bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment Patterns and Burden of Illness in Patients Initiating Targeted Therapy or Chemotherapy for Pancreatic Neuroendocrine Tumors
Authors: Broder Michael S. , Chang Eunice , Reddy Sheila R. , Neary Maureen P. 
Published: July 2017

Objective
The aim of this study was to characterize treatment patterns and burden of pancreatic neuroendocrine tumors (PNET).

Methods
Using 2 claims databases, we identified patients with PNET initiating targeted therapy (everolimus, sunitinib) or chemotherapy from 2009 to 2012. The first targeted/cytotoxic therapy was considered index treatment. Treatment patterns were graphically evaluated from index treatment initiation until enrollment or study end, whichever occurred first. Disease burden was examined by index group for first follow-up year.

Results
In treatment pattern analyses (582 newly treated patients with PNET), 72.2% received chemotherapy index treatment, 16.2% everolimus, and 11.7% received sunitinib. Median index treatment duration was 242, 146, and 126 days for everolimus, sunitinib, and cytotoxics (P < 0.01). Sunitinib initiators switched most often followed by everolimus and cytotoxic initiators. In disease burden analyses, 338 patients met inclusion criteria, with mean age of 54.5 (standard deviation, 9.9) years, 45.6% were female, and there were no significant between-group differences. Targeted therapy initiators had more prior somatostatin analog use versus cytotoxics (53.4% vs 25.1%, P < 0.001); 72.5% had comorbidities after treatment initiation; 42.9% had 1 or more inpatient hospitalization; and 47.9% had 1 or more emergency department visit.

Conclusions
Pancreatic neuroendocrine tumor treatment patterns varied; cytotoxics were more often used as early therapy than targeted agents, but for less time. Patients had high health care utilization, irrespective of treatment, potentially from burdensome symptoms and comorbidities.
Validation of the 2012 Fukuoka Consensus Guideline for Intraductal Papillary Mucinous Neoplasm of the Pancreas From a Single Institution Experience
Authors: Yu Songfeng , Takasu Naoki , Watanabe Toshihiro , Fukumoto Tsuyoshi , Okazaki Shinji , Tezuka Koji , Sugawara Shuichiro , Hirai Ichiro , Kimura Wataru 
Published: July 2017

Objectives
The 2012 Fukuoka consensus guideline has stratified the risks of malignant intraductal papillary mucinous neoplasm (IPMN) of the pancreas into “high-risk stigmata” (HRS) and “worrisome feature” (WF). This study aimed to evaluate its clinical validity based on a single institution experience.

Methods
Eighty-nine patients who underwent surgical resection with pathological diagnosis of IPMN were retrospectively studied.

Results
High-risk stigmata was significantly correlated with the prevalence of malignant IPMN as compared with WF. The positive predictive values of HRS and WF were 66.7% and 35.7% for branch duct IPMN and 80% and 38.1% for main duct IPMN, respectively. Univariate analysis indicated that all the factors in HRS and WF had statistical significance. Whereas multivariate analysis revealed only enhanced solid component (odds ratio [OR], 50.01; P = 0.008), presence of mural nodule (OR, 73.83; P < 0.001) and lymphadenopathy (OR, 20.85; P = 0.03) were independent predictors. Scoring HRS and WF by different numbers of positive factors resulted in improved predictive value. The area under the curve of HRS score was significantly lower than that of WF or HRS + WF score (0.680 vs 0.900 or 0.902, respectively; P < 0.001).

Conclusions
As supplementary to the 2012 Fukuoka guideline, we suggest that calculating scores of WF and HRS may have superior diagnostic accuracy in predicting malignant IPMN.
Clinical Profile of Pancreatic Cystic Lesions in von Hippel-Lindau Disease
Authors: Sharma Ayush , Mukewar Saurabh , Vege Santhi Swaroop 
Published: July 2017

Objectives
Little is known about the association between pancreatic cystic lesions (PCLs) with von Hippel-Lindau disease (VHLD). In this study, we describe the clinical presentation, type of PCLs, and risk for malignancy in PCLs in VHLD.

Methods
Patients given a diagnosis of both VHLD and PCLs were identified from electronic medical records at Mayo Clinic, Rochester, MN, from January 1, 2000, to January 1, 2016. Various demographic, clinical, and radiologic variables were recorded.

Results
Forty-eight patients were identified with PCLs and VHLD. Most were female (73%), and mean (standard deviation) age was 35.9 (14.2) years. Most (92%) were asymptomatic. PCLs included simple cysts (n = 34, 69%), serous cystadenoma (n = 14, 29%), branch duct intraductal papillary neoplasm (n = 5, 10%), and cystic neuroendocrine tumors (n = 2, 4%). Eight (19%) had mixed PCLs. Cyst aspiration was performed in 8 (53%) patients who underwent EUS, and all were negative for malignancy. At a median follow-up of 84 months, no PCL-associated cancers were seen.

Conclusions
Simple cyst is the most common type of PCL found in VHL disease; however, other PCLs were also seen with no malignancy potential. Branch duct intraductal papillary mucinous neoplasms were present in 10%, and this association was not hitherto reported.
Patterns of Care for Locally Advanced Pancreatic Adenocarcinoma Using the National Cancer Database
Authors: Amini Arya , Jones Bernard L. , Stumpf Priscilla , Leong Stephen , Lieu Christopher H. , Weekes Colin , Davis S. Lindsey , Messersmith Wells A. , Purcell William T. , Ghosh Debashis , Schefter Tracey , Goodman Karyn A. 
Published: July 2017

Objectives
The role of radiotherapy (RT) in locally advanced pancreatic cancer (LAPC) is uncertain. This study examines patterns of care and survival outcomes of LAPC undergoing chemotherapy alone versus chemotherapy plus RT (C + RT).

Methods
The National Cancer Database was queried for nonmetastatic LAPC patients who received chemotherapy alone or C + RT.

Results
Of the 13,695 patients included, 5306 underwent chemotherapy alone and 4971, C + RT. Use of C + RT declined from 2003 to 2011 (73%–53%), whereas chemotherapy alone increased. Of those receiving RT, rates of intensity-modulated radiotherapy (IMRT) increased (27%–72%), whereas 3-dimensional (3D) RT decreased (73%–28%). Unadjusted 1-year overall survival (OS) was longer for versus chemotherapy (45.6% vs 38.7%), as was 2-year OS (12.9% vs 11.9%) (hazard ratio, 0.88; 0.85–0.91; P < 0.001). Under multivariate analysis, C + RT was associated with improved OS (hazard ratio, 0.84; 0.81–0.87; P < 0.001). On subgroup analysis comparing C + IMRT, C + 3D RT, and chemotherapy alone, 1-year OS was 49.1%, 45.1%, and 38.7%, and 2-year OS was 13.1%, 11.6%, and 11.9% accordingly.

Conclusions
Utilization of RT in LAPC is decreasing, whereas chemotherapy alone is increasing. Of patients undergoing RT, rates of IMRT are increasing. Whereas C + IMRT appeared to be associated with improved OS compared with chemotherapy alone, 3D RT was not.
Association of Waist-Hip Ratio to Sudden Cardiac Death and Severe Coronary Atherosclerosis in Medicolegal Autopsies
Authors: Kocovski Linda , Lee Joshua Dogyeong , Parpia Sameer , Fernandes John , Nair Vidhya 
Published: July 2017

Abstract
Various modifiable and nonmodifiable risk factors, such as abdominal obesity, are known to affect the development of atherosclerotic cardiovascular disease and subsequent sudden cardiac death (SCD). The waist-hip ratio is a surrogate marker of visceral obesity that has been shown in various studies to be a better predictor of cardiovascular risk than the body mass index (BMI), a measurement of generalized obesity. Waist-hip ratio was measured prospectively on medicolegal autopsies performed for 1 year, in addition to standard measurements of BMI and heart weight, and histologic determination of severe coronary atherosclerosis (SCA, coronary artery diameter stenosis >75%). Logistic modeling was performed to determine any association between WHR, BMI, cardiovascular disease risk factors, heart weight, and SCD or SCA. Waist-hip ratio was not shown to be statistically significantly associated with either SCD (P = 0.68) or SCA (P = 0.14). Body mass index was shown to be significantly associated with SCA (P < 0.001), and heart weight was shown to be significantly associated with both SCD and SCA (P < 0.001, both). Waist-hip ratio, as a surrogate marker of central obesity and increased risk of atherosclerotic cardiovascular disease, is shown not to be statistically significantly associated with either SCD or SCA in postmortem cases.
Occupational Safety and Health and Healthy Housing: A Review of Opportunities and Challenges
Authors: Jacobs David E. , Forst Linda 
Published: July 2017

Purpose:
Occupational safety and health (OSH) risks in construction of healthy housing (HH) have not been examined and collaboration between HH and OSH professionals is inadequate. The World Health Organization is developing international HH guidelines and the International Labour Organization is working to improve OSH in construction globally.

Methods:
We searched for exemplary reports (including gray literature) on construction hazards; preventive measures for occupants and workers; OSH frameworks, laws, and regulations; definitions; and HH.

Results:
Healthy housing construction typically improves ventilation, moisture and mold, pest control, injury hazards, cleanability, maintenance, accessibility, thermal conditioning, and avoidance of toxic building materials. To date, this work is done without explicit requirements for worker health. Construction is among the most hazardous sectors around the globe, although protective measures are well known, including engineering and administrative controls and provision of personal protective equipment. Residential construction, renovation, repair, and maintenance are fragmented, consisting mostly of small companies without proper OSH training, equipment, and knowledge of HH principles. Residential construction is often undertaken by informal or unauthorized workers, putting them at high risk. Reduced exposure to toxic building materials is an example of a benefit for both workers and occupants if OSH and HH collaboration can be improved. By recognizing that homes under new construction or renovation are both a workplace and a residence, HH and OSH initiatives can apply public health principles to occupants and workers simultaneously. This article publishes key definitions, hazards and interventions common to both fields.

Conclusions:
A global increase in residential construction and renewed global interest in HH poses both risks and opportunities for primary prevention. Policy and practice interventions can benefit the health of occupants and those who work on their homes. Improvements in legislation, regulation, and international frameworks are needed to maximize OSH and HH collaboration and realize significant cobenefits. Occupational safety and health and HH standards should include requirements to protect both workers and occupants. Because homes can also be workplaces, both workers and housing occupants will receive important cobenefits when OSH and HH standards use proven interventions to protect workers and occupants.
Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study
Authors: Dalmolin Gerusa D. , Bannister Kirsty , Gonçalves Leonor , Sikandar Shafaq , Patel Ryan , Cordeiro Marta do Nascimento , Gomez Marcus Vinícius , Ferreira Juliano , Dickenson Anthony H. 
Published: July 2017

Abstract

Introduction:
Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models.

Objectives:
In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL).

Methods:
In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain.

Results:
Tx3-3 (0.3–100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy.

Conclusion:
Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.
R0 Versus R1 Resection Matters after Pancreaticoduodenectomy, and Less after Distal or Total Pancreatectomy for Pancreatic Cancer
Authors: Demir Ihsan Ekin , Jäger Carsten , Schlitter A. Melissa , Konukiewitz Björn , Stecher Lynne , Schorn Stephan , Tieftrunk Elke , Scheufele Florian , Calavrezos Lenika , Schirren Rebekka , Esposito Irene , Weichert Wilko , Friess Helmut , Ceyhan Güralp O. 
Published: July 2017

Objective:
The aim of this study was to decipher the true importance of R0 versus R1 resection for survival in pancreatic ductal adenocarcinoma (PDAC).

Summary of Background Data:
PDAC is characterized by poor survival, even after curative resection. In many studies, R0 versus R1 does not result in different prognosis and does not affect the postoperative management.

Methods:
Pubmed, Embase, and Cochrane databases were screened for prognostic studies on the association between resection status and survival. Hazard ratios (HRs) were pooled in a meta-analysis. Furthermore, our prospective database was retrospectively screened for curative PDAC resections according to inclusion criteria (n = 254 patients) between July 2007 and October 2014.

Results:
In the meta-analysis, R1 was associated with a decreased overall survival [HR 1.45 (95% confidence interval, 95% CI 1.37–1.52)] and disease-free survival [HR 1.44 (1.30–1.59)] in PDAC when compared with R0. Importantly, this effect held true only for pancreatic head resection both in the meta-analysis [R0 ≥0 mm: HR 1.21 (1.05–1.39) vs R0 ≥1 mm: HR 1.66 (1.46–1.89)] and in our cohort (R0 ≥0 mm: 31.8 vs 14.5 months, P < 0.001; R0 ≥1 mm, 41.2 vs 16.8 months; P < 0.001). Moreover, R1 resections were associated with advanced tumor disease, that is, larger tumor size, lymph node metastases, and extended resections. Multivariable Cox proportional hazard model suggested G3, pN1, tumor size, and R1 (0 mm/1 mm) as independent predictors of overall survival.

Conclusion:
Resection margin is not a valid prognostic marker in publications before 2010 due to heterogeneity of cohorts and lack of standardized histopathological examination. Within standardized pathology protocols, R-status’ prognostic validity may be primarily confined to pancreatic head cancers.
Ten-year Outcomes of a Prospective Randomized Trial of Laparoscopic Gastric Bypass Versus Laparoscopic Gastric Banding
Authors: Nguyen Ninh T. , Kim Eric , Vu Stephen , Phelan Michael 
Published: July 2017

Objective:
The primary endpoints of this study were long-term weight loss, morbidity, and changes in comorbidities and quality of life.

Background:
Bariatric surgery is an effective option for the treatment of severe obesity and its related comorbidities. However, few studies have reported on the long-term outcome (>5 yrs) of bariatric surgery.

Methods:
Between 2002 and 2007, 250 patients with a body mass index (BMI) of 35 to 60 kg/m2 were randomly assigned to undergo laparoscopic gastric bypass or laparoscopic gastric banding. After exclusions, 111 patients underwent gastric bypass and 86 patients underwent gastric banding. Factors predictive of improved weight loss were analyzed using multiple logistic regressions.

Results:
At baseline, the mean age was 43 ± 10 years and the mean BMI was 46.5 ± 5.6 kg/m2. At 10-year follow-up, the mean total body weight loss for the entire cohort was −37.5 ± 19.4 kg, −42.4 ± 19.6 kg for gastric bypass versus −27.4 ± 14.5 kg for gastric banding. Late reoperation was significantly higher after gastric banding compared with the gastric bypass group (31.4% vs. 8.1%, respectively, P < 0.01). For the entire cohort, improvement or remission of diabetes occurred in 68%; 61% for hypertension; and 57% for dyslipidemia. The long-term mortality for the entire cohort was 1.0% at a mean follow-up of 9.5 ± 0.4 years. Factors predictive of improved weight loss included the type of operation (ie, gastric bypass), female sex, and the absence of diabetes at baseline. At long-term follow-up, quality of life continues to be improved from baseline for both the groups.

Conclusions:
Bariatric surgery is an effective treatment for severe obesity with durable 10-year weight loss and improvement in comorbidities and quality of life. Compared with gastric banding, gastric bypass was associated with better long-term weight loss, lower rate of late reoperation, and improved remission of comorbidities.
Design and Methods of the Korean Organ Transplantation Registry
Authors: Yang Jaeseok , Jeong Jong Cheol , Lee Joongyub , Kim Young Hoon , Paik Hyo Chae , Kim Jae-Joong , Park Hyun-young , Kim Myoung Soo , Ahn Curie 
Published: July 2017

Background
Beneficial aspects of solid organ transplantation, which encompass survival benefit, improved quality of life, and cost efficacy, have been clearly demonstrated. However, regional and ethnic differences require further studies to identify prognostic factors and transplant outcomes against various backgrounds. After previous efforts of a nationwide, retrospective study on the kidney transplant outcomes in Korea, a new prospective-designed version of the Korean Organ Transplantation Registry (KOTRY) was launched in 2014.

Methods
Cohorts of kidney, liver, heart, lung, and pancreas transplantation were developed. Data on demographics, comorbid conditions, laboratory tests, including tissue typing and panel reactive antibody tests, immunosuppressive regimen followed, concentration and dosage of immunosuppressants, allograft rejection type, infectious events, cardiovascular outcomes, malignancies, donor comorbidity, and outcomes of living donors are collected. Longitudinal data collection is based on a regular annual interval, and blood samples are collected before organ transplantation and again at 1 and 3 years posttransplantation. To enhance data quality, a predefined data verification system operates on a Web-based database, and transplant center users receive regular education about updates. Data are cleansed thrice a year, and feedback given to centers about outlier values and missing data. Annual auditing is conducted.

Results
Currently, 59 centers are participating in KOTRY. The estimated annual enrollment is more than 2000 cases.

Conclusions
KOTRY, as a systematic Korean transplant cohort, is expected to provide important information on Asian organ transplantation. The processes used to establish KOTRY provide a good model for launching new nationwide transplant cohort studies.
A common neural network among state, trait, and pathological anxiety from whole-brain functional connectivity
Authors: Takagi Yu , Sakai Yuki , Abe Yoshinari , Nishida Seiji , Harrison Ben J. , Martínez-Zalacaín Ignacio , Soriano-Mas Carles , Narumoto Jin , Tanaka Saori C. 
Published: July 2017

AbstractAnxiety is one of the most common mental states of humans. Although it drives us to avoid frightening situations and to achieve our goals, it may also impose significant suffering and burden if it becomes extreme. Because we experience anxiety in a variety of forms, previous studies investigated neural substrates of anxiety in a variety of ways. These studies revealed that individuals with high state, trait, or pathological anxiety showed altered neural substrates. However, no studies have directly investigated whether the different dimensions of anxiety share a common neural substrate, despite its theoretical and practical importance. Here, we investigated a neural network of anxiety shared by different dimensions of anxiety in a unified analytical framework using functional magnetic resonance imaging (fMRI). We analyzed different datasets in a single scale, which was defined by an anxiety-related neural network derived from whole brain. Through the fMRI task for provoking anxiety, we found a common neural network of state anxiety across participants (1,638 trials obtained from 10 participants). Then, using the resting-state fMRI in combination with the participants’ trait anxiety scale (879 participants from the Human Connectome Project), we demonstrated that trait anxiety also shared the same neural network as state anxiety. Furthermore, the common neural network between state and trait anxiety could detect patients with obsessive-compulsive disorder, which is characterized by pathological anxiety-driven behaviors (174 participants from multi-site datasets). Our findings provide direct evidence that different dimensions of anxiety are not completely independent but have a substantial biological inter-relationship. Our results also provide a biologically defined dimension of anxiety, which may promote further investigation of various human characteristics, including psychiatric disorders, from the perspective of anxiety.
Imaging and dynamic causal modelling reveal brain-wide changes in effective connectivity and synaptic dynamics during epileptic seizures
Authors: Rosch RE , Hunter PR , Baldeweg T , Friston KJ , Meyer MP 
Published: July 2017

SummaryPathophysiological explanations of epilepsy typically focus on either the micro/mesoscale (e.g. excitation-inhibition imbalance), or on the macroscale (e.g. network architecture). Linking abnormalities across spatial scales remains difficult, partly because of technical limitations in measuring neuronal signatures concurrently at the scales involved. Here we use light sheet imaging of the larval zebrafish brain during acute epileptic seizure induced with pentylenetetrazole. Empirically measured spectral changes of spontaneous neuronal activity during the seizure are then modelled using neural mass models, allowing Bayesian inference on changes in effective network connectivity and their underlying synaptic dynamics. This dynamic causal modelling of seizures in the zebrafish brain reveals concurrent changes in synaptic coupling at macro- and mesoscale. Fluctuations of synaptic connection strength and their temporal dynamics are both required to explain observed seizure patterns. These findings challenge a simple excitation-inhibition account of seizures, and highlight changes in synaptic transmission dynamics as a possible seizure generation pathomechanism.AbbreviationsLFPlocal field potentialPTZpentylenetetrazoleDCMdynamic causal modellingCSDcross spectral densitiesPEBParametric Empirical Bayes