bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landscape of Tumor Mutation Load, Mismatch Repair Deficiency, and PD-L1 Expression in a Large Patient Cohort of Gastrointestinal Cancers
Authors: Salem Mohamed E. , Puccini Alberto , Grothey Axel , Raghavan Derek , Goldberg Richard M. , Xiu Joanne , Korn W. Michael , Weinberg Benjamin A. , Hwang Jimmy J. , Shields Anthony F. , Marshall John L. , Philip Philip A. , Lenz Heinz-Josef 
Published: March 2018

Abstract
The efficacy of immunotherapy varies widely among different gastrointestinal cancers. Response to immune checkpoint inhibitors is shown to correlate with tumor mutation load (TML), mismatch repair deficiency (dMMR) status, and programmed cell death-ligand 1 (PD-L1) expression. Herein, we quantify TML, dMMR, and PD-L1 expression and determine their interrelationship in gastrointestinal cancers. Here, a total of 4,125 tumors from 14 different gastrointestinal cancer sites were studied using validated assays. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tumor specimens using the NextSeq platform. TML was calculated using only somatic nonsynonymous missense mutations sequenced with a 592-gene panel. Microsatellite instability (MSI) was assessed using direct analysis of altered known MSI loci in the target regions of the sequenced genes. PD-L1 expression was analyzed by IHC. Interestingly, right-sided colon and small-bowel adenocarcinomas had the highest prevalence of TML-high tumors (14.6% and 10.2%, respectively). Pancreatic neuroendocrine tumors and gastrointestinal stromal tumors had the lowest rates of TML-high (1.3% and 0%, respectively). TML-high was strongly associated with MSI-H (P &lt; 0.0001). However, all TML-high anal cancers (8.3%) were microsatellite stable (MSS). Higher PD-L1 expression was more likely to be seen in MSI compared with MSS tumors (20.6% vs. 7.8%, P &lt; 0.0001).
Implications: TML-high rate varied widely among gastrointestinal cancers. Although MSI is conceivably the main driver for TML-high, other factors may be involved. Future clinical trials are needed to evaluate whether the integration of TML, MSI, and PD-L1 could better identify potential responders to immunotherapy. Mol Cancer Res; 16(5); 805–12. ©2018 AACR.
Cross-Talk between Myeloid-Derived Suppressor Cells and Mast Cells Mediates Tumor-Specific Immunosuppression in Prostate Cancer
Authors: Jachetti Elena , Cancila Valeria , Rigoni Alice , Bongiovanni Lucia , Cappetti Barbara , Belmonte Beatrice , Enriquez Claudia , Casalini Patrizia , Ostano Paola , Frossi Barbara , Sangaletti Sabina , Chiodoni Claudia , Chiorino Giovanna , Pucillo Carlo E. , Tripodo Claudio , Colombo Mario P. 
Published: March 2018

Abstract
Immunotherapy, including the use of checkpoint inhibitors, is a potent therapeutic approach for some cancers, but has limited success with prostate tumors, in which immune suppression is instigated by the tumor. The immunosuppressive capacity of mast cells, which promote adenocarcinoma development in the prostate, prompted our investigation on whether mast cells promote tolerance to SV40 Large-T antigen, the transforming oncogene in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. The incidence of adenocarcinoma was reduced in the offspring of a cross between TRAMP mice and mast cell–deficient KitWsh mice. TRAMP mice are tolerant to the SV40 Large T antigen, which is otherwise immunogenic in normal syngeneic B6 mice. Genetic ablation of mast cells in TRAMP mice restored their ability to mount a tumor-specific cytotoxic T-cell response. In KitWsh-TRAMP mice, the restored T-cell immunity correlated with the reduced activity of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), along with their reduced expression of Arg1, Nos2, and Stat3. Having found that CD40L-expressing mast cells can interact in vivo with CD40-expressing PMN-MDSC, we then determined that only KitWsh-TRAMP mice reconstituted with mast cells expressing CD40L could restore PMN-MDSCs suppressive functions, T-cell unresponsiveness and adenocarcinoma development. Thus, mast cells have an immunoregulatory effect on PMN-MDSCs activity through CD40L-CD40 interaction, favoring immunosuppression and tumor onset. In prostate cancer patients, in silico analyses correlated poor clinical outcomes with high expression of genes related to mast cells and PMN-MDSCs. Cancer Immunol Res; 6(5); 552–65. ©2018 AACR.
Association of Liver Fibrosis With Cardiovascular Diseases in the General Population
Authors: Ostovaneh Mohammad R. , Ambale-Venkatesh Bharath , Fuji Tomoki , Bakhshi Hooman , Shah Ravi , Murthy Venkatesh L. , Tracy Russell P. , Guallar Eliseo , Wu Colin O. , Bluemke David A. , Lima João A.C. 
Published: March 2018

Background—
The association of cardiovascular diseases (CVD) with liver fibrosis is poorly understood. We aim to assess the association of liver fibrosis by T1-mapping magnetic resonance imaging and CVD in MESA (Multi-Ethnic Study of Atherosclerosis).

Methods and Results—

MESA enrolled 6814 participants free of clinical CVD at baseline (2000–2002). A subsample of participants underwent T1-mapping magnetic resonance imaging 10 years after the baseline (Y10 MESA exam, 2010–2012). Liver T1 maps were generated avoiding vessels and biliary ducts from which native T1 (n=2087) and extracellular volume fraction (ECV, n=1234) were determined. Higher ECV and native T1 were indicators of liver fibrosis. Linear regression analysis evaluated the cross-sectional relationship between liver native T1 and ECV at Y10 MESA exam with a history of CVD events (atrial fibrillation, heart failure, and coronary heart disease [CHD]). Of the 2087 participants (68.7±9.1 years; 46% females), 153 had prior CVD events (78 atrial fibrillation, 25 heart failure, and 78 CHD). History of CVD events was associated with 18.5 ms higher liver native T1 (
P
<0.001) and 1.4% greater ECV (
P
=0.06). Prior atrial fibrillation was related to higher liver native T1 (β=21.1;
P
=0.001) and greater ECV (β=2.2;
P
=0.02), whereas previous heart failure was associated with greater liver ECV (β=4.1;
P
=0.02). There was also a relationship of prior CHD with liver native T1 (β=13;
P
=0.05) and ECV (β=1.9;
P
=0.05), which was attenuated by adjustment for coronary artery calcium score (β=7.1 and 1.6;
P
=0.37 and 0.13, respectively).

Conclusions—
Liver fibrosis by T1-mapping magnetic resonance imaging is associated with history of heart failure, atrial fibrillation, and CHD in a multiethnic cohort. The association of liver fibrosis and CHD is at least in part mediated by atherosclerosis.
Hospital Readmission After Perioperative Acute Myocardial Infarction Associated With Noncardiac Surgery
Authors: Smilowitz Nathaniel R. , Beckman Joshua A. , Sherman Scott E. , Berger Jeffrey S. 
Published: March 2018

Background:
Acute myocardial infarction (AMI) is a major cardiovascular complication of noncardiac surgery. We aimed to evaluate the frequency, causes, and outcomes of 30-day hospital readmission after perioperative AMI.

Methods:
Patients who were diagnosed with AMI during hospitalization for major noncardiac surgery were identified using the 2014 US Nationwide Readmission Database. Rates, causes, and costs of 30-day readmissions after noncardiac surgery with and without perioperative AMI were identified.

Results:

Among 3 807 357 hospitalizations for major noncardiac surgery, 8085 patients with perioperative AMI were identified. A total of 1135 patients (14.0%) with perioperative AMI died in-hospital during the index admission. Survivors of perioperative AMI were more likely to be readmitted within 30 days than surgical patients without perioperative AMI (19.1% versus 6.5%,
P
<0.001). The most common indications for 30-day rehospitalization were management of infectious complications (30.0%), cardiovascular complications (25.3%), and bleeding (10.4%). In-hospital mortality during hospital readmission in the first 30 days after perioperative AMI was 11.3%. At 6 months, the risk of death was 17.6% and ≥1 hospital readmission was 36.2%.

Conclusions:
Among patients undergoing noncardiac surgery who develop a perioperative MI, ≈1 in 3 suffer from in-hospital death or hospital readmission in the first 30 days after discharge. Strategies to improve outcomes of surgical patients early after perioperative AMI are warranted.
Genome Wide Association Study Identifies the
HMGCS2
Locus to be Associated With Chlorthalidone Induced Glucose Increase in Hypertensive Patients
Authors: Singh Sonal , McDonough Caitrin W. , Gong Yan , Alghamdi Wael A. , Arwood Meghan J. , Bargal Salma A. , Dumeny Leanne , Li Wen‐Yi , Mehanna Mai , Stockard Bradley , Yang Guang , de Oliveira Felipe A. , Fredette Natalie C. , Shahin Mohamed H. , Bailey Kent R. , Beitelshees Amber L. , Boerwinkle Eric , Chapman Arlene B. , Gums John G. , Turner Stephen T. , Cooper‐DeHoff Rhonda M. , Johnson Julie A. 
Published: March 2018

Background
Thiazide and thiazide‐like diuretics are first‐line medications for treating uncomplicated hypertension. However, their use has been associated with adverse metabolic events, including hyperglycemia and incident diabetes mellitus, with incompletely understood mechanisms. Our goal was to identify genomic variants associated with thiazide‐like diuretic/chlorthalidone‐induced glucose change.

Methods and Results

Genome‐wide analysis of glucose change after treatment with chlorthalidone was performed by race among the white (n=175) and black (n=135) participants from the
PEAR
‐2 (Pharmacogenomic Evaluation of Antihypertensive Responses‐2). Single‐nucleotide polymorphisms with
P
<5×10
−8
were further prioritized using in silico analysis based on their expression quantitative trait loci function. Among blacks, an intronic single‐nucleotide polymorphism (rs9943291) in the

HMGCS
2

was associated with increase in glucose levels following chlorthalidone treatment (ß=12.5;
P
=4.17×10
−8
). G‐allele carriers of

HMGCS
2

had higher glucose levels (glucose change=+16.29 mg/dL) post chlorthalidone treatment compared with noncarriers of G allele (glucose change=+2.80 mg/dL). This association was successfully replicated in an independent replication cohort of hydrochlorothiazide‐treated participants from the
PEAR
study (ß=5.54;
P
=0.023). A meta‐analysis of the 2 studies was performed by race in Meta‐Analysis Helper, where this single‐nucleotide polymorphism, rs9943291, was genome‐wide significant with a meta‐analysis
P
value of 3.71×10
−8
.

HMGCS
2

, a part of the
HMG
‐CoA synthase family, is important for ketogenesis and cholesterol synthesis pathways that are essential in glucose homeostasis.

Conclusions

These results suggest that

HMGCS
2

is a promising candidate gene involved in chlorthalidone and Hydrochlorothiazide (HCTZ)‐induced glucose change. This may provide insights into the mechanisms involved in thiazide‐induced hyperglycemia that may ultimately facilitate personalized approaches to antihypertensive selection for hypertension treatment.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifiers:
NCT
00246519 and
NCT
01203852.
Acute Myocardial Infarction Mortality During Dates of National Interventional Cardiology Meetings
Authors: Jena Anupam B. , Olenski Andrew , Blumenthal Daniel M. , Yeh Robert W. , Goldman Dana P. , Romley John 
Published: March 2018

Background
Previous research has found that patients with acute cardiovascular conditions treated in teaching hospitals have lower 30‐day mortality during dates of national cardiology meetings.

Methods and Results

We analyzed 30‐day mortality among Medicare beneficiaries hospitalized with acute myocardial infarction (overall, ST‐segment–elevation myocardial infarction, and non–ST‐segment–elevation myocardial infarction) from January 1, 2007, to November 31, 2012, in major teaching hospitals during dates of a major annual interventional cardiology meeting (Transcatheter Cardiovascular Therapeutics) compared with identical nonmeeting days in the ±5 weeks. Treatment differences were assessed. We used a database of US physicians to compare interventional cardiologists who practiced and did not practice during meeting dates (“stayers” and “attendees,” respectively) in terms of demographic characteristics and clinical and research productivity. Unadjusted and adjusted 30‐day mortality rates were lower among patients admitted during meeting versus nonmeeting dates (unadjusted, 15.3% [482/3153] versus 16.7% [5208/31 556] [
P
=0.04]; adjusted, 15.4% versus 16.7%; difference −1.3% [95% confidence interval, −2.7% to −0.1%] [
P
=0.05]). Rates of interventional cardiologist involvement were similar between dates (59.5% versus 59.8% of hospitalizations;
P
=0.88), as were percutaneous coronary intervention rates (30.2% versus 29.1%;
P
=0.20). Mortality reductions were largest among patients with non–ST‐segment–elevation myocardial infarction not receiving percutaneous coronary intervention (16.9% versus 19.5% adjusted 30‐day mortality;
P
=0.008). Compared with stayers, attendees were of similar age and sex, but had greater publications (18.9 versus 6.3;
P
<0.001), probability of National Institutes of Health funding (5.3% versus 0.4%;
P
<0.001), and clinical trial leadership (10.3% versus 3.9%;
P
<0.001), and they performed more percutaneous coronary interventions annually (85.6 versus 63.3;
P
<0.001).

Conclusions
Hospitalization with acute myocardial infarction during Transcatheter Cardiovascular Therapeutics meeting dates was associated with lower 30‐day mortality, predominantly among patients with non–ST‐segment–elevation myocardial infarction who were medically managed.
Venovenous extracorporeal life support in patients with HIV infection and Pneumocystis jirovecii pneumonia
Authors: Capatos Gerry , Burke Christopher R. , Ogino Mark T. , Lorusso Roberto R. , Brogan Thomas V. , McMullan D. Michael , Dalton Heidi J. 
Published: March 2018

Aim: As experience with extracorporeal life support (ECLS) increases, indications for its use have expanded to diverse patient populations, including those with HIV infection. Pneumocystis jirovecii pneumonia (PJP) is a particularly devastating complication of HIV infections. The objective of this study was to review ECLS use in HIV-positive patients, with particular emphasis on those with concomitant PJP infection. Methods: All patients were treated by the same ECLS team, consisting of an ECLS specialist intensivist, cardiothoracic surgeon and allied medical professionals at three healthcare institutions. The same ECLS protocol was utilized for all patients during the study period. A retrospective review was performed for all HIV-positive patients placed on ECLS from May 2011 to October 2014. Demographic, clinical, ECLS and complication data were reviewed to identify risk factors for death. Results: A total of 22 HIV-positive patients received ECLS therapy during the study period. All patients were supported with venovenous ECLS and overall survival to hospital discharge was 68%. Survival amongst the PJP positive cohort was 60%. Non-survivors were more likely to require inotropic medications on ECLS (100% non-survivors vs. 46.7% survivors, p=0.022) and had a longer total duration of ECLS (13 days non-survivors vs. 7 days survivors, p=0.011). No difference was observed between PJP-positive and PJP-negative patients with regard to demographic data, complication rates or survival. Conclusion: ECLS is a viable treatment option in carefully selected HIV-positive patients, including those with severe disease as manifested by PJP infection.
The retroneural approach: an alternative technique for lumbar transforaminal epidural steroid injections
Authors: Ignjatovic Stefan , Omidi Reza , Kubik-Huch Rahel A , Anderson Suzanne , Ahlhelm Frank J 
Published: March 2018

Background Compared with other available injection techniques for lumbar transforaminal epidural steroid injections (LTFESIs), the traditionally performed subpedicular approach is associated with a higher risk of spinal cord infarction, a rare but catastrophic complication. Purpose To assess the short-term efficacy of the retroneural approach for computed tomography (CT)-guided LTFESIs with respect to different needle-tip positions. Material and Methods This retrospective analysis included 238 patients receiving 286 CT-guided LTFESIs from January 2013 to January 2016. Short-term outcomes in terms of pain relief were assessed using the visual analogue scale (VAS) at baseline and 30 min after. The needle-tip location was categorized as extraforaminal, junctional, or foraminal relative to the neural foramen. Additionally, the distance from the needle tip to the nerve root was measured. Results A mean pain reduction of 3.22 points (±2.17 points) on the VAS was achieved. The needle-tip location was extraforaminal in 48% (136/286), junctional in 42% (120/286), and foraminal in 10% (28/286) of the cases. The mean distance from the needle tip to the nerve root was 3.83 mm (±3.37 mm). There was no significant correlation between pain relief and needle-tip position in relation to the neural foramen. Therapy success was not dependent on the distance between the needle tip and the nerve root. No major complications were observed. Conclusion In our population treated with LTFESIs, the retroneural approach was shown to be an effective technique, with no significant differences in pain relief following different needle-tip positions.
White matter lesions and brain atrophy in systemic lupus erythematosus patients: correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus
Authors: Cannerfelt B , Nystedt J , Jönsen A , Lätt J , van Westen D , Lilja A , Bengtsson A , Nilsson P , Mårtensson J , Sundgren P C 
Published: March 2018

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.
Introducing consumer directed care in residential care settings for older people in Australia: views of a citizens’ jury
Authors: Laver Kate , Gnanamanickam Emmanuel , Whitehead Craig , Kurrle Susan , Corlis Megan , Ratcliffe Julie , Shulver Wendy , Crotty Maria 
Published: March 2018

Objectives Health services worldwide are increasingly adopting consumer directed care approaches. Traditionally, consumer directed care models have been implemented in home care services and there is little guidance as to how to implement them in residential care. This study used a citizens’ jury to elicit views of members of the public regarding consumer directed care in residential care. Methods A citizens’ jury involving 12 members of the public was held over two days in July 2016, exploring the question: For people with dementia living in residential care facilities, how do we enable increased personal decision making to ensure that care is based on their needs and preferences? Jury members were recruited through a market research company and selected to be broadly representative of the general public. Results The jury believed that person-centred care should be the foundation of care for all older people. They recommended that each person’s funding be split between core services (to ensure basic health, nutrition and hygiene needs are met) and discretionary services. Systems needed to be put into place to enable the transition to consumer directed care including care coordinators to assist in eliciting resident preferences, supports for proxy decision makers, and accreditation processes and risk management strategies to ensure that residents with significant cognitive impairment are not taken advantage of by goods and service providers. Transparency should be increased (perhaps using technologies) so that both the resident and nominated family members can be sure that the person is receiving what they have paid for. Conclusions The views of the jury (as representatives of the public) were that people in residential care should have more say regarding the way in which their care is provided and that a model of consumer directed care should be introduced. Policy makers should consider implementation of consumer directed care models that are economically viable and are associated with high levels of satisfaction among users.
Reconciliatory socialization: Conceptualizing the experiences of Evangelical Christian doctoral students in secular higher education
Authors: Espinoza Benjamin D 
Published: March 2018

Weidman, Twale and Stein’s (2001) model of graduate student socialization has served as a theoretical starting point for understanding the experiences of doctoral students. Although a number of scholars have critiqued the model for failing to account for the unique experiences of different student groups, none has specifically approached the model with Evangelical Christian doctoral students in mind. Building on the literature on Evangelical Christian students in secular higher education, this article offers a reconceptualization of Weidman et al.’s (2001) model that accounts for the unique experiences of Evangelical Christian doctoral students in secular higher education. This revised model, called reconciliatory socialization, serves as a conceptual framework by which to conduct empirical research on the experiences of Evangelical Christian doctoral students in secular settings.
Stringent or nonstringent complete remission and prognosis in acute myeloid leukemia: a Danish population-based study
Authors: Øvlisen Andreas K. , Oest Anders , Bendtsen Mette D. , Bæch John , Johansen Preben , Lynggaard Line S. , Mølle Ingolf , Mortensen Thomas B. , Weber Duruta , Ertner Gideon , Schöllkopf Claudia , Thomassen Jesper Q. , Nielsen Ove Juul , Østgård Lene Sofie Granfeldt , Bøgsted Martin , Dybkær Karen , Johnsen Hans E. , Severinsen Marianne T. 
Published: March 2018

Key Points
sCR and non-sCR in acute myeloid leukemia are associated with different prognoses. Three lineage blood cell recoveries have independent impacts on prognosis.