bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model
Authors: Vreman Rick A , Goodell Alex J , Rodriguez Luis A , Porco Travis C , Lustig Robert H , Kahn James G 
Published: August 2017

ObjectivesExcessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars.MethodsUsing data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015–2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%.FindingsThe model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%.ConclusionsThe decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits.
The American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale; translation and validation of the Dutch language version for ankle fractures
Authors: de Boer A Siebe , Tjioe Roderik J C , Van der Sijde Fleur , Meuffels Duncan E , den Hoed Pieter T , Van der Vlies Cornelis H , Tuinebreijer Wim E , Verhofstad Michael H J , Van Lieshout Esther M M 
Published: August 2017

ObjectivesThe American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale is among the most commonly used instruments for measuring outcome of treatment in patients who sustained a complex ankle or hindfoot injury. It consists of a patient-reported and a physician-reported part. A validated, Dutch version of this instrument is currently not available. The aim of this study was to translate the instrument into Dutch and to determine the measurement properties of the AOFAS Ankle-Hindfoot Scale Dutch language version (DLV) in patients with a unilateral ankle fracture.SettingMulticentre (two Dutch hospitals), prospective observational study.ParticipantsIn total, 142 patients with a unilateral ankle fracture were included. Ten patients were lost to follow-up.Primary and secondary outcome measuresPatients completed the subjective (patient-reported) part of the AOFAS Ankle-Hindfoot Scale-DLV. A physician or trained physician-assistant completed the physician-reported part. For comparison and evaluation of the measuring characteristics, the Foot Function Index and the Short Form-36 were completed by the patient. Descriptive statistics (including floor and ceiling effects), reliability (ie, internal consistency), construct validity, reproducibility (ie, test–retest reliability, agreement and smallest detectable change) and responsiveness were determined.ResultsThe AOFAS-DLV and its subscales showed good internal consistency (Cronbach’s α >0.90). Construct validity and longitudinal validity were proven to be adequate (76.5% of predefined hypotheses were confirmed). Floor effects were not present. Ceiling effects were present from 6 months onwards, as expected. Responsiveness was adequate, with a smallest detectable change of 12.0 points.ConclusionsThe AOFAS-DLV is a reliable, valid and responsive measurement instrument for evaluating functional outcome in patients with a unilateral ankle fracture. This implies that the questionnaire is suitable to compare different treatment modalities within this population or to compare outcome across hospitals.Trial registrationThe Netherlands Trial Register (NTR5613; 05-jan-2016).
Development of autoimmune pancreatitis is independent of CDKN1A/p21-mediated pancreatic inflammation
Authors: Seleznik Gitta M , Reding Theresia , Peter Lukas , Gupta Anurag , Steiner Sabrina G , Sonda Sabrina , Verbeke Caroline S , Dejardin Emmanuel , Khatkov Igor , Segerer Stephan , Heikenwalder Mathias , Graf Rolf 
Published: August 2017

ObjectiveChronic pancreatitis (CP) and autoimmune pancreatitis (AIP) are characterised by different inflammatory processes. If pancreatic inflammation is a prerequisite for autoimmunity is still unclear. AIP is considered mostly a T cell-mediated disease; however, in induction of CP, macrophages play a pivotal role. p21—a member of cyclin-dependent kinase inhibitors—can influence inflammatory processes, in particular can regulate T cell activation and promote macrophage development. We therefore examined the role of p21-mediated inflammation in AIP.DesignWe intercrossed lymphotoxin (LT) overexpressing mice (Tg(Ela1-LTa,b))—a model to study AIP development—with p21-deficient mice. Furthermore, we characterised p21 expression in human AIP and non-AIP specimens.Resultsp21 deficiency in LT mice (LTp21−/−) prevented early pancreatic injury and reduced inflammation. In acinar cells, diminished proliferation and abrogated activation of non-canonical nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway was observed. In contrast, 12-month-old LT mice with and without p21 had similar inflammatory signatures and T–B cell infiltration. Interestingly, LT and LTp21−/−mice had comparable tertiary lymphoid organs (TLOs), autoantibodies and elevated IgG levels. However, acinar cell proliferation, acinar-to-ductal metaplasia and acinar non-canonical NF-κB pathway activation remained impaired in LTp21−/−pancreata.ConclusionsOur findings indicate that p21 is crucial for pancreatic inflammation in LT-driven pancreatic injury. p21 is involved in early acinar secretion of inflammatory mediators that attract innate immune cells. However, p21 is not essential for humoral immune response, accountable for autoimmunity. Remarkably, p21 renders acinar cells less susceptible to proliferation and transdifferentiation. We therefore suggest that AIP can also develop independent of chronic inflammatory processes.
Generating a city’s first report on bicyclist safety: lessons from the field
Authors: Lopez Dahianna S , Hemenway David 
Published: August 2017

BackgroundFor cities aiming to create a useful surveillance system for bicycle injuries, a common challenge is that city crash reporting is scattered, faulty or non-existent. We document some of the lessons we learnt in helping the city of Boston, Massachusetts, USA, do the following: (1) Create a prototype for a comprehensive police crash data set (2) Produce the city’s first cyclist safety report, (3) Make crash data available to the public and (4) Generate policy recommendations for both specific roadside improvements and for sustainable changes to the police department’s crash reporting database.MethodsWe provided research and technical assistance to government partners to generate the report and used participant-observation field notes to generate the list of learnt lessons.ResultsAfter the release of the report, the city implemented immediate activities aimed at making an effort to prevent injuries, including: (1) Furnishing over 1800 taxis with stickers to prevent ‘dooring,’ (2) Adding pavement markings at trolley tracks to decrease the likelihood that cyclists would fall from getting their wheels lodged in the tracks, (3) Conducting targeted enforcement of traffic laws and (4) Working directly with state and federal agencies to fund a more comprehensive surveillance system. As of January of 2017, nearly 4 years after its public release, 19 170 users have viewed the crash data set 23 247 times. Some of the lessons include finding and using committed champions, prioritising the use of existing data, creating opportunities to bridge divisions between stakeholders, partnering with local universities for assistance with advanced analytics and using deliverables, such as a cyclist safety report, to advocate for sustainability.ConclusionProviding an initial report on bicycle crashes in Boston served to identify specific problems, showed the value of a data system, and provided a blueprint for an improved data system. Building a useful surveillance system depends in no small part on the wise use of advocacy, group dynamics, and politics. Our hope is that the lessons learnt from our experience in Boston can help others do even better.
Non-tuberculous Mycobacterium or Fungus Induced Chronic Tenosynovitis with Rice Body of the Hand
Authors: Yamamoto Daiki , Tada Kaoru , Suganuma Seigo , Ikeda Kazuo , Tsuchiya Hiroyuki 
Published: August 2017

Background: Chronic tenosynovitis of the wrist and hand is commonly seen by orthopedists, especially hand surgeons. However, cases with rice body formation are comparatively rare. Thus, we retrospectively reviewed the cases of chronic tenosynovitis in our department and evaluated the necessity of antibiotic therapy in the early post-surgical stage. Methods: We analyzed the medical and surgical records of patients who had undergone surgery for chronic tenosynovitis with rice body formation in our department from 1997 to 2015. We evaluated the causes of chronic tenosynovitis, culture findings, pathological findings, and post-operative treatment courses. Results: Nineteen patients with 23 involved hands underwent surgery for chronic tenosynovitis, and 9 patients had rice body formation. The most common cause of chronic tenosynovitis was non-tuberculous mycobacteriosis, and other causes were fungal infection and infection of unknown origin. Recurrence was observed in 2 cases of mycobacteriosis and 1 case of fungal infection; 1 case of mycobacteriosis also had a re-recurrence. Conclusions: In the diagnosis of chronic tenosynovitis with rice body formation, it is necessary to consider not only non-tuberculous mycobacteriosis, but also fungal infection as its origin. However, it is difficult to define the cause of synovitis, but in cases in which these infections are suspected, anti-bacterial therapy in the early post-surgical period could be effective.
Relationship of gastric emptying or accommodation with satiation, satiety, and postprandial symptoms in health
Authors: Halawi Houssam , Camilleri Michael , Acosta Andres , Vazquez-Roque Maria , Oduyebo Ibironke , Burton Duane , Busciglio Irene , Zinsmeister Alan R. 
Published: August 2017

The contributions of gastric emptying (GE) and gastric accommodation (GA) to satiation, satiety, and postprandial symptoms remain unclear. We aimed to evaluate the relationships between GA or GE with satiation, satiety, and postprandial symptoms in healthy overweight or obese volunteers (total n = 285, 73% women, mean BMI 33.5 kg/m2): 26 prospectively studied obese, otherwise healthy participants and 259 healthy subjects with previous similar GI testing. We assessed GE of solids, gastric volumes, calorie intake at buffet meal, and satiation by measuring volume to comfortable fullness (VTF) and maximum tolerated volume (MTV) by using Ensure nutrient drink test (30 ml/min) and symptoms 30 min after MTV. Relationships between GE or GA with satiety, satiation, and symptoms were analyzed using Spearman rank ( rs) and Pearson ( R) linear correlation coefficients. We found a higher VTF during satiation test correlated with a higher calorie intake at ad libitum buffet meal ( rs = 0.535, P < 0.001). There was a significant inverse correlation between gastric half-emptying time (GE T1/2) and VTF ( rs = −0.317, P < 0.001) and the calorie intake at buffet meal ( rs = −0.329, P < 0.001), and an inverse correlation between GE Tlag and GE25% emptied with VTF ( rs = −0.273, P < 0.001 and rs = −0.248, P < 0.001, respectively). GE T1/2 was significantly associated with satiation (MTV, R = −0.234, P < 0.0001), nausea ( R = 0.145, P = 0.023), pain ( R = 0.149, P = 0.012), and higher aggregate symptom score ( R = 0.132, P = 0.026). There was no significant correlation between GA and satiation, satiety, postprandial symptoms, or GE. We concluded that GE of solids, rather than GA, is associated with postprandial symptoms, satiation, and satiety in healthy participants. NEW & NOTEWORTHY A higher volume to comfortable fullness postprandially correlated with a higher calorie intake at ad libitum buffet meal. Gastric emptying of solids is correlated to satiation (volume to fullness and maximum tolerated volume) and satiety (the calorie intake at buffet meal) and symptoms of nausea, pain, and aggregate symptom score after a fully satiating meal. There was no significant correlation between gastric accommodation and either satiation or satiety indices, postprandial symptoms, or gastric emptying.
Temporal changes in the exercise pressor reflex in type 1 diabetic rats
Authors: Grotle Ann-Katrin , Garcia Elizabeth A. , Huo Yu , Stone Audrey J. 
Published: August 2017

Previous studies have shown that diabetic peripheral neuropathy affects both unmyelinated and myelinated afferents, similar to those evoking the exercise pressor reflex. However, the effect of type 1 diabetes (T1DM) on this reflex is not known. We examined, in decerebrate male and female T1DM [streptozotocin (STZ)] and healthy control (CTL) rats, pressor and cardioaccelerator responses to isometric contraction of the hindlimb muscles during the early and late stages of the disease. STZ (50 mg/kg) was injected to induce diabetes, and experiments were conducted at 1, 3, and 6 wk after injection. On the day of the experiment, we statically contracted the hindlimb muscles by stimulating the sciatic nerve and measured changes in mean arterial pressure and heart rate. We found that the pressor but not cardioaccelerator response was exaggerated in STZ rats at 1 wk (STZ: 21 ± 3 mmHg, n = 10, and CTL: 14 ± 2 mmHg, n = 10, P < 0.05) and at 3 wk (STZ: 26 ± 5 mmHg, n = 10, and CTL: 17 ± 3 mmHg, n = 11, P < 0.05) after injection. However, at 6 wk, and only in male rats, both the pressor (STZ: 13 ± 3 mmHg, n = 12, and CTL: 17 ± 3 mmHg, n = 13, P < 0.05) and cardioaccelerator responses (STZ: 7 ± 3 beats/min, n = 12, and CTL: 10 ± 3 beats/min, n = 13, P < 0.05) to contraction were significantly attenuated in STZ rats compared with CTL rats. These data indicate that T1DM exaggerates the exercise pressor reflex during the early stages of the disease in both male and female rats. Conversely, T1DM attenuates this reflex in the late stage of the disease in male but not female rats. NEW & NOTEWORTHY This is the first study to provide evidence that the pressor and cardioaccelerator responses to skeletal muscle contraction vary depending on the duration of type 1 diabetes.
Aneuploid Cell Survival Relies upon Sphingolipid Homeostasis
Authors: Tang Yun-Chi , Yuwen Hui , Wang Kaiying , Bruno Peter M. , Bullock Kevin , Deik Amy , Santaguida Stefano , Trakala Marianna , Pfau Sarah J. , Zhong Na , Huang Tao , Wang Lan , Clish Clary B. , Hemann Michael T. , Amon Angelika 
Published: August 2017

Abstract
Aneuploidy, a hallmark of cancer cells, poses an appealing opportunity for cancer treatment and prevention strategies. Using a cell-based screen to identify small molecules that could selectively kill aneuploid cells, we identified the compound N-[2-hydroxy-1-(4-morpholinylmethyl)-2-phenylethyl]-decanamide monohydrochloride (DL-PDMP), an antagonist of UDP-glucose ceramide glucosyltransferase. DL-PDMP selectively inhibited proliferation of aneuploid primary mouse embryonic fibroblasts and aneuploid colorectal cancer cells. Its selective cytotoxic effects were based on further accentuating the elevated levels of ceramide, which characterize aneuploid cells, leading to increased apoptosis. We observed that DL-PDMP could also enhance the cytotoxic effects of paclitaxel, a standard-of-care chemotherapeutic agent that causes aneuploidy, in human colon cancer and mouse lymphoma cells. Our results offer pharmacologic evidence that the aneuploid state in cancer cells can be targeted selectively for therapeutic purposes, or for reducing the toxicity of taxane-based drug regimens. Cancer Res; 77(19); 5272–86. ©2017 AACR.
Identification of Novel Breast Cancer Risk Loci
Authors: Chan Claire Hian Tzer , Munusamy Prabhakaran , Loke Sau Yeen , Koh Geok Ling , Wong Edward Sern Yuen , Law Hai Yang , Yoon Chui Sheun , Tan Min-Han , Yap Yoon Sim , Ang Peter , Lee Ann Siew Gek 
Published: August 2017

AbstractIt has been estimated that &gt;1,000 genetic loci have yet to be identified for breast cancer risk. Here we report the first study utilizing targeted next-generation sequencing to identify single-nucleotide polymorphisms (SNP) associated with breast cancer risk. Targeted sequencing of 283 genes was performed in 240 women with early-onset breast cancer (≤40 years) or a family history of breast and/or ovarian cancer. Common coding variants with minor allele frequencies (MAF) &gt;1% that were identified were presumed initially to be SNPs, but further database inspections revealed variants had MAF of ≤1% in the general population. Through prioritization and stringent selection criteria, we selected 24 SNPs for further genotyping in 1,516 breast cancer cases and 1,189 noncancer controls. Overall, we identified the JAK2 SNP rs56118985 to be significantly associated with overall breast cancer risk. Subtype analysis performed for patient subgroups defined by ER, PR, and HER2 status suggested additional associations of the NOTCH3 SNP rs200504060 and the HIF1A SNP rs142179458 with breast cancer risk. In silico analysis indicated that coding amino acids encoded at these three SNP sites were conserved evolutionarily and associated with decreased protein stability, suggesting a likely impact on protein function. Our results offer proof of concept for identifying novel cancer risk loci from next-generation sequencing data, with iterative data analysis from targeted, whole-exome, or whole-genome sequencing a wellspring to identify new SNPs associated with cancer risk. Cancer Res; 77(19); 5428–37. ©2017 AACR.
89Zr-anti-γH2AX-TAT but not 18F-FDG Allows Early Monitoring of Response to Chemotherapy in a Mouse Model of Pancreatic Ductal Adenocarcinoma
Authors: Knight James C. , Mosley Michael J. , Bravo Luisa Contreras , Kersemans Veerle , Allen P. Danny , Mukherjee Somnath , O'Neill Eric , Cornelissen Bart 
Published: August 2017

Abstract
Purpose: Late-stage, unresectable pancreatic ductal adenocarcinoma (PDAC) is largely resistant to chemotherapy and consequently has a very poor 5-year survival rate of &lt;5%. The ability to assess the efficacy of a treatment soon after its initiation would enable rapid switching to potentially more effective therapies if the current treatment is found to be futile. We have evaluated the ability of the PET imaging agent, 89Zr-anti-γH2AX-TAT, to monitor DNA damage in response to fluorouracil (5-FU), gemcitabine, or capecitabine treatment in a mouse model of pancreatic cancer. We have also compared the utility of this approach against the standard clinical PET radiotracer, 18F-FDG.
Experimental Design: C57BL/6 mice bearing subcutaneous pancreatic cancer (KPC; B8484) allografts were treated with 5-FU, gemcitabine, or capecitabine. Therapeutic response was monitored by PET and ex vivo biodistribution experiments using either 89Zr-anti-γH2AX-TAT or 18F-FDG as imaging agents. To further examine the effect of therapeutic response upon uptake of these imaging agents, IHC analysis of harvested tumor allograft tissue was also performed.
Results: Accumulation of 89Zr-anti-γH2AX-TAT in the tumors of mice that received chemotherapy was higher compared with vehicle-treated mice and was shown to be specifically mediated by γH2AX. In contrast, 18F-FDG did not provide useful indications of therapeutic response.
Conclusions: 89Zr-anti-γH2AX-TAT has shown a superior ability to monitor early therapeutic responses to chemotherapy by PET imaging compared with 18F-FDG in an allograft model of PDAC in mice. Clin Cancer Res; 23(21); 6498–504. ©2017 AACR.
A Multikinase and DNA-PK Inhibitor Combination Immunomodulates Melanomas, Suppresses Tumor Progression, and Enhances Immunotherapies
Authors: Tsai Alexander K. , Khan Asra Y. , Worgo Christina E. , Wang Lucy L. , Liang Yuanyuan , Davila Eduardo 
Published: August 2017

AbstractCombination therapies have the potential to improve outcomes in melanoma patients but have not yet been clinically efficacious. Here, we used high-throughput flow cytometry-based screening to identify and characterize candidate therapies that might synergize with and augment T-cell immunotherapy efficacy. Two lead therapies, regorafenib (Reg) and NU7441, were selected based on their ability to alter a variety of immunomodulatory proteins, including CD55, CD73, CD155, programmed death-ligand 1 (PD-L1), nerve growth factor receptor (NGFR), and HLA class I in a heterogeneous panel of melanomas. The therapies also upregulated several melanoma antigens, inhibited proliferation, and perturbed activation of oncogenic signaling pathways in melanomas. T cells treated with the therapies proliferated normally and exhibited a favorably altered phenotype, including increased CD25, CD28, inducible T-cell costimulator (ICOS), and reduced expression of coinhibitory receptors. Cytokine production was also increased in treated T cells. When administered in mice, REg suppressed melanoma progression in a CD8+ T cell–dependent manner when used alone and with various immunotherapies. Additionally, Reg altered the number, phenotype, and function of various T-cell subsets in the tumor microenvironment. These studies reveal that Reg and NU7441 influence the immunobiology of both tumor cells and T cells and enhance the efficacy of various immunotherapies. Cancer Immunol Res; 5(9); 790–803. ©2017 AACR.