bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlling Intramolecular Förster Resonance Energy Transfer and Singlet Fission in a Subporphyrazine–Pentacene Conjugate by Solvent Polarity
Authors: Guzmán David , Papadopoulos Ilias , Lavarda Giulia , Rami Parisa R. , Tykwinski Rik R. , Rodríguez‐Morgade M. Salomé , Guldi Dirk M. , Torres Tomás
Published: October 2020

Due its complementary absorptions in the range of 450 and 600 nm, an energy‐donating hexaaryl‐subporphyrazine has been linked to a pentacene dimer, which acts primarily as an energy acceptor and secondarily as a singlet fission enabler. In the corresponding conjugate, efficient intramolecular Förster resonance energy transfer (i‐FRET) is the modus operandi to transfer energy from the subporphyrazine to the pentacene dimer. Upon energy transfer, the pentacene dimer undergoes intramolecular singlet fission (i‐SF), that is, converting the singlet excited state, via an intermediate state, into a pair of correlated triplet excited states. Solvatochromic fluorescence of the subporphyrazine is a key feature of this system and features a red‐shift as large as 20 nm in polar media. Solvent is thus used to modulate spectral overlap between the fluorescence of subporphyrazine and absorption of the pentacene dimer, which controls the Förster rate constant, on one hand, and the triplet quantum yield, on the other hand. The optimum spectral overlap is realized in xylene, leading to Förster rate constant of 3.52×1011 s−1 and a triplet quantum yield of 171 % ±10 %. In short, the solvent polarity dependence, which is a unique feature of subporphyrazines, is decisive in terms of adjusting spectral overlap, ensuring a sizable Förster rate constant, and maximizing triplet quantum yields. Uniquely, this optimization can be achieved without a need for synthetic modification of the subporphyrazine donor.
The impact of extreme skull morphology in domestic dogs on cribriform plate shape
Authors: Jacquemetton Christiane , Drexler Abigail , Kellerman Gavin , Bird Deborah , Van Valkenburgh Blaire
Published: October 2020

Dog owners are often impressed by their dog's sense of smell. Many of these dogs, however, have skulls that are quite altered from those of their closest canid relatives. Housed within these skulls are essential olfactory structures like the cribriform plate that play a role in olfaction and the transmission of olfactory nerve impulses to the olfactory bulb of the brain. With improvements in CT technology and accessibility, we are now able to digitally reconstruct in 3D cribriform plate morphology and study its variation within and among species. In this study, we CT scanned the skulls of 95 dog specimens from 45 different domestic dog breeds and 12 species of wild canid and compared the shape of the cribriform plate among three main groups: domestic dog breeds, wolf‐like canids, and fox‐like canids. Despite only recent selective pressure for extreme skull morphology, domestic dogs display much more variation in cribriform plate shape than wild canids, indicating that cribriform plate shape is plastic and linked to skull shape. Intense artificial selection on domestic dog skull phenotype in the last 200 years has clear effects on secondary features of the domestic dog skull, implying that selection for overt phenotypes also can impact other anatomical features associated with the skull, like the cribriform plate.
Dissecting the Cellular Mechanism of Prostacyclin Analog Iloprost in Reversing Vascular Dysfunction in Scleroderma
Authors: Tsou Pei‐Suen , Palisoc Pamela J. , Flavahan Nicholas A. , Khanna Dinesh
Published: October 2020

Objective

Intravenous iloprost improves Raynaud’s phenomenon (RP) and promotes healing of digital ulcers in systemic sclerosis (SSc; scleroderma). Despite a short half‐life, its clinical efficacy lasts weeks. Endothelial adherens junctions, which are formed by VE‐cadherin clustering between endothelial cells (ECs), regulate endothelial properties including barrier function, endothelial‐to‐mesenchymal transition (EndoMT), and angiogenesis. We undertook this study to investigate the hypothesis that junctional disruption contributes to vascular dysfunction in SSc, and that the protective effect of iloprost is mediated by strengthening of those junctions.

Methods

Dermal ECs from SSc patients and healthy controls were isolated. The effect of iloprost on ECs was examined using immunofluorescence, permeability assays, Matrigel tube formation, and quantitative polymerase chain reaction.

Results

Adherens junctions in SSc were disrupted compared to normal ECs, as indicated by reduced levels of VE‐cadherin and increased permeability in SSc ECs (P < 0.05). Iloprost increased VE‐cadherin clustering at junctions and restored junctional levels of VE‐cadherin in SSc ECs (mean ± SD 37.3 ± 4.3 fluorescence units) compared to normal ECs (mean ± SD 29.7 ± 3.4 fluorescence units; P < 0.05), after 2 hours of iloprost incubation. In addition, iloprost reduced permeability of monolayers, increased tubulogenesis, and blocked EndoMT in both normal and SSc ECs (n ≥ 3; P < 0.05). The effects in normal ECs were inhibited by a function‐blocking antibody that prevents junctional clustering of VE‐cadherin.

Conclusion

Our data suggest that the long‐lasting effects of iloprost reflect its ability to stabilize adherens junctions, resulting in increased tubulogenesis and barrier function and reduced EndoMT. These findings provide a mechanistic basis for the use of iloprost in treating SSc patients with RP and digital ulcers.
Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis
Authors: Rodríguez‐Carrio Javier , Coras Roxana , Alperi‐López Mercedes , López Patricia , Ulloa Catalina , Ballina‐García Francisco Javier , Armando Aaron M. , Quehenberger Oswald , Guma Mónica , Suárez Ana
Published: October 2020

Objective

Eicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are linked to rheumatoid arthritis (RA), suggesting that metabolization is enhanced, the role of oxylipins in disease stratification remains unexplored. This study was undertaken to characterize oxylipin networks during the earliest stages of RA and evaluate their associations with clinical features and treatment outcomes.

Methods

In total, 60 patients with early RA (according to the American College of Rheumatology/European League Against Rheumatism 2010 criteria), 11 individuals with clinically suspect arthralgia (CSA), and 28 healthy control subjects were recruited. Serum samples were collected at the time of onset. In the early RA group, 50 patients who had not been exposed to disease‐modifying antirheumatic drug (DMARD) or glucocorticoid treatment at the time of recruitment were prospectively followed up at 6 and 12 months after having received conventional synthetic DMARDs. A total of 75 oxylipins, mostly derived from arachidonic, eicosapentanoic, and linoleic acids, were identified in the serum by liquid chromatography tandem mass spectrometry.

Results

Univariate analyses demonstrated differences in expression patterns of 14 oxylipins across the RA, CSA, and healthy control groups, with each exhibiting a different trajectory. Network analyses revealed a strong grouping pattern of oxylipins in RA patients, whereas in individuals with CSA, a fuzzy network of oxylipins with higher degree and closeness was found. Partial least‐squares discriminant analyses yielded variable important projection scores of >1 for 22 oxylipins, which allowed the identification of 2 clusters. Cluster usage differed among the groups (P = 0.003), and showed associations with disease severity and low rates of remission at 6 and 12 months in RA patients who were initially treatment‐naive. Pathway enrichment analyses revealed different precursors and pathways between the groups, highlighting the relevance of the arachidonic acid pathway in individuals with CSA and the lipooxygenase pathway in patients with early RA. In applying distinct oxylipin signatures, subsets of seropositive and seronegative RA could be identified.

Conclusion

Oxylipin networks differ across stages during the earliest phases of RA. These distinct oxylipin networks could potentially elucidate pathways with clinical relevance for disease progression, clinical heterogeneity, and treatment response.
An iterative method to protect the type I error rate in bioequivalence studies under two‐stage adaptive 2×2 crossover designs
Authors: Molins Eduard , Labes Detlew , Schütz Helmut , Cobo Erik , Ocaña Jordi
Published: October 2020

Bioequivalence studies are the pivotal clinical trials submitted to regulatory agencies to support the marketing applications of generic drug products. Average bioequivalence (ABE) is used to determine whether the mean values for the pharmacokinetic measures determined after administration of the test and reference products are comparable. Two‐stage 2×2 crossover adaptive designs (TSDs) are becoming increasingly popular because they allow making assumptions on the clinically meaningful treatment effect and a reliable guess for the unknown within‐subject variability. At an interim look, if ABE is not declared with an initial sample size, they allow to increase it depending on the estimated variability and to enroll additional subjects at a second stage, or to stop for futility in case of poor likelihood of bioequivalence. This is crucial because both parameters must clearly be prespecified in protocols, and the strategy agreed with regulatory agencies in advance with emphasis on controlling the overall type I error.

We present an iterative method to adjust the significance levels at each stage which preserves the overall type I error for a wide set of scenarios which should include the true unknown variability value. Simulations showed adjusted significance levels higher than 0.0300 in most cases with type I error always below 5%, and with a power of at least 80%. TSDs work particularly well for coefficients of variation below 0.3 which are especially useful due to the balance between the power and the percentage of studies proceeding to stage 2. Our approach might support discussions with regulatory agencies.
Chemoenzymatic Total Syntheses of Artonin I with an Intermolecular Diels–Alderase
Authors: Liu Xiaojing , Yang Jun , Gao Lei , Zhang Liyun , Lei Xiaoguang
Published: October 2020

Diels–Alder reaction is one of the most important transformations used in organic synthesis, with the ability to construct two new CC bonds and up to four chiral centers simultaneously. However, the biggest synthetic challenge in Diels–Alder reaction lies in controlling its regio‐, diastereo‐, and enantioselectivity. Using Stille cross‐coupling and enzymatic Diels–Alder reaction as the key steps, the first chemoenzymatic total synthesis of artonin I is achieved in 30% overall yield over only seven steps. This enzymatic Diels–Alder reaction catalyzed by MaDA is featured with excellent endo‐ and enantioselectivity and high catalytic efficiency (kcat/KM = 362 ± 54 mm−1 s−1). These successful chemoenzymatic total syntheses of artonin I and dideoxyartonin I demonstrated the remarkable potential of the intermolecular Diels–Alderase MaDA in biocatalysis.
Mechanisms of epitranscriptomic gene regulation
Authors: Seo Kyung W. , Kleiner Ralph E.
Published: October 2020

Chemical modifications on RNA can regulate fundamental biological processes. Recent efforts have illuminated the chemical diversity of posttranscriptional (“epitranscriptomic”) modifications on eukaryotic messenger RNA and have begun to elucidate their biological roles. In this review, we discuss our current molecular understanding of epitranscriptomic RNA modifications and their effects on gene expression. In particular, we highlight the role of modifications in mediating RNA‐protein interactions, RNA structure, and RNA‐RNA base pairing, and how these macromolecular interactions control biological processes in the cell.
Enhanced Photothermal Heating from One‐dimensional Assemblies of Au Nanoparticles Encapsulated by TiO2 Shell
Authors: Biutty Merreta Noorenza , Zakia Maulida , Yoo Seong Il
Published: October 2020

One‐dimensional assemblies of metal nanoparticles (NPs) may represent an interesting plasmonic superstructure, in which localized surface plasmon resonance of individual NPs can be coupled to modify the strength and wavelength of extinction of metal NPs. In this study, we explored a simple method to assemble Au NPs into a linear chain by utilizing a low‐dielectric solvent and salts. The aggregation states of Au NPs were engineered by the concentration of salts, which resulted in isolated and linearly assembled Au NPs. In addition, the TiO2 shell, as a stabilizing layer, was synthesized on the surface of the isolated and assembled Au NPs by a slow hydrolysis process. Because the linearly assembled Au NPs with a TiO2 shell had a broad extinction spectrum by plasmon hybridization, they could absorb more photons under simulated solar irradiation. As a result, the linearly assembled Au NPs with a TiO2 shell exhibited an enhanced photothermal effect, compared with the isolated ones.
Not So Far, Not So Close: A Configurational Study of a Carbon Nanotube Bundle for Better Dielectric Phenomena
Authors: Orhan Mehmet
Published: October 2020

Size of pores or spacing among nano‐protrusions such as nanotubes on an electrode surface greatly affects diffusive, viscous, and dielectric phenomena of electrolyte through openings. In this study, a configurational study was conducted to examine the effect of spacing among the single‐walled carbon nanotubes on dielectric and viscous phenomena. Behavior of a polar liquid, acetonitrile, was investigated by molecular simulations at two low densities. Results show that viscosity of the liquid is greatly enhanced by interaction with closely packed tubes' bundle. In conjunction with such increase in viscosity, relaxation of dipoles takes longer times inside such closed packed bundle. Most importantly, spacing among the tubes with diameter D should be at about D/2 in a direction for better dielectric phenomena.
Actualizing sustainable shrimp cultivation: Innovative knowledge transfer at Dr. Shrimp
Authors: Chen Po‐Chang , Li Li‐Te
Published: October 2020

Due to virus infection and unfriendly farming methods, aquatic technology has encountered a series of challenges. Though many efforts have been made, very few studies have focused on the cultivation of shrimp. Therefore, this study aimed to investigate how the founder of Dr. Shrimp transferred innovative and professional knowledge to his trainees, so as to achieve the healthy, non‐toxic, ecofriendly, and sustainable shrimp cultivation that Dr. Shrimp has consistently valued. There are five participants, including the founder, one partner, two clients, and one intern. The data were collected via interview, observation, documents, and analyzed using qualitative content analysis. The results indicated six phases of knowledge and techniques applied at Dr. Shrimp: incentives, communication, acceptance, acquisition, execution, diffusion, which helped to establish the six‐phase model for knowledge transfer and innovation diffusion. It is hoped that the findings can pave the way for other aquatic cultivation to promote sustainable cultivation.
Business strategy and sustainable development: Evidence from China
Authors: Liu Chen , Kong Dongmin
Published: October 2020

This study examines whether and how business strategies affect firms' sustainable development from the view of green innovation. We show that firms following prospector strategy engage in less sustainable development behaviors than those following defender strategies. The negative relation between business strategy and green innovation continues to hold when addressing robustness with alternatives of business strategy and green innovation and addressing potential endogeneity with instrumental variable. We further find that political connection strengthens whereas environmental regulation weakens the negative relation between business strategy and green innovation. Finally, we explore the economic consequences of green innovation caused by strategic differences. Regrettably, the win–win situation of environment and development does not come true.
l‐Lactate Dehydrogenase Identified as a Protein Tyrosine Phosphatase 1B Substrate by Using K‐BIPS
Authors: Acharige Nuwan P. N. , Pflum Mary Kay H.
Published: October 2020

Kinases and phosphatases are major players in a variety of cellular events, including cell signaling. Aberrant activity or mutations in kinases and phosphatases can lead to diseases such as cancer, diabetes, and Alzheimer's. Compared to kinases, phosphatases are understudied; this is partly a result of the limited methods for identifying substrates. As a solution, we developed a proteomics‐based method called kinase‐catalyzed biotinylation to identify phosphatase substrates (K‐BIPS) that previously identified substrates of Ser/Thr phosphatases using small molecule inhibitors. Here, for the first time, K‐BIPS was applied to identify substrates of a tyrosine phosphatase, protein tyrosine phosphatase 1B (PTP1B), under siRNA knockdown conditions. Eight possible substrates of PTP1B were discovered in HEK293 cells, including the known substrate pyruvate kinase. In addition, l‐lactate dehydrogenase (LDHA) was validated as a novel PTP1B substrate. With the ability to use knockdown conditions with Ser/Thr or Tyr phosphatases, K‐BIPS represents a general discovery tool to explore phosphatases biology by identifying unanticipated substrates.
Impact of cleft‐like indentations on procedural outcome of percutaneous edge‐to‐edge mitral valve repair
Authors: Körber Maria Isabel , Friedrichs Kai Peter , Aydin Fatma , Pfister Roman , Mauri Victor , Baldus Stephan , Rudolph Volker , Huntgeburth Michael
Published: October 2020

Objectives and Background

Percutaneous edge‐to‐edge mitral valve (MV) repair (PMVR) is broadly applied in high‐risk patients with relevant mitral regurgitation (MR). We investigated the incidence of cleft‐like indentations (CLI) and their impact on PMVR.

Methods and Results

In a retrospective single center analysis including 263 patients undergoing PMVR with the MitraClip®‐system between 11/2012 and 7/2016, MV anatomy was assessed by 3‐dimensional transesophageal echocardiography. CLI were present in 37/263 patients (14.1%). Of these, 62.2% had 1 CLI, 27% had 2 CLI, and 10.8% had 3 CLI, mostly concerning segment P2 or P2/3 of the MV. Baseline characteristics were similarly distributed. Interestingly, most patients with CLI suffered from secondary MR (n = 29, 78%). The number of deployed MitraClips was higher in patients with CLI (2 [1.25–2] vs. 2 [1, 2], p = .035), whereas procedural as well as clinical success was similar: MR grade (1.2 vs. 1.5, p = .061), vena contracta width (4.2 vs. 4.5 mm, p = .293), dPmean (4.2 vs. 4.0 mmHg, p = .618) at discharge and NYHA class at 30 days did not differ between groups. Periprocedural complications were rare and equally distributed between groups. At 30 days, MR reduction persisted in patients with CLI (95.8% of these selected patients had a MR grade ≤ 2).

Conclusions

CLI of the MV are common in patients undergoing PMVR, also when presenting mainly with secondary MR. While the number of clips needed to address MR is slightly higher in patients with CLI, procedural success rates appear not to be affected. PMVR seems to be a safe treatment option for patients with CLI.
Intracardiac echocardiographic‐guided right‐sided cardiac biopsy: Case series and literature review
Authors: Pearman Joseph L. , Wall Stephen L. , Chen Lily , Rogers Jason H.
Published: October 2020

Endomyocardial biopsy (EMB) is a common procedure used to aid in the diagnosis of diffuse myocardial diseases and, less commonly, in the diagnosis of cardiac tumors. As cardiac tumors are often found in high‐risk locations (ventricular free wall or atria), precision biopsy is paramount, and additional imaging, like transesophageal echocardiography is often required for guidance. The use of intracardiac echocardiography (ICE) to guide biopsy has been described, but there is no consensus on a standardized approach. We report our institutional approach with three cases of ICE‐directed EMB performed with the 2.4 mm Jawz bioptome directed with an 8.5‐Fr Agilis NxT steerable introducer. All cases were performed under guidance with the AcuNav ICE probe. There were no procedural complications and a definitive diagnosis was obtained in all three cases. We also review the available published cases of ICE‐guided EMB in the literature–noting the different procedural approaches, complication rate, and diagnostic yield. There were only two negative biopsies reported among the published cases and no reported complications. Our review of all these cases suggests that ICE‐guidance for EMB is superior to other forms of imaging in its ease of use and high definition of right‐sided cardiac structures. We also feel that the use of the Agilis steerable sheath allows for more precise directing of the bioptome and is a critical component in performing a successful targeted biopsy.
Role of the Partial Charge Transfer on the Chloride Adlayers on Au(100)
Authors: Ávila Milagros , Juárez María F. , Santos Elizabeth
Published: October 2020

We focused on a controversial old issue of the electrochemistry community, partial charge transfer reactions. We chose as paradigmatic example the adlayers of chloride on Au(100) electrodes. In the light of new developments we have investigated the nature of the bond of 84 different geometrical configurations and 102 single adsorption events for different coverages. In all the cases the adsorbed chloride is partially charged. The electronic properties of these adlayers are discussed on the basis of the analysis of dipole moments, electronic charge density redistribution, density of electronic states and changes in the work function.
Design of a Functional Chromene‐Type Kobayashi Precursor: Gram‐Scale Total Synthesis of Natural Xanthones by Highly Regioselective Aryne Annulation
Authors: Xu Yuan‐Ze , Sha Feng , Wu Xin‐Yan
Published: October 2020

The 2,2‐dimethyl‐2H‐chromene motif is widely found in many bioactive molecules, and is a privileged structure in the pharmaceutical arena. We have developed a concise and regioselective approach to chromenes and chromanes through an aryne‐based synthetic strategy. A practical, gram‐scale synthetic route to a chromene‐type aryne precursor was explored. Subsequently, cyclization under mild conditions afforded tetracyclic xanthone skeletons with excellent regioselectivity. Our approach provides a concise strategy for the gram‐scale synthesis of chromene‐type xanthones such as 6‐deoxyisojacareubin, cylindroxanthone D, staudtiixanthone D, brasilixanthone A and cudracuspixanthone O.
Building C(sp3) Molecular Complexity on 2,2′‐Bipyridine and 1,10‐Phenanthroline in Rhenium Tricarbonyl Complexes
Authors: Arevalo Rebeca , López Ramón , Falvello Larry R. , Riera Lucía , Perez Julio
Published: October 2020

The reactions of [Re(N‐N)(CO)3(PMe3)]OTf (N‐N=2,2′‐bipyridine, bipy; 1,10‐phenanthroline, phen) compounds withtBuLi and with LiHBEt3have been explored. Addition to the N‐N chelate took place with different site‐selectivity depending on both chelate and nucleophile. Thus, withtBuLi, an unprecedented addition to C5 of bipy, a regiochemistry not accessible for free bipy, was obtained, whereas coordinated phen underwenttBuLi addition to C2 and C4. Remarkably, when LiHBEt3reacted with [Re(bipy)(CO)3(PMe3)]OTf, hydride addition to the 4 and 6 positions of bipy triggered an intermolecular cyclodimerization of two dearomatized pyridyl rings. In contrast, hydride addition to the phen analog resulted in partial reduction of one pyridine ring. The resulting neutral ReIproducts showed a varied reactivity with HOTf and with MeOTf to yield cationic complexes. These strategies rendered access to ReIcomplexes containing bipy‐ and phen‐derived chelates with several C(sp3) centers.
Effect of pulmonary vein isolation on atrial fibrillation recurrence after accessory pathway ablation in patients with Wolff‐Parkinson‐White syndrome
Authors: Wu Jin‐Tao , Zhao Dan‐Qing , Li Fei‐Fei , Zhang Lei‐Ming , Hu Juan , Fan Xian‐Wei , Hu Guang‐Ling , Yang Hai‐Tao , Yan Li‐Jie , Liu Jing‐Jing , Xu Xian‐Jing , Wang Shan‐Ling , Chu Ying‐Jie
Published: October 2020

Background

Although successful ablation of the accessory pathway (AP) eliminates atrial fibrillation (AF) in some of patients with Wolff‐Parkinson‐White (WPW) syndrome and paroxysmal AF, in other patients it can recur.

Hypothesis

Whether adding pulmonary vein isolation (PVI) after successful AP ablation effectively prevents AF recurrence in patients with WPW syndrome is unknown.

Methods

We retrospectively studied 160 patients (102 men, 58 women; mean age, 46 ± 14 years) with WPW syndrome and paroxysmal AF who underwent AP ablation, namely 103 (64.4%) undergoing only AP ablation (AP group) and 57 (35.6%) undergoing AP ablation plus PVI (AP + PVI group). Advanced interatrial block (IAB) was defined as a P‐wave duration of >120 ms and biphasic (±) morphology in the inferior leads, using 12‐lead electrocardiography (ECG).

Results

During the mean follow‐up period of 30.9 ± 9.2 months (range, 3‐36 months), 22 patients (13.8%) developed AF recurrence. The recurrence rate did not differ in patients in the AP + PVI group and AP group (15.5% vs 10.5%, respectively; P = .373). Univariable and multivariable Cox regression analyses showed that PVI was not associated with the risk of AF recurrence (hazard ratio, 0.66; 95% confidence interval, 0.26‐1.68; P = .380). In WPW patients with advanced IAB, the recurrence rate was lower in patients in the AP + PVI group vs the AP group (90% vs 33.3%, respectively; P = .032).

Conclusions

PVI after successful AP ablation significantly reduced the AF recurrence rate in WPW patients with advanced IAB. Screening of a resting 12‐lead ECG immediately after AP ablation helps identify patients in whom PVI is beneficial.
Model‐Based Cellular Kinetic Analysis of Chimeric Antigen Receptor‐T Cells in Humans
Authors: Liu Can , Ayyar Vivaswath S. , Zheng Xirong , Chen Wenbo , Zheng Songmao , Mody Hardik , Wang Weirong , Heald Donald , Singh Aman P. , Cao Yanguang
Published: October 2020

Chimeric antigen receptor (CAR)‐T cell therapy has achieved considerable success in treating B‐cell hematologic malignancies. However, the challenges of extending CAR‐T therapy to other tumor types, particularly solid tumors, remain appreciable. There are substantial variabilities in CAR‐T cellular kinetics across CAR‐designs, CAR‐T products, dosing regimens, patient responses, disease types, tumor burdens, and lymphodepletion conditions. As a “living drug,” CAR‐T cellular kinetics typically exhibit four distinct phases: distribution, expansion, contraction, and persistence. The cellular kinetics of CAR‐T may correlate with patient responses, but which factors determine CAR‐T cellular kinetics remain poorly defined. Herein, we developed a cellular kinetic model to retrospectively characterize CAR‐T kinetics in 217 patients from 7 trials and compared CAR‐T kinetics across response status, patient populations, and tumor types. Based on our analysis results, CAR‐T cells exhibited a significantly higher cell proliferation rate and capacity but a lower contraction rate in patients who responded to treatment. CAR‐T cells proliferate to a higher degree in hematologic malignancies than in solid tumors. Within the assessed dose ranges (107‒109 cells), CAR‐T doses were weakly correlated with CAR‐T cellular kinetics and patient response status. In conclusion, the developed CAR‐T cellular kinetic model adequately characterized the multiphasic CAR‐T cellular kinetics and supported systematic evaluations of the potential influencing factors, which can have significant implications for the development of more effective CAR‐T therapies.
A reconfigurable real‐time neuromorphic hardware for spiking winner‐take‐all network
Authors: Abdoli Behrooz , Safari Saeed
Published: October 2020

The central nervous system receives a vast amount of sensory inputs, and it should be able to discriminate and recognize different kinds of multisensory information. Winner‐take‐all (WTA) consists of a simple recurrent neural network carrying out discrimination of input signals through competition. This paper presents a real‐time scalable digital hardware implementation of the spiking WTA network. The need for concurrent computing, real‐time performance, proper accuracy, and the reconfigurable device has led to the field‐programmable gate array (FPGA) as the target hardware platform. A set of techniques is employed to lessen memory and resource usage. The proposed architecture consists of multiprocessing elements, which share hardware resources between a specific number of neurons. We introduce a novel connectivity array for neurons (dedicated to the WTA network) to cut down memory usage. Also, a multiplier‐less method in the neuron model and a novel tree adder in the synapse processing unit are designed to improve computational efficiency. The proposed network simulates 4,500 neurons in real time on a Xilinx Artix‐7 FPGA, while a scalable architecture facilitates the implementation of up to 20,000 neurons on this device. The pipeline structure can guarantee real‐time performance for large‐scale networks. Based on simulation and physical synthesis results, the presented network mimics biological WTA dynamics and consumes efficient hardware resources.
Automated leukocyte parameters are useful in the assessment of myelodysplastic syndromes
Authors: Shestakova Anna , Nael Ali , Nora Virgilita , Rezk Sherif , Zhao Xiaohui
Published: October 2020

Background

Study utility of seven automated VCS parameters (V‐volume, C‐conductivity and S‐scatter) in leukocytes as an objective read‐out of dysplasia in Myelodysplastic Syndromes (MDS).

Methods

Peripheral blood was analyzed by Beckman‐Coulter DxH800 hematology analyzer in 43 patients with low‐grade, high‐grade MDS and 21 control individuals. The differences in mean (MN) and standard deviation (SD) of each parameter were examined. The optimal sensitivity and specificity to predict MDS were determined by statistical analysis.

Results

In neutrophils, all means of the light scatters were significantly lower in high‐grade MDS than in the control group. Mean median angle light scatter (MN‐MALS‐NE) and mean upper median angle light scatter (MN‐UMALS‐NE) were significantly different between low‐grade MDS and control patients. MN‐MALS‐NE as a MDS predictor revealed 63% sensitivity and 67% specificity with a cutoff value of ≤133. SDs of each parameter in neutrophils differed significantly among three groups. SD of neutrophil upper median angle light scatter (SD‐UMALS‐NE) had 77% sensitivity and 82% specificity (cutoff value of ≥11.16) to predict MDS.

Conclusions

MDS patients have a significant decrease with a linear trend in VCS parameters in neutrophils, indicating cell dysplasia. The degree of the heterogeneity measured by SD is the most predictive of MDS.
Retrospective implementation of the Milan system for reporting salivary gland cytopathology; a review of 5 years in a specialized cancer center
Authors: Jaber Omar I. , Shawash Sarah I.
Published: October 2020

Background

The Milan system for reporting salivary gland cytopathology (MSRSGC) aims to standardize terminology, facilitate communication, and optimize management by providing risk of malignancy (ROM) for each category. Our retrospective cohort aims to study the reproducibility of reporting using the MSRSGC and to calculate the ROM for each category.

Methods

Cases of fine needle aspiration (FNA) of salivary glands and related cervical lymph nodes were retrieved from our files between 2015 to 2019. From a total of 63 cytology cases, 57 cases had available material for cytological reexamination of which 45 cases had follow up data. All cases were reviewed independently by two pathologists and reclassified based on the MSRSGC. The reclassification of cases for both pathologists was compared and the ROM for each diagnostic category was calculated.

Results

The 57 cases were studied. Both pathologists had initial concordance in classification of 52 of 57 cases. The remainder five cases were concurred upon after combined review. The cases were classified as: Non Diagnostic (ND); (n = 8), Non Neoplastic (NN); (n = 7), Atypia of Undetermined Significance (AUS); (n = 8), Neoplasm Benign (NB) (n = 10), Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) (n = 5), Suspicious for Malignancy (SM) (n = 1) and Malignant (M) (n = 18). The ROM was: ND: (33.3%); NN: (0%); AUS (33.3%); NB (0%); SUMP (25%); SM (100%) and M (100%).

Conclusion

Applying the MSRSGC is reproducible which facilitates standardization of reports and stratifying cases preoperatively. In general, the ROM for our cases was close to that reported in the literature.
Linking autonomic nervous system reactivity with sleep in adolescence: Sex as a moderator
Authors: Martin‐Piñón Olivia , Erath Stephen A. , El‐Sheikh Mona
Published: October 2020

The purpose of the present study was to investigate relations between autonomic nervous system (ANS) reactivity across the parasympathetic and sympathetic branches and multiple sleep parameters in adolescence. Participants were 244 adolescents (Mage = 15.79 years old, SD = 9.56 months; 67.2% White/European‐American, 32.8% Black/African‐American). Parasympathetic activity was indexed by respiratory sinus arrhythmia (RSA) withdrawal and sympathetic activity was indexed by skin conductance level reactivity (SCL‐r), which were examined in response to a laboratory‐based stressor (star‐tracing task). Sleep was assessed with actigraphs in adolescents’ homes for seven consecutive nights. Two sleep parameters were examined: sleep duration indexed by actual sleep minutes and sleep quality indexed by sleep efficiency from sleep onset to wake time. Regression analyses showed that more RSA withdrawal (lower RSA during task than baseline) was associated with shorter sleep, and more SCL‐r (higher SCL during task than baseline) was associated with poorer sleep efficiency. Moderation analyses showed that associations linking RSA withdrawal with fewer sleep minutes and poorer sleep efficiency, and SCL‐r with fewer sleep minutes were significant only for boys. Results illustrate that higher daytime physiological reactivity (increased RSA withdrawal and SCL‐r) is negatively associated with sleep duration and efficiency for adolescents, especially boys.
There’s a storm a‐coming: Ecological resilience and resistance to extreme weather events
Authors: Neilson Eric W. , Lamb Clayton T. , Konkolics Sean M. , Peers Michael J. L. , Majchrzak Yasmine N. , Doran‐Myers Darcy , Garland Laura , Martinig April Robin , Boutin Stan
Published: October 2020

Extreme weather events (EWEs) are expected to increase in stochasticity, frequency, and intensity due to climate change. Documented effects of EWEs, such as droughts, hurricanes, and temperature extremes, range from shifting community stable states to species extirpations. To date, little attention has been paid to how populations resist and/or recover from EWEs through compensatory (behavioral, demographic, or physiological) mechanisms; limiting the capacity to predict species responses to future changes in EWEs. Here, we systematically reviewed the global variation in species’ demographic responses, resistance to, and recovery from EWEs across weather types, species, and biogeographic regions. Through a literature review and meta‐analysis, we tested the prediction that population abundance and probability of persistence will decrease in populations after an EWE and how compensation affects that probability. Across 524 species population responses to EWEs reviewed (27 articles), we noted large variation in responses, such that, on average, the effect of EWEs on population demographics was not negative as predicted. The majority of species populations (80.4%) demonstrated compensatory mechanisms during events to reduce their deleterious effects. However, for populations that were negatively impacted, the demographic consequences were severe. Nearly 20% of the populations monitored experienced declines of over 50% after an EWE, and 6.8% of populations were extirpated. Population declines were reflected in a reduction in survival. Further, resilience was not common, as 80.0% of populations that declined did not recover to before EWE levels while monitored. However, average monitoring time was only two years with over a quarter of studies tracking recovery for less than the study species generation time. We conclude that EWEs have positive and negative impacts on species demography, and this varies by taxa. Species population recovery over short‐time intervals is rare, but long‐term studies are required to accurately assess species resilience to current and future events.
An exploration of spiritual superiority: The paradox of self‐enhancement
Authors: Vonk Roos , Visser Anouk
Published: October 2020

Spiritual training is assumed to reduce self‐enhancement, but may have the paradoxical effect of boosting superiority feelings. It can thus operate like other self‐enhancement tools and contribute to a contingent self‐worth that depends on one's spiritual accomplishments. In three studies (N = 533, N = 2,223, N = 965), a brief measure of spiritual superiority showed good internal consistency and discriminant validity. As predicted, it was distinctly related to spiritual contingency of self‐worth, illustrating that the self‐enhancement function of spirituality is similar to other contingency domains. It was correlated with self‐esteem and, more strongly, with communal narcissism, corroborating the notion of spiritual narcissism. Spiritual Superiority scores were consistently higher among energetically trained participants than mindfulness trainees and were associated with supernatural overconfidence and self‐ascribed spiritual guidance. Our results illustrate that the self‐enhancement motive is powerful and deeply ingrained so that it can hijack methods intended to transcend the ego and, instead, adopt them to its own service.
Specific Removal of Nitrite from Lake Urmia Sediments by Biohydrogel Based on Isolated Soy Protein/Tragacanth/Mesoporous Silica Nanoparticles/Lycopene
Authors: Asadzadeh Farrokh , Pirsa Sajad
Published: October 2020

In this study, a biodegradable biohydrogel based on isolated soy protein/tragacanth containing mesoporous silica nanoparticles and lycopene pigment (ISP/TG/MPS/Lyc) is prepared. The physicochemical characteristics and structure of the biohydrogel are investigated by scanning electron microscopy, Fourier‐transform infrared spectroscopy (FTIR), X‐ray diffraction, and thermal gravimetry analysis (TGA) techniques. Mechanical properties (tensile strength and elongation at break point), antioxidant activity, water solubility, water absorption capacity (WAC), and the humidity content of the biohydrogels are studied. Five optimal biohydrogels including pure ISP, ISP/TG, ISP/MPS, ISP/Lyc, and ISP/TG/MPS/Lyc are used for chemical treatment of Lake Urmia sediments. For this purpose, biochemical oxygen demand (BOD), chemical oxygen demand (COD), nitrate, and nitrite of sediments are examined before and after treatment with biohydrogels. According to the FTIR results, there is only physical interaction between lycopene and isolated soy protein. According to the TGA results, adding silica mesoporous to biohydrogel increases its thermal stability. Tragacanth gum and lycopene pigment reduce water solubility and increase the WAC of biohydrogel. The biohydrogel significantly reduces the BOD and COD of the sediments. The biohydrogel reduces nitrite content up to 90%, while reducing nitrate content by almost 30%. The results show that the biohydrogel containing lycopene selectively purifies nitrite from the sediment solution of Lake Urmia.
Driving performance and neurocognitive skills of long‐term users of sedating antidepressants
Authors: van der Sluiszen Nick N.J.J.M. , Vermeeren Annemiek , van Dijken Joke H. , J.A.E. van de Loo Aurora , Veldstra Janet L. , de Waard Dick , C. Verster Joris , A. Brookhuis Karel , Ramaekers Johannes G.
Published: October 2020

Objective

To assess driving performance and neurocognitive skills of long‐term users of sedating antidepressants, in comparison to healthy controls.

Methods

Thirty‐eight long‐term (>6 months) users of amitriptyline (n= 13) and mirtazapine (n= 25) were compared to 65 healthy controls. Driving performance was assessed using a 1‐h standardised highway driving test in actual traffic, with road‐tracking error (standard deviation of lateral position [SDLP]) being the primary measure. Secondary measures included neurocognitive tasks related to driving. Performance differences between groups were compared to those of blood alcohol concentrations of 0.5 mg/ml to determine clinical relevance.

Results

Compared to controls, mean increase in SDLP of all antidepressant users was not significant, nor clinically relevant (+0.75 cm, 95% CI: −0.83 cm; +2.33 cm). However, users treated less than 3 years (n= 20) did show a significant and clinically relevant increase in SDLP (+2.05 cm). No significant effects were observed on neurocognitive tasks for any user group, although large individual differences were present. Most results from neurocognitive tests were inconclusive, while a few parameters confirmed non‐inferiority for users treated longer than 3 years.

Conclusion

The impairing effects of antidepressant treatment on driving performance and neurocognition mitigate over time following long‐term use of 3 years.
A low‐cost treatment system for underground water using Moringa oleifera seeds and Musa cavendish peels for remote communities
Authors: Aziz Nur AA , Jayasuriya Niranjali , Fan Linhua , Al‐Gheethi Adel
Published: October 2020

BACKGROUND

Nemours plant‐based biomass exhibit higher removal capacities in comparison to chemical treatment methods. The present study aimed to investigate the potential of Moringa oleifera (MO) seeds and Musa cavendish (MC) peel biomass pre‐treated by HNO3 (1 N) and NaOH (0.1 M) for removing nickel (Ni), lead (Pb) and cadmium (Cd) ions from synthetic groundwater. It further aimed to establish the design and test the efficiency of an individual domestic groundwater treatment system with low‐cost using local materials. The batch tests with biomass (MC, MO and MC + MO) were conducted at pH 7. Adsorption was investigated using Freundlich and Langmuir models for single elements, and the Sheindorf–Rebhun–Sheintuch (SRS) model for multicontaminant elements. By contrast, the simulation of actual groundwater quality was studied using a Monte Carlo simulation model.

RESULTS

The adsorption results fitted with the Freundlich model revealed that ≈91%, 98% and 84% of groundwater samples met WHO standards for Pb2+, Ni2+ and Cd2+, respectively. The FTIR analysis of MC, MO and MC + MO revealed that CC, CO and NH were the main functional groups playing roles in the removal of heavy metals from the water samples. The mechanism of adsorption took place by chemisorption and physisorption. The total cost of the water treatment system with a capacity of 50 L was US$17, and considered suitable for remote, lower income communities.

CONCLUSION

The MC + MO biomass was efficient in adsorbing heavy metal ions from water samples owing to the presence of abundant functional groups.
Teaching methodologies for improving dental students’ implementation of ergonomic operator and patient positioning
Authors: Faust Andrea M. , Ahmed Sumitha N. , Johnston Lisa B. , Harmon Jennifer B.
Published: October 2020

Objectives

Musculoskeletal disorders (MSDs) related to operator and patient positioning are prevalent among dentists. Knowledge of correct operator and patient positioning promotes safe working postures that can prevent the development of MSDs. The aim of this study was to assess the impact of inter‐professional teaching on the application of those skills associated with correct operator and patient positioning in dental settings.

Methods

A randomized case‐control study was conducted with 83 first‐year dental students at the UNC—Chapel Hill Adams School of Dentistry in 2019. Forty‐one (n = 41) of the students solicited for the project participated. All 83 students in the cohort participated in a didactic lecture on ergonomics and correct operator and patient positioning, along with a pre‐clinical practice session with peer patients. During the clinical practice session, students in the case group received an additional 10 minutes of 1‐on‐1 instruction by a trained physical therapy student or dental faculty member. Two weeks later, the final cohort (n = 41) was assessed by 2 faculty members using a scored rubric on operator and patient positioning for restorative work on an anterior tooth, posterior mandibular tooth, and posterior maxillary tooth.

Results

There was a statistically significant difference between the 2 groups with respect to the composite ergonomic positioning score (P = 0.006), operator shoulder abduction position (P = 0.03), and lateral flexion of the spinal column (P = 0.02).

Conclusions

Hands on instruction with physical therapists and trained dental faculty positively affects ergonomic compliance and provides students with tailored feedback that can be applied to clinical practice.
Sexually transmitted infection screening, prevalence and incidence among South African men and transgender women who have sex with men enrolled in a combination HIV prevention cohort study: the Sibanye Methods for Prevention Packages Programme (MP3) project
Authors: Jones Jeb , Sanchez Travis H , Dominguez Karen , Bekker Linda‐Gail , Phaswana‐Mafuya Nancy , Baral Stefan D , McNaghten AD , Kgatitswe Lesego B , Valencia Rachel , Yah Clarence S , Zahn Ryan , Siegler Aaron J , Sullivan Patrick S
Published: October 2020

Introduction

Men who have sex with men (MSM) and transgender women (TGW) experience high incidence and prevalence of sexually transmitted infections (STI), and data are needed to understand risk factors for STIs in these populations. The Sibanye Health Project was conducted in Cape Town and Port Elizabeth, South Africa from 2015 to 2016 to develop and test a package of HIV prevention interventions for MSM and TGW. We describe the incidence, prevalence and symptoms of Chlamydia trachomatis (CT), Neisseria gonorrhea (NG) and syphilis observed during the study.

Methods

Participants completed HIV testing at baseline. All participants who were HIV negative were followed prospectively. Additionally, a sample of participants identified as living with HIV at baseline was selected to be followed prospectively so that the prospective cohort was approximately 20% HIV positive; the remaining participants identified as HIV positive at baseline were not followed prospectively. Prospective participants were followed for 12 months and returned for clinic‐based STI/HIV testing and assessment of STI symptoms at months 6 and 12. Additional HIV/STI testing visits could be scheduled at participant request.

Results

Following consent, a total of 292 participants attended a baseline visit (mean age = 26 years), and 201 were enrolled for the 12‐month prospective study. Acceptance of screening for syphilis and urethral NG/CT was near universal, though acceptance of screening for rectal NG/CT was lower (194/292; 66%). Prevalence of urethral CT and NG at baseline was 10% (29/289) and 3% (8/288) respectively; incidence of urethral CT and NG was 12.8/100 person‐years (PY) and 7.1/100 PY respectively. Prevalence of rectal CT and NG at baseline was 25% (47/189) and 16% (30/189) respectively; incidence of rectal CT and NG was 33.4/100 PY and 26.8/100 PY respectively. Prevalence of syphilis at baseline was 17% (45/258) and incidence was 8.2/100 PY. 91%, 95% and 97% of diagnosed rectal NG/CT, urethral NG/CT and syphilis infections, respectively, were clinically asymptomatic.

Conclusions

Prevalence and incidence of urethral and rectal STIs were high among these South African MSM and TGW, and were similar to rates in other settings in the world. Clinical symptoms from these infections were rare, highlighting limitations of syndromic surveillance and suggesting the need for presumptive testing and/or treatment to address the STI epidemic among MSM/TGW in South Africa.