bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ansatzpunkte für Resilienzförderung im Medizinstudium – Was hält angehende Ärztinnen und Ärzte gesund?
Authors: Kötter Thomas 
Published: March 2019

ZusammenfassungDie Entwicklung hin zu einer verminderten Stressresilienz und beeinträchtigten psychosozialen Gesundheit, die wir in der Ärzteschaft beobachten können, beginnt bereits früh im Medizinstudium. Eigene Ergebnisse bestätigen die international beobachtete negative Entwicklung der Gesundheit von Medizinstudierenden. Studierende, die gleichzeitig ein hohes Perfektionsstreben und eine geringe Distanzierungsfähigkeit aufweisen und nicht regelmäßig körperlich aktiv sind, scheinen eine besondere Risikogruppe darzustellen. Es erscheint daher sinnvoll, möglichst früh im Studium Interventionen zu implementieren, die dieser Entwicklung durch Stärkung von individuellen Ressourcen und Vermeidung schädigender Einflüsse durch das Studium selbst entgegenwirken können. Interventionen sollten sowohl auf die individuellen Verhaltens- und Erlebensmuster der Studierenden abzielen als auch auf das Setting. Von den Studierenden selbst wird das medizinische Curriculum selbst als prioritärer Ansatzpunkt für resilienzfördernde Interventionen angesehen. Es sollte daher das Interesse aller Beteiligten sein, möglichst allen Studierenden ein Studium bei guter Gesundheit zu ermöglichen und sie darüber hinaus für das Berufsleben mit Ressourcen wie einer guten Resilienz auszustatten, die sich nachhaltig positiv auf die Qualität der Patientenversorgung auswirken. Die Evidenzlage sowohl hinsichtlich protektiver Faktoren für die Gesundheit von Medizinstudierenden als auch wirksamer resilienzfördernder Interventionen ist bislang quantitativ und qualitativ unzureichend. Gerade aus dem deutschen Sprachraum gibt es nur wenige aussagekräftige Studien. Eigene Studien zeigen, dass die Teilnahmebereitschaft an solchen Angeboten trotz des zusätzlichen Zeitaufwandes hoch ist, die Studierenden erachten diese als hilfreich. Interventionen nach den Konzepten der Mind-Body-Medizin erscheinen im Kontext Medizinstudium dabei besonders vielversprechend.
Amputationen der unteren Extremität in Deutschland – Regionale Analyse mit Krankenhausabrechnungsdaten von 2011 bis 2015
Authors: Spoden Melissa 
Published: March 2019

Zusammenfassung
Ziel der Arbeit Amputationen vermindern irreversibel die Lebensqualität. Das Ziel vorangehender Versorgung ist stets eine Amputation zu verhindern. Diese Versorgung sollte bundesweit mit derselben Ergebnisqualität gewährleistet sein. Ziel dieser Arbeit ist es, regionale Versorgungsunterschiede sichtbar zu machen, indem Amputationsfallzahlen nach Amputationshöhen auf Kreisebene analysiert werden.
Methodik In den deutschlandweiten Krankenhausabrechnungsdaten (DRG-Statistik) wurden alle Behandlungsfälle mit Amputation an der unteren Extremität zwischen 2011 und 2015 identifiziert. Auf Kreisebene wurden rohe Raten sowie alters- und geschlechtsstandardisierte Raten pro 100 000 Einwohner dargestellt. Daneben wurde die systematische Variationskomponente (SCV) zwischen den Kreisen betrachtet und das standardisierte Morbiditätsverhältnis (SMR) in Funnel Plots dargestellt.
Ergebnisse Im Beobachtungszeitraum belief sich die mediane jährliche Amputationsrate auf 67 Fälle pro 100 000 Einwohner. Auf Kreisebene variierte die rohe Rate um das 6-fache. Unabhängig von demografischen Unterschieden zeigten sich Variationen zwischen den Kreisen. Erhöhte Amputationsraten wurden überwiegend im Osten und Südosten beobachtet. Die Variationen waren bei den Amputationshöhen Zeh/Zehenstrahl (SCV 11,8) und Fuß komplett & Mittel-/Vorfuß (SCV 11,7) am stärksten ausgeprägt.
Schlussfolgerung Es bestehen deutliche regionale Unterschiede in den Amputationsraten. Bei peripheren Amputationshöhen ist die systematische Variation am stärksten. Insbesondere im Osten und Südosten sind regionale Cluster erkennbar, die Anhaltspunkte für einen möglichen regionalen Verbesserungsbedarf in der Versorgung liefern.
Lymphatic micrometastases predict biochemical recurrence in patients undergoing radical prostatectomy and pelvic lymph node dissection for prostate cancer
Authors: Maxeiner Andreas , Grevendieck Andreas , Pross Therese , Rudl Marc , Arnold Alexander , Stephan Carsten , Jung Klaus , Miller Kurt , Kilic Ergin , Busch Jonas 
Published: March 2019

Abstract
Background Nodal metastasis is a strong prognostic parameter in prostate cancer (PCa). We analysed the detection of micrometastases (miN + ) in initially nodal-negative (pN0) radical prostatectomy specimens from pT2a-c and pT3a PCa patients by immunohistochemistry (IHC).
Material and Methods A total of 2352 lymph nodes of 193 PCa patients were centrally re-examined for miN + or miN- status using IHC. Results were correlated with clinical and follow-up data. Recurrence-free survival (RFS) was calculated with the log-rank test using the Kaplan-Meier method. In addition, a logistic regression analysis was performed.
Results IHC detected miN + in a total of 17 patients (8.8 %). miN + seemed to be significantly associated with a higher Gleason score and was detected in more advanced pT stages. A total of 45 patients (23.1 %) had a biochemical recurrence (BCR). BCR was associated with miN +. Patients with miN + had a significantly shorter RFS (22.9 versus 58.7 months; p < 0.001). In the univariate (OR: 5.04; 95 % CI: 2.46 – 10.6; p-value: < 0.0001) and multivariate (OR: 3.29; 95 % CI: 1.54 – 7.08; p-value: 0.002) regression model, the miN + status was the strongest predictor of a BCR.
Conclusions IHC seems to be of high diagnostic value for the detection of micrometastases in initially nodal-negative PCa patients. IHC should therefore be performed in PCa patients with nodal-negative findings.
Surgical Management of Deep-Seated Metastatic Brain Tumors Using Minimally Invasive Approaches
Authors: Gassie Kelly , Alvarado-Estrada Keila , Bechtle Perry , Chaichana Kaisorn 
Published: March 2019

Background and Study Aims/Objective Metastatic brain tumors are the most common type of adult brain tumors. Treatment involves surgery and/or radiation therapy. Surgery is typically reserved for patients with good neurologic function, solitary and accessible lesions, symptomatic lesions, and/or those with good systemic control of their primary cancer. Deep-seated lesions, however, are typically treated with palliative options including radiation and medical therapies. We summarize our personal experience with minimally invasive surgical approaches for these deep-seated metastatic brain tumors using tubular retractors with exoscopic visualization.
Material and Methods Patients with deep-seated metastatic brain tumors who were operated on from January 2016 to December 2017 by the senior author were collected prospectively. “Deep seated” was defined as any subcortical location below the deepest adjacent sulcus in close proximity to the basal ganglia and/or thalamus. “Minimally invasive” was defined as the use of tubular retractors with exoscopic visualization.
Results A total of 15 consecutive patients with an average ± standard deviation age of 63 ± 12 years underwent surgical resection of a deep-seated metastasis. The tumor was located in the centrum semiovale in seven (47%) (3 corticospinal tract, 2 superior longitudinal fasciculus, 1 visual tract, 1 inferior frontal occipital fasciculus), basal ganglia in three (20%), thalamus in two (13%), and cerebellum in three (20%). Median percentage resection was 100% (interquartile range:100–100%), and, following surgery, seven (47%), seven (47%), and one (7%) had an improved, stable, and worse Karnofsky Performance Score, respectively. No patients had notable local complications including stroke, infection, hemorrhage, and/or seizure. All patients underwent postoperative stereotactic radiosurgery.
Conclusion This minimally invasive approach can be used to achieve extensive resection with minimal morbidity for arguably the highest risk metastatic brain tumors.
Alcohol Consumption and Risk of First-Time Venous Thromboembolism in Men and Women
Authors: Johansson Magdalena , Johansson Lars , Wennberg Maria , Lind Marcus 
Published: March 2019

Background The relationship between alcohol intake and risk of venous thromboembolism (VTE) is unclear. Men and women differ in their drinking habits, which may affect a possible association.
Objective This article investigates the association between alcohol consumption, alcohol dependence and VTE in the total population as well as in men and women separately.
Methods We performed a prospective, population-based cohort study in northern Sweden. Study participants were 108,025 (51% women) persons aged 30 to 60 years who underwent a health examination between 1985 and 2014. We assessed alcohol consumption and defined alcohol dependence using a questionnaire. The outcome was a validated first-time VTE.
Results The mean follow-up time was 13.9 years, and 2,054 participants had a first-time VTE. The mean alcohol consumption was 3.5 standard drinks weekly in men and 1.5 in women. Alcohol dependence was found in 10% of men and 3% of women. There was an association between alcohol consumption (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00–1.03 per standard drink weekly) as well as alcohol dependence (HR, 1.27; 95% CI, 1.06–1.52) and VTE after adjustments. In men, the risk of VTE increased over quartiles of weekly alcohol consumption (p for trend 0.02), with a HR of 1.22 (95% CI, 1.01–1.47) for the highest quartile. Alcohol dependence was associated with VTE in men (HR, 1.30; 95% CI, 1.07–1.59). In women, there were no significant associations.
Conclusion High alcohol consumption and alcohol dependence were associated with increased risk of first-time VTE in men, but not in women.
Effect of Diabetes on the Male Reproductive System—A Histomorphological Study
Authors: Kotian Sushma , Kumar Ashok , Mallik Sanchari , Bhat Nandini , Souza Anne , Pandey Arvind 
Published: March 2019

Introduction Type 1 diabetes is an autoimmune disorder characterized by lack of insulin production by the β cells of the pancreas. This lack of insulin causes a variety of systemic effects on the metabolism of the body, one of which is reproductive dysfunction. The present study investigates the effects of diabetes on the male reproductive system of streptozotocin (STZ)-induced diabetic rats.
Material and Methods A total of 18 adult male Wistar rats weighing ∼ between 250 and 300 g were included in the present study. The animals were divided into normal and diabetic groups. The diabetic group was further subdivided into 2 subgroups with durations of 24 and 48 days. A single dose of STZ (40 mg/kg body weight) was administrated intraperitoneally to the animals of the diabetic group. After the planned duration, the testes and epididymides were dissected, and their gross weight was measured. The tissues were then processed for histological study.
Results The gross weight of the testes and epididymides in diabetic rats at 24 and 48 days showed a decrease in comparison to the control. (p < 0.01 for testes and epididymides).Diabetic animals presented a significant decrease in the diameter of the seminiferous tubules compared with the control group (p < 0.01). The epididymides in the diabetic groups showed a considerable reduction in the tubular surface area compared with the control group (p < 0.01). There was also a reduction in the mean diameter, which was measured using the maximum and minimum diameter of the tubules (p < 0.01).
Conclusion The present study is an insight into the adverse effects that diabetes can have on the tissue structure of the testes, of the epididymides, and ultimately on the process of spermatogenesis.
Participation of the Intercostal Nerves to the Innervation of the Diaphragm Muscle in Cavia porcellus
Authors: de Faria Marcelo , Gradela Adriana , Santos Ana , Lopes Ítalo , Inoue Vanessa , Brito Bárbara 
Published: March 2019

Introduction The diaphragm is the leading respiratory muscle. It is innervated mainly by the diaphragmatic nerve, and, in some species, by the delicate fibers of the intercostal nerves. In guinea pigs, there is no description of these anatomic structures that innerve this important muscle. This study aimed to analyze the participation of the intercostal nerves to the innervations of the diaphragm of guinea pigs of both sexes.
Materials and Methods We studied 40 guinea pigs (Cavia porcellus) of both sexes. We fixed and dissected the diaphragm of the specimens used in the experiment to assess the path of the intercostals nerves in both the body antimeres.
Results The diaphragm was innervated by the intercostal nerve pairs 6 through 12, and, less frequently, by the 8th nerve (38/40 = 95%), followed by the 7th (36/40 = 90%) and subsequently by the 9th (32/40 = 80%). The 12th nerve presented the lowest frequency (2/20 = 10%) in both genders. All nerve pairs displayed similar occurrence compared with the gender and the antimeric disposition. The only exception was the 9th nerve, which presented a significant variation of the occurrence, both in relation to gender and antimeric disposition. From a statistic point of view, all nerves were independent. We observed no correlation between the gender and their position.
Conclusions We shall conclude that the diaphragm of guinea pigs is innervated by the 6th through 12th pairs of intercostal nerves, with the 7th, 8th, and 9th being the primary providers. There is no interference of the variables gender or antimeric disposition on the behavior of the intercostal nerves of guinea pigs as refers to their origin and participation to the innervations of the diaphragm.
Optimisation of imaging flow cytometry for the analysis of single extracellular vesicles by using fluorescence‐tagged vesicles as biological reference material
Authors: Görgens André , Bremer Michel , Ferrer‐Tur Rita , Murke Florian , Tertel Tobias , Horn Peter A. , Thalmann Sebastian , Welsh Joshua A. , Probst Christine , Guerin Coralié , Boulanger Chantal M. , Jones Jennifer C. , Hanenberg Helmut , Erdbrügger Uta , Lannigan Joanne , Ricklefs Franz L. , El‐Andaloussi Samir , Giebel Bernd 
Published: March 2019

ABSTRACTExtracellular vesicles (EVs) mediate targeted cellular interactions in normal and pathophysiological conditions and are increasingly recognised as potential biomarkers, therapeutic agents and drug delivery vehicles. Based on their size and biogenesis, EVs are classified as exosomes, microvesicles and apoptotic bodies. Due to overlapping size ranges and the lack of specific markers, these classes cannot yet be distinguished experimentally. Currently, it is a major challenge in the field to define robust and sensitive technological platforms being suitable to resolve EV heterogeneity, especially for small EVs (sEVs) with diameters below 200 nm, i.e. smaller microvesicles and exosomes. Most conventional flow cytometers are not suitable for the detection of particles being smaller than 300 nm, and the poor availability of defined reference materials hampers the validation of sEV analysis protocols. Following initial reports that imaging flow cytometry (IFCM) can be used for the characterisation of larger EVs, we aimed to investigate its usability for the characterisation of sEVs. This study set out to identify optimal sample preparation and instrument settings that would demonstrate the utility of this technology for the detection of single sEVs. By using CD63eGFP‐labelled sEVs as a biological reference material, we were able to define and optimise IFCM acquisition and analysis parameters on an Amnis ImageStreamX MkII instrument for the detection of single sEVs. In addition, using antibody‐labelling approaches, we show that IFCM facilitates robust detection of different EV and sEV subpopulations in isolated EVs, as well as unprocessed EV‐containing samples. Our results indicate that fluorescently labelled sEVs as biological reference material are highly useful for the optimisation of fluorescence‐based methods for sEV analysis. Finally, we propose that IFCM will help to significantly increase our ability to assess EV heterogeneity in a rigorous and reproducible manner, and facilitate the identification of specific subsets of sEVs as useful biomarkers in various diseases.
History of Benzodiazepine Prescriptions and Risk of Dementia: Possible Bias Due to Prevalent Users and Covariate Measurement Timing in a Nested Case-Control Study
Authors: Richardson Kathryn , Mattishent Katharina , Loke Yoon K , Steel Nicholas , Fox Chris , Grossi Carlota M , Bennett Kathleen , Maidment Ian , Boustani Malaz , Matthews Fiona E , Myint Phyo K , Campbell Noll L , Brayne Carol , Robinson Louise , Savva George M 
Published: March 2019

Abstract
Previous estimates of whether long-term exposure to benzodiazepines increases dementia risk are conflicting and are compromised by the difficulty of controlling for confounders and by reverse causation. We investigated how estimates for the association between benzodiazepine use and later dementia incidence varied based on study design choices, using a case-control study nested within the United Kingdom’s Clinical Practice Research Datalink. A total of 40,770 dementia cases diagnosed between April 2006 and July 2015 were matched on age, sex, available data history, and deprivation to 283,933 control subjects. Benzodiazepines and Z-drug prescriptions were ascertained in a drug-exposure period 4–20 years before dementia diagnosis. Estimates varied with the inclusion of new or prevalent users, with the timing of covariate ascertainment, and with varying time between exposure and outcome. There was no association between any new prescription of benzodiazepines and dementia (adjusted odds ratio (OR) = 1.03, 95% confidence interval (CI): 1.00, 1.07), whereas an inverse association was observed among prevalent users (adjusted OR = 0.91, 95% CI: 0.87, 0.95), although this was likely induced by unintentional adjustment for colliders. By considering the choice of confounders and timing of exposure and covariate measurement, our findings overall are consistent with no causal effect of benzodiazepines or Z-drugs on dementia incidence.
Invited Commentary: The Causal Association Between Obesity and Stillbirth—Strengths and Limitations of the Consecutive-Pregnancies Approach
Authors: Snowden Jonathan M , Leonard Stephanie A 
Published: March 2019

Abstract
There has been a resurgence in analyses of consecutive pregnancies (or similarly, sibling designs) in perinatal and pediatric epidemiology. These approaches have attractive qualities for estimating associations with complex multifactorial exposures like obesity. In an article appearing in this issue of the Journal, Yu et al. (Am J Epidemiol. 2019;188(7):1328–1336) apply a consecutive-pregnancies approach to characterize the risk of stillbirth among women who develop obesity between pregnancies (“incident obesity”). Working within a causal framework and using parametric and nonparametric estimation techniques, the authors find an increase in stillbirth risk associated with incident obesity. Risk differences varied between 0.4 per 1,000 births (95% confidence interval (CI): 0.1, 0.7) and 6.9 per 1,000 births (95% CI: 3.7, 10.0), and risk ratios ranged from 1.12 (95% CI: 1.02, 1.23) to 2.99 (95% CI: 2.19, 4.08). The strengths of this approach include starting from a clearly defined causal estimand and exploring the sensitivity of parameter estimates to model selection. In this commentary, we put these findings in the broader context of research on obesity and birth outcomes and highlight concerns regarding the generalizability of results derived from within-family designs. We conclude that while causal inference is an important goal, in some instances focusing on formulation of a causal question drives results away from broad applicability.
Comparison of Parametric and Nonparametric Estimators for the Association Between Incident Prepregnancy Obesity and Stillbirth in a Population-Based Cohort Study
Authors: Yu Ya-Hui , Bodnar Lisa M , Brooks Maria M , Himes Katherine P , Naimi Ashley I 
Published: March 2019

AbstractWhile prepregnancy obesity increases risk of stillbirth, few studies have evaluated the role of newly developed obesity independent of long-standing obesity. Additionally, researchers have relied almost exclusively on parametric models, which require correct specification of an unknown function for consistent estimation. We estimated the association between incident obesity and stillbirth in a cohort constructed from linked birth and death records in Pennsylvania (2003–2013). Incident obesity was defined as body mass index (weight (kg)/height (m)2) greater than or equal to 30. We used parametric G-computation, semiparametric inverse-probability weighting, and parametric/nonparametric targeted minimum loss-based estimation (TMLE) to estimate the association between incident prepregnancy obesity and stillbirth. Compared with pregnancies from women who stayed nonobese, women who became obese prior to their next pregnancy were estimated to have 2.0 (95% confidence interval (CI): 0.5, 3.5) more stillbirths per 1,000 pregnancies using parametric G-computation. However, despite well-behaved stabilized inverse probability weights, risk differences estimated from inverse-probability weighting, nonparametric TMLE, and parametric TMLE represented 6.9 (95% CI: 3.7, 10.0), 0.4 (95% CI: 0.1, 0.7), and 2.9 (95% CI: 1.5, 4.2) excess stillbirths per 1,000 pregnancies, respectively. These results, particularly those derived from nonparametric TMLE, were highly sensitive to covariates included in the propensity score models. Our results suggest that caution is warranted when using nonparametric estimators to quantify exposure effects.
Pancreatic AT1aR Deficiency Decreases Insulin Secretion in Obese C57BL/6 Mice
Authors: Shoemaker Robin , AlSiraj Yasir , Chen Jeff , Cassis Lisa A 
Published: March 2019

Abstract

BACKGROUND
Previously, we demonstrated that obese mice have marked elevations in systemic concentrations of angiotensin II (AngII). Drugs that inhibit the renin–angiotensin system (RAS), including angiotensin type 1 receptor (AT1R) antagonists, have been reported to delay the onset of type 2 diabetes (T2D), suggesting improvements in insulin sensitivity or regulation of pancreatic insulin secretion. Pancreatic islets possess components of the RAS, including AT1R, but it is unclear if AngII acts at islets to regulate insulin secretion during the development of T2D.

METHODS
We deleted AT1aR from pancreatic islets and examined effects on insulin secretion in mice fed a low-fat (LF) or high-fat (HF) diet. In separate studies, to exacerbate the system, we infused HF-fed mice of each genotype with AngII.

RESULTS
Pancreatic AT1aR deficiency impaired glucose tolerance and elevated plasma glucose concentrations in HF, but not LF-fed mice. In HF-fed mice, high glucose increased insulin secretion from islets of AT1aRfl/fl, but not AT1aRpdx mice. In AngII-infused mice, following glucose challenge, plasma glucose or insulin concentrations were not significantly different between genotypes. Moreover, high glucose stimulated insulin secretion from islets of AT1aRfl/fl and AT1aRpdx mice, presumably related to weight loss, and improved insulin sensitivity in both groups of AngII-infused HF-fed mice.

CONCLUSIONS
Our results suggest that during the adaptive response to insulin resistance from HF feeding, AngII promotes insulin secretion from islets through an AT1aR mechanism. These results suggest the timing of initiation of AT1R blockade may be important in the progression from prediabetes to T2D with β-cell failure.