bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impacts of training pathways and experiences during intern year on doctor emigration from Ireland
Authors: Cronin Frances , Clarke Nicholas , Hendrick Louise , Conroy Ronan , Brugha Ruairi 
Published: November 2019

Abstract

Background
Emigration of domestically-trained health professionals is widespread, including in Ireland which has the highest rate of medical graduates in the OECD. Ireland’s failure to retain graduates necessitates high levels of international recruitment. This study aimed to identify factors associated with recently graduated doctors’ intention to migrate, focusing on their work experiences during the mandatory post-graduation year, their wellbeing, and their perceptions of postgraduate training in Ireland.

Methods
A baseline survey was administered online to all final year students in Ireland’s six medical schools. A subsequent sweep surveyed those who consented to follow-up (n = 483) during the final month of first year of practice.

Results
Of the 232 respondents (48% response rate), 210 (94%) were Irish passport holders. Of these, only 36% intended to remain in Ireland after their internship, 57% intended to leave but return later, and 7% intended to leave permanently. A strong predictor of intention was study pathway: 60% of Graduate Entry Medicine (GEM) graduates and 25% of Direct Entry Medicine (DEM) graduates intended to remain in Ireland. Equal proportions intended to leave permanently (8% DEM, 6% GEM). Being a GEM graduate significantly reduced the likelihood of leaving to return (relative risk ratio (RRR) 0.20, 95% confidence interval (CI) (0.11–0.39), p < 0.001).
When adjusted for study pathway, a negative experience as an intern increased the likelihood of leaving to return (RRR 1.16 CI (1.00–1.34), p = 0.043) and leaving permanently (1.54 (1.15–2.04), p = 0.003). Similarly, experience of callousness was associated with leaving to return (1.23 (1.03–1.46), p = 0.023) and leaving permanently (1.77 (1.24–2.53), p = 0.002), as was burnout with leaving permanently (1.57 (1.08–2.27), p = 0.017). Those planning to specialise in Medicine versus General Practice were more likely to leave and return (3.01 (1.09–8.34), p = 0.034). Those with negative perceptions of training in Ireland were more likely to leave and return (1.16 (1.01–1.34), p = 0.037); a positive perception reduced the likelihood of leaving permanently (0.50 (0.26–0.94), p = 0.032).

Conclusions
Increasing GEM training places might improve Ireland’s retention of domestically-trained doctors, reducing reliance on non-EU-trained doctors. However, improvements in the working experiences, perceptions of training, and protection of wellbeing are essential for retaining this highly sought-after and geographically mobile cohort.
The link between chronic pain and Alzheimer’s disease
Authors: Cao Song , Fisher Daniel W. , Yu Tain , Dong Hongxin 
Published: November 2019

Abstract
Chronic pain often occurs in the elderly, particularly in the patients with neurodegenerative disorders such as Alzheimer’s disease (AD). Although studies indicate that chronic pain correlates with cognitive decline, it is unclear whether chronic pain accelerates AD pathogenesis. In this review, we provide evidence that supports a link between chronic pain and AD and discuss potential mechanisms underlying this connection based on currently available literature from human and animal studies. Specifically, we describe two intertwined processes, locus coeruleus noradrenergic system dysfunction and neuroinflammation resulting from microglial pro-inflammatory activation in brain areas mediating the affective component of pain and cognition that have been found to influence both chronic pain and AD. These represent a pathological overlap that likely leads chronic pain to accelerate AD pathogenesis. Further, we discuss potential therapeutic interventions targeting noradrenergic dysfunction and microglial activation that may improve patient outcomes for those with chronic pain and AD.
mTOR signaling in Brown and Beige adipocytes: implications for thermogenesis and obesity
Authors: Ye Yuqing , Liu Hailan , Zhang Feng , Hu Fang 
Published: November 2019

Abstract
Brown and beige adipocytes are mainly responsible for nonshivering thermogenesis or heat production, despite the fact that they have distinguished features in distribution, developmental origin, and functional activation. As a nutrient sensor and critical regulator of energy metabolism, mechanistic target of rapamycin (mTOR) also plays an important role in the development and functional maintenance of adipocytes. While the recent studies support the notion that mTOR (mTORC1 and mTORC2) related signaling pathways are of great significance for thermogenesis and the development of brown and beige adipocytes, the exact roles of mTOR in heat production are controversial. The similarities and disparities in terms of thermogenesis might be ascribed to the use of different animal models and experimental systems, distinct features of brown and beige adipocytes, and the complexity of regulatory networks of mTORC1 and mTORC2 in energy metabolism.
Pension and state funds dominating biomedical R&D investment: fiduciary duty and public health
Authors: Roller Slavek 
Published: November 2019

AbstractBackgroundWho benefits from the commercial biomedical research and development (R&D)? Patients-consumers and investors-shareholders have traditionally been viewed as two distinct groups with conflicting interests: shareholders seek maximum profits, patients - maximum clinical benefit. However, what happens when patients are the shareholders? With billions of dollars of public risk capital channeled into the drug development industry, analysing the complex financial architecture and the market for corporate control is essential for understanding industry’s characteristics, such as pricing strategies or R&D priorities.ResultsAdding investments by governmentally-mandated retirement schemes, central and promotional banks, and sovereign wealth funds to tax-derived governmental financing shows that the majority of biomedical R&D funding is public in origin. Despite this, even in the high-income countries patients can be denied access to effective treatments due to their high cost. Since these costs are set by the drug development firms that are owned in substantial part by the retirement accounts of said patients, the complex financial architecture of biomedical R&D may be inconsistent with the objectives of the ultimate beneficiaries.ConclusionsThe divergence in economic and public health performance of the drug development industry is resultant from its financial underwriting by enormously expanded pension schemes, governmentally mandated to represent the interests of “captive” beneficiaries, as well as similar policymaker-designed funding flows, whose standards of transparency, accountability and representation are substantially lower than that of governments themselves. Strengthening those elements of institutional design and thus ensuring active responsible shareholding in the interest of the patients-savers is an under-utilised, but potentially high-impact opportunity for advancing public health.
Extensive aortic surgery in acute aortic dissection type A on outcome – insights from 25 years single center experience
Authors: Dib Bashar , Seppelt Philipp Christian , Arif Rawa , Weymann Alexander , Veres Gábor , Schmack Bastian , Beller Carsten J. , Ruhparwar Arjang , Karck Matthias , Kallenbach Klaus 
Published: November 2019

Abstract

Background
This single center study compares the different surgical techniques used in the treatment of acute aortic dissection type A (AADA) analyzing the influence of the extent of the surgical approach on outcome.

Methods
From 1988 to 2012, 407 patients were operated for AADA. The cohort was divided into subgroups according to the surgical approach. These groups were compared with the supracommissural replacement group (SCR; n = 141). Groups included aortic valve sparing techniques (AVS; n = 29), Composite replacement (COMP; n = 119), COMP with total arch replacement (COMP+TAR; n = 27) and SCR with TAR (n = 75).

Results
Compared to SCR alone, operation (p = 0.005), bypass-, cross-clamp and circulatory arrest times were longer in SCR + TAR (all p < 0.001). Moreover, operation, bypass and cross clamp times were longer in COMP+TAR (p = 0.003, p = 0.002 and p < 0.001 respectively). COMP alone and AVS required longer cross-clamp time, too (p < 0,001 and p = 0.002, respectively). Overall 30-day mortality was 21% with the observed lowest rate after AVS (14%, SCR 18%, COMP 25%) but differences in 30-day mortality were not statistically significant. The estimated 10-year survival was 42%, especially AVS demonstrated a good 10-year survival (69%). David technique was superior to Yacoub technique concerning incidence of redo interventions (p = 0.036). Risk factors for early mortality included age, circulatory arrest, general malperfusion, bypass and operation time. Circulatory arrest per se was revealed as risk factor for long-term survival.

Conclusions
Within our single center retrospective study concomitant aortic root repair or aortic arch replacement for AADA demonstrated acceptable early and long-term survival. Circulatory arrest, long bypass and operation times per se might be important risk factors for early mortality. AVS techniques can be performed safely and have good outcomes in acute aortic dissection repair.
Sonographic features of the testicular adrenal rests tumors in patients with congenital adrenal hyperplasia: a single-center experience and literature review
Authors: Ma Li , Xia Yu , Wang Linlin , Liu Ruifeng , Huang Xuepei , Ye Tiantian , Zhang Li , Zhu Qingli , Li Jianchu , Jiang Yuxin 
Published: November 2019

Abstract

Purpose
Testicular adrenal rests tumor (TART) is a rare kind of benign tumor in the testis. It usually occurred secondary to congenital adrenal hyperplasia (CAH), a hormonal disorder caused by hydroxylase deficiency. As the first-line examination method, ultrasound provides crucial diagnostic information for TART, although misdiagnosis to malignancy is quite common because of its rare prevalence. We aimed to summarize the sonographic manifestations of TART to improve the diagnostic accuracy and specificity.

Methods
Eight CAH patients with TART identified by ultrasound in our medical center were retrospectively reviewed. Clinical and hormonal profile, semen analysis and treatment choices were collected. Sonographic examinations were performed at the first evaluation and interpreted by experienced radiologists individually. All patients received regular follow-up, and 5 patients undertook repeated scrotal ultrasound. A literature review of TART in CAH patients was conducted, with 123 patients from 23 articles since 1990 included.

Results
A total of 8 patients aged between 4 to 27 years old were enrolled. 7 of 8 (87.5%) patients exhibited bilateral testicular lesions. The sizes of the testicular lesions were between 0.18 ml to 5.68 ml, and all showed a clear boundary. 10/15 (66.7%) lesions were homogenously hypoechoic, 4/15 (26.7%) were heterogeneously iso-hypoechoic, and 1/15 (6.7%) were homogenously isoechoic. 10/15 (66.7%) lesions were hyper-vascular. The longitudinal follow-up of 5 patients showed testicular lesions changed in terms of size, echogenicity, and vascularity after steroid treatment. A potential correlation may exist between ACTH levels and tumor size (p = 0.066). From the literature review, 100/123 (81%) patients got bilateral lesions, and 95% of them were located near the mediastinum. 80/103 (78%) lesions exhibited a clear boundary, and predominant lesions (74%) were hypoechogenic. Vascularity was with great diversity. Seventy-nine lesions of 44 patients were followed-up by scrotal ultrasound, among which 29 (37%) remained unchanged, 29(37%) shrank, and 21(27%) disappeared.

Conclusions
Key sonographic characteristics of TART are: resembled lesions on both testes, located near the mediastinum, clear boundary, and changed in size or echogenicity after steroid treatment. These features can help radiologists to make an accurate diagnosis of TART.
Effect of intraoperative paravertebral or intravenous lidocaine versus control during lung resection surgery on postoperative complications: A randomized controlled trial
Authors: De la Gala Francisco , Piñeiro Patricia , Reyes Almudena , Simón Carlos , Vara Elena , Rancan Lisa , Huerta Luis Javier , Gonzalez Guillermo , Benito Carmen , Muñoz Marta , Grande Pilar , Paredes Sergio D. , Aznar Pablo Tomas , Perez Alvaro , Martinez David , Higuero Fernando , Sanz David , De Miguel Juan Pedro , Cruz Patricia , Olmedilla Luis , Lopez Gil Elena , Duque Patricia , Sanchez-Pedrosa Guillermo , Valle Mayte , Garutti Ignacio 
Published: November 2019

AbstractBackgroundUse of minimally invasive surgical techniques for lung resection surgery (LRS), such as video-assisted thoracoscopy (VATS), has increased in recent years. However, there is little information about the best anesthetic technique in this context. This surgical approach is associated with a lower intensity of postoperative pain, and its use has been proposed in programs for enhanced recovery after surgery (ERAS). This study compares the severity of postoperative complications in patients undergoing LRS who have received lidocaine intraoperatively either intravenously or via paravertebral administration versus saline.Methods/designWe will conduct a single-center randomized controlled trial involving 153 patients undergoing LRS through a thoracoscopic approach. The patients will be randomly assigned to one of the following study groups: intravenous lidocaine with more paravertebral thoracic (PVT) saline, PVT lidocaine with more intravenous saline, or intravenous remifentanil with more PVT saline. The primary outcome will be the comparison of the postoperative course through Clavien-Dindo classification. Furthermore, we will compare the perioperative pulmonary and systemic inflammatory response by monitoring biomarkers in the bronchoalveolar lavage fluid and blood, as well as postoperative analgesic consumption between the three groups of patients. We will use an ANOVA to compare quantitative variables and a chi-squared test to compare qualitative variables.DiscussionThe development of less invasive surgical techniques means that anesthesiologists must adapt their perioperative management protocols and look for anesthetic techniques that provide good analgesic quality and allow rapid rehabilitation of the patient, as proposed in the ERAS protocols. The administration of a continuous infusion of intravenous lidocaine has proven to be useful and safe for the management of other types of surgery, as demonstrated in colorectal cancer. We want to know whether the continuous administration of lidocaine by a paravertebral route can be substituted with the intravenous administration of this local anesthetic in a safe and effective way while avoiding the risks inherent in the use of regional anesthetic techniques. In this way, this technique could be used in a safe and effective way in ERAS programs for pulmonary resection.Trial registrationEudraCT, 2016–004271-52; ClinicalTrials.gov,NCT03905837. Protocol number IGGFGG-2016 version 4.0, 27th April 2017.
Serum lysophosphatidylcholines to phosphatidylcholines ratio is associated with symptomatic responders to symptomatic drugs in knee osteoarthritis patients
Authors: Zhai Guangju , Pelletier Jean-Pierre , Liu Ming , Randell Edward W. , Rahman Proton , Martel-Pelletier Johanne 
Published: November 2019

Abstract

Background
Identification of the optimal treatment for a given patient is of paramount importance. This is of particular relevance in osteoarthritis (OA) because of the high prevalence of the disease, extensive heterogeneity of the disease, and need for long-term treatment. The aim of the study was to examine whether serum lysophosphatidylcholines (lysoPCs) to phosphatidylcholines (PCs) ratio can predict clinical response to licofelone and naproxen treatments in symptomatic knee OA patients.

Methods
One hundred fifty-eight OA patients who completed the study according to protocol (ATP) of a previous 24-month clinical trial cohort comparing the effect of licofelone vs. naproxen in symptomatic knee OA patients were included. Symptomatic responses to either treatments were classified according to the OARSI-OMERACT criteria based on the WOMAC scores at 24 months. Total concentrations of PCs and lysoPCs were measured in the serum samples collected before the initiation of the treatments, and the lysoPCs to PCs ratio was calculated. Student’s t test was utilized to compare the difference in the ratio of lysoPCs to PCs between the symptomatic responders and non-responders. Logistic regression was utilized to adjust for the potential confounders. Receiver operating characteristic (ROC) analysis was performed to identify the optimal cutoff of the ratio for prediction.

Results
Data showed that 61.4% of the patients symptomatically responded to licofelone and naproxen and 38.6% were deemed as therapeutic failures (non-responders). There was no difference in responders between licofelone and naproxen (p = 0.87). Responders had a significantly higher lysoPCs to PCs ratio than non-responders (0.097 ± 0.003 vs. 0.085 ± 0.003; p = 0.006). Patients with a ratio greater than the optimal cutoff of 0.088 had 2.93 times more likely to respond to licofelone and naproxen (p = 0.002).

Conclusions
Serum lysoPCs to PCs ratio is a marker for response to licofelone and naproxen and may aid in the personalized treatment to knee OA.
Three novel variants in the arylsulfatase A (ARSA) gene in patients with metachromatic leukodystrophy (MLD)
Authors: Hettiarachchi D. , Dissanayake V. H. W. 
Published: November 2019

Abstract

Objective
To describe the genetic variants in the ARSA gene in Sri Lankan patients with metachromatic leukodystrophy (MLD). As the variant profile of MLD in the Sri Lankan population is currently unknown.

Results
Twenty patients from eighteen Sri Lankan families were screened for ARSA gene mutations. We found 13 different genetic variants of these three were novel. The three novel variants were p.Asp281Asn, p.Asp283Asn, p.Ala344Asp. Seven patients out of 20 were also positive for the pseudodeficiency (PD) allele c.1049A>G (p.Asn350Ser). This is the first report to describe the molecular genetic variants of Sri Lankan patients with MLD.
Blood donors’ knowledge and attitude towards blood donation at North Gondar district blood bank, Northwest Ethiopia: a cross-sectional study
Authors: Enawgaw Bamlaku , Yalew Aregawi , Shiferaw Elias 
Published: November 2019

Abstract

Objective
Blood transfusion saves millions of lives. But, the need and the actual number of donations are not balanced in Ethiopia. The actual reason is not clearly assessed; however, level of knowledge and attitude may be the main contributing factors. Thus, the current study aimed to assess blood donors’ knowledge and attitude towards blood donation at North Gondar district blood bank.

Results
Of 401 blood donors, 142 (35.4%) and 379 (94.5%) were had adequate knowledge and positive attitude towards blood donation, respectively. About 343 (85.5%) of study participants had no previous experience of blood donation. Perceptions of fear of pain, medically unfitness to donate and lack of information on when, where and how to donate blood were mentioned as a reason for not donating blood. Educational status and residence were significantly associated with knowledge of blood donors. On the other hand, participants with secondary and higher education were more likely to have good attitude towards blood donation. Thus, blood banks should design strategies for health education about blood donation and transfusion.
Gender differences in asthma perception and its impact on quality of life: a post hoc analysis of the PROXIMA (Patient Reported Outcomes and Xolair® In the Management of Asthma) study
Authors:   the PROXIMA study centers, Colombo Delia , Zagni Emanuela , Ferri Fabio , Canonica Giorgio Walter 
Published: November 2019

Abstract

Background
Gender differences in asthma perception and control have been reported. The PROXIMA observational study assessed these outcomes in a cohort of Italian severe allergic asthma (SAA) patients. This post hoc analysis of the PROXIMA results was aimed at assessing gender differences in SAA in a real-world setting, focusing on disease perception and impact on quality of life (QoL).

Methods
The PROXIMA study was an observational, multicenter study, consisting of a cross-sectional and a prospective longitudinal phase, including adult outpatients diagnosed with SAA at step 4 requiring a therapeutic step-up. Patients on omalizumab treatment at baseline were included in the 12-month longitudinal phase. Disease control was assessed by the Asthma Control Questionnaire (ACQ) score, patients’ disease perception by the Brief Illness Perception Questionnaire (BIPQ), and QoL by the EuroQoL five-dimensional three-level questionnaire (EQ-5D-3 L) at baseline and after 6 and 12 months. Two regression models were used to evaluate the association between gender and BIPQ total score and EQ-5D-3L score, respectively.

Results
357 patients (65% females) were analyzed for the cross-sectional phase and 99 (62.6% females) for the longitudinal phase. The prevalence of perennial and seasonal aeroallergens was similar between genders. ACQ score decreased similarly during omalizumab treatment at 6 and 12 months in both genders; no gender differences were observed in control rates. Asthma perception was worse among females at all study visits reaching statistical significance at 12 months (mean (SD) B-IPQ total score 41.8 (9.4) vs 35.6 (12.0); T test p-value (males vs females) < 0.05). Statistically significant gender differences were observed for some specific items, with males reporting less symptom experience, concern about the disease, and emotional impact at 12-months. The results of the multivariate regression model for repeated measures showed that overall treatment with omalizumab improved disease perception overtime regardless from gender. Males reported a significantly better QoL compared to females at both 6 and 12 months.

Conclusions
In this real-world setting, females confirmed to have a worse perception of asthma, feel it as more symptomatic and suffer a greater impact on their QoL, even though having similar baseline severity and obtaining similar level of control.
Reply to “Missed opportunities in large scale comparison of QSAR and conformal prediction methods and their applications in drug discovery”
Authors: Bosc Nicolas , Atkinson Francis , Félix Eloy , Gaulton Anna , Hersey Anne , Leach Andrew R. 
Published: November 2019

Abstract
In response to Krstajic’s letter to the editor concerning our published paper, we here take the opportunity to reply, to re-iterate that no errors in our work were identified, to provide further details, and to re-emphasise the outputs of our study. Moreover, we highlight that all of the data are freely available for the wider scientific community (including the aforementioned correspondent) to undertake follow-on studies and comparisons.
Sign-constancy of Green’s functions for impulsive nonlocal boundary value problems
Authors: Domoshnitsky A. , Mizgireva Iu. 
Published: November 2019

Abstract
We consider the following second order impulsive differential equation with delays:
$$ \textstyle\begin{cases} (Lx)(t)\equiv x''(t)+\sum_{j=1}^{p} a_{j}(t) x'(t-\tau _{j}(t)) + \sum_{j=1}^{p} b_{j}(t) x(t-\theta _{j}(t)) = f(t), \quad t \in [0, \omega ], \\ x(t_{k})=\gamma _{k} x(t_{k}-0), \quad\quad x'(t_{k})=\delta _{k} x'(t_{k}-0), \quad k=1,2,\ldots,r. \end{cases} $${(Lx)(t)≡x″(t)+∑j=1paj(t)x′(t−τj(t))+∑j=1pbj(t)x(t−θj(t))=f(t),t∈[0,ω],x(tk)=γkx(tk−0),x′(tk)=δkx′(tk−0),k=1,2,…,r.
In this paper we consider sufficient conditions of nonpositivity of Green’s function for impulsive differential equation with nonlocal boundary conditions.