bluuebunny/crossref_metadata_2025_split huggingface dataset:
How many cases of disease in a pedigree imply familial disease?
Authors: Dudbridge Frank , Brown Suzanne J. , Ward Lynley , Wilson Scott G. , Walsh John P. 
Published: October 2017

AbstractThe ability to perform whole‐exome and, increasingly, whole‐genome sequencing on large numbers of individuals has led to increased efforts to identify rare genetic variants that affect the risk of both common and rare diseases. In such applications, it is important to identify families that are segregating the rare variants of interest. For rare diseases or rare familial forms of common diseases, pedigrees with multiple affected members are clearly harbouring risk variants. For more common diseases, however, it may be unclear whether a family with a few affected members is segregating a familial disease, is the result of multiple sporadic cases, or is a mixture of familial cases and phenocopies. We provide calculations for the probability that a family is harbouring familial disease, presented in general terms that admit working guidelines for selecting families for current sequencing studies. Using examples motivated by our own studies of thyroid cancer and published studies of colorectal cancer, we show that for common diseases, families with exactly two affected first‐degree relatives have only a moderate probability of segregating familial disease, but this probability is higher for families with three or more affected relatives, and those families should therefore be prioritised in sequencing studies.
Phone calls to an Australian pregnancy and lactation counselling service regarding use of galactagogues during lactation – the MotherSafe experience
Authors: Grzeskowiak Luke E. , Hill Majella , Kennedy Debra S. 
Published: October 2017

Galactagogues represent substances used to enhance breast milk production. Between 2001 and 2014 we identified 2034 phone calls regarding the use of galactagogues made to MotherSafe. The majority involved discussion of domperidone (n = 1884; 92.6%), with the remainder relating to metoclopramide (n = 153; 7.5%) or other herbal galactagogues (eg fenugreek, milk thistle; n = 262; 12.9%). A 50% decrease in total calls occurred from 2011 to 2014, while the percentage of calls regarding herbal galactagogues increased from 0% in 2001 to 23% in 2014. These findings support the need for more robust research surrounding the use of galactagogues in clinical practice.
Omalizumab rapidly improves angioedema‐related quality of life in adult patients with chronic spontaneous urticaria: X‐ACT study data
Authors: Staubach P. , Metz M. , Chapman‐Rothe N. , Sieder C. , Bräutigam M. , Maurer M. , Weller K. 
Published: October 2017

AbstractBackgroundThe X‐ACT study aimed to examine the effect of omalizumab treatment on quality of life (QoL) in chronic spontaneous urticaria (CSU) patients with angioedema refractory to high doses of H1‐antihistamines.MethodsIn X‐ACT, a phase III, double‐blind, placebo‐controlled study, CSU patients (18‐75 years) with ≥4 angioedema episodes during the 6 months before inclusion were randomized (1:1) to receive omalizumab 300 mg or placebo every 4 weeks for 28 weeks. Angioedema‐related QoL, skin‐related QoL impairment, and psychological well‐being were assessed.ResultsNinety‐one patients were randomized and 68 (omalizumab, n = 35; placebo, n = 33) completed the 28‐week treatment period. At baseline, the mean (SD) total Angioedema QoL (AE‐QoL; 56.2 [18.7] and 59.9 [19.2]) and Dermatology Life Quality Index (DLQI; 14.6 [5.7] and 16.6 [7.3]) score were high in the omalizumab and placebo group, respectively. At Week 4 (after the first treatment), the least squares mean difference in the AE‐QoL and DLQI score between groups was −17.6 (P < .001) and −7.2 (P < .001), respectively. Significant QoL improvements in the omalizumab vs placebo groups continued until Week 28, but returned to placebo levels at the follow‐up visit. The mean (SD) baseline 5‐item World Health Organization Well‐being Index was 10.0 (5.5, omalizumab) and 7.7 (5.3, placebo), which increased above the depression threshold (<13) from Week 4 and throughout with omalizumab but not placebo treatment. Compared to placebo, omalizumab was also associated with decreased fear of suffocation due to angioedema.ConclusionsOur findings support omalizumab treatment in patients with severe H1‐antihistamine‐refractory CSU with angioedema.
Small fetal thymus and adverse obstetrical outcome: a systematic review and a meta‐analysis
Authors: Caissutti Claudia , Familiari Alessandra , Khalil Asma , Flacco Maria E. , Manzoli Lamberto , Scambia Giovanni , Cagnacci Angelo , D'antonio Francesco 
Published: October 2017

AbstractIntroductionThe aim of this study was to explore the association between small fetal thymus on ultrasound and adverse obstetrical outcome.Material and methodsMedline, Embase, Cochrane and Web of Science databases were searched. Primary outcome was the risk of preterm birth before 37 and 34 weeks of gestation in fetuses with, compared to those without, a small thymus on ultrasound. Secondary outcomes: occurrence of chorioamnionitis, intrauterine growth restriction, neonatal sepsis, gestational age at birth, birthweight, neonatal morbidity and preeclampsia.ResultsTwelve studies including 1744 fetuses who had ultrasound assessment of thymus during pregnancy were included. Women with preterm premature rupture of the membranes or with preterm labor were at higher risk of preterm birth before 37 weeks (p = 0.01), or before 34 weeks (p < 0.001) for fetuses with a small fetal thymus compared to those without a small thymus, and the risk of chorioamnionitis was higher when the thymus was small (p < 0.001). Fetuses with small thymus were not at higher risk of intrauterine growth restriction (p = 0.3). A small thymus increased the risk of neonatal sepsis (p = 0.007) and morbidity (p = 0.003), but not the risk of preeclampsia (p = 0.9).ConclusionsA small fetal thymus is associated with a higher risk of preterm birth, chorioamnionitis, neonatal sepsis and morbidity, but not with intrauterine growth restriction and preeclampsia.
Neonatal Eating Outcome Assessment: tool development and inter‐rater reliability
Authors: Pineda Roberta , Harris Rachel , Foci Felicia , Roussin Jessica , Wallendorf Michael 
Published: October 2017

AbstractAimTo define the process of tool development and revision for the Neonatal Eating Outcome (NEO) Assessment and to report preliminary inter‐rater reliability.MethodsTool development consisted of a review of the literature and observations of feeding performance among 178 preterm infants born ≤32 weeks gestation. 11 neonatal therapy feeding experts provided structured feedback to establish content validity and define the scoring matrix. The tool was then used to evaluate feeding in 50 preterm infants born ≤32 weeks of gestation and 50 full‐term infants. Multiple revisions occurred at each stage of development. Finally, six neonatal occupational therapists participated in reliability testing by independently scoring five videos of oral feeding of preterm infants using version 4 of the tool.ResultsThe intraclass correlation for the ‘prefeeding’ score was 0.71 (0.37–0.96), and the intraclass correlation for the ‘total’ score was 0.83 (0.56–0.98).ConclusionThe ‘total’ score had good to excellent reliability. Fleiss’ Kappa scores for all 18 scorable items ranged from slight agreement to moderate agreement. Items with the lowest Kappa scores were revised, and additional feedback from therapists engaged in reliability testing was incorporated, resulting in final version 5.
QTc prolongation during ciprofloxacin and fluconazole combination therapy: prevalence and associated risk factors
Authors: Berger Florine A. , Monadian Nico , de Groot Natasja M. S. , Santbergen Bart , van der Sijs Heleen , Becker Matthijs L. , Broers Annoek E. C. , van Gelder Teun , van den Bemt Patricia M. L. A. 
Published: October 2017

Aim(s)Ciprofloxacin and fluconazole combination therapy is frequently used as prophylaxis for, and treatment of, infections in patients with haematological malignancies. However, both drugs are known to prolong the heart rate‐corrected QT (QTc) interval, which is a serious risk factor for torsade de pointes (TdP). Therefore, the aim of the current study was to assess the prevalence of QTc prolongation during ciprofloxacin and fluconazole use. The secondary objective was to determine associated risk factors of QTc prolongation in these patients.MethodsA prospective observational study was performed in patients admitted to the Erasmus University Medical Centre and treated with ciprofloxacin and fluconazole. A 12‐lead electrocardiogram (ECG) was recorded at the estimated time to peak concentration (Tmax) for the last added drug. The main outcome was the proportion of patients with QTc prolongation during treatment. Data on the following potential risk factors were collected: patient characteristics, serum electrolyte levels, dosage of ciprofloxacin and fluconazole, renal and liver function and concomitant use of other QTc‐prolonging drugs and cytochrome P450 3A4 inhibitors.ResultsA total of 170 patients were included, of whom 149 (87.6%) were treated for haematological malignancies. The prevalence of QTc prolongation was 4.7%. No risk factors were found to be associated with QTc prolongation. The QTc interval increased by 10.7 ms [95% confidence interval (CI) 7.2, 14.1 ms] during ciprofloxacin and fluconazole combination therapy.ConclusionThe prevalence of QTc prolongation in patients using ciprofloxacin and fluconazole is low compared with the prevalence in the general population, which varies from 5% to 11%. In addition, no risk factors were found. Given the low prevalence, routine ECG monitoring in patients on this therapy should be reconsidered.
Late Holocene stable isotopic (δ13C and δ15N) records of lacustrine organic matter in Guangdong Province, south China, and their palaeoenvironmental implications
Authors: Zhong Wei , Wei Zhiqiang , Shang Shengtan , Chen Yu , Ye Susu , Tang Xiaowen , Zhu Chan , Ouyang Jun , Xue Jibin 
Published: October 2017

This study presents the results of TOC/TN (C/N) ratio, δ13C and δ15N analyses of lake sedimentary organic matter (OM) from the Hedong section, western Guangdong Province in south China, with the objective to reveal the history of hydrological and ecological variations in the region influenced by both the Indian summer monsoon (ISM) and East Asian summer monsoon (EASM). Variations in δ13C and δ15N of sedimentary OM may be closely related to past climatic conditions, which results in variations in surface runoff, lake level, allochthonous and autochthonous sources of OM, and lake productivity. Based on the interpretation of these proxies, four periods, i.e. 4370–4100, 3700–2900, 2400–2100 and 1900–900 cal. a BP, are characterized by low lake level, weakened surface runoff and deteriorated status of terrestrial and aquatic ecosystems, whereas the periods 4100–3700, 2900–2400, 2100–1900 and 900–600 cal. a BP are dominated by high lake level, strengthened surface runoff, and flourishing terrestrial and aquatic plants. A remarkable positive correlation between the δ13C values of the section and the ENSO number record obtained from the tropical Pacific implies that the impact of the ISM is greater than that of the EASM in the study area. The abnormal correspondence between the δ13C and solar activity reconstructed from 10Be and 14C records in GRIP ice‐core occurred from 1500–800 and particularly from 4200–4000 cal. a BP, suggesting that these two cool and dry intervals may be caused by stronger volcanic activities that are recorded in the GISP2 and Dome C ice‐cores. This study reveals that changes in solar insolation and solar activity, as well as changes in oceanic–atmospheric circulation (e.g. the ENSO intensity) and intensive volcano eruptions may have exerted influence on late Holocene climate variability in the study area.
Differential effects of selective agonists of neuromedin U1 and U2 receptors in obese and diabetic mice
Authors: Nagai Hiroaki , Kaisho Tomoko , Yokoyama Kotaro , Asakawa Tomoko , Fujita Hisashi , Matsumiya Kouta , Noguchi Jiro , Tsuchimori Kazue , Nishizawa Naoki , Kanematsu‐Yamaki Yoko , Dote Katsuko , Inooka Hiroshi , Sakamoto Jun‐ichi , Ohtaki Tetsuya , Asami Taiji , Takekawa Shiro 
Published: October 2017

Background and PurposeNeuromedin U (NmU) may be a novel target for obesity treatment owing to its anorectic and energy expenditure enhancing effects. Although two receptors, NMU1 and NMU2, are both responsible for the NmU‐mediated anti‐obesity effects, the receptor agonist with the most appropriate profiles for treating obesity and diabetes in terms of efficacy and safety is as yet unknown. Thus, we developed and evaluated novel NMU1/2 receptor‐selective agonists.Experimental ApproachEfficacy and safety were assessed in mice with diet‐induced obesity (DIO) and those with leptin‐deficient diabetes (ob/ob) through repeated peripheral administration of selective agonists to NMU1 (NMU‐6102) and NMU2 (NMU‐2084), along with non‐selective NMU1/2 agonists (NMU‐0002 and NMU‐6014). We also performed immunohistochemistry for c‐Fos protein expression in the brain to probe their mechanisms of action.Key ResultsAlthough both non‐selective NMU1/2 agonists and the NMU2‐selective agonist had high efficacy compared with the NMU1‐selective agonist, only the NMU2‐selective agonist led to relatively low adverse effects, such as diarrhoea, in DIO mice. However, the non‐selective NMU1/2 agonist and the NMU1‐selective agonist, but not the NMU2‐selective agonist, were effective in diabetic ob/ob mice. Mechanistically, NMU2‐selective agonists preferentially activate pro‐opiomelanocortin neurons in the hypothalamic arcuate nucleus but not in the paraventricular nucleus.Conclusions and ImplicationsThese results suggest that an NMU2 receptor‐selective agonist may be a well‐balanced drug for the treatment of obesity and that an NMU1 receptor‐selective agonist may also be beneficial for treating obesity and diabetes once its side effects are minimized.
Insulin‐like growth factor‐1 activates PI3K/Akt signalling to protect human retinal pigment epithelial cells from amiodarone‐induced oxidative injury
Authors: Liao Rifang , Yan Fengxia , Zeng Zhuanping , Wang Haitao , Qiu Kaifeng , Xu Jinying , Zheng Wenhua 
Published: October 2017

Background and PurposeAmiodarone is one of the most effective anti‐arrhythmic drugs available, but its clinical applications are limited by toxic side effects including optic toxicity. The purpose of this study was to investigate the toxic effect of amiodarone on D407 cells (a human retinal pigmented epithelial (RPE) cell line) and the mechanisms of the protective effect of insulin‐like growth factor‐1 (IGF‐1).Experimental ApproachThe involvement of the kinases, Akt and ERK, was analysed by Western blot. Intracellular accumulation of ROS was measured using fluorophotometric quantification. A pharmacological approach with inhibitors was used to investigate the pathways involved in the protective action of IGF‐1.Key ResultsAmiodarone concentration‐dependently augmented the production of ROS, lipid peroxidation and apoptosis in D407 cells. IGF‐1 time‐ and concentration‐dependently reversed these effects of amiodarone and protected D407 cells from amiodarone‐mediated toxicity. Amiodarone inhibited the pAkt but not pErk, and IGF‐1 reversed this inhibitory effect of amiodarone. However, IGF‐1 failed to suppress amiodarone‐induced cytotoxicity in the presence of PI3K/Akt inhibitor LY294002 suggesting the direct involvement of the PI3K/Akt pathway. Furthermore, in vivo rat flash electroretinogram (FERG) recordings showed that IGF‐1 reverses the amiodarone‐induced decrease in a‐ and b‐waves. The immunocytochemistry findings confirmed that vitreous IGF‐1 injections promote the survival of RPE cells in rat retina treated with amiodarone.Conclusion and ImplicationsIGF‐1 can protect RPE cells from amiodarone‐mediated injury via the PI3K/Akt pathway in vivo and in vitro. IGF‐1 has potential as a protective drug for the prevention and treatment of amiodarone‐induced optic toxicity.
Selectivity, cell permeability and oral availability studies of novel bromophenol derivative HPN as protein tyrosine phosphatase 1B inhibitor
Authors: Luo Jiao , Xu Qi , Jiang Bo , Zhang Renshuai , Jia Xiaoling , Li Xiangqian , Wang Lijun , Guo Chuanlong , Wu Ning , Shi Dayong 
Published: October 2017

Background and PurposeProtein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signalling by tyrosine dephosphorylation of the insulin receptor. It is a highly validated target for type 2 diabetes therapeutics. Here, the anti‐diabetic effects of HPN were evaluated in the diabetic BKS db mice.Experimental ApproachThe mode of inhibition of PTP1B by HPN was determined according to the Lineweaver–Burk plot. A surface plasmon resonance assay and molecular docking were used to study the interaction between HPN and PTP1B. C2C12 skeletal muscle cells were used to investigate the cell permeability of HPN and the effect of HPN on insulin signalling pathways. Long‐term effects of HPN on glycaemic control were investigated in diabetic BKS db mice. Glycogen contents in liver and muscle were determined. Furthermore, changes in the number of beta cells were evaluated by Gomori staining.Key ResultsHPN was identified as a specific PTP1B inhibitor. HPN directly interacted with PTP1B by binding to the catalytic domain through hydrogen bonds in a competitive mode. Approximately 56.98% of HPN entered into the cultured C2C12 myotubes. HPN ameliorated the impaired insulin signalling in palmitate‐treated C2C12 myocytes. Notably, oral administration of HPN significantly protected mice from hyperglycaemia, dyslipidemia and hyperinsulinaemia. HPN also enhanced the storage of glycogen in liver and muscle. Moreover, HPN obviously improved the beta cell numbers of the pancreatic islets.Conclusion and ImplicationsOur results indicate that HPN is a specific PTP1B inhibitor, with anti‐diabetic properties and good cell permeability and oral availability.
Increased T‐helper 17 cell differentiation mediated by exosome‐mediated microRNA‐451 redistribution in gastric cancer infiltrated T cells
Authors: Liu Feng , Bu Zhouyan , Zhao Feng , Xiao Daping 
Published: October 2017

MicroRNA (miR)‐451 is a cell metabolism‐related miRNA that can mediate cell energy‐consuming models by several targets. As miR‐451 can promote mechanistic target of rapamycin (mTOR) activity, and increased mTOR activity is related to increased differentiation of T‐helper 17 (Th17) cells, we sought to investigate whether miR‐451 can redistribute from cancer cells to infiltrated T cells and enhance the distribution of Th17 cells through mTOR. Real‐time PCR was used for detecting expression of miR‐451 in gastric cancer, tumor infiltrated T cells and exosomes, and distribution of Th17 was evaluated by both flow cytometry and immunohistochemistry (IHC). Immunofluorescence staining was used in monitoring the exosome‐enveloped miR‐451 from cancer cells to T cells with different treatments, and signaling pathway change was analyzed by western blot. miR‐451 decreased significantly in gastric cancer (GC) tissues but increased in infiltrated T cells and exosomes; tumor miR‐451 was negatively related to infiltrated T cells and exosome miR‐451. Exosome miR‐451 can not only serve as an indicator for poor prognosis of post‐operation GC patients but is also related to increased Th17 distribution in gastric cancer. miR‐451 can redistribute from cancer cells to T cells with low glucose treatment. Decreased 5′ AMP‐activated protein kinase (AMPK) and increased mTOR activity was investigated in miR‐451 redistributed T cells and the Th17 polarized differentiation of these T cells were also increased. Exosome miR‐451 derived from tumor tissues can serve as an indicator for poor prognosis and redistribution of miR‐451 from cancer cells to infiltrated T cells in low glucose treatment can enhance Th17 differentiation by enhancing mTOR activity.
CyPA and Emmprin play a role in peri‐implantitis
Authors: Yang Lei , Zhu Qing , Gong Jingjue , Xie Ming , Jiao Ting 
Published: October 2017

AbstractBackgroundCyclophilin A (CyPA) and Emmprin play important roles in peri‐implantitis. However, their roles in the diagnosis and treatment of the disease are still unclear.PurposeThe aim of this split‐mouth animal study was to describe variable trends of biomarkers during the progression of peri‐implantitis and to define relationships among CyPA, Emmprin, and peri‐implantitis.Materials and MethodsSix male adult Labradors were used. The mandibular premolars and the first molar were extracted, and sixteen implants were placed after 3 months. Peri‐implantitis was induced around the implants on one side, which were the test group, and the implants on the other side were included in the control group. Clinical parameters such as probing depth, gingival index, and bleeding index and periapical X‐rays were recorded at weeks 0, 2, 4, 6, 8, 10, and 12. Peri‐implant crest fluid (PICF) and gingiva around the implants were collected and analyzed by ELISA and real‐time PCR, respectively.ResultsThe clinical parameters of the test group indicated severe inflammation around the implants. Radiographs showed obvious bone loss beginning at week 4, and it continued over time. The concentration of CyPA in the peri‐implantitis group increased at first and then decreased beginning at week 6, and the concentration of Emmprin decreased at first and then increased beginning at week 6. Emmprin, matrix metalloproteinase‐9 and Tissue Inhibitor of Metalloproteinase‐1 showed similar changes over time. CyPA showed a consistent trend with Interleukin‐1β, but showed an opposite trend to Transforming growth factor‐β. Both the concentration of CyPA in PICF and gene expression in gingival tissue increased before bone absorption occurred.ConclusionDespite the limitations of this study, CyPA may be an early signal for peri‐implantitis. A CyPA‐Emmprin interaction exists in peri‐implantitis and is Emmprin‐dependent. Emmprin is related to clinical attachment loss in peri‐implantitis.
Surgical management of colonic basidiobolomycosis among adolescent and adult patients: presentation and outcome
Authors: Abd El Maksoud W. M. , Bawahab M. A. , Ashraf T. H. , Al Shehri D. M. , Mirza N. I. 
Published: October 2017

AbstractAimThe aim of this study was to review retrospectively the clinical presentations, indications for surgery and surgical outcomes of adolescent and adult patients who were diagnosed with colonic basidiobolomycosis in the last 10 years.MethodThe study was carried out in Aseer Central Hospital, Abha, Saudi Arabia by reviewing the medical files of all patients in the last 10 years who were diagnosed with colonic basidiobolomycosis and required surgical intervention.ResultsThere were 22 patients. Common findings in all patients were weight loss, abdominal pain and an abdominal mass. The right colon was affected in 21 patients. The initial diagnosis was correct in seven patients while nine were thought to be malignant. All patients underwent colonic resection followed by at least 1 year of antifungal medical treatment. Intra‐operatively, all patients had moderate or dense adhesions, an abdominal mass and lymphadenopathy. Most surgeons had the impression intra‐operatively that the diagnosis was inflammatory rather than malignant. Postoperatively, three patients died within 6 months of the operation due to progression of the disease. Four patients developed severe wound infections, three of whom had abdominal dehiscence and required re‐closure.ConclusionColonic basidiobolomycosis is a life‐threatening fungal infection that should be considered a surgical condition. A high index of suspicion including basidiobolomycosis in the differential diagnosis for the acute abdomen with a colonic mass is required for a proper diagnosis. Early aggressive surgical management followed by a prolonged course of itraconazole postoperatively could improve the outcome of the condition.