tbuckley/cabot-search huggingface dataset:
NKG2D signaling certifies effector CD8 T cells for memory formation
Authors: Cynthia Perez, Kushal Prajapati, Brianna Burke, Lourdes Plaza-Rojas, Nancy J. Zeleznik-Le, Jose A. Guevara-Patino
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> The development of memory responses is an evolutionary function of the adaptive immune system. We propose that for the immune system to populate the memory compartment with the best-suited CD8 T cells it utilizes a process of certification or molecular accreditation mediated through Natural Killer Group 2D (NKG2D). This process of certification assures that the memory compartment is filled with CD8 T cells that have demonstrated their ability to kill their cognate targets through a two-step process that utilizes T cell receptor (TCR) and NKG2D signaling. <h3>Methods</h3> One week after immunization with peptide-pulsed dendritic cells, NKG2D signaling was transiently blocked in vivo with a single injection of neutralizing antibodies. Under such conditions, we determined the importance of NKG2D signaling during the effector phase for memory formation without compromising NKG2D signaling at the memory phase<b>.</b> Both open (polyclonal) and closed (monoclonal) CD8 T cell repertoires were studied. <h3>Results</h3> We show that signaling through NKG2D mediated this certification. Temporary blockade of NKG2D signaling during the effector phase resulted in the formation of highly defective memory CD8 T cells characterized by altered expression of the ribosomal protein S6 and epigenetic modifiers, suggesting modifications in the T cell translational machinery and epigenetic programming. Finally, these uncertified memory cells were not protective against a B16 tumor challenge. <h3>Conclusion</h3> Signaling through NKG2D during the effector phase (certification) favors the development of functional memory CD8 T cells, a previously undescribed role for NKG2D. Temporary blockade of NKG2D signaling during the effector phase results in the formation of highly defective memory CD8 T cells potentially by affecting the expression of the ribosomal protein S6 and epigenetic modifiers, suggesting alterations in T cell translational machinery and epigenetic programming.
Perspectives on Conversations About Costs of Cancer Care of Breast Cancer Survivors and Cancer Center Staff
Authors: Maria Pisu, Yu-Mei Schoenberger, Ivan Herbey, Aquila Brown-Galvan, Margaret I. Liang, Kevin Riggs, Karen Meneses
Journal: Annals of Internal Medicine (2019)

Background: Despite recommendations to discuss the cost of care (CoC) with patients with cancer, little formal guidance is available on how to conduct these sensitive conversations in ways that are acceptable to both patients and providers. Objective: To explore the perspectives of patients and medical and nonmedical cancer center staff on CoC conversations. Design: In individual interviews, participants were asked to discuss the content of, timing of, and ideal person to hold CoC conversations. Interviews were transcribed verbatim. Content was analyzed to identify emerging essential elements. Setting: Division of Preventive Medicine, University of Alabama at Birmingham. Participants: 42 women aged 60 to 79 years with a history of breast cancer and 20 cancer center staff (6 physicians, 4 nurses, 5 patient navigators, 3 social workers, and 2 billing specialists). Results: Both patients and providers identified reassurance and action as essential elements of CoC conversations. Participants expressed the importance of reassurance that recommended medical care would not be affected by affordability challenges. Action was intended as discussions on ways to help patients cover treatment-related costs, such as discussion of payment plans or linkage to financial resources. Optimal timing for CoC conversations was felt to be after an initial consult visit but before treatment started. The person to hold these conversations should be compassionate, helpful, and knowledgeable of the patient's specific situation (for example, treatment plan, insurance coverage) and of the resources available to attain the patient's goals of care. Limitation: Interviews were limited to older breast cancer survivors and staff at 1 institution. Conclusion: Conversations about CoC extend beyond discussing costs and must be sensitive to the vulnerability experienced by patients. These findings can guide training of personnel involved in CoC conversations. Primary Funding Source: Robert Wood Johnson Foundation.
West goes East
Authors: Delilah Khan, Jiawei Liao
Journal: BMJ (2005)

When medical student, Lisa Teoh, discovered her family still owned their ancestral home in China, she decided that the building should be used by the local community. It9s now the base for a cultural exchange between British and Chinese medical students. <b>Delilah Khan</b> and <b>Jiawei Liao</b> explain
Students' union launches new writing award on mental health
Authors: Rhona MacDonald
Journal: BMJ (2001)

The National Union of Students (NUS) has announced an innovative award to be given for the positive portrayal of people with mental health problems.

One in four people will be affected by mental health problems during the course of a year, yet discrimination is still rife, particularly in the media where negative stereotypes and derogatory language are often used. “Tomorrow's Minds” research conducted by Opinion Leader Research showed that among young …
Risk of surgery for inflammatory bowel disease: record linkage studies
Authors: Leanne Tite
Journal: BMJ (2008)

### This month's paper

“Mortality in patients with and without colectomy admitted to hospital for ulcerative colitis and Crohn's disease: record linkage studies” by Stephen E Roberts and colleagues ( BMJ 2007;335:1033-6; doi: 10.1136/bmj.39345.714039.55).

#### Abstract

Inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis, is a debilitating and sometimes life threatening disease that affects about 250,000 people in the United Kingdom. Since the 1950s Crohn's disease has become more common. Each year 2000 colectomies are performed to treat inflammatory bowel disease, with varying risk depending on …
Japan's unhealthy use of “herbal” weight loss pills
Authors: Mitesh Desai
Journal: BMJ (2002)

The Japanese health minister, Chikara Sakaguchi, has called for tighter regulations on the Chinese industries for pharmaceuticals and herbal remedies after a recent spate of deaths.

The Japanese media have reported that in the past two years, four deaths and 148 cases of thyroid and liver problems have been linked with the consumption of Chinese “herbal” weight loss pills.

The ministry is concerned that the grey area between the regulatory …
Selective EGLN Inhibition Enables Ablative Radiotherapy and Improves Survival in Unresectable Pancreatic Cancer
Authors: Tara N. Fujimoto, Lauren E. Colbert, Yanqing Huang, Jessica M. Molkentine, Amit Deorukhkar, Laura Baseler, Marimar de la Cruz Bonilla, Meifang Yu, Daniel Lin, Sonal Gupta, Peter K. Cabeceiras, Charles V. Kingsley, Ramesh C. Tailor, Gabriel O. Sawakuchi, Eugene J. Koay, Helen Piwnica-Worms, Anirban Maitra, Cullen M. Taniguchi
Journal: Cancer Research (2019)

Abstract When pancreatic cancer cannot be removed surgically, patients frequently experience morbidity and death from progression of their primary tumor. Radiation therapy (RT) cannot yet substitute for an operation because radiation causes fatal bleeding and ulceration of the nearby stomach and intestines before achieving tumor control. There are no FDA-approved medications that prevent or reduce radiation-induced gastrointestinal injury. Here, we overcome this fundamental problem of anatomy and biology with the use of the oral EGLN inhibitor FG-4592, which selectively protects the intestinal tract from radiation toxicity without protecting tumors. A total of 70 KPC mice with autochthonous pancreatic tumors received oral FG-4592 or vehicle control ± ablative RT to a cumulative 75 Gy administered in 15 daily fractions to a limited tumor field. Although ablative RT reduced complications from local tumor progression, fatal gastrointestinal bleeding was observed in 56% of mice that received high-dose RT with vehicle control. However, radiation-induced bleeding was completely ameliorated in mice that received high-dose RT with FG-4592 (0% bleeding, P &amp;lt; 0.0001 compared with vehicle). Furthermore, FG-4592 reduced epithelial apoptosis by half (P = 0.002) and increased intestinal microvessel density by 80% compared with vehicle controls. EGLN inhibition did not stimulate cancer growth, as treatment with FG-4592 alone, or overexpression of HIF2 within KPC tumors independently improved survival. Thus, we provide a proof of concept for the selective protection of the intestinal tract by the EGLN inhibition to enable ablative doses of cytotoxic therapy in unresectable pancreatic cancer by reducing untoward morbidity and death from radiation-induced gastrointestinal bleeding. Significance: Selective protection of the intestinal tract by EGLN inhibition enables potentially definitive doses of radiation therapy. This might allow radiation to be a surgical surrogate for unresectable pancreatic cancer.
The Caribbean islands
Authors: Leonard Yuen
Journal: BMJ (2002)

Leonard Yuen gives a diary account of his tour of the Caribbean and takes a look at the different ophthalmic screening programmes

The Caribbean islands are often seen as a homogeneous tropical destination, but in reality each island has its own distinctive “personality.” Their reputation for warm weather, spectacular scenery, and friendliness have made them a target for holiday makers, and now they are becoming increasingly popular as an elective destination for students wanting to escape the winter months.

Common health problems on the islands are diabetes and hypertension. Diabetic eye disease comes in many forms, including diabetic retinopathy and cataracts, which accounts for 50% of blindness (an estimated 17 million people) worldwide. Many complications can be detected early and treated, so screening programmes for diabetic eye disease are essential.

With this in mind and, after a great deal of time and planning, I arranged to island hop to compare differences in health care and culture. Visiting 13 different islands gave me insight into the impact of politics and the importance of funding and education to establish effective screening and a good healthcare system. It was intriguing to see vast differences among the …
Addressing critical needs in the fight to end tuberculosis with innovative tools and strategies
Authors: Mark Hatherill, Richard E. Chaisson, Claudia M. Denkinger
Journal: PLoS Medicine (2019)

This month in PLOS Medicine we launched a Special Issue on New Tools and Strategies for Tuberculosis Diagnosis, Care, and Elimination. In this issue's Editorial, the Guest Editors Claudia Denkinger, Richard Chaisson, and Mark Hatherill highlight some of the research that will publish and how these studies focusing on discovery, clinical trials and implementation research collectively add to the prospects for reaching the EndTB targets of the WHO by 2035.
Leading problem based learning
Authors: Maria Ahmed, Faizan Ahmed
Journal: BMJ (2007)

You can make or break a session when it's your turn to lead. Maria Ahmed and Faizan Ahmed explain how to succeed COMSTOCKCOMPELETE.COM The widespread introduction of problem based, self directed methods of learning demands a shift in power from the tutor to the student leader of problem based learning (PBL) groups. Chairing a PBL session is no mean task because the student must lead members of a similar age and ability. This must be done considerately to avoid resistance or resentment. So how can you effectively chair a discussion? How can you maintain control and not be drowned out by fellow students or taken over by a dictatorial tutor? Perhaps more importantly, how can you ensure that the session is productive while preserving your reputation as a cool, minimal effort, high attainment student? Pace yourself --Be structured in your approach; follow the PBL process (box 1). Agree on how long to spend on each step and leave room for manoeuvre should the case prove easier or harder to tackle than expected. Don't over-run into lectures or lunch time. Summarise discussions at appropriate points, especially to break up periods of silence, and ensure the group has sufficient time and opportunity to dissect and learn from the case. ### Box 1: PBL tutorial processRETURN TO TEXT
Association of Time From Primary Diagnosis to First Distant Relapse of Metastatic Melanoma With Progression of Disease and Survival
Authors: Anaïs Vallet, Bastien Oriano, Laurent Mortier, Stéphane Dalle, Caroline Dutriaux, Bernard Guillot, Marie-Thérèse Leccia, Sophie Dalac, Philippe Saiag, Jean-Philippe Lacour, Delphine Legoupil, Julie de Quatrebarbes, Florence Brunet-Possenti, Thierry Lesimple, Jean-Philippe Arnault, François Aubin, Florence Granel-Brocard, Pierre-Emmanuel Stoebner, Eve Maubec, Brigitte Dréno, Clara Allayous, Raphael Porcher, Céleste Lebbé
Journal: JAMA Dermatology (2019)

The prognosis of advanced melanoma has been greatly improved by new therapeutic agents and clinicians rely on dynamic signals to drive their therapeutic choices. Although the kinetics of metastatic disease seem to be correlated with survival, progression of the localized disease is not predictable.To assess whether progression of metastatic disease is associated with the time to the first distant recurrence of melanoma.This study was conducted from March 1, 2013, to September 1, 2017, among 638 adults with unresectable stage III or IV melanoma within the French multicentric prospective cohort MelBase. Patients treated with first-line immunotherapies, targeted therapies, or chemotherapy were included. Patients with unknown primary or de novo metastatic melanoma were not included. Data were analyzed from March 1, 2013, to December 1, 2017.The date of primary excision and time to first distant recurrence, progression-free survival, and overall survival were collected. Cox proportional hazards regression models were planned to assess the association between time to first distant recurrence and progression-free survival or overall survival, which was evaluated in terms of hazard ratio (HR). Time to recurrence was analyzed both as a continuous and categorical variable (<12 months, 12-24 months, and >24 months).A total of 638 patients (272 women and 366 men; median age, 64 years [interquartile range, 52-73 years]) were included in the study. The median time from primary excision to first distant recurrence was 25 months (interquartile range, 12-55 months). There was no evidence of association of the time to recurrence with progression-free survival, both when analyzed as a continuous variable (HR, 0.99; 95% CI, 0.99-1.01) or after categorization (12-24 months: HR, 0.75; 95% CI, 0.56-1.02; >24 months: HR, 0.62; 95% CI; 0.47-1.01). There was no evidence of association of the time to recurrence with overall survival, both when analyzed as a continuous variable (HR, 0.99; 95% CI, 0.98-1.02) or after categorization (12-24 months: HR, 0.76; 95% CI, 0.54-1.07; >24 months: HR, 0.61; 95% CI, 0.54-1.03). Those results remained nonsignificant after stratification by treatment.In the MelBase cohort, time to recurrence of metastatic melanoma appears not to be associated with progression-free survival or overall survival.
Defer fees and restore grants, says Scottish inquiry
Authors: Amina Hussain
Journal: BMJ (2000)

Payment of tuition fees should be deferred, and grants should be reintroduced. These are the main findings of a Scottish inquiry into student finance, chaired by Sir Andrew Cubie. The recommendations laid out in the report, published on 21 December 1999, would require a package of financial measures from the Scottish Executive to the tune of an additional £63m.

The proposals would mean that once the income of graduates reaches £25 000 per year or more, they will be expected to contribute an overall total of £3075 to a planned education fund, irrespective of their degree course. This would be index linked to …
Objective structured clinical examination
Authors: Carl Morris
Journal: BMJ (2001)

“OSCE, schmOSCE,” that's what I say. Structured? Well yes, there's the buzzer that goes off every five minutes, usually just as you're saying “now, if we could move on to your main problem.” Objective? Hmmm, sort of. The examiners all have those lists of check boxes to tick off as you flounder away. As long as you are one of the early …
Less cannulation and more caring
Authors: Katie Wright
Journal: BMJ (1999)

How did I get to be a final year student already? Where did the past four years go? And how did I manage to retain such a pathetic amount of information and forget so much? It's now or never - I feel that there is a lot of stuff to be learnt before I could ever be a doctor. I throw myself into the deep end with a rotation in the accident and emergency department of a district general hospital in Yorkshire, something of a shock after my sun drenched elective. The pace could be fast and furious, with a rapid turnover of patients and an incredible diversity. From someone with a head injury, to a little boy with …
Sex law criminalises agony aunts
Authors: Stephen Goldie
Journal: BMJ (2003)

A new law going through parliament could result in agony aunts who give advice to teenagers being liable to prosecution. Last minute amendments to prevent this have been rejected by the House of Lords.

The Sexual Offences Bill was written in an attempt to modernise the law and tackle paedophiles who “groom” young children in internet chat rooms. The need for change was highlighted by a recent case in which a 36 year old man persuaded two 13 year olds to meet him for sex, having chatted to them online.



Due to the indiscriminate wording of the bill, however, anyone who “communicates with a child” about sex, or “causes or incites another …
Milk substitute marketing violation persist
Authors: Susan Mayor
Journal: BMJ (2004)

Many manufacturers of breast milk substitutes continue to violate an international code on marketing, a new report published last week says.

The report analysed the promotional practices of 16 international baby food companies and 14 bottle and teat companies between January 2002 and April 2004. It was published by the International Baby Food Action Network, a coalition of public interest groups working to reduce infant morbidity and mortality, as …
Guadecitabine (SGI-110) in patients with intermediate or high-risk myelodysplastic syndromes: phase 2 results from a multicentre, open-label, randomised, phase 1/2 trial
Authors: Guillermo Garcia-Manero, Gail Roboz, Katherine Walsh, Hagop Kantarjian, Ellen Ritchie, Patricia Kropf, Casey O'Connell, Raoul Tibes, Scott Lunin, Todd Rosenblat, Karen Yee, Wendy Stock, Elizabeth Griffiths, Joseph Mace, Nikolai Podoltsev, Jesus Berdeja, Elias Jabbour, Jean-Pierre J Issa, Yong Hao, Harold N Keer, Mohammad Azab, Michael R Savona
Journal: The Lancet Haematology (2019)
Using Public Cost Information During Low Back Pain Visits
Authors: Kimberley S. Fox, Carolyn E. Gray, Martha Elbaum Williamson, Jennifer A. MacKenzie
Journal: Annals of Internal Medicine (2019)

Background: Patients desire information about health care costs because they are increasingly responsible for these costs. Public Web sites that offer cost information could inform provider–patient discussions of costs at the point of care. Objective: To evaluate tools to facilitate the use of publicly available cost information during clinical visits for low back pain (LBP). Design: Qualitative study using individual and group interviews and surveys. Setting: 6 rural primary care practices in 2 health systems in Maine. Participants: Practice staff (n = 50) and adult patients with LBP (n = 72). Intervention: Participating health systems and practices were offered financial incentives, a series of trainings, and technical assistance to pilot tools for discussing costs of LBP care using CompareMaine.org, Maine's cost and quality transparency Web site. Measurements: Integration of tools into workflow, awareness and value to providers, and patient experience were identified through 11 group interviews with practice staff (n = 25) and health system leaders (n = 11), provider (n = 25), and patient (n = 47) surveys; patient interviews (n = 5); and administrative data. Results: The intervention increased provider and consumer awareness of CompareMaine.org, but minimally changed use in clinical discussions as a result of fewer-than-expected patients with LBP, limited system support, workflow barriers, and providers' reluctance to adopt the tools because of perceptions of limited value for their patients. In contrast, patients valued cost conversations and found the tools useful, and over one half reported intending to use CompareMaine.org during future care decisions. Limitations: Generalizability was limited by the small number of practices and participants. Lower-than-anticipated participation precluded examination of the effect of the tool on the frequency of cost-of-care conversations. Conclusion: This multicomponent intervention to introduce publicly reported cost information into LBP clinical discussions had low provider uptake. Whereas cost conversations and CompareMaine.org were perceived as useful by participating patients with LBP, providers were uncomfortable discussing cost variation at the point of care. Successful use of public cost information during clinical visits will require normalizing use to a broader group of patients and greater provider outreach and health system engagement. Primary Funding Source: Robert Wood Johnson Foundation.
Studies in Clinical Shock and Hypotension
Authors: JAY N. COHN, MYRON H. LURIA, ROBERT C. DADDARIO, FELIX E. TRISTANI
Journal: Circulation (1967)

Thirty-one patients with nonhemorrhagic shock or hypotension of diverse etiologies accompanied by low cardiac output and normal or low right atrial pressure were given a rapid infusion of dextran. Cardiac output returned to normal in 20 patients and shock or hypotension was corrected in 16. In 10 patients with evidence of vasoconstriction and normal cardiac function, dextran reversed the circulatory abnormality, returning blood pressure, cardiac output, and peripheral vascular resistance to normal. Twelve patients with hypotension without evidence of reflex vasoconstriction were improved by dextran but the hypotension persisted occasionally. In nine patients, dextran revealed heart failure as manifested by a precipitous rise in right atrial pressure without much increase in cardiac output. Control hemodynamic observations and the response to dextran could not necessarily be predicted from the nature of the disease which precipitated the shock. The efficacy of a rapid infusion of low molecular weight or clinical dextran associated with its freedom from significant toxicity should make it the treatment of choice in non-hemorrhagic shock of any cause associated with normal central venous pressure.
Telling strangers not to shave: not everyone speaks English
Authors: Layla McCay
Journal: BMJ (2002)

Going on elective wasn9t all fun for <b>Layla McCay</b>. She didn9t have a clue what was going on, though she wouldn9t have been able to tell her Japanese hosts that. Contrary to the sometimes lazy outlook native English speakers have, maybe you ought to learn the language before going.
Lymphatic Endothelial Cells Are Essential Components of the Subcapsular Sinus Macrophage Niche
Authors: Isabelle Mondor, Myriam Baratin, Marine Lagueyrie, Lisa Saro, Sandrine Henri, Rebecca Gentek, Delphine Suerinck, Wolfgang Kastenmuller, Jean X. Jiang, Marc Bajénoff
Journal: Immunity (2019)