bluuebunny/crossref_metadata_2025 huggingface dataset:
Asthma‐inducing potential of 28 substances in spray cleaning products—Assessed by quantitative structure activity relationship (QSAR) testing and literature review
Authors: Hadrup Niels , Frederiksen Marie , Wedebye Eva B. , Nikolov Nikolai G. , Carøe Tanja K. , Sørli Jorid B. , Frydendall Karen B. , Liguori Biase , Sejbaek Camilla S. , Wolkoff Peder , Flachs Esben M. , Schlünssen Vivi , Meyer Harald W. , Clausen Per A. , Hougaard Karin S.
Published: July 2021

Exposure to spray cleaning products constitutes a potential risk for asthma induction. We set out to review whether substances in such products are potential inducers of asthma. We identified 101 spray cleaning products for professional use. Twenty‐eight of their chemical substances were selected. We based the selection on (a) positive prediction for respiratory sensitisation in humans based on quantitative structure activity relationship (QSAR) in the Danish (Q)SAR Database, (b) positive QSAR prediction for severe skin irritation in rabbits and (c) knowledge on the substances' physico‐chemical characteristics and toxicity. Combining the findings in the literature and QSAR predictions, we could group substances into four classes: (1) some indication in humans for asthma induction: chloramine, benzalkonium chloride; (2) some indication in animals for asthma induction: ethylenediaminetetraacetic acid (EDTA), citric acid; (3) equivocal data: hypochlorite; (4) few or lacking data: nitriloacetic acid, monoethanolamine, 2‐(2‐aminoethoxy)ethanol, 2‐diethylaminoethanol, alkyldimethylamin oxide, 1‐aminopropan‐2‐ol, methylisothiazolinone, benzisothiazolinone and chlormethylisothiazolinone; three specific sulphonates and sulfamic acid, salicylic acid and its analogue sodium benzoate, propane‐1,2‐diol, glycerol, propylidynetrimethanol, lactic acid, disodium malate, morpholine, bronopol and benzyl alcohol. In conclusion, we identified an asthma induction potential for some of the substances. In addition, we identified major knowledge gaps for most substances. Thus, more data are needed to feed into a strategy of safe‐by‐design, where substances with potential for induction of asthma are avoided in future (spray) cleaning products. Moreover, we suggest that QSAR predictions can serve to prioritise substances that need further testing in various areas of toxicology.
Toxicity of polymer‐modified CuS nanoclusters on zebrafish embryo development
Authors: Zhang Qiuping , Wang Lifeng , Gao Qian , Zhang Xinge , Lin Yushuang , Huang Shuhong , Chen Dongyan
Published: July 2021

Despite the vast amount of research on the toxicity of copper‐based nanoparticles, the toxicity of CuS nanoparticles is still largely unknown. Due to the application of CuS‐based nanomaterials in biomedical engineering, it is necessary to study their potential toxicity and biological effects. In this study, we evaluated the toxicity of polymer‐modified CuS nanoclusters (PATA3‐C4@CuS) on embryo development through exposing zebrafish embryos to 1, 2.5, 5, 7.5, and 10 mg/L PATA3‐C4@CuS at 0.75‐h post‐fertilization. The morphological results demonstrated that PATA3‐C4@CuS at concentrations greater than 1 mg/L PATA3‐C4@CuS induced abnormal phenotypes including smaller heads and eyes, pericardial edema, and epiboly retardation and it increased mortality, lowered the hatching rate, and inhibited swim bladder inflation. In situ hybridization and quantitative reverse transcription polymerase chain reaction showed that PATA3‐C4@CuS could alter the expression patterns of tbxta, dlx3, and cstlb and increase the expression levels of wnt5 and wnt11, which suggested that PATA3‐C4@CuS disrupts cell migration by increasing the levels of wnt5 and wnt11 during gastrulation. It was also discovered that PATA3‐C4@CuS exposure caused a slow heart rate and smaller ventricles in zebrafish larvae. Immunofluorescence and behavioral analyses showed that PATA3‐C4@CuS could damage the ventral projection of the primary motor neurons CaP, which was in accordance with the reduction in locomotion ability. Together, our data demonstrated that functional PATA3‐C4@CuS could disrupt cell migration during gastrulation, affect cardiac development and function, and decrease locomotive activity.
Low serum level of apolipoprotein A1 may predict the severity of COVID‐19: A retrospective study
Authors: Zhu Zhe , Yang Yayun , Fan Lingyan , Ye Shuyuan , Lou Kehong , Hua Xin , Huang Zuoan , Shi Qiaoyun , Gao Guosheng
Published: July 2021

Background

Dyslipidemia has been observed in patients with coronavirus disease 2019 (COVID‐19). This study aimed to investigate blood lipid profiles in patients with COVID‐19 and to explore their predictive values for COVID‐19 severity.

Methods

A total of 142 consecutive patients with COVID‐19 were included in this single‐center retrospective study. Blood lipid profile characteristics were investigated in patients with COVID‐19 in comparison with 77 age‐ and gender‐matched healthy subjects, their predictive values for COVID‐19 severity were analyzed by using multivariable logistic regression analysis, and their prediction efficiencies were evaluated by using receiver operator characteristic (ROC) curves.

Results

There were 125 and 17 cases in the non‐severe and severe groups, respectively. Total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and apolipoprotein A1 (ApoA1) gradually decreased across the groups in the following order: healthy controls, non‐severe group, and severe group. ApoA1 was identified as an independent risk factor for COVID‐19 severity (adjusted odds ratio [OR]: 0.865, 95% confidence interval [CI]: 0.800–0.935, p < 0.001), along with interleukin‐6 (IL‐6) (adjusted OR: 1.097, 95% CI: 1.034–1.165, p = 0.002). ApoA1 exhibited the highest area under the ROC curve (AUC) among all single markers (AUC: 0.896, 95% CI: 0.834–0.941); moreover, the risk model established using ApoA1 and IL‐6 enhanced prediction efficiency (AUC: 0.977, 95% CI: 0.932–0.995).

Conclusion

Blood lipid profiles in patients with COVID‐19 are quite abnormal compared with those in healthy subjects, especially in severe cases. Serum ApoA1 may represent a good indicator for predicting the severity of COVID‐19.
A dual gate material tunnel field effect transistor model incorporating two‐dimensional Poisson and Schrodinger wave equations
Authors: Mohanty Sadhana Subhadarshini , Dutta Pradipta , Das Jitendra Kumar
Published: July 2021

This paper presents an accurate analytical model of surface potential and drain current for a long channel dual material gate (DMG) tunneling field‐effect transistor (TFET) with the addition of nonlinear inversion charge developed at the channel/drain interface region, ambipolar characteristic, and quantum confinement. The model includes the effect of dual metal gate work function as it controls the threshold voltage without considering a fully depleted undoped channel region. The current model includes the effect of charge accumulation at the interface of two gates and an appropriate mathematical expression of nonlinear inversion charge developed at the interface of two gates has been derived from the two‐dimensional (2D) Schrodinger wave equation incorporating quantum confinement. The model is effective to capture transfer characteristics at Sub 10 nm body thickness. A high ION/IOFF ratio and less than 27 mV/decade subthreshold swing are achieved at 2 nm body thickness which is desirable for low power VLSI application. The proposed model has been compared and calculated by Sentaurus TCAD with fair accuracy and a good resemblance, including ambipolar characteristics at sub 10 nm body thickness has been achieved.
Can near‐infrared autofluorescence imaging be used for intraoperative confirmation of parathyroid tissue?
Authors: Berber Eren , Akbulut Serkan
Published: July 2021

Background and Objectives

Whether ex vivo autofluorescence (AF) imaging findings could be quantified to intraoperatively differentiate parathyroid tissue has not been reported. Our aim was to assess the ability of AF imaging to confirm parathyroid tissue during thyroidectomy and parathyroidectomy procedures.

Methods

This was a retrospective Institutional Review Board‐approved study. AF signals of specimens imaged ex vivo before submission to pathology during thyroidectomy and parathyroidectomy procedures were quantified. Using receiver operating characteristic (ROC) curves, optimal values for sensitivity/specificity to differentiate parathyroid tissue were calculated.

Results

166 parathyroid and 217 non‐parathyroid specimens were analyzed. With surgical drapes as background, the optimal normalized AF intensity threshold to predict parathyroid tissue on ROC curve analysis was 1.72 (86.1% sensitivity, 84.8% specificity, and area under the curve [AUC]: 0.919). The cutoff for 97% sensitivity was 1.31 and for 99.1% specificity was 3.16. With Telfa as background, the optimal threshold to predict parathyroid tissue was 1.46 (88.4% sensitivity, 76.8% specificity, and AUC: 0.896). The threshold for 96.8% sensitivity was 1.18 and for 98.8% specificity was 2.44. If thresholds for highest specificity were used, 40% of frozen sections to confirm parathyroid tissue could have been avoided.

Conclusion

Quantified brightness analysis of ex vivo AF signals may have utility in intraoperative differentiation of parathyroid tissue for 40% of surgical specimens.
Influence of grazing on the structure and biological activity of dry steppe soils of the southern Russian Plain
Authors: Khomutova Tatiana E. , Fornasier Flavio , Yeltsov Maksim V. , Chernysheva Elena V. , Borisov Aleksandr V.
Published: July 2021

A comparative analysis of physicochemical and biological properties of Kastanozems and Solonetzes, the two most common soil types in the Caspian region of the post‐Soviet territory was carried out. The carbonate, salt, Corg, mineral N (NH4+ and NO3−) contents, microbial biomass (measured by ds‐DNA and phospholipids), and activity of 17 hydrolases involved in the C, N, P, and S cycles were measured along the grazing attenuation gradient near a typical sheep farm with year‐round grazing. Heavy grazing increases the number of Solonetz areas, they occupy up to 70% of the soil cover. Further away from the farm the areas decrease, and Kastanozems dominate there instead. Both in Kastanozems and Solonetzes, heavy grazing leads to soil salinisation, accumulation of carbonates and nitrates, decrease in ammonia and Corg content, microbial biomass, and enzymatic activity. At moderate grazing, a significant increase in microbial biomass and enzymatic activity throughout the soil profile, particularly in the 0–10 cm layer was found; at light grazing, it was observed mainly in deeper soil layers, not in the upper 0–10 cm. The microbial biomass and enzymatic activity of soils did not directly follow grazing load and was maximal at moderate grazing, where negative effect of reducing phytomass is compensated by large inputs of animal excreta, stimulating development of soil microbial community. Compared to Kastanozems, Solonetzes were more resistant to pasture load, and under heavy grazing, their properties changed to a lesser extent.
Quantification of internal dosimetry in PET patients II: Individualized Monte Carlo‐based dosimetry for [18F]fluorocholine PET
Authors: Neira Sara , Guiu‐Souto Jacobo , Pais Paulino , Rodríguez Martínez de Llano Sofía , Fernández Carlos , Pubul Virginia , Ruibal Álvaro , Pombar Miguel , Gago‐Arias Araceli , Pardo‐Montero Juan
Published: July 2021

Purpose

To obtain individualized internal doses with a Monte Carlo (MC) method in patients undergoing diagnostic [18F]FCH‐PET studies and to compare such doses with the MIRD method calculations.

Methods

A patient cohort of 17 males were imaged after intravenous administration of a mean [18F]FCH activity of 244.3 MBq. The resulting PET/CT images were processed in order to generate individualized input source and geometry files for dose computation with the MC tool GATE. The resulting dose estimates were studied and compared to the MIRD method with two different computational phantoms. Mass correction of the S‐factors was applied when possible. Potential sources of uncertainty were closely examined: the effect of partial body images, urinary bladder emptying, and biokinetic modeling.

Results

Large differences in doses between our methodology and the MIRD method were found, generally in the range ±25%, and up to ±120% for some cases. The mass scaling showed improvements, especially for non‐walled and high‐uptake tissues. Simulations of the urinary bladder emptying showed negligible effects on doses to other organs, with the exception of the prostate. Dosimetry based on partial PET/CT images (excluding the legs) resulted in an overestimation of mean doses to bone, skin, and remaining tissues, and minor differences in other organs/tissues. Estimated uncertainties associated with the biokinetics of FCH introduce variations of cumulated activities in the range of ±10% in the high‐uptake organs.

Conclusions

The MC methodology allows for a higher degree of dosimetry individualization than the MIRD methodology, which in some cases leads to important differences in dose values. Dosimetry of FCH‐PET based on a single partial PET study seems viable due to the particular biokinetics of FCH, even though some correction factors may need to be applied to estimate mean skin/bone doses.
Covalent organic frameworks: From materials design to electrochemical energy storage applications
Authors: Lin Jiamin , Zhong Yiren , Tang Lingyu , Wang Liuqi , Yang Mei , Xia Hui
Published: July 2021

Covalent organic frameworks (COFs), with large surface area, tunable porosity, and lightweight, have gained increasing attention in the electrochemical energy storage realms. In recent years, the development of high‐performance COF‐based electrodes has, in turn, inspired the innovation of synthetic methods, selection of linkages, and design of the topological structures. This review aims to present an overview of the recent advances in designing COF materials for various energy storage technologies. The fundamentals of COF materials, including synthetic chemistry, linkage diversity, and structure design, are first introduced. An in‐depth understanding of the charge storage mechanism and the structure‐property relationships of the COF electrodes is subsequently provided, highlighting their designing strategies in the latest energy storage applications. The last section of this review discusses the challenges COFs are facing and outlines new directions that could advance COF research in emerging energy technologies.
Ultrasound Imaging of Treatment‐Needed Cardiac Rejection with CD4‐Targeted Nanobubbles
Authors: Xie Yu , Xie Yuji , Chen Yihan , Deng Cheng , Fang Lingyun , Li He , Sun Zhenxing , Gao Tang , Liu Jie , Yuan Jing , Li Yuman , Jin Qiaofeng , Zhang Li , Xie Mingxing
Published: July 2021

Acute cardiac allograft rejection (ACAR) is one of the main reasons for mortality after heart transplantation. The timely diagnosis of treatment‐needed ACAR is of great importance in the clinic. Molecular imaging may make accurate diagnoses at the early stage to visualize the activity of specific pathological processes. The amount of CD4+‐lymphocyte infiltration is a crucial index in ACAR grading. CD4‐targeted nanobubbles (NBCD4) are fabricated to assess the infiltrating CD4+ lymphocytes, while isotype control nanobubbles (NBIso) are also fabricated. Animal models with ACAR grades from 0R to 3R are established. Ultrasound molecular imaging (USMI) is performed to distinguish different rejection grades with NBCD4. In the grade 2R and 3R groups, the USMI signals of NBCD4 are significantly higher than those of NBIso. The signals of NBCD4 in the 2R group are significantly lower than those in the 3R group and significantly higher than those in the 1R and 0R groups. Moreover, the signals of NBCD4 are strongly correlated with the rejection grades and the number of infiltrating CD4+ lymphocytes. As asymptomatic rejection with 2R or higher grades should be seriously treated, USMI with NBCD4 may be a new approach to timely diagnosis of treatment‐needed ACAR.
Vibrational Signatures of Substitutional Oxygen in CdTe and CdSe
Authors: Herklotz Frank , Thiede Sebastian , Lavrov Eduard
Published: July 2021

Vibrational modes of substitutional oxygen on the anion site in cubic CdTe and wurtzite CdSe are identified from infrared (IR) absorption measurements on single crystals codoped with 18O and 16O. The 16O isotope variety of the defect in CdTe gives rise to a local vibrational mode at 349.8  (10 K), whereas the corresponding species in CdSe results in a doublet structure at 370.6 and 372.5  (10 K). The latter two modes are fully polarized for light parallel and perpendicular to the c axis of the CdSe crystal, respectively, and belong to the nondegenerate and the twofold degenerate E representations of the C3v point group.
Osteoporotic fractures and subsequent fractures: imminent fracture risk from an analysis of German real-world claims data
Authors: Hadji Peyman , Schweikert Bernd , Kloppmann Edda , Gille Patrick , Joeres Lars , Toth Emese , Möckel Luis , Glüer Claus-C.
Published: July 2021

Purpose

In osteoporosis, prior fracture is a strong predictor of subsequent fracture. This study aimed to assess the imminent risk of subsequent fracture following an initial fracture in osteoporosis patients in Germany, and to identify clinical and demographic characteristics that are independently associated with subsequent fracture risk.

Methods

In this retrospective, observational cohort study using German real-world claims data, male and female patients aged ≥ 50 years with osteoporosis who experienced an initial (“index”) hip/femur, vertebral, forearm/wrist/hand or shoulder/upper arm fracture between 2010 and 2014 were included. The incidence and timing of subsequent fractures during a 1-year follow-up period were analyzed. Independent risk factors for subsequent fracture were identified by multivariate regression analysis.

Results

A total of 18,354 patients (mean age: 77 years; standard deviation: 9.8) were included. Of these, 2918 (15.9%) suffered a subsequent fracture during the 1-year follow-up period. The incidence of subsequent fracture was higher following an index vertebral fracture (18.0%) than after an index forearm/wrist/hand fracture (14.1%) or index hip/femur fracture (12.1%). Subsequent 1-year fracture incidence was generally higher in older patients. Index fracture type, age, epilepsy/use of antiepileptics, and heart failure were all independently associated with subsequent fracture risk.

Conclusion

Osteoporosis patients in Germany are at imminent risk of subsequent fracture during the first year following an initial fracture. They should be targeted for immediate post-fracture treatment to reduce the risk of further fractures, especially in the presence of specific risk factors such as old age or index vertebral fracture.
Does delaying curative surgery for colorectal cancer influence long-term disease-free survival? A cohort study
Authors: Garcia-Botello Stephanie , Martín-Arevalo J. , Cozar-Lozano C. , Benitez-Riesco A. , Moro-Valdezate D. , Pla-Martí V. , Espí-Macías A.
Published: July 2021

Background

Surgical wait list time is a major problem in many health-care systems and its influence on survival is unclear. The aim of this study is to assess the impact of wait list time on long-term disease-free survival in patients scheduled for colorectal cancer resection.

Materials and methods

A prospective study was carried out in patients with colorectal cancer scheduled for surgery at a tertiary care center. Wait list time was defined as the time from completion of diagnostic workup to definitive surgery and divided into 2-week intervals from 0 to 6 weeks. The outcome variables were 2-year and 5-year disease-free survival.

Results

A total of 602 patients, 364 (60.5%) male, median age 73 years (range = 71) were defined. The median wait list time was 28 days (range = 99). Two and 5-year disease-free survival rates were 521 (86.5%) and 500 (83.1%) respectively. There were no differences in 2-year or 5-year disease-free survival for the whole cohort or by tumor stage between wait list time intervals except for AJCC stage II tumors which showed a higher 5-year disease-free survival for the 2–4 and 4–6-week wait list time interval (p = 0.021).

Conclusions

Time from diagnosis to definitive surgery up to 6 weeks is not associated with a decrease in 2-year or 5-year disease-free survival (DFS) in AJCC stage I through III colorectal cancer patients. These are important findings in the light of the COVID-19 pandemic and offer a window of opportunity for preoperative optimization and prehabilitation.
Local-aware spatio-temporal attention network with multi-stage feature fusion for human action recognition
Authors: Hou Yaqing , Yu Hua , Zhou Dongsheng , Wang Pengfei , Ge Hongwei , Zhang Jianxin , Zhang Qiang
Published: July 2021

In the study of human action recognition, two-stream networks have made excellent progress recently. However, there remain challenges in distinguishing similar human actions in videos. This paper proposes a novel local-aware spatio-temporal attention network with multi-stage feature fusion based on compact bilinear pooling for human action recognition. To elaborate, taking two-stream networks as our essential backbones, the spatial network first employs multiple spatial transformer networks in a parallel manner to locate the discriminative regions related to human actions. Then, we perform feature fusion between the local and global features to enhance the human action representation. Furthermore, the output of the spatial network and the temporal information are fused at a particular layer to learn the pixel-wise correspondences. After that, we bring together three outputs to generate the global descriptors of human actions. To verify the efficacy of the proposed approach, comparison experiments are conducted with the traditional hand-engineered IDT algorithms, the classical machine learning methods (i.e., SVM) and the state-of-the-art deep learning methods (i.e., spatio-temporal multiplier networks). According to the results, our approach is reported to obtain the best performance among existing works, with the accuracy of 95.3% and 72.9% on UCF101 and HMDB51, respectively. The experimental results thus demonstrate the superiority and significance of the proposed architecture in solving the task of human action recognition.
Profile of urinary amino acids and their post-translational modifications (PTM) including advanced glycation end-products (AGEs) of lysine, arginine and cysteine in lean and obese ZSF1 rats
Authors: Baskal Svetlana , Büttner Petra , Werner Sarah , Besler Christian , Lurz Philipp , Thiele Holger , Tsikas Dimitrios
Published: July 2021

Heart failure with preserved ejection fraction (HFpEF) is associated with high mortality and has an increasing prevalence associated with the demographic change and limited therapeutic options. Underlying mechanisms are largely elusive and need to be explored to identify specific biomarkers and new targets, which mirror disease progression and intervention success. Obese ZSF1 (O-ZSF1) rats are a useful animal model, as they spontaneously develop hypertension, hyperlipidemia and glucose intolerance and finally HFpEF. The urinary profile of amino acids and their metabolites of post-translational modifications (PTM), including the advanced glycation end-products (AGEs) of lysine, arginine and cysteine, are poorly investigated in HFpEF and ZSF1 rats. The aim of the present study was to characterize the status of free amino acids and their metabolites of PTM and glycation in lean ZSF1 (L-ZSF1) and O-ZSF1 rats in urine aiming to find possible effects of glucose on the excretion of native and modified amino acids. In the urine of twelve L-ZSF1 and twelve O-ZFS1 rats collected at the age of 20 weeks, we measured the concentration of native and modified amino acids by reliable previously validated stable-isotope dilution gas chromatography-mass spectrometry (GC–MS) approaches. Serum glucose was 1.39-fold higher in the O-ZSF1 rats, while urinary creatinine concentration was 2.5-fold lower in the O-ZSF1 rats. We observed many differences in urinary amino acids excretion between L-ZSF1 and O-ZSF1 rats. The creatinine-corrected homoarginine excretion was twofold lower in the O-ZSF1 rats. We also observed distinct associations between the concentrations of serum glucose and urinary amino acids including their PTM and AGE metabolites in the L-ZSF1 and O-ZSF1 rats. Our study shows that PTM metabolites and AGEs are consistently lower in the L-ZSF1 than in the O-ZSF1 rats. Serum malondialdehyde (MDA) concentration was higher in the O-ZSF1 rats. These results suggest that hyperglycemia, hyperlipidemia and elevated oxidative stress in the O-ZSF1 rats favor PTM methylation of arginine and lysine and the glycation of lysine and cysteine. The area under the receiver operation characteristic (ROC) curve values were 0.996 for serum glucose, 0.951 for urinary creatinine, 0.939 for serum MDA, 0.885 for Nε-carboxyethyl-lysine, 0.830 for carboxyethyl-cysteine, and 0.792 for monomethyl-lysine. Non-invasive measurement of methylation and glycation products of arginine, lysine and cysteine residues in proteins in urine of L-ZSF1 and O-ZSF1 rats may be useful in studying pathophysiology and pharmacology of HFpEF.
ChoiceNet: CNN learning through choice of multiple feature map representations
Authors: Rayhan Farshid , Galata Aphrodite , Cootes Tim F.
Published: July 2021

We introduce a new architecture called ChoiceNet where each layer of the network is highly connected with skip connections and channelwise concatenations. This enables the network to alleviate the problem of vanishing gradients, reduces the number of parameters without sacrificing performance and encourages feature reuse. We evaluate our proposed architecture on three independent tasks: classification, segmentation and facial landmark localisation. For this, we use benchmark datasets such as ImageNet, CIFAR-10, CIFAR-100, SVHN CamVid and 300W.
Stochastic radiotherapy appointment scheduling
Authors: Braune Roland , Gutjahr Walter J. , Vogl Petra
Published: July 2021

When scheduling the starting times for treatment appointments of patients in hospitals or outpatient clinics such as radiotherapy centers, minimizing patient waiting time and simultaneously maximizing resource usage is crucial. Significant uncertainty in the treatment durations makes scheduling those activities particularly challenging. In addition to the treatments themselves, also preparation times and exiting times have to be considered, which are uncertain as well. To address and analyze this type of problems, the current study develops a model for planning appointment times under uncertain activity durations for a medical unit with a single “core resource” (in our application case a radiotherapy beam device), several treatment rooms, and required preparation and exiting phases for each patient. We employ a novel buffer concept based on quantiles of duration distributions and introduce a reactive procedure that adapts a pre-determined baseline schedule to the actual patient flow. For heuristically solving the resulting stochastic optimization model, a combination of a Genetic Algorithm and Monte Carlo simulation is proposed. A case study uses real-world data on activity durations gathered from an ion beam therapy facility in Austria. Experimental results comparing different variants of the method are carried out. In particular, comparisons of the stochastic optimization approach to a simpler deterministic approach are given.
Er:YAG laser-induced damage to a dental composite in simulated clinical scenarios for inadvertent irradiation: an in vitro study
Authors: Kuhn Katharina , Schmid Carmen U. , Luthardt Ralph G. , Rudolph Heike , Diebolder Rolf
Published: July 2021

Inadvertent Er:YAG laser irradiation occurs in dentistry and may harm restorative materials in teeth. The aim of this in vitro study was to quantify Er:YAG laser-induced damage to a nanohybrid composite in simulated clinical scenarios for inadvertent direct and indirect (reflection) laser irradiation. The simulation was performed by varying the output energy (OE;direct˃indirect) reaching the specimen and the operating distance (OD;direct˂indirect). Composite specimens were irradiated by an Er:YAG laser. The ablation threshold was determined and clinically relevant parameters were applied (n = 6 for each OE/OD combination) for direct (OE: 570 mJ/OD: 10 mm, OE: 190 mJ/OD: 10 mm) and indirect irradiation (OE: 466 mJ/OD: 15 mm, OE: 57 mJ/OD: 15 mm, OE: 155 mJ/OD: 15 mm, OE: 19 mJ/OD: 15 mm). The extent of damage in the form of craters was evaluated using a laser scanning microscope (LSM) and a conventional light microscope (LM). The ablation threshold was determined to be 2.6 J/cm2. The crater diameter showed the highest value (LM: 1075 ± 18 µm/LSM: 1082 ± 17 µm) for indirect irradiation (reflectant:dental mirror) (OE: 466 mJ/OD: 15 mm). The crater depth showed the highest and comparable value for direct (OE: 570 mJ/OD: 10 mm; LSM: 89 ± 2 µm) and indirect irradiation (OE: 466 mJ/OD: 15 mm; LSM: 90 ± 4 µm). For each OD, the crater diameter, depth, and volume increased with higher laser fluence. However, the OD—and thus the laser spot diameter—also had an enlarging effect. Thus, indirect irradiation (reflectant:dental mirror) with only 47% of the laser fluence of direct irradiation led to a larger diameter and a comparable depth. The three-dimensional extent of the crater was large enough to cause roughening, which may lead to plaque accumulation and encourage caries, gingivitis, and periodontitis under clinical conditions. Clinicians should be aware that reflected irradiation can still create such craters.
Delivering PrEP to Young Women in a Low-Income Setting in South Africa: Lessons for Providing Both Convenience and Support
Authors: Cassidy Tali , Ntuli Nelisiwe , Kilani Charllen , Malabi Nikiwe , Rorwana Bulelwa , Mutseyekwa Tabitha , O’Connell Rebecca , Steele Sarah Jane , Ndlovu Zee , Ellman Tom , de Azevedo Virginia , Pfaff Colin , Nelson Aurelie , Duran Laura Trivino
Published: July 2021

Daily oral pre-exposure prophylaxis (PrEP) is a key tool in addressing high HIV incidence among young women, and breaking the cycle of transmission. From 2017 to 2020, Médecins Sans Frontières (MSF) offered PrEP, in conjunction with contraception and risk-reduction counselling, to women aged 18–25, in a government-run clinic in Khayelitsha, a low income high HIV prevalence area in South Africa. Drawing on clinical, quantitative, and qualitative interview data, we describe participants’ experiences and engagement with the PrEP program, participant adherence (measured by TFV-DP levels in dried blood spots) over time, and the indirect benefits of the PrEP program. Of 224 screened and eligible participants, 164 (73.2%) initiated PrEP, with no large differences between those who initiated and those who did not. Overall, 47 (29%) completed 18 months follow-up, with 15 (9.1%) attending all visits. 76 (46.9%) participants were lost to follow-up, 15 (9.1%) exited when leaving the area, and 28.7% of exits happened in the first month of the study. We identified two different trajectories of PrEP adherence: 67% of participants had, on average, consistently low TFV-DP levels, with the remaining 33% having sustained high adherence. Few baseline characteristics predicted good adherence. The main reported barrier to taking PrEP was forgetting to take or travel with the pills. Encouragement from others declined as a reported facilitator from month 6 to 18 (family: 93.1% vs 77.6%, p = 0.016, friends: 77.6% vs 41.4%, p ≤ 0.001, partners: 62.1% vs 46.6%, p = 0.096, other PrEP users: 89.7% vs 74.1%, p = 0.020). Disclosure to friends and family in some cases opened dialogue around sex, and helped to educate others about PrEP. Self-reported sex with more than one partner, and sex without a condom, decreased significantly after enrolment (p < 0.001, p = 0.063). In the individual interviews, participants credited their PrEP experience with changing their behaviour. Recognising the challenges with, but overall benefits from a package of care that includes the option of PrEP, lessons drawn from this study can help maximise persistence on PrEP within resource constraints. PrEP providers need to address participants’ need for both convenience and social support.
Type of broadleaf forest matters most for ptyctimous mite communities (Acari, Oribatida) in Norway
Authors: Seniczak Anna , Niedbała Wojciech , Iturrondobeitia J. Carlos , Seniczak Stanisław , Roth Steffen , Jordal Bjarte H.
Published: July 2021

We studied ptyctimous moss mites, which are characteristic of forest habitats, in Norwegian broadleaf forests considered as biodiversity hotspot areas in Fennoscandia. The study aimed to evaluate the effect of different factors (regional locality, annual precipitation, mean annual temperature, forest type, forest wetness and microhabitat) on the ptyctimous mites and on discovering their richness in broadleaf forests. Samples were collected from nine broadleaf forests in Western, Southern and Eastern Norway, in different climatic conditions, six forest types, three forest wetness states and eight microhabitats. Overall, 3341 ptyctimous mites were collected and their abundance differed significantly among the regions, forest types and microhabitats. Forest type turned out to be the most important factor, responsible for 24.5% of the total variation in the abundance of the ptyctimous mites. Other important factors were forest wetness and microhabitat. In total, 27 species, i.e., 87% of all ptyctimous mites known from before in Norway were found and the species richness was highest in the east and lowest in the west of the country.Atropacarus (Atropacarus) striculuswas most common and most abundant; it made nearly 30% of all ptyctimous mites collected. On the other hand, a quarter of the species were represented by less than 10 specimens; most of these were new records for Norway. Among ten species discovered as new to Norway, four were also new to Fennoscandia. These findings confirm the unique character and high biological diversity of Norwegian broadleaf forests.
Phase 1 dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors
Authors: Denlinger Crystal S. , Keedy Vicki L. , Moyo Victor , MacBeath Gavin , Shapiro Geoffrey I.
Published: July 2021

Background Overactivation of human epidermal growth factor receptor 3 (HER3) triggers multiple intracellular pathways resulting in tumor cell survival. This Phase 1 study assessed the safety, efficacy, and pharmacokinetics (PK) of seribantumab, a fully human anti-HER3 monoclonal antibody. Methods Adult patients with advanced or refractory solid tumors were treated in six dose cohorts of seribantumab: 3.2, 6, 10, 15, or 20 mg/kg weekly, or 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose (40/20 mg/kg) using a modified 3 + 3 dose escalation strategy with cohort expansion. Primary objectives were identification of a recommended Phase 2 dose (RP2D) and determination of objective response rate. Secondary objectives were assessment of safety, dose-limiting toxicities, and PK. Results Forty-four patients (26 dose escalation; 18 dose expansion) were enrolled. Seribantumab monotherapy was well tolerated with most adverse events being transient and mild to moderate (grade 1 or 2) in severity; maximum tolerated dose was not reached. The highest dose, 40/20 mg/kg, was identified as RP2D. Best response was stable disease, reported in 24% and 39% of patients during the dose escalation and expansion portions of the study, respectively. Seribantumab terminal half-life was ≈100 h; steady state concentrations were reached after 3–4 weekly doses. Conclusions Seribantumab monotherapy was well tolerated across all dose levels. Safety and PK data from this study support further seribantumab investigations in genomically defined populations.

Clinical trial registration NCT00734305. August 12, 2008.
Risk stratification in cardiogenic shock: a focus on the available evidence
Authors: Sciaccaluga C. , Mandoli G. E. , Ghionzoli N. , Anselmi F. , Dini C. Sorini , Righini F. , Cesareo F. , D’Ascenzi F. , Focardi M. , Valente S. , Cameli M.
Published: July 2021

Cardiogenic shock is a clinical syndrome which is defined as the presence of primary cardiac disorder that results in hypotension together with signs of organ hypoperfusion in the state of normovolaemia or hypervolaemia. It represents a complex life-threatening condition, characterized by a high mortality rate, that requires urgent diagnostic assessment as well as treatment; therefore, it is of paramount important to advocate for a thorough risk stratification. In fact, the early identification of patients that could benefit the most from more aggressive and invasive approaches could facilitate a more efficient resource allocation. This review attempts to critically analyse the current evidence on prognosis in cardiogenic shock, focusing in particular on clinical, laboratoristic and echocardiographic prognostic parameters. Furthermore, it focuses also on the available prognostic scores, highlighting the strengths and the possible pitfalls. Finally, it provides insights into future direction that could be followed in order to ameliorate risk stratification in this delicate subset of patients.
Fighting Insurgency, Ruining the Environment: the Case of Forest Fires in the Dersim Province of Turkey
Authors: Dinc Pinar , Eklund Lina , Shahpurwala Aiman , Mansourian Ali , Aturinde Augustus , Pilesjö Petter
Published: July 2021

Environmental destruction has long been used as a military strategy in times of conflict. A long-term example of environmental destruction in a conflict zone can be found in Dersim/Tunceli province, located in Eastern Turkey. In the last century, at least two military operations negatively impacted Dersim’s population and environment: 1937–38 and 1993–94. Both conflict and environmental destruction in the region continued after the 1990s. Particularly after July 2015, when the brief peace process that began in 2013 ended, conflict between the Turkish state and the Kurdistan Workers’ Party (PKK) resumed and questions arose about the cause of forest fires in Dersim. In this research we investigate whether there is a relationship between conflict and forest fires in Dersim. This is denied by the Turkish state but asserted by many Dersim residents, civil society groups, and political parties. We use a multi-disciplinary approach, combining methods of qualitative analysis of print media (newspapers), social media (Twitter), and local accounts, together with quantitative methods: remote sensing and spatial analysis. Interdisciplinary analysis combining quantitative datasets with in-depth, qualitative data allows a better understanding of the role of conflict in potentially exacerbating the frequency and severity of forest fires. Although we cannot determine the cause of the fires, the results of our statistical analysis suggest a significant relationship between fires and conflict in Dersim, indicating that the incidence of conflicts is generally correlated with the number of fires.
Chronically Activated T-cells Retain Their Inflammatory Properties in Common Variable Immunodeficiency
Authors: Berbers Roos-Marijn , van der Wal M. Marlot , van Montfrans Joris M. , Ellerbroek Pauline M. , Dalm Virgil A. S. H. , van Hagen P. Martin , Leavis Helen L. , van Wijk Femke
Published: July 2021

Purpose

Immune dysregulation complications cause significant morbidity and mortality in common variable immunodeficiency (CVID), but the underlying pathophysiology is poorly understood. While CVID is primarily considered a B-cell defect, resulting in the characteristic hypogammaglobulinemia, T-cells may also contribute to immune dysregulation complications. Here, we aim to further characterize T-cell activation and regulation in CVID with immune dysregulation (CVIDid).

Methods

Flow cytometry was performed to investigate T-cell differentiation, activation and intracellular cytokine production, negative regulators of immune activation, regulatory T-cells (Treg), and homing markers in 12 healthy controls, 12 CVID patients with infections only (CVIDio), and 20 CVIDid patients.

Results

Both CD4 + and CD8 + T-cells in CVIDid showed an increased activation profile (HLA-DR + , Ki67 + , IFNγ +) when compared to CVIDio, with concomitant upregulation of negative regulators of immune activation PD1, LAG3, CTLA4, and TIGIT. PD1 + and LAG3 + subpopulations contained equal or increased frequencies of cells with the capacity to produce IFNγ, Ki67, and/or GzmB. The expression of PD1 correlated with serum levels of CXCL9, 10, and 11. Treg frequencies were normal to high in CVIDid, but CVIDid Tregs had reduced CTLA-4 expression, especially on CD27 + effector Tregs. Increased migratory capacity to inflamed and mucosal tissue was also observed in CVIDid T-cells.

Conclusion

CVIDid was characterized by chronic activation of peripheral T-cells with preserved inflammatory potential rather than functional exhaustion, and increased tissue migratory capacity. While Treg numbers were normal in CVIDid Tregs, low levels of CTLA-4 indicate possible Treg dysfunction. Combined studies of T-cell dysfunction and circulating inflammatory proteins may direct future treatment strategies.
Alexithymia and Emotion Regulation Strategies in Adolescent Gamblers with and Without At-Risk Profiles
Authors: Estévez Ana , Jauregui Paula , Macía Laura , Martín-Pérez Cristina
Published: July 2021

Alexithymia, difficulties in emotion regulation, and negative affect play an important role in adolescents who present pathological gambling. Therefore, the objectives of the present study were, firstly, to analyze the differences between alexithymia, difficulties in emotion regulation, and positive and negative affect in adolescents with and without risk of gambling problems. Secondly, the relationships between all the variables of the study in adolescents with and without risk of problem gambling were analyzed separately. Thirdly, we analyzed the mediating role of positive and negative affect in the relationship between alexithymia and dysfunctional emotion regulation strategies (ERS) in adolescents at risk of gambling problems. The sample was composed of 206 adolescents with ages ranging from 12 to 18 years (M = 15.52; SD = 1.43). They were divided into two groups according to the score obtained in the South Oaks Gambling Screen-Revised for Adolescents (SOGS-RA). Thus, 84 were included in the group without risk of gambling problems and 122 in the group at risk of gambling problems. The results obtained revealed higher scores in negative affect and pathological gambling in the group at risk of gambling problems. Likewise, positive relationships between alexithymia, maladaptive emotion regulation strategies (MERS), and affect were found. Mediation analyses showed that difficulties in identifying feelings were indirectly related to greater use of dysfunctional ERS through their relationship with negative affect in at-risk gamblers.
Computing Dynamic User Equilibrium on Large-Scale Networks Without Knowing Global Parameters
Authors: Thong Duong Viet , Gibali Aviv , Staudigl Mathias , Vuong Phan Tu
Published: July 2021

Dynamic user equilibrium (DUE) is a Nash-like solution concept describing an equilibrium in dynamic traffic systems over a fixed planning period. DUE is a challenging class of equilibrium problems, connecting network loading models and notions of system equilibrium in one concise mathematical framework. Recently, Friesz and Han introduced an integrated framework for DUE computation on large-scale networks, featuring a basic fixed-point algorithm for the effective computation of DUE. In the same work, they present an open-source MATLAB toolbox which allows researchers to test and validate new numerical solvers. This paper builds on this seminal contribution, and extends it in several important ways. At a conceptual level, we provide new strongly convergent algorithms designed to compute a DUE directly in the infinite-dimensional space of path flows. An important feature of our algorithms is that they give provable convergence guarantees without knowledge of global parameters. In fact, the algorithms we propose are adaptive, in the sense that they do not need a priori knowledge of global parameters of the delay operator, and which are provable convergent even for delay operators which are non-monotone. We implement our numerical schemes on standard test instances, and compare them with the numerical solution strategy employed by Friesz and Han.
Model order reduction based on direct normal form: application to large finite element MEMS structures featuring internal resonance
Authors: Opreni Andrea , Vizzaccaro Alessandra , Frangi Attilio , Touzé Cyril
Published: July 2021

Dimensionality reduction in mechanical vibratory systems poses challenges for distributed structures including geometric nonlinearities, mainly because of the lack of invariance of the linear subspaces. A reduction method based on direct normal form computation for large finite element (FE) models is here detailed. The main advantage resides in operating directly from the physical space, hence avoiding the computation of the complete eigenfunctions spectrum. Explicit solutions are given, thus enabling a fully non-intrusive version of the reduction method. The reduced dynamics is obtained from the normal form of the geometrically nonlinear mechanical problem, free of non-resonant monomials, and truncated to the selected master coordinates, thus making a direct link with the parametrisation of invariant manifolds. The method is fully expressed with a complex-valued formalism by detailing the homological equations in a systematic manner, and the link with real-valued expressions is established. A special emphasis is put on the treatment of second-order internal resonances and the specific case of a 1:2 resonance is made explicit. Finally, applications to large-scale models of micro-electro-mechanical structures featuring 1:2 and 1:3 resonances are reported, along with considerations on computational efficiency.
Do equidistant energy levels necessitate a harmonic potential?
Authors: Teichert Fabian , Kuhn Eduard , Thränhardt Angela
Published: July 2021

Experimental results from literature show equidistant energy levels in thin Bi films on surfaces, suggesting a harmonic oscillator description. Yet this conclusion is by no means imperative, especially considering that any measurement only yields energy levels in a finite range and with a nonzero uncertainty. Within this study we review isospectral potentials from the literature and investigate the applicability of the harmonic oscillator hypothesis to recent measurements. First, we describe experimental results from literature by a harmonic oscillator model, obtaining a realistic size and depth of the resulting quantum well. Second, we use the shift-operator approach to calculate anharmonic non-polynomial potentials producing (partly) equidistant spectra. We discuss different potential types and interpret the possible modeling applications. Finally, by applying nth order perturbation theory we show that exactly﻿ equidistant eigenenergies cannot be achieved by polynomial potentials, except by the harmonic oscillator potential. In summary, we aim to give an overview over which conclusions may be drawn from the experimental determination of energy levels and which may not.