bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcranial direct current stimulation for upper extremity spasticity rehabilitation in stroke survivors: A systematic review of randomized controlled trials
Authors: Alashram Anas R. , Padua Elvira , Aburub Aseel , Raju Manikandan , Annino Giuseppe 
Published: March 2022

AbstractObjectivesTo examine the effects of transcranial direct current stimulation (tDCS) on upper extremity spasticity after stroke and to define the most effective tDCS parameters.Literature SurveySystematic review in the following databases: PubMed, SCOPUS, PEDro, CINAHL, MEDLINE, REHABDATA, AMED, and Web of Science databases. Studies up to June 2020 were included.MethodologyStudies were included if the sample was composed of individuals with stroke, the intervention followed a tDCS intervention (alone or combined with another intervention), and the study was a randomized controlled trial including at least one measurement assessing upper extremity spasticity. Two authors independently screened the included studies. Conflicting decisions between authors were resolved by discussion with the third author. The methodological quality was assessed using the Cochrane Collaboration's tool. The authors determined that the meta‐analysis was not feasible due to the heterogeneity in the protocols among the included studies.SynthesisAfter the screening of 1204 records, a total of seven studies met the specified inclusion criteria and involved 320 participants (mean age = 60.3), 31.1% of whom were females. Patients with ischemic stroke comprised 77.2% of the total patients, and 42.2% were with right hemispheric stroke. Six studies exhibited “high” quality and one exhibited “moderate” quality. Five of the selected studies that combined the tDCS intervention and other traditional interventions showed a significant reduction in upper extremity spasticity after stroke following tDCS intervention. The other two studies that delivered tDCs alone did not show a significant difference.ConclusionsThe evidence for the effect of tDCS on upper extremity spasticity after stroke was limited. The optimal tDCS treatment dosage remains unclear. Additional studies with large sample sizes and long‐term follow‐up are strongly warranted.
Prospective clinical trial of disulfiram plus copper in men with metastatic castration‐resistant prostate cancer
Authors: Zhang Tian , Kephart Julie , Bronson Elizabeth , Anand Monika , Daly Christine , Spasojevic Ivan , Bakthavatsalam Subha , Franz Katherine , Berg Hannah , Karachaliou Georgia S. , James Olga G. , Howard Lauren , Halabi Susan , Harrison Michael R. , Armstrong Andrew J. , George Daniel J. 
Published: March 2022

AbstractBackgroundIn preclinical models of prostate cancer (PC), disulfiram (DSF) reduced tumor growth only when co‐administered with copper (Cu), and Cu uptake in tumors is partially regulated by androgen‐receptor signaling. However, prior trials of DSF in PC used DSF as monotherapy.ObjectiveTo assess the safety and efficacy of concurrent administration of DSF with Cu, we conducted a phase 1b clinical trial of patients with metastatic castration‐resistant prostate cancer (mCRPC) receiving Cu with DSF.Design, setting, and participantsPatients with mCRPC were treated in two cohorts: mCRPC with nonliver/peritoneal metastases (A), and mCRPC with liver and/or peritoneal metastases (B). Baseline Cu avidity was measured by 64CuCl2 PET scan. Intravenous (IV) CuCl2 was given weekly for three doses with oral daily DSF followed by daily oral Cu gluconate and DSF until disease progression. DSF and metabolite diethyldithiocarbamic acid methyl ester (Me‐DDC) levels in plasma were measured. DSF and Me‐DDC were then assessed for cytotoxicity in vitro.ResultsWe treated nine patients with mCRPC (six on cohort A and three on cohort B). Bone and nodal metastases showed differential and heterogeneous Cu uptake on 64CuCl2 PET scans. No confirmed PSA declines or radiographic responses were observed. Median PFS was 2.8 months and median OS was 8.3 months. Common adverse events included fatigue and psychomotor depression; no Grade 4/5 AEs were observed. Me‐DDC was measurable in all samples (LOQ = 0.512 ng/ml), whereas DSF was not (LOQ = 0.032 ng/ml, LOD = 0.01 ng/ml); Me‐DDC was not cytotoxic in vitro.ConclusionsOral DSF is not an effective treatment for mCRPC due to rapid metabolism into an inactive metabolite, Me‐DDC. This trial has stopped enrollment and further work is needed to identify a stable DSF formulation for treatment of mCRPC.
Wind‐Topo: Downscaling near‐surface wind fields to high‐resolution topography in highly complex terrain with deep learning
Authors: Dujardin Jérôme , Lehning Michael 
Published: March 2022

AbstractPredicting wind flow in highly complex terrain like the Alps is a challenge for all models. When physical processes need to be resolved in a spatially explicit manner, grids with high horizontal resolution of a few hundred meters are often required and drastically limit, in many cases, the extent and duration of the simulations. Many surface process models, like the simulation of heterogeneous snow cover across a season, however, need long time series on large domains as inputs. Statistical downscaling can provide the required data, but no model can reach the desired resolutions effectively and provide temporally resolved wind speed and direction on highly complex topography. The assessment of the potential for wind energy in the Alps, a promising player in the energy transition, is an example where the current shortcomings cause strong limitations. We present “Wind‐Topo”, a novel approach based on deep learning that discovers some of the interactions between high‐resolution topography and coarser‐resolution states of the atmosphere to generate near‐surface wind fields with a 50‐m resolution. In our test case, we use a large number of measurement stations in Switzerland to train the model and an operational weather prediction model (COSMO‐1) as predictor. Wind‐Topo employs a custom architecture that analyses the state of the atmosphere on various scales and associates it with high‐resolution topography. A dedicated loss function leads to good scoring metrics as well as accurate wind‐speed distributions at 60 independent stations used for a thorough validation. 50‐m resolution wind fields are generated efficiently and exhibit several expected orographic effects like ridge acceleration, sheltering, and deflection. Furthermore, the bias and mean absolute error from COSMO‐1 at the alpine validation stations, which are 0.72 and 1.77 ms respectively, are reduced to 0.07 and 1.21 ms.
Mapping terrestrial groundwater‐dependent ecosystems in arid Australia using Landsat‐8 time‐series data and singular value decomposition
Authors: Brim Box Jayne , Leiper Ian , Nano Catherine , Stokeld Danielle , Jobson Peter , Tomlinson Adrian , Cobban Dale , Bond Tim , Randall Debbie , Box Paul 
Published: March 2022

AbstractThe spatial extent of terrestrial vegetation types reliant on groundwater in arid Australia is poorly known, largely because they are located in remote areas that are expensive to survey. In previous attempts, the use of traditional remote sensing approaches failed to discriminate vegetation using groundwater from surrounding vegetation. Difficulties in discerning vegetation groundwater use by remote sensing may be exacerbated by the unpredictable rainfall patterns and lack of annual wet and dry seasons common in arid Australia. This study presents a novel approach to mapping terrestrial groundwater‐dependent ecosystems (GDEs) by applying singular value decomposition (SVD) to time‐series of vegetation indices derived from Landsat‐8 data, to isolate the temporal and spatial sources of variation associated with groundwater use. In‐situ data from 442 sites were used to supervise and validate logistic regression models and neural networks, to determine whether sites could be correctly classified as GDEs using components obtained from the SVD. These results were used to produce a probability map of GDE occurrence across a 557 000 ha study area. Overall accuracy of the final classification map was 79%, with 72% of sites correctly identified as GDEs (true positives) and 16% incorrectly classified as GDEs (false positives). The approach is broadly applicable in arid regions globally, and is easily validated if general background knowledge of regional vegetation exists. Globally, and going forward, increased water extraction is expected to severely limit water available for GDEs. Successfully mapping GDEs in arid environments is a critical step towards their sustainable management, and the human and natural systems reliant upon them.
Recent Advances and Prospects of Small Molecular Organic Thermoelectric Materials
Authors: Zhou Dan , Zhang Hehui , Zheng Haolan , Xu Zhentian , Xu Haitao , Guo Huilong , Li Peining , Tong Yongfen , Hu Bin , Chen Lie 
Published: March 2022

AbstractThermoelectric (TE) materials possess unique energy conversion capabilities between heat and electrical energy. Small organic semiconductors have aroused widespread attention for the fabrication of TE devices due to their advantages of low toxicity, large area, light weight, and easy fabrication. However, the low TE properties hinder their large‐scale commercial application. Herein, the basic knowledge about TE materials, including parameters affecting the TE performance and the remaining challenges of the organic thermoelectric (OTE) materials, are initially summarized in detail. Second, the optimization strategies of power factor, including the selection and design of dopants and structural modification of the dope‐host are introduced. Third, some achievements of p‐ and n‐type small molecular OTE materials are highlighted to briefly provide their future developing trend; finally, insights on the future development of OTE materials are also provided in this study.
Inverse Material Search and Synthesis Verification by Hand Drawings via Transfer Learning and Contour Detection
Authors: Serov Nikita , Vinogradov Vladimir 
Published: March 2022

AbstractNano‐ and micromaterials of various morphologies and compositions have extensive use in many different areas. However, the search for procedures giving custom nanomaterials with the desired structure, shape, and size remains a challenge and is often implemented by manual article screening. Here, for the first time, scanning and transmission electron microscopy inverse image search and hand drawing‐based search via transfer learning are developed, namely, VGG16 convolution neural network repurposing for image features extraction and image similarity determination. Moreover, the case use of this platform is demonstrated on the calcium carbonate system, where the data are acquired by random high throughput experimental synthesis, and on Au nanoparticles data extracted from the articles. This approach can be used for advanced nanomaterials search, synthesis procedure verification, and can be further combined with machine learning solutions to provide data‐driven nanomaterials discovery.
Extraordinary Ordovician trilobite Fantasticolithus gen. nov. from Peru and its bearing on the trinucleimorph hypothesis
Authors: Fortey Richard A. , Gutiérrez‐Marco Juan C. 
Published: March 2022

AbstractFantasticolithus isabelae, a new genus and species of trinucleid trilobite from the Lower Ordovician of Peru, developed anterior ventral cephalic ‘props’ that are unique in the Trilobita. Its broad and finely pitted genal prolongations are unlike those of any previously known trinucleid, and closely resemble those invariably present in the unrelated Family Harpetidae, supporting the hypothesis that the two families shared a similar mode of life, as ‘trinucleimorphs’. Fantasticolithus was probably derived from an early trinucleid with a marginal girder, although it resembles younger genera such as Marrolithus in its enlarged anterolateral pits. The new genus provides a natural experiment to test the hypothesis of trinucleimorphs as filter feeders that used a ventral feeding chamber. The role of the pitted marginal fringe as an egress for feeding currents is discussed. Fantasticolithus had an unusual anterior vent that provided a simpler exit mechanism for feeding currents than the pitted fringe. However, the pits were probably important for trinucleids that lacked an anterior arch.
Effects of mokuboito, a Japanese Kampo medicine, on long‐term clinical outcomes in patients with heart failure
Authors: Ezaki Hirotaka , Ayaori Makoto , Sato Hiroki , Sakurada Masami 
Published: March 2022

ABSTRACTAimWe previously reported that oral administration of mokuboito (a Japanese Kampo medicine) significantly improved symptoms in hospitalized patients with heart failure (HF). However, it remains unclear whether mokuboito treatment affects the long‐term clinical prognosis in patients with HF.MethodsWe retrospectively investigated the long‐term prognosis in 40 patients who participated in our previous study. Patients were allocated randomly to Group S (standard therapy alone) or Group M (oral administration of mokuboito plus standard therapy). The primary outcome was the composite endpoint of major adverse cardiovascular events (MACE; death from any cause, myocardial infarction or unstable angina, and readmission due to worsening HF) during 2 years.ResultsMACE were respectively observed in 13 and 5 patients in Group S and Group M (incidence rate per 100 person‐years, 57.7 versus 17.3; P = 0.02), and the hazard ratio (HR) was 0.32 (95% CI 0.12–0.91; P = 0.02). Death from any cause was respectively observed in seven and three patients in Group S and Group M (incidence rate per 100 person‐years, 22.6 versus 9.00; P = 0.18), and the HR was 0.41 (95% CI 0.11–1.58; P = 0.18). Readmission due to worsening HF was respectively observed in 11 and 5 in Group S and Group M (incidence rate per 100 person‐years, 44.4 versus 16.8; P = 0.08), and the HR was 0.39 (95% CI 0.13–1.12; P = 0.07).ConclusionsOral administration of mokuboito significantly improved long‐term clinical outcomes in patients hospitalized for HF during 2 years after discharge.
MicroRNA‐455‐3p functions as a tumor suppressor by targeting HDAC2 to regulate cell cycle in hepatocellular carcinoma
Authors: Ma Fuquan , Huang Jin , Li Weizhi , Li Peijie , Liu Mengying , Xue Hui 
Published: March 2022

AbstractHepatocellular carcinoma (HCC) is one of the most common cancers. MicroRNA has been studied more and more deeply and may become a new target for the treatment of HCC. Here, we investigated the role of miR‐455‐3p in HCC progression. Compared with non‐tumor tissues and normal human hepatic cells, miR‐455‐3p expression was significantly downregulated in HCC tissues and cell lines. And overexpression of miR‐455‐3p inhibited cell proliferation and migration but promoted cell apoptosis in HCC cell lines HepG2 and Huh7. Mechanism studies displayed that miR‐455‐3p targeted HDAC2 and negatively regulated HDAC2 expression. Moreover, HDAC2 was highly expressed in HCC tissues and cell lines. Overexpression of HDAC2 reversed the inhibitory effects of miR‐455‐3p on cell proliferation, migration and cell cycle protein (CDK6 and cyclin D1) expression, and neutralized the promotion effects of miR‐455‐3p on cell apoptosis and the activation of p53 pathway. Furthermore, a p53 inhibitor Pifithrin‐α (PFT‐α) effectively abolished the effects of miR‐455‐3p on HCC cell behaviors. Additionally, the role of miR‐455‐3p in tumorigenesis was evaluated by using a mouse xenograft model, and the data showed that miR‐455‐3p suppressed tumor growth in vivo. In summary, our results suggested that miR‐455‐3p targeted HDAC2 to inhibit cell proliferation, migration and promote cell apoptosis via the activation of p53 pathway.
Application of predictive models in boosting power of Alzheimer's disease clinical trials: A post hoc analysis of phase 3 solanezumab trials
Authors: Ezzati Ali , Davatzikos Christos , Wolk David A. , Hall Charles B. , Habeck Christian , Lipton Richard B. 
Published: March 2022

AbstractBackgroundThe ideal participants for Alzheimer's disease (AD) clinical trials would show cognitive decline in the absence of treatment (i.e., placebo arm) and would also respond to the therapeutic intervention.ObjectiveTo investigate if predictive models can be an effective tool for identifying and excluding people unlikely to show cognitive decline as an enrichment strategy in AD trials.MethodWe used data from the placebo arms of two phase 3, double‐blind trials, EXPEDITION and EXPEDITION2. Patients had 18 months of follow‐up. Based on the longitudinal data from the placebo arm, we classified participants into two groups: one showed cognitive decline (any negative slope) and the other showed no cognitive decline (slope is zero or positive) on the Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS‐cog). We used baseline data for EXPEDITION to train regression‐based classifiers and machine learning classifiers to estimate probability of cognitive decline. Models were applied to EXPEDITION2 data to assess predicted performance in an independent sample. Features used in predictive models included baseline demographics, apolipoprotein E ε4 genotype, neuropsychological scores, functional scores, and volumetric magnetic resonance imaging.ResultIn EXPEDITION, 46.3% of placebo‐treated patients showed no cognitive decline and the proportion was similar in EXPEDITION2 (45.6%). Models had high sensitivity and modest specificity in both the training (EXPEDITION) and replication samples (EXPEDITION2) for detecting the stable group. Positive predictive value of models was higher than the base prevalence of cognitive decline, and negative predictive value of models were higher than the base rate of participants who had stable cognition.ConclusionExcluding persons with AD unlikely to decline from the active and placebo arms of clinical trials using predictive models may boost the power of AD trials through selective inclusion of participants expected to decline.
Faecal microbiota transplantation for the treatment of acute haemorrhagic diarrhoea syndrome in two dogs
Authors: Wen Tsung Fei , Cho Ying Chu , Li Chia Yin 
Published: March 2022

AbstractA 2‐year‐old, male, entire mixed breed dog and a 10‐year‐old, spayed, female mixed breed dog were presented for acute onset of bloody diarrhoea and hypovolaemic shock. Faecal microbiota transplantation was introduced in addition to antibiotics and supportive care after resuscitation. Faecal condition improved after treatment, and both dogs recovered within 3 weeks.
Identifying potential paraben transformation products and evaluating changes in toxicity as a result of transformation
Authors: Penrose Michael T. , Cobb George P. 
Published: March 2022

AbstractParabens are a class of compounds often used as preservatives in personal care products, pharmaceuticals, and food. They have received attention recently due to findings that demonstrate estrogenic impacts and other adverse effects of parabens. Release into wastewater effluent is considered a major contributor to the spread of parabens into surface water. Current regulations in areas such as Japan, Europe, and Southeast Asia limit the concentrations of parabens that can be used in formulations but do not address concentrations discharged into waterbodies. Recent studies suggest that parent parabens are effectively eliminated by transformation during the wastewater treatment processes. Common tertiary treatments include ultrafiltration, chlorination, UV disinfection and ozonation. Ultrafiltration is used to remove solids before a disinfection step. Of the disinfection steps, ozonation is often the most effective at removing parabens. Not much is known about the toxicities of paraben transformation products. Of the transformation products, chlorinated parabens and PHBA are the most studied. Previous studies have shown that chlorinated parabens have greatly reduced estrogen agonistic activity when compared with the activity of parents. However, more recent studies have found that halogenated parabens actually have estrogen antagonistic activity. Further research involving chlorinated parabens could include other toxic endpoints. No known studies have evaluated adverse effects of oxygenated parabens. Parabens can interact with chlorine residues in the environment and form chlorinated products, this will occur at a faster rate during chlorination. Ozonation will oxidize parabens and UV disinfection can both oxidize and halogenate parabens. All studies determining potential transformation products have been done in laboratory settings or specific conditions. Further research is needed to determine if these transformations occur in situ.Practitioner Points
Common chemical processes utilized by wastewater treatment facilities are effective at transforming parabens.
Paraben transformation products are released in greater concentration in effluent than parent paraben compounds.
Halogenated transformation products have been identified as estrogen receptor antagonists.
Time-Domain Fluorescence Lifetime Imaging of cAMP Levels with EPAC-Based FRET Sensors
Authors: Kukk Olga , Klarenbeek Jeffrey , Jalink Kees 
Published: March 2022

AbstractSecond messenger molecules in eukaryotic cells relay the signals from activated cell surface receptors to intracellular effector proteins. FRET-based sensors are ideal to visualize and measure the often rapid changes of second messenger concentrations in time and place. Fluorescence Lifetime Imaging (FLIM) is an intrinsically quantitative technique for measuring FRET. Given the recent development of commercially available, sensitive and photon-efficient FLIM instrumentation, it is becoming the method of choice for FRET detection in signaling studies. Here, we describe a detailed protocol for time domain FLIM, using the EPAC-based FRET sensor to measure changes in cellular cAMP levels with high spatiotemporal resolution as an example.
Recent Directions in the Regulation of Insurance Claims Handling in the United Kingdom and Australia: A Model for Other Jurisdictions to Consider?
Authors: Bowley Robin 
Published: March 2022

AbstractThis chapter examines recent developments in the regulation of insurance claims handling in the United Kingdom and in Australia. It commences by reviewing the relevant Insurance Core Principles developed by the International Association of Insurance Supervisors which articulate the standards that national supervisors should implement to effectively regulate the handling of claims and the resolution of disputes with policyholders. From this basis, it then examines the various rules developed by the Financial Conduct Authority to regulate claims handling in the United Kingdom, and through the use of case studies discusses how compliance with these rules has been monitored and enforced. The chapter then examines the legal framework for regulating insurance claims handling in Australia, which has been significantly expanded following the implementation of the reforms recommended by the 2019 Royal Commission into Misconduct in the Banking, Superannuation and Financial Services Industry. The chapter concludes that the approaches adopted in these two jurisdictions could provide a model for similar jurisdictions considering similar regulatory challenges.
The Role of the Compliance Function in the Process of Managing the Risk of Non-Compliance in an Insurance Undertaking
Authors: Paś Wojciech 
Published: March 2022

AbstractThis chapter is devoted to the role and significance of the compliance function in an insurance undertaking. This chapter presents selected models of compliance functions in European insurance undertakings. The main assumption of the chapter was an attempt to determine the importance of the compliance function in the process of managing the risk of non-compliance by means of the functioning and organisation of this unit within the structures of an insurance undertaking.