related prolamins from some other cereals. The disease is strongly associated with certain HLA-DQ heterodimers, for example, DQ2 (DQ alpha 1*0501, beta 1*0201) in most patients and apparently DQ8 (DQ alpha 1*0301, beta 1*0302) in a small subset. Gluten specific T cell clones (TCC) from coeliac intestinal lesions were recently established and found to be mainly restricted by HLA-DQ2 or HLA-DQ8. Antigen induced production of cytokines was studied in 15 TCC from three patients, 10 being DQ2 and five DQ8 restricted. Cell culture supernatants were prepared by stimulation with gluten peptides in the presence of DQ2+ or DQ8+ Epstein-Barr virus transformed B cells as antigen presenting cells (APC). Supernatants were analysed for cytokines by bioassays, ELISA, and CELISA. Cellular cytokine mRNA was analysed semi-quantitatively by slot blotting and polymerase chain reaction (PCR). All TCC were found to secrete interferon (IFN) gamma, often at high concentrations (> 2000 U/ml); some secreted in addition interleukin (IL) 4, IL 5, IL 6, IL 10, tumour necrosis factor (TNF), and transforming growth factor (TGF) beta. The last TCC thus displayed a Th0-like cytokine pattern. However, other TCC produced IFN gamma and TNF but no IL 4, or IL 5, compatible with a Th1-like pattern. In conclusion, most DQ8 restricted TCC seemed to fit with a Th0 profile whereas the DQ2 restricted TCC secreted cytokines more compatible with a Th1 pattern. The TCC supernatants induced upregulation of HLA-DR and secretory component (poly-Ig receptor) in the colonic adenocarcinoma cell line HT-29.E10, most probably reflecting mainly the high IFN gamma concentrations. This cytokine, particularly in combination with TNF alpha, might be involved in several pathological features of the coeliac lesion. The characterised cytokine profiles thus support the notion that mucosal T cells activated in situ by gluten in a DQ restricted fashion play a central part in the pathogenesis of coeliac disease.