bluuebunny/crossref_metadata_2025_split huggingface dataset:
Editorial: breaking the cycle of cough in GERD—neuromodulators to the rescue? Authors’ reply
Authors: Dong Ran , Xu Xianghuai , Yu Li , Qiu Zhongmin 
Published: April 2019

Linked ContentThis article is linked to Dong et al and Naik and Vaezi papers. To view these articles, visit https://doi.org/10.1111/apt.15169 and https://doi.org/10.1111/apt.15205.
Letter: meta‐analysis of prebiotics, probiotics, synbiotics and antibiotics in IBS. Authors’ reply
Authors: Ford Alexander C. , Harris Lucinda A. , Lacy Brian E. , Quigley Eamonn M. M. , Moayyedi Paul 
Published: April 2019

Linked ContentThis article is linked to Ford et al and Sun et al papers. To view these articles, visit https://doi.org/10.1111/apt.15001 and https://doi.org/10.1111/apt.15230.
Editorial: post‐operative elevation of liver enzymes and modern volatile anaesthetics—guilty as charged? Authors’ reply
Authors: Nicoll Amanda , Sood Siddharth , Bishop Bridget , Njoku Dolores 
Published: April 2019

Linked ContentThis article is linked to Bishop et al and Laschtowitz et al papers. To view these articles, visit https://doi.org/10.1111/apt.15168 and https://doi.org/10.1111/apt.15207.
Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels
Authors: Nicoll Amanda J. , Roberts Stuart K. , Lim Ricky , Mitchell Joanne , Weltman Martin , George Jacob , Wigg Alan , Stuart Katherine , Gow Paul , MacQuillan Gerry , Tse Edmund , Levy Miriam , Sood Siddharth , Zekry Amany , Cheng Wendy , Mitchell Jonathan , Skoien Richard , Sievert William , Strasser Simone I. , McCaughan Geoffrey W. ,   the ALA Clinical Research Network, Gastroenterological Society of Australia
Published: April 2019

SummaryBackgroundMycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH).AimTo evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making.MethodsWe performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response.ResultsA total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre‐treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively.ConclusionMycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre‐treatment IgG levels.
Investigation of the absolute bioavailability and human mass balance of navoximod, a novel IDO1 inhibitor
Authors: Ma Shuguang , Suchomel Julia , Yanez Evelyn , Yost Edward , Liang Xiaorong , Zhu Rui , Le Hoa , Siebers Nicholas , Joas Lori , Morley Roland , Royer‐Joo Stephanie , Pirzkall Andrea , Salphati Laurent , Ware Joseph A. , Morrissey Kari M. 
Published: April 2019

AimsNavoximod (GDC‐0919, NLG‐919) is a small molecule inhibitor of indoleamine‐2,3‐dioxygenase 1 (IDO1), developed to treat the acquired immune tolerance associated with cancer. The primary objectives of this study were to assess navoximod's absolute bioavailability (aBA), determine the mass balance and routes of elimination of [14C]‐navoximod, and characterize navoximod's metabolite profile.MethodsA phase 1, open‐label, two‐part study was conducted in healthy volunteers. In Part 1 (aBA), subjects (n = 16) were randomized to receive oral (200 mg tablet) or intravenous (5 mg solution) navoximod in a crossover design with a 5‐day washout. In Part 2 (mass balance), subjects (n = 8) were administered [14C]‐navoximod (200 mg/600 μCi) as an oral solution.ResultsThe aBA of navoximod was estimated to be 55.5%, with a geometric mean (%CV) plasma clearance and volume of distribution of 62.0 L/h (21.0%) and 1120 L (28.4%), respectively. Mean recovery of total radioactivity was 87.8%, with 80.4% detected in urine and the remainder (7.4%) in faeces. Navoximod was extensively metabolized, with unchanged navoximod representing 5.45% of the dose recovered in the urine and faeces. Glucuronidation was identified as the primary route of metabolism, with the major glucuronide metabolite, M28, accounting for 57.5% of the total drug‐derived exposure and 59.7% of the administered dose recovered in urine.ConclusionsNavoximod was well tolerated, quickly absorbed and showed moderate bioavailability, with minimal recovery of the dose as unchanged parent in the urine and faeces. Metabolism was identified as the primary route of clearance and navoximod glucuronide (M28) was the most abundant metabolite in circulation with all other metabolites accounting for <10% of drug‐related exposure.
Hepatic exposure of metformin in patients with non‐alcoholic fatty liver disease
Authors: Sundelin Elias Immanuel Ordell , Gormsen Lars Christian , Heebøll Sara , Vendelbo Mikkel Holm , Jakobsen Steen , Munk Ole Lajord , Feddersen Søren , Brøsen Kim , Hamilton‐Dutoit Stephen Jacques , Pedersen Steen Bønløkke , Grønbæk Henning , Jessen Niels 
Published: April 2019

AimsMetformin is first‐line treatment of type 2 diabetes mellitus and reduces cardiovascular events in patients with insulin resistance and type 2 diabetes. Target tissue for metformin action is thought to be the liver, where metformin distribution depends on facilitated transport by polyspecific transmembrane organic cation transporters (OCTs). Non‐alcoholic fatty liver disease (NAFLD) is the most common liver disease in the western world with strong associations to insulin resistance and the metabolic syndrome, but whether NAFLD affects metformin biodistribution to the liver is not known. In this study, the primary aim was to investigate in vivo hepatic uptake of metformin dynamically in humans with variable degrees of liver affection. As a secondary aim, we wished to correlate hepatic metformin distribution with OCT gene transcription determined in diagnostic liver biopsies.MethodsEighteen patients with biopsy‐proven NAFLD were investigated using 11C‐metformin PET/CT technique. Gene transcripts of OCTs were determined by real‐time polymerase chain reaction (PCR).ResultsWe observed similar hepatic volume of distribution of metformin between patients with simple steatosis and non‐alcoholic steatohepatitis (NASH) (Vd 2.38 ± 0.56 vs. 2.10 ± 0.39, P = 0.3). There was no association between hepatic exposure to metformin and the degree of inflammation or fibrosis, and no clear correlation between metformin distribution and OCT gene transcription.ConclusionMetformin is distributed to the liver in patients with NAFLD and the distribution is not impaired by inflammation or fibrosis. The findings imply that metformin action in liver in patients with NAFLD may be preserved.
Bone marrow characterization in sickle cell disease: inflammation and stress erythropoiesis lead to suboptimal CD34 recovery
Authors: Leonard Alexis , Bonifacino Aylin , Dominical Venina M. , Luo Min , Haro‐Mora Juan J. , Demirci Selami , Uchida Naoya , Pierciey Francis J. , Tisdale John F. 
Published: April 2019

SummaryStress erythropoiesis and chronic inflammation in subjects with sickle cell disease (SCD) may have an impact on the bone marrow (BM) haematopoietic stem and progenitor cell (HSPC) quality and yield necessary for effective autologous, ex vivo HSPC gene therapy. BM from 19 subjects with SCD and five volunteers without SCD (non‐SCD) was collected in different anticoagulants and processed immediately (day 0) or the following day (day 1). Inflammatory, contamination and aggregation markers within the mononuclear layer, and CD34, CD45 and Glycophorin‐A (GPA) expression on HSPCs after CD34+ selection were analysed by conventional and imaging flow cytometry. Compared to non‐SCD BM, multiple markers of inflammation, contamination (red cells, P < 0·01; platelets, P < 0·01) and aggregates (platelet/granulocytes, P < 0·01; mononuclear/red cells, P < 0·01) were higher in SCD BM. Total CD34+ cell count was lower in SCD BM (P < 0·05), however CD34+ count was higher in SCD BM when collected in acid citrate dextrose‐A (ACDA) versus heparin (P < 0·05). Greater than 50% of CD34+ HSPCs from SCD BM are CD34dim due to higher erythroid lineage expression (P < 0·01) as single cell CD34+CD45+GPA+ (P < 0·01) and CD34+CD45−GPA+ (P < 0·01) HSPCs. SCD BM is characterized by increased inflammation, aggregation and contamination contributing to significant differences in HSPC quality and yield compared to non‐SCD BM.
Anthropometric factors and risk of myeloid leukaemias and myelodysplastic syndromes: a prospective study and meta‐analysis
Authors: Teras Lauren R. , Patel Alpa V. , Carter Brian D. , Rees‐Punia Erika , McCullough Marjorie L. , Gapstur Susan M. 
Published: April 2019

SummaryThere is insufficient evidence linking excess body weight to risk of myeloid malignancies. We investigated this association using data from the Cancer Prevention Study‐II(CPS‐II), and a meta‐analysis of published cohort studies. Among 152 090CPS‐IIparticipants, 387 acute myeloid leukaemias (AML), 100 chronic myeloid leukaemias (CML) and 170MDSwere identified over 21 years of follow‐up. InCPS‐II, body mass index (BMI) was weakly associated with risk ofCML(hazard ratio [HR] = 1·04, 95% confidence interval [CI]: 0·99–1·09 per 1 unit increase inBMI),AML(HR = 1·01, 95%CI: 0·98–1·03) andMDS(HR = 1·03, 95%CI: 0·99–1·07). After controlling for other anthropometric factors, no clear association was observed for height,BMIat age 18 years or weight change. In the meta‐analysis (n = 7117 myeloid leukaemias),BMI25–29·9 kg/m2(HRpooled = 1·36, 95%CI: 1·12–1·59) andBMI≥30 kg/m2(HRpooled = 1·43, 95%CI: 1·18–1·69) were associated with higher risk of myeloid leukaemia overall, compared to aBMI<25 kg/m2. Likewise,BMI≥25 kg/m2was positively associated with bothAMLandCMLrisk individually in the meta‐analysis. These results underscore the need for large studies to detect associations with rare cancers, and show a modest, but positive association between excess body weight and myeloid malignancy risk.
Transport infrastructure, growth and persistence: The rise and demise of the Sui Canal
Authors: Flückiger Matthias , Ludwig Markus 
Published: April 2019

AbstractThis paper investigates the effect of transport infrastructure on the spatial distribution of population over two millennia. Focusing on the Sui Canal, one of history's greatest infrastructure projects, we show that its completion in the 7th century CE led to a strong increase in population concentration along the newly established transport artery. We exploit the fact that large parts of the canal fell into disrepair after the 12th century to analyze the persistence of this effect. We find that in 2010, more than 800 years after the Sui Canal fell into disuse, regions once directly connected to the canal are still more populous than areas that never had access. However, this population concentration is not mirrored in economic development. GDP per capita is lower in areas that lay along the course of the canal. One potential explanation for this finding is a change in the value of locational fundamentals as well as a shift in investments to the benefit of coastal regions since the initiation of the Open Door Policy in 1978.
Epidermal growth factor receptor‐targeted molecular imaging of colorectal tumors: Detection and treatment evaluation of tumors in animal models
Authors: Miyamoto Yoshihiko , Muguruma Naoki , Fujimoto Shota , Okada Yasuyuki , Kida Yoshifumi , Nakamura Fumika , Tanaka Kumiko , Nakagawa Tadahiko , Kitamura Shinji , Okamoto Koichi , Miyamoto Hiroshi , Sato Yasushi , Takayama Tetsuji 
Published: April 2019

AbstractTo overcome the problem of overlooking colorectal tumors, a new and highly sensitive modality of colonoscopy is needed. Moreover, it is also important to establish a new modality to evaluate viable tumor volume in primary lesions of colorectal cancer (CRC) during chemotherapy. Therefore, we carried out molecular imaging of colorectal tumors targeting epidermal growth factor receptor (EGFR), which is highly expressed on tumor cells, for evaluating chemotherapeutic efficacy and for endoscopic detection of colorectal adenomas. We first attempted to image five CRC cell lines with various levels of EGFR expression using an Alexa Fluor‐labeled anti‐EGFR monoclonal antibody (AF‐EGFR‐Ab). A strong fluorescence signal was observed in the cells depending on the level of EGFR expression. When nude mice xenografted with LIM1215 CRC cells, which highly express EGFR, were i.v. injected with AF‐EGFR‐Ab, a strong fluorescence signal appeared in the tumor with a high signal to noise ratio, peaking at 48 hours after injection and then gradually decreasing, as shown using an IVIS Spectrum system. When the xenografted mice were treated with 5‐fluorouracil, fluorescence intensity in the tumor decreased in proportion to the viable tumor cell volume. Moreover, when the colorectum of azoxymethane‐treated rats was observed using a thin fluorescent endoscope with AF‐EGFR‐Ab, all 10 small colorectal adenomas (≤3 mm) were detected with a clear fluorescence signal. These preliminary results of animal experiments suggest that EGFR‐targeted fluorescent molecular imaging may be useful for quantitatively evaluating cell viability in CRC during chemotherapy, and also for detecting small adenomas using a fluorescent endoscope.
T‐score differences and nonprogression in lumbar vertebrae as predictors of vertebral fractures
Authors: Lajlev Siv E. , Rejnmark Lars , Harsløf Torben 
Published: April 2019

AbstractPurposeIn case of a vertebral fracture, the area of the vertebrae decreases with a concomitant increase in BMD, as assessed by a DXA scanning. Furthermore, a vertebral fracture may disrupt the normal increase in vertebral body area from L1 to L4 (nonprogression). We aimed to examine associations between T‐score difference and nonprogression of vertebral area and vertebral fractures.MethodsWe identified 100 patients with 1 or more fractures in L1‐L4 and 106 patients without fractures. All patients had undergone a DXA scan and a lumbar spine X‐ray. In fracture patients, we recorded T‐score difference between the fractured vertebra and the adjacent vertebra, and whether the fractured vertebra was smaller than the one above (nonprogression). In nonfracture patients, the greatest positive T‐score difference was recorded, and nonprogression was present if vertebral area did not increase successively from L1 to L4.ResultsWith a T‐score difference ≥1 SD odds ratio for fracture was 1.30 (0.74‐2.29). Sensitivity and specificity were 0.40 and 0.66, respectively. With T‐score difference ≥1.5 SD, odds ratio for fracture was 2.26 (1.08‐4.73). Sensitivity and specificity were 0.24 and 0.88, respectively. Nonprogression was very common in the no‐fracture group (38%), while only 23% of X‐ray verified fractures had nonprogression.ConclusionA randomly found T‐score difference ≥1.5 SD between adjacent vertebrae on a DXA scan is associated with a small increased risk of compression fracture. Nonprogression is very common in patients without fractures.
Trueness of cone beam computed tomography versus intra‐oral scanner derived three‐dimensional digital models: An ex vivo study
Authors: Al‐Rimawi Ali , Shaheen Eman , Albdour Emad A. , Shujaat Sohaib , Politis Constantinus , Jacobs Reinhilde 
Published: April 2019

AbstractObjectivesTo compare the trueness of 3D digital models derived from CBCT and IOS and to evaluate their accuracy for implementation in oral implant rehabilitation.Materials and methodsA dry human mandible with a full set of intact teeth was included in the study. The mandible was scanned using Trios IOS and four different CBCT machines with various protocols for generation of 3D digital models. A µCT was utilized to scan each tooth individually. Following registration and segmentation, the trueness evaluation of 3D digital models was carried out by part comparison analysis and color‐coded mapping of the superimposed teeth surfaces.ResultsThe four CBCT‐derived 3D digital models with different protocols had better trueness than Trios IOS. NewTom VGi evo (110 KV), ProMax 3D (90 kV), 3D Accuitomo 170 (90 kV), Green 21 (110 kV), and Green 21 (90 kV) showed significantly better trueness than IOS. However, 3D Accuitomo 170 and ProMax 3D CBCT devices with 70 kV protocol showed better trueness without any significant difference with IOS.ConclusionCBCT‐derived 3D digital models showed better trueness when compared with IOS. When CBCT data are available for preoperative planning for oral implant rehabilitation, it may preclude the need for IOS for obtaining 3D study models.
Changing trends of contact allergens in Thailand: A 12‐year retrospective study
Authors: Sukakul Thanisorn , Chaweekulrat Pichanee , Limphoka Pichaya , Boonchai Waranya 
Published: April 2019

AbstractBackgroundContact allergen prevalences often change. Continual surveillance is necessary to detect trends in sensitization rates and emerging allergens.ObjectiveTo identify the prevalence of, and trends in, the positive reactions to each allergen in the baseline series during a 12‐year period in Thailand.MethodsThe medical records of 2803 patients who underwent patch testing at the Contact Dermatitis Clinic, Siriraj Hospital, between 2006 and 2018, were retrospectively reviewed. The baseline series used by the clinic was adapted from the European and the International baseline series. The patch testing results were subdivided into 2‐year blocks in order to compare the prevalences of each allergen.ResultsThe prevalences of positive reactions to nickel, fragrance mixes I and II, dichromate, cobalt, carba mix, methyldibromo glutaronitrile, paraben mix, neomycin sulfate, methylisothiazolinone (MI), epoxy resin, N‐isopropyl‐N‐phenyl‐4‐phenylenediamine and the corticosteroids significantly decreased. Methylchloroisothiazolinone (MCI)/MI was the only allergen associated with a significant increase of positive reactions, from 2.4% to 10.7%. However, the proportion of positive reactions to MCI/MI decreased in the final 2‐year period.ConclusionsApproximately half of the substances in the screening patch test series showed a decline in the number of positive reactions, whereas MCI/MI showed an increasing prevalence.
Human parvovirus B19 in solid organ transplantation: Guidelines from the American society of transplantation infectious diseases community of practice
Authors: Eid Albert J. , Ardura Monica I. ,   the AST Infectious Diseases Community of Practice
Published: April 2019

AbstractClinical manifestations of human parvovirus B19 infection can vary widely and may be atypical in solid organ transplant (SOT) recipients. However, disease is apparent when there is destruction of erythrocyte progenitor cells leading to severe acute or chronic anemia with lack of an appropriate reticulocyte response in the setting of active parvovirus B19 infection. Serology may not reliably establish the diagnosis. High‐level viremia is more likely to be associated with symptomatic disease. Conversely, ongoing DNAemia after infection may not be clinically significant, if detected at low levels. Despite lack of robust data, intravenous immunoglobulin (IVIG) is frequently used for the treatment of SOT recipients with symptomatic parvovirus B19 infection. Although the optimal dosage and duration of IVIG is not known, most patients receive a total of 2 g/kg over a period of 2‐5 days. A daily dose of 1 g/kg or more seems to be associated with higher incidence of toxicity. Application of standard and droplet isolation precautions remains the cornerstone for preventing human parvovirus B19 transmission. Additional research is needed to assess the efficacy of current and novel therapies and to develop a safe and effective parvovirus B19 vaccine.
A rare variant of extraskeletal osteosarcoma presenting as a clinically benign subcutaneous neoplasm
Authors: Ryan Michael P. , Woolridge Katelyn F. , Sedrak Michael , Berlingeri‐Ramos Alma C. , Group Ashley R. 
Published: April 2019

AbstractExtraskeletal osteosarcoma (ESOS) is a rare variant of osteosarcoma that arises without attachment to the underlying skeleton. These cancers are typically found embedded in deeper tissues, most commonly the muscle or fascia, and are rarely found within the skin or subcutis. Most tumors are large in size upon initial presentation, and carry a poor prognosis. We discuss the case of a 48‐year‐old Caucasian woman who presented to a dermatology clinic with an asymptomatic, small, mobile, subcutaneous mass that appeared clinically benign. After elective removal and histopathologic examination, the patient was diagnosed with ESOS. ESOS presenting in this manner is exceedingly rare, and this case highlights the importance of sending all excised specimens, even those with a benign presentation, for pathologic examination.
Effect of dual versus mono antiplatelet therapy on recurrent stroke modulated by activated partial thromboplastin time
Authors: Xie X. , Wang X. , Laskowitz D. T. , Zhao X. , Miao Z. , Liu L. , Li H. , Meng X. , Wang Y. , Wang Y. ,   the CHANCE investigators
Published: April 2019

Background and purposeThe efficacy of dual antiplatelet treatment may be modified by many factors. The aim was to assess whether the effect of clopidogrel plus aspirin versus aspirin alone on recurrent stroke would be affected by admission activated partial thromboplastin time (aPTT).MethodsData were derived from the Clopidogrel in High‐Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. A total of 5074 patients were categorized into three groups based on the aPTT distribution according to the 15th and 85th percentile. The primary outcome was any stroke within 90 days. The interaction of aPTT with antiplatelet therapy on stroke risk was assessed with a Cox proportional hazards model with adjustment for covariates.ResultsIn the high aPTT group (defined as ≥35.9 s), stroke occurred in 6.7% of patients in the clopidogrel–aspirin arm and 11.9% in the aspirin arm [adjusted hazard ratio (HR) 0.50; 95% confidence interval (CI) 0.29–0.85]. In the medium aPTT group (24.6–35.8 s), stroke occurred in 7.7% of patients in the clopidogrel–aspirin arm and 11.8% in the aspirin arm (adjusted HR 0.62; 95% CI 0.50–0.75). Furthermore, in the low aPTT group (≤24.5 s), stroke occurred in 11.2% of patients in the clopidogrel–aspirin arm and 9.9% in the aspirin arm (adjusted HR 1.07; 95% CI 0.65–1.62). The interaction P value of antiplatelet therapy with aPTT level at the cut‐point of approximately 25 s or below was significant (P < 0.05).ConclusionsDual antiplatelet therapy was superior to single antiplatelet therapy in the high or medium aPTT group but not in the low aPTT group.