bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular aging and its relationship with lifestyles and other risk factors in the general Spanish population: Early Vascular Ageing Study
Authors: Gomez-Sanchez Marta , Gomez-Sanchez Leticia , Patino-Alonso Maria C. , Cunha Pedro G. , Recio-Rodriguez Jose I. , Alonso-Dominguez Rosario , Sanchez-Aguadero Natalia , Rodriguez-Sanchez Emiliano , Maderuelo-Fernandez Jose A. , Garcia-Ortiz Luis , Gomez-Marcos Manuel A. 
Published: March 2020

Objectives:
To describe the prevalence of healthy vascular aging (HVA), normal vascular aging and early vascular aging (EVA) in a sample of Spanish population without cardiovascular disease. The relationship of vascular aging with lifestyle, cardiovascular risk factors, psychological and inflammatory risk factors is also analyzed.

Methods:
A total of 501 participants were recruited (49.70% men, aged 55.90 ± 14.24 years) by random sampling. Vascular aging was defined in three steps: Step 1: participants with vascular damage in carotid arteries or peripheral artery disease were classified as EVA. Step 2: with the percentiles of carotid-to-femoral pulse wave velocity (cfPWV) we used three criteria, first, the 10th and 90th cfPWV percentiles of the population studied by age and sex; second, the 10th and 90th percentiles of the European population reference values and third, the 25th and 75th cfPWV percentiles of the population studied by age and sex. Step 3: participants with hypertension or type 2 diabetes mellitus included in HVA were reclassified as normal vascular aging. Arterial stiffness was assessed with cfPWV using a Sphygmocor device. Physical activity was measured with an accelerometer. Psychological factors, lifestyle and other clinical information were obtained by standard questionnaire.

Results:
The global prevalence of HVA was 8 and 14% (men 8 and 10%, women 9 and 18%), and 22 and 18% (men 26 and 23%, women 17 and 12%) for EVA, using criteria a and b, respectively. In the logistic regression analysis, vascular aging maintains positive associations with more sedentary time [odds ratio (OR) = 2.37 and 4.51], having triglycerides above 150 mg/dl (OR = 6.55 and 4.06), abdominal obesity (OR = 2.73 and 2.90), increased uric acid (OR = 4.63 and 2.98) and insulin resistance index homeostatic model assessment (OR = 4.05 and 6.78), and a negative association with less physical activity (OR = 0.29 and 0.28) using criteria a and b, respectively.

Conclusion:
One in 10 has HVA and one in five EVA. The prevalence of EVA is higher in men. Study results suggest that preventive strategies aimed at increasing physical activity, reducing sedentary time and decreasing obesity and insulin resistance improve vascular aging.
The retina revolution: signaling pathway therapies, genetic therapies, mitochondrial therapies, artificial intelligence
Authors: Wood Edward H. , Korot Edward , Storey Philip P. , Muscat Stephanie , Williams George A. , Drenser Kimberly A. 
Published: March 2020

Purpose of review
The aim of this article is to review and discuss the history, current state, and future implications of promising biomedical offerings in the field of retina.

Recent findings
The technologies discussed are some of the more recent promising biomedical developments within the field of retina. There is a US Food and Drug Administration-approved gene therapy product and artificial intelligence device for retina, with many other offerings in the pipeline.

Summary
Signaling pathway therapies, genetic therapies, mitochondrial therapies, and artificial intelligence have shaped retina care as we know it and are poised to further impact the future of retina care. Retina specialists have the privilege and responsibility of shaping this future for the visual health of current and future generations.
Cohort Study of Nonmelanoma Skin Cancer and the Risk of Exfoliation Glaucoma
Authors: Kang Jae H. , VoPham Trang , Laden Francine , Rosner Bernard A. , Wirostko Barbara , Ritch Robert , Wiggs Janey L. , Qureshi Abrar , Nan Hongmei , Pasquale Louis R. 
Published: March 2020

Precis:In a cohort study of 120,307 participants with 25+ years of follow-up, a history of nonmelanoma skin cancer (NMSC) was associated with a 40% higher exfoliation glaucoma (XFG) risk.Purpose:The purpose of this study was to evaluate the relationship between NMSC (a marker of ultraviolet radiation exposure) and XFG.Methods:We performed a cohort study of US women (n=79,102; 1980-2014) and men (n=41,205; 1986-2014), aged 40+ years and at risk for glaucoma who reported eye examinations. From 1984 (women)/1988 (men), we asked about basal cell carcinoma or squamous cell carcinoma history separately; in prior years, we asked about any NMSC history in a single question. Squamous cell carcinoma was confirmed with histopathology reports while basal cell carcinoma and any early (<1984/<1988) NMSC history was self-reported. Incident XFG cases (362 women and 83 men) were confirmed with medical records. Using pooled data, we estimated multivariable-adjusted relative risks [MVRRs; 95% confidence intervals (CIs)] with Cox proportional hazards models that were stratified by age (in mo), 2-year time period at risk and average lifetime residential latitude.Results:In multivariable-adjusted analyses, we observed a 40% higher XFG risk with any NMSC history (MVRR=1.40; 95% CI=1.08-1.82); the association was observed even with 4 and 8-year lags in NMSC history. Also, the NMSC association was stronger in younger (below 65 y; MVRR=2.56; 95% CI=1.62-4.05) versus older participants (65 y and above; MVRR=1.25; 95% CI=0.94-1.66;Pfor interaction=0.01) and those living in the northern latitudes (≥42°N; MVRR=1.92; 95% CI=1.28-2.88) versus more southern latitudes (<42°N; MVRR=1.19; 95% CI=0.86-1.66;Pfor interaction=0.04).Conclusion:NMSC was associated with higher XFG risk, particularly among younger participants and those living in the Northern US.
A clinical algorithm for management of fertility in adolescents with the Klinefelter syndrome
Authors: Masterson Thomas A. , Nassau Daniel E. , Ramasamy Ranjith 
Published: March 2020

Purpose of review
The review presents a clinical algorithm for the evaluation and treatment for adolescents with Klinefelter's syndrome who desire fertility preservation.

Recent findings
Sperm is present in the ejaculate in around 8% of men with Klinefelter's syndrome. Although most are severely oligospermic/azoospermic, 43–45% of men will have sperm found during a testicular sperm extraction, reaching up to 70% in adolescents.

Summary
Klinefelter's syndrome (47, XXY) causes hypogonadotophic hypogonadism and severe oligospermia/azoospermia rendering natural conception rare. During puberty, boys often require testosterone replacement therapy to develop secondary sexual characteristics, which can further decrease spermatogenesis. There is a progressive decrease of testicular germ cells after the onset of puberty, suggesting that fertility evaluation and preservation should begin shortly thereafter. In adolescents desiring fertility evaluation, any testosterone therapy should be discontinued, hormones and gonadotrophins measured, and a semen analysis obtained. Adolescents with low testosterone are administered aromatase inhibitors, selective estrogen receptors modulators and/or human chorionic gonadotropin to increase endogenous testosterone production. After testosterone levels are normalized, semen analysis is performed, and cryopreservation encouraged if sperm is present. For those without sperm in the ejaculate, a testicular sperm extraction is offered.
Advanced sperm testing
Authors: Softness Kenneth A. , Trussler James T. , Carrasquillo Robert J. 
Published: March 2020

Purpose of reviewThe sensitivity of semen analysis for detection of infertility remains low. Many factors not measured in traditional semen analysis may contribute to male factor infertility. DNA fragmentation, oxidative stress, and sperm aneuploidy are three factors that may contribute further information to the evaluation when semen analysis is inconclusive.Recent findingsDNA fragmentation measures the destruction of and failure to repair damage to DNA. Increased DNA fragmentation has been used as a marker for oxidative stress as well as toxic exposure. The oxidative stress adduct measures DNA aberrations, which sperm cannot repair and has been used to support use of antioxidants. Lastly, the aneuploid sperm frequency is a quantitative measure of deviation from the normal chromosomal complement. Although elevated sperm aneuploid frequency has been associated with recurrent pregnancy loss and implantation failures, barriers remain to its routine use.SummaryWe identified these three adjunctive tests, which have the potential to alter either management or counseling of patients with regards to male factor infertility. Elevated DNA fragmentation or significant sperm aneuploidy may suggest the need for further investigation or further preimplantation genetic testing prior to IVF. The oxidative stress adduct may lend further explanation and improved counseling of the infertile patient.
Frontiers in combining immune checkpoint inhibitors for advanced urothelial cancer management
Authors: Rebhan Katharina , Laukhtina Ekaterina , Shariat Shahrokh F. , Gust Kilian M. 
Published: March 2020

Purpose of review
This review provides an overview of currently ongoing clinical trials evaluating the combination of immune checkpoint inhibitors (CPI) with other therapies in locally advanced or metastatic urothelial cancer and the rationale for this combination approach. We discuss the preliminary results from early data presented at recent meetings regarding the efficacy and safety of novel combination therapies including a CPI for metastatic urothelial cancer.

Recent findings
CPI emerged as novel first-line or second-line treatment options in advanced and metastatic urothelial cancer (mUC). Although the response rates and their sustainability are promising, it is far from a home run. Combination therapies have already shown improved efficacy in several other tumor entities.

Summary
Numerous clinical trials currently investigate combinations of CPI with other CPI, previously established systemic chemotherapy, targeted therapies, vaccines, or accompanied with radiotherapy. Preliminary data shows promising results. These results suggest that targeting pathways of immune response combined with established or novel oncological therapies may lead to a synergistic antitumor effect.
Postmortem Magnetic Resonance Imaging and Postmortem Computed Tomography in Ligature and Manual Strangulation
Authors: Deininger-Czermak Eva , Heimer Jakob , Tappero Carlo , Thali Michael J. , Gascho Dominic 
Published: March 2020

Purpose
The aim of this study was to evaluate magnetic resonance imaging (MRI) findings in cases of fatal manual or ligature strangulation. Verification of strangulation by computed tomography (CT), MRI, and at autopsy as well as its detectability in each modality was assessed.

Methods
We retrospectively analyzed 6 manual and ligature strangulation cases between 2013 and 2019 who all underwent a whole-body CT, head and neck MRI, and an autopsy. Two radiologists examined head and neck imaging data and compared the data to autopsy findings.

Results
Magnetic resonance imaging showed a high efficiency in verifying intramuscular hemorrhages, which were confirmed in autopsy. Moreover, in one case without a visible strangulation mark, soft tissue injuries associated with strangulation were detected. Fractures, especially thyroid cartilage fractures, were successfully diagnosed by CT.

Conclusions
As MRI showed a successful detection of soft tissue lesions in relation to strangulation, it can serve as an alternative method or provide additional value to an autopsy. Intramuscular hemorrhages are a common finding in manual and ligature strangulation, providing a useful sign of applied pressure on the neck. However, to evaluate fractures, an additional CT or autopsy is recommended.
Oligometastatic and Oligoprogression Disease and Local Therapies in Prostate Cancer
Authors: Deek Matthew P. , Tran Phuoc T. 
Published: March 2020

Abstract
Our understanding of metastatic disease is rapidly advancing, with recent evidence supporting an oligometastatic state currently defined by patients having a limited (typically ≤5) number of metastatic deposits. The optimal management of these patients is also shifting toward increased integration of local therapies, with emerging evidence suggesting metastasis-directed therapy can improve overall survival. Additionally, the use of stereotactic ablative radiation therapy within castration-sensitive oligometastatic prostate cancer cohorts appears to forestall the need to initiate systemic therapy, which has unfavorable side effect profiles, such as androgen deprivation therapy, while itself being associated with little toxicity. We review the literature surrounding the use of metastasis-directed therapy in the treatment of oligometastatic prostate cancer by reviewing the evidence for its use within 3 subgroups: de novo synchronous, oligorecurrent, and oligoprogressive disease.
Radiomics, Radiogenomics, and Next-Generation Molecular Imaging to Augment Diagnosis of Hepatocellular Carcinoma
Authors: Bell Meghan , Turkbey Evrim B. , Escorcia Freddy E. 
Published: March 2020

Abstract
Ultrasound, computed tomography, magnetic resonance imaging, and [18F]F-fluorodeoxyglucose positron emission tomography are invaluable in the clinical evaluation of human cancers. Radiomics and radiogenomics tools may allow clinicians to standardize interpretation of these conventional imaging modalities, while better linking radiographic hallmarks to disease biology and prognosis. These advances, coupled with next-generation positron emission tomography imaging tracers capable of providing biologically relevant tumor information, may further expand the tools available in our armamentarium against human cancers. We present current imaging methods and explore emerging research that may improve diagnosis and monitoring of local, oligometastatic, and disseminated cancers exhibiting heterogeneous uptake of [18F]F-fluorodeoxyglucose, using hepatocellular carcinoma as an example.
Radiation in the Treatment of Oligometastatic and Oligoprogressive Disease
Authors: Zayed Sondos , Correa Rohann J.M. , Palma David A. 
Published: March 2020

Abstract
The use of local ablative therapy or metastasis-directed therapy is an emerging management paradigm in oligometastatic and oligoprogressive cancer. Recent randomized evidence has demonstrated that stereotactic ablative radiotherapy (SABR) targeting all metastatic deposits is tolerable and can improve progression-free and overall survival. While SABR is noninvasive, minimally toxic, and generally safe, rare grade 5 events have been reported. Given this and recognizing the often-uncertain prognosis of patients with metastatic disease, equipoise persists regarding the therapeutic window within which to deploy SABR for this indication. Ongoing phase III trials are aimed at validating the demonstrated safety, tolerability, and survival benefits while also refining patient selection, possibly with the aid of novel biomarkers. This narrative review of the role of SABR in oligometastatic and oligoprogressive disease summarizes recent randomized evidence and ongoing clinical trials, discusses our rationale for treatment and key management principles, and posits that SABR should be considered the preferred modality for multisite, metastasis-directed ablative therapy.
Augmenting Interpretation of Chest Radiographs With Deep Learning Probability Maps
Authors: Hurt Brian , Yen Andrew , Kligerman Seth , Hsiao Albert 
Published: March 2020

Purpose:
Pneumonia is a common clinical diagnosis for which chest radiographs are often an important part of the diagnostic workup. Deep learning has the potential to expedite and improve the clinical interpretation of chest radiographs. While earlier approaches have emphasized the feasibility of “binary classification” to accomplish this task, alternative strategies may be possible. We explore the feasibility of a “semantic segmentation” deep learning approach to highlight the potential foci of pneumonia on frontal chest radiographs.

Materials and Methods:
In this retrospective study, we trained a U-net convolutional neural network (CNN) to predict pixel-wise probability maps for pneumonia using a public data set provided by the Radiological Society of North America (RSNA) comprised of 22,000 radiographs and radiologist-defined bounding boxes. We reserved 3684 radiographs as an independent validation data set and assessed overall performance for localization using Dice overlap and classification performance using the area under the receiver-operator characteristic curve.

Results:
For classification/detection of pneumonia, area under the receiver-operator characteristic curve on frontal radiographs was 0.854 with a sensitivity of 82.8% and specificity of 72.6%. Using this strategy of neural network training, probability maps localized pneumonia to lung parenchyma for essentially all validation cases. For segmentation of pneumonia for positive cases, predicted probability maps had a mean Dice score (±SD) of 0.603±0.204, and 60.0% of these had a Dice score >0.5.

Conclusions:
A “semantic segmentation” deep learning approach can provide a probabilistic map to assist in the diagnosis of pneumonia. In combination with the patient’s history, clinical findings and other imaging, this strategy may help expedite and improve diagnosis.
Pretest and Posttest Evaluation of a Longitudinal, Residency-Integrated Microsurgery Course
Authors: Chacon Miranda A. , Myers Paige L. , Patel Alap U. , Mitchell Drew C. , Langstein Howard N. , Leckenby Jonathan I. 
Published: March 2020

Introduction
Current microsurgical training courses average 5 consecutive 8-hour days and cost US $1500 to US $2500/individual, making training a challenge for residents who are unable to take leave from clinical duties. This residency-integrated microsurgery course was designed for integration with a residency program, averaging 3 hours/week over 7 weeks. This allows for one-on-one training, beginning with synthetic tissue and concluding with in vivo stimulation. This study was performed to validate this longitudinal training course.

Methods
After recruitment and before the start of coursework, subjects completed a baseline anastomosis without guidance and a survey regarding microsurgical experience. Subjects completed approximately 3 hours/week of practical exercises. Weeks 1 to 5 used synthetic models, whereas 6 to 7 used in vivo rodent models. Nine minimum anastomoses of increasing complexity were completed and assessed with the Anastomosis Lapse Index and the Stanford Microsurgery and Residency Training scale. Scoring was performed by 3 independent reviewers and averaged for comparison.

Results
Five subjects completed the course for study. Presurvey results showed an average confidence in theoretical knowledge of 2/5; technical ability to perform procedures, 1.8/5; and ability to manage complications, 1.8/5. Postsurvey revealed confidence in theoretical knowledge of 2.5/5; technical ability to perform procedures, 2.25/5; and ability to manage complications, 2.25/5. None of these differences were significant. Each individual component of the Stanford Microsurgery and Residency Training scale scoring system improved postcourse with P < 0.05, and overall performance score improved from an average of 2.6 to 3.9 (P = 0.006). The total number of errors recorded using the Anastomosis Lapse Index reduced from 6.58 to 3.41 (P = 0.02). Time to completion reduced from an average of 28 minutes, 8 seconds to 24 minutes, 5 seconds (P = 0.003).

Conclusions
Despite a lack in significant confidence improvement, completion of the residency-integrated microsurgery course leads to significant and quantifiable improvement in resident microsurgical skill and efficiency.
Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome
Authors: Hollis Robert L , Thomson John P , Stanley Barbara , Churchman Michael , Meynert Alison M , Rye Tzyvia , Bartos Clare , Iida Yasushi , Croy Ian , Mackean Melanie , Nussey Fiona , Okamoto Aikou , Semple Colin A , Gourley Charlie , Herrington C. Simon 
Published: March 2020

AbstractEndometrioid ovarian carcinoma (EnOC) is an under-investigated type of ovarian carcinoma. Here, we report the largest genomic study of EnOCs to date, performing whole exome sequencing of 112 cases following rigorous pathological assessment. High frequencies of mutation were detected in CTNNB1(43%), PIK3CA(43%), ARID1A(36%), PTEN(29%), TP53(26%) and SOX8(19%), a novel target of recurrent mutation in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy was constructed using a novel algorithm (PRISTINE), identifying clinically distinct EnOC subtypes: TP53m cases demonstrated greater genomic complexity, were frequently FIGO stage III/IV at diagnosis (48%) and incompletely debulked (44%), and demonstrated inferior survival; conversely, CTNNB1m cases demonstrated low complexity and excellent clinical outcome, were predominantly stage I/II at diagnosis (89%) and completely resected (87%). Tumour complexity provides further resolution within the TP53wt/CTNNB1wt group. Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.
Mouse-specific but infection-unspecific IgM repertoire fingerprint following viral infection
Authors: Yermanos Alexander , Kräutler Nike Julia , Pedrioli Alessandro , Menzel Ulrike , Greiff Victor , Stadler Tanja , Oxenius Annette , Reddy Sai T. 
Published: March 2020

AbstractAntibody repertoire sequencing provides a molecular fingerprint of current and past pathogens encountered by the immune system. Most repertoire studies in humans require measuring the B cell response in the blood, resulting in a large bias to the IgM isotype. The extent to which the circulating IgM antibody repertoire correlates to lymphoid tissue-resident B cells in the setting of viral infection remains largely uncharacterized. Therefore, we compared the IgM repertoires from both blood and bone marrow (BM) plasma cells (PCs) following acute or chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Despite previously reported serum alterations between acute and chronic infection, IgM repertoire signatures based on clonal diversity metrics, public clones, network and phylogenetic analysis were largely unable to distinguish infection cohorts. Our findings, however, revealed mouse-specific congruence between the blood and PC repertoires irrespective of infection status. Our study reveals that IgM repertoire analyses may be unsuitable for providing a fingerprint of current or previous immune challenges.