bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural, thermal, and mechanical properties of silanized boron carbide doped epoxy nanocomposites
Authors: Gültekin Kürşat , Uğuz Gediz , Topcu Yıldıray , Özel Adnan
Published: June 2021

In the presented study, the structural, thermal, and mechanical properties of the nanocomposites were investigated by doping silanized hexagonal boron carbide (h‐B4C) nanoparticles in varying proportions (0.5%, 1%, 2%, 3%, 4%, and 5%) into the epoxy resin by weight. For this purpose, the surfaces of h‐B4C nanoparticles were silanized by using 3‐(glycidyloxypropyl) trimethoxysilane (GPS) to improve adhesion between h‐B4C nanoparticles and epoxy matrix. Then, the silanized nanoparticles were added to the resin by ultrasonication and mechanical stirring techniques to produce nanocomposites. The bond structure differences of silanized B4C nanoparticles (s‐B4C) and nanoparticle doped composites were investigated by using Fourier transform infrared spectroscopy. Scanning electron microscopy and energy dispersion X‐ray spectroscopy (SEM‐EDS) technique was used to examine the distribution of nanoparticles in the modified nanocomposites. Differential scanning calorimetry and thermogravimetric analysis techniques were used to determine the thermal properties of the neat and s‐B4C doped nanocomposites. The tensile test and dynamic mechanical analysis were performed to determine the mechanical properties. When the experimental results were examined, changes in the bonding structure of the s‐B4C nanoparticles doped nanocomposites and significant improvements in the mechanical and thermal properties were observed. The optimum doping ratio was determined as 2% by weight. At this doping ratio, the Tg, tensile strength and storage modulus increased approximately 18%, 35%, and 44% compared to the neat composite, respectively.
On arginine‐based polyurethane‐blends specific to vascular prostheses
Authors: Zumbardo‐Bacelis Gualberto Antonio , Meza‐Villegas Linnette Aracely , Pérez‐Aranda Cesar Antonio , Vargas‐Coronado Rossana , Castillo‐Cruz Omar , Montaño‐Machado Vanessa , Mantovani Diego , Cauich‐Rodríguez Juan Valerio
Published: June 2021

Polymer blends based on Tecoflex™ and an experimental aliphatic polyurethane (HMDI‐PCL‐arginine stands for 4,4 (metylene‐biscyclohexyl) isocyanate ‐ poly (ε caprolactone) diol, SPUUR stands for segmented poly(urea)urethanes using amino acid of L‐Arginine as chain extender) were obtained by solvent casting, and further studied by fourier transform infrared (FTIR) and Raman spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis, and X‐ray diffraction (XRD). Their biological performances were assessed in terms of hemocompatibility and Human umbilical vein endothelial cell (HUVEC) cytotoxicity. Tensile properties of dumbbell specimens were compared to longitudinal and circumferential tensile properties of tubular vascular graft. FTIR showed that as the SPUUR content increased in the blend, absorptions at 2860 cm−1 increased, carbonyl absorptions at 1724 cm−1 broaden and the small peak at 2796 cm−1, typical of Tecoflex™ disappeared. Raman spectroscopy showed that the low intensity carbonyl absorption at 1724 cm−1 also increased with SPUUR content. DSC allowed detection of PCL soft segment melting (Tm = 50°C) in agreement with X‐ray reflections at 21.3° and 23.6°, assigned to SPUUR. However, no improvements in thermal stability were detected by TGA by blending. The addition of SPUUR to Tecoflex™ improved hemocompatibility and HUVEC cytotoxicity. The vascular grafts performance showed that 40% SPUUR blends exhibited the highest force in the longitudinal test whereas 50% SPUUR blends showed the highest circumferential force. Pressure burst strength was higher than 1000 mmHg for all blends. Overall, these blends can be used for high caliber vascular grafts.
The pandemic as a developmental risk
Authors: Leuzinger‐Bohleber Marianne , Montigny Nadine
Published: June 2021

In this study, we explore the influence of the pandemic on the intergenerational dialogue. Our thesis is that the images of totally dependent people in intensive care units wrestling with death remind us of earliest experiences in the first year of life. The “embodied memories” of the ubiquitous basic human experience of existential dependence and helplessness remain in the unconscious for a lifetime and are reactivated in situations of diffuse life threat and death. In order not to be flooded by the enacted death anxieties, relatively primitive defense mechanisms such as denial, splitting, omnipotent negation, and projection, may be mobilized. It takes a great psychic effort to recognize such regressive mental processes and to counteract them in order to deal constructively with the pandemic on a mature mental level. The pandemic thus absorbs—consciously and unconsciously—a large part of our psychic energies. This also may have an impact on the empathic dialog between adults and adolescents. We discuss how the pandemic puts a particularly heavy burden on the demanding and disturbance‐prone developmental and identity formation processes of adolescence. In addition, there is a danger that the family and nonfamily adult caregivers will not be able to provide the adolescent with enough understanding and support for this challenge, as they themselves are hindered and limited in their ability to empathize by the constant confrontation with unbearable affects and threats during the pandemic. This makes it more difficult for parents and caregivers to deal with ambivalences, which always characterize the dialog between generations. Thus, the pandemic increases the likelihood that, especially for those growing up who have already felt the downside of life in childhood, their adolescence will now become a “second hazard” rather than a second chance.
Osteoarthritis Care and Risk of Total Knee Arthroplasty Among Medicare Beneficiaries: A Population‐Based Study of Regional Covariation
Authors: Ward Michael M.
Published: June 2021

Objective

To examine health care utilization among patients with knee osteoarthritis (OA) and assess whether utilization differs among residents of regions with high and low rates of total knee arthroplasty (TKA).

Methods

This was a retrospective cohort study of US Medicare beneficiaries with knee OA enrolled from 2005 to 2010. Health care utilization data for knee complaints, including rates of physician visits, physical therapy, knee injections, and arthroscopy, were abstracted from claims files until time of TKA or the end of the study in 2015. Utilization was compared among beneficiaries who lived in regions with high or low rates of TKA.

Results

Among 988,570 beneficiaries with knee OA, 327,499 (33.1%) underwent TKA during follow‐up (median 5.6 years). Higher frequency of visits for knee complaints was associated with increased risk of TKA, whereas physical therapy, specialist care, and intraarticular treatments were associated with lower risk of TKA. Frequency of TKA varied from 26.4% in the lowest regional TKA rate quintile to 42.1% in the highest regional TKA rate quintile. Rates of physician visits, physical therapy, specialist care, and treatment with intraarticular injections varied inversely with regional TKA rate quintile. For example, 32.5% of beneficiaries in the lowest region quintile and 23.6% in the highest region quintile underwent physical therapy. Across all quintiles, physical therapy was associated with lower TKA rates.

Conclusion

Dedicated nonsurgical OA care was infrequently used to treat elderly Americans with knee OA. Nonsurgical care was more common in regions with low TKA rates, suggesting reciprocal emphasis on medical treatment compared to surgical treatment across regions.
Prediction of the Progression of Undifferentiated Arthritis to Rheumatoid Arthritis Using DNA Methylation Profiling
Authors: de la Calle‐Fabregat Carlos , Niemantsverdriet Ellis , Cañete Juan D. , Li Tianlu , van der Helm‐van Mil Annette H. M. , Rodríguez‐Ubreva Javier , Ballestar Esteban
Published: June 2021

Objective

The term “undifferentiated arthritis (UA)” is used to refer to all cases of arthritis that do not fit a specific diagnosis. A significant percentage of UA patients progress to rheumatoid arthritis (RA), others to a different definite rheumatic disease, and the rest undergo spontaneous remission. Therapeutic intervention in patients with UA can delay or halt disease progression and its long‐term consequences. It is therefore of inherent interest to identify those UA patients with a high probability of progressing to RA who would benefit from early appropriate therapy. This study was undertaken to investigate whether alterations in the DNA methylation profiles of immune cells may provide information on the genetically or environmentally determined status of patients and potentially discriminate between disease subtypes.

Methods

We performed DNA methylation profiling of a UA patient cohort, in which progression to RA occurred for a significant proportion of the patients.

Results

We found differential DNA methylation in UA patients compared to healthy controls. Most importantly, our analysis identified a DNA methylation signature characteristic of those UA cases that differentiated to RA. We demonstrated that the methylome of peripheral mononuclear cells can be used to anticipate the evolution of UA to RA, and that this methylome is associated with a number of inflammatory pathways and transcription factors. Finally, we designed a machine learning strategy for DNA methylation‐based classification that predicts the differentiation of UA toward RA.

Conclusion

Our findings indicate that DNA methylation profiling provides a good predictor of UA‐to‐RA progression to anticipate targeted treatments and improve clinical management.
Optimizing the Start Time of Biologics in Polyarticular Juvenile Idiopathic Arthritis: A Comparative Effectiveness Study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans
Authors: Kimura Yukiko , Schanberg Laura E. , Tomlinson George A. , Riordan Mary Ellen , Dennos Anne C. , Del Gaizo Vincent , Murphy Katherine L. , Weiss Pamela F. , Natter Marc D. , Feldman Brian M. , Ringold Sarah ,   the CARRA STOP‐JIA Investigators
Published: June 2021

Objective

The optimal time to start biologics in polyarticular juvenile idiopathic arthritis (JIA) remains uncertain. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed 3 consensus treatment plans (CTPs) for untreated polyarticular JIA to compare strategies for starting biologics.

Methods

Start Time Optimization of Biologics in Polyarticular JIA (STOP‐JIA) was a prospective, observational, CARRA Registry study comparing the effectiveness of 3 CTPs: 1) the step‐up plan (initial nonbiologic disease‐modifying antirheumatic drug [DMARD] monotherapy, adding a biologic if needed, 2) the early combination plan (DMARD and biologic started together), and 3) the biologic first plan (biologic monotherapy). The primary outcome measure was clinically inactive disease according to the provisional American College of Rheumatology (ACR) criteria, without glucocorticoids, at 12 months. Secondary outcome measures included Patient‐Reported Outcomes Measurement Information System (PROMIS) pain interference and mobility scores, inactive disease as defined by the clinical Juvenile Arthritis Disease Activity Score in 10 joints (JADAS‐10), and the ACR Pediatric 70 criteria (Pedi 70).

Results

Of 400 patients enrolled, 257 (64%) began the step‐up plan, 100 (25%) the early combination plan, and 43 (11%) the biologic first plan. After propensity score weighting and multiple imputation, clinically inactive disease according to the ACR criteria was achieved in 37% of those on the early combination plan, 32% on the step‐up plan, and 24% on the biologic first plan (P = 0.17). Inactive disease according to the clinical JADAS‐10 (score ≤2.5) was also achieved in more patients on the early combination plan than the step‐up plan (59% versus 43%; P = 0.03), as was ACR Pedi 70 (81% versus 62%; P = 0.008), but generalizability was limited by missing data. PROMIS measures improved in all groups, but without significant differences. Twenty serious adverse events were reported (mostly infections).

Conclusion

Achievement of clinically inactive disease without glucocorticoids did not significantly differ between groups at 12 months. While there was a significantly higher likelihood of early combination therapy achieving inactive disease according to the clinical JADAS‐10 and ACR Pedi 70, these results require further exploration.
Digital humanities as a cross‐disciplinary battleground: An examination of inscriptions in journal publications
Authors: Ma Rongqian , Li Kai
Published: June 2021

Inscriptionsare defined as traces of scientific research production that are embodied in material artifacts and media, which encompass a wide variety of nonverbal forms such as graphs, diagrams, and tables. Inscription serves as a fundamental rhetorical device in research outputs and practices. As many inscriptions are deeply rooted in a scientific research paradigm, they can be used to evaluate the level of scientificity of a scientific field. This is specifically helpful to understand the relationships between research traditions in digital humanities (DH), a highly cross‐disciplinary between various humanities and scientific traditions. This paper presents a quantitative, community‐focused examination of how inscriptions are used in English‐language research articles in DH journals. We randomly selected 252 articles published between 2011 and 2020 from a representative DH journal list, and manually classified the inscriptions and author domains in these publications. We found that inscriptions have been increasingly used during the past decade, and their uses are more intensive in publications led by STEM authors comparing to other domains. This study offers a timely survey of the disciplinary landscape of DH from the perspective of inscriptions and sheds light on how different research approaches collaborate and combat in the field of DH.
Keep it simple: Identification of basic versus complex emotions in spoken language in individuals with autism spectrum disorder without intellectual disability: A meta‐analysis study
Authors: Icht Michal , Zukerman Gil , Ben‐Itzchak Esther , Ben‐David Boaz M.
Published: June 2021

Daily functioning involves identifying emotions in spoken language, a fundamental aspect of social interactions. To date, there is inconsistent evidence in the literature on whether individuals with autism spectrum disorder without intellectual disability (ASD‐without‐ID) experience difficulties in identification of spoken emotions. We conducted a meta‐analysis (literature search following the PRISMA guidelines), with 26 data sets (taken from 23 peer‐reviewed journal articles) comparing individuals with ASD‐without‐ID (N = 614) and typically‐developed (TD) controls (N = 640), from nine countries and in seven languages (published until February 2020). In our analyses there was no sufficient evidence to suggest that individuals with HF‐ASD differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, individuals with ASD‐without‐ID were found to perform significantly worse than controls in identification of complex prosodic emotions (e.g., envy and boredom). The level of the semantic content of the stimuli presented (e.g., sentences vs. strings of digits) was not found to have an impact on the results. In conclusion, the difference in findings between simple and complex emotions calls for a new‐look on emotion processing in ASD‐without‐ID. Intervention programs may rely on the intact abilities of individuals with ASD‐without‐ID to process simple emotions and target improved performance with complex emotions.

Lay summary

Individuals with autism spectrum disorder without intellectual disability (ASD‐without‐ID) do not differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, they were found to perform significantly worse than controls in the identification of complex prosodic emotions (e.g., envy, boredom). This was found in a meta‐analysis of 26 data sets with 1254 participants from nine countries and in seven languages. Intervention programs may rely on the intact abilities of individuals with ASD‐without‐ID to process simple emotions.
Exposure to alirocumab during the first trimester of pregnancy: A case report
Authors: Vuignier Yann , Beaud Floriane , Kosinski Christophe , Panchaud Alice , Lebon Sébastien , Baud David , Kissling Sébastien , Collet Tinh‐Hai
Published: June 2021

Background

Familial hypercholesterolemia can be efficiently treated with combined lipid‐lowering drugs. Lipid‐lowering drugs are usually withdrawn for pregnancy and breastfeeding, ideally preconception, followed by lipid apheresis, however, careful plans can be precipitated due to unexpected pregnancy.

Case

A 28‐year old woman with familial hypercholesterolemia due to heterozygous LDLR mutations had an LDL‐cholesterol level at 14.6 mmol/L and Lp(a) at 1150 mg/L. She required a three‐vessel coronary artery bypass graft, drug‐eluting stents, rosuvastatin, ezetimibe, and alirocumab at maximal dosage. Contraception was advised during the following 12 months, with a planned drug withdrawal to bridge with lipid apheresis, such as the direct adsorption of lipoproteins (DALI). However, an unplanned pregnancy required an abrupt stop of all oral medications at six gestational weeks, except for aspirin. Lipid apheresis controlled LDL‐cholesterol in the range of 4.9–7.9 mmol/L (before DALI session) to 1.2–3.2 mmol/L (after DALI session). Later, the regular pregnancy ultrasounds highlighted an isolated agenesis of the corpus callosum later confirmed by magnetic resonance imaging.

Conclusions

A causal link between the early pregnancy exposure to PCSK9 inhibitors (or statins and ezetimibe taken concomitantly) and the observed complete agenesis of the corpus callosum seems unlikely in this case. Guidelines do not specifically recommend preconception measures to lower fetal and/or maternal risks of patients with severe FH considering pregnancy. We argue that lipid apheresis and other measures should be discussed with women with FH and maternity project on an individual basis, until pharmacoepidemiology studies assessing the safety of PCSK9 inhibitors in pregnancy are available.
Ribozyme‐processed guide RNA enhances virus‐mediated plant genome editing
Authors: Oh Youngbin , Kim Hyeonjin , Lee Hyo‐Jun , Kim Sang‐Gyu
Published: June 2021

In virus‐induced gene‐editing system, subgenomic promoters have been used to express guide RNAs (gRNAs). However, the transcription initiation site of the subgenomic promoters remains elusive. Here, we examined the sequence of gRNAs expressed by subgenomic promoters and found the variable length of overhangs at 5′‐end of gRNAs. The overhangs at 5′‐end of gRNA decrease the cleavage activity of SpCas9. To overcome this problem, we inserted hammerhead ribozyme between the subgenomic promoter and gRNA and confirmed that gRNAs with a precise 5′‐end increase the editing efficacy in wild tobacco. This system will be widely used for editing target genes in plants with high efficiency.
Comparative metabolomics and lipidomics study to evaluate the metabolic differences between first‐ and second‐generation mammalian or mechanistic target of rapamycin inhibitors
Authors: Rashid Md Mamunur , Lee Hyunbeom , Park Jinyoung , Jung Byung Hwa
Published: June 2021

Mammalian or mechanistic target of rapamycin (mTOR) drives its fundamental cellular functions through two distinct catalytic subunits, mTORC1 and mTORC2, and is frequently dysregulated in most cancers. To treat cancers, developed mTOR inhibitors have been classified into first and second generations based on their ability to inhibit single (first‐generation) and dual (second‐generation) mTOR subunits. However, the underlying metabolic differences due to the effects of first‐ and second‐generation mTOR inhibitors have not been clearly evaluated. In this study, rapamycin (sirolimus) and AZD8055 and PP242 were selected as first‐ and second‐generation mTOR inhibitors, respectively, to evaluate the metabolic differences due to these two generations of mTOR inhibitors after a single oral dose using untargeted metabolomics and lipidomics approaches. The metabolic differences at each time point were compared using multivariate analysis. The multivariate and data analyses showed that metabolic disparity was more prominent within 8 h after drug administration and a broad class of metabolites were affected by the administration of both generations of mTOR inhibitors. Among the metabolite classes, changes in the pattern of fatty acids and glycerophospholipids were opposite, specifically at 4 and 8 h between the two generations of mTOR inhibitors. We speculate that the inhibition of the mTORC2 subunit by the second‐generation mTOR inhibitor may have resulted in a distinct metabolic pattern between the first‐ and second‐generation inhibitors. Finally, the findings of this study could assist in a more detailed understanding of the key metabolic differences caused by first‐ and second‐generation mTOR inhibitors.
Characterizing online crowdfunding campaigns for patients with kidney cancer
Authors: Thomas Hannah S. , Lee Austin W. , Nabavizadeh Behnam , Namiri Nikan K. , Hakam Nizar , Martin‐Tuite Patrick , Rios Natalie , Enriquez Anthony , Mmonu Nnenaya A. , Cohen Andrew J. , Breyer Benjamin N.
Published: June 2021

Background

Cancer patients incur high care costs; however, there is a paucity of literature characterizing unmet financial obligations for patients with urologic cancers. Kidney cancer patients are particularly burdened by costs associated with novel systemic treatments. This study aimed to ascertain the characteristics of GoFundMe® crowdfunding campaigns for patients with kidney cancer, in order to better understand the financial needs of this population.

Methods

We performed a cross‐sectional, quantitative, and qualitative analysis of all kidney cancer GoFundMe® campaigns since 2010. Fundraising metrics such as goal funds and amount raised, were extracted. Eight independent investigators collected patient, disease and campaign‐level variables from campaign stories (κ = 0.72). In addition, we performed a content analysis of campaign narratives spotlighting the primary appeal of the patient's life story.

Results

A total of 486 GoFundMe® kidney cancer campaigns were reviewed. The median goal funds were 10,000USD [IQR = 5000, 20,000] and the median amount raised was 1450USD [IQR = 578, 4050]. Most campaigns were for adult males (53%) and 62% of adults had children. A minority were for pediatric patients (17%). Thirty‐seven percent of adult patients were primary wage earners and 43% reported losing their job or substantially reducing hours due to illness. Twenty‐nine percent reported no insurance or insufficient coverage. Campaigns most frequently sought funds for medical bills (60%), nonmedical bills (27%), and medical travel (23%). Qualitative campaign narratives mostly emphasized patients’ hardship (46.3%) or high moral character (35.2%). Only 8% of campaigns achieved their target funds.

Conclusions

Despite fundraising efforts, patients with kidney cancer face persistent financial barriers, incurring both medical and nonmedical cost burdens. This may be compounded by limited or no insurance. Cancer care providers should be aware of financial constraints placed on kidney cancer patients, and consider how these may impact treatment regimens.
Approaches to Introduce Helical Structure in Cysteine‐Containing Peptides with a Bimane Group
Authors: Horsfall Aimee J. , McDougal Daniel P. , Scanlon Denis B. , Bruning John B. , Abell Andrew D.
Published: June 2021

An i−i+4 or i−i+3 bimane‐containing linker was introduced into a peptide known to target Estrogen Receptor alpha (ERα), in order to stabilise an α‐helical geometry. These macrocycles were studied by CD and NMR to reveal the i−i+4 constrained peptide adopts a 310‐helical structure in solution, and an α‐helical conformation on interaction with the ERα coactivator recruitment surface in silico. An acyclic bimane‐modified peptide is also helical, when it includes a tryptophan or tyrosine residue; but is significantly less helical with a phenylalanine or alanine residue, which indicates such a bimane modification influences peptide structure in a sequence dependent manner. The fluorescence intensity of the bimane appears influenced by peptide conformation, where helical peptides displayed a fluorescence increase when TFE was added to phosphate buffer, compared to a decrease for less helical peptides. This study presents the bimane as a useful modification to influence peptide structure as an acyclic peptide modification, or as a side‐chain constraint to give a macrocycle.
Career Search Self‐Efficacy and STEM Major Persistence
Authors: Cabell Autumn L.
Published: June 2021

Large gaps in the science, technology, engineering, and mathematics (STEM) labor market exist due to high STEM undergraduate attrition rates. I examined career search self‐efficacy as a predictor of STEM major persistence in a sample of undergraduate engineering students (N = 100). Results suggested that higher career search self‐efficacy scores were associated with increased odds of persisting in an engineering major. Implications for using career development theory in STEM career planning courses and future STEM undergraduate persistence research are discussed.
Screen‐printed Nickel‐Cerium Hydroxide Sensor for Acetaminophen Determination in Body Fluids
Authors: Azeredo Nathália F. B. , Gonçalves Josué M. , Lima Irlan S. , Araki Koiti , Wang Joseph , Angnes Lúcio
Published: June 2021

The possibility of fast, reliable, and sensitive (μmol L−1) quantification of acetaminophen (AAP) directly in saliva and sweat was demonstrated in the pH range of 4 to 7 using a new user‐friendly and cost‐effective graphite screen‐printed electrode (SPE) modified with 2–3 nm diameter alpha‐nickel‐cerium hydroxide nanoparticles. The nanoparticles (NPs) were fully characterized by transmission electron microscopy (TEM, HRTEM and STEM), XRD, and the electrochemical conditions for AAP analysis optimized, pushing down the limit of detection with good selectivity. The possibility of real‐time measurements of AAP was demonstrated by carrying out experiments directly in biofluids, without significant interference from species such as lactate, glucose, ascorbic and uric acid usually present in this kind of samples. This is the first report combining the catalytic properties and easy incorporation of alpha‐nickel‐cerium hydroxide nanoparticles into graphite ink to prepare an SPE for AAP electrochemical detection in secreting body fluids. The α‐Ni0.9Ce0.1(OH)2 SPE features good accuracy and selectivity, fast response, good accuracy and selectivity, as well as low reagent consumption for determination of AAP in real saliva and sweat samples.
Practical Enzymatic Production of Carbocycles
Authors: Wang Weijin , Taber Douglass F. , Renata Hans
Published: June 2021

The Pd‐catalyzed carbon‐carbon bond formation pioneered by Heck in 1969 has dominated medicinal chemistry development for the ensuing fifty years. As the demand for more complex three‐dimensional active pharmaceuticals continues to increase, preparative enzyme‐mediated assembly, by virtue of its exquisite selectivity and sustainable nature, is poised to provide a practical and affordable alternative for accessing such compounds. In this minireview, we summarize recent state‐of‐the‐art developments in practical enzyme‐mediated assembly of carbocycles. When appropriate, background information on the enzymatic transformation is provided and challenges and/or limitations are also highlighted.
Tracking the Electrocatalytic Activity of a Single Palladium Nanoparticle for the Hydrogen Evolution Reaction
Authors: Chen Mengjie , Lu Si‐Min , Peng Yue‐Yi , Ding Zhifeng , Long Yi‐Tao
Published: June 2021

The nanoparticle‐based electrocatalysts’ performance is directly related to their working conditions. In general, a number of nanoparticles are uncontrollably fixed on a millimetre‐sized electrode for electrochemical measurements. However, it is hard to reveal the maximum electrocatalytic activity owing to the aggregation and detachment of nanoparticles on the electrode surface. To solve this problem, here, we take the hydrogen evolution reaction (HER) catalyzed by palladium nanoparticles (Pd NPs) as a model system to track the electrocatalytic activity of single Pd NPs by stochastic collision electrochemistry and ensemble electrochemistry, respectively. Compared with the nanoparticle fixed working condition, Pd NPs in the nanoparticle diffused working condition results in a 2–5 orders magnitude enhancement of electrocatalytic activity for HER at various bias potential. Stochastic collision electrochemistry with high temporal resolution gives further insights into the accurate study of NPs’ electrocatalytic performance, enabling to dramatically enhance electrocatalytic efficiency.
Trapping of Terminal Platinapolyynes by Copper(I) Catalyzed Click Cycloadditions; Probes of Labile Intermediates in Syntheses of Complexes with Extended sp Carbon Chains, and Crystallographic Studies
Authors: Amini Hashem , Weisbach Nancy , Gauthier Sébastien , Kuhn Helene , Bhuvanesh Nattamai , Hampel Frank , Reibenspies Joseph H. , Gladysz John A.
Published: June 2021

The silylated hexatriynyl complex trans‐(C6F5)(p‐tol3P)2Pt(C≡C)3SiEt3 (PtC6TES) is converted in situ to PtC6H (wet n‐Bu4N+ F−, THF) and cross coupled with the diyne H(C≡C)2SiEt3 (HC4TES; CuCl/TMEDA, O2) to give PtC10TES (71 %). This sequence is repeated twice to afford PtC14TES (65 %) and then PtC18TES (27 %). An analogous series of reactions starting with PtC8TES gives PtC12TES (60 %), then PtC16TES (43 %), and then PtC20TES (17 %). Similar cross couplings with H(C≡C)2Si(i‐Pr)3 (HC4TIPS) give PtC12TIPS (68 %), PtC14TIPS (68 %), and PtC16TIPS (34 %). The trialkylsilyl species (up to PtC18TES) are converted to 3+2 “click” cycloadducts or 1,4‐disubstituted 1,2,3‐triazoles trans‐(C6F5)(p‐tol3P)2Pt(C≡C)n‐1C=CHN(CH2C6H5)N=N (29–92 % after workups). The most general procedure involves generating the terminal polyynes PtCxH (wet n‐Bu4N+ F−, THF) in the presence of benzyl azide in DMF and aqueous CuSO4/ascorbic acid. All of the preceding complexes are crystallographically characterized and the structural and spectroscopic properties analyzed as a function of chain length. Two pseudopolymorphs of PtC20TES are obtained, both of which feature molecules with parallel sp carbon chains in a pairwise head/tail packing motif with extensive sp/sp van der Waals contacts.
Flexible Energy from Biogas: Use of Secondary Digesters for Heat Storage—Results of Fermentation Tests
Authors: Seick Ingolf , Vergara‐Araya Mónica , Wiese Jürgen
Published: June 2021

A process for a more efficient and flexible use of the produced heat in biogas plants is tested under real operational conditions. The process uses a mesophilic digester and a thermophilic secondary digester, and the heat demand of the plant is covered by using the heat stored in the secondary digester. The efficient heat use is achieved by a controlled variation of temperature in combination with a suitable process monitoring, without affecting the biogas production or disturbing the biological process. The concept was previously tested in ideal laboratory conditions. Here, the validation tests, in preparation for a planned large‐scale trial, comprising one‐year semicontinuous fermentation tests in the laboratory (close to real operational conditions) are presented. These real conditions are characterized by a high organic load of the reactors as well as by a more manifold substrate mix. During the experimental phase, it is determined that the maximum temperature, at high variation rates between −4 and +2 K per day, reaches 54 °C, allowing a stable process. These experiments confirm that the adaptability to temperature changes depends on the boundary conditions of the fermentation and case‐specific experiments are required before significant changes are made to the temperature management of anaerobic digestion systems.
Randomized trial on acute toxicities of weekly vs three‐weekly cisplatin‐based chemoradiation in head and neck cancer
Authors: Ameri Ahmad , Norouzi Shokoufe , Sourati Ainaz , Azghandi Samira , Novin Kambiz , Taghizadeh‐Hesary Farzad
Published: June 2021

Background

The current first‐line treatment of locally advanced head and neck carcinoma (LAHNC) is concurrent chemoradiation with three‐weekly cisplatin 100 mg/m2. However, prescribing cisplatin at this dose increases the treatment toxicity, which may compromise the treatment results. An alternative schedule is weekly 40 mg/m2 cisplatin.

Aim

To compare the acute hematologic and renal toxicities of these two regimens.

Methods

This randomized clinical trial included 77 LAHNC patients who were allocated to a high dose (100 mg/m2 every 3 weeks) or low dose (40 mg/m2 weekly) cisplatin group concurrent with radiotherapy. Hematologic and renal indices were measured weekly during chemoradiation.

Results

The average age of patients was 55.3 years. Overall, 71.4% of patients were treated in a definitive setting. The incidence of severe hematologic events was not significantly different. However, the average estimated glomerular filtration rate (eGFR) was significantly greater in the three‐weekly group (67.85 vs. 58.57% mL/min per 1.73 m2; P‐value = .02). Cumulative cisplatin dose of ≥240 mg/m2 was significantly greater in the weekly group. Totally, treatment breaks occurred in 40.3% of patients due to treatment toxicity. Treatment interruption was primarily due to neutropenia in the three‐weekly and renal dysfunction and thrombocytopenia in the weekly group.

Conclusions

Severe acute hematologic toxicities were comparable for three‐weekly and weekly groups. The decrease in eGFR through treatment was more significant with weekly cisplatin. Further follow‐up, however, is needed to confirm its impact on delayed renal function.
Neoadjuvant lenvatinib for inoperable thyroid cancer: A case report and literature review
Authors: Alshehri Khalid , Alqurashi Yousuf , Merdad Mazin , Samargandy Shaza , Daghistani Razan , Marzouki Hani
Published: June 2021

Background

Poorly differentiated thyroid cancer (PDTC) is now classified as a separate thyroid tumor entity. It has male predominance and poor prognosis compared to differentiated TC.

Case

We report a case of a patient with PDTC who was previously deemed inoperable. A trial of neoadjuvant lenvatinib therapy was given to the patient after that the tumor become operable and the surgery went successfully.

Conclusions

Lenvatinib is a feasible option in patients with inoperable TC and can stabilize the lesion size or even reduce it, leading to a more favorable surgical outcome.
Evaluating the therapeutic effect of lenvatinib against advanced hepatocellular carcinoma by measuring blood flow changes using contrast‐enhanced ultrasound
Authors: Kamachi Naoki , Nakano Masahito , Okamura Shusuke , Niizeki Takashi , Iwamoto Hideki , Shimose Shigeo , Shirono Tomotake , Noda Yu , Kuromatsu Ryoko , Koga Hironori , Torimura Takuji
Published: June 2021

Background

The antitumor effect of a drug is considered to be associated with a decrease in tumor blood flow.

Aims

We investigated whether the efficacy of lenvatinib (LEN) could be accurately assessed by measuring blood flow in hepatocellular carcinoma (HCC) during early treatment stages.

Methods and results

Blood flow changes and treatment results of 19 patients who underwent contrast‐enhanced ultrasound (CEUS), before and after LEN administration, in Kurume University Hospital from July 2018 to June 2020 were examined. Blood flow was evaluated after the intravenous administration of perflubutane (0.015 ml/kg). The vascular phase was photographed and used as RAW data, and time‐intensity curve analysis was used to obtain the region of interest (ROI) on the entire tumor nodule and quantify tumor blood flow. The evaluation was performed before and 1 and 4 weeks after LEN administration. Mean ± standard deviation (SD) values of the brightness of blood flow in the background liver before and 1 and 4 weeks after LEN administration were 2.84 × 10−4 ± 2.94 × 10−4, 3.07 × 10−4 ± 3.79 × 10−4, and 10.0 × 10−4 ± 20.8 × 10−4 dB, respectively. Blood flow in the background liver did not significantly decrease at 1 and 4 weeks compared with that before treatment. Mean ± SD values of the brightness of blood flow in HCC before and 1 and 4 weeks after administration were 3.49 × 10−3 ± 4.58 × 10−3, 1.16 × 10−3 ± 1.57 × 10−3, and 6.39 × 10−3 ± 22.8 × 10−3 dB, respectively. Blood flow in HCC after 1 week was significantly lower than that before administration (p = .0192). The therapeutic effects were significantly higher in the group with ≥50% blood flow reduction in HCC at 1 week after administration (p = .0038) and the group with reduced blood flow in HCC at 4 weeks after administration (p = .0051) than those before administration.

Conclusion

Early blood flow evaluation by CEUS may be useful in predicting the therapeutic effect of LEN for unresectable advanced HCC.
Bioequivalence of 2 Aripiprazole Orally Disintegrating Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions
Authors: Xiang Jin , Xu Nan , Wang Xueyan , LI Songfan , Yu Qin , Liang Maozhi , Nan Feng , Shu Shiqing , Yan Rui , Zhu Yuqi , Liao Linchuan
Published: June 2021

To assess the bioequivalence of 2 formulations of aripiprazole orally disintegrating tablets and to monitor their safety and tolerability in Chinese subjects, a single‐site, open‐label, randomized, 2‐preparation, single‐dose, 2‐period crossover design was conducted. All 60 subjects were randomly divided into the fasting group and the fed group. Blood samples were collected at scheduled times after a single oral dose of orodispersible tablets containing 10 mg of aripiprazole. In the fasting state, the geometric mean ratios (90% confidence intervals [CIs]) of the test/reference formulation were 92.22%‐100.20% for the area under the concentration‐time curve (AUC) from time zero to the last measured concentration (AUC0‐t), 91.73%‐100.14% for the AUC from administration to infinite time (AUC0‐∞), and 98.52%‐112.52% for the maximum plasma concentration (Cmax). In the fed state, AUC0‐t, AUC0‐∞, and Cmax were 92.23%‐100.20%, 91.73%‐100.14%, and 95.91%‐105.13%, respectively. The 90%CIs of the test/reference AUC ratio and Cmax ratio were within the acceptance range of 80.00%‐125.00% for bioequivalence. Neither the maximum peak plasma concentration (tmax) nor the terminal elimination half‐life (t1/2) showed any significant difference. No serious adverse events) were encountered during the study. The test and reference formulations were bioequivalent under both fasting and fed conditions and were found to be safe and tolerated.
Cloud‐assisted Parkinson disease identification system for remote patient monitoring and diagnosis in the smart healthcare applications
Authors: Harimoorthy Karthikeyan , Thangavelu Menakadevi
Published: June 2021

The development of a cloud‐based Parkinson's disease identification system is identified as one of the most challenging issues for predictive telediagnosis and telemonitoring in the emerging smart healthcare applications. The traditional way of Parkinson's disease identification by clinical parameters is more costly and uncomfortable for rural people to avail the testing and diagnosis from the remote place. So, the cloud‐assisted Parkinson's disease identification system (CAPDIS) is proposed based on non‐clinical parameters with patient‐centric and cost‐effective features for helping the poor patients living in rural as well as urban areas. In addition, the proposed system diagnoses the remote patient by examining the symptoms like dysphonia which is identified as the most severe neurodegenerative disorder in the world. Further, the proposed system has experimented with the benchmark voice dataset collected from the University of California‐Irvine (UCI) repository. It shows that the proposed CAPDIS system with adaptive linear kernel support vector machines (k‐SVM) classifier has significant improvements on detection accuracy, specificity, sensitivity, and Matthews's correlation coefficient scores while comparing to the existing classifiers. Therefore, the proposed adaptive linear k‐SVM classifiers provide 10% improvements on prediction accuracy and F1‐Score over the existing polynomial, radial basis, and sigmoidal‐based k‐SVM classifiers.
Elastic deployment of container clusters across geographically distributed cloud data centers for web applications
Authors: Aldwyan Yasser , Sinnott Richard O. , Jayaputera Glenn T.
Published: June 2021

Containers such as Docker provide a lightweight virtualization technology. They have gained popularity in developing, deploying and managing applications in and across Cloud platforms. Container management and orchestration platforms such as Kubernetes run application containers in virtual clusters that abstract the overheads in managing the underlying infrastructures to simplify the deployment of container solutions. These platforms are well suited for modern web applications that can give rise to geographic fluctuations in use based on the location of users. Such fluctuations often require dynamic global deployment solutions. A key issue is to decide how to adapt the number and placement of clusters to maintain performance, whilst incurring minimum operating and adaptation costs. Manual decisions are naive and can give rise to: over‐provisioning and hence cost issues; improper placement and performance issues, and/or unnecessary relocations resulting in adaptation issues. Elastic deployment solutions are essential to support automated and intelligent adaptation of container clusters in geographically distributed Clouds. In this article, we propose an approach that continuously makes elastic deployment plans aimed at optimizing cost and performance, even during adaptation processes, to meet service level objectives (SLOs) at lower costs. Meta‐heuristics are used for cluster placement and adjustment. We conduct experiments on the Australia‐wide National eResearch Collaboration Tools and Resources Research Cloud using Docker and Kubernetes. Results show that with only a 0.5 ms sacrifice in SLO for the 95th percentile of response times we are able to achieve up to 44.44% improvement (reduction) in cost compared to a naive over‐provisioning deployment approach.
Grammar guided embedding based Chinese long text sentiment classification
Authors: Zhang Chaoli , Lin Dazhen , Cao Donglin , Li Shaozi
Published: June 2021

Although the state‐of‐the‐art sentiment classification approaches, such as LSTM and TextCNN, have achieved a good performance on Chinese short text sentiment analysis, the Chinese long text sentiment classification is still a challenge because of the sentiment change problem and the long text structure problem. Therefore, we propose a grammar guided embedding model (GGE) and a novel Chinese long text sentiment classification framework. First, the part‐of‐speech (POS) tags are introduced as the Chinese long text grammar guided information which can help classification approaches to model the Chinese long text structure and the important structure of sentiment change. Second, we proposed a simple GGE training method which considers the combination representation of word sequence and POS sequence. Finally, we proposed a unified framework which combines our novel GGE with TextCNN. Experiment results show that after using GGE, the model outperforms the state‐of‐the‐art approaches. At the same time, we also found that the GGE achieves the model converge faster, that is, it can achieve better results than without GGE when there is only a small amount of training data. Thus, we believe that the GGE can help machines better understand human language sentiment expression structure.
Efficient Derivation of Excitatory and Inhibitory Neurons from Human Pluripotent Stem Cells Stably Expressing Direct Reprogramming Factors
Authors: Song Saera , Ashok Archana , Williams Damian , Kaufman Maria , Duff Karen , Sproul Andrew
Published: June 2021

It is essential to generate isolated populations of human neuronal subtypes in order to understand cell‐type‐specific roles in brain function and susceptibility to disease pathology. Here we describe a protocol for in‐parallel generation of cortical glutamatergic (excitatory) and GABAergic (inhibitory) neurons from human pluripotent stem cells (hPSCs) by using the neurogenic transcription factors Ngn2 and a combination of Ascl1 and Dlx2, respectively. In contrast to the majority of neural transdifferentiation protocols that use transient lentiviral infection, the use of stable hPSC lines carrying doxycycline‐inducible transcription factors allows neuronal differentiation to be initiated by addition of doxycycline and neural medium. This article presents a method to generate lentivirus from cultured mammalian cells and establish stable transcription factor–expressing cell lines (Basic Protocol 1), followed by a method for monolayer excitatory and inhibitory neuronal differentiation from the established lines (Basic Protocol 2). The resulting neurons reproducibly exhibit properties consistent with human cortical neurons, including the expected morphologies, expression of glutamatergic and GABAergic genes, and functional properties. Our approach enables the scalable and rapid production of human neurons suitable for modeling human brain diseases in a subtype‐specific manner and examination of differential cellular vulnerability. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Lentivirus production and generation of stable hPSC lines

Support Protocol 1: Expansion and maintenance of hPSCs

Basic Protocol 2: Differentiation of EX‐ and IN‐neurons

Support Protocol 2: Experimental methods for validation of EX‐ and IN‐neurons
Enrichment Protocol for Rat Models
Authors: Ismail Teh Rasyidah , Yap Christina Gertrude , Naidu Rakesh , Pamidi Narendra
Published: June 2021

An environmental enrichment (EE) cage consisting of a broad living area and various stimulators triggers social, cognitive, and physical activities. EE has been utilized in a wide range of neurological and non‐neurological studies. However, the details of the environmental enrichment protocol were not well described in these studies. This has resulted in uncertainty and inconsistency in methodology, which may thus fail to replicate environmental enrichment effects, influencing the study outcome. Here we describe the basic guidelines and present an easy‐to‐follow protocol for environmental enrichment in rat models. © 2021 Wiley Periodicals LLC.

Basic Protocol: Environmental enrichment housing