tbuckley/cabot-search huggingface dataset:
Specific T cells for the treatment of cytomegalovirus and/or adenovirus in the context of hematopoietic stem cell transplantation
Authors: Rita Creidy, Despina Moshous, Fabien Touzot, Caroline Elie, Bénédicte Neven, Aurélie Gabrion, Marianne Leruez-Ville, Sébastien Maury, Brigitte Ternaux, Jennifer Nisoy, Jean-Marc Luby, Sébastien Héritier, Jean-Hugues Dalle, Marie Ouachée-Chardin, Aliénor Xhaard, Xavier Thomas, Patrice Chevallier, Laetitia Souchet, Jean-Marc Treluyer, Capucine Picard, Salima Hacein-Bey-Abina, Liliane Dal Cortivo, Stéphane Blanche, Marina Cavazzana
Journal: Journal of Allergy and Clinical Immunology (2016)

Viral infections following allogeneic hematopoietic stem cell transplantation (HSCT) are associated with elevated morbidity and mortality rates because HSCT exposes patients to a transient state of profound T- and B-cell immunodeficiency. Most post-HSCT viral infections are caused by the endogenous reactivation of opportunistic pathogens such as adenovirus (ADV), cytomegalovirus (CMV), and EBV.1 The risk of mortality associated with these viral infections is directly proportional to (1) the degree of HLA mismatch between the donor and the recipient and (2) the time of T-cell reconstitution.
Tuning Cell Differentiation into a 3D Scaffold Presenting a Pore Shape Gradient for Osteochondral Regeneration
Authors: Andrea Di Luca, Ivan Lorenzo‐Moldero, Carlos Mota, Antonio Lepedda, Dietmar Auhl, Clemens Van Blitterswijk, Lorenzo Moroni
Journal: Advanced Healthcare Materials (2016)

Osteochondral regeneration remains nowadays a major problem since the outcome of current techniques is not satisfactory in terms of functional tissue formation and development. A possible solution is the combination of human mesenchymal stem cells (hMSCs) with additive manufacturing technologies to fabricate scaffolds with instructive properties. In this study, the differentiation of hMSCs within a scaffold presenting a gradient in pore shape is presented. The variation in pore shape is determined by varying the angle formed by the fibers of two consequent layers. The fiber deposition patterns are 0-90, which generate squared pores, 0-45, 0-30, and 0-15, that generate rhomboidal pores with an increasing major axis as the deposition angle decreases. Within the gradient construct, squared pores support a better chondrogenic differentiation whereas cells residing in the rhomboidal pores display a better osteogenic differentiation. When cultured under osteochondral conditions the trend in both osteogenic and chondrogenic markers is maintained. Engineering the pore shape, thus creating axial gradients in structural properties, seems to be an instructive strategy to fabricate functional 3D scaffolds that are able to influence hMSCs differentiation for osteochondral tissue regeneration.
Sparse data bias: a problem hiding in plain sight
Authors: Sander Greenland, Mohammad Ali Mansournia, Douglas G Altman
Journal: BMJ (2016)

Effects of treatment or other exposure on outcome events are commonly measured by ratios of risks, rates, or odds. Adjusted versions of these measures are usually estimated by maximum likelihood regression (eg, logistic, Poisson, or Cox modelling). But resulting estimates of effect measures can have serious bias when the data lack adequate case numbers for some combination of exposure and outcome levels. This bias can occur even in quite large datasets and is hence often termed sparse data bias. The bias can arise or be worsened by regression adjustment for potentially confounding variables; in the extreme, the resulting estimates could be impossibly huge or even infinite values that are meaningless artefacts of data sparsity. Such estimate inflation might be obvious in light of background information, but is rarely noted let alone accounted for in research reports. We outline simple methods for detecting and dealing with the problem focusing especially on penalised estimation, which can be easily performed with common software packages.
The impact of FDG PET in the staging of breast cancer
Authors: C. E. Carr, E. F. Conant, M. A. Rosen, M. D. Schnall, R. Davidson
Journal: Journal of Clinical Oncology (2006)

530 Background: To evaluate the impact of whole-body fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in staging breast cancer beyond the breast and axilla. Methods: 200 women, mean age 51 yrs (range 28–81) with breast cancer were enrolled in an IRB approved multi-modality imaging trial from 3/02 to 5/05. After imaging with film screen mammography ± ultrasound (US), patients underwent digital mammography, whole breast US, magnetic resonance imaging (MRI), and whole body FDG PET. Imaging reports and patient charts were reviewed and distant lesions were classified: 1 = no uptake; 2 = physiologic uptake; 3 = non-suspicious uptake; 4 = suspicious uptake without work-up; 5 = suspicious uptake with work-up. Decisions to forego work-up in class 4 lesions were clinical. Class 5 PET lesions were evaluated by confirmatory studies, including computed tomography (CT), MRI, x-ray (XR), bone scan (BS), or pathology. Patients also underwent standard staging with chest XR and BS per clinical judgment. Results: 189/200 (95%) women received PET scans. PET identified 71 distant areas of increased uptake in 42/189 (22%) women. 59/71 (83%) lesions were considered suspicious in 33/42 (79%) women: 50/59 (85%) lesions were class 5 and 9/59 (15%) class 4. Of the 50 class 5 lesions, 19 (38%) were true positive (TP) for neoplastic disease, 2 (4%) were TP for non-neoplastic disease, and 29 (58%) were false positive (FP). The positive predictive value (PPV) for class 5 lesions was 40%. The 19 TP distant sites of malignancy occurred in 6/189 (3%) patients; 4 of these patients (67%) also had TP distant sites identified by standard staging procedures. PET alone identified TP distant disease in 2/189 (1%) women. PET identified 29 FP findings in 22/189 (12%) patients. FP findings prompted 17 CTs, 8 XRs, 2 MRIs, and 1 BS. MRI revealed 2 additional neoplasms that had been false negatives (FN) by PET in 2/189 (1%) women. Conclusions: Whole-body FDG-PET added little additional information in staging our patients with known primary breast cancer, based on low PPV and equivalent TP and FN rates. Additionally, the high FP rate of PET in these patients may prompt unnecessary, costly, and invasive follow-up studies. No significant financial relationships to disclose.
Biliary tract intraductal papillary mucinous neoplasm: single-operator cholangioscopy and clearance of mucin obstruction
Authors: Tomazo Franzini, Renata Moura, Silvia de Lima, Gustavo Rodela, Frederico Teixeira, Humberto Kishi, Eduardo de Moura
Journal: Endoscopy (2016)

Biliary tract intraductal papillary mucinous neoplasm (BT-IPMNs) are the counterparts of pancreatic IPMNs, and are characterized as papillary lesions that produce mucin and spread along the biliary mucosa causing obstructive jaundice [1]. These tumors can develop anywhere along the biliary tree, and are considered to be premalignant lesions [2]. We report a case of a BT-IPMN diagnosed by cholangioscopy-guided biopsy, and a novel technique of clearing the biliary tree with a mucolytic solution.
Image Gallery: Dermatologic and retinal manifestations of pseudoxanthoma elasticum
Authors: D. Gologorsky, N.Z. Gregori, R. Goldhardt
Journal: British Journal of Dermatology (2016)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 55‐year‐old woman presented to the ophthalmology clinic to establish care. Her past medical history was significant for pseudoxanthoma elasticum, diagnosed 30 years earlier. Physical examination was notable for (A) a prominent mental crease, (B) yellow waxy papules associated with loose and thickened skin in the neck, (C) axilla, (D) antecubital fossa, and groin area. Dilated funduscopic examination revealed characteristic angioid streaks and a classic peau d'orange pattern in both the (E) right and (F) left eyes without any choroidal nonvascular membranes.
Gene Therapy for Coagulation Disorders
Authors: Laura L. Swystun, David Lillicrap
Journal: Circulation Research (2016)

Molecular genetic details of the human coagulation system were among the first successes of the genetic revolution in the 1980s. This information led to new molecular diagnostic strategies for inherited disorders of hemostasis and the development of recombinant clotting factors for the treatment of the common inherited bleeding disorders. A longer term goal of this knowledge has been the establishment of gene transfer to provide continuing access to missing or defective hemostatic proteins. Because of the relative infrequency of inherited coagulation factor disorders and the availability of safe and effective alternative means of management, the application of gene therapy for these conditions has been slow to realize clinical application. Nevertheless, the tools for effective and safe gene transfer are now much improved, and we have started to see examples of clinical gene therapy successes. Leading the way has been the use of adeno-associated virus-based strategies for factor IX gene transfer in hemophilia B. Several small phase 1/2 clinical studies using this approach have shown prolonged expression of therapeutically beneficial levels of factor IX. Nevertheless, before the application of gene therapy for coagulation disorders becomes widespread, several obstacles need to be overcome. Immunologic responses to the vector and transgenic protein need to be mitigated, and production strategies for clinical grade vectors require enhancements. There is little doubt that with the development of more efficient and facile strategies for genome editing and the application of other nucleic acid-based approaches to influence the coagulation system, the future of genetic therapies for hemostasis is bright.
Hybrid Polycaprolactone/Alginate Scaffolds Functionalized with VEGF to Promote de Novo Vessel Formation for the Transplantation of Islets of Langerhans
Authors: Giulia Marchioli, Andrea Di Luca, Eelco de Koning, Marten Engelse, Clemens A. Van Blitterswijk, Marcel Karperien, Aart A. Van Apeldoorn, Lorenzo Moroni
Journal: Advanced Healthcare Materials (2016)

Although regarded as a promising treatment for type 1 diabetes, clinical islet transplantation in the portal vein is still hindered by a low transplantation outcome. Alternative transplantation sites have been proposed, but the survival of extra-hepatically transplanted islets of Langerhans critically depends on quick revascularization after engraftment. This study aims at developing a new 3D scaffold platform that can actively boost vascularization and may find an application for extra-hepatic islet transplantation. The construct consists of a 3D ring-shaped polycaprolactone (PCL) scaffold with heparinized surface to electrostatically bind vascular endothelial growth factor (VEGF), surrounding a hydrogel core for islets encapsulation. Heparin immobilization improves the amount of VEGF retained by the construct, up to 3.6 fold, compared to untreated PCL scaffolds. In a chicken chorioallanthoic membrane model, VEGF immobilized on the construct enhances angiogenesis in close proximity and on the surface of the scaffolds. After 7 days, islets encapsulated in the alginate core show functional response to glucose stimuli comparable to free-floating islets. Thus, the developed platform has the potential to support rapid vascularization and islet endocrine function.
Francis Anthony Almond
Authors: Janet Almond, Katie Leslie, Patricia Bell
Journal: BMJ (2016)

Francis Anthony Almond (“Frank”) was a Lancashire man and proud of it. He was born in Lower Darwen near Blackburn, and grew up in Blackpool, but he chose London to pursue his ambition to study medicine. His first three years at Barts were spent at Queens’ College in Cambridge, where the preclinical school had remained evacuated since the war. Frank’s years as a clinical student and on the house were spent at Hill End and Barts. While administering an anaesthetic he was told off by the nurse in charge for resting his feet on her clean trolley. Romance blossomed, and Diana soon became the love of his life. They married in 1954.

After training at Netley Hospital, Southampton, and within weeks of marrying Diana, Frank was …
Factors associated with change in radiographic damage scores in gout: a prospective observational study
Authors: Alastair Eason, Meaghan E House, Zoe Vincent, Julie Knight, Paul Tan, Anne Horne, Gregory D Gamble, Anthony J Doyle, William J Taylor, Nicola Dalbeth
Journal: Annals of the Rheumatic Diseases (2016)

Background/aims Radiographic damage is frequently observed in patients with longstanding gout. The aim of this prospective observational study was to determine factors associated with change in radiographic damage scores in gout. Methods People with gout and disease duration &lt;10 years were recruited into this prospective observational study. At the baseline visit, structured assessment was undertaken in 290 participants including detailed clinical examination and plain radiographs (XR) of the hands and feet. Participants were invited to attend a further study visit with repeat XR 3 years after the baseline visit. XR were scored for erosion and joint space narrowing according to the gout-modified Sharp/van der Heijde XR damage score. Results Age, subcutaneous tophus count and tender joint count were independently associated with XR damage score at the baseline visit. Paired serial XR were available for 140 participants. In stepwise linear regression analysis, change in total damage score over 3 years was positively associated with change in subcutaneous tophus count and baseline XR damage score, and inversely associated with baseline subcutaneous tophus count (model R 2 =0.39, p&lt;0.001). Change in subcutaneous tophus count contributed most to the change in erosion score (partial R 2 change=0.31, p&lt;0.001), and baseline XR damage score contributed most to the change in narrowing score (partial R 2 change=0.31, p&lt;0.001). Conclusions Development of new subcutaneous tophi and baseline radiographic damage are associated with progressive joint damage scores in people with gout. These data provide further evidence that the tophus plays a central role in bone erosion in gout.
Up-Regulation of Long Non-Coding RNA <i>TUG1</i> in Hibernating Thirteen-Lined Ground Squirrels
Authors: Jacques J. Frigault, Daneck Lang-Ouellette, Pier Jr. Morin
Journal: Genomics Proteomics & Bioinformatics (2016)

Abstract Mammalian hibernation is associated with multiple physiological, biochemical, and molecular changes that allow animals to endure colder temperatures. We hypothesize that long non-coding RNAs (lncRNAs), a group of non-coding transcripts with diverse functions, are differentially expressed during hibernation. In this study, expression levels of lncRNAsH19 and TUG1 were assessed via qRT-PCR in liver, heart, and skeletal muscle tissues of the hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus). TUG1 transcript levels were significantly elevated 1.94-fold in skeletal muscle of hibernating animals when compared with euthermic animals. Furthermore, transcript levels of HSF2 also increased 2.44-fold in the skeletal muscle in hibernating animals. HSF2 encodes a transcription factor that can be negatively regulated by TUG1 levels and that influences heat shock protein expression. Thus, these observations support the differential expression of the TUG1–HSF2 axis during hibernation. To our knowledge, this study provides the first evidence for differential expression of lncRNAs in torpid ground squirrels, adding lncRNAs as another group of transcripts modulated in this mammalian species during hibernation.
Laterally spreading tumor through the magnifying glass: we only see what we know
Authors: Silvia Sanduleanu, Peter Siersema
Journal: Endoscopy (2016)

The practice of high-quality colonoscopy has changed the natural history of colorectal cancer (CRC), with CRC and its precursors being diagnosed at earlier stages at which curative endoscopic resection is the preferred therapy. Both CRC incidence and mortality continue to decline. Assuming such favorable time trends, why, then, has the post-colonoscopy CRC rate remained unchanged [1] [2]? One reason is that approximately one in five post-colonoscopy CRCs still results from incomplete polyp resection [3]. A subgroup of precursor lesions of CRC includes colorectal laterally spreading tumors (LSTs), which are associated with a high risk of malignancy. Performing endotherapy on these lesions is technically challenging, leading to incomplete resection and local recurrence. LSTs have only recently been recognized in Western countries [4] [5], and many questions on their endoscopic characteristics, histological diagnosis, and optimal treatment remain unanswered [6].
Sixty seconds on . . . placing GPs in hospital emergency departments
Authors: Nigel Hawkes
Journal: BMJ (2016)

Tsk! Patients are never wrong. The service has to adjust to what they want, not vice versa.

Good idea, on the face of it. The Royal College of Emergency Medicine backed it in a 2014 report, and the college’s president, Clifford Mann, called the argument “compelling.”1 Many emergency departments have followed the advice. …
Abstract 13319: Distinct Mechanism of Lidocaine Interaction With the DIII Voltage Sensor of the Cardiac Sodium Channel
Authors: Zoltan Varga, Alexandra B Asaro, Angela R Schubert, Jonathan R Silva
Journal: Circulation (2013)

Background: The human voltage-gated Na+ channel, hNaV1.5, which initiates the cardiac action potential, can be formed by monomeric α subunits containing 4 domains (DI-DIV), each with 6 membrane-spa...
Increased Circulating Colony-Stimulating Factor-1 (CSF-1) in SJL/J Mice With Radiation-Induced Acute Myeloid Leukemia (AML) Is Associated With Autocrine Regulation of AML Cells by CSF-1
Authors: Nechama Haran-Ghera, Rita Krautghamer, Tsvee Lapidot, Alpha Peled, Melissa G. Dominguez, E. Richard Stanley
Journal: Blood (1997)
Microvascular Ischemia in Patients With Myotonic Dystrophy
Authors: Hideki Itoh, Masami Shimizu, Yuki Horita, Hidekazu Ino, Tomio Taguchi, Kouji Kajinami, Kunimasa Yagi, Daisuke Chujo, Hiroshi Mabuchi
Journal: Circulation (2000)

Two women with myotonic dystrophy underwent dipyridamole thallium-201 ( 201 T1) myocardial perfusion imaging, after which one patient developed flat T waves in lead I and aVL, and inverted T waves in leads V 2-6 , The other patient developed a nonspecific intraventricular block that progressed to complete left bundle branch block and was associated with chest discomfort. Reversible scintigraphic defects were observed in both women. Although there was evidence that suggested myocardial ischemia on the ECG changes and  201 T1 scintigraphic findings, coronary angiography demonstrated no significant stenoses in either patient. These findings suggest that microvascular dysfunction may lead to myocardial ischemia and conduction disturbances in patients with myotonic dystrophy.
Conditional survival for patients with colon cancer: An analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) trials C-03 through C-06
Authors: S. J. Wang, B. A. Zamboni, H. S. Wieand, G. Yothers, J. J. Dignam, P. C. Raich, M. J. O’Connell, N. Wolmark, C. R. Thomas
Journal: Journal of Clinical Oncology (2006)

6005 Background: Survival for cancer patients is usually only reported as survival from time of diagnosis to some time landmark (e.g., 5 yrs). For pts surviving one or more years after diagnosis, however, their survival probability changes, and is more accurately depicted by conditional survival (CS), defined as the probability of surviving for an additional fixed time interval given that the pt has already survived a period of time. The purpose of this study was to determine the 5-yr CS of colon cancer pts in 4 NSABP trials. Methods: We analyzed long-term overall survival data from the 5587 colon cancer pts who were enrolled in fluorouracil (or equivalent) arms of NSABP trials C-03 through C-06. We computed observed 5-yr overall CS for pts who had already survived without disease from 0 to 5 yrs after diagnosis, and stratified the results by age, sex, race, stage, number of positive nodes, number of nodes resected, tumor location, and performance status. Results: The Table below shows the 5-yr overall CS for all pts and for selected subgroups for different survival times since diagnosis. As disease-free survival time since diagnosis increased, 5-yr observed overall CS increased from 76% to 90% at 5 yrs. For pts under age 50, CS increased from 78% to 95% at 5 yrs, but for pts &gt; 70 yrs, CS remained fairly constant (71–82%). For pts with &gt; 10 positive nodes, CS increased from 37% to 81% at 5 yrs, but did not change appreciably for node-negative pts (87–92%). Dukes’ C pts saw an increase in CS from 68% to 88% at 5 yrs, while CS for Dukes’ B pts did not change appreciably. Conclusion: Projected survival probability generally increases with time for colon cancer pts who remain disease-free for a period of time after diagnosis, and conditional survival can provide more informative prognostic information for these pts. An additional effect is that prognostic factors that are important at baseline become less important for conditional survival as the disease-free period increases. [Table: see text] No significant financial relationships to disclose.
Soundings: Me and Mrs Jones
Authors: Liam Farrell
Journal: BMJ (2005)

When I woke up in the morning she'd be lying there beside me, golden hair cascading on the pillow, white founts falling in the courts of the sun, eyes as blue as cornflowers, her pearl-pale hand in mine. We were children of the 1960s, Woodstock, Janis Joplin, Country Joe and the Fish, the summer of peace, love, and rock'n'roll.

We had to be discreet, of course, but, in those days we were a united profession and we had plenty of opportunities to be together. The BMA meetings were a regular forum for general practitioners and consultants to meet and get to know and understand each other, to exchange views, to network.

I used to visit the hospital every week, to see how my patients were getting on, and to snatch a moment of privacy and perhaps a soft but eager kiss in her office. Best of all, I'd often request a domiciliary consultation, and we'd spend a golden afternoon driving through the countryside and kicking through the leaves; we'd put Harry Chapin and Marvin Gaye on the stereo and picnic out in Lincoln Park.

We weren't abusing the system; the domiciliary consultation is the only opportunity in the NHS for general practitioners and consultants to jointly examine a patient and jointly decide on the most appropriate management. The specialist and the generalist, slender yang to my sturdy yin, what a combination of skills and disciplines we were; who could have possibly have suspected that we had a thing going on?

Times change, as feelings do. General practitioners and consultants slowly became more remote, our opportunities grew more limited, and as our jobs grew apart so did we. The BMA meetings became less congenial. More consultants came to work in her hospital, she had to share an office. My practice got bigger, I had no more time for hospital rounds. She became a subspecialist, I a managing partner. She knew more and more about less and less, I knew less and less about more and more, and our last cold goodbye was between strangers.

But there is still love left in the world, and when she rang me this morning I felt my heart go pippity-pop at the sound of her voice, just like the old days.

“I've been invited to go on Jerry Springer,” she said “and I would like you to come along, and bring your dog.”