bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determining kinematic order and relative age of faulting via flexural‐kinematic restoration: A case study in far western Nepal
Authors: Olsen Joshua E. S. , McQuarrie Nadine , Robinson Delores M. 
Published: March 2019

AbstractForward modeled, balanced cross sections that account for the flexural response to thrust loading and erosional unloading can verify and refine the kinematic sequence of deformation in fold‐thrust belts as well as help assess the validity of a balanced cross section. Results from flexural‐kinematic reconstructions that indicate either the cross section, the kinematic order or both are invalid include: (a) a predicted final topography that is dramatically different from the actual topography; (b) large normal fault or thrust fault bounded synorogenic basins that are not present in the mapped geology; and/or (c) an exhumation history that is not consistent with provenance records in the basin or measured thermochronometers. Where detailed measured foreland basin sections exist, flexural‐kinematic modeling of fold‐thrust belt deformation, including out‐of‐sequence (OOS) faults can predict a foreland basin evolution that can be compared to measured data. The modeling process creates a “pseudostratigraphy” in the modeled foreland. The pseudostratigraphy and predicted provenance of each modeled stratigraphic increment can be directly compared to measured stratigraphic sections. We present a case study using two cross sections through the Himalaya of far western Nepal (Api and Simikot) to assess the validity of the section geometries and the resulting kinematic histories, displacement rates, flexural wave response and predicted provenance for both sections. Insights from combining the flexural‐kinematic models with existing stratigraphic data include: (a) Changing the order of proposed OOS and normal faults to earlier in the evolution of the fold‐thrust belt was necessary to reproduce the foreland provenance data. We argue that OOS thrust and normal faults in the Api section occurred between 11 and 4 Ma. (b) Published shortening estimates for the Simikot cross section are too high (>50 km), resulting in unrealistic shortening rates up to 80 mm/yr between 25 and 20 Ma. (c) Flexural forward models with and without an additional sediment loading modeling step indicate that while sediment loading does not have a measurable effect on the magnitude and location of erosion within the fold‐thrust belt, it does have a small effect on accumulation rates and thus the predicted age of stratigraphic boundaries when compared to measured stratigraphic thicknesses and age. Thickness difference range from 0.2 to 0.5 km and can result in predicted age differences of ca. 1 Ma. Accounting for both flexural isostacy and erosion can eliminate unviable kinematic sequences and when combined with provenance data from measured stratigraphic sections, can provide insight into the order, age and rate of deformation.
Synthesis and antitumor activity of isolongifoleno[7,8‐d]thiazolo[3,2‐a]pyrimidine derivatives via enhancing ROS level
Authors: Ma Chonghui , Wang Yunyun , Dong Fuhao , Wang Zhonglong , Zhao Yuxun , Shan Yu , Gu Wen , Wang Shifa 
Published: March 2019

AbstractA series of novel isolongifoleno[7,8‐d]thiazolo[3,2‐a]pyrimidine derivatives (4a–4x) were synthesized from isolongifolanone according fragment‐based design strategy, and their anticancer activity against human aortic smooth muscle cells (HASMC), human breast cancer (MCF‐7) cells, human cervical cancer (HeLa) cells, and human liver cancer (HepG2) cells were investigated. Results of the anticancer activity illustrated that most of the compounds showed potent antitumor activity and compound 4i proved to be the most active derivative with IC50 values of 0.33 ± 0.24 (for MCF‐7 cells), 0.52 ± 0.13 (for HeLa cells), and 3.09 ± 0.11 μM (for HepG2 cells), respectively. Moreover, we assessed the effects of 4i on cell apoptosis, cell cycle distribution, mitochondrial membrane potential, and reactive oxygen species (ROS) generation. The results indicated that compound 4i altered mitochondrial membrane potential and produced ROS leading to cell apoptosis of MCF‐7 cells in a dose‐dependent manner, however, without affecting cell cycle progression. These findings suggested that 4i was an effective compound and provided a promising candidate for anticancer drugs.
Peri‐implant marginal bone loss rate pre‐ and post‐loading: An exploratory analysis of associated factors
Authors: Acharya Aneesha , Leung Ming Chi Terrence , Ng King Tung , Fan Michael H.M. , Fokas George , Mattheos Nikos 
Published: March 2019

AbstractObjectivesTo perform an exploratory analysis of factors influencing annual rates of peri‐implant marginal bone loss (RBL) calculated over different time frames, at implants unaffected by peri‐implantitis.Material and methodsA total of 154 implants from 86 patients were reviewed at 1.6–6.8 years after placement. Marginal bone levels (MBL) were assessed on intraoral radiographs at three time‐points: immediately post‐placement, time of loading, and least 1‐year post‐loading. RBLs (mm/year) were computed using these three time frames and corresponding MBL changes as: RBL placement‐loading, RBL loading‐review, RBL placement‐review. Exploratory ordination of three RBLs, corresponding time durations, and 17 background factors were used for visualization. Hierarchical linear mixed‐effects models (MEM) with predictor selection were applied to RBL outcomes. The correlation of actual MBL with MBLs predicted by RBL placement‐loading and RBL loading‐review was tested.ResultsMedian RBL placement‐loading was 0.9 mm/year (IQR = 2.02), loading‐review was 0.06 mm/year (IQR = 0.16), and overall RBL placement‐review was 0.21 mm/year (IQR = 0.33). Among‐patient variance was highest for RBL placement‐loading (SD = 0.66). Longer time predicted lower RBL in all time frames. Shorter time of loading significantly predicted lower RBL placement‐review. Augmentation predicted lower RBL placement‐loading, while anterior location and older age predicted lower RBLs placement‐loading placement‐review. Only MBL projected using RBL placement‐loading significantly correlated with actual MBL.ConclusionsExploratory analysis indicated RBL varied with the time duration used for calculation in pre‐ and post‐loading, and overall periods. In each period, RBL declined with increasing time. Earlier loading predicted lower overall RBL. Higher pre‐loading RBL predicted worse actual bone level.
Lifetime change in central and peripheral haemodynamics in relation to exercise capacity
Authors: Lind Lars , Lampa Erik 
Published: March 2019

SummaryExercise capacity as well as many resting central and peripheral haemodynamic features declines by age. We aimed to investigate which haemodynamic features change the most during life and which change in parallel to exercise capacity. We performed a maximal bicycle exercise test with gas exchange in 103 healthy subjects (24 young, 55 middle‐aged and 24 elderly). Endothelial function, arterial compliance/stiffness and heart rate variability (HRV) were evaluated, and the myocardium and carotid arteries were investigated by ultrasound. Exercise capacity declined by almost 50% over the lifespan. Several markers reflecting arterial compliance/stiffness and HRV, as well as carotid intima–media thickness (IMT), showed lifetime impairments by >100%, while markers of LV systolic function, diastolic blood pressure and carotid artery blood flow showed only minor changes with age. The decline in exercise capacity clusters closely with many other variables measured during the exercise test, but also to resting vital capacity, left ventricular end‐diastolic diameter and resting gas exchange (VO2, VCO2) to a lesser degree. Resting vital capacity was closely related to exercise capacity in the middle‐aged group. We conclude that many of the resting markers of central and peripheral haemodynamics declined during life, in parallel to the decline in exercise capacity. However, some haemodynamic features, such as LF/HF ratio at HRV, stiffness index beta of the carotid artery, and heart rate reserve at the exercise test, showed a more exaggerated decline, indicating that those are not closely linked to exercise capacity.
Exposure–Response Modeling and Simulation of Progression‐Free Survival and Adverse Events of Sorafenib Treatment in Patients With Advanced Thyroid Cancer
Authors: Grevel Joachim , Jentsch Garrit , Austin Rupert , Prins Nicolaas H. , Lettieri John , Mitchell David , Huang Funan , Brose Marcia S. , Schlumberger Martin , Meinhardt Gerold , Peña Carol E. A. , Ploeger Bart A. 
Published: March 2019

Sorafenib is an oral multikinase inhibitor approved for the treatment of differentiated thyroid carcinoma (DTC), renal cell carcinoma, and hepatocellular carcinoma. In the phase III DECISION trial in patients with DTC, sorafenib exposure and the incidence of some adverse events (AEs) were higher than in previous trials; therefore, we analyzed exposure–response relationships, including progression‐free survival (PFS) and selected AEs in patients with DTC. A novel, stratified prediction‐corrected visual predictive check (pc‐VPC) was developed to show robustness of the exposure–response relationships. Time‐to‐event simulations confirmed the benefit of the recommended dosing schedule of 800 mg/day: initial doses of 800 mg/day were associated with the highest PFS, whereas lower doses (600 or 400 mg/day) were associated with improved tolerability but reduced PFS. A simulated dose‐reduction strategy of 800 mg/day for an initial two cycles followed by dose reductions seemed likely to maintain efficacy while possibly mitigating selected AEs (e.g., diarrhea and hand‐foot skin reactions).
Systemische Therapien bei Pityriasis rubra pilaris: eine systematische Übersicht
Authors: Kromer Christian , Sabat Robert , Celis Daniel , Mössner Rotraut 
Published: March 2019

ZusammenfassungPityriasis rubra pilaris (PRP) ist eine seltene papulosquamöse Erkrankung. Die Behandlung ist schwierig; das therapeutische Arsenal umfasst topische Corticosteroide, Phototherapie, klassische Systemtherapien wie Retinoide oder Immunsuppressiva sowie, seit Kurzem, Biologika. Die relative Wirksamkeit der Behandlungen ist jedoch unklar. Unser Ziel war die Durchsicht der Literatur zur systemischen Behandlung der PRP. In PubMed und der Cochrane Library wurde eine systematische Recherche bis zum 5. September 2017 durchgeführt. Eingeschlossen wurden Studien, in denen systemische Behandlungen der PRP (ausgenommen historische Behandlungen) geprüft wurden. Insgesamt erfüllten 182 Studien die vorgegebenen Einschlusskriterien; sie enthielten Daten über 475 Patienten und 652 Behandlungszyklen. 42,0 % (225/514) aller mit Retinoiden behandelten Patienten sprachen hervorragend an (Isotretinoin: 61,1 % [102/167], Etretinat: 47 % [54/115] und Acitretin: 24,7 % [43/174]), verglichen mit einer hervorragenden Ansprechrate von 33,1 % (53/160) unter Methotrexat. Therapien mit Biologika waren bei 51,0 % der Patienten (71/133) erfolgreich (Ustekinumab: 62,5 % [10/16], Infliximab: 57,1 % [28/49], Etanercept: 53,3 % [16/30] und Adalimumab: 46,4 % [13/28]). In dieser Übersicht werden Wirksamkeit, Nebenwirkungen, Erfahrungen und Arzneimittelkosten gegeneinander abgewogen und es wird ein Behandlungsregime mit Isotretinoin als Erstlinien‐, Methotrexat als Zweitlinien‐ und Biologika als Drittlinienbehandlung vorgeschlagen.
S2k guidelines for skin and soft tissue infections Excerpts from the S2k guidelines for “calculated initial parenteral treatment of bacterial infections in adults – update 2018“
Authors: Sunderkötter Cord , Becker Karsten , Eckmann Christian , Graninger Wolfgang , Kujath Peter , Schöfer Helmut 
Published: March 2019

SummaryThese first German S2k guidelines for bacterial skin and soft tissue infections were developed as one chapter of the recommendations for “calculated initial parenteral treatment of bacterial infections” issued under the auspices of the Paul‐Ehrlich Society, of which the main part is presented here.Well‐calculated antibiotic therapies require precise diagnostic criteria. Erysipelas is defined as non‐purulent infection considered to be caused by beta‐hemolytic strepto­cocci. It is diagnosed clinically by its bright‐red erythema and early fever or chills at disease onset. Penicillin is the treatment of choice. Limited soft tissue infection (cellulitis) is usually caused by Staphylococcus (S.) aureus, frequently originates from chronic wounds and presents with a more violaceous‐red hue and only rarely with initial fever or chills. Treatment consists of first‐ or second‐­generation cephalosporins or flucloxacillin (IV).Severe cellulitis is a purulent, partially necrotic infection which extends through tissue boundaries to fascias and requires surgical management in addition to antibiotics. Moreover, it frequently fulfills the criteria for “complicated soft tissue infections”, as previously defined by the Food and Drug Administration for use in clinical trials (they include comorbidities such as uncontrolled diabetes, peripheral artery disease, neutropenia). It requires antibiotics which besides S. aureus target anaerobic and/or gramnegative bacteria. The rare so‐called necrotizing skin and soft tissue infections represent a distinct entity. They are characterized by rapid, life‐threatening progression due to special bacterial toxins that cause ischemic necrosis and shock and need rapid and thorough debridement in addition to appropriate antibiotics. For cutaneous abscesses the first‐line treatment is adequate drainage. Additional antibiotic therapy is required only under certain circumstances (e.g., involvement of the face, hands, or anogenital region, or if drainage is somehow complicated).The present guidelines also contain consensus‐based recommendations for higher doses of antibiotics than those approved or usually given in clinical trials. The goal is to deliver rational antibiotic treatment that is both effective and well‐tolerated and that exerts no unnecessary selection pressure in terms of multidrug resistance.
Bakterielle sexuell übertragbare Infektionen
Authors: Buder Susanne , Schöfer Helmut , Meyer Thomas , Bremer Viviane , Kohl Peter K. , Skaletz‐Rorowski Adriane , Brockmeyer Norbert 
Published: March 2019

ZusammenfassungBakterielle sexuell übertragbare Infektionen (STI) zeigen seit Jahren weltweit eine deutliche Zunahme. In Deutschland wird diese Tatsache durch steigende Meldezahlen für Syphilis bestätigt. Auch für die nicht meldepflichtigen STI Gonorrhoe, Chlamydia‐trachomatis‐ und Mycoplasma‐genitalium‐Infektionen wird eine zunehmende Inzidenz beobachtet. Entscheidend für die Weiterverbreitung ist, dass das breite klinische Spektrum, welches neben Urogenitalsitus auch Pharynx und Rektum einbezieht, durch eine hohe Zahl asymptomatischer Verläufe ergänzt wird. Neue Real‐Time‐Multiplex‐Diagnostikverfahren ermöglichen einen schnellen und gezielten Nachweis von STI‐Erregern. Die häufigste bakterielle STI ist die urogenitale Chlamydieninfektion mit den Serovaren D–K, die besonders bei jungen Erwachsenen auftritt. Einer Chlamydien‐Proktitis kann eine Infektion mit L‐Serovaren und damit eine Lymphogranuloma‐venereum (LGV)‐Infektion zugrunde liegen. Neisseria (N.) gonorrhoeae zeigte in den letzten Jahren eine starke Resistenzentwicklung mit Ausbildung von Einzel‐ und Multiresistenzen gegenüber bisher gängigen Antibiotika. Daher ist für N. gonorrhoeae zusätzlich zum nucleic acid amplification test (NAAT) eine kulturelle Empfindlichkeitstestung durchzuführen. Auch für Mycoplasma genitalium sind Resistenzentwicklungen bekannt, die eine Therapie erschweren können.
Proprotein convertase subtilisin/kexin type 9 and mortality in patients starting hemodialysis
Authors: Strålberg Towe , Nordenskjöld Anna , Cao Yang , Kublickiene Karolina , Nilsson Erik 
Published: March 2019

AbstractBackgroundCardiovascular events are the leading cause of death in end stage renal disease (ESRD), but traditional markers of dyslipidemia are not clearly associated with cardiovascular risk in this population. Proprotein Convertase Subtilsin/Kexin type 9 (PCSK‐9) could be of interest as a novel cardiovascular risk marker in ESRD due to the emergence of lipid lowering therapy based on PCSK‐9 inhibition. The aim of the present study was to investigate if the convertase PCSK‐9 is a potential risk marker for mortality among patients starting haemodialysis treatment.Materials and methodsThis is a cohort study of 265 patients starting haemodialysis between 1991‐2009, with 3 years follow‐up. The association between baseline PCSK‐9 levels and mortality was assessed using Cox proportional hazards‐ and quantile regression models, with adjustment for potential confounders.ResultsPCSK‐9 levels at initiation of haemodialysis were associated to mortality in multivariable adjusted analysis. PCSK‐9 levels exhibited an U‐shaped association to mortality. Inclusion of the quadratic term of PCSK‐9 in regression modelling optimized model performance. At baseline, PCSK‐9 levels had positive correlations to Davies comorbidity score, haemoglobin and C‐reactive protein while negative correlations were found for high‐density lipoprotein and total cholesterol. PCSK‐9 levels were higher in statin users and patients with a history of cardiovascular disease.ConclusionsThis study shows, for the first time, that the level of PCSK‐9 is associated with all‐cause mortality in haemodialysis patients, independently of a number of potential confounders.
Species‐rich boreal forests grew more and suffered less mortality than species‐poor forests under the environmental change of the past half‐century
Authors: Hisano Masumi , Chen Han Y. H. , Searle Eric B. , Reich Peter B. 
Published: March 2019

AbstractClimate and other global environmental changes are major threats to ecosystem functioning and biodiversity. However, the importance of plant diversity in mitigating the responses of functioning of natural ecosystems to long‐term environmental change remains unclear. Using inventory data of boreal forests of western Canada from 1958 to 2011, we found that aboveground biomass growth increased over time in species‐rich forests but decreased in species‐poor forests, and importantly, aboveground biomass loss from tree mortality was smaller in species‐rich than species‐poor forests. A further analysis indicated that growth of species‐rich (but not species‐poor) forests was statistically positively associated with rising CO2, and that mortality in species‐poor forests increased more as climate moisture availability decreased than it did in species‐rich forests. In contrast, growth decreased and mortality increased as the climate warmed regardless of species diversity. Our results suggest that promoting high tree diversity may help reduce the climate and environmental change vulnerability of boreal forests.
Survival prediction models in motor neuron disease
Authors: Agosta F. , Spinelli E. G. , Riva N. , Fontana A. , Basaia S. , Canu E. , Castelnovo V. , Falzone Y. , Carrera P. , Comi G. , Filippi M. 
Published: March 2019

Background and purposeThis study aimed to assess the predictive value of multimodal brain magnetic resonance imaging (MRI) on survival in a large cohort of patients with motor neuron disease (MND), in combination with clinical and cognitive features.MethodsTwo hundred MND patients were followed up prospectively for a median of 4.13 years. At baseline, subjects underwent neurological examination, cognitive assessment and brain MRI. Grey matter volumes of cortical and subcortical structures and diffusion tensor MRI metrics of white matter tracts were obtained. A multivariable Royston–Parmar survival model was created using clinical and cognitive variables. The increase of survival prediction accuracy provided by MRI variables was assessed.ResultsThe multivariable clinical model included predominant upper or lower motor neuron presentations and diagnostic delay as significant prognostic predictors, reaching an area under the receiver operating characteristic curve (AUC) of a 4‐year survival prediction of 0.79. The combined clinical and MRI model including selected grey matter fronto‐temporal volumes and diffusion tensor MRI metrics of the corticospinal and extra‐motor tracts reached an AUC of 0.89. Considering amyotrophic lateral sclerosis patients only, the clinical model including diagnostic delay and semantic fluency scores provided an AUC of 0.62, whereas the combined clinical and MRI model reached an AUC of 0.77.ConclusionOur study demonstrated that brain MRI measures of motor and extra‐motor structural damage, when combined with clinical and cognitive features, are useful predictors of survival in patients with MND, particularly when a diagnosis of amyotrophic lateral sclerosis is made.
Ecological factors affecting flight initiation distance in Daurian ground squirrels (Spermophilus dauricus)
Authors: Shuai Ling‐Ying , Zhou Yang , Yang Yu‐Xia , Xue Qi‐Qian , Xie Zi‐Yang , Zhang Fu‐Shun 
Published: March 2019

AbstractMore often than not, animals forage under predation risk. Foragers, therefore, face a challenge to balance between two conflicting tasks, namely energy intake and safety. Flight initiation distance (FID, defined as the distance between a prey and a predator when the prey starts to flee) has been widely measured in many taxa to study such economic trade‐offs. However, FID may also be affected by limitations on the prey's ability to detect predators, especially when there is visual obstruction caused by surrounding vegetation. Although both vegetation cover and vegetation height may contribute to such obstruction, the effect of vegetation height on FID has not been well studied. In this study, we explored the effects of vegetation height, vegetation cover and distance to refuge on FID in free‐living Daurian ground squirrels (Spermophilus dauricus) inhabiting a grassland in Inner Mongolia, China. Multiple linear regressions suggested that both vegetation height and distance to refuge significantly affected FID in S. dauricus. Ground squirrels fled earlier when vegetation was low or when foraging farther away from a refuge. No significant effect of vegetation cover on FID was detected. Our results have implications for ecologically based pest control, and FID may be used as an effective and easy‐to‐use behavioral indicator in wildlife management.