bluuebunny/crossref_metadata_2025 huggingface dataset:
CoSe2/MoS2 Heterostructures to Couple Polysulfide Adsorption and Catalysis in Lithium‐Sulfur Batteries†
Authors: Shen Zihan , Zhou Qingwen , Yu Huiling , Tian Jiaming , Shi Man , Hu Chaoquan , Zhang Huigang
Published: January 2021

Main observation and conclusion

Lithium‐sulfur batteries have been regarded as one of most promising next‐generation energy storage devices because of their high energy density and low cost. However, polysulfide shuttling and slow kinetics hinder the practical application. We fabricated hierarchically heterostructured CoSe2/MoS2 nanoarrays on carbon clothes as the sulfur cathode host. The resulting heterostructures facilitate electron conduction and improve electrolyte wetting. More importantly, the composite heterostructures couple the strong polysulfide adsorption of CoSe2 and high catalytic activity of MoS2 to synergistically accelerate polysulfide conversion, demonstrating higher catalytic activity than their individual components.
Morphological, immunohistochemical, and genetic analyses of bronchiolar adenoma and its putative variants
Authors: Shao Jinchen , Yin Jiani C , Bao Hairong , Zhao Ruiying , Han Yuchen , Zhu Lei , Wu Xue , Shao Yang , Zhang Jie
Published: January 2021

We collected 26 cases of bronchiolar adenoma (BA) and its variants, and performed a comprehensive characterization using a combination of morphological, immunohistochemical, and genetic assessments. Of these 26, 13 were classic bilayered cases, including 10 proximal and 3 distal‐type BAs. Of note, we also identified 13 cases that lacked a continuous basal cell layer. In five cases, the adenomas were partially classic bilayered, leaving a single layer of columnar or cuboidal epithelial cells in some areas of the lesion (BA with monolayered cell lesions). In the other eight cases, the glandular or papillary structures were entirely composed of monolayered columnar or cuboidal epithelial cells, which were morphologically identical to the luminal epithelial cells of classic BA (monolayered BA‐like lesions). Immunohistochemical analysis revealed thyroid transcription factor 1 expression by ciliated columnar epithelial cells, basal cells, and nonciliated columnar and cuboidal epithelial cells. Basal cells also expressed p40 and p63. Twenty‐five cases underwent next‐generation sequencing using a 422‐cancer‐gene panel (GeneseeqPrime). Oncogenic driver mutations were detected in 23 cases, including 13 (52%) with EGFR mutations, 4 (16%) with KRAS G12D/V mutations, 3 (12%) with BRAF V600E mutations, 2 (8%) with ERBB2 exon 20 insertions, and 1 (4%) with a RET fusion. EGFR exon 20 insertions were present in 100% of BAs with monolayered cell lesions, 37.5% of monolayered BA‐like lesions, and 8% of classic BA (Fisher's exact test, p = 0.002, false discovery rate = 0.014). Collectively, our study revealed a gradual morphological transition between BA and its variants. The genetic composition of BAs with monolayered structures differed significantly from those of classic BAs or lung adenocarcinoma.
Seminatural habitats and their proximity to the crop enhances canola (Brassica napus) pollination and reproductive parameters in Argentina
Authors: Mazzei Mariana Paola , Vesprini José Luis , Galetto Leonardo
Published: January 2021

The diversity and abundance of pollinators increase in cultivated areas in proximity to natural and seminatural habitats (pastures, forests, tree lines, etc.). Managing ecosystem services, such as insect pollination, is essential to increase crop yields. Although insect pollination is linked to better yields in many crops, pollinators are usually not considered as an input to be managed in crop production. In this study, we evaluate, for the first time, the influence of pollinators on the reproductive parameters of three canola (Brassica napus L.) stands placed at different distances from seminatural habitats in central Argentina. Insect visits to inflorescences with exposed and nonexposed flowers (covered with voile bags) were compared in plants growing in proximity (<50 m) and distant from (>50 m) seminatural habitats. Observations of flower visitations by the insects were recorded during the flowering period. The most frequent pollinator was Apis mellifera, although 12 additional pollinator morpho‐species were registered. Seven of them were observed in canola flowers for the first time. Pollinators increased the amount of pollen deposited on stigmas and all measured reproductive parameters (fruit set, seeds per pod, seed mass). Seed production per infructescence increased with proximity to seminatural habitats and with pollinators by 34 and 35%, respectively. Therefore, the pollination ecosystem service is a relevant input for canola production in central Argentina. It will be important to develop policies that encourage diversified farming systems securing the protection of natural flora and pollinators.
Frequency‐tunable circularly polarized twin dual folded inverted‐L antenna with varactor‐loaded split‐ring resonator structures
Authors: Kumar P.C. Praveen , Rao P. Trinatha
Published: January 2021

The design of a miniaturized frequency‐tunable circularly polarized twin dual folded inverted‐L antenna with varactor‐loaded split‐sing resonator structure is proposed in the paper. The design integrates two linearly polarized inverted‐L antenna elements with double‐folded arms and with a split‐ring resonator (SRR) structures on both sides. To improve the impedance matching and radiation characteristics the double‐folded structure plays a significant role. Although the use of SRRs to the dual inverted‐L antenna elements achieves compact volume, the antenna's radiation efficiency rapidly decreases around the SRR's resonant frequency. The decrease is avoided by employing a variable capacitance diode loaded on both SRR structures (dual folded inverted‐L antenna, VLSRR). The antenna structure is minimized to be about 66 mm in length, 10 mm width, and 1 mm in height (66 × 10 × 1 mm3). The configuration is simplified by using wave feeding. The better values are obtained between the theoretical calculations and simulated results, which validate the design concept and have a wide varactor tuning bandwidth. The simulated and measured results show that the proposed antennas resonate at multiband frequencies: Band 1 (3.28–3.70 GHz) with varactor tuning of 425 MHz; Band 2 (6.42–6.75GHz) with varactor tuning of 331 MHz; and Band 3 (13.75–14.21 GHz) with varactor tuning of 463 MHz, with the impedance bandwidth of 6%, VSWR < 2, and 3‐dB axial ratio (AR) < 3 across the entire operating bands.
Relationships between patterns of weight‐related self‐monitoring and eating disorder symptomology among undergraduate and graduate students
Authors: Hahn Samantha L. , Bauer Katherine W. , Kaciroti Niko , Eisenberg Daniel , Lipson Sarah K. , Sonneville Kendrin R.
Published: January 2021

Objective

To characterize patterns of weight‐related self‐monitoring (WRSM) among US undergraduate and graduate students and examine associations between identified patterns of WRSM and eating disorder symptomology.

Method

Undergraduate and graduate students from 12 US colleges and universities (N = 10,010) reported the frequency with which they use WRSM, including self‐weighing and dietary self‐monitoring. Eating disorder symptomology was assessed using the Eating Disorder Examination Questionnaire. Gender‐specific patterns of WRSM were identified using latent class analysis, and logistic regressions were used to identify differences in the odds of eating disorder symptomology across patterns of WRSM.

Results

Among this sample, 32.7% weighed themselves regularly; 44.1% reported knowing the nutrition facts of the foods they ate; 33.6% reported knowing the caloric content of the foods they ate; and 12.8% counted the calories they ate. Among women, four patterns of WRSM were identified: “no WRSM,” “all forms of WRSM,” “knowing nutrition/calorie facts,” and “self‐weigh only.” Compared with the “no WRSM” pattern, women in all other patterns experienced increased eating disorder symptomology. Among men, three patterns were identified: “no WRSM,” “all forms of WRSM,” and “knowing nutrition/calorie facts.” Only men in the “all forms WRSM” pattern had increased eating disorder symptomatology compared with those in the “no WRSM” pattern.

Discussion

In a large sample of undergraduate and graduate students, engaging in any WRSM was associated with increased eating disorder symptomology among women, particularly for those who engaged in all forms. Among men, engaging in all forms of WRSM was the only pattern associated with higher eating disorder symptomology.
Healthcare quality and mortality among patients hospitalized for heart failure by hospital level in Beijing, China
Authors: He Liu , Dong Zhao‐Jie , Du Xin , Jiang Chao , Chen Ning , Xia Shi‐Jun , Hou Xiao‐Xia , Yu Hai‐Rong , Lv Qiang , Yu Rong‐Hui , Long De‐Yong , Bai Rong , Liu Nian , Sang Cai‐Hua , Jiang Chen‐Xi , Li Song‐Nan , Huffman Mark D. , Dong Jian‐Zeng , Ma Chang‐Sheng
Published: January 2021

Aims

This study sought to compare healthcare quality and 30 day, 90 day, and 1 year mortality rates among patients admitted to secondary and tertiary hospitals for heart failure (HF) in Beijing.

Methods and results

This study retrospectively enrolled patients hospitalized with a primary discharge diagnosis of HF during January 2014 to December 2015, from five tertiary and four secondary hospitals, in Beijing, China. Mortality data were extracted from Beijing Death Surveillance Database. HF healthcare quality indices were used to evaluate in‐hospital care. Associations between hospital level and mortality rates were assessed using generalized linear mixed models, adjusting for patients' baseline characteristics and intra‐hospital correlation. Data from 1413 patients (median [interquartile range] age = 74 [65–80] years, 52.7% female) from secondary hospitals and 1250 patients (median [interquartile range] age = 72 [61–79] years, 43.3% female) from tertiary hospitals were collected. Rates of left ventricular ejection fraction assessment (73.2% vs. 90.1%) and combined use of β‐blockers and angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers (30.1% vs. 49.3%) were lower in secondary hospitals than those in tertiary hospitals, respectively. Patients admitted to secondary hospitals had a higher 90 day mortality [10.8% vs. 5.0%; adjusted odds ratio (OR): 2.06; 95% confidence interval (CI): 1.10–3.84, P = 0.024 and a higher 1 year mortality rate [21.0% vs. 12.1%; adjusted OR: 1.64; 95% CI: 1.02–2.62, P = 0.039], but 30 day mortality rates were not significantly different (5.5% vs. 3.0%; adjusted OR: 1.49; 95% CI: 0.63–3.52, P = 0.368).

Conclusions

Worse quality of care for patients with HF in secondary hospitals was associated with higher 90 day and 1 year mortality rates. Improving care quality in secondary hospitals is crucial to improve prognosis of patients they served.
Time course of red cell volume and plasma volume over six months in compensated chronic heart failure
Authors: Ahlgrim Christoph , Seiler Florian , Birkner Philipp , Staudacher Dawid Leander , Grundmann Sebastian , Bode Christoph , Pottgiesser Torben
Published: January 2021

Background

In patients with chronic heart failure (CHF), volume overload is usually described as an expansion of plasma volume (PV). Additional red cell volume (RCV) expansion also occurs in a relevant fraction of compensated CHF patients. So far, little is known about the stability of these vascular volumes and possible volume excess in compensated CHF patients over time.

Methods and results

This study aims at quantification of blood volume and its components, RCV and PV (raw values and adjusted for sex and anthropometric characteristics, expressed as per cent of the expected normal value), using an abbreviated carbon monoxide (CO) rebreathing method (aCORM) in 14 patients (two women) with systolic CHF at baseline and at a follow‐up visit after approximately 6 months. While a vast heterogeneity was observed concerning RCV (82% to 134% of normalized alues) and PV (72% to 131% of normalized values), the vascular volumes showed a mean change of 1.2% and −1.3% after a mean follow‐up of 183 days.

Conclusions

The vascular volumes including individual volume excess appear to be stable in compensated CHF patients. The reason for this individual volume response concerning both RCV and PV in CHF remains unclear and deserves further clarification.
Structurally Defined Ring‐Opening and Insertion of Pinacolborane into Aluminium‐Nitrogen Bonds of Sterically Demanding Dialkylaluminium Amides
Authors: Pollard Victoria A. , Kennedy Alan R. , McLellan Ross , Ross Duncan , Tuttle Tell , Mulvey Robert E.
Published: January 2021

Dialkylaluminium amides iBu2Al(TMP) and iBu2Al(HMDS) can perform catalytic hydroboration of ketones with pinacolborane to form the expected boronic esters. However, repeating the same reactions stoichiometrically without a ketone leads unexpectedly to ring‐opening of pinacolborane and insertion of its open chain into the Al−N(amido) bond. To date there has been limited knowledge on decomposition pathways of HBpin despite its prominent role in hydroboration chemistry. X‐ray crystallography shows these mixed Al−B products [iBu2Al{OC(Me)2C(Me)2O}B(H)(NR2)]2 (NR2=TMP or HMDS) form dimers with an (AlO)2 core and terminal B−N bonds. Since the bond retention (B−H) and bond breaking (B−O) in these transformations seemed surprising, DFT calculations run using M11/6‐31G(d,p) gave an energy profile consistent with a σ‐bond metathesis mechanism where London dispersion interactions between iBu and (amide) Me groups play an important stabilising role in the final outcome.
Synthesis and Catalytic Applications of Multinuclear Gold(I)‐1,2,3‐Triazolylidene Complexes
Authors: Rendón‐Nava David , Álvarez‐Hernández Alejandro , Mendoza‐Espinosa Daniel
Published: January 2021

A series of mono‐ to trinuclear gold(I) complexes (1–3) supported by oxo‐functionalized 1,2,3‐triazolylidenes have been prepared. All new compounds were fully characterized by means of 1H and 13C NMR spectroscopy, elemental analyses, and in the case of complexes 1 and 2 by x‐ray diffraction. The catalytic performance of the new triazolylidene gold complexes was tested in several hydroelementation and cyclization processes employing a variety of alkynes as starting materials. According to the overall results, the trinuclear complex 3 displayed the highest catalytic activity in all processes, providing good to excellent yields under mild reaction conditions.
Small Variations, Big Impact: Structural Diversity of the Complexes of a Phosphane‐Decorated Benzenedithiol with Group‐11 Metals
Authors: Schlindwein Simon H. , Nieger Martin , Gudat Dietrich
Published: January 2021

Reaction of a phosphane‐decorated benzenedithiol (pbdtH2) with coinage metal salts furnished polynuclear complexes [M2(pbdtH)2] (M=AuI) or [cat][M5(pbdt)3] (cat=unipositive cation, M=AgI, CuI), which were characterized by analytical and spectroscopic techniques and single‐crystal X‐ray diffraction studies. Furthermore, a double salt with an anion [Ag5(pbdt)3(PPh3)]− that proved unstable in solution was characterized crystallographically. The spectroscopic and crystallographic data revealed that the Cu(I) and Ag(I) complexes exhibit, despite their like stoichiometric composition, isomeric molecular structures. The observed disparities were reproduced by DFT studies. The dinuclear Au(I) complex was found to undergo air‐oxidation to furnish a mixed‐valent complex [(AuIII)2(AuI)2(pbdt)4]. The copper(I) – but not the isomeric silver(I) complexes – showed luminescence in the solid state.
Synthesis, Chiral Resolution, and Optical Properties of 2,18‐Dihydoxy‐5,10,15‐trioxa[9]helicene
Authors: Sundar M. Shyam , Klepetářová Blanka , Bednárová Lucie , Muller Gilles
Published: January 2021

Herein, we report a simple and efficient approach to synthesize a functionalized 2,18‐dimethoxy‐5,10,15‐trioxa[9]helicene. It was synthesized from simple phenol building blocks using two subsequent reactions namely oxidative coupling and dehydrative cyclization or palladium mediated cyclization. The molecular integrity of the helical core was determined by single‐crystal X‐ray diffraction and NMR techniques. Its crystal structure showed the spontaneous resolution which was attributed to the conglomerate formation of the same helical isomer via C−H⋅⋅⋅O and π⋅⋅⋅π or H⋅⋅⋅π interactions. Then, it was converted to racemic 2,18‐dihydoxy‐5,10,15‐trioxa[9]helicene. Enantiomers were separated on preparative HPLC with high optical purity (>99 % ee). Based on electronic circular dichroism, the absolute configurations of dextrorotary and levorotatory antipodes were assigned as P and M, respectively. We also studied the absorption, emission and chiroptical behavior of these helical compounds in the solution state.
Stereochemistry of a Cyclic Epicatechin Trimer with C3 Symmetry Produced by Oxidative Coupling
Authors: Kawazoe Rina , Matsuo Yosuke , Saito Yoshinori , Tanaka Takashi
Published: January 2021

A cyclic epicatechin trimer with C3 symmetry, connected through C−C bonds between A‐ and B‐rings, was isolated as an oxidative coupling product of (−)‐epicatechin with polyphenol oxidase. It was previously isolated as an oxidation product of epicatechin with CuCl2; however, only the 2D structure was proposed. Its stereochemistry was assigned using various spectroscopic techniques, including 1D and 2D NMR, and theoretical calculations of the NMR and ECD data. It was suggested that the less strained cyclic trimer with the (aR,aR,aR) configuration was formed atroposelectively in the cyclization process.
Impaired exercise‐induced hypoalgesia in individuals reporting an increase in low back pain during acute exercise
Authors: Vaegter Henrik B. , Petersen Kristian K. , Sjodsholm Line V. , Schou Pia , Andersen Michael B. , Graven‐Nielsen Thomas
Published: January 2021

Objectives

Exercise therapy is recommended for low back pain (LBP) although the immediate effects on pain are highly variable. In 96 individuals with LBP this cross‐sectional study explored (a) the magnitude of exercise‐induced hypoalgesia (EIH) and (b) measures of pain sensitivity and clinical pain manifestations in individuals reporting a clinical relevant increase in back pain during physical activity compared with individuals reporting low or no increase in back pain during physical activity.

Methods

Cuff algometry was performed at baseline on the leg to assess pressure pain threshold (cPPT), tolerance (cPTT) and temporal summation of pain (cTSP). Manual PPTs were assessed on the back and leg before and after a 6‐min walk test (6MWT). Back pain was scored on a numerical rating scale (NRS) after each minute of walking. The EIH‐effect was estimated as the increase in PPTs after the walk exercise.

Results

Twenty‐seven individuals reported an increase of ≥2/10 in pain NRS scores during walking and compared with the individuals with <2/10 NRS scores: cPPT and EIH‐effects were lower whereas cTSP, pain intensity and disability were increased (p < 0.03). Baseline NRS scores, EIH and pain thresholds were associated with the likelihood of an increase of ≥2/10 in back pain intensity during walking (p < 0.05).

Conclusions

Pain flares in response to physical activity in individuals with LBP seem to be linked with baseline pain sensitivity and pain intensity, and impair the beneficial EIH. Such information may better inform when individuals with LBP will have a beneficial effect of physical activity.

Significance

Pain flares in response to physical activity in individuals with LBP seem to be linked with baseline pain sensitivity and pain intensity, and impair the beneficial exercise‐induced hypoalgesia. Such information may better inform when individuals with LBP will have a beneficial effect of physical activity.
Antidepressant, anxiolytic, antipyretic, and thrombolytic profiling of methanol extract of the aerial part of Piper nigrum: In vivo, in vitro, and in silico approaches
Authors: Emon Nazim Uddin , Alam Safaet , Rudra Sajib , Riya Susmita Roy , Paul Avi , Hossen S M Moazzem , Kulsum Ummay , Ganguly Amlan
Published: January 2021

Piper nigrum L. also called black pepper is popular for its numerous uses. The present research is designed to investigate the pharmacological potential of methanol extract of Piper nigrum (MEPN). The antidepressant investigation was performed by using both in vivo forced swimming test (FST) and tail suspension test (TST) methods while the anxiolytic research by hole‐board test (HBT) method. Again, the antipyretic analysis was conducted through yeast‐induced pyrexia method, whereas clot lysis activity was employed by the thrombolytic method. Furthermore, in silico studies followed by molecular docking analysis of several secondary metabolites, pass prediction, and ADME/T were evaluated with AutoDock Vina, Discovery Studio 2020, UCSF Chimera software PASS online, and ADME/T online tools. The plant extract demonstrated dose‐dependent potentiality in antidepressant, anxiolytic, antipyretic, and thrombolytic activities. Induction of MEPN produced a significant (p < .5, p < .001) increase of mobility in FST and TST, and increased the head dipping and decreased the latency of time (p < .01, p < .001) in HBT. MEPN 400 (mg/kg; b.w.; p.o.) lowered the rectal temperature of yeast‐induced pyrexia substantially (p < .001). Besides, MEPN produced promising (p < .001) clot lysis activity. In the computational approach, among all the proteins, a docking score was found ranging from −1.0 to −7.90 kcal/mol. Besides, all the compounds were found safe in ADME/T study. The results of our scientific research validate the suitability of this plant as an alternative source of novel therapeutics.
Putamen volume predicts real‐time fMRI neurofeedback learning success across paradigms and neurofeedback target regions
Authors: Zhao Zhiying , Yao Shuxia , Zweerings Jana , Zhou Xinqi , Zhou Feng , Kendrick Keith M , Chen Huafu , Mathiak Klaus , Becker Benjamin
Published: January 2021

Real‐time fMRI guided neurofeedback training has gained increasing interest as a noninvasive brain regulation technique with the potential to modulate functional brain alterations in therapeutic contexts. Individual variations in learning success and treatment response have been observed, yet the neural substrates underlying the learning of self‐regulation remain unclear. Against this background, we explored potential brain structural predictors for learning success with pooled data from three real‐time fMRI data sets. Our analysis revealed that gray matter volume of the right putamen could predict neurofeedback learning success across the three data sets (n = 66 in total). Importantly, the original studies employed different neurofeedback paradigms during which different brain regions were trained pointing to a general association with learning success independent of specific aspects of the experimental design. Given the role of the putamen in associative learning this finding may reflect an important role of instrumental learning processes and brain structural variations in associated brain regions for successful acquisition of fMRI neurofeedback‐guided self‐regulation.
National Early Career Transplant Hepatologist Survey: Compensation, Burnout, and Job Satisfaction
Authors: Kriss Michael , Te Helen S. , Verna Elizabeth C. , VanWagner Lisa B. , Scott Frank I. , Lai Jennifer C.
Published: January 2021

Despite the growth of transplant hepatology as a subspecialty over the past decade, data on professional roles and compensation models remain lacking. Furthermore, the prevalence of physician burnout and job satisfaction are unknown in this profession. We aimed to conduct a comprehensive assessment of early career transplant hepatologists to fill these voids in knowledge and to inform current and future transplant hepatologists. An online survey designed to quantify clinical and nonclinical roles, compensation and structure, job satisfaction, and burnout was sent to 256 early career transplant hepatologists. Respondents were divided into three practice settings: university hospital clinical (n = 79), non–university hospital clinical (n = 35), and research (n = 25). The median age of respondents was 38 (interquartile range [IQR] 36‐40) years, and 44% were women. The median half‐days/week spent in clinic was 4 (IQR 3‐6) and in endoscopy was 1 (IQR 1‐2). Most of the respondents provided inpatient care (88%) for a median of 9 (IQR 6.5‐10) weeks/year. The median base compensation was $300,000 (IQR US $263,750‐$326,250), and most (76%) had salary‐based compensation. Although only 8% of respondents were dissatisfied with their position, the prevalence of burnout was high at 35%. Conclusion: This survey is a comprehensive assessment focusing on early career transplant hepatologists, is reflective of the current training paradigm and practice of transplant hepatology, and provides transparency to guide professional negotiations and empower both trainees pursuing careers in transplant hepatology and early career transplant hepatologists.
MiR‐455‐5p monitors myotube morphogenesis by targeting mylip
Authors: Dong Yan‐hua , Zhou Cheng‐jie , Zhang Meng‐yuan , Tao Jin , Zhang Xiao‐meng , An Lu , Zhang Ju , Yang Jie , Liu Dong‐jun , Cang Ming
Published: January 2021

As a posttranscriptional regulatory factor, microRNA (miRNA) plays an important role in the formation of myotubes. However, little is known about the mechanism of miRNA regulating myotube morphogenesis. Here, we aimed to characterize the function of miR‐455‐5p in myotube morphogenesis by inducing differentiation in C2C12 myoblasts containing murine Mylip fragments with the miR‐455‐5p target sequence. We found that miR‐455‐5p overexpression promoted the differentiation and hypertrophy of myotubes, while miR‐455‐5p inhibition led to the failure of myotube differentiation and formation of short myotubes. Furthermore, we demonstrated that miR‐455‐5p directly targeted the Mylip 3’‐untranslated region, which plays a key role in monitoring myotube morphogenesis. Interestingly, the expression and function of Mylip were opposite to those of miR‐455‐5p during myogenesis. Our data uncovered novel miR‐455‐5p targets and established a functional link between Mylip and myotube morphogenesis. Understanding the involvement of Mylip in myotube morphogenesis provides insight into the function of the gene regulatory network.
Combined inhibition/silencing of diacylglycerol kinase α and ζ simultaneously and synergistically enhances interleukin‐2 production in T cells and induces cell death of melanoma cells
Authors: Takao Saki , Akiyama Rino , Sakane Fumio
Published: January 2021

The α‐isozyme of diacylglycerol kinase (DGK) enhances cancer cell proliferation and, conversely, it promotes the nonresponsive immune state known as T‐cell anergy. Moreover, a DGKα‐selective inhibitor, CU‐3, induced cell death in cancer‐derived cells and simultaneously enhanced T‐cell interleukin‐2 production. In addition to DGKα, DGKζ is also known to induce T‐cell anergy. In the present study, we examined whether combined inhibition/silencing of DGKα and DGKζ synergistically enhanced T‐cell activity. Combined treatment with CU‐3 or DGKα‐small interfering RNA (siRNA) and DGKζ‐siRNA more potently enhanced T‐cell receptor‐crosslink‐dependent interleukin‐2 production in Jurkat T cells than treatment with either alone. Intriguingly, in addition to activating T cells, dual inhibition/silencing of DGKα and DGKζ synergistically reduced viability and increased caspase 3/7 activity in AKI melanoma cells. Taken together, these results indicate that combined inhibition/silencing of DGKα and DGKζ simultaneously and synergistically enhances interleukin‐2 production in T cells and induces cell death in melanoma. Therefore, dual inhibition/silencing of these DGK isozymes represents an ideal therapy that potently attenuates cancer cell proliferation and simultaneously enhances immune responses that impact anticancer immunity.
N‐(3‐oxododecanoyl)‐l‐homoserine lactone disrupts intestinal epithelial barrier through triggering apoptosis and collapsing extracellular matrix and tight junction
Authors: Tao Shiyu , Xiong Yi , Han Dandan , Pi Yu , Zhang Hanlu , Wang Junjun
Published: January 2021

Microbes employ autoinducers of quorum sensing (QS) for population communication. Although the autoinducer of Pseudomonas aeruginosa LasI‐LasR system, N‐(3‐oxododecanoyl)‐
l
‐homoserine lactone (3OC12), has been reported with deleterious effects on host cells, its biological effects on integrity of the intestinal epithelium and epithelial barrier are still unclear and need further investigation. In the present study, flow cytometry, transcriptome analysis and western blot technology have been adopted to investigate the potential molecular mechanisms of 3OC12 and its structurally similar analogs damage to intestinal epithelial cells. Our results indicated that 3OC12 and 3OC14 trigger apoptosis rather than necrosis and ferroptosis in intestinal epithelial cells. RNA‐sequencing combined with bioinformatics analysis showed that 3OC12 and 3OC14 reduced the expression of genes from extracellular matrix (ECM)‐receptor interaction pathway. Consistently, protein expressions from ECM and tight junction‐associated pathway were significantly reduced after 3OC12 and 3OC14 challenge. In addition, 3OC12 and 3OC14 led to blocked cell cycle, decreased mitochondrial membrane potential, increased reactive oxygen species level and elevated Ca2+ concentration. Reversely, the antioxidant NAC could effectively mitigate the reduced expression of ECM and tight junction proteins caused by 3OC12 and 3OC14 challenge. Collectively, this study demonstrated that QS autoinducer exposure to intestinal epithelial cells ablates the ECM and tight junctions by triggering oxidative stress and apoptosis, and finally disrupts the intestinal epithelial barrier. These findings provide a rationale for defensing QS‐dependent bacterial infections and potential role of NAC for alleviating the syndrome.
Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection
Authors: Eser Alexander , Reinisch Walter , Schreiber Stefan , Ahmad Tariq , Boulos Suliman , Mould Diane R.
Published: January 2021

Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced treatment efficacy, and increased risk of infusion‐related reactions. The aim of this study was to identify predictors of baseline infliximab clearance and early antidrug antibody formation. Pharmacokinetic and pharmacokinetic/pharmacodynamic models for infliximab were developed using 21 178 observations from 859 patients from the PLANETRA (ClinicalTrials.gov identifier: NCT01217086) and PLANETAS (NCT01220518) studies in rheumatoid arthritis and ankylosing spondylitis, respectively, to address the specified aims. Infliximab pharmacokinetics were well described by a 2‐compartment model with linear mean estimated baseline clearance of 0.26 L/day. Alongside increased body weight, serum C‐reactive protein, and antidrug antibody concentrations and decreased serum albumin, elevated serum glucose levels predicted higher clearance. In patients with rheumatoid arthritis, baseline infliximab clearance and body weight were the only identified predictors of early antidrug antibody detection. The odds ratio for antidrug antibody detection for each 0.1 L/day increase in baseline infliximab clearance was 1.78 (95% confidence interval, 1.50–2.12); for each 10‐kg increase in body weight, this was 1.19 (1.06–1.33). Here we describe increased serum glucose levels as a novel independent predictor of baseline infliximab clearance. Estimates of baseline infliximab clearance should be incorporated to guide dosing modifications and/or antidrug antibody prophylaxis in clinical practice.
The optimal cut‐off values for tumor size, number of lesions, and CEA levels in patients with surgically treated colorectal cancer liver metastases: An international, multi‐institutional study
Authors: Kamphues Carsten , Andreatos Nikolaos , Kruppa Jochen , Buettner Stefan , Wang Jaeyun , Sasaki Kazunari , Wagner Doris , Morioka Daisuke , Fitschek Fabian , Løes Inger Marie , Imai Katsunori , Sun Jinger , Poultsides George , Kaczirek Klaus , Lønning Per Eystein , Endo Itaru , Baba Hideo , Kornprat Peter , Aucejo Federico N , Wolfgang Christopher L. , Kreis Martin E. , Weiss Matthew J , Margonis Georgios Antonios
Published: January 2021

Background and Objectives

Despite the long‐standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long‐term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut‐offs for these variables have not been established.

Methods

Patients who underwent curative‐intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi‐institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut‐offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut‐offs in the surgical literature.

Results

A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut‐offs were identified: 2.95 cm for tumor size, 1.5 for tumor number and 6.15 ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut‐offs.

Conclusion

The current study was able to identify optimal cut‐offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut‐offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores.
Spine biomechanical testing methodologies: The controversy of consensus vs scientific evidence
Authors: Costi John J. , Ledet Eric H. , O'Connell Grace D.
Published: January 2021

Biomechanical testing methodologies for the spine have developed over the past 50 years. During that time, there have been several paradigm shifts with respect to techniques. These techniques evolved by incorporating state‐of‐the‐art engineering principles, in vivo measurements, anatomical structure‐function relationships, and the scientific method. Multiple parametric studies have focused on the effects that the experimental technique has on outcomes. As a result, testing methodologies have evolved, but there are no standard testing protocols, which makes the comparison of findings between experiments difficult and conclusions about in vivo performance challenging. In 2019, the international spine research community was surveyed to determine the consensus on spine biomechanical testing and if the consensus opinion was consistent with the scientific evidence. More than 80 responses to the survey were received. The findings of this survey confirmed that while some methods have been commonly adopted, not all are consistent with the scientific evidence. This review summarizes the scientific literature, the current consensus, and the authors' recommendations on best practices based on the compendium of available evidence.
Immediate Postoperative Radiation Therapy after Free Tissue Transfer for Keloid Treatment
Authors: Wulu Jacqueline A. , Finlay Scott W. , Truong Minh‐Tam , Ezzat Waleed H.
Published: January 2021

Keloids present a challenging clinical problem due to their propensity for recurrence and need for adjuvant therapy. We present a case where a large keloid resection required free tissue transfer and immediate radiation therapy was employed 24 hours postoperatively. There were no significant issues with flap survival, wound healing, or recurrence 2 years postoperatively. This is the first case report of successful radiation treatment 1 day after reconstruction of the head and neck with a free flap. Laryngoscope, 131:E1818–E1820, 2021
QcrB in Mycobacterium tuberculosis: The new drug target of antitubercular agents
Authors: Bahuguna Aparna , Rawat Srishti , Rawat Diwan S.
Published: January 2021

Drug‐resistance in mycobacterial infections is a major global health problem that leads to high mortality and socioeconomic pressure in developing countries around the world. From finding new targets to discovering novel chemical scaffolds, there is an urgent need for the development of better approaches for the cure of tuberculosis. Recently, energy metabolism in mycobacteria, particularly the oxidative phosphorylation pathway of cellular respiration, has emerged as a novel target pathway in drug discovery. New classes of antibacterials which target oxidative phosphorylation pathway either by interacting with a protein or any step in the pathway of oxidative phosphorylation can combat dormant mycobacterial infections leading to shortening of tuberculosis chemotherapy. Adenosine triphosphate synthase is one such recently discovered target of the newly approved antitubercular drug bedaquiline. Cytochrome bcc is another new target of the antitubercular drug candidate Q203, currently in phase II clinical trial. Research suggests that b subunit of cytochrome bcc, QcrB, is the target of Q203. The review article describes the structure, function, and importance of targeting QcrB throwing light on all chemical classes of QcrB inhibitors discovered to date. An understanding of the structure and function of validated targets and their inhibitors would enable the development of new chemical entities.
Fast online‐customized (FOCUS) parallel transmission pulses: A combination of universal pulses and individual optimization
Authors: Herrler Jürgen , Liebig Patrick , Gumbrecht Rene , Ritter Dieter , Schmitter Sebastian , Maier Andreas , Schmidt Manuel , Uder Michael , Doerfler Arnd , Nagel Armin M.
Published: January 2021

Purpose

To mitigate spatial flip angle (FA) variations under strict specific absorption rate (SAR) constraints for ultra‐high field MRI using a combination of universal parallel transmit (pTx) pulses and fast subject‐specific optimization.

Methods

Data sets consisting of B0, maps, and virtual observation point (VOP) data were acquired from 72 subjects (study groups of 48/12 healthy Europeans/Asians and 12 Europeans with pathological or incidental findings) using an 8Tx/32Rx head coil on a 7T whole‐body MR system. Combined optimization values (COV) were defined as combination of spiral‐nonselective (SPINS) trajectory parameters and an energy regularization weight. A set of COV was optimized universally by simulating the individual RF pulse optimizations of 12 training data sets (healthy Europeans). Subsequently, corresponding universal pulses (UPs) were calculated. Using COV and UPs, individually optimized pulses (IOPs) were calculated during the sequence preparation phase (maximum 15 s). Two different UPs and IOPs were evaluated by calculating their normalized root‐mean‐square error (NRMSE) of the FA and SAR in simulations of all data sets. Seven additional subjects were examined using an MPRAGE sequence that uses the designed pTx excitation pulses and a conventional adiabatic inversion.

Results

All pTx pulses resulted in decreased mean NRMSE compared to a circularly polarized (CP) pulse (CP = ~28%, UPs = ~17%, and IOPs = ~12%). UPs and IOPs improved homogeneity for all subjects. Differences in NRMSE between study groups were much lower than differences between different pulse types.

Conclusion

UPs can be used to generate fast online‐customized (FOCUS) pulses gaining lower NRMSE and/or lower SAR values.
On topology optimization of design‐dependent pressure‐loaded three‐dimensional structures and compliant mechanisms
Authors: Kumar Prabhat , Langelaar Matthijs
Published: January 2021

This article presents a density‐based topology optimization method for designing three‐dimensional (3D) compliant mechanisms (CMs) and loadbearing structures with design‐dependent pressure loading. Instead of interface‐tracking techniques, the Darcy law in conjunction with a drainage term is employed to obtain pressure field as a function of the design vector. To ensure continuous transition of pressure loads as the design evolves, the flow coefficient of a finite element (FE) is defined using a smooth Heaviside function. The obtained pressure field is converted into consistent nodal loads using a transformation matrix. The presented approach employs the standard FE formulation and also, allows consistent and computationally inexpensive calculation of load sensitivities using the adjoint‐variable method. For CM designs, a multicriteria objective is minimized, whereas minimization of compliance is performed for designing loadbearing structures. Efficacy and robustness of the presented approach is demonstrated by designing various pressure‐actuated 3D CMs and structures.
An adaptive granular representative volume element model with an evolutionary periodic boundary for hierarchical multiscale analysis
Authors: Qu Tongming , Feng Yuntian , Wang Min
Published: January 2021

The hierarchical multiscale analysis normally utilizes a microscopic representative volume element (RVE) model to capture path/history‐dependent macroscopic responses instead of using phenomenological constitutive models. However, for problems involving large deformation, the current RVE model used in geomechanics may lose representative properties due to the progressive distortion of the RVE box, unless a proper reinitialization is applied. This work develops an adaptive RVE model in conjunction with an evolutionary periodic boundary (EPB) algorithm for hierarchical multiscale analysis of granular materials undergoing large deformation based on a recent RVE model proposed for coupling molecular dynamics and the material point method. The proposed adaptive RVE model avoids the reinitialization of the RVE box that even undergoes extremely large shear deformation; meanwhile, it accounts for the deformation history of the RVE model and treats the interaction between boundary particles and other image particles in a more efficient way. Numerical examples with extremely large deformation are used to illustrate the adaptive granular RVE model enhanced by the proposed EPB algorithm. Furthermore, some key features of this new methodology are further discussed for clarification.
Oral health among older adults in nursing homes: A survey in a national quality register, the Senior Alert
Authors: Bellander Lisa , Andersson Pia , Nordvall Dennis , Hägglin Catharina
Published: January 2021

Aim

To investigate the extent to which the Revised Oral Assessment Guide–Jönköping (ROAG‐J) is used by nursing staff routinely in nursing homes in Sweden and to describe oral health status of the residents.

Design

An observational, retrospective register‐based study.

Methods

Data from different validated health assessments instruments, including ROAG‐J, for the period 2011–2016 were obtained from the Web‐based national quality register Senior Alert. The basis for the analyses was 190,016 assessments.

Results

About half of all residents had underwent at least one annual ROAG‐J assessment (2014–2016). During the period 2011–2016, 42% of the residents (n = 92,827) were registered to have oral health problems. Significantly more oral health problems were found for men and for those with younger age, poorer physical condition, neurophysiological problems, underweight, impaired mobility and many medications. In conclusion, poorer oral health was found for more care‐dependent individuals, which shows a need of preventive actions.
An improved numerical technique for distributed‐order time‐fractional diffusion equations
Authors: Dehestani Haniye , Ordokhani Yadollah , Razzaghi Mohsen
Published: January 2021

This paper considers a novel numerical method based on Lucas‐fractional Lucas functions (L‐FL‐Fs) and collocation method for solving the distributed‐order time‐fractional diffusion equations. In the current investigation, we express the new computational process to gain the integral operational matrix for Lucas polynomials (LPs) and fractional Lucas functions (FLFs). The proposed method creates operational matrices with high accuracy that affect to accuracy and efficiency of the computational scheme directly. The operational matrices, by combining Legendre–Gauss quadrature rule and collocation method, reduce the given distributed‐order time‐fractional diffusion equation to a system of algebraic equations. Also, we investigate the error estimation associated with the presented idea. At last, several examples are given to demonstrate the accuracy and easy implementation of the proposed method.
Quadratic B‐spline collocation method for time dependent singularly perturbed differential‐difference equation arising in the modeling of neuronalactivity
Authors: Shivhare Meenakshi , Podila Pramod Chakravarthy , Ramos Higinio , Vigo‐Aguiar Jesús
Published: January 2021

In this paper, we consider a time‐dependent singularly perturbed differential‐difference equation with small shifts arising in the field of neuroscience. The terms containing the delay and advance parameters are approximated by using the Taylor's series expansion. The continuous problem is semi‐discretized using the Crank–Nicolson finite difference method in the time direction on uniform mesh and quadratic B‐spline collocation method in the space direction on exponentially graded mesh. The method is shown to be second‐order uniformly convergent in space and time direction. Theoretical estimates are carried out which support the obtained numerical experiments.
Mechanical strength retention and service life of Kevlar fiber woven mat reinforced epoxy laminated composites for structural applications
Authors: Sathishkumar T. P. , Muralidharan M. , Ramakrishnan S. , Sanjay M. R. , Siengchin Suchart
Published: January 2021

This work investigates the diffusivity, long‐term tensile performance and prediction of service life of Kevlar fiber woven mat reinforced epoxy laminated composites (KFMRELC). The composites were prepared by hand layup method with compression molding process. The tensile test was conducted on dry and aged composites as per ASTM D 638 standard. These composites were immersed in water at various temperatures of 20°C, 40°C and 60°C and various time periods. The diffusivity was calculated by Fick's law. The activation energy and service life were calculated by Arrhenius principle. In results, the tensile strength was gradually decreased by increasing the immersion time, and the maximum reduction was found at 60°C and 300 days due to loss of bonding between the fiber and matrix. Increasing the aging temperature was decreased bonding between the fiber and matrix which reduced the tensile strength. Therefore, the KFMRELC composite retained long life and exhibited less reduction in tensile stress at 20°C environment. Considering 80% of tensile strength retention, the life of KFMRELC composite was found 50 year less at higher temperature because the rate of diffusivity and degradation were found higher. Hence, the maximum tensile strength retention was showed for 50 years. Based on the life cycle curve, the KFMRELC composite can be selected for suitable applications.