bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitigating SOX2-potentiated Immune Escape of Head and Neck Squamous Cell Carcinoma with a STING-inducing Nanosatellite Vaccine
Authors: Tan Yee Sun , Sansanaphongpricha Kanokwan , Xie Yuying , Donnelly Christopher R. , Luo Xiaobo , Heath Blake R. , Zhao Xinyi , Bellile Emily , Hu Hongxiang , Chen Hongwei , Polverini Peter J. , Chen Qianming , Young Simon , Carey Thomas E. , Nör Jacques E. , Ferris Robert L. , Wolf Gregory T. , Sun Duxin , Lei Yu L. 
Published: May 2018

Abstract
Purpose: The response rates of Head and Neck Squamous Cell Carcinoma (HNSCC) to checkpoint blockade are below 20%. We aim to develop a mechanism-based vaccine to prevent HNSCC immune escape.
Experimental Design: We performed RNA-Seq of sensitive and resistant HNSCC cells to discover central pathways promoting resistance to immune killing. Using biochemistry, animal models, HNSCC microarray, and immune cell deconvolution, we assessed the role of SOX2 in inhibiting STING-type I interferon (IFN-I) signaling-mediated antitumor immunity. To bypass SOX2-potentiated STING suppression, we engineered a novel tumor antigen–targeted nanosatellite vehicle to enhance the efficacy of STING agonist and sensitize SOX2-expressing HNSCC to checkpoint blockade.
Results: The DNA-sensing defense response is the most suppressed pathway in immune-resistant HNSCC cells. We identified SOX2 as a novel inhibitor of STING. SOX2 facilitates autophagy-dependent degradation of STING and inhibits IFN-I signaling. SOX2 potentiates an immunosuppressive microenvironment and promotes HNSCC growth in vivo in an IFN-I-dependent fashion. Our unique nanosatellite vehicle significantly enhances the efficacy of STING agonist. We show that the E6/E7–targeted nanosatellite vaccine expands the tumor-specific CD8+ T cells by over 12-fold in the tumor microenvironment and reduces tumor burden. A combination of nanosatellite vaccine with anti-PD-L1 significantly expands tumor-specific CTLs and limits the populations expressing markers for exhaustion, resulting in more effective tumor control and improved survival.
Conclusions: SOX2 dampens the immunogenicity of HNSCC by targeting the STING pathway for degradation. The nanosatellite vaccine offers a novel and effective approach to enhance the adjuvant potential of STING agonist and break cancer tolerance to immunotherapy. Clin Cancer Res; 24(17); 4242–55. ©2018 AACR.
Feasibility of Segmental Colectomy Followed by Endoscopic Surveillance as a Treatment Strategy for Colorectal Cancer Patients with Lynch Syndrome
Authors: Nagasaki Toshiya , Arai Masami , Chino Akiko , Akiyoshi Takashi , Fukunaga Yosuke , Ueno Masashi 
Published: May 2018

<b><i>Background:</i></b> Initial surgical procedures for colorectal cancer (CRC) patients with Lynch syndrome remain controversial. This study assessed the validity of segmental colectomy (SGC) followed by endoscopic surveillance as a treatment strategy for CRC patients with Lynch syndrome. <b><i>Methods:</i></b> Among consecutive patients who underwent surgery for primary CRC between April 1985 and December 2014, 49 patients were observed to have germline mutations in a mismatch repair gene, and 38 patients who underwent SGC followed by periodic endoscopic surveillance at our institution were evaluated for metachronous CRC, need for secondary surgery, and the details of endoscopic surveillance. <b><i>Results:</i></b> Of the 38 patients who underwent SGC followed by periodic endoscopic surveillance at our institution, 6 (15.8%) patients showed metachronous CRC, 3 (7.9%) patients underwent endoscopic resection, and the other 3 patients (7.9%) underwent secondary surgery. The dispersion of the endoscopic surveillance interval was significantly greater in patients with metachronous CRC (364 ± 332.9 days) than in those without metachronous CRC (370 ± 129.7 days; <i>p &#x3c;</i> 0.001). <b><i>Conclusions:</i></b> SGC followed by annual endoscopic surveillance was feasible as a treatment strategy for CRC patients with Lynch syndrome, because the incidence of metachronous CRC and the need for secondary surgery were low. Annual and periodic endoscopic surveillance might be essential for early detection of metachronous CRC and prevention of secondary surgery because of metachronous CRC in CRC patients with Lynch syndrome after SGC.
Transient Outward K
+
Current (I
to
) Underlies the Right Ventricular Initiation of Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long-QT Syndrome Type 1
Authors: Choi Bum-Rak , Li Weiyan , Terentyev Dmitry , Kabakov Anatoli Y. , Zhong Mingwang , Rees Colin M. , Terentyeva Radmila , Kim Tae Yun , Qu Zhilin , Peng Xuwen , Karma Alain , Koren Gideon 
Published: May 2018

Background:
Sudden death in long-QT syndrome type 1 (LQT1), an inherited disease caused by loss-of-function mutations in KCNQ1, is triggered by early afterdepolarizations (EADs) that initiate polymorphic ventricular tachycardia (pVT). We investigated ionic mechanisms that underlie pVT in LQT1 using a transgenic rabbit model of LQT1.

Methods:
Optical mapping, cellular patch clamping, and computer modeling were used to elucidate the mechanisms of EADs in transgenic LQT1 rabbits.

RESULTS:

The results showed that shorter action potential duration in the right ventricle (RV) was associated with focal activity during pVT initiation. RV cardiomyocytes demonstrated higher incidence of EADs under 50 nmol/L isoproterenol. Voltage-clamp studies revealed that the transient outward potassium current (I
to
) magnitude was 28% greater in RV associated with KChiP2 but with no differences in terms of calcium-cycling kinetics and other sarcolemmal currents. Perfusing with the I
to
blocker 4-aminopyridine changed the initial focal sites of pVT from the RV to the left ventricle, corroborating the role of I
to
in pVT initiation. Computer modeling showed that EADs occur preferentially in the RV because of the larger conductance of the slow-inactivating component of I
to
, which repolarizes the membrane potential sufficiently rapidly to allow reactivation of I
Ca,L
before I
Kr
has had sufficient time to activate.

Conclusions:

I
to
heterogeneity creates both triggers and an arrhythmogenic substrate in LQT1. In the absence of I
Ks
, I
to
interactions with I
Ca,L
and I
Kr
promote EADs in the RV while prolonging action potential duration in the left ventricle. This heterogeneity of action potential enhances dispersion of refractoriness and facilitates conduction blocks that initiate pVTs.
Early and Chronic Dipeptidyl‐Peptidase‐IV Inhibition and Cardiovascular Events in Patients With Type 2 Diabetes Mellitus After an Acute Coronary Syndrome: A Landmark Analysis of the EXAMINE Trial
Authors: Sharma Abhinav , Cannon Christopher P. , White William B. , Liu Yuyin , Bakris George L. , Cushman William C. , Zannad Faiez 
Published: May 2018

Background

Antihyperglycemic therapies may increase the risk of cardiovascular events including hospitalization for heart failure. There is a paucity of data evaluating the cardiovascular safety of antihyperglycemic therapies in the high‐risk period following an acute coronary syndrome (
ACS
).

Methods and Results

The
EXAMINE
(Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial randomized 5380 patients who were 15 to 90 days post
ACS
to the dipeptidyl dipeptidase‐IV (
DPP
‐
IV
) inhibitor alogliptin versus placebo; mean follow‐up was 18 months. Using a landmark analysis, we assessed the (1) burden of cardiovascular events from randomization to 6 months (early period) and from 6 months to the end of follow‐up (late period) and (2) the risk of cardiovascular events associated with early (up to 6 months) and chronic (6 months to end of follow‐up)
DPP
‐
IV
inhibition with alogliptin. Patients with early versus late events had similar baseline demographic profiles. Overall, 42.1% of the composite of cardiovascular death/myocardial infarction/stroke and 47.5% of hospitalization for heart failure occurred in the early period. Early
DPP
‐
IV
inhibition did not increase the risk of early cardiovascular death/myocardial infarction/stroke (hazard ratio 0.96, 95% confidence interval, 0.76–1.21) or hospitalization for heart failure (1.23, 95% confidence interval, 0.84–1.82). Similarly, chronic
DPP
‐
IV
inhibition did not increase the risk of late cardiovascular death/myocardial infarction/stroke (hazard ratio 1.03, 95% confidence interval, 0.89–1.26) or hospitalization for heart failure (hazard ratio 1.02, 95% confidence interval, 0.85–1.22).

Conclusions

Early after an
ACS
, patients with type 2 diabetes mellitus experience a significant burden of
HF
events and recurrent
ACS
.
DPP
‐
IV
inhibition with alogliptin appears to be safe even in the high‐risk period following an
ACS
.
Factors Predictive of Postoperative Acute Respiratory Failure Following Inpatient Sinus Surgery
Authors: Burton Brittany N. , Gilani Sapideh , Swisher Matthew W. , Urman Richard D. , Schmidt Ulrich H. , Gabriel Rodney A. 
Published: May 2018

Objective: The impact of perioperative risk factors on outcomes following outpatient sinus surgery is well defined; however, risk factors and outcomes following inpatient surgery remain poorly understood. We aimed to define risk factors of postoperative acute respiratory failure following inpatient sinus surgery. Methods: Utilizing data from the Nationwide Inpatient Sample Database from the years 2010 to 2014, we identified patients (≥18 years of age) with an Internal Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code of sinus surgery. We used multivariable logistic regression to identify risk factors of postoperative acute respiratory failure. Results: We identified 4919 patients with a median age of 53 years. The rate of inpatient postoperative acute respiratory failure was 3.35%. Chronic sinusitis (57.7%) was the most common discharge diagnosis. The final multivariable logistic regression analysis suggested that pneumonia, bleeding disorder, alcohol dependence, nutritional deficiency, heart failure, paranasal fungal infections, and chronic kidney disease were associated with increased odds of acute respiratory failure (all P < .05). Conclusion: To our knowledge, this represents the first study to evaluate potential risk factors of acute respiratory failure following inpatient sinus surgery. Knowledge of these risk factors may be used for risk stratification.
The Patient-to-Prisoner Pipeline: The IMD Exclusion's Adverse Impact on Mass Incarceration in United States
Authors: Onah Michael E. 
Published: May 2018

A component of the 1965 Medicaid Act, the Institutions for Mental Diseases (“IMD”) Exclusion was supposed to be a remedy for the brutal, dysfunctional mental healthcare system run through state hospitals. In the years since Medicaid was created, the IMD Exclusion has instead barred thousands of those in need of intensive, inpatient treatment from receiving it. As a result, many severely mentally ill individuals are left without adequate care and without a home. They struggle in the street where they are otherized by those in their community and are susceptible to confrontational episodes with law enforcement. Many are ultimately incarcerated, where they are thrust into an abusive environment known to exacerbate mental health issues.This Note's central contention is that the IMD Exclusion creates an access gap for the poorest Americans who suffer from mental illness. Subsequently, prisons and jails fill that gap to the detriment of those individuals. The Note will proceed first by explaining the IMD Exclusion and how it applies to state-run medical care services and facilities. This Note will discuss the nationwide movement, in the 1950s through the 1960s and ‘70s, to deinstitutionalize notoriously abusive state psychiatric hospitals, a movement that culminated in the passage of the Medicaid Act in 1965, along with the IMD Exclusion. This Note will then shift focus to criticize the practical effects of the IMD Exclusion and its extensive role in the mass incarceration issue today. In doing so, this Note will identify the major weaknesses of the IMD Exclusion and explain how these weaknesses create an access gap for mentally ill persons, while simultaneously making them more vulnerable to contact with the police and the criminal justice system.
Impact of paliperidone palmitate one-month formulation on relapse prevention in patients with schizophrenia: A post-hoc analysis of a one-year, open-label study stratified by medication adherence
Authors: Si Tianmei , Li Nan , Lu Huafei , Cai Shangli , Zhuo Jianmin , Correll Christoph U , Zhang Lili , Feng Yu 
Published: May 2018

Background: Limited data are available to help identify patients with schizophrenia who are most likely to benefit from long-acting injectable antipsychotics. Aim: To investigate the efficacy of long-acting injectable antipsychotic paliperidone palmitate one-month formulation for preventing relapses, factors influencing time to first relapse, and the effect of different antipsychotic adherence levels on time to first relapse in Chinese patients with schizophrenia. Methods: This was a post-hoc analysis from an open-label, single-arm study of stable patients (Positive and Negative Syndrome Scale total score <70; n=367) receiving paliperidone palmitate one-month formulation at the end of an acute 13-week treatment phase, who entered a naturalistic one-year follow-up period, either continuing with flexibly dosed paliperidone palmitate one-month formulation (75–150 mg eq.) or switching to another antipsychotic(s). Results: There were 362/367 patients (age=31.4±10.75 years) included in the analysis of time to first relapse (primary outcome) and 327/362 patients (39/327, poor antipsychotic adherence (<80%)) willing to receive antipsychotics were included in the exposure/adherence analysis. Overall, 84.6% (95% confidence interval=79.2–88.7) patients remained relapse-free. Poor adherence during follow-up (hazard ratio=2.97, 95% confidence interval=1.48–5.98, p=0.002) and frequent hospitalizations in the previous year (hazard ratio=1.29, 95% confidence interval=1.02–1.62, p=0.03) were associated with a significant risk of shorter time to first relapse in the univariate analysis. In patients with poor adherence, ‘no use’ (hazard ratio=13.13, 95% confidence interval=1.33–129.96, p=0.03) and ‘interrupted use’ (hazard ratio=11.04, 95% confidence interval=1.03–118.60, p=0.047) of paliperidone palmitate one-month formulation (vs continued use) showed a significantly higher risk of relapse; this was not observed in patients with good (≥80%) antipsychotic adherence. No new safety concerns were identified. Conclusion: Continued use of paliperidone palmitate one-month formulation/long-acting injectable antipsychotic was effective in preventing schizophrenia relapses, especially in patients with suboptimal antipsychotic adherence.
Return-to-Play and Performance Outcomes of Professional Athletes in North America After Hip Arthroscopy From 1999 to 2016
Authors: Schallmo Michael S. , Fitzpatrick Thomas H. , Yancey Hunter B. , Marquez-Lara Alejandro , Luo T. David , Stubbs Allston J. 
Published: May 2018

Background: The effect of hip arthroscopy on athletic performance compared with preinjury levels for professional athletes in different sports remains unknown. In addition, while return rates have been reported for professional baseball, football, and hockey players, return rates have not been reported for professional basketball players. Hypothesis: Professional athletes in 4 major North American sports would be able to return to their sport and preoperative level of performance at a high rate after arthroscopic hip surgery. Study Design: Descriptive epidemiology study. Methods: Major League Baseball (MLB), National Basketball Association (NBA), National Football League (NFL), and National Hockey League (NHL) athletes who underwent hip arthroscopy were identified through a previously reported protocol based on public sources. Successful return to play (RTP) was defined as returning for at least 1 professional regular season game after surgery. Performance scores were calculated by use of previously established scoring systems. Each player served as his own control, with the season prior to surgery defined as baseline. To make comparisons across sports, the authors adjusted for expected season and career length differences between sports and calculated percentage changes in performance. Results: The authors identified 227 procedures performed on 180 professional athletes between 1999 and 2016. Successful RTP was achieved in 84.6% (192/227) of the procedures. Compared with all other athletes, NBA athletes returned at a similar rate (85.7%, P ≥ .999). NFL offensive linemen returned at a significantly lower rate than all other athletes (61.1%, P = .010). NHL athletes returned at a significantly higher rate than all other athletes (91.8%, P = .048) and demonstrated significantly decreased performance during postoperative season 1 compared with baseline (–35.1%, P = .002). Lead leg surgery for MLB athletes (batting stance for hitters, pitching stance for pitchers) resulted in a 12.7% reduction in hitter performance score ( P = .041), a 1.3% reduction in pitcher fastball velocity ( P = .004), and a 60.7% reduction in pitch count ( P = .007) one season after surgery compared with baseline. Players in nearly every sport demonstrated significant reductions in game participation after surgery. Conclusion: This study supports the hypothesis that hip arthroscopy in professional athletes is associated with excellent rates of return at the professional level. However, postoperative performance outcomes varied based on sport and position.
Preliminary results of the first cervical cancer screening programme in the North Eastern region of Romania
Authors: Păvăleanu Ioana , Gafiţanu Dumitru , Ioanid Nicolae , Grigore Mihaela 
Published: May 2018

Objective Cervical cancer represents a major health problem in Romania. A national population-based cervical cancer screening programme was launched in 2012. The aims of the study were to assess the participation rate and to estimate the prevalence of epithelial cell abnormalities in the first four years of the programme in North Eastern Romania. Methods The participation rate, representing the proportion of eligible women screened in the programme, was evaluated for 2012–2016. The prevalence of cytological abnormalities was estimated by age group and calendar year. Results Of 107,968 Pap smears taken, 312 were unsatisfactory (0.3%). The number of smears decreased by year. The participation rate over the four years was 16.9%. Of the 107,656 satisfactory smears, 6.5% were positive for squamous and/or glandular lesion, among which 0.5% contained high-grade squamous intraepithelial or worse lesions. Conclusion The participation rate in the first four years of the programme was low. The effectiveness of the screening programme should be improved by attendance monitoring of the target population, and follow-up of screen-positive women. Measures should be taken to raise coverage and assure quality at all steps of the screening chain. The data collected should include all screening tests from both opportunistic and organized settings.
‘It’s our everyday life’ – The perspectives of persons with intellectual disabilities in Norway
Authors: Witsø Aud Elisabeth , Hauger Brit 
Published: May 2018

This study illuminates how adults with intellectual disabilities understand and describe their everyday life and its shortcomings when it comes to equal rights in the context of Norwegian community living. An inclusive research design, including nine persons with mild intellectual disability, two university researchers and two intellectual disability nurses from the municipality, was undertaken. An inductive thematic analysis of data identified three key themes: everyday life – context, rhythm and structure, social participation and staff – an ambiguous part of everyday life. Results show that service provision had institutional qualities; participants experienced lack of information and reduced possibilities for social inclusion and community participation like everyone else. More attention on the role of policy development, support staff and leadership, in relation to facilitating an everyday life with more user involvement, social inclusion and community participation of people needing support, is essential. Participatory, appreciative, action and reflection in workshops for persons with intellectual disabilities and support staff represent a promising approach to promote the voices and interests of persons with intellectual disabilities. This article tells you about the everyday life of people with intellectual disabilities living in Norway. Nine people with intellectual disabilities worked together with two university researchers and two intellectual disability nurses in the community, in workshops. The people with intellectual disabilities liked to have their own apartment and going to work every day. They said that they wanted more social participation with friends and more participation in activities in the community, just like everyone else. They wanted to be treated with more respect by their staff. All participants in the project saw great value in working together and some of them are working together in a new project about involvement in the improvement of support services for people with intellectual disabilities.
Minimally invasive thread trigger digit release: a preliminary report on 34 digits of the adult hands
Authors: Guo Danqing , McCool Logan , Senk Alexander , Tonkin Brionn , Guo Joseph , Lytie Rachel M. , Guo Danzhu 
Published: May 2018

The trigger finger release was performed in 34 digits (11 thumbs and 23 fingers) of 24 patients through the thread transecting technique with the tip-to-tip approach, in which a 22-gauge needle inserts into a 18-gauge needle when both needles are inside the hand, guiding the 22-gauge needle to exit the hand at the same access point of 18-gauge needle. We prospectively evaluated the effectiveness and functional recovery of these patients. In all 34 digits, triggering and locking were resolved, and complete extension and flexion occurred immediately following the release. There were no complications, such as incomplete release, neurovascular or flexor tendon or A2 pulley injury, infection, or tendon bow-stringing. Patients did not require prescription pain medications. Most patients used their hands to meet their basic living needs the same day of the procedure. The hand function evaluated with the Quick Disabilities of the Arm, Shoulder and Hand questionnaire, and scored 4 within 3 months. Level of evidence: II