bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution to the ongoing discussion on fluoride toxicity
Authors: Guth Sabine , Hüser Stephanie , Roth Angelika , Degen Gisela , Diel Patrick , Edlund Karolina , Eisenbrand Gerhard , Engel Karl-Heinz , Epe Bernd , Grune Tilman , Heinz Volker , Henle Thomas , Humpf Hans-Ulrich , Jäger Henry , Joost Hans-Georg , Kulling Sabine E. , Lampen Alfonso , Mally Angela , Marchan Rosemarie , Marko Doris , Mühle Eva , Nitsche Michael A. , Röhrdanz Elke , Stadler Richard , van Thriel Christoph , Vieths Stefan , Vogel Rudi F. , Wascher Edmund , Watzl Carsten , Nöthlings Ute , Hengstler Jan G.
Published: June 2021

Since the addition of fluoride to drinking water in the 1940s, there have been frequent and sometimes heated discussions regarding its benefits and risks. In a recently published review, we addressed the question if current exposure levels in Europe represent a risk to human health. This review was discussed in an editorial asking why we did not calculate benchmark doses (BMD) of fluoride neurotoxicity for humans. Here, we address the question, why it is problematic to calculate BMDs based on the currently available data. Briefly, the conclusions of the available studies are not homogeneous, reporting negative as well as positive results; moreover, the positive studies lack control of confounding factors such as the influence of well-known neurotoxicants. We also discuss the limitations of several further epidemiological studies that did not meet the inclusion criteria of our review. Finally, it is important to not only focus on epidemiological studies. Rather, risk analysis should consider all available data, including epidemiological, animal, as well as in vitro studies. Despite remaining uncertainties, the totality of evidence does not support the notion that fluoride should be considered a human developmental neurotoxicant at current exposure levels in European countries.
Topological Singular Set of Vector-Valued Maps, II: $$\varGamma $$-convergence for Ginzburg–Landau type functionals
Authors: Canevari Giacomo , Orlandi Giandomenico
Published: June 2021

We prove a $$\varGamma $$Γ-convergence result for a class of Ginzburg–Landau type functionals with $${\mathscr {N}}$$N-well potentials, where $${\mathscr {N}}$$Nis a closed and$$(k-2)$$(k-2)-connected submanifold of $${\mathbb {R}}^m$$Rm, in arbitrary dimension. This class includes, for instance, the Landau-de Gennes free energy for nematic liquid crystals. The energy density of minimisers, subject to Dirichlet boundary conditions, converges to a generalised surface (more precisely, a flat chain with coefficients in $$\pi _{k-1}({\mathscr {N}})$$πk-1(N)) which solves the Plateau problem in codimension k. The analysis relies crucially on the set of topological singularities, that is, the operator $${\mathbf {S}}$$Swe introduced in the companion paper [17].
Management of Obscurely Dilated Common Bile Duct with Normal Liver Function Tests: A Pragmatic Approach
Authors: Saluja Sundeep Singh , Varshney Vaibhav Kumar , Bhat Vidya Sharada , Nekarakanti Phani Kumar , Arora Asit , Sachdeva Sanjeev , Mishra Pramod Kumar
Published: June 2021

Objective

Dilated common bile duct (CBD) (8–15 mm) with normal liver function tests is seen not infrequently, while management of such patients is ambiguous. We propose a treatment algorithm for this cohort of patients after observing them over a period of 8 years.

Methods

Seventy‐eight such patients were managed from 2009 to 2017 and categorized as: Group A—dilated CBD with post‐cholecystectomy status (n = 15); B—dilated CBD with cholelithiasis (n = 34); C—dilated CBD without cholelithiasis (n = 16); D—dilated CBD with no cause identified and underwent CBD excision (n = 13). Causes for CBD dilatation were evaluated. The outcome of patients in Group B + C without any cause (n = 33) was compared with Group D.

Result

Median age, CBD diameter, bilirubin and alkaline phosphatase were 51 years (13–79), 10 mm (8–20), 0.6 mg/dl (0.2–2.5) and 126 IU (60–214), respectively. Group‐A patients who did not manifest any cause of CBD dilatation were managed conservatively. The aetiology was identified in 17/50 patients in Group B & C [acute pancreatitis (n = 6), passed CBD calculi (n = 3), perivaterian diverticulum (n = 3), viral aetiology (n = 4) and tumour (n‐1)]. In Group‐C, 7 patients with no obvious cause underwent endoscopic sphincterotomy, pancreatoduodenectomy (n = 1), and the rest were managed conservatively (n = 8). There was no significant difference in the complication between Group B + C (without any cause) and Group D (3/33 vs. 1/13; p = 0.58) at a median follow‐up of 72 months (30–90).

Conclusion

Dilated CBD with normal LFT's without apparent cause is mostly benign and of no consequence. Excision of the CBD is not required for most of these patients.
Reversible protein aggregation as cytoprotective mechanism against heat stress
Authors: Gallardo Paola , Salas-Pino Silvia , Daga Rafael R.
Published: June 2021

Temperature fluctuation is one of the most frequent threats to which organisms are exposed in nature. The activation of gene expression programs that trigger the transcription of heat stress-protective genes is the main cellular response to resist high temperatures. In addition, reversible accumulation and compartmentalization of thermosensitive proteins in high-order molecular assemblies are emerging as critical mechanisms to ensure cellular protection upon heat stress. Here, we summarize representative examples of membrane-less intracellular bodies formed upon heat stress in yeasts and human cells and highlight how protein aggregation can be turned into a cytoprotective mechanism.
Hypertension and dyslipidemia are risk factors for herpes zoster in patients with rheumatoid arthritis: a retrospective analysis using a medical information database
Authors: Tanaka Keiko , Kimura Eizen , Oryoji Kensuke , Mizuki Shin-ichi , Kobayashi Tomoko , Nishikawa Atsushi , Yoshinaga Eiko , Miyake Yoshihiro
Published: June 2021

This study used data from a large-scale multicenter medical information database in Japan to estimate the incidence rate of herpes zoster (HZ) and to examine the relationship between hypertension, dyslipidemia, and diabetes mellitus (DM), and the risk of HZ among patients with rheumatoid arthritis (RA). The research dataset consisted of 221,196 records of potential target patients with RA extracted between April 1, 2008 and August 31, 2017 from the Medical Data Vision database. To assess the association between hypertension, dyslipidemia, and DM and the risk of HZ, a case–control study was set up. Records of 101,498 study subjects met the inclusion criteria. During the observation period, 2566 patients developed HZ and the overall incidence rate was 5.2 (95% confidence interval: 5.0–5.4 per 1000 patient-years). Hypertension, dyslipidemia, and DM were significantly associated with an increased risk of HZ after adjustment for sex, age, hospital size, and use of anti-rheumatic drugs. When mutual adjustment was made for hypertension, dyslipidemia, and DM, the positive associations between hypertension and dyslipidemia and the risk of HZ remained significant; however, the positive association with DM completely disappeared. RA patients with hypertension or dyslipidemia may be at higher risk of HZ.
COVID-19 pneumonia in a patient with granulomatosis with polyangiitis on rituximab: case-based review
Authors: Rodriguez-Pla Alicia , Vikram Holenarasipur R. , Khalid Vanood , Wesselius Lewis J.
Published: June 2021

A 77-year-old man with past medical history of granulomatosis with polyangiitis (GPA) on rituximab and prednisone, presented to the hospital with worsening cough and shortness of breath. He had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by nasal swab polymerase chain reaction (PCR) while asymptomatic, 6 weeks earlier. He started with cough and shortness of breath 2 weeks after his initial positive test. After developing symptoms, he tested negative twice by nasal swab PCR, but the PCR of his bronchioloalveolar lavage was positive for SARS-CoV-2. He did not develop antibodies against coronavirus. Prednisone 15 mg daily was continued, and he received remdesivir, and convalescent plasma with quick recovery. We reviewed the literature to search for similar cases. Our case suggests that SARS-CoV-2 infection in patients on rituximab may have an atypical presentation and the diagnosis may be delayed due to negative PCR testing in the nasal swab. Patients may benefit from treatment with convalescent plasma.
Utilizing MIKC-type MADS-box protein SOC1 for yield potential enhancement in maize
Authors: Song Guo-qing , Han Xue , Ryner John T. , Thompson Addie , Wang Kan
Published: June 2021

Key message

Overexpression of Zea mays SOC gene promotes flowering, reduces plant height, and leads to no reduction in grain production per plant, suggesting enhanced yield potential, at least, through increasing planting density.

MIKC-type MADS-box gene SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) is an integrator conserved in the plant flowering pathway. In this study, the maize SOC1 (ZmSOC1) gene was cloned and overexpressed in transgenic maize Hi-II genotype. The T0 plants were backcrossed with nontransgenic inbred B73 to produce first generation backcross (BC1) seeds. Phenotyping of both transgenic and null segregant (NT) BC1 plants was conducted in three independent experiments. The BC1 transgenic plants showed new attributes such as increased vegetative growth, accelerated flowering time, reduced overall plant height, and increased grain weight. Second generation backcross (BC2) plants were evaluated in the field using two planting densities. Compared to BC2 NT plants, BC2 transgenic plants, were 12–18% shorter, flowered 5 days earlier, and showed no reduction in grain production per plant and an increase in fat, starch, and simple sugars in the grain. Transcriptome comparison in young leaves of 56-day-old BC1 plants revealed that the overexpressed ZmSOC1 resulted in 107 differentially expressed genes. The upregulated transcription factor DNA BINDING WITH ONE FINGER 5.4 (DOF5.4) was among the genes responsible for the reduced plant height. Modulating expression of SOC1 opens a new and effective approach to promote flowering and reduce plant height, which may have potential to enhance crop yield and improve grain quality.
A parallel dual marching cubes approach to quad only surface reconstruction
Authors: Grosso Roberto , Zint Daniel
Published: June 2021

We present a novel method that reconstructs surfaces from volume data using a dual marching cubes approach without lookup tables. The method generates quad only meshes which are consistent across cell borders, i.e., they are manifold and watertight. Vertices are positioned exactly on the reconstructed surface almost everywhere, leading to higher accuracy than other reconstruction methods. A halfedge data structure is used for storing the meshes which is convenient for further processing. The method processes elements in parallel and therefore runs efficiently on GPU. Due to the transition between layers in volume data, meshes have numerous vertices with valence three. We use simplification patterns for eliminating quads containing these vertices wherever possible which reduces the number of elements and increases quality. We briefly describe a CUDA implementation of our method, which allows processing huge amounts of data on GPU at almost interactive time rates. Finally, we present runtime and quality results of our method on medical and synthetic data sets.
Effects of face masks on performance and cardiorespiratory response in well-trained athletes
Authors: Egger Florian , Blumenauer Dominic , Fischer Patrick , Venhorst Andreas , Kulenthiran Saarraaken , Bewarder Yvonne , Zimmer Angela , Böhm Michael , Meyer Tim , Mahfoud Felix
Published: June 2021

Background

During the COVID-19 pandemic, compulsory masks became an integral part of outdoor sports such as jogging in crowded areas (e.g. city parks) as well as indoor sports in gyms and sports centers. This study, therefore, aimed to investigate the effects of medical face masks on performance and cardiorespiratory parameters in athletes.

Methods

In a randomized, cross-over design, 16 well-trained athletes (age 27 ± 7 years, peak oxygen consumption 56.2 ± 5.6 ml kg−1 min−1, maximum performance 5.1 ± 0.5 Watt kg−1) underwent three stepwise incremental exercise tests to exhaustion without mask (NM), with surgical mask (SM) and FFP2 mask (FFP2). Cardiorespiratory and metabolic responses were monitored by spiroergometry and blood lactate (BLa) testing throughout the tests.

Results

There was a large effect of masks on performance with a significant reduction of maximum performance with SM (355 ± 41 Watt) and FFP2 (364 ± 43 Watt) compared to NM (377 ± 40 Watt), respectively (p < 0.001; ηp2 = 0.50). A large interaction effect with a reduction of both oxygen consumption (p < 0.001; ηp2 = 0.34) and minute ventilation (p < 0.001; ηp2 = 0.39) was observed. At the termination of the test with SM 11 of 16 subjects reported acute dyspnea from the suction of the wet and deformed mask. No difference in performance was observed at the individual anaerobic threshold (p = 0.90).

Conclusion

Both SM and to a lesser extent FFP2 were associated with reduced maximum performance, minute ventilation, and oxygen consumption. For strenuous anaerobic exercise, an FFP2 mask may be preferred over an SM.
Prospective study on the Eustachian tube function during Frenzel maneuver in a hypobaric/hyperbaric pressure chamber
Authors: Wolber Philipp , Meyer Moritz Friedo , Knesic Kristijana , Rink Svenja , Jansen Stefanie , Klussmann Jens Peter , Grosheva Maria
Published: June 2021

Introduction

The Frenzel maneuver describes a technique for middle ear equalizing which is frequently used by apnea divers. It offers advantages compared to the most commonly used techniques such as the Valsalva or Toynbee maneuver. Until now, there is insufficient literature about the pressure dynamics and Eustachian tube (ET) function during the Frenzel maneuver. The aim of the present study was to characterize the ET function during the Frenzel maneuver.

Materials and methods

By means of an established standardized profile of compression and decompression in a hypo/hyperbaric pressure chamber, we examined different parameters such as the ET opening pressure (ETOP), ET opening duration (ETOD), and ET opening frequency (ETOF) in 11 experienced apnea divers and compared them to the parameters during the Valsalva and Toynbee maneuver.

Results

Standard values for ETOP, ETOD, and ETOF could be established for the Frenzel maneuver under standardized conditions in a hypo/hyperbaric pressure chamber. Compared to the Frenzel maneuver, ETOP was higher and ETOD longer (both p < 0.001) during the Valsalva maneuver whereas ETOP was lower and ETOD shorter (both p < 0.001) during the Toynbee maneuver. No difference regarding ETOF was observed between the Frenzel, Valsalva, and Toynbee maneuver.

Discussion

The Frenzel maneuver was shown to be at least as effective as the Valsalva maneuver concerning ET opening. We believe that knowledge of the Frenzel technique might facilitate the pressure equalization during diving and recommend implementation of an appropriate equalization training in apnea and scuba diving education.
Frequent short sickness absence, occupational health service utilisation and long-term sickness absence due to mental disorders among young employees
Authors: Harkko Jaakko , Nordquist Hilla , Pietiläinen Olli , Piha Kustaa , Mänty Minna , Lallukka Tea , Rahkonen Ossi , Kouvonen Anne
Published: June 2021

Objectives

We examined whether frequent short-term sickness absence (FSTSA) and primary care use in occupational health service (OHS) were associated with medically-certified long-term sickness absence (LTSA) due to mental disorders among young employees.

Methods

We used record-linkage data covering the young employees (< 35 years) of the City of Helsinki, Finland (n = 8,282) from 2010 to 2014. The outcome was LTSA due to mental disorders. Cox regression models were fitted.

Results

FSTSAs were associated with subsequent LTSA. Also OHS use predicted LTSA due to mental disorders; however, this association was not found for those with prior FSTSA.

Conclusions

Both FSTSA and primary care use indicate subsequent LTSA independently, and together these indicators identify a larger proportion of individuals at risk of LTSA due to mental disorders.
Transmission of cell-associated human cytomegalovirus isolates between various cell types using polymorphonuclear leukocytes as a vehicle
Authors: Braun Berenike , Sinzger Christian
Published: June 2021

Polymorphonuclear leukocytes (PMNs) are regarded as vehicles for the hematogenous dissemination of human cytomegalovirus (HCMV). In cell culture, this concept has been validated with cell-free laboratory strains but not yet with clinical HCMV isolates that grow strictly cell-associated. We, therefore, aimed to evaluate whether PMNs can also transmit such isolates from initially infected fibroblasts to other cell types, which might further clarify the role of PMNs in HCMV dissemination and provide a model to search for potential inhibitors. PMNs, which have been isolated from HCMV-seronegative individuals, were added for 3 h to fibroblasts infected with recent cell-associated HCMV isolates, then removed and transferred to various recipient cell cultures. The transfer efficiency in the recipient cultures was evaluated by immunofluorescence staining of viral immediate early antigens. Soluble derivatives of the cellular HCMV entry receptor PDGFRα were analyzed for their potential to interfere with this transfer. All of five tested HCMV isolates could be transferred to fibroblasts, endothelial and epithelial cells with transfer rates ranging from 2 to 9%, and the transferred viruses could spread focally in these recipient cells within 1 week. The PDGFRα-derived peptides IK40 and GT40 reduced transfer by 40 and 70% when added during the uptake step. However, when added during the transfer step, only IK40 was effective, inhibiting transmission by 20% on endothelial cells and 50–60% on epithelial cells and fibroblasts. These findings further corroborate the assumption of cell-associated HCMV dissemination by PMNs and demonstrate that it is possible to inhibit this transmission mode.
Effects of plant species diversity on nematode community composition and diversity in a long-term biodiversity experiment
Authors: Dietrich Peter , Cesarz Simone , Liu Tao , Roscher Christiane , Eisenhauer Nico
Published: June 2021

Diversity loss has been shown to change the soil community; however, little is known about long-term consequences and underlying mechanisms. Here, we investigated how nematode communities are affected by plant species richness and whether this is driven by resource quantity or quality in 15-year-old plant communities of a long-term grassland biodiversity experiment. We extracted nematodes from 93 experimental plots differing in plant species richness, and measured above- and belowground plant biomass production and soil organic carbon concentrations (Corg) as proxies for resource quantity, as well as C/Nleaf ratio and specific root length (SRL) as proxies for resource quality. We found that nematode community composition and diversity significantly differed among plant species richness levels. This was mostly due to positive plant diversity effects on the abundance and genus richness of bacterial-feeding, omnivorous, and predatory nematodes, which benefited from higher shoot mass and soil Corg in species-rich plant communities, suggesting control via resource quantity. In contrast, plant-feeding nematodes were negatively influenced by shoot mass, probably due to higher top–down control by predators, and were positively related to SRL and C/Nleaf, indicating control via resource quality. The decrease of the grazing pressure ratio (plant feeders per root mass) with plant species richness indicated a higher accumulation of plant-feeding nematodes in species-poor plant communities. Our results, therefore, support the hypothesis that soil-borne pathogens accumulate in low-diversity communities over time, while soil mutualists (bacterial-feeding, omnivorous, predatory nematodes) increase in abundance and richness in high-diversity plant communities, which may contribute to the widely-observed positive plant diversity–productivity relationship.
Pediatric idiopathic steroid-sensitive nephrotic syndrome: diagnosis and therapy —short version of the updated German best practice guideline (S2e) — AWMF register no. 166-001, 6/2020
Authors: Ehren Rasmus , Benz Marcus R. , Brinkkötter Paul T. , Dötsch Jörg , Eberl Wolfgang R. , Gellermann Jutta , Hoyer Peter F. , Jordans Isabelle , Kamrath Clemens , Kemper Markus J. , Latta Kay , Müller Dominik , Oh Jun , Tönshoff Burkhard , Weber Stefanie , Weber Lutz T. ,   on behalf of the German Society for Pediatric Nephrology
Published: June 2021

Idiopathic nephrotic syndrome is the most frequent glomerular disease in children in most parts of the world. Children with steroid-sensitive nephrotic syndrome (SSNS) generally have a good prognosis regarding the maintenance of normal kidney function even in the case of frequent relapses. The course of SSNS is often complicated by a high rate of relapses and the associated side effects of repeated glucocorticoid (steroid) therapy. The following recommendations for the treatment of SSNS are based on the comprehensive consideration of published evidence by a working group of the German Society for Pediatric Nephrology (GPN) based on the systematic Cochrane reviews on SSNS and the guidelines of the KDIGO working group (Kidney Disease - Improving Global Outcomes).
Smart aging monitoring and early dementia recognition (SAMEDR): uncovering the hidden wellness parameter for preventive well-being monitoring to categorize cognitive impairment and dementia in community-dwelling elderly subjects through AI
Authors: Ghayvat Hemant , Gope Prosanta
Published: June 2021

Reasoning weakening because of dementia degrades the performance in activities of daily living (ADL). Present research work distinguishes care needs, dangers and monitors the effect of dementia on an individual. This research contrasts in ADL design execution between dementia-affected people and other healthy elderly with heterogeneous sensors. More than 300,000 sensors associated activation data were collected from the dementia patients and healthy controls with wellness sensors networks. Generated ADLs were envisioned and understood through the activity maps, diversity and other wellness parameters to categorize wellness healthy, and dementia affected the elderly. Diversity was significant between diseased and healthy subjects. Heterogeneous unobtrusive sensor data evaluate behavioral patterns associated with ADL, helpful to reveal the impact of cognitive degradation, to measure ADL variation throughout dementia. The primary focus of activity recognition in the current research is to transfer dementia subject occupied homes models to generalized age-matched healthy subject data models to utilize new services, label classified datasets and produce limited datasets due to less training. Current research proposes a novel Smart Aging Monitoring and Early Dementia Recognition system that provides the exchange of data models between dementia subject occupied homes (DSOH) to healthy subject occupied homes (HSOH) in a move to resolve the deficiency of training data. At that point, the key attributes are mapped onto each other utilizing a sensor data fusion that assures to retain the diversities between various HSOH & DSOH by diminishing the divergence between them. Moreover, additional tests have been conducted to quantify the excellence of the offered framework: primary, in contradiction of the precision of feature mapping techniques; next, computing the merit of categorizing data at DSOH; and, the last, the aptitude of the projected structure to function thriving due to noise data. The outcomes show encouraging pointers and highlight the boundaries of the projected approach.
Effect of the Rock Stress on the Water Jet Cutting Performance
Authors: Grosso Battista , Dentoni Valentina , Bortolussi Augusto
Published: June 2021

Underground quarrying is rarely adopted for granite extraction due to the difficulties in the implementation of traditional technologies (drilling and explosive). As alternative to drilling and explosive, the combination of diamond wire and water jet seems to be the most promising available technology. The cutting performance achievable with the water jet technology depends on the operative parameters, the material characteristics and the state of stress within the rock massif. To assess the effect of the state of stress on the cutting rate, laboratory tests have been performed with an oscillating water jet machine on granite samples subjected to a static load. The stress distribution in the layer of rock to be removed has been evaluated by numerical simulation with the FLAC code (Fast Lagrangian Analysis of Continua). The correlation between the results of the cutting tests and the numerical models of the rock samples has been inferred. Starting from a conceptual model, which theoretically describes the relationship between the cutting rate and the stress, a step function was defined that indicates the ranges of stress where predefined values of the cutting rate are workable.
A novel genomic classification system of gastric cancer via integrating multidimensional genomic characteristics
Authors: Wang Haiyong , Ding Yongfeng , Chen Yanyan , Jiang Junjie , Chen Yiran , Lu Jun , Kong Mei , Mo Fan , Huang Yingying , Zhao Wenyi , Fang Ping , Chen Xiangliu , Teng Xiaodong , Xu Nong , Lu Yimin , Yu Xiongfei , Li Zhongqi , Zhang Jing , Wang Haohao , Bao Xuanwen , Zhou Donghui , Chi Ying , Zhou Tianhua , Zhou Zhan , Chen Shuqing , Teng Lisong
Published: June 2021

Background

Gastric cancer (GC) is one of the leading causes of cancer deaths with high heterogeneity. There is currently a paucity of clinically applicable molecular classification system to guide precise medicine.

Methods

A total of 70 Chinese patients with GC were included in this study and whole-exome sequencing was performed. Unsupervised clustering was undertaken to identify genomic subgroups, based on mutational signature, copy number variation, neoantigen, clonality, and essential genomic alterations. Subgroups were characterized by clinicopathological factors, molecular features, and prognosis.

Results

We identified 32 significantly mutated genes (SMGs), including TP53, ARID1A, PIK3CA, CDH1, and RHOA. Of these, PREX2, PIEZO1, and FSIP2 have not been previously reported in GC. Using a novel genome-based classification method that integrated multidimensional genomic features, we categorized GC into four subtypes with distinct clinical phenotypes and prognosis. Subtype 1, which was predominantly Lauren intestinal type, harbored recurrent TP53 mutation and ERBB2 amplification, high tumor mutation burden (TMB)/tumor neoantigen burden (TNB), and intratumoral heterogeneity, with a liver metastasis tendency. Subtype 2 tended to occur at an elder age, accompanying with frequent TP53 and SYNE1 mutations, high TMB/TNB, and was associated with poor prognosis. Subtype 3 and subtype 4 included patients with mainly diffuse/mixed type tumors, high frequency of peritoneal metastasis, and genomical stability, whereas subtype 4 was associated with a favorable prognosis.

Conclusions

By integrating multidimensional genomic characteristics, we proposed a novel genomic classification system of GC associated with clinical phenotypes and provided a new insight to facilitate genome-guided risk stratification and disease management.
Comparison between 1973 and 2004/2016 World Health Organization grading in upper tract urothelial carcinoma treated with radical nephroureterectomy
Authors: Collà Ruvolo Claudia , Würnschimmel Christoph , Wenzel Mike , Nocera Luigi , Celentano Giuseppe , Mangiapia Francesco , Tian Zhe , Shariat Shahrokh F. , Saad Fred , Chun Felix H. C. , Briganti Alberto , Longo Nicola , Mirone Vincenzo , Karakiewicz Pierre I.
Published: June 2021

Aims

The European Association of Urology guideline for upper tract urothelial carcinoma (UTUC) relies on two grading system: 1973 World Health Organization (WHO) and 2004/2016 WHO. No consensus has been made which classification should supersede the other and both are recommended in clinical practice. We hypothesized that one may be superior to the other.

Methods

Newly diagnosed non-metastatic UTUC patients treated with radical nephroureterectomy were abstracted from the Surveillance, Epidemiology, and End Results database (2010–2016). Kaplan–Meier plots and multivariable Cox regression models (CRMs) tested cancer-specific mortality (CSM), according to 1973 WHO (G1 vs. G2 vs. G3) or to 2004/2016 WHO (low-grade vs. high-grade) grading systems. Haegerty’s C-index quantified accuracy.

Results

Of 4271 patients, according to 1973 WHO grading system, 134 (3.1%) were G1, 436 (10.2%) were G2 and 3701 (86.7%) were G3; while according to 2004/2016 WHO grading system, 508 (11.9%) were low grade vs 3763 (88.1%) high grade. In multivariable CRMs, high grade predicted higher CSM (Hazard ratio: 1.70, p < 0.001). Conversely, neither G2 (p = 0.8) nor G3 (p = 0.1) were independent predictors of worse survival. The multivariable models without consideration of either grading system were 74% accurate in predicting 5-year CSM. Accuracy increased to 76% after either addition of the 1973 WHO or 2004/2016 WHO grade.

Conclusions

From a statistical standpoint, either 1973 WHO or 2004/2016 WHO grading system improves the accuracy of CSM prediction to the same extent. In consequence, other considerations such as intra- and interobserver variability may represent additional metrics to consider in deciding which grading system is better.
Comparing the measurement properties of the ICECAP-A and ICECAP-O instruments in ages 50–70: a cross-sectional study on a representative sample of the Hungarian general population
Authors: Baji Petra , Farkas Miklós , Dobos Ágota , Zrubka Zsombor , Kovács Levente , Gulácsi László , Péntek Márta
Published: June 2021

Objective

The ICECAP-A and ICECAP-O were validated as capability wellbeing measures of adults aged 18 + and 65 + years, respectively. We aimed to compare their measurement properties in age group 50–70.

Methods

Data were derived from a cross-sectional survey among a sample representative for the adult Hungarian population. Respondents aged between 50 and 70 filled in both the ICECAP-A and ICECAP-O questionnaires. We assessed and compared feasibility, agreement, discriminatory power, convergent and content validity of the two instruments and explored the determinants of the differences between the two measures.

Results

707 respondents (99.4%) provided full answers to both questionnaires (46.3% women, average age 60.1 years). The instruments showed similar construct and convergent validity and discriminatory power. Pearson-correlations between instrument items were strong (r > 0.5). ICECAP-A and ICECAP-O scores could be calculated from each other with a good confidence (R2 = 0.69 and 0.71). ICECAP-O scores (mean 0.87, SD = 0.12) were systematically higher than ICECAP-A scores (0.85, SD = 0.15) in most subgroups. The difference increased with the deterioration of capability and health, and with age. Regression results showed that employment and health status had larger marginal effect on the ICECAP-A than on the ICECAP-O scores, and these effects were larger than the effect of age on both measures.

Conclusion

Validity of both instruments was confirmed in the age groups 50–70. Given that employment and health status are important determinants of the differences between the two instruments besides age, the possibility of linking the choice between ICECAP-A and ICECAP-O to these factors should be investigated by further research.
Applying NLP techniques to malware detection in a practical environment
Authors: Mimura Mamoru , Ito Ryo
Published: June 2021

Executable files still remain popular to compromise the endpoint computers. These executable files are often obfuscated to avoid anti-virus programs. To examine all suspicious files from the Internet, dynamic analysis requires too much time. Therefore, a fast filtering method is required. With the recent development of natural language processing (NLP) techniques, printable strings became more effective to detect malware. The combination of the printable strings and NLP techniques can be used as a filtering method. In this paper, we apply NLP techniques to malware detection. This paper reveals that printable strings with NLP techniques are effective for detecting malware in a practical environment. Our dataset consists of more than 500,000 samples obtained from multiple sources. Our experimental results demonstrate that our method is effective to not only subspecies of the existing malware, but also new malware. Our method is effective against packed malware and anti-debugging techniques.
The cost of risk management and multifunctionality in forestry: a simulation approach for a case study area in Southeast Germany
Authors: Friedrich Stefan , Hilmers Torben , Chreptun Claudia , Gosling Elizabeth , Jarisch Isabelle , Pretzsch Hans , Knoke Thomas
Published: June 2021

Forest management faces growing uncertainty concerning environmental conditions and demand for ecosystem services. To help forest managers consider uncertainty, we applied a robust and multi-criteria approach to select the optimal composition of a forest enterprise from 12 stand types. In our simulation, the forest enterprise strives for either financial return or a multi-criteria forest management considering financial return, carbon storage and forest ecosystem stability. To quantify the influence of climate change on these decision criteria, we used the concept of analogous climate zones. Our results provide recommendations for long-term strategies for tree species selection in a Southeast German forest enterprise. The results show that considering both uncertainty and multifunctionality in forest management led to more diversified forest compositions. However, robust and multi-criteria optimisation required the forest enterprise to pay a premium in terms of lower income. Financial returns decreased when forest composition accounted for uncertainty or multiple objectives. We also found that adaptation measures could only partly financially compensate the effects of climate change. As the study is limited to two tree species, including additional tree species, variants of mixing proportions and further silvicultural strategies in the optimisation appears a promising avenue for future research.
Meta-analysis of epigenome-wide association studies of carotid intima-media thickness
Authors: Portilla-Fernández Eliana , Hwang Shih-Jen , Wilson Rory , Maddock Jane , Hill W. David , Teumer Alexander , Mishra Pashupati P. , Brody Jennifer A. , Joehanes Roby , Ligthart Symen , Ghanbari Mohsen , Kavousi Maryam , Roks Anton J. M. , Danser A. H. Jan , Levy Daniel , Peters Annette , Ghasemi Sahar , Schminke Ulf , Dörr Marcus , Grabe Hans J. , Lehtimäki Terho , Kähönen Mika , Hurme Mikko A. , Bartz Traci M. , Sotoodehnia Nona , Bis Joshua C. , Thiery Joachim , Koenig Wolfgang , Ong Ken K. , Bell Jordana T. , Meisinger Christine , Wardlaw Joanna M. , Starr John M. , Seissler Jochen , Then Cornelia , Rathmann Wolfgang , Ikram M. Arfan , Psaty Bruce M. , Raitakari Olli T. , Völzke Henry , Deary Ian J. , Wong Andrew , Waldenberger Melanie , O’Donnell Christopher J. , Dehghan Abbas
Published: June 2021

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.
Impact of COVID-19 pandemic lockdown on myocardial infarction care
Authors: Schmitz Timo , Meisinger Christa , Kirchberger Inge , Thilo Christian , Amann Ute , Baumeister Sebastian E. , Linseisen Jakob
Published: June 2021

The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors in the German model region for complete AMI registration. The analysis was based on data from the population-based KORA Myocardial Infarction Registry located in the region of Augsburg, Germany. All cases of AMI (n = 210) admitted to one of four hospitals in the city of Augsburg or the county of Augsburg from February 10th, 2020, to May 19, 2020, were included. Patients were divided into three groups, namely pre-lockdown, strict lockdown, and attenuated lockdown period. An additional survey was conducted asking the patients for stress and fears in the 4 weeks prior to their AMI. The AMI rate declined by 44% in the strict lockdown period; in the attenuated lockdown period the rate was 17% lower compared to the pre-lockdown period. The downward trend in AMI rates during lockdown was seen in STEMI and NSTEMI patients, and independent of sex and age. The door-to-device time decreased by 70–80% in the lockdown-periods. In the time prior to the infarction, patients felt stressed mainly due to fear of infection with Sars-CoV-2 and less because of the restrictions and consequences of the lockdown. A strict lockdown due to the Covid-19 pandemic had a marked impact on AMI care even in a non-hot-spot region with relatively few cases of COVID-19. Fear of infection with the virus is presumably the main reason for the drop in hospitalizations due to AMI.
Structural Characterization of Heterodinuclear ZnII-LnIII Complexes (Ln = Pr, Nd) with a Ring-Contracted H2valdien-Derived Schiff Base Ligand
Authors: Noor Shabana , Goddard Richard , Khatoon Fehmeeda , Kumar Sarvendra , Seidel Rüdiger W.
Published: June 2021

Synthesis and structural characterization of two heterodinuclear ZnII-LnIII complexes with the formula [ZnLn(HL)(µ-OAc)(NO3)2(H2O)x(MeOH)1-x]NO3 · n H2O · n MeOH [Ln = Pr (1), Nd (2)] and the crystal and molecular structure of [ZnNd(HL)(µ-OAc)(NO3)2(H2O)] [ZnNd(HL)(OAc)(NO3)2(H2O)](NO3)2 · n H2O · n MeOH (3) are reported. The asymmetrical compartmental ligand (E)-2-(1-(2-((2-hydroxy-3-methoxybenzylidene)amino)-ethyl)imidazolidin-2-yl)-6-methoxyphenol (H2L) is formed from N1,N3-bis(3-methoxysalicylidene)diethylenetriamine (H2valdien) through intramolecular aminal formation, resulting in a peripheral imidazoline ring. The structures of 1–3 were revealed by X-ray crystallography. The smaller ZnII ion occupies the inner N2O2 compartment of the ligand, whereas the larger and more oxophilic LnIII ions are found in the outer O2O2’ site.

Graphic Abstract

Synthesis and structural characterization of two heterodinuclear ZnII-LnIII complexes (Ln = Pr, Nd) bearing an asymmetrical compartmental ligand formed in situ from N1,N3-bis(3-methoxysalicylidene)diethylenetriamine (H2valdien) through intramolecular aminal formation are reported.
Economic value of tropical cyclone conditions of readiness
Authors: Gulati Sneh , Sampson Charles R.
Published: June 2021

U. S. Military bases are especially vulnerable to tropical cyclones (TCs) because they concentrate extremely expensive equipment in a small area. A TC hit at a base can result in upwards of 2 billion dollars in damage, as demonstrated by the recent loss of F-22 aircraft at Tyndall Air Base during Hurricane Michael. To mitigate these events, the Department of Defense defines tropical cyclone conditions of readiness (TCCOR), a set of preparedness levels that are adhered to by bases in preparation of an approaching TC. TCCOR are set by base commanders and are dependent on the likelihood of 50-knot sustained winds impacting the base within a forecast time. These TC-CORs generally drop from V (generally seasonal preparedness) to IV (50 kt or higher winds possible within 72 h); III (50 kt or higher winds possible within 48 h), II (50 kt or higher winds expected within 24 h), and I (50 kt or higher winds expected in 12 h or occurring now). Each TCCOR is associated with a specific set of preparedness actions whose cost generally increases as the TCCOR level drops. As preparing a base for a specific TCCOR level can be extremely time consuming and expensive, it is important that we assess the economic value of the preparation. In this work, we develop a simple cost-loss/savings model to estimate and compare the economic value of skillful TC forecasting against a no-skill forecast baseline. The cost-loss/savings model developed demonstrates that skilled forecasts offer considerable savings over non-skilled forecasts. The algorithm has been implemented in an Excel spreadsheet so that it can be customized to specific bases of interest.
Fostering word fluency of struggling third graders from Germany through motivational peer-tutorial reading racetracks
Authors: Barwasser Anne , Urton Karolina , Grünke Matthias , Sperling Marko , Coker David L.
Published: June 2021

Automation of frequently used words is a key component in the development of reading fluency. However, acquiring fast word recognition skills is a serious challenge for many children in their early years of formal education. Lagging word recognition leads to general reading problems, as fluency is a vital prerequisite for text comprehension. Recent research shows that the percentage of struggling elementary school readers in Germany is increasing, speaking to the need for widespread implementation of effective word recognition interventions. This pilot study aims to provide preliminary evidence of the effectiveness of peer-tutorial reading racetrack training with an integrated motivational system for the sight word fluency of German struggling elementary school students. The intervention comprised twelve 15-min teaching units over a period of three weeks. To encourage reading motivation, the intervention included graphing of performance scores and a group contingency procedure. A control-experimental group design (N = 44) with pre-, post-, and two follow-up measurements (each after five weeks) was employed to investigate the impact of the treatment on decoding sight words at an appropriate speed. Results demonstrated a significant performance increase in the treatment group, relative to the control group. The effect size can be considered very high (partialη2 = .76), indicating that this brief training has the potential to enhance the word recognition of struggling elementary students.
Climate change impacts on migration of Pinus koraiensis during the Quaternary using species distribution models
Authors: Shitara Takuto , Fukui Shunsuke , Matsui Tetsuya , Momohara Arata , Tsuyama Ikutaro , Ohashi Haruka , Tanaka Nobuyuki , Kamijo Takashi
Published: June 2021

Clarifying the influences of paleoclimate changes on the disjunct distribution formation of plants allows a historical and mechanical understanding of current vegetation and biodiversity. This study investigated the influences of paleoclimate changes on the present disjunct distribution formation of Pinus koraiensis (Korean pine) using species distribution modeling. A species distribution model (SDM) was built using maximum entropy principle algorithms (MaxEnt), data from 152 occurrences of the species, and four bioclimatic variables at 2.5 arcminute (approximately 5 km) spatial resolution. The simulation revealed the excellent fit of the MaxEnt model performance, with an area under the curve (AUC) value of 0.922 and continuous Boyce index (BCI) value of 0.925 with fivefold cross-validation. The most important climatic factor was the minimum temperature of the coldest month. Suitable habitats for the species ranged between − 30.1 and − 4.1 °C. Projected suitable habitats under the Last Glacial Maximum (approximately 22,000 years ago [ka BP]: LGM) period showed wide distributions in eastern China, the southern part of the Korean Peninsula, and the Japanese Archipelago. After the mid-Holocene (approximately 6 ka BP), the suitable habitats expanded northwards in continental regions and retreated from both north and southwest of Japan. This eventually formed disjunct suitable habitats in central Japan. An increase in temperature after the LGM period caused the migration of P. koraiensis toward new, suitable habitats in continental Northeast Asia, while species in the Japanese Archipelago retreated, forming the present disjunct distributions.
COVID-19 and beyond: development of a comprehensive telemedical diagnostic framework
Authors: Fuchtmann Jonas , Krumpholz Roman , Berlet Maximilian , Ostler Daniel , Feussner Hubertus , Haddadin Sami , Wilhelm Dirk
Published: June 2021

Purpose

During the COVID-19 pandemic, a threatening bottleneck of medical staff arose due to a shortage of trained caregivers, who became infected while working with infectious patients. While telemedicine is rapidly evolving in the fields of teleconsultation and telesurgery, proper telediagnostic systems are not yet available, although the demand for contactless patient–doctor interaction is increasing.

Methods

In this project, the current limitations were addressed by developing a comprehensive telediagnostic system. Therefore, medical examinations have been assessed in collaboration with medical experts. Subsequently, a framework was developed, satisfying the relevant constraints of medical-, technical-, and hygienic- aspects in order to transform in-person examinations into a contactless procedure. Diagnostic steps were classified into three groups: assisted procedures carried out by the patient, teleoperated examination methods, and adoptions of conventional methods.

Results

The Telemedical Diagnostic Framework was implemented, resulting in a functional proof of concept, where potentially infectious patients could undergo a full medical examination. The system comprises, e.g., a naso-pharyngeal swab, an inspection of the oral cavity, auscultation, percussion, and palpation, based on robotic end-effectors. The physician is thereby connected using a newly developed user-interface and a lead robot, with force feedback control, that enables precise movements with the follower robot on the patient’s side.

Conclusion

Our concept proves the feasibility of a fully telediagnostic system, that consolidates available technology and new developments to an efficient solution enabling safe patient-doctor interaction. Besides infectious situations, this solution can also be applied to remote areas.