bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of the right temporoparietal junction and ventromedial prefrontal cortex to theory of mind in autism: A randomized, sham‐controlled tDCS study
Authors: Salehinejad Mohammad Ali , Paknia Nasim , Hosseinpour Amir Hossein , Yavari Fatemeh , Vicario Carmelo M. , Nitsche Michael A. , Nejati Vahid 
Published: May 2021

AbstractTheory of mind (ToM) is the ability to attribute subjective mental states to oneself and others and is significantly impaired in autism spectrum disorder (ASD). A frontal‐posterior network of regions including the ventromedial prefrontal cortex (vmPFC) and temporoparietal junction (TPJ) is involved in ToM. Previous studies show an underactivation of these regions in ASD. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation method for causally investigating brain‐behavior relationships via induction of cortical excitability alterations. tDCS, mostly over the dorsolateral prefrontal cortex, has been increasingly applied for improving behavioral problems in ASD leaving other potentially interesting regions untouched. Here we investigated contribution of the vmPFC and right TPJ in ToM abilities of ASD children via tDCS in a pilot study. Sixteen children with ASD (mean age = 10.7 ± 1.9) underwent three tDCS sessions (1 mA, 20 min) in a randomized, sham‐controlled design. Stimulation protocols included: (a) anodal vmPFC tDCS, (b) anodal r‐TPJ tDCS, and (c) sham tDCS. ToM abilities were explored during tDCS using the theory of mind test (TOMT). Our results show that activation of the vmPFC with anodal tDCS significantly improved ToM in children with ASD compared with both, r‐TPJ tDCS, and sham stimulation. Specifically, precursors of ToM (e.g., emotion recognition, perception, and imitation) and elementary ToM skills (e.g., first‐order mental state reasoning) were significantly improved by anodal vmPFC tDCS. Based on these results, the vmPFC could be a potential target region for the reduction of ASD symptoms via noninvasive brain stimulation, which should be examined in larger detail in future studies.Lay SummaryTheory of mind (ToM) is the ability to infer mental states of oneself and others, which is impaired in autism. Brain imaging studies have shown involvement of two brain regions in ToM (ventromedial prefrontal cortex, temporoparietal junction) which are underactivated in autism. We increased activation of these regions via noninvasive brain stimulation in this experiment to see how it would affect ToM abilities in autism. We found that increased activation of the ventromedial prefrontal cortex improved ToM abilities in children with autism.
In vitro and In silico biopharmaceutic regulatory guidelines for generic bioequivalence for oral products: Comparison among various regulatory agencies
Authors: Kollipara Sivacharan , Ahmed Tausif , Bhattiprolu Adithya Karthik , Chachad Siddharth 
Published: May 2021

AbstractGeneric drug development is a complex process that involves development of formulation similar to reference product. Because of the complexity associated with generic drug development, many regulatory agencies have come up with various guidelines. Out of many guidelines, the biopharmaceutics classification system that was introduced in 1995 based on aqueous solubility and permeability helped many pharmaceutical scientists across the globe to utilize the tool for formulation development, waiver of in vivo studies. Later on in vitro guidelines based on dissolution and in vitro in vivo correlation were introduced by many regulatory agencies with an intent to reduce number of in vivo human testing thereby facilitating shorter development time and faster approvals and launch. Most recently, understanding the importance in silico approaches such as physiologically based pharmacokinetic modelling, regulatory agencies such as United States Food and Drug Administration (USFDA) and European Middle East and Africa (EMA) came up with modelling guidance documents. Even though consensus exists between guidance documents from various regulatory agencies, still there are many minor to major differences exists between these guidance documents that needs to be considered while submitting a generic drug application. This review aims to compare all the in vitro and in silico guidance documents from major regulatory agencies with emphasis on latest trends and technologies combined with regulatory acceptability with an intention to harmonize regulations. Guidance documents from major regulatory agencies such as USFDA, EMA, World Health Organization, International Council for Harmonization and other emerging markets were compared. Similarities &differences among these guidance documents are critically reviewed to provide the reader a detailed overview of these guidance documents at one place.
Attributions for ambiguity in a treatment‐decision context can create ambiguity aversion or seeking
Authors: Stuart Jillian O'Rourke , Windschitl Paul D. , Miller Jane E. , Smith Andrew R. , Zikmund‐Fisher Brian J. , Scherer Laura D. 
Published: May 2021

AbstractThe phenomenon of ambiguity aversion suggests that people prefer options that offer precisely rather than imprecisely known chances of success. However, past work on people's responses to ambiguity in health treatment contexts found ambiguity seeking rather than aversion. The present work addressed whether such findings reflected a broad tendency for ambiguity seeking in health treatment contexts or whether specific attributions for ambiguity play a substantial role. In three studies, people choose between two treatment options that involved similar underlying probabilities, except that the probabilities for one option involved ambiguity. The attributions offered for the ambiguity played an important role in the results. For example, when the range of probabilities associated with an ambiguous treatment was attributed to the fact that different studies yield different results, participants tended to show ambiguity aversion or indifference. However, when the range was attributed to something that participants could control (e.g., regular application of a cream) or something about which they were overoptimistic (e.g., their immune system function), participants tended to show ambiguity seeking. Health professionals should be mindful of how people will interpret and use information about ambiguity when choosing among treatments.
Site‐Specific Small Molecule Labeling of an Internal Loop in JC Polyomavirus Pentamers Using the π‐Clamp‐Mediated Cysteine Conjugation
Authors: Baccile Joshua A. , Voorhees Peter J. , Chillo Anthony J. , Berry Madeline , Morgenstern Robin , Schwertfeger Tyler J. , Rossi Francis M. , Nelson Christian D. S. 
Published: May 2021

AbstractThe major capsid protein VP1 of JC Polyomavirus assembles into pentamers that serve as a model for studying viral entry of this potentially severe human pathogen. Previously, labeling of viral proteins utilized large fusion proteins or non‐specific amine‐ or cysteine‐functionalization with fluorescent dyes. Imaging of these sterically hindered fusion proteins or heterogeneously labeled virions limits reproducibility and could prevent the detection of subtle trafficking phenomena. Here we advance the π‐clamp‐mediated cysteine conjugation for site‐selective fluorescent labeling of VP1‐pentamers. We demonstrate a one‐step synthesis of a probe consisting of a bio‐orthogonal click chemistry handle bridged to a perfluoro‐biphenyl π‐clamp reactive electrophile by a polyethylene glycol linker. We expand the scope of the π‐clamp conjugation by demonstrating selective labeling of an internal, surface exposed loop in VP1. Thus, the π‐clamp conjugation offers a general method to selectively bioconjugate tags‐of‐interest to viral proteins without impeding their ability to bind and enter cells.
Methods to increase native warm‐season grass diversity in bermudagrass
Authors: Rogers James K. , Robertson Scott G. 
Published: May 2021

AbstractBermudagrass [Cynodon dactylon (L.) Pers.] is the most common warm‐season introduced forage species grown in the southern portion of the United States. Often grown as a monoculture, bermudagrass responds well to fertilizer and intensive management but provides little wildlife or microbial soil community benefits due to the lack of species diversity. A methods study to evaluate methods of increasing diversity of bermudagrass by adding switchgrass (SG) or a native warm‐season grass mixture (NGMIX) was conducted in southern Oklahoma. An established bermudgrass stand was suppressed using either 7, 11, or 19 months of seedbed preparation time (PREP) with either zero, one, two, or three cover crops depending on PREP time and applied to either till or no‐till strips. Initiation of PREP times were staggered so a common date for SG and NGMIX planting was achieved in two consecutive planting years, April 2011 (Year 1) and April 2012 (Year 2). On both soil textures, till establishment increased stand frequency of SG and NGMIX the year of establishment compared to no‐till. Stand frequency was repeated in 2015 (3 and 4 years post planting, respectively). The loam soil, no‐till stand frequency counts in 2015 had improved for SG and NGMIX and were similar to till. The sandy loam site 2015 stand frequency counts of till established SG and NGMIX remained higher than no‐till. No‐till establishment was slower than and not as successful as till but it still achieved plant diversity in bermudagrass at a lower cost compared to till. Cover crops and PREP time had little effect on establishment.
Application of direct stochastic optical reconstruction microscopy (dSTORM) to the histological analysis of human glomerular disease
Authors: Garcia Edwin , Lightley Jonathan , Kumar Sunil , Kalita Ranjan , Gőrlitz Frederik , Alexandrov Yuriy , Cook Terry , Dunsby Christopher , Neil Mark AA , Roufosse Candice A , French Paul MW 
Published: May 2021

AbstractElectron microscopy (EM) following immunofluorescence (IF) imaging is a vital tool for the diagnosis of human glomerular diseases, but the implementation of EM is limited to specialised institutions and it is not available in many countries. Recent progress in fluorescence microscopy now enables conventional widefield fluorescence microscopes to be adapted at modest cost to provide resolution below 50 nm in biological specimens. We show that stochastically switched single‐molecule localisation microscopy can be applied to clinical histological sections stained with standard IF techniques and that such super‐resolved IF may provide an alternative means to resolve ultrastructure to aid the diagnosis of kidney disease where EM is not available. We have implemented the direct stochastic optical reconstruction microscopy technique with human kidney biopsy frozen sections stained with clinically approved immunofluorescent probes for the basal laminae and immunoglobulin G deposits. Using cases of membranous glomerulonephritis, thin basement membrane lesion, and lupus nephritis, we compare this approach to clinical EM images and demonstrate enhanced imaging compared to conventional IF microscopy. With minor modifications in established IF protocols of clinical frozen renal biopsies, we believe the cost‐effective adaptation of conventional widefield microscopes can be widely implemented to provide super‐resolved image information to aid diagnosis of human glomerular disease.
Mechanistic Insights into the Selective Electroreduction of Crotonaldehyde to Crotyl Alcohol and 1‐Butanol
Authors: Ting Louisa Rui Lin , Peng Yujie , Yeo Boon Siang 
Published: May 2021

AbstractThe electroreduction of crotonaldehyde, which can be derived from the aldol condensation of acetaldehyde (sustainably produced from CO2 reduction or from biomass ethanol), is potentially a carbon‐neutral route for generating high‐value C4 chemicals such as crotyl alcohol and 1‐butanol. Developing functional catalysts is necessary toward this end. Herein, the electrocatalytic conversion of crotonaldehyde to crotyl alcohol and 1‐butanol was achieved in 0.1 m potassium phosphate buffer electrolyte (pH=7). More importantly, the mechanisms and structure‐activity relationships of these transformations were elucidated. Crotyl alcohol was formed on oxide‐derived Ag at −0.75 V versus the reversible hydrogen electrode (RHE) with a faradaic efficiency (FE) of 84.3 % (reactant conversion after 75 min electrolysis=9.8 %), which is 1.6 times higher than that on polished Ag foils. The coordinatively‐unsaturated sites on oxide‐derived Ag surfaces were proposed to facilitate crotonaldehyde adsorption via its oxygen atom in order to promote crotyl alcohol formation. On electrodeposited Fe nanoflakes, crotonaldehyde could be reduced to 1‐butanol with an outstanding FE of 60.6 % (reactant conversion after 75 min electrolysis=9.4 %) at −0.70 V vs. RHE. This is nearly 3 times higher than the FE of 1‐butanol observed on polished Fe foils at the same potential. More strikingly, the corresponding partial current density of 1‐butanol was −9.19 mA cm−2, which is 43 times higher than that on Fe foils. The presence of tensile strains and grain boundaries on the Fe nanoflakes were elucidated and suggested to activate a concerted reduction of the C=O and C=C bonds in crotonaldehyde to produce 1‐butanol selectively.
Generalization of shadow filters in fractional domain
Authors: Varshney Garima , Pandey Neeta , Pandey Rajeshwari 
Published: May 2021

AbstractThis work is intended to generalize the design of shadow filters to the fractional‐order domain. Shadow filters, in integer‐order domain, introduced by Lakys and Fabre, consist of an external amplifier in the feedback loop of the basic filter cell and by varying the gain of this amplifier the parameters of the resulting filter are modified without disturbing the active and passive components of the filter itself. In particular, we consider here the case where a basic 2α order filter is constructed using two fractional‐order capacitors both of the same order α. Mathematical formulations are drafted for pole frequency and pole quality factor for different feedback signals with various cases of stability and demonstrated using MATLAB simulations. Functional verification of the proposed theory is verified using an active filter example, designed around operational transconductance amplifier (OTA), through SPICE using 180 nm CMOS technology model parameters.
Bootstrapped LARAC algorithm for fast delay‐sensitive QoS provisioning in SDN networks
Authors: BinSahaq Ahmed , Sheltami Tarek , Mahmoud Ashraf , Nasser Nidal 
Published: May 2021

SummaryIn today's networks, QoS provisioning becomes a major concern for service providers due to the massive increase in connected devices (e.g., mobile devices, servers, and Things), traffic in between, and the diverse service requirements (e.g., delay and bandwidth). Software‐Defined Networking (SDN) promises solution for such issues with its central network control flexibility compared to traditional networking; nonetheless, a design of a fast and QoS guaranteeing routing algorithm is still needed. Delay Constrained Least Cost (DCLC) is a well‐known NP‐hard problem. LAgrange Relaxation‐based Aggregated Cost (LARAC) algorithm is a Dijkstra‐based QoS‐aware algorithm and one of many heuristic algorithms proposed in the literature to solve the DCLC problem. Despite its outstanding performance over other algorithms in SDN, it still needs improvement. In this article, we present a modified version of LARAC, called MODLARAC, to improve the solution feasibility search state by exploiting LARAC's lower‐bound paths before the approximation process start. Also, we modify its stop condition to avoid extra non‐useful Dijkstra calls. We implement and evaluate MODLARAC using a realistic ISP network topology using Mininet and controlled by Floodlight SDN controller. We then compare MODLARAC against the original LARAC and BiLAD algorithms. The obtained results showed improvement up to 20% reduction in Dijkstra calls count compared to original LARAC and BiLAD algorithms without a significant increase in path's cost or delay metrics. It reached only 3% increase in path cost and 7% in path delay in its worst case with a safe distance of 11% lower than the delay demand.
Exogenous ketosis in patients with type 2 diabetes: Safety, tolerability and effect on glycaemic control
Authors: Soto‐Mota Adrian , Norwitz Nicholas G. , Evans Rhys , Clarke Kieran , Barber Thomas M. 
Published: May 2021

AbstractIntroductionKetogenic diets have shown to improve glycaemic control in patients with type 2 diabetes. This study investigated the safety, tolerability, and effects on glycaemic control in patients with type 2 diabetes of an exogenous ketone monoester (KE) capable of inducing fasting‐like elevations in serum β‐hydroxybutyrate (βHB) without the need for caloric or carbohydrate restriction.MethodsTwenty one participants (14 men and 7 women, aged 45 ± 11 years) with insulin‐independent type 2 diabetes, and unchanged hypoglycaemic medication for the previous 6 months, were recruited for this non‐randomised interventional study. Participants wore intermittent scanning glucose monitors (IS‐GM) for a total of 6 weeks and were given 25 ml of KE 3 times daily for 4 weeks. Serum electrolytes, acid‐base status, and βHB concentrations were measured weekly and cardiovascular risk markers were measured before and after the intervention. The primary endpoints were safety and tolerability, with the secondary endpoint being glycaemic control.ResultsThe 21 participants consumed a total of 1,588 drinks (39.7 litres) of KE over the course of the intervention. Adverse reactions were mild and infrequent, including mild nausea, headache, and gastric discomfort following fewer than 0.5% of the drinks. Serum electrolyte concentrations, acid‐base status, and renal function remained normal throughout the study. Compared to baseline, exogenous ketosis induced a significant decrease in all glycaemic control markers, including fructosamine (335 ± 60 μmol/L to 290 ± 49 μmol/L, p < .01), HbA1c (61 ± 10 mmol/mol to 55 ± 9 mmol/mol [7.7 ± 0.9% to 7.2 ± 0.9%], p < .01), mean daily glucose (7.8 ± 1.4 mM to 7.4 ± 1.3 mM [140 ± 23 mg/dl to 133 ± 25 mg/dl], p < .01) and time in range (67 ± 11% to 69 ± 10%, p < .01).ConclusionsConstant ketone monoester consumption over 1 month was safe, well tolerated, and improved glycaemic control in patients with type 2 diabetes.
Palliative care in metastatic head and neck cancer
Authors: Civantos Alyssa M. , Prasad Aman , Carey Ryan M. , Bur Andrés M. , Mady Leila J. , Brody Robert M. , Rajasekaran Karthik , Cannady Steven B. , Hartner Lee , Ibrahim Said A. , Newman Jason G. , Brant Jason A. 
Published: May 2021

AbstractBackgroundDue to inherent impact on quality of life, metastatic head and neck cancer patients are well‐suited to benefit from palliative care (PC). Our objective was to examine factors that shape PC utilization and implications for overall survival in stage IVc head and neck cancer patients.MethodsA retrospective study of patients with stage IVc head and neck cancer in the National Cancer Database from 2004 and 2015 was conducted.Results7794 cases met inclusion criteria, of which 19.3% received PC. PC use was associated with more recent years of diagnosis, Northeast facility geography, and non‐private insurances (p < 0.05). Compared to no PC, “interventional” PC, defined as palliative surgery, radiation, and/or chemotherapy, and “pain management only” PC were associated with lower overall survival (p < 0.05).ConclusionsPC use increased over time and was associated with demographic and clinical factors. There remains opportunity for improvement in optimal implementation of palliative care.
The effects of health insurance on the choice of medical procedures: Evidence from heart attacks and childbirths
Authors: Castaneda Marco A. , Saygili Meryem 
Published: May 2021

AbstractThis paper investigates the effect of health insurance on the use of alternative procedures to treat a given medical condition. In particular, we estimate the effect of health insurance on the use of bypass surgery after a heart attack and on the use of a C‐section after a normal pregnancy. These procedures are the most expensive, compared to the alternatives. Theoretically, the demand for some procedures like bypass surgery is likely to be inelastic. In this situation, health insurance should have no effect on the use of the procedure. For other procedures such as C‐section, demand may be more elastic, especially after a normal pregnancy without complications. We use a nationally representative dataset of inpatient hospital admissions from the United States and control for individual and hospital characteristics. The results from our empirical analysis support our predictions. For patients admitted to a hospital because of a heart attack, being uninsured has no effect on the probability of bypass surgery. However, for patients admitted for childbirth, the uninsured have a substantially lower probability of a C‐section delivery.
Early childhood education and care (ECEC) during COVID‐19 boosts growth in language and executive function
Authors: Davies Catherine , Hendry Alexandra , Gibson Shannon P. , Gliga Teodora , McGillion Michelle , Gonzalez‐Gomez Nayeli 
Published: May 2021

AbstractHigh‐quality, centre‐based education and care during the early years benefit cognitive development, especially in children from disadvantaged backgrounds. During the COVID‐19 pandemic and its associated lockdowns, access to early childhood education and care (ECEC) was disrupted. We investigate how this period affected the developmental advantages typically offered by ECEC. Using parent‐report data from 189 families living in the UK, we explore associations between time spent in ECEC by 8‐to‐36‐month‐olds, their socioeconomic background, and their growth in language and executive functions between Spring and Winter 2020. Receptive vocabulary growth was greater in children who continued to attend ECEC during the period, with a stronger positive effect for children from less advantaged backgrounds. The growth of cognitive executive functions (CEFs) was boosted by ECEC attendance during the period, regardless of socioeconomic background. Our findings highlight the importance of high‐quality ECEC for the development of key skills and for levelling socioeconomic inequalities.
Designing for Mathematical Literacy: Introducing Exponential Growth Using Critical and Meaningful Problem Contexts
Authors: Zahner William 
Published: May 2021

AbstractThis department explores the concept of disciplinary literacy—the conceptual understandings and ways of reading, thinking, and writing involved in critiquing and constructing knowledge in a discipline—and its intersections with aspects of culturally sustaining pedagogy. Columns highlight high‐quality disciplinary literacy learning opportunities across subject areas that engage students in critically examining the world around them, interrogating accepted knowledge, contributing their own perspectives to shape that knowledge, and sustaining and developing the literacies needed to do this work.