bluuebunny/crossref_metadata_2025_split huggingface dataset:
The HEART Pathway Randomized Controlled Trial One‐year Outcomes
Authors: Stopyra Jason P. , Riley Robert F. , Hiestand Brian C. , Russell Gregory B. , Hoekstra James W. , Lefebvre Cedric W. , Nicks Bret A. , Cline David M. , Askew Kim L. , Elliott Stephanie B. , Herrington David M. , Burke Gregory L. , Miller Chadwick D. , Mahler Simon A. 
Published: June 2018

AbstractObjectiveThe objective was to determine the impact of the HEART Pathway on health care utilization and safety outcomes at 1 year in patients with acute chest pain.MethodsAdult emergency department (ED) patients with chest pain (N = 282) were randomized to the HEART Pathway or usual care. In the HEART Pathway arm, ED providers used the HEART score and troponin measures (0 and 3 hours) to risk stratify patients. Usual care was based on American College of Cardiology/American Heart Association guidelines. Major adverse cardiac events (MACE—cardiac death, myocardial infarction [MI], or coronary revascularization), objective testing (stress testing or coronary angiography), and cardiac hospitalizations and ED visits were assessed at 1 year. Randomization arm outcomes were compared using Fisher's exact tests.ResultsA total of 282 patients were enrolled, with 141 randomized to each arm. MACE at 1 year occurred in 10.6% (30/282): 9.9% in the HEART Pathway arm (14/141; 10 MIs, four revascularizations without MI) versus 11.3% in usual care (16/141; one cardiac death, 13 MIs, two revascularizations without MI; p = 0.85). Among low‐risk HEART Pathway patients, 0% (0/66) had MACE, with a negative predictive value (NPV) of 100% (95% confidence interval = 93%–100%). Objective testing through 1 year occurred in 63.1% (89/141) of HEART Pathway patients compared to 71.6% (101/141) in usual care (p = 0.16). Nonindex cardiac‐related hospitalizations and ED visits occurred in 14.9% (21/141) and 21.3% (30/141) of patients in the HEART Pathway versus 10.6% (15/141) and 16.3% (23/141) in usual care (p = 0.37, p = 0.36).ConclusionsThe HEART Pathway had a 100% NPV for 1‐year safety outcomes (MACE) without increasing downstream hospitalizations or ED visits. Reduction in 1‐year objective testing was not significant.
Cigarette consumption and biomarkers of nicotine exposure during pregnancy and postpartum
Authors: Taghavi Taraneh , Arger Christopher A. , Heil Sarah H. , Higgins Stephen T. , Tyndale Rachel F. 
Published: June 2018

AbstractBackground and AimsSmokers can regulate their nicotine intake by altering the number of cigarettes smoked per day (CPD) and their smoking intensity. The current study aimed to compare the utility of self‐reported CPD, total nicotine equivalents (TNE) and urinary cotinine to estimate nicotine intake during pregnancy.DesignLongitudinal smoking behavior and biomarker data were collected at early pregnancy, late pregnancy and at postpartum as part of a smoking cessation trial to examine voucher‐based incentives for decreasing smoking.SettingObstetric practices in Burlington, Vermont, United States.ParticipantsA subset of participants (n = 47) from the parent trial, recruited between December 2006 and June 2012, who provided a urine sample at each assessment during early pregnancy, late pregnancy and postpartum.MeasurementsSmoking was assessed using self‐reported CPD, TNE, TNE/CPD and urinary cotinine.FindingsPregnant smokers reported smoking 10.4 CPD at early pregnancy, 7.2 CPD at late pregnancy (a 31% reduction at late pregnancy, P = 0.001) and 8.6 CPD at postpartum (a 19% increase from late pregnancy, P = 0.08). TNE exposure was 41% (P = 0.07) and 48% (P = 0.03) lower at early and late pregnancy, respectively, compared to postpartum. TNE/CPD was on average 167% higher at late pregnancy compared to early pregnancy (P = 0.01) and remained high at postpartum, where it was 111% higher compared to early pregnancy (P = 0.007). Uriniary cotinine underestimated nicotine intake by 55% during early pregnancy and by 65% during late pregnancy compared to postpartum (Pinteraction < 0.001); the underestimation was greater in slower (Pinteraction < 0.001) versus faster (Pinteraction = 0.04) nicotine metabolizers.ConclusionsNeither cigarettes smoked per day (CPD) nor cotinine provides an accurate estimate of nicotine exposure during pregnancy. CPD underestimates nicotine intake substantially due to under‐reporting and/or higher intensity of smoking, while cotinine underestimates nicotine intake markedly due to accelerated nicotine (and cotinine) metabolism during pregnancy.
After how many drinks does someone experience acute consequences—determining thresholds for binge drinking based on two event‐level studies
Authors: Labhart Florian , Livingston Michael , Engels Rutger , Kuntsche Emmanuel 
Published: June 2018

AbstractBackground and AimsThe threshold of 4+/5+ drinks per occasion has been used for decades in alcohol research to distinguish between non‐risky versus risky episodic drinking. However, no study has assessed the validity of this threshold using event‐level data. This study aimed to determine the optimal thresholds for the detection of five acute alcohol‐related consequences (hangover, blackout, risky sex, fights and injury) using data from two event‐level studies.DesignAn event‐level study to assess the ability to use the number of drinks consumed to discriminate between nights with and without consequences using the area under the receiver operating characteristic (AUROC) curve. Optimal thresholds were determined using the Youden Index based on sensitivity and specificity. Separate thresholds were estimated for gender and age groups (16–17 versus 18–25).SettingLausanne and Zurich, Switzerland.ParticipantsThree hundred and sixty‐nine participants aged 16–25 years.MeasurementsOn 3554 weekend nights, participants reported total number of alcoholic drinks consumed the previous night and acute consequences (hangover, blackout, risky sex, fights and injury)FindingsHangover was the most frequently reported consequence and injury the least for both genders. Throughout age groups and studies, optimal thresholds for any consequence, and for hangover only, were equal to 4+/5+ (40+/50+ g alcohol) while those for blackouts, risky sex, fights and injuries were up to three drinks higher. Adolescents tended to experience consequences more often and at slightly lower drinking levels than did adults. For all consequences but injuries, the optimal thresholds were one to two drinks lower for women than for men.ConclusionsEvent‐level data collection techniques appear particularly suitable to estimate thresholds at which acute alcohol‐related consequences occur. Binge drinking thresholds of 4+/5+ (women/men) drinks, equivalent to 40+/50+ g pure alcohol, predict the occurrence of consequences accurately in general but are too low to predict severe acute alcohol‐related consequences.
Recent trends in the management of pelvic organ prolapse in Australia and New Zealand
Authors: Miller Brendan J. , Seman Elvis I. , O'Shea Robert T. , Hakendorf Paul H. , Nguyen Tran T.T. 
Published: June 2018

ObjectiveTo compare current practice in the management of female pelvic organ prolapse in Australia and New Zealand with that in 2007, and assess the impact on practice of the withdrawal of Prolift® and Prosima® mesh kits in 2015.Materials and MethodsIn early 2015, two invitations to participate in a survey, including a link to Surveymonkey, were emailed to 2506 Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) trainees and fellows. The online survey closely resembled a printed survey that was posted to RANZCOG trainees and fellows in 2007 and had additional questions relating to the impact of withdrawal of Prolift® and Prosima® products.ResultsFour‐hundred‐and‐three doctors participated, giving a response rate of 16%. Native tissue repair was the procedure of choice for primary and recurrent prolapse of the anterior and posterior vaginal wall. An implant was used to treat 45% of anterior recurrences and 25% of posterior recurrences. Vaginal hysterectomy and repair were the procedures of choice for uterovaginal prolapse. Sacrospinous hysteropexy was the uterine preservation procedure of choice, preferred by 41%. For post‐hysterectomy vault prolapse, sacrospinous colpopexy and vaginal repair was preferred by 65% of respondents. Between 2007 and 2015, there was a substantial decrease in respondents’ usage of implants across all indications except for midurethral slings and sacrocolpo/hysteropexy. Forty‐two percent of respondents changed their practice as a result of Prolift® and Prosima® being withdrawn.ConclusionThere is a trend toward increasing use of various native tissue prolapse repair procedures and midurethral slings, and less utilisation of transvaginal mesh for prolapse.
LAMP‐1 gene is overexpressed in high grade glioma
Authors: Sarafian Victoria S. , Koev Ilian , Mehterov Nikolay , Kazakova Maria , Dangalov Krassimir 
Published: June 2018

High‐grade gliomas (HGG) are the most frequent brain tumors in adults. Glioblastoma multiforme (GBM) is their most aggressive form resistant to therapy. It was shown that inhibition of autophagy reduced GBM development and autophagy interfering agents are regarded as a new strategy to fight glioma cells. The lysosome‐associated membrane proteins (LAMPs) display differential expression particularly in cancer. There are few data on their expression and especially on their molecular profile. The aim of the present study is to investigate the expression of LAMP‐1 and LAMP‐2 genes and proteins in HGG. Newly diagnosed patients with HGG and healthy controls were examined by immunohistochemistry and qPCR for both protein and mRNA levels of LAMP‐1 and LAMP‐2. The transcriptional activity of LAMP‐1 in HGG was significantly higher compared to normal brain and to LAMP‐2. The two glycoproteins were detected in the cytosol of tumor cells with varying intensity, LAMP‐1 showing again enhanced expression. In conclusion, novel data on LAMP‐1 overexpression in HGG are presented suggesting involvement of this gene and protein in cell adhesion and tumor progression. These findings might help the elucidation of the complex biological role of the multifunctional LAMPs proteins and to predict novel therapeutic targets in lysosomes.
High incidence of autoimmune gastritis in patients misdiagnosed with two or more failures of H. pylori eradication
Authors: Furuta T. , Baba S. , Yamade M. , Uotani T. , Kagami T. , Suzuki T. , Tani S. , Hamaya Y. , Iwaizumi M. , Osawa S. , Sugimoto K. 
Published: June 2018

SummaryBackgroundAlthough autoimmune gastritis (AIG) is generally considered relatively rare, we frequently encounter AIG among patients at to our hospital who have experienced at least two episodes of Helicobacter pylori eradication failure.AimsWe investigated the incidence of AIG in consecutive patients who consulted our department for H. pylori eradication with reference to eradication history.MethodsA total of 404 consecutive patients who visited the H. pylori‐specific out‐patient unit of our hospital from June 2015 to June 2017 were enrolled. Of these, 137 were treatment‐naive, 47 had failed treatment once (single failure), and 220 had failed treatment twice or more (multiple failures) by 13C‐UBT. Gastroscopy was performed in all patients. Culture tests of gastric mucosal samples were performed for H. pylori and other bacteria positive for urease activity. Anti‐parietal cell antibody (APCA) was measured. Patients with severe atrophy in the gastric corpus and positivity for APCA were diagnosed as having AIG.ResultsA total of 43 patients were diagnosed as having AIG, of whom two were treatment‐naive (1.5%, 2/137), 1 failed eradication once (2.1% 1/47), and 40 failed treatment at least twice (18.2%, 40/220). The incidence of AIG was significantly higher in the multiple failure group than in the single failure or treatment‐naive groups. Urease‐positive bacteria, such as Klebsiella pneumoniae and alpha‐streptococcus, were identified in 33 of the 35 AIG patients who underwent culture testing.ConclusionAIG patients were often misdiagnosed as refractory to eradication therapy, probably because achlorhydria in AIG might allow urease‐positive bacteria other than H. pylori to colonise the stomach, causing positive 13C‐UBT results.
Self‐ownership, relational dignity, and organ sales
Authors: Hershenov David 
Published: June 2018

AbstractMaterial property has traditionally been conceived of as separable from its owner and thus alienable in an exchange. So it seems that you could sell your watch or even your kidney because it can be removed from your wrist or abdomen and transferred to another. However, if we are each identical to a living human animal, self‐ownership is impossible for self‐separation is impossible. We thus cannot sell our parts if we don't own the whole that they compose. It would be incoherent to own all of your body's parts but not the whole body; and it would be arbitrary to own some but not all of your removable parts. These metaphysical obstacles to organ sales do not apply to the selling of the organs of the deceased. The human being goes out of existence at death and is not identical to the body's remains. Any objections to selling the organs of the deceased must instead be due to dignity rather than metaphysical or conceptual considerations. But the remains lack the intrinsic dignity of the human being, instead possessing, at best, relational dignity. Relational dignity would not provide sufficient reason to prohibit life‐saving sales.
Physical Activity Classification with Dynamic Discriminative Methods
Authors: Ray Evan L. , Sasaki Jeffer E. , Freedson Patty S. , Staudenmayer John 
Published: June 2018

Summary
A person's physical activity has important health implications, so it is important to be able to measure aspects of physical activity objectively. One approach to doing that is to use data from an accelerometer to classify physical activity according to activity type (e.g., lying down, sitting, standing, or walking) or intensity (e.g., sedentary, light, moderate, or vigorous). This can be formulated as a labeled classification problem, where the model relates a feature vector summarizing the accelerometer signal in a window of time to the activity type or intensity in that window. These data exhibit two key characteristics: (1) the activity classes in different time windows are not independent, and (2) the accelerometer features have moderately high dimension and follow complex distributions. Through a simulation study and applications to three datasets, we demonstrate that a model's classification performance is related to how it addresses these aspects of the data. Dynamic methods that account for temporal dependence achieve better performance than static methods that do not. Generative methods that explicitly model the distribution of the accelerometer signal features do not perform as well as methods that take a discriminative approach to establishing the relationship between the accelerometer signal and the activity class. Specifically, Conditional Random Fields consistently have better performance than commonly employed methods that ignore temporal dependence or attempt to model the accelerometer features.
Phase III randomized study of the proposed adalimumab biosimilar GP2017 in psoriasis: impact of multiple switches
Authors: Blauvelt A. , Lacour J.-P. , Fowler J.F. , Weinberg J.M. , Gospodinov D. , Schuck E. , Jauch-Lembach J. , Balfour A. , Leonardi C.L. 
Published: June 2018

Summary

Background
Adalimumab is used to treat several inflammatory diseases, including plaque psoriasis. GP2017 is a proposed adalimumab biosimilar.

Objectives
To assess the impact of multiple switches between GP2017 and reference adalimumab (ref-ADMB) following the demonstration of equivalent efficacy and similar safety and immunogenicity, in adult patients with active, clinically stable, moderate-to-severe plaque psoriasis.

Methods
This 51-week double-blinded, phase III study randomly assigned patients to GP2017 (n = 231) or ref-ADMB (n = 234) 80 mg subcutaneously at week 0, then 40 mg biweekly from week 1. At week 17, patients were rerandomized to switch (n = 126) or continue (n = 253) treatment. The primary end point was patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 16, with equivalence confirmed if the 95% confidence interval (CI) for the difference in PASI 75 between treatments was ± 18%. The key secondary end point was the change from baseline to week 16 in continuous PASI. Other end points were PASI over time; PASI 50, 75, 90 and100; pharmacokinetics; safety; tolerability and immunogenicity for the switched and continued treatment groups.

Results
Equivalent efficacy between GP2017 and ref-ADMB was confirmed for the primary (66·8% and 65·0%, respectively; 95% CI −7·46 to 11·15) and key secondary end points (−60·7% and −61·5%, respectively; 95% CI –3·15 to 4·84). PASI improved over time and was similar between treatment groups at week 16, and the switched and continued groups from weeks 17 to 51. There were no relevant safety or immunogenicity differences between GP2017 and ref-ADMB at week 16, or the switched and continued groups from weeks 17 to 51. No hypersensitivity to adalimumab was reported upon switching.

Conclusions
Following the demonstration of GP2017 biosimilarity to ref-ADMB, switching up to four times between GP2017 and ref-ADMB had no detectable impact on efficacy, safety or immunogenicity.
Role of histone deacetylase 1 in distant metastasis of pancreatic ductal cancer
Authors: Shinke Go , Yamada Daisaku , Eguchi Hidetoshi , Iwagami Yoshifumi , Asaoka Tadafumi , Noda Takehiro , Wada Hiroshi , Kawamoto Koichi , Gotoh Kunihito , Kobayashi Shogo , Takeda Yutaka , Tanemura Masahiro , Mori Masaki , Doki Yuichiro 
Published: June 2018

Current therapies for pancreatic ductal cancer (PDAC) do not sufficiently control distant metastasis. Thus, new therapeutic targets are urgently needed. Numerous studies have suggested that the epithelial‐mesenchymal transition (EMT) is pivotal for metastasis of carcinomas. The fact that the EMT is reversible suggests the possibility that it is induced by an epigenetic mechanism. In this study, we aimed to investigate the role of histone deacetylase 1 (HDAC1), which is an epigenetic mechanism on distant metastasis of PDAC. We investigated the HDAC1 expression in 103 resected PDAC specimens obtained from patients who were treated with/without preoperative therapy using immunohistochemistry. To validate the findings in the clinical samples, we evaluated the HDAC1 activity, the EMT‐associated genes and the migration/invasion ability in vitro, and performed an HDAC1 inhibitor assay. The high expression of HDAC1 in clinical samples was significantly associated with poor progression‐free survival, especially distant metastasis‐free survival. In vitro, HDAC1 inhibitors decreased the invasion ability and reversed the EMT change; the only factor to show a concomitant decrease was the expression of SNAIL. We confirmed that the HDAC1 expression was associated with the SNAIL expression in clinical samples. Moreover, the resistant cells and parental cells did not show any significant differences in the expression of HDAC1; this was consistent with the finding that preoperative therapy did not alter the HDAC1 expression in clinical samples. The targeting of HDAC1, which could suppress metastasis by inhibiting the EMT, is a promising treatment option for PDAC.
Immunotherapy with oral administration of humanized anti-CD3 monoclonal antibody: a novel gut-immune system-based therapy for metaflammation and NASH
Authors: Ilan Y , Shailubhai K , Sanyal A 
Published: June 2018

Summary
The immune system plays a role in the pathogenesis of non-alcoholic steatohepatitis (NASH) underlying hepatocyte injury and fibrosis progression at all disease stages. Oral administration of anti-CD3 monoclonal antibody (mAb) has been shown in preclinical studies to be an effective method for systemic immune modulation and alleviates immune-mediated disorders without T cell depletion. In the present review, we summarize the concept of the oral administration of humanized anti-CD3 mAb in patients with NASH and discuss the potential of this treatment to address the current requirements of treatments for NASH. Recently published preclinical and clinical data on oral administration of anti CD3 are discussed. Human trials have shown that the oral administration of anti-CD3 in healthy volunteers, patients with chronic hepatitis C virus (HCV) infection and patients with NASH and type 2 diabetes is safe and well tolerated, as well as biologically active. Oral anti-CD3 induces regulatory T cells, suppresses the chronic inflammatory state associated with NASH and exerts a beneficial effect on clinically relevant parameters. Foralumab is a fully human anti-CD3 mAb that has recently been shown to exert a potent anti-inflammatory effect in humanized mice. It is being developed for treatment of NASH and primary biliary cholangitis (PBC). Oral administration of anti CD3 may provide an effective therapy for patients with NASH.
Long‐term follow‐up of a large prospective cohort of patients with nonfunctioning pituitary adenomas: The outcome of a conservative management policy
Authors: Levy Miles J. , Robertson Iain J , Khalk Naima , Vitello Sabrina , Reddy Narendra , Bhake Ragini , Howlett Trevor A. 
Published: June 2018

AbstractObjectiveTo assess the clinical outcome of a strategy of conservative monitoring of patients with nonfunctioning pituitary adenomas (NFPA) after pituitary surgery and in patients without surgery.DesignRetrospective study of outcomes, using a clinical information system.PatientsAn unselected, clinical series of patients seen in a single centre between 1989 and 2015.MeasurementsReview of clinical information system data to obtain details and dates of surgery, radiotherapy, pituitary imaging and outcomes.ResultsWe identified 190 cases of NFPA. Trans‐sphenoidal surgery (TSS) had been performed as primary therapy in 132 cases (all macro‐adenomas). At a mean 7.6‐years follow‐up after TSS without immediate pituitary radiotherapy, recurrence occurred in 10.7% of cases with no visible postoperative residual adenoma, 38.8% with intrasellar and 66.7% with extrasellar residuum. Recurrence was defined as growth of residual tumour requiring intervention. On survival analysis, at 10 years, recurrence‐free survival was 75% in patients with no residual tumour and 40% with intrasellar residuum. Recurrence occurred in 12.5% of 24 patients who had received postop radiotherapy. Patients were monitored conservatively without initial surgery in 65 patients. After a mean of 5‐year monitoring, only 20% required intervention during follow‐up (18.5% TSS) and 30.8% died of nonpituitary causes during follow‐up.ConclusionThis study suggests that a conservative approach may be safe and appropriate in patients with NFPA if followed up with appropriate imaging surveillance, whether postoperative or without primary surgery.