bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic changes in microbiota and mycobiota during spontaneous ‘VinoSantoTrentino’ fermentation
Authors: Stefanini Irene , Albanese Davide , Cavazza Agostino , Franciosi Elena , De Filippo Carlotta , Donati Claudio , Cavalieri Duccio
Published: January 2016

VinoSanto is a sweet wine produced from late harvesting and pressing of Nosiola grapes in a small, well‐defined geographical area in theItalian Alps. We used metagenomics to characterize the dynamics of microbial communities in the products of three wineries, resulting from spontaneous fermentation with almost the same timing and procedure. Comparing fermentation dynamics and grape microbial composition, we show a rapid increase in a small number of wine yeast species, with a parallel decrease in complexity. Despite the application of similar protocols, slight changes in the procedures led to significant differences in the microbiota in the three cases of fermentation: (i) fungal content of the must varied significantly in the different wineries, (ii)Pichia membranifacienspersisted in only one of the wineries, (iii) one fermentation was characterized by the balanced presence ofSaccharomyces cerevisiaeandHanseniaspora osmophiladuring the later phases. We suggest the existence of a highly winery‐specific ‘microbial‐terroir’ contributing significantly to the final product rather than a regional ‘terroir’. Analysis of changes in abundance during fermentation showed evident correlations between different species, suggesting that fermentation is the result of a continuum of interaction between different species and physical–chemical parameters.
“Ministering to the Social Needs of the People”: Samuel Jones, Strong Mayor Government, and Municipal Ownership, 1897–1904
Authors: Liazos Ariane
Published: January 2016

Debates in the Progressive era between supporters of the franchise system and supporters of municipal ownership provide an example of conflicting views of appropriate models of state development. The former wanted to continue the public‐private partnerships that characterized much of 19th‐century state building, while the latter maintained that this system inevitably led to corruption and exacerbated inequality, calling for a new system of publicly run programs. Mayor Samuel Jones of Toledo worked to expand municipally owned utilities and transportation. Jones argued that granting franchises for the provision of public services enabled private companies to accrue profits that belonged to the people. He actively promoted an alternative model based on his faith in the potential of government, through a program of public ownership, to exemplify a sense of community, brotherhood, and love. Yet obstruction by the city council and lack of mayoral power blocked his efforts. As a result, he attempted to secure a “strong mayor” charter that would enable him to enact his program. The voters, however, rejected the plan, fearing centralization of power and loss of popular accountability. This outcome highlights the importance of the relationship between electoral structures and functional expansion in American political development.
Antibiotic Therapy Increases the Risk of Preterm Birth in Preterm Labor without Intra‐Amniotic Microbes, but may Prolong the Gestation Period in Preterm Labor with Microbes, Evaluated by Rapid and High‐Sensitive PCR System
Authors: Yoneda Satoshi , Shiozaki Arihiro , Yoneda Noriko , Ito Mika , Shima Tomoko , Fukuda Kaori , Ueno Tomohiro , Niimi Hideki , Kitajima Isao , Kigawa Mika , Saito Shigeru
Published: January 2016

Objectives

To examine the efficacy of the use of antibiotics in preterm labor (PTL) with intact membranes, after evaluating intra‐amniotic microbes by our rapid and bacteria‐free polymerase chain reaction (PCR) system.

Materials and methods

One hundred and four PTL patients before 32 weeks of gestation were recruited. Until 2012, antibiotics were empirically prescribed based on the clinical severity of PTL. Intra‐amniotic microbes in stored samples were evaluated later by our newly established PCR system, and the efficacy of the use of antibiotics in PTL was evaluated.

Results

In the amniotic fluid (AF) microbe‐negative patients (n = 67), antibiotic therapy significantly shortened the gestation period (P < 0.0001), whereas in the microbe‐positive patients (n = 37), appropriate antibiotic therapy (proper antibiotic selection against identified AF microbes) was significantly associated with an increase in gestation period (P < 0.0001).

Conclusion

Appropriate antibiotic therapy in PTL with intact membranes prolonged the gestation period.
État de siège: A dying domesticating colonialism?
Authors: HAGE GHASSAN
Published: January 2016

The sentiment of being “surrounded by barbarians” was once specific to settler‐colonial societies. But as the European refugee crisis made headlines in 2015, it became evident that this sentiment is gaining widespread currency in the Western world. Three developments lie behind its extension: first, the resurgence in the militarized Western appropriation of world resources and its colonial imaginary; second, the crisis in the order of the national borders that has regulated the exploitation of land, resources, and labor in the neocolonial era; and third, the ecological crisis, which equally manifests itself as a crisis in the order of the borders of domestication that defined the modern exploitation of nature. Analyzing the intersection of these social processes offers us important insights into some of the dominant dynamics of Western culture today. [settler colonialism, primitive accumulation, refugee crisis, national borders, ecological crisis, Agamben]
Causes of hypogonadotropic hypogonadism predict response to gonadotropin substitution in adults
Authors: Rohayem J. , Sinthofen N. , Nieschlag E. , Kliesch S. , Zitzmann M.
Published: January 2016

Germ cell and Sertoli cell proliferation and maturation in human testes occur in three main waves, during the late fetal and early neonatal period and at early puberty. They are triggered by periods of increased activity of the hypothalamic‐pituitary‐gonadal (HPG) axis. In hypogonadotropic hypogonadism (HH), these processes are variably disturbed. The objective of this study was to explore whether success of gonadotropin replacement in HH men is predictable by the origin of HH, indicating time of onset and severity of GnRH/gonadotropin deficiency. The data of 51 adult HH patients who had undergone one cycle of hCG/FSH treatment were reviewed. Five groups were established, according to the underlying HH origin. Therapeutic success by final bi‐testicular volumes (BTVs) final sperm concentrations (SC) and conception rates were compared and related to baseline parameters, indicative of the degree of HPG‐axis disruption. Overall, BTVs rose from 13 ± 15 to 27 ± 15 mL, spermatogenesis was induced in 98%, with mean SCs of 15 ± 30 mill/mL, spontaneous pregnancies in 37% and additional 18% via intracytoplasmic sperm injection. Kallmann syndrome patients had the poorest responses (BTV: 16.9 ± 10 mL; SC: 3.5 ± 5.6 mill/mL), followed by patients with congenital/infancy‐acquired multiple pituitary hormone deficiencies (MPHD) and patients with HH+absent puberty (BTV: 21 ± 14/24 ± 9 mL; SC: 5.5 ± 6.5/ 14.5 ± 23.8 mill/mL). HH men with pubertal arrest and with post‐pubertally acquired MPHD had the best results (BTV: 36 ± 14/38 ± 16 mL; SC: 25.4 ± 34.2/29.9 ± 50.5 mill/mL). Earlier conception after 20.3 ± 11.5 months (vs. 43.1 ± 43.8; p = 0.047) of gonadotropin treatment with higher pregnancy rates (62% vs. 42%) was achieved in the two post‐pubertally acquired HH subgroups, compared to the three pre‐pubertally acquired. Therapeutic success was higher in patients without previously undescended testes, with higher baseline BTVs (pre‐ vs. post‐pubertal HH: 5 ± 4 mL vs. 26 ± 16 mL; p < 0.0001) and higher baseline inhibinB levels (pre‐ vs. post‐pubertal HH: 16.6 vs. 144.5 pg/mL; p = 0.0004). The cause of HH is a valuable predictor of outcome of gonadotropin replacement in adults.
Distinctive Electrocardiographic Features in African Americans Diagnosed with Takotsubo Cardiomyopathy
Authors: Franco Emiliana , Dias Andre , Koshkelashvili Nikoloz , Pressman Gregg S. , Hebert Kathy , Figueredo Vincent M.
Published: January 2016

Background

Takotsubo cardiomyopathy (TC) can resemble acute anterior ST‐elevation myocardial infarction. Most studies have examined TC in Asians and Caucasians (non‐African Americans [AA]), while very few cases have been reported in AA. We aimed to assess the electrocardiographic features of TC in AA patients and compare them to non‐AA TC patients.

Methods

We retrospectively compared electrocardiograms of 52 AA and 47 non‐AA patients diagnosed with TC. All patients met the modified Mayo Clinic criteria for the diagnosis of TC. Information collected included PR interval, QRS duration and amplitude, QT interval in milliseconds (msec) adjusted for heart rate (QTc), ST‐segment deviation at the J point in limb and precordial leads (≥1 mm), ST elevation (≥1 mm), and T‐wave inversion (≥0.5 mm).

Results

T‐wave inversion was more prevalent on presentation among AA patients (82% vs 48% in non‐AA; P < 0.01), whereas ST depression was more common among non‐AA (21% vs 7% in AA; P = 0.05). T‐wave inversions in AA patients were frequent in both limb and precordial leads, whereas T‐wave inversions in non‐AA were limited to precordial leads. The average QTc upon presentation in AA was longer than non‐AA (491 msec in AA vs 456 msec in non‐AA; P < 0.01) as was the maximum average QTc during index hospitalization (527 msec in AA vs 497 msec in non‐AA, P = 0.03).

Conclusion

In patients presenting with TC, AA patients more frequently present with diffuse T‐wave inversions and a more prolonged QTc, whereas non‐AA patients more often present with ST depressions. AA patients also more frequently present with T‐wave inversions diffusely, whereas non‐AA patients present with T‐wave inversions more limited to the precordial leads.
Exhaled nitric oxide is associated with postnatal adaptation to hypoxia in Tibetan and non‐Tibetan newborn infants
Authors: Wu Panpan , Shanminna  , Liang Kun , Yue Hongni , Qian Liling , Sun Bo
Published: January 2016

Aim

This Chinese study assessed partial pressure of exhaled nitric oxide (PeNO) in healthy Tibetan and non‐Tibetan newborn infants born at a very high altitude.

Methods

Full‐term Tibetan and non‐Tibetan neonates born in Lhasa, 3658 metres above sea level, were compared to non‐Tibetan neonates born in Kunming (1891 m) and Huai'an (16 m). The chemiluminiscence technique was used to measure the fraction of exhaled nitric oxide during spontaneous tidal breathing and this was then converted to partial pressure of exhaled nitric oxide (PeNO).

Results

In their first week, Tibetan and non‐Tibetan neonates born in Lhasa had persistently higher PeNO levels than non‐Tibetan neonates born in Kunming and Huai'an, which was further verified by partial pressure of inspired oxygen adjustment. However, the non‐Tibetans born in Lhasa required short‐term oxygen therapy to improve their early postnatal oxygenation. The temporal changes of PeNO and cardio‐respiratory function measurements demonstrated that Tibetan and non‐Tibetan newborns in Lhasa initially needed to adapt to attain homoeostasis in oxygenation and gas exchange.

Conclusion

Tibetan and non‐Tibetan newborn infants living at the same high altitude demonstrated comparable PeNO levels during postnatal adaptation to hypobaric hypoxia, which warrants further investigation of the mechanism of endogenous nitric oxide and hypoxic tolerance.
Immunohistochemistry of ductal adenocarcinoma of the prostate and adenocarcinomas of non‐prostatic origin: a comparative study
Authors: Seipel Amanda H. , Samaratunga Hemamali , Delahunt Brett , Wiklund Peter , Clements Mark , Egevad Lars
Published: January 2016

Ductal adenocarcinoma of the prostate (DAC) has morphological similarities to adenocarcinomas of other organs. DAC behaves in an aggressive manner and may present with metastases. These metastases may occur at unusual sites, which itself may cause diagnostic difficulties. It is important for therapeutic decisions that a prostatic origin of these metastases be established. Our aim was to compare the protein expression of DAC and adenocarcinomas of colon, endometrium, lung, pancreas, stomach and urinary bladder. A tissue microarray was constructed using 60 DAC, 6 colonic, 7 endometrial, 7 lung, 5 pancreatic, 5 gastric, and 9 urinary bladder adenocarcinomas. Slides were stained for estrogen, progesterone and androgen receptor, prolactin, PSA, prostein, PSMA, PSAP, CDX2, lysozyme, villin, monoclonal CEA, CK7, CK20, HMWCK, p63, p504s, c‐Myc, EGFR, Ki‐67, p16, p21, p27, p53, PTEN, ERG, and PAX‐8. Androgen receptor, prostein, PSA, and PSAP were almost invariably expressed in DAC. Ki‐67‐labeling index was lower in DAC than in other adenocarcinomas. The expression patterns of intestinal markers and cytokeratins in DAC were less specific and may lead to diagnostic errors if not combined with prostate‐specific markers.
Late Pleistocene hyena skeleton remains of a communal/prey depot cave den in the Bohemian Mountains (Czech Republic) – its osteology, taphonomy and palaeoecology
Authors: Diedrich Cajus G.
Published: January 2016

A total of 366 bones are arranged to six incomplete individual skeletons (=MNI) of different age classes and taphonomic preservation from the Late Pleistocene Crocuta crocuta spelaea (Goldfuss 1823) hyena den Srbsko Chlum–Komín Cave, Czech Republic, Bohemian Mountains (Central Europe). The hyena assemblage counts no siblings, 37% cub, 33% early adult/subadult and 30% adult/senile individuals. A senile scavenged individual demonstrates the cannibalism within the cave. About 10% of the 3569 megafauna bones are from hyenas which larger amounts are typical at communal/prey depot den sites. This site is different to three other larger natal/birth and communal or prey depot hyena den cave sites in Czech Republic. The Chlum–Komín Cave hyena prey bone assemblage (=NISP) consists, similar as at two other Czech Republic sites, mainly of Equus ferus przewalskii (50%), including pregnant females being hunted in spring/early summer. The fewer amounts of Coelodonta antiquitatis (4%), Bison priscus (2%), Rangifer tarandus (15%), and alpine Rupicapra rupicapra (2%) or Capra ibex (1%) and the absence of mammoth correlate to hyena den bone assemblages in middle high elevated mountain regions of northern/central Europe. The rareness of cave bears in the Bohemian Mountains, on which hyenas specialized to feed additionally in European mountain regions, explains predominant predation on horses.
Improving Access to Antenatal Care for Aboriginal Women in South Australia: Evidence from a Population‐Based Study
Authors: Brown Stephanie , Glover Karen , Weetra Donna , Ah Kit Jackie , Stuart‐Butler Deanna , Leane Cathy , Turner May , Gartland Deirdre , Yelland Jane
Published: January 2016

Introduction

Aboriginal and Torres Strait Islander women are two to three times more likely to experience adverse maternal and perinatal outcomes than non‐Aboriginal women in Australia. Persisting health inequalities are at least in part explained by late and/or inadequate access to antenatal care.

Methods

This study draws on data collected in a population‐based study of 344 women giving birth to an Aboriginal infant between July 2011 and June 2013 in South Australia to investigate factors associated with engagement in antenatal care.

Results

About 79.8 percent of mothers accessed antenatal care in the first trimester of pregnancy, and 90 percent attended five or more antenatal visits. Compared with women attending mainstream regional services, women attending regional Aboriginal Family Birthing Program services were more likely to access antenatal care in the first trimester (Adj OR 2.5 [1.0–6.3]) and markedly more likely to attend a minimum of five visits (Adj OR 4.3 [1.2–15.1]). Women attending metropolitan Aboriginal Family Birthing Program services were also more likely to attend a minimum of five visits (Adj OR 12.2 [1.8–80.8]) compared with women attending mainstream regional services. Women who smoked during pregnancy were less likely to attend a visit in the first trimester and had fewer visits.

Conclusions

Scaling up of Aboriginal Family Birthing Program Services in urban and regional areas of South Australia has increased access to antenatal care for Aboriginal families. The involvement of Aboriginal Maternal Infant Care workers, provision of transport for women to get to services, and outreach have been critical to the success of this program.
Empathy in adolescence: Relations with emotion awareness and social roles
Authors: Rieffe Carolien , Camodeca Marina
Published: January 2016

In this study, we aimed at gaining a better understanding of the individual differences contributing to feelings of empathy in adolescents. Therefore, we examined the extent to which emotion awareness (e.g., recognizing and appreciating one's own and the emotions of others) and a tendency for certain social roles (e.g., helping or teasing peers when being bullied) are related to adolescents’ levels of empathy. The sample was comprised of 182 adolescents aged between 11 and 16. Empathy and emotion awareness were assessed using self‐report measures. Peer reports were used to indicate adolescents’ different social roles: Bullying, defending the victim, and outsider behaviour. Outcomes demonstrated that evaluating one's own and the emotions of others, and more defending nominations were associated with both affective and cognitive empathy, whereas aspects of emotion awareness which are linked with internalizing symptoms were related to empathic distress, suggesting maladaptive emotion appraisal. Furthermore, outsider behaviour was associated with empathic distress, emphasizing a self‐focused orientation. In contrast, more bullying was negatively associated with cognitive empathy. Overall, these outcomes demonstrate that, besides social roles, emotion awareness is an important factor for adaptive empathic reactions, whereas emotion dysregulation might cause distress when witnessing the negative feelings of others.
MicroRNA‐30a as a prognostic factor in urothelial carcinoma of bladder inhibits cellular malignancy by antagonising Notch1
Authors: Zhang Chao , Ma Xin , Du Jun , Yao Zhiyong , Shi Taoping , Ai Qing , Chen Xusheng , Zhang Zhenting , Zhang Xu , Yao Xin
Published: January 2016

Objective

To explore the relation between microRNA‐30a (miR‐30a) and Notch1, and to evaluate the potential prognostic role of miR‐30a in invasive urothelial carcinoma of the bladder (UCB).

Patients and methods

In all, 50 invasive UCB tissue specimens, along with the adjacent bladder tissue specimens were obtained, and the clinical parameters of the 50 patients were analysed. Bioinformatics analysis was performed and miR‐30a was selected as a potential miRNA targeting Notch1, with a luciferase assay performed to verify the binding site between miR‐30a and Notch1. Quantitative real‐time reverse transcriptase‐polymerase chain reaction was used to assess the RNA expressions of miR‐30a and Notch1, while Western Blotting and immunohistochemical staining were used to assess the protein expression of Notch1. Finally, cell proliferation, cell cycle, cell migration and invasion assays were used to evaluate the cellular effects of miR‐30a and Notch1 on the UCB cell lines T24 and 5637.

Results

MiR‐30a was downregulated in tumour tissues when compared with adjacent bladder tissues (P < 0.001), negatively correlating with Notch1 messenger RNA (R2 0.106, P = 0.021) in invasive UCB, and miR‐30a expression further decreased in patients with shorter overall survival and disease‐free survival (P = 0.039 and P = 0.037, respectively). The luciferase assay showed that miR‐30a inhibited the Notch1 3′‐untranslated region reporter activities in the T24 and 5637 cell lines (both P < 0.001). Both miR‐30a and small interfering RNA Notch1 negatively regulated cell proliferation (P = 0.002 and P = 0.035 in T24; P = 0.029 and P = 0.037 in 5637 cell lines), activated cell cycle arrest (both P < 0.001 in T24; both P < 0.001 in 5637 cell lines), and prevented cellular migration (both P < 0.001 in T24; P = 0.003 and P < 0.001 in 5637 cell lines) and invasion (P = 0.009 and P = 0.006 in T24; P = 0.006 and P = 0.002 in 5637 cell lines) abilities. Ectopic Notch1 without the 3′untranslated region partially rescued the above‐mentioned cellular effects of over‐expressed miR‐30a on T24 and 5637 cells.

Conclusions

MiR‐30a lessens cellular malignancy by antagonising oncogene Notch1 and plays an effective prognostic role in invasive UCB.
Phase II trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration‐resistant prostate cancer
Authors: Madan Ravi A. , Karzai Fatima H. , Ning Yang‐Min , Adesunloye Bamidele A. , Huang Xuan , Harold Nancy , Couvillon Anna , Chun Guinevere , Cordes Lisa , Sissung Tristan , Beedie Shaunna L. , Dawson Nancy A. , Theoret Marc R. , McLeod David G. , Rosner Inger , Trepel Jane B. , Lee Min‐Jung , Tomita Yusuke , Lee Sunmin , Chen Clara , Steinberg Seth M. , Arlen Philip M. , Gulley James L. , Figg William D. , Dahut William L.
Published: January 2016

Objective

To determine the safety and clinical efficacy of two anti‐angiogenic agents, bevacizumab and lenalidomide, with docetaxel and prednisone.

Patients and methods

Eligible patients with metastatic castration‐resistant prostate cancer enrolled in this open‐label, phase II study of lenalidomide with bevacizumab (15 mg/kg), docetaxel (75 mg/m2) and prednisone (10 mg daily). Docetaxel and bevacizumab were administered on day 1 of a 3‐week treatment cycle. To establish safety, lenalidomide dosing in this combination was escalated in a conventional 3 + 3 design (15, 20 and 25 mg daily for 2 weeks followed by 1 week off). Patients received supportive measures including prophylactic pegfilgrastim and enoxaparin. The primary endpoints were safety and clinical efficacy.

Results

A total of 63 patients enrolled in this trial. Toxicities were manageable with most common adverse events (AEs) being haematological, and were ascertained by weekly blood counts. Twenty‐nine patients (46%) had grade 4 neutropenia, 20 (32%) had grade 3 anaemia and seven (11%) had grade 3 thrombocytopenia. Despite frequent neutropenia, serious infections were rare. Other common non‐haematological grade 3 AEs included fatigue (10%) and diarrhoea (10%). Grade 2 AEs in >10% of patients included anorexia, weight loss, constipation, osteonecrosis of the jaw, rash and dyspnoea. Of 61 evaluable patients, 57 (93%), 55 (90%) and 33 (54%) had PSA declines of >30, >50 and >90%, respectively. Of the 29 evaluable patients, 24 (86%) had a confirmed radiographic partial response. The median times to progression and overall survival were 18.2 and 24.6 months, respectively.

Conclusions

With appropriate supportive measures, combination angiogenesis inhibition can be safely administered and potentially provide clinical benefit. These hypothesis‐generating data would require randomized trials to confirm the findings.
A prospective study of the short‐term quality‐of‐life outcomes of patients undergoing transperineal prostate biopsy
Authors: Dowrick Adam S. , Wootten Addie C. , Howard Nicholas , Peters Justin S. , Murphy Declan G.
Published: January 2016

Objective

To investigate in a prospective, observational study whether transperineal prostate biopsy (TPbx) results in patient‐reported quality‐of‐life (QoL) changes from baseline in the first 3‐months after TPbx.

Patients and methods

Consenting patients completed the 26‐item Expanded Prostate cancer Index Composite (EPIC‐26), the Sexual Health Inventory for Men, the International Prostate Symptom Score, the Generalised Anxiety Disorder seven‐item scale, the Patient Health Questionnaire nine‐item scale, and a global question about willingness to have a repeat TPbx in a years' time. The instruments were scored using published scoring methods. Wilcoxon signed–rank tests and Mann–Whitney U‐tests were used to investigate statistically significant differences. Clinically significant differences were also investigated defined by published minimal important differences for the EPIC‐26 and changes in established categorical groups for the other instruments.

Results

In all, 53 patients consented to participate and completed the baseline questionnaire, in addition to at least one of the 1‐ or 3‐month follow‐up questionnaires. We found that most patients having a TPbx had no clinically significant change in QoL in the first 3 months after TPbx. However, 24% had clinically worse urinary function and 18% had worse sexual function at 1 month. At 3 months, 3% of patients had clinically worse urinary function and 25% continued to have worse sexual function compared with baseline. Patients who were subsequently diagnosed with cancer based on the results of the TPbx, had statistically significantly reduced QoL for the EPIC‐26 urinary scales and reduced improvements in scores on the psychological scales at the 1‐month follow‐up compared with those who were not diagnosed with cancer.

Conclusions

Most patients having a TPbx had no clinically significant change in QoL in the first 3 months after TPbx. However, patients should be advised that a quarter may have clinically worse urinary function and nearly 20% have clinically worse sexual function in the first month, and that sexual function deficits may continue up to 3 months. The results of this study provide a resource that the clinician can use when discussing TPbx with patients.
Plasma fibrinogen level: an independent prognostic factor for disease‐free survival and cancer‐specific survival in patients with localised renal cell carcinoma
Authors: Obata Jun , Tanaka Nobuyuki , Mizuno Ryuichi , Kanao Kent , Mikami Shuji , Matsumoto Kazuhiro , Kosaka Takeo , Kikuchi Eiji , Jinzaki Masahiro , Oya Mototsugu
Published: January 2016

Objectives

To investigate the impact of perioperative plasma fibrinogen level as a biomarker of oncological outcome in localised renal cell carcinoma (RCC).

Patients and methods

We consecutively identified 601 patients with localised RCC who underwent curative surgery at a single institution. Subsequent disease recurrence and cancer‐specific survival (CSS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, multivariate analysis was performed for these outcomes.

Results

Using the defined threshold level of preoperative plasma fibrinogen of ≥420 mg/dL as elevated, we found 56 patients (9.3%) with an elevated plasma fibrinogen level preoperatively. In Kaplan–Meier analysis, there was a significant difference in disease‐free survival and CSS rates between patients with and without preoperative plasma fibrinogen levels of ≥420 mg/dL. Multivariate analysis showed that elevated preoperative plasma fibrinogen level was an independent predictor of subsequent disease recurrence and cancer‐specific mortality. In a subgroup analysis of the elevated preoperative plasma fibrinogen level group, postoperative normalisation of plasma fibrinogen level was significantly associated with CSS, showing that patients with non‐normalised plasma fibrinogen levels tended to have a higher incidence of cancer‐specific mortality after surgery.

Conclusion

Patients with elevated preoperative plasma fibrinogen levels could be significantly predicted to have subsequent tumour metastasis and cancer‐specific mortality, while there was a significant difference in CSS between patients in the normalised and non‐normalised postoperative plasma fibrinogen groups. While these are hypothesis generating results, plasma fibrinogen levels may be a useful biomarker due to its low cost and ease of assessment.
Phase II study of dual phosphoinositol‐3‐kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with locally advanced or metastatic transitional cell carcinoma
Authors: Seront Emmanuel , Rottey Sylvie , Filleul Bertrand , Glorieux Philippe , Goeminne Jean‐Charles , Verschaeve Vincent , Vandenbulcke Jean‐Marie , Sautois Brieuc , Boegner Petra , Gillain Aline , van Maanen Aline , Machiels Jean‐Pascal
Published: January 2016

Objective

To assess, in a multicentre phase II trial, the safety and efficacy of BEZ235, an oral pan‐class I phosphoinositol‐3‐kinase (PI3K) and mammalian target of rapamycin (mTOR) complex1/2 inhibitor, in locally advanced or metastatic transitional cell carcinoma (TCC) after failure of platinum‐based therapy.

Patients and Methods

Patients with locally advanced or metastatic TCC progressing after platinum therapy were prospectively stratified by PI3K/Akt/mTOR pathway alterations, defined as PTEN loss and PIK3CA mutation. All patients received BEZ235 until progressive disease or unacceptable toxicity. The primary endpoint was the progression‐free survival (PFS) rate at 16 weeks. This study was, however, closed prematurely because BEZ235 was withdrawn from further development.

Results

A total of 20 patients (18 without and two with PI3K/Akt/mTOR alterations) were enrolled and received BEZ235. One partial response (5%) and two cases of stable disease (10%) were observed, all in patients without PI3K/mTOR pathway alterations. The PFS rate at 8 and 16 weeks was 15 and 10%, respectively; the median (range) PFS was 62 (38–588) days (95% confidence interval [CI] 53–110); and the median (range) overall survival was 127 (41–734) days (95% CI 58–309). Among the 90% of patients who experienced drug‐related adverse events of any grade, 50% experienced grade 3–4 adverse events, including stomatitis (15%), fatigue (5%), nausea (5%), diarrhoea (5%), renal failure (5%), cutaneous rash (5%), hepatotoxicity (5%) and hypertension (5%).

Conclusion

BEZ235 showed modest clinical activity and an unfavourable toxicity profile in patients with advanced and pretreated TCC; however, a minority of patients experienced a clinical benefit, suggesting that a complete blockade of the PI3K/mTOR axis could improve outcome in some specific patients. Furthermore, this study showed that molecular stratification of patients for personalized medicine before treatment is feasible.
Prevalence of the HOXB13 G84E mutation in Danish men undergoing radical prostatectomy and its correlations with prostate cancer risk and aggressiveness
Authors: Storebjerg Tine M. , Høyer Søren , Kirkegaard Pia , Bro Flemming ,   the LuCamp Study Group, Ørntoft Torben F. , Borre Michael , Sørensen Karina D.
Published: January 2016

Objectives

To determine the prevalence of the HOXB13 G84E mutation (rs138213197) in Danish men with or without prostate cancer (PCa) and to investigate possible correlations between HOXB13 mutation status and clinicopathological characteristics associated with tumour aggressiveness.

Materials and Methods

We conducted a case–control study including 995 men with PCa (cases) who underwent radical prostatectomy (RP) between 1997 and 2011 at the Department of Urology, Aarhus University Hospital, Denmark. As controls, we used 1622 healthy men with a normal prostate specific antigen (PSA) level.

Results

The HOXB13 G84E mutation was identified in 0.49% of controls and in 2.51% of PCa cases. The mutation was associated with a 5.12‐fold increased relative risk (RR) of PCa (95% confidence interval [CI] 2.26–13.38; P = 13 × 10−6). Furthermore, carriers of the risk allele were significantly more likely to have a higher PSA level at diagnosis (mean PSA 19.9 vs 13.6 ng/mL; P = 0.032), a pathological Gleason score ≥7 (83.3 vs 60.9%; P = 0.032), and positive surgical margins (56.0 vs 28.5%; P = 0.006) than non‐carriers. Risk allele carriers were also more likely to have aggressive disease (54.2 vs 28.6%; P = 0.011), as defined by a preoperative PSA ≥20 ng/mL, pathological Gleason score ≥ (4+3) and/or presence of regional/distant disease. At a mean follow‐up of 7 months, we found no significant association between HOXB13 mutation status and biochemical recurrence in this cohort of men who underwent RP.

Conclusions

This is the first study to investigate the HOXB13 G84E mutation in Danish men. The mutation was detected in 0.49% of controls and in 2.51% of cases, and was associated with 5.12‐fold increased RR of being diagnosed with PCa. In our RP cohort, HOXB13 mutation carriers were more likely to develop aggressive PCa. Further studies are needed to assess the potential of HOXB13 for future targeted screening approaches.
New In Vitro Models to Study Amyotrophic Lateral Sclerosis
Authors: Myszczynska Monika , Ferraiuolo Laura
Published: January 2016

Amyotrophic Lateral Sclerosis (ALS) is a complex multifactorial disorder, characterized by motor neuron loss with involvement of several other cell types, including astrocytes, oligodendrocytes and microglia. Studies in vivo and in in vitro models have highlighted that the contribution of non‐neuronal cells to the disease is a primary event and ALS pathogenesis is driven by both cell‐autonomous and non‐cell autonomous mechanisms. The advancements in genetics and in vitro modeling of the past 10 years have dramatically changed the way we investigate the pathogenic mechanisms involved in ALS. The identification of mutations in transactive response DNA‐binding protein gene (TARDBP), fused in sarcoma (FUS) and, more recently, a GGGGCC‐hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) and their link with familial ALS have provided new avenues of investigation and hypotheses on the pathophysiology of this devastating disease. In the same years, from 2007 to present, in vitro technologies to model neurological disorders have also undergone impressive developments. The advent of induced pluripotent stem cells (iPSCs) gave the field of ALS the opportunity to finally model in vitro not only familial, but also the larger part of ALS cases affected by sporadic disease. Since 2008, when the first human iPS‐derived motor neurons from patients were cultured in a petri dish, several different techniques have been developed to produce iPSC lines through genetic reprogramming and multiple direct conversion methods have been optimised. In this review, we will give an overview of how human in vitro models have been used so far, what discoveries they have led to since 2007, and how the recent advances in technology combined with the genetic discoveries, have tremendously widened the horizon of ALS research.
New ALS‐Related Genes Expand the Spectrum Paradigm of Amyotrophic Lateral Sclerosis
Authors: Sabatelli Mario , Marangi Giuseppe , Conte Amelia , Tasca Giorgio , Zollino Marcella , Lattante Serena
Published: January 2016

Amyotrophic Lateral Sclerosis (ALS) is characterized by the degeneration of upper and lower motor neurons. Clinical heterogeneity is a well‐recognized feature of the disease as age of onset, site of onset and the duration of the disease can vary greatly among patients. A number of genes have been identified and associated to familial and sporadic forms of ALS but the majority of cases remains still unexplained. Recent breakthrough discoveries have demonstrated that clinical manifestations associated with ALS‐related genes are not circumscribed to motor neurons involvement. In this view, ALS appears to be linked to different conditions over a continuum or spectrum in which overlapping phenotypes may be identified. In this review, we aim to examine the increasing number of spectra, including ALS/Frontotemporal Dementia and ALS/Myopathies spectra. Considering all these neurodegenerative disorders as different phenotypes of the same spectrum can help to identify common pathological pathways and consequently new therapeutic targets in these incurable diseases.
Spatial Ecology of the Fungal Genus Xylaria in a Tropical Cloud Forest
Authors: Thomas Daniel C. , Vandegrift Roo , Ludden Ashley , Carroll George C. , Roy Bitty A.
Published: January 2016

Fungal symbioses with plants are ubiquitous, ancient, and vital to both ecosystem function and plant health. However, benefits to fungal symbionts are not well explored, especially in non‐mycorrhizal fungi. The Foraging Ascomycete hypothesis proposes that some wood‐decomposing fungi may shift life‐history strategies to endophytism to bridge gaps in time and space between suitable substrates. To test this hypothesis we examine spatial relationships of Xylaria endophytic fungi in the forest canopy with Xylaria decomposer fungi on the forest floor. We sampled for fungi of the genus Xylaria using a spatially explicit sampling scheme in a remote Ecuadorian cloud forest, and concurrently carried out an extensive culture‐based sampling of fungal foliar endophytes. We found 36 species of Xylaria in our 0.5 ha plot, 31 of which were found to only occur as fruiting bodies. All five species of Xylaria found as endophytes were also found as fruiting bodies. We also tested the relationships of both stages of these fungi to environmental variables. Decomposer fungi were differentiated by species‐specific habitat preferences, with three species being found closer to water than expected by chance. In contrast, endophytes displayed no sensitivity to environmental conditions, such as host, moisture, or canopy cover. We found evidence of spatial linkage between life stages in two species. We also demonstrate that direct transmission of endophytes from leaves to woody substrates is possible. These results indicate that endophytism may represent one way for decomposer fungi to escape moisture limitation, and that endophytic fungi may act as sources of dispersal for decomposer fungi consistent with predictions of the Foraging Ascomycete hypothesis.
Bird Communities in Amazonian White‐Sand Vegetation Patches: Effects of Landscape Configuration and Biogeographic Context
Authors: Borges Sergio H. , Cornelius Cintia , Moreira Marcelo , Ribas Camila C. , Conh‐Haft Mario , Capurucho João M. , Vargas Claudeir , Almeida Ricardo
Published: January 2016

Vegetation growing on white‐sand soils is patchily distributed across the Amazon and is characterized by scrublands or open vegetation types (white‐sand campinas) and by forests (white‐sand forests) surrounded by contrasting habitat types. We studied birds in patches of white‐sand campinas in contrasting landscapes in four regions located in distinct biogeographic units delimited by major rivers. Our aim was to investigate the contribution of landscape configuration and biogeographic context to patterns of species diversity and distribution. Aracá and Viruá landscapes (on opposite sides of Rio Branco) are composed by large and continuous patches of white‐sand campinas, while Jaú, Novo Airão and Uatumã landscapes (on opposite sides of Rio Negro) are composed by small patches of white‐sand campinas isolated by continuous terra firme forests. Birds were sampled using mist‐nets and qualitative censuses, and were classified as white‐sand vegetation specialists or non‐specialists. Bird species diversity was significantly different among studied regions, and composition was significantly different for both, specialists and non‐specialists birds. Local variability in species diversity and composition was best explained by white‐sand campina area, patch proximity, and distance to major rivers. We conclude that landscape configuration and biogeographical context influence patterns of bird diversity, abundance, and composition in Amazonian white‐sand campinas.
Low Phylogenetic Beta Diversity and Geographic Neo‐endemism in Amazonian White‐sand Forests
Authors: Guevara Juan Ernesto , Damasco Gabriel , Baraloto Christopher , Fine Paul V. A. , Peñuela María Cristina , Castilho Carolina , Vincentini Alberto , Cárdenas Dairón , Wittmann Florian , Targhetta Natalia , Phillips Oliver , Stropp Juliana , Amaral Ieda , Maas Paul , Monteagudo Abel , Jimenez Eliana M. , Thomas Rachel , Brienen Roel , Duque Álvaro , Magnusson William , Ferreira Cid , Honorio Eurídice , de Almeida Matos Francisca , Arevalo Freddy R. , Engel Julien , Petronelli Pascal , Vasquez Rodolfo , ter Steege Hans
Published: January 2016

Over the past three decades, many small‐scale floristic studies of white‐sand forests across the Amazon basin have been published. Nonetheless, a basin‐wide description of both taxonomic and phylogenetic alpha and beta diversity at regional scales has never been achieved. We present a complete floristic analysis of white‐sand forests across the Amazon basin including both taxonomic and phylogenetic diversity. We found strong regional differences in the signal of phylogenetic community structure with both overall and regional Net Relatedness Index and Nearest Taxon Index values found to be significantly positive leading to a pattern of phylogenetic clustering. Additionally, we found high taxonomic dissimilarity but low phylogenetic dissimilarity in pairwise community comparisons. These results suggest that recent diversification has played an important role in the assembly of white‐sand forests causing geographic neo‐endemism patterns at the regional scale.
The White‐sand Vegetation of Acre, Brazil
Authors: Daly Douglas C. , Silveira Marcos , Medeiros Herison , Castro Wendeson , Obermüller Flávio A.
Published: January 2016

For vegetation on white sand in Amazonia, the topography, soil nutrients, level of the water table, and rainfall combine to result in distinct formations, each with a characteristic physiognomy and each with a rather distinct floristic composition and very distinct dominants. We describe the physiognomies and present the floristic composition of nine formations, based on intensive fieldwork in NW Acre state, Brazil, where on six sites we have documented 222 species; 170 of them are woody plants or trunked palms ≥5 cm diam. Herbaceous species are good indicators for some of the formations. Distribution patterns and habitat specialization can be difficult to interpret because they often require familiarity with the localities and local terminologies involved. Many of the species show disjunct distributions congruent with the occurrence of other white‐sand areas in northern South America. The nine formations within Acre are strongly dissimilar, with only two pairwise comparisons showing >50 percent similarity. Comparison of the Acre white‐sand flora with datasets from Peruvian and Central + Eastern Amazonia show striking differences in composition and in taxonomic dominance, with more than 95 percent dissimilarity. White‐sand formations in Acre and elsewhere are gravely affected by expanding human settlement; little is known about the regeneration and recovery of the degraded white‐sand habitats. This complex sector of Acre's biological diversity is still virtually unrepresented in conservation units anywhere in Brazil's part of southwestern Amazonia, so it should be made an immediate conservation priority.
Pre‐settlement vegetation maps generated using Ontario early survey: An online database providing enhanced map access for researchers
Authors: Karrow Thomas , Suffling Roger
Published: January 2016

Key Messages

Early survey data from Ontario and elsewhere in Canada are vastly under‐utilized research resources.

Pre‐settlement vegetation data embedded in early survey notes provide reliable baseline data sets for vegetation mapping.

Existing vegetation maps derived from early survey data are largely unknown and inaccessible, but are now inventoried and available online through the University of Waterloo Library's Geospatial Centre.
Utility of FDG‐PET imaging in screening for succinate dehydrogenase B and D mutation‐related lesions
Authors: Kornaczewski E.R. , Pointon O.P. , Burgess J.R.
Published: January 2016

Objective

Mutations of the genes encoding succinate dehydrogenase B and D (SDHB, SDHD) are associated with highly penetrant phenotypes, including paragangliomas and phaeochromocytomas. Patients with these mutations require lifelong surveillance; however, there is currently ambiguity regarding the optimal screening regimen. We sought to determine the utility of fluorodeoxyglucose (18F) positron emission tomography (18F‐FDG PET) imaging, compared to other modalities for detecting SDHB and SDHD mutation‐related lesions.

Design

A retrospective audit of patients with SDHB or SDHD mutation.

Patients

All adult patients with confirmed SDHB and SDHD mutations who underwent 18F‐FDG PET/CT at our institution between 1 July 2011 and 30 May 2015.

Measurements

18F‐FDG PET/computed tomography (CT) performed during surveillance of patients with SDHB and SDHD mutations. Lesion numbers and locations detected by 18F‐FDG PET were compared to those identified on the CT component, as well as other imaging modalities and histology when available.

Results

Thirty‐one 18F‐FDG PET/CT studies were completed on 22 patients. For SDHB (20 patients), there were five positive and 21 negative studies. There were no false‐negative 18F‐FDG PET studies. Positive 18F‐FDG PET findings correlated with magnetic resonance imaging (MRI), CT and [68 Ga]‐DOTA(0)‐Tyr(3)‐octreotate (68 Ga DOTATATE PET/CT) imaging with no missed lesions; the only potential false‐positive result relating to nonspecific postoperative changes (sensitivity 100·0%, specificity 95·5%).

For SDHD (two patients), lesions were detected on 18F‐FDG PET and correlated with other imaging in three of five studies. Metastatic lesions were incompletely visualized on 18F‐FDG PET but were detected on the noncontrast fusion CT.

Conclusions

18F‐FDG PET/CT is suitable for detecting SDHB and SDHD mutation‐related lesions and may be considered effective for periodic surveillance of patients with these mutations.
Adrenal surgery in England: better outcomes in high‐volume practices
Authors: Palazzo Fausto , Dickinson Andrew , Phillips Barbara , Sahdev Anju , Bliss Richard , Rasheed Ashraf , Krukowski Zygmunt , Newell‐Price John
Published: January 2016

Aims and Background

Adrenal surgery is performed by a variety of surgical specialities in differing environments and volumes. International data suggest that there is a correlation between adrenal surgery volume and outcomes but there are no UK data to support this or UK surgical guidelines. A multidisciplinary team representing the stakeholders in adrenal disease is preparing a national guidance on adrenal surgery. A review of the outcomes for adrenal surgery in England was performed to correlate outcomes with the volume of surgeon practice.

Methods

Hospital Episode Statistics (HES) data for the National Health Service (NHS) in England in the tax year 2013–2014 were examined for adrenal surgery. Length of hospital stay and rate of postoperative readmission were assessed as surrogate quality markers and a comparison made between ‘high‐’ and ‘low‐’ volume surgeons.

Results

A total of 795 adult adrenalectomies were performed by 222 different surgeons with a range of between 1 and 34 adrenalectomies performed per surgeon. Only thirty‐six (16%) adrenal surgeons performed 6 or more adrenalectomies. A total of 186 surgeons (84%) performed a median of one adrenalectomy a year. Length of stay and readmission rate within thirty days of operation was 60% longer and 47% higher, respectively, when performed by low‐volume surgeons.

Conclusion

The current provision of adrenal surgery in the UK is not in the best interests of patients and is not cost‐effective for the NHS. Adrenal surgery is best performed by higher volume surgeons in centres with dedicated adrenal multidisciplinary teams expert in all aspects of care of the adrenal patient.