bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomedical PhD Education – An International Perspective
Authors: Mulvany Michael J. 
Published: April 2013

AbstractThe PhD, otherwise known as the doctor of philosophy or Dr. Phil., is an internationally recognized degree, indicating that the PhD graduate has received training in research under supervision. Traditionally, the PhD was the route to an academic career, with most successful PhD graduates receiving tenured university positions. However, over the past 20–30 years, and particularly the past 10 years, the situation has changed dramatically. Governments in many countries have invested massively in PhD education, believing that trained researchers will contribute to the ‘knowledge society’, and thus increase the competitiveness of their countries in the future economies of the world. Thus, only a small fraction of PhD graduates now end up in academic research. Yet, the PhD remains a research degree, and indeed, institutions have become heavily dependent on PhD students for their research output. The situation has thus created a paradox. On the one hand, it has become essential for institutions to have many PhD students and for the research performed to be of the highest level. On the other hand, the careers of PhD students are not necessarily going to be directly related to the research performed during their PhD studies. The purpose of this article is to explore how this seeming paradox is being addressed in biomedicine and to show that far from being inconsistent that the two aspects are in fact complementary. The article is based on the author's experience as Head of Aarhus Graduate School of Health Sciences 2002–2011 and his work with graduate schools across Europe and internationally through the organization ORPHEUS.
A systematic review and meta‐analysis of laparoscopic vs open restorative proctocolectomy
Authors: Singh P. , Bhangu A. , Nicholls R. J. , Tekkis P. 
Published: April 2013

AbstractAimThe benefits of a laparoscopic approach to restorative proctocolectomy (RPC) are controversial. The aim of this meta‐analysis was to compare the outcome following laparoscopic and open RPC, with particular attention to adverse events and long‐term function.MethodA systematic search of the MEDLINE, EMBASE and Ovid databases was performed for studies published until March 2012. The primary end‐point was long‐term function. Secondary end‐points were intra‐operative details, short‐term postoperative outcome and postoperative adverse events. Weighted mean difference (WMD) and odds ratio (OR) were calculated using fixed/random effect meta‐analytic techniques.ResultsThe final analysis included 27 comparative studies of 2428 patients, of whom 1097 (45.1%) underwent laparoscopic surgery. A laparoscopic approach was associated with a significantly longer operation time (WMD 70.1 min, P < 0.001), shorter length of hospital stay (WMD −1.00 day, P < 0.001), reduced intra‐operative blood loss (WMD −89.10 ml, P < 0.001) and a lower incidence of wound infection (OR 0.60, P < 0.005). No significant differences were observed in the rate of pouch failure. Although there was no significant difference in the number of daily bowel movements (OR 0.04, P = 0.950), laparoscopic surgery led to fewer nocturnal bowel movements (WMD −1.14, P < 0.001) and reduced pad usage during the day (OR 0.22, P < 0.001) and night (OR 0.33, P < 0.001). The post hoc power to detect differences in adverse event rates ranged from 5% to 42%.ConclusionLaparoscopic and open approaches to RPC produced equivalent adverse event rates and long‐term functional results. However, the present evidence is underpowered to detect true differences in adverse event rates.
Risk factors for early re‐bleeding and associated hospitalization in patients with colonic diverticular bleeding
Authors: Fujino Y. , Inoue Y. , Onodera M. , Kikuchi S. , Endo S. , Shozushima T. , Suzuki K. 
Published: April 2013

AbstractAimThe annual incidence of colonic diverticular bleeding is increasing, but treatments are not yet well established. Here we aimed to identify the risk factors for early re‐bleeding and to determine the associated duration of hospitalization.MethodRecords of 90 emergent patients with colonic diverticular bleeding between 1999 and May 2012 were retrospectively reviewed. They were divided into an early re‐bleeding within 1 month group (n = 24) and a no re‐bleeding group (n = 66) and we investigated the risk factors for early re‐bleeding. In the former group, we calculated the time from the first haemostasis to early re‐bleeding and the associated duration of hospitalization.ResultsUnivariate analysis showed that there were significantly more patients with signs of shock (P = 0.00055) and active bleeding on the first colonoscopy after admission (P = 0.020) in the early re‐bleeding group. Multivariate conditional logistic regression analysis using stepwise variable selection showed that signs of shock on admission (odds ratio, 5.23; 95% confidence interval, 1.84–14.90; P = 0.0019) remained statistically significant. All patients who re‐bled without signs of shock (n = 7) and 16 of 17 with signs of shock re‐bled within 126 h (5.25 days) of initial hospitalization.ConclusionShock was an independent risk factor for early re‐bleeding. The associated duration of hospitalization was 6 days.
Incidence and phylogenetic analyses of Armillaria spp. associated with root disease in peach orchards in the State of Mexico, Mexico
Authors: Elías‐Román R. D. , Guzmán‐Plazola R. A. , Klopfenstein N. B. , Alvarado‐Rosales D. , Calderón‐Zavala G. , Mora‐Aguilera J. A. , Kim M.‐S. , García‐Espinosa R. 
Published: April 2013

SummaryIncidence of peach [Prunus persica (L.) Batsch] tree mortality attributed to Armillaria root disease was assessed from 2009 to 2011 in 15 orchards in the State of Mexico, Mexico. Incidence increased gradually every year of assessment, reaching average values of 9.7, 15.3 and 20.3% tree mortality and 23.2, 24.7 and 28.3% disease‐impacted area of the orchards during 2009, 2010 and 2011, respectively. The cultivars ‘Nemaguard’ and ‘Criollo of La Goleta’, a local rootstock used in the region, were both susceptible to the disease. To identify species of Armillaria isolated from infected peach trees, two nuclear rDNA regions (partial 5.8S‐ITS2‐LSU D‐domains and partial 3′ LSU‐IGS1) and the translation elongation factor‐1α (tef‐1α) gene were sequenced and compared with sequences of known Armillaria species. DNA sequence analysis from 49 Armillaria isolates revealed that five isolates (10.2%) were Armillaria mellea and eight isolates (16.3%) were Armillaria gallica. DNA sequences from the remaining 36 isolates (73.5%) showed no close similarity to Armillaria sequences in GenBank, and apparently represent an undescribed Armillaria species. This undescribed species was the most widely distributed in the region of study. Separate phylogenetic analyses of the LSU region (D1–D3 domains concatenated with the partial 3′ end) and the tef‐1α region show that the undescribed species is quite distinct from other Armillaria spp. reported in North America.
Cell cycle regulation score predicts relapse‐free survival in non‐germinal centre diffuse large B‐cell lymphoma patients treated by means of immunochemotherapy
Authors: Pasanen Anna Kaisa , Haapasaari Kirsi‐Maria , Peltonen Jenni , Soini Ylermi , Jantunen Esa , Bloigu Risto , Turpeenniemi‐Hujanen Taina , Kuittinen Outi 
Published: April 2013

AbstractObjectivesThe cell cycle is under strict regulation by the retinoblastoma, p53 and p27 pathways, and the disruption of these pathways is an important characteristic of diffuse large B‐cell lymphoma (DLBCL). In this study, we wanted to assess the function and prognostic significance of these pathways in DLBCL patients.MethodsTissue samples from 120 DLBCL patients treated by means of R‐CHOP‐type chemotherapy were stained for the cell cycle–regulating proteins p16, p21, p27 and p53, and the germinal centre (GC) phenotype was determined according to Hans' algorithm. Based on the number of impaired cell cycle–regulating pathways a predictive score was obtained, covering three different prognostic groups: a ‘favourable’ group with damage in 0–1 of the studied pathways, a ‘poor’ group with damage in all three pathways and an ‘intermediate’ group comprising the rest of the patients.ResultsThe prognosis of non‐GC DLBCL patients was significantly poorer vs. GC phenotype patients (P = 0.015). The prognostic score proved especially useful among non‐GC phenotype patients, with 3‐yrs relapse‐free survival of 100% vs. 62.6% vs. 24.3% in the ‘favourable‐’, ‘intermediate‐’ and ‘poor prognosis’ groups, respectively (P = 0.003).ConclusionThe prognosis of non‐GC DLBCL patients is progressively impaired with the accumulation of damage in different cell cycle–regulating pathways.
Clinical correlates of acute pulmonary events in children and adolescents with sickle cell disease
Authors: Paul Rabindra , Minniti Caterina P. , Nouraie Mehdi , Luchtman‐Jones Lori , Campbell Andrew , Rana Sohail , Onyekwere Onyinye , Darbari Deepika S. , Ajayi Olaid , Arteta Manuel , Ensing Gregory , Sable Craig , Dham Niti , Kato Gregory J. , Gladwin Mark T. , Castro Oswaldo L. , Gordeuk Victor R. 
Published: April 2013

AbstractObjectivesWe aimed to identify risk factors for acute pulmonary events in children and adolescents in the Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study.MethodsPatients with hemoglobin SS (n = 376) and other sickle cell genotypes (n = 127) aged 3–20 yrs were studied at four centers in a cross‐sectional manner. A subgroup (n = 293) was followed for a median of 21 months (range 9–35).ResultsA patient‐reported history of one or more acute pulmonary events, either acute chest syndrome (ACS) or pneumonia, was obtained in 195 hemoglobin SS patients (52%) and 51 patients with other genotypes (40%). By logistic regression, history of acute pulmonary events was independently associated with patient‐reported history of asthma (P < 0.0001), older age (P = 0.001), >3 severe pain episodes in the preceding 12 months (P = 0.002), higher tricuspid regurgitation velocity (TRV) (P = 0.028), and higher white blood cell (WBC) count (P = 0.043) among hemoglobin SS patients. History of acute pulmonary events was associated with >3 severe pain episodes (P = 0.009) among patients with other genotypes. During follow‐up, 43 patients (15%) had at least one new ACS episode including 11 without a baseline history of acute pulmonary events. History of acute pulmonary events (odds ratio 5.0; P < 0.0001) and younger age (odds ratio 0.9; P = 0.007) were independently associated with developing a new episode during follow‐up.ConclusionsAsthma history, frequent pain, and higher values for TRV and WBC count were independently associated with history of acute pulmonary events in hemoglobin SS patients and frequent pain was associated in those with other genotypes. Measures to reduce pain episodes and control asthma may help to decrease the incidence of acute pulmonary events in SCD.
Metal‐dependent protein phosphatase 1A functions as an extracellular signal‐regulated kinase phosphatase
Authors: Li Rong , Gong Zheng , Pan Chang , Xie Di‐Dong , Tang Jun‐Yi , Cui Min , Xu Yun‐Fei , Yao Wei , Pang Qi , Xu Zhi‐gang , Li Min‐yong , Yu Xiao , Sun Jin‐Peng 
Published: April 2013

Protein phosphorylation is an important post‐translational modification that regulates almost every aspect of signal transduction in cells. Activation of the mitogen‐activated protein kinase (MAPK) family kinase extracellular signal‐regulated kinase (ERK) is a point of convergence for many cellular activities in response to external stimulation. With stimuli, ERK activity is significantly increased by the phosphorylation of Thr202 and Tyr204 at its activation loop. Downregulation of ERK phosphorylation at these two sites by several phosphatases, such as protein phosphatase 2A, HePTP and MAPK phosphatase 3, is essential for maintaining appropriate ERK function in different cellular processes. However, it is unknown whether metal‐dependent protein phosphatase (PPM) family phosphatases directly dephosphorylate ERK. In this study, we found that PPM1A negatively regulated ERK by directly dephosphorylating its pThr202 position early in EGF stimulation. Additional kinetic studies revealed that key residues participated in phospho‐ERK recognition by PPM1A. Importantly, PPM1A preferred the phospho‐ERK peptide sequence over a panel of other phosphopeptides through the interactions of basic residues in the active site of PPM1A with the pThr‐Glu‐pTyr motif of ERK. Whereas Lys165 and Arg33 were required for efficient catalysis or phosphosubstrate binding of PPM1A, Gln185 and Arg186 were determinants of PPM1A substrate specificity. The interaction between Arg186 of PPM1A and Glu203 and pTyr204 of phospho‐ERK was identified as a hot‐spot for phospho‐ERK–PPM1A interaction.Structured digital abstract

PPM1A physically interacts with ERK2 by pull down (View interaction)

PPM1A dephosphorylates p38 by phosphatase assay (View Interaction: 1, 2)

PPM1A binds to ERK2 by pull down (View interaction)

PPM1A dephosphorylates ERK2 by phosphatase assay (View Interaction: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
Detection of Epstein–Barr virus‐specific memory CD4+T cells using a peptide‐based cultured enzyme‐linked immunospot assay
Authors: Calarota Sandra A. , Chiesa Antonella , Zelini Paola , Comolli Giuditta , Minoli Lorenzo , Baldanti Fausto 
Published: April 2013

SummaryApproaches to evaluate T‐cell responses to Epstein–Barr virus (EBV) include enzyme‐linked immunospot (ELISPOT), which quantifies cells capable of immediate interferon‐γ secretion upon antigen stimulation. However, evaluation of expandable EBV‐specific memory T cells in an ELISPOT format has not been described previously. We quantified EBV‐specific T‐cell precursors with high proliferative capacity by using a peptide‐based cultured interferon‐γ ELISPOT assay. Standard and cultured ELISPOT responses to overlapping peptide pools (15‐mers overlapping by 11 amino acids) covering the lytic (BZLF1 and BMRF1) and latent (EBNA1, EBNA3a, EBNA3b, EBNA3c, LMP1 and LMP2) EBV proteins were evaluated in 20 healthy subjects with remote EBV infection and, for comparison, in four solid organ transplant recipients. Cultured ELISPOT responses to both lytic and latent EBV antigens were significantly higher than standard ELISPOT responses. The distribution of EBV‐specific T‐cell responses detected in healthy virus carriers showed more consistent cultured ELISPOT responses compared with standard ELISPOT responses. T‐cell responses quantified by cultured ELISPOT were mainly mediated by CD4+ T cells and a marked pattern of immunodominance to latent‐phase antigens (EBNA1 > EBNA3 family antigens > LMP2 > LMP1) was shown. Both the magnitude and distribution of EBV‐specific T‐cell responses were altered in solid organ transplant recipients; in particular, cultured ELISPOT responses were almost undetectable in a lung‐transplanted patient with EBV‐associated diseases. Analysis of T‐cell responses to EBV by ELISPOT assays might provide new insights into the pathogenesis of EBV‐related diseases and serve as new tools in the monitoring of EBV infection in immunocompromised patients.
The Role of Waixenicin A as Transient Receptor Potential Melastatin 7 Blocker
Authors: Kim Byung J. , Nam Joo H. , Kwon Young K. , So Insuk , Kim Seon J. 
Published: April 2013

AbstractTransient receptor potential melastatin 7 (TRPM7) plays a role in a number of physiological and pharmacological functions in variety of cells. The aim of this study was to clarify the role for TRPM7 channels and the effect of waixenicin A on the pacemaking activity of interstitial cells of Cajal (ICCs) and on the cell viability of the human gastric and breast adenocarcinoma cell lines, AGS and MCF‐7, respectively. Waixenicin A decreased the amplitude of pacemaker potentials in cultured ICC clusters and inhibited TRPM7 currents, but had no effect on Ca2+‐activated Cl− conductance (ANO1). Furthermore, waixenicin A was found to inhibit the growth and survival of AGS and MCF‐7 cells. These findings indicate that TRPM7 channel modulates intestinal motility and regulates the pathophysiology of human gastric and breast adenocarcinoma cells. These findings suggest that TRPM7 channel be considered a potential target for the treatment of gut motor disorders and gastric and breast cancer.
Improved In Vivo Performance of Second‐Generation Cryoballoon for Pulmonary Vein Isolation
Authors: COULOMBE NICOLAS , PAULIN JAIME , SU WILBER 
Published: April 2013

Coulombe—Improved Performance of Second‐Generation CryoballoonIntroductionA novel cryoballoon with improved refrigerant distribution promises better pulmonary vein (PV) isolation success rate without sacrificing the technology's safety profile. This study aimed to compare the Arctic Front® (AF) balloon to the new Arctic Front Advance™ (AFA).Methods and ResultsTwenty pulmonary PVs from 10 healthy dogs weighing 29.8 ± 1.1 kg were assigned to ablation with AF and AFA, using a 23 mm or 28 mm balloon. A single 4‐minute ablation was performed in each vessel, with no phrenic nerve monitoring. The Achieve™ mapping catheter was used to confirm acute isolation. Thirty days post‐treatment the ablation sites were assessed for electrical PV isolation and ablation completeness via gross and histological examination. The phrenic nerve, PVs, lungs, esophagus, kidneys, and brain were collected for evaluation of potential damage. A preprocedural and prenecropsy CT were performed to assess incidence of PV stenosis. All 10 PVs were fully isolated with AFA; 6 of 10 PVs were fully isolated with AF. In all cases, lesion gaps with AF are believed to stem from inadequate cooling of the most distal balloon segment that was in contact with the unablated PV tissue. No untoward findings were detected on gross examination of the heart, esophagus, kidneys, brain, or PVs. One phrenic nerve had cross‐sectional ablation associated with an AFA 23 mm balloon. Superficial regions of subpleural lung fibrosis were noted adjacent to 7 PVs.ConclusionsPV isolation and lesion completeness were improved with Arctic Front Advance, while no unexpected findings were found related to safety.
Management of advanced non‐melanoma skin cancers using helical tomotherapy
Authors: Kramkimel N. , Dendale R. , Bolle S. , Zefkili S. , Fourquet A. , Kirova Y.M. 
Published: April 2013

AbstractBackgroundHelical tomotherapy (HT) is a relatively new method of radiotherapy, the main advantages of which are an increase of irradiation dose on the target tumour volume and best protection of adjacent organs at risk.ObjectiveTo provide an accurate evaluation of efficiency and tolerance of HT on different kinds of non‐melanoma skin tumours.Patients and methodsWe analysed, retrospectively, 25 patients (pts) who were treated with HT for advanced non‐melanoma skin cancers. We studied the characteristics of patients and tumours, associated treatments, characteristics, efficacy and tolerance of HT treatment.ResultsEight had basal cell carcinoma, Eight had cutaneous squamous cell carcinoma, five Merkel cell carcinoma and four adnexal carcinoma. The median age was 75 years (range 51–89). The median follow‐up was 12 months. HT was used because of incomplete excision (n = 12), lymph node involvement (n = 6), non‐operable lesions (n = 4) and high risk of relapse (n = 4). The delivered dose for the tumour bed was between 50 and 70 Gy and for the lymph node it was between 50 and 64 Gy. There was no grade III–IV adverse event, except one grade III mucositis. Fourteen pts suffered from limited toxic effects 6 months after the end of the treatment, mainly loss of eyebrow and teared eye. Complete remission was noticed for 22 pts (88%); one pt had progressive disease and two pts died.ConclusionHT is an effective option for advanced non‐melanoma skin cancers as radical treatment or in association with surgery. Early and late toxicity and cosmetic results are acceptable.
Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies
Authors: Maurovich‐Horvat Eszter , Kemlink David , Högl Birgit , Frauscher Birgit , Ehrmann Laura , Geisler Peter , Ettenhuber Katharina , Mayer Geert , Peraita‐Adrados Rosa , Calvo Elena , Lammers Gert Jan , Van der Heide Astrid , Ferini‐Strambi Luigi , Plazzi Giuseppe , Poli Francesca , Dauvilliers Yves , Jennum Poul , Leonthin Helle , Mathis Johannes , Wierzbicka Aleksandra , Puertas Francisco J. , Beitinger Pierre A. , Arnulf Isabelle , Riha Renata L. , Tormášiová Maria , Slonková Jana , Nevšímalová Sona , Šonka Karel ,   the European Narcolepsy Network
Published: April 2013

SummaryIn a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self‐administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P < 0.001) and had a higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More patients with narcolepsy–cataplexy during pregnancy had impaired glucose metabolism and anaemia. Three patients experienced cataplexy during delivery. The rate of caesarean sections was higher in the narcolepsy–cataplexy group compared to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of neonates were within the normal range and did not differ across groups. Neonatal care was affected adversely by symptoms of narcolepsy in 60.1% of those with narcolepsy during pregnancy. This study reports more obstetric complications in patients with narcolepsy–cataplexy during pregnancy; however, these were not severe. This group also had a higher BMI and higher incidence of impaired glucose metabolism during pregnancy. Caesarian section was conducted more frequently in narcolepsy–cataplexy patients, despite cataplexy being a rare event during delivery. Furthermore, symptoms of narcolepsy may render care of the infant more difficult.