bluuebunny/crossref_metadata_2025 huggingface dataset:
Arbeiten zur falschen Zeit
Authors: Opalka Markus
Published: October 2021

Die innere Uhr synchronisiert sich mit äußeren Gegebenheiten – insbesondere mit dem Tag-Nacht-Rhythmus – und steuert zahlreiche Prozesse im Organismus.Insbesondere durch Nachtschichten erfolgt eine Betätigung gegen die innere Uhr, was körperliche und psychische Konsequenzen nach sich ziehen kann. Wenn nächtliche Arbeit nicht beendet werden kann, können einige Maßnahmen den Rhythmuswechsel unterstützen, beispielsweise eine leichte Kost während der Nachtschicht.
Herz im Abschaltmodus
Authors: Jahn Claus
Published: October 2021

Ein 50-jähriger, sportlicher Patient entwickelt plötzlich bei jedem Training kardioforme Symptome wie Übelkeit, Schwindel und Atemnot. Nachdem die kardiologische Diagnostik außer einem sogenannten Sportlerherz keine Erklärung für die Symptome eröffnen konnte, liefert eine Smartwatch den entscheidenden Hinweis auf ein Sick-Sinus-Syndrom. Durch pulsbegrenztes Training und eine begleitende phytotherapeutische, segmentale und homöopathische Therapie gelingt eine deutliche Verbesserung bis hin zur Vermeidung der sinuatrialen Krisen.
Frühe Diagnostik und Therapie der Kleingefäßvaskulitiden
Authors: Kavruk Hilal , Baraliakos Xenofon
Published: October 2021

Die Kleingefäßvaskulitiden als Untergruppe der Vaskulitiden stellen selbst auch ein Spektrum an verschiedenen Subentitäten dar, deren Diagnostik und Therapie teilweise fachübergreifend erfolgt. Man unterscheidet die ANCA-assoziierten von den Nicht-ANCA-assoziierten Vaskulitiden. Es handelt sich um die Granulomatose mit Polyangiitis, die mikroskopische Polyangiitis, die antiglomeruläre Basalmembran-Erkrankung, die kryoglobulinämische Vaskulitis, die IgA-Vaskulitis und die hypokomplementämische Urtikariavaskulitis. Epidemiologische Kennzahlen schwanken, nicht zuletzt aufgrund ihrer Seltenheit, allerdings konnten verbesserte diagnostische Möglichkeiten, erhöhtes Bewusstsein und vertiefte Kenntnis für diese Erkrankungen auch besser regionale und Altersunterschiede erkennbar machen. Eine breite Zahl an Organen kann betroffen sein, häufig liegt, je nach Subentität, eine Organprädilektion vor. Die Behandlung der Kleingefäßvaskulitiden orientiert sich an Schwere und Ausmaß der Krankheit und variiert zwischen den einzelnen Subentitäten. Hauptvertreter der medikamentösen Therapie sind Glukokortikoide, Rituximab und Cyclophosphamid.
Adäquate Versorgungsstrukturen und Bedeutung von Big-Data-Analysen bei EMAH-Patienten
Authors: Diller Gerhard-Paul , Baumgartner Helmut
Published: October 2021

Da immer mehr Kinder mit angeborenem Herzfehler (AHF) überleben und ins Erwachsenenalter
eintreten, sind nunmehr rund zwei Drittel der aktuellen AHF-Patienten Erwachsene mit
angeborenen Herzfehlern (EMAH). Es wird geschätzt, dass in Deutschland aktuell ca. 350000
EMAH-Patienten leben, wobei die Zahl weiter rasch zunimmt. Die lebenslange kardiologische
Anbindung von EMAH-Patienten ist nach aktuellen Leitlinienempfehlungen erforderlich und mit
einer niedrigeren Letalität und Morbidität assoziiert. Somit ist die ausschließliche
hausärztliche Versorgung von EMAH-Patienten nicht ausreichend. EMAH-Patienten sind an
spezialisierte EMAH-Zentren/bei EMAH-Kardiologen anzubinden und sollten gemeinschaftlich mit
niedergelassenen kardiologischen Kollegen behandelt werden. Big Data und Methoden des
maschinellen Lernens sind integraler Bestandteil der Forschungsbemühungen bei EMAH-Patienten,
die unter einer chronischen, lebenslangen Erkrankung leiden. Methoden der künstlichen
Intelligenz werden die Versorgung von EMAH-Patienten in Zukunft effizienter machen und die
Reproduzierbarkeit von Bildgebungsuntersuchungen erhöhen.
Psychokardiologische Aspekte bei Erwachsenen mit angeborenem Herzfehler (EMAH)
Authors: Kahl Kai G. , Westhoff-Bleck Mechthild
Published: October 2021

Bedingt durch die verbesserte medizinische Versorgung von Patienten mit angeborenen
Herzfehlern und die damit einhergehende verlängerte Lebenserwartung treten
psychokardiologische Aspekte stärker in den Vordergrund. Hierzu zählen u. a. die Inzidenz
komorbider psychischer Störungen, Fragen nach den Faktoren, die eine optimale Lebensqualität
ermöglichen, den Einfluss eines angeborenen Herzfehlers auf Partnerschaft und Lebensgestaltung
sowie Lebensstilfaktoren und Adhärenz. In Zeiten knapper Personalressourcen und zunehmenden
ökonomischen Drucks ist darüber hinaus eine effektive Diagnostik psychosozialer Probleme und
ggf. Einleitung einer wirkungsvollen psychosozialen Therapie wichtig. Die interdisziplinäre
Zusammenarbeit unter Einbezug moderner psychokardiologischer Konzepte ist daher in der
langfristigen Therapie von EMAH-Patienten von entscheidender Bedeutung.
Relationship of Change in Cervical Curvature after Laminectomy with Lateral Mass Screw Fixation to Spinal Cord Shift and Clinical Efficacy
Authors: Hou Shu-bing , Sun Xian-ze , Liu Feng-yu , Gong Rui , Zhao Zheng-qi , Lu Kuan , Liu Yan-bing
Published: October 2021

Background and Study Aims Although laminectomy with lateral mass screw fixation (LCSF) is an effective surgical treatment for cervical spondylotic myelopathy (CSM), loss of cervical curvature may result. This study aimed to investigate the effect of cervical curvature on spinal cord drift distance and clinical efficacy.

Patients and Methods We retrospectively analyzed 78 consecutive CSM patients with normal cervical curvature who underwent LCSF. Cervical curvature was measured according to Borden's method 6 months after surgery. Study patients were divided into two groups: group A, reduced cervical curvature (cervical lordosis depth 0–7mm; n = 42); and group B, normal cervical curvature (cervical lordosis depth 7–17mm; n = 36). Spinal cord drift distance, laminectomy width, neurologic functional recovery, axial symptom (AS) severity, and incidence of C5 palsy were measured and compared.

Results Cervical lordosis depth was 5.1 ± 1.2 mm in group A and 12.3 ± 2.4 mm in group B (p < 0.05). Laminectomy width was 21.5 ± 2.6 mm in group A and 21.9 ± 2.8 mm in group B (p > 0.05). Spinal cord drift distance was significantly shorter in group A (1.9 ± 0.4 vs. 2.6 ± 0.7 mm; p < 0.05). The Japanese Orthopaedic Association (JOA) score significantly increased after surgery in both groups (p < 0.05). Neurologic recovery rate did not differ between the two groups (61.5 vs. 62.7%; p > 0.05). AS severity was significantly higher in group A (p < 0.05). C5 palsy occurred in three group A patients (7.1%) and four group B patients (11.1%), but the difference was not significant (p > 0.05).

Conclusion After LCSF, 53.8% of the patients developed loss of cervical curvature. A smaller cervical curvature resulted in a shorter spinal cord drift distance. Loss of cervical curvature was related to AS severity but not improvement of neurologic function or incidence of C5 palsy.
Cervical Single-Level Pincer Stenosis Causing Myelopathy: A Technical Note and Medium-term Results of a One-Session Microsurgical 360-Degree Treatment
Authors: Papavero Luca , Pietrek Markus , Marques Carlos J. , Schmeiser Gregor
Published: October 2021

Background and Study Aims Single-level circumferential or pincer stenosis (PS) affects few patients with degenerative cervical myelopathy (DCM). The surgical technique and medium-term results of a one-session microsurgical 360-degree (m360°) procedure are presented.

Patients Between 2013 and 2018, the data of 23 patients were prospectively collected out of 371 patients with DCM. The m360° procedure comprised a microsurgical anterior cervical decompression and fusion (ACDF), with additional plate fixation, followed by flipping the patient and performing a microsurgical posterior bilateral decompression via a unilateral approach in crossover technique.

Results The mean age of the patients was 72 years (range: 50–84); 17 patients were males. The mean follow-up time was 12 months (range: 6–31). The patients filled in the patient-derived modified Japanese Orthopaedic Association (P-mJOA) questionnaire on average 53 months after surgery. One patient received a two-level ACDF. Lesions were mostly (92%) located at the C3/C4 (8/24), C4/C5 (7/24), and C5/C6 (7/24) levels. Functional X-rays showed segmental instability in 10 of 23 patients (44%). All preoperative T2-weighted magnetic resonance imaging (MRI) showed an intramedullary hyperintensity. The median preoperative mJOA score was 13 (range 3), and it improved to 16 (range 3) postoperatively. The mean improvement rate in the mJOA score was 73%. When available, postoperative MRI confirmed good circumferential decompression with persistent intramedullary hyperintensity. There were two complications: a long-lasting radicular paresthesia at C6 and a transient C5 palsy. No revision surgery was required.

Conclusion The one-session m360° procedure was found to be a safe surgical procedure for the treatment of PS, and the medium-term clinical outcome was satisfactory.
Tibial Tuberosity Transposition Fixation with a Locking Plate during Medial Patellar Luxation Surgery: An Ex Vivo Mechanical Study
Authors: Eskelinen Esa V. , Suhonen Ari P. , Virolainen Juha V. , Liska William D.
Published: October 2021

Objectives The purpose of this study was to compare the load at failure, stiffness and mode of failure between three types of tibial tuberosity transposition fixation techniques: (a) pin and figure-8 tension band wire (Pin-TBW), (b) locking plate with pin and a tension band wire (Plate-Pin-TBW) and (c) locking plate with a pin (Plate-Pin).

Methods Six pairs of raccoon dog cadaveric tibiae were tested in Phase I Pin-TBW versus Plate-Pin-TBW and seven pairs in Phase II Plate-Pin-TBW versus Plate-Pin. One limb of each pair was randomly assigned to one of two groups for each phase. A tensile force was applied to the patellar ligament until construct failure.

Results Pin-TBW (342N ± 54.7N) failed at a lower load than Plate-Pin-TBW (469N ± 77.3N), p = 0.00748, with all Pin-TBW failing by fracture and the majority of Plate-Pin-TBW failing by rupture of patellar ligament. Pin-TBW group Phase I, normalized with Plate-Pin-TBW Phase I, failed at a lower load than Plate-Pin group Phase II, normalized with Plate-Pin-TBW Phase II, p = 0.00467. There was no significant difference in mean load at failure, stiffness or mode at failure between the groups in the Phase II study.

Clinical Significance Although ex vivo mechanical testing does not replicate the postoperative live dog or cat, these results demonstrate lower construct strength of the Pin-TBW construct compared with the Plate-Pin construct in the raccoon dog cadaver model.
Single-ion optical clocks and the redefinition of time
Authors: Cockshott Anne
Published: October 2021

Improvements in the systematic uncertainty and stability of 40Ca+ optical clocks could contribute to changing the reference of time or frequency in the future.
Improvement of HHV prediction model of biomass based on the ultimate analysis
Authors: Kim Se Ung , Yun Jong Sun , Ri Jong Sim , Hong Kwang Il , Chon Ok Sim , Ri Jin Hyok , Ri Jang Mi
Published: October 2021

This paper presents an improved prediction model for the higher heating value (HHV) of biomass based on the ultimate analysis by using the standard least squares method. This study intends for us to predict the HHV of biomass within a wide range of elemental distributions rather than the range of literature in order to create an optimal prediction model. To this end, many experimental data, comprising a wide range of biomass elements, regression models, and neural networks, are used for its comparative validation. As a result, the proposed prediction model, HHV = 2.8799 + 0.2965 * C + 0.4826 * H – 0.0187 * O demonstrates a better HHV prediction performance for biomass in a comparative validation of 250 samples presented in the literature, and the fitness model using a neural network shows a high fitness in the training, validation, and testing for 430 samples.
Collective stimulated Brillouin scattering modes of two crossing laser beams with shared scattered wave
Authors: Qiu Jie , Hao Liang , Cao Lihua , Zou Shiyang
Published: October 2021

In inertial confinement fusion (ICF), overlapping of laser beams is common. Owing to the effective high laser intensity of the overlapped beams, the collective mode of stimulated Brillouin scattering (SBS) with a shared scattered light wave is potentially important. In this work, an exact analytic solution for the convective gain coefficient of the collective SBS modes with shared scattered wave is presented for two overlapped beams based on a linear kinetic model. The effects of the crossing angle, polarization states, and finite beam overlapping volume of the two laser beams on the shared light modes are analyzed for cases with zero and nonzero wavelength difference between the two beams. It is found that all these factors have a significant influence on the shared light modes of SBS. Furthermore, the out-of-plane modes, in which the wavevectors of daughter waves lie in different planes from the two overlapped beams, are found to be important for certain polarization states and especially for obtuse crossing angles. In particular, adjusting the polarization directions of the two beams to be orthogonal to each other or tuning the wavelength difference to a sufficiently large value (of the order of nanometers) are found to be effective methods to suppress the shared light modes of SBS. This work will be helpful for comprehending and suppressing collective SBS with shared scattered waves in ICF experiments.
The interphonology of contemporary English corpus (IPCE-IPAC)
Authors: Herry-Bénit Nadine , Lopez Stéphanie , Kamiyama Takeki , Tennant Jeff
Published: October 2021

This article presents the IPCE-IPAC corpus, an ongoing project, which has been collected in France, Italy, Spain
and China since 2014. The data is collected to investigate the acquisition of segmental and suprasegmental phenomena by L2
learners of English, with a focus on phonemes. The article discusses the methods for the compilation of this original spoken
learner corpus, designed to study L2 “interphonology” (Detey, Racine, Kawaguchi, & Zay,
2016), or interlanguage phonology.
Lexical diversity in an L2 Spanish learner corpus
Authors: Fernández-Mira Paloma , Morgan Emily , Davidson Sam , Yamada Aaron , Carando Agustina , Sagae Kenji , Sánchez-Gutiérrez Claudia H.
Published: October 2021

This study examines the impact of two topic-related variables (i.e., valence polarity and everyday-life closeness)
on the lexical diversity scores (i.e., MTLD) of learners of L2 Spanish at different proficiency levels. The analysis included
3,045 texts written in response to two pairs of prompts by 1,165 students enrolled in an L2 Spanish program. The first pair of
prompts asked learners to narrate an event: prompt 1 focused on a perfect vacation (positive event), while prompt 2 asked
participants to tell a terrible story (negative event). The second pair asked to describe a person: prompt 1 required that the
subject be famous, thus not close to the writer, whereas prompt 2 required that the subject be special and close to the writer.
Results indicate that lexical diversity scores were higher for the texts written about the positive event and the famous subject
across all proficiency levels.
Interpretations based on delayed-domain (dis)appearance in printed advertising
Authors: Herrero-Ruiz Javier
Published: October 2021

In the Cognitive Linguistics literature, the way viewers understand printed ads whose interpretation is based on metaphors and/or metonymies is conditioned by the principle whereby the source and target domains are called upon by the linguistic expression at roughly the same time (cf.Gibbs, 2006).

Nonetheless,Herrero-Ruiz (2019)has shown how certain contextual effects are generated when one of the metaphoric/metonymic domains appears at a later stage in the interpretation process (directvs.delayed domain appearance). In this paper, we shall describe various analytical patterns grounded in this new perspective as well as the specific interpretive routes that they imply. In doing so, we offer an alternative to the existing approaches that try to account for the possible interpretations printed ads based on metaphors and/or metonymies may elicit.
Gastric neurons in the nucleus tractus solitarius are selective to the orientation of gastric electrical stimulation
Authors: Cao Jiayue , Wang Xiaokai , Powley Terry L , Liu Zhongming
Published: October 2021

Objective. Gastric electrical stimulation (GES) is a bioelectric intervention for gastroparesis, obesity, and other functional gastrointestinal disorders. In a potential mechanism of action, GES activates the nerve endings of vagal afferent neurons and induces the vago-vagal reflex through the nucleus tractus solitarius (NTS) in the brainstem. However, it is unclear where and how to stimulate in order to optimize the vagal afferent responses. Approach. To address this question with electrophysiology in rats, we applied mild electrical currents to two serosal targets on the distal forestomach with dense distributions of vagal intramuscular arrays (IMAs) that innervated the circular and longitudinal smooth muscle layers. During stimulation, we recorded single and multi-unit responses from gastric neurons in NTS and evaluated how the recorded responses depended on the stimulus orientation and amplitude. Main results. We found that NTS responses were highly selective to the stimulus orientation for a range of stimulus amplitudes. The strongest responses were observed when the applied current flowed in the same direction as the IMAs in parallel with the underlying smooth muscle fibers. Our results suggest that gastric neurons in NTS may encode the orientation-specific activity of gastric smooth muscles relayed by vagal afferent neurons. Significance. This finding suggests that the orientation of GES is critical to effective engagement of vagal afferents and should be considered in light of the structural phenotypes of vagal terminals in the stomach.
Integral order photonic RF signal processors based on a soliton crystal micro-comb source
Authors: Tan Mengxi , Xu Xingyuan , Wu Jiayang , Corcoran Bill , Boes Andreas , Nguyen Thach G , Chu Sai T , Little Brent E , Morandotti Roberto , Mitchell Arnan , Moss David J
Published: October 2021

Soliton crystal micro-combs are powerful tools as sources of multiple wavelength channels for radio frequency (RF) signal processing. They offer a compact device footprint, a large number of wavelengths, very high versatility, and wide Nyquist bandwidths. Here, we demonstrate integral order RF signal processing functions based on a soliton crystal micro-comb, including a Hilbert transformer and first, second and third-order differentiators. We compare and contrast the results and the trade-offs involved with varying the comb spacing, and tap design and shaping methods.
MS2AI: automated repurposing of public peptide LC-MS data for machine learning applications
Authors: Rehfeldt Tobias Greisager , Krawczyk Konrad , Bøgebjerg Mathias , Schwämmle Veit , Röttger Richard
Published: October 2021

Motivation

Liquid-chromatography mass-spectrometry (LC-MS) is the established standard for analyzing the proteome in biological samples by identification and quantification of thousands of proteins. Machine learning (ML) promises to considerably improve the analysis of the resulting data, however, there is yet to be any tool that mediates the path from raw data to modern ML applications. More specifically, ML applications are currently hampered by three major limitations: (i) absence of balanced training data with large sample size; (ii) unclear definition of sufficiently information-rich data representations for e.g. peptide identification; (iii) lack of benchmarking of ML methods on specific LC-MS problems.

Results

We created the MS2AI pipeline that automates the process of gathering vast quantities of MS data for large-scale ML applications. The software retrieves raw data from either in-house sources or from the proteomics identifications database, PRIDE. Subsequently, the raw data are stored in a standardized format amenable for ML, encompassing MS1/MS2 spectra and peptide identifications. This tool bridges the gap between MS and AI, and to this effect we also present an ML application in the form of a convolutional neural network for the identification of oxidized peptides.

Availability and implementation

An open-source implementation of the software can be found at https://gitlab.com/roettgerlab/ms2ai

Supplementary information

Supplementary data are available at Bioinformatics online.
Reflections after TWILIGHT study: a new era in secondary prevention without aspirin?
Authors: Occhipinti Giovanni , Capodanno Davide
Published: October 2021

Dual antiplatelet therapy (DAPT) is mandatory in patients undergoing percutaneous coronary interventions (PCIs), but carries an increased bleeding risk which must be weighed over the expected antithrombotic benefit. In recent years, DAPT optimization strategy has been enriched by the concept of early withdrawal of aspirin (‘aspirin-free’ strategy). This strategy is supported by the modern advancements in pharmacological and procedural fields (i.e. the availability of P2Y12 receptor inhibitors with a concomitant ‘aspirin-like’ effect), the advocated use of pharmacological non-antiplatelet secondary prevention strategies (i.e. angiotensin-converting enzyme inhibitor, statins, beta-blockers), the use of modern stents and the increasingly widespread use of intra-coronary imaging techniques. In the last few years, five clinical trials (GLOBAL LEADERS, TWILIGHT, STOP-DAPT2, SMART CHOICE, TICO) and their own meta-analysis have been followed, aiming to evaluate the efficacy and safety of different ‘aspirin-free’ strategies. They showed that aspirin withdrawal (1–3 months after PCI), determines a consistent reduction of bleeding risk, without compromising efficacy endpoints. It resulted in a class IIa indication in the 2020 European Society of Cardiology Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation, which suggested the early withdrawal of aspirin in patients undergoing PCI and considered to be at low ischaemic and low bleeding risk, or at high bleeding risk.
New insights from the MESA study: increased high-sensitivity troponins as a cardiovascular risk factor
Authors: Muscente Francesca , De Caterina Raffaele
Published: October 2021

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

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

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

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

Hypercholesterolaemic patients at an advanced age (>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 >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

Objectives

This 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.

Method

The 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.

Results

LCA 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.

Discussion

War 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

To 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

Offensive 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

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

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

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 < .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 < .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

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

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

Introduction

Dynamics 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.

Methods

Data 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.

Results

One 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.

Discussion

Although 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.
Design and assembly of DNA molecules using multi-objective optimization
Authors: Gaeta Angelo , Zulkower Valentin , Stracquadanio Giovanni
Published: October 2021

Rapid engineering of biological systems is currently hindered by limited integration of manufacturing constraints into the design process, ultimately reducing the yield of many synthetic biology workflows. Here we tackle DNA engineering as a multi-objective optimization problem aiming at finding the best tradeoff between design requirements and manufacturing constraints. We developed a new open-source algorithm for DNA engineering, called Multi-Objective Optimisation algorithm for DNA Design and Assembly, available as a Python and Anaconda package, as well as a Docker image. Experimental results show that our method provides near-optimal constructs and scales linearly with design complexity, effectively paving the way to rational engineering of DNA molecules from genes to genomes.