bluuebunny/crossref_metadata_2025_split huggingface dataset:
New insights from the MESA study: increased high-sensitivity troponins as a cardiovascular risk factor
Authors: Muscente Francesca , De Caterina Raffaele 
Published: October 2021

Abstract
The most recent high-sensitivity assays for troponins I and T (hs-TnI and hs-TnT) have made it possible to detect blood concentrations up to 10 times lower than previous assays, making troponins detectable even in asymptomatic subjects without manifest cardiovascular disease. For this reason, hs-Tn, initially introduced as markers of myocardial damage in an acute setting, have also become possible markers of subclinical myocardial damage in baseline conditions. In fact, recent evidence suggests that hs-TnT and hs-TnI predict the risk of future cardiovascular events also in the context of primary prevention, and offer incremental information when added to current risk stratification models. The different association highlighted with different outcome measures, such as coronary heart disease, atherosclerotic cardiovascular disease, heart failure, and death from all causes, seems to indicate that the risk observed in asymptomatic subjects with high levels of hs-Tn is an expression of subclinical damage secondary to multiple pathophysiological mechanisms, and not only to atherothrombosis. However, the ability of hs-TnT and hs-TnI (until now used interchangeably), to provide differential predictive information, and not redundant with respect to more traditional factors, remains to be definitively clarified, both for the purpose of predicting specific outcomes and for the implementation of specific preventive strategies. To date, evidences available allow us to hypothesize their role more as markers than as risk factors.
Does sacubitril/valsartan work in acute myocardial infarction? The PARADISE-AMI study
Authors: Gatto Laura 
Published: October 2021

Abstract
Patients with acute myocardial infarction (AMI) complicated by left ventricular dysfunction have an increased risk of death and heart failure. Numerous clinical studies have demonstrated the ability of ACE inhibitors in optimizing the outcome in this particular clinical setting. In recent years, the sacubitril/valsartan association has drastically improved the prognosis of patients with heart failure with reduced ejection fraction with a significant decrease in mortality from cardiovascular causes and hospitalizations due to acute heart failure. However, it has not yet been fully clarified whether this pharmacological association may play a role in patients with AMI. Pre-clinical studies have suggested the possibility that sacubitril/valsartan can reduce the size of the infarct scar and prevent the onset of ventricular arrhythmias in laboratory animals in which myocardial infarction was induced. On the other hand, small clinical experiences with patients after myocardial infarction have provided conflicting data. The results of the PARADISE-MI study were recently presented, which enrolled 5661 patients with AMI complicated by pulmonary congestion and left ventricular dysfunction randomized to therapy with ramipril or sacubitril/valsartan and followed up for ∼2 years. Although combination therapy was associated with an ∼10% reduction in the risk of death from cardiovascular causes or an episode of heart failure, this was not enough to achieve statistical significance. However, treatment with sacubitril/valsartan was shown to be more effective than ramipril in preventing recurrence of heart failure after the first one.
Treatment of carotid stenosis: surgery and stent in comparison
Authors: Giudice Rocco , Spataro Claudio 
Published: October 2021

Abstract
Carotid stenosis in the extracranial tract determines 10–15% of all ischaemic strokes. The aim of treatment, therefore, is to prevent major neurological events. Carotid endarterectomy surgery has proved effective in this regard, with various randomized studies that have demonstrated its validity in both symptomatic and asymptomatic patients. As an alternative, since the late 1990s, the endovascular treatment of carotid stenosis by stenting has gradually established itself. Numerous controlled clinical trials have compared surgery and carotid stenting in terms of perioperative outcomes (death, stroke, and myocardial infarction within 30 days of the procedure) and stroke prevention ipsilateral to the lesion treated during follow-up, evaluating both symptomatic and asymptomatic patients. From the systematic review of the data, it is legitimate to state that stenting may represent a safe alternative to conventional surgery in patients with symptomatic carotid stenosis under the age of 70, while endarterectomy is clearly safer and more effective than endovascular treatment for symptomatic older patients. On the other hand, as regards asymptomatic patients, the available evidence is limited and further data are needed to compare the two methods and to compare them with the best current medical therapy in order to draw conclusions.
Implantable ventricular assistance systems (VAD) as a bridge to transplant or as ‘destination therapy’
Authors: Nesta Marialisa , Cammertoni Federico , Bruno Piergiorgio , Massetti Massimo 
Published: October 2021

Abstract
Heart failure is a complex clinical syndrome associated with a high mortality and morbidity rate. Despite the extensive pharmacological armamentarium, a non-negligible percentage of patients develop advanced heart failure and require further therapies. In these circumstances, heart transplantation remains the treatment of choice, but the limited number of donors and the reduction of potential candidates have made necessary to develop new technologies. Since the 1980s, left ventricular assist devices (LVADs) have been introduced and have completely revolutionized the landscape of advanced heart failure treatments. This article has identified the categories of patients who can benefit from the implantation of an LVAD and summarized the new classifications. In addition, the main LVADs are described, analysing the results of the main clinical studies, with particular reference to adverse events. Although there is no perfect LVAD, a multidisciplinary team approach, dedicated to the treatment of advanced heart failure, can guide the choices on the best device to implant, in order to minimize complications and improve the patient’s quality of life.
Statins and age: is there a limit beyond which primary prevention is futile?
Authors: Perna Gian Piero 
Published: October 2021

Abstract
Hypercholesterolaemic patients at an advanced age (&gt;75 years) with and without known cardiovascular disease are at higher cardiovascular risk than younger subjects, and the frequency of vascular events in this group of the patient increases with increasing age. However, in clinical practice, these subjects are undertreated for various reasons: conservative cultural attitude, fear of side effects, doubts about efficacy, lack of specific trials. Two recent meta-analyses have shown that the use of lipid-lowering drugs is as safe and effective in this age group as in younger subjects. Subjects aged &gt;75 years in primary prevention are poorly represented in trials but should be considered for treatment in daily clinical practice, because, in the risk assessment (SCORE algorithm), they are very often classified as intermediate or high risk but can also be reclassified at increased risk if an additional assessment step with clinical markers (diabetes and reduced glomerular filtrate) or cardiovascular imaging is used for the detection of subclinical atherosclerosis. Greater attention to treatment methods and monitoring of possible side effects is recommended, but the only limit to the treatment is its ‘futility’ in the fragile patient.
Early-Life War Exposure and Later-Life Frailty Among Older Adults in Vietnam: Does War Hasten Aging?
Authors: Zimmer Zachary , Korinek Kim , Young Yvette , Teerawichitchainan Bussarawan , Toan Tran Khanh 
Published: October 2021

AbstractObjectivesThis study aimed to assess the nature and degree of association between exposure to potentially traumatic wartime experiences in early life, such as living in a heavily bombed region or witnessing death firsthand, and later-life frailty.MethodThe Vietnam Health and Aging Study included war survivors in Vietnam, 60+, who completed a survey and health exam between May and August 2018. Latent class analysis (LCA) is used to construct classes exposed to similar numbers and types of wartime experiences. Frailty is measured using a deficit accumulation approach that proxies biological aging. Fractional logit regression associates latent classes with frailty scores. Coefficients are used to calculate predicted frailty scores and expected age at which specific levels of frailty are reached across wartime exposure classes.ResultsLCA yields 9 unique wartime exposure classes, ranging from extreme exposure to nonexposed. Higher frailty is found among those with more heavy/severe exposures with a combination of certain types of experiences, including intense bombing, witnessing death firsthand, having experienced sleep disruptions during wartime, and having feared for one’s life during war. The difference in frailty-associated aging between the most and least affected individuals is more than 18 years.DiscussionWar trauma hastens aging and warrants greater attention toward long-term implications of war on health among vast postconflict populations across the globe.
Estimation of size of megathrust zone in the Makran subduction system by thermal modelling
Authors: Khaledzadeh Matin , Ghods Abdolreza 
Published: October 2021

SUMMARYTo estimate the maximum possible size of megathrust earthquakes, we calculate the thermal structure along two profiles in west and east Makran subduction zone by solving the steady-state 2-D energy equation. For the western profile, we derive the slab geometry from a recent receiver function study along IASBS (Institute for Advanced Studies in Basic Sciences) seismic profile in the onshore part of the Iranian Makran. For the eastern profile, the slab geometry is derived from a recent relocation of seismicity of Makran. Using the improved slab geometry and a force balance establishment in the accretionary wedge, the effective coefficient of friction, $\mu ^{\prime}$, is assumed to be equal to 0.03. We estimate the updip and downdip of the megathrust zone by simultaneously considering the seismicity related to the events with thrust and normal mechanisms and intersection between 100–150 and 350–450 °C isotherms and the subducting slab interface. Along the western profile, the megathrust updip locates ∼95 km north of the deformation front (DF) at the depth of ∼20 km and the downdip locates ∼300 km north of the DF at the depth of ∼35 km. Presence of normal mechanism events at deeper depths indicates that the downdip limit of the megathrust zone is consistent with the 350 °C isotherm. The megathrust width is ∼205 km along the western profile. Along the eastern profile, the megathrust updip locates ∼60 km north of the DF at the depth of ∼15 km and the downdip locates ∼280 km north of the DF at the depth of ∼35 km. The downdip limit of the megathrust zone is closely related to the 350 °C isotherm. The megathrust width is ∼220 km along the eastern profile. Assuming a segmentation of the thrust zone into the western and eastern parts, the areal size of the megathrust zones in west and east Makran is ∼82 000 and 88 000 km2, respectively. We estimate the magnitude of the largest possible megathrust earthquakes in the west and east Makran to be 8.65 ± 0.26 and 8.75 ± 0.26 Mw, respectively.
Offensive Cyber Capabilities and State Violence: Three Logics of Integration
Authors: Egloff Florian J , Shires James 
Published: October 2021

AbstractOffensive cyber capabilities (OCCs) are the combination of people, technologies, and organizational attributes that jointly enable offensive cyber operations: the adversarial manipulation of digital services or networks. Most works on OCCs focus on their (de-)escalatory potential in terms of diplomatic tension, instability, or power. This article argues for a re-orientation toward the normatively prior question of their relative violence. It asks: how are OCCs integrated into violent state capacities and what are the consequences? The article proposes three logics of integration by which OCCs are included in violent state actions, in both repressive and interstate situations. These logics—substitution, support, and complement—weigh the benefits of using OCCs against an adversary instead of, as part of, and in addition to other means of violence, respectively. The article argues that the violence of OCCs depends on two things: first, whether one adopts a narrowly physical or a more expansive definition of violence and, second, which logic of integration governs their use. On a narrow definition of violence, substitutive and supportive uses of OCCs are less likely to be violent than conventional alternatives, and complementary uses of OCCs are not violent at all. On a wider definition, both substitutive and supportive uses of OCCs can lead to more violence than conventional alternatives, while complementary uses of OCCs are highly likely to increase violence overall. Acknowledging the different logics of integration for OCCs, and understanding their violent effects, has important analytical and policy benefits for global security studies.
Vitamin D Deficiency in the Military: It’s Time to Act!
Authors: Fogleman Sarah A , Janney Cory , Cialdella-Kam Lynn , Flint James H 
Published: October 2021

ABSTRACT
Vitamin D is critically important to numerous physiologic functions, including bone health. Poor vitamin D status is a common but underrecognized problem that predisposes the military population to stress fracture and completed fracture. This has significant implications for force health protection, warfighter readiness, attrition, and cost. Despite this, vitamin D deficiency is still underdiagnosed and undertreated in the military. This is a major hindrance to military readiness and one that could easily be modified with awareness, prevention, and early treatment. In this commentary, we review the literature on vitamin D deficiency and critically examine the current status of policies and clinical practice related to vitamin D in the military health system. We offer several practical recommendations to increase awareness and readiness while decreasing musculoskeletal injury and the associated costs.
Urticaria and increased risk of rheumatoid arthritis: a two-sample Mendelian randomisation study in European population
Authors: Yu Xue , Deng Ming-Gang , Tang Zi-Ying , Zhang Zhi-Jiang 
Published: October 2021

ABSTRACT

Background
In recent years, a growing body of observational studies suggest that urticaria is associated with a higher risk of rheumatoid arthritis (RA). However, the causal association between urticaria and RA remains unknown.

Objective
To investigate the causal relationship of urticaria and RA in European populations by Mendelian randomisation (MR) approach.

Methods
We conducted two-sample MR analyses. Eleven single-nucleotide polymorphisms associated with urticaria were used as instrumental variables. The summary data on urticaria were derived from FinnGen Data Freeze 2. The summary data on RA were obtained from a published meta-analysis using European samples. Four MR methods were applied to the MR estimates. Three heterogeneity tests, including Cochran’s Q test, single variant analysis, and leave-one-out variant analysis, were used. The pleiotropy and horizontal pleiotropy among instrumental variables were assessed with MR-Egger regression intercept, MR pleiotropy residual sum and outlier global test, and PhenoScanner.

Results
The MR analysis suggested that urticaria was causally associated with RA (odds ratio = 1.114, 95% confidence interval = 1.024–1.211, p = .011). No genetic pleiotropy or horizontal pleiotropy was revealed by MR-Egger regression intercept and MR pleiotropy residual sum and outlier global test. The sensitivity analysis results were relatively robust.

Conclusions
The MR analysis suggested there was sufficient evidence to indicate urticaria is the cause of RA.
Tacrolimus as an alternative treatment for patients with juvenile idiopathic arthritis
Authors: Yamazaki Susumu , Shimizu Masaki , Akutsu Yuko , Shimbo Asami , Mori Masaaki 
Published: October 2021

ABSTRACT

Objective
To evaluate the efficacy and safety of tacrolimus in patients with juvenile idiopathic arthritis (JIA).

Methods
We retrospectively analysed 27 patients with JIA who received tacrolimus therapy at the Department of Pediatric Rheumatology of the Tokyo Medical and Dental University between April 2019 and August 2020. We collected background and clinical characteristics at the time of add-on tacrolimus therapy initiation (baseline; Month 0) and after 3, 6, and 12 months. The primary outcome was successful medication reduction after 12 months. Patients requiring reduced and additional treatments were assigned as ‘did not require additional treatment patients’ and ‘required additional treatment patients’, respectively. The Wilcoxon signed-rank test was used to evaluate the continuous distribution of laboratory data and Juvenile Arthritis Disease Activity Score-27 at 3, 6, and 12 months relative to baseline values. Statistical significance was set as p &lt; .05.

Results
Among the 27 included cases, 17 patients were classified as did not require additional treatment patients, and there was a significant improvement in Juvenile Arthritis Disease Activity Score-27 scores in this group (p &lt; .05). No patients presented tacrolimus-related adverse events throughout the study period.

Conclusion
Tacrolimus is an effective and safe therapeutic alternative for approximately 60% of patients with JIA.
Rheumatologic manifestations in a cohort of patients with Vogt–Koyanagi–Harada disease
Authors: Kocaer Sinem Burcu , Kaya Mahmut , Yilmaz Suzan Guven , Ayhan Ziya , Saatci Ali Osman , Onen Fatos , Sari Ismail 
Published: October 2021

ABSTRACT

Objectives
Vogt–Koyanagi–Harada Disease (VKHD) is a systemic autoimmune disorder characterized by granulomatous panuveitis. Inflammatory rheumatic diseases (IRDs) are among the differential diagnosis of VKHD. However, current knowledge on the rheumatological aspects of VKHD is still limited. We aimed to investigate the prevalence of rheumatic conditions in VKHD patients.

Methods
VKHD patients were included in the study and they were reviewed in terms of the presence of any rheumatological manifestations.

Results
There were 18 patients with a female preponderance (83.3%, female). Inflammatory type of peripheral joint pain (11%) and sicca symptoms (33%) were the most common rheumatological findings. The frequency of spondyloarthritis-related features such as inflammatory back pain and HLA-B27 rate was not increased. None of the patients had radiographic sacroiliitis. Anti-nuclear antibody was positive in high titres nearly in 30% of the patients and three patients had antibodies against extractable nuclear antigens. Nailfold capillaroscopy was abnormal in about one-third of the patients. Pathergy test was negative in all cohorts. While angiotensin-converting enzyme was elevated in nearly 20% of the patients, there were no abnormalities on chest X-rays.

Conclusion
VKHD shares some features with IRDs. The common features were mostly suggestive of connective tissue disease rather than SpA or rheumatoid arthritis.
Intraoperative DNA methylation classification of brain tumors impacts neurosurgical strategy
Authors: Djirackor Luna , Halldorsson Skarphedinn , Niehusmann Pitt , Leske Henning , Capper David , Kuschel Luis P , Pahnke Jens , Due-Tønnessen Bernt J , Langmoen Iver A , Sandberg Cecilie J , Euskirchen Philipp , Vik-Mo Einar O 
Published: October 2021

Abstract

Background
Brain tumor surgery must balance the benefit of maximal resection against the risk of inflicting severe damage. The impact of increased resection is diagnosis-specific. However, the precise diagnosis is typically uncertain at surgery due to limitations of imaging and intraoperative histomorphological methods. Novel and accurate strategies for brain tumor classification are necessary to support personalized intraoperative neurosurgical treatment decisions. Here, we describe a fast and cost-efficient workflow for intraoperative classification of brain tumors based on DNA methylation profiles generated by low coverage nanopore sequencing and machine learning algorithms.

Methods
We evaluated 6 independent cohorts containing 105 patients, including 50 pediatric and 55 adult patients. Ultra-low coverage whole-genome sequencing was performed on nanopore flow cells. Data were analyzed using copy number variation and ad hoc random forest classifier for the genome-wide methylation-based classification of the tumor.

Results
Concordant classification was obtained between nanopore DNA methylation analysis and a full neuropathological evaluation in 93 of 105 (89%) cases. The analysis demonstrated correct diagnosis in 6/6 cases where frozen section evaluation was inconclusive. Results could be returned to the operating room at a median of 97 min (range 91-161 min). Precise classification of the tumor entity and subtype would have supported modification of the surgical strategy in 12 out of 20 patients evaluated intraoperatively.

Conclusion
Intraoperative nanopore sequencing combined with machine learning diagnostics was robust, sensitive, and rapid. This strategy allowed DNA methylation-based classification of the tumor to be returned to the surgeon within a timeframe that supports intraoperative decision making.
Group, Subgroup, and Person-Specific Symptom Associations in Individuals at Different Levels of Risk for Psychosis: A Combination of Theory-based and Data-driven Approaches
Authors: van der Tuin Sara , Groen Robin Nikita , Castro-Alvarez Sebastian , Oldehinkel Albertine J , Booij Sanne H , Wigman Johanna T W 
Published: October 2021

AbstractIntroductionDynamics between symptoms may reveal insights into mechanisms underlying the development of psychosis. We combined a top-down (theory-based) and bottom-up (data-driven) approach to examine which symptom dynamics arise on group-level, on subgroup levels, and on individual levels in early clinical stages. We compared data-driven subgroups to theory-based subgroups, and explored how the data-driven subgroups differed from each other.MethodsData came from N = 96 individuals at risk for psychosis divided over four subgroups (n1 = 25, n2 = 27, n3 = 24, n4 = 20). Each subsequent subgroup represented a higher risk for psychosis (clinical stages 0-1b). All individuals completed 90 days of daily diaries, totaling 8640 observations. Confirmatory Subgrouping Group Iterative Multiple Model Estimation (CS-GIMME) and subgrouping (S-)-GIMME were used to examine group-level associations, respectively, theory-based and data-driven subgroups associations, and individual-specific associations between daily reports of depression, anxiety, stress, irritation, psychosis, and confidence.ResultsOne contemporaneous group path between depression and confidence was identified. CS-GIMME identified several subgroup-specific paths and some paths that overlapped with other subgroups. S-GIMME identified two data-driven subgroups, with one subgroup reporting more psychopathology and lower social functioning. This subgroup contained most individuals from the higher stages and those with more severe psychopathology from the lower stages, and shared more connections between symptoms.DiscussionAlthough subgroup-specific paths were recovered, no clear ordering of symptom patterns was found between different early clinical stages. Theory-based subgrouping distinguished individuals based on psychotic severity, whereas data-driven subgrouping distinguished individuals based on overall psychopathological severity. Future work should compare the predictive value of both methods.