bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycolysis, via NADH‐dependent dimerisation of CtBPs, regulates hypoxia‐induced expression of CAIX and stem‐like breast cancer cell survival
Authors: Kreuzer Mira , Banerjee Arindam , Birts Charles N. , Darley Matthew , Tavassoli Ali , Ivan Mircea , Blaydes Jeremy P.
Published: July 2020

Adaptive responses to hypoxia are mediated by the hypoxia‐inducible factor (HIF) family of transcription factors. These responses include the upregulation of glycolysis to maintain ATP production. This also generates acidic metabolites, which require HIF‐induced carbonic anhydrase IX (CAIX) for their neutralisation. C‐terminal binding proteins (CtBPs) are coregulators of gene transcription and couple glycolysis with gene transcription due to their regulation by the glycolytic coenzyme NADH. Here, we find that experimental manipulation of glycolysis and CtBP function in breast cancer cells through multiple complementary approaches supports a hypothesis whereby the expression of known HIF‐inducible genes, and CAIX in particular, adapts to available glucose in the microenvironment through a mechanism involving CtBPs. This novel pathway promotes the survival of stem cell‐like cancer (SCLC) cells in hypoxia.
Small molecule 3PO inhibits glycolysis but does not bind to 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase‐3 (PFKFB3)
Authors: Emini Veseli Besa , Perrotta Paola , Van Wielendaele Pieter , Lambeir Anne‐Marie , Abdali Anahita , Bellosta Stefano , Monaco Giovanni , Bultynck Geert , Martinet Wim , De Meyer Guido R. Y.
Published: July 2020

6‐Phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase isoform 3 (PFKFB3) is a key enzyme of the glycolytic pathway, and it plays an essential role in angiogenesis. 3‐(3‐Pyridinyl)‐1‐(4‐pyridinyl)‐2‐propen‐1‐one (3PO) is frequently used as a glycolysis inhibitor and is thought to inhibit PFKFB3. However, this latter effect of 3PO has never been investigated in detail and was the aim of the present study. To demonstrate binding of 3PO to PFKFB3, we used isothermal titration calorimetry. However, 3PO did not bind to PFKFB3, even up to 750 µm, in contrast to 3 µm of AZ67, which is a potent and specific PFKFB3 inhibitor. Instead, 3PO accumulated lactic acid inside the cells, leading to a decrease in the intracellular pH and an inhibition of enzymatic reactions of the glycolytic pathway.
Soft‐constrained model predictive control based on data‐driven distributionally robust optimization
Authors: Lu Shuwen , Lee Jay H. , You Fengqi
Published: July 2020

This article proposes a novel distributionally robust optimization (DRO)‐based soft‐constrained model predictive control (MPC) framework to explicitly hedge against unknown external input terms in a linear state‐space system. Without a priori knowledge of the exact uncertainty distribution, this framework works with a lifted ambiguity set constructed using machine learning to incorporate the first‐order moment information. By adopting a linear performance measure and considering input and state constraints robustly with respect to a lifted support set, the DRO‐based MPC is reformulated as a robust optimization problem. The constraints are softened to ensure recursive feasibility. Theoretical results on optimality, feasibility, and stability are further discussed. Performance and computational efficiency of the proposed method are illustrated through motion control and building energy control systems, showing 18.3% less cost and 78.8% less constraint violations, respectively, while requiring one third of the CPU time compared to multi‐stage scenario based stochastic MPC.
From Bit to Bedside: A Practical Framework for Artificial Intelligence Product Development in Healthcare
Authors: Higgins David , Madai Vince I.
Published: July 2020

Artificial intelligence (AI) in healthcare holds great potential to expand access to high‐quality medical care, while reducing systemic costs. Despite hitting headlines regularly and many publications of proofs‐of‐concept, certified products are failing to break through to the clinic. AI in healthcare is a multiparty process with deep knowledge required in multiple individual domains. A lack of understanding of the specific challenges in the domain is the major contributor to the failure to deliver on the big promises. Herein, a “decision perspective” framework for the development of AI‐driven biomedical products from conception to market launch is presented. The framework highlights the risks, objectives, and key results which are typically required to navigate a three‐phase process to market‐launch of a validated medical AI product. Clinical validation, regulatory affairs, data strategy, and algorithmic development are addressed. The development process proposed for AI in healthcare software strongly diverges from modern consumer software development processes. Key time points to guide founders, investors, and key stakeholders throughout the process are highlighted. This framework should be seen as a template for innovation frameworks, which can be used to coordinate team communications and responsibilities toward a viable product development roadmap, thus unlocking the potential of AI in medicine.
Characteristics of late transplant‐associated thrombotic microangiopathy in patients who underwent allogeneic hematopoietic stem cell transplantation
Authors: Heybeli Cihan , Sridharan Meera , Alkhateeb Hassan B. , Villasboas Bisneto Jose C. , Buadi Francis K. , Chen Dong , Dingli David , Dispenzieri Angela , Gertz Morie A. , Go Ronald S. , Hashmi Shahrukh K. , Hayman Suzanne R. , Hogan William J. , Inwards David J. , Kenderian Saad S. , Kumar Shaji K. , Litzow Mark R. , Porrata Luis F. , Lacy Martha Q. , Micallef Ivana N. , Patnaik M. M. , Shah Mithun V. , Leung Nelson
Published: July 2020

Transplant‐associated thrombotic microangiopathy (TA‐TMA) has a wide range of presentations after hematopoietic stem‐cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA‐TMA. Among the 1451 HSCT recipients, early TA‐TMA occurred in 45 (3.1%) patients at a median of 27 (3‐91) days, and late TA‐TMA in 39 (2.7%) patients at a median of 303 (122‐2595) days. Patients with early TA‐TMA were more likely to have high blood calcineurin‐inhibitor levels (P < .001) and acute graph‐vs‐host disease (GVHD, P < .001), while late TMA patients were more likely to have chronic GVHD (P < .001). The estimated median overall survival after onset of TMA for the entire cohort was 6 months. The estimated median overall survival was not reached in patients with an improvement of TMA vs 2 months in patients with no improvement (P < .001). In the early TMA group, older age (for every 10 years, HR 1.40; 95% CI 1.00‐1.94; P = .049) and bacterial infection (HR 2.42; 95% CI 0.98‐6.00; P = .056) were positively associated with mortality. Switching to MMF treatment (HR 0.40; 95% CI 0.16‐0.99; P = .047) and improvement of TMA (HR 0.08; 95% CI 0.03‐0.25; P < .001) were negatively associated with mortality in the multivariate analysis. In the late TMA group, the improvement of TMA was the only independent predictor associated with a lower risk of death (HR 0.05; 95% CI 0.02‐0.19; P < .001). Mortality rates in both early and late TMA remain unacceptably high. Future studies are needed for early diagnosis, trigger identifications, and use of targeted treatments.
Characterization of the rate, predictors, and thrombotic complications of thrombocytosis in iron deficiency anemia
Authors: Song Andrew B. , Kuter David J. , Al‐Samkari Hanny
Published: July 2020

The association of thrombocytosis with iron deficiency anemia (IDA) is well‐recognized, but data describing the rate, predictors, and risk of thrombotic complications associated with IDA‐related thrombocytosis are limited. We queried an institutional patient data repository containing comprehensive chart data for over 6 million patients to identify IDA patients with and without thrombocytosis and thrombotic events over a 40‐year time period (1979 to 2019). Demographics, hematological parameters, thrombosis history, and other medical history were collected. Fidelity of query data was assessed via detailed manual chart review of 700 patients, including confirmation of ferritin and hematologic parameters in addition to temporal and clinical association of thrombocytosis. Our queries identified 36 327 cases of IDA of which 15 022 had thrombocytosis. Following assessment for data integrity, we observed a thrombocytosis rate of 32.6% in patients with IDA. The rate of thrombosis was calculated to be 7.8% in patients with IDA and 15.8% in patients with IDA and thrombocytosis. Platelet mass index at time of peak thrombocytosis was significantly higher than at baseline and was strongly negatively correlated with hemoglobin at peak thrombocytosis. A multivariable model demonstrated a significant predictive relationship between decreasing hemoglobin and increasing platelet count at peak thrombocytosis. In conclusion, we observed reactive thrombocytosis in one‐third of IDA patients, and a 2‐fold thrombosis risk in patients with IDA and thrombocytosis compared with patients with IDA alone. Given the global burden of untreated and undertreated IDA, adequate IDA treatment may reduce thrombotic complications and associated morbidity and mortality.
Developmental delay, intellectual disability, short stature, subglottic stenosis, hearing impairment, onychodysplasia of the index fingers, and distinctive facial features: A newly reported autosomal recessive syndrome
Authors: Mégarbané André , Hana Sayeeda , El‐Hayek Stephany , Gambarini Alicia , Al‐Ali Mahmoud Taleb , Delague Valérie
Published: July 2020

We report on a multiply consanguineous Syrian family where two siblings, a boy and a girl, presented with a compilation of symptoms including developmental delay, severe intellectual disability, absent speech, hearing impairment, short stature, subglottic stenosis, increased length of the palpebral fissures, onychodysplasia of index fingers, scoliosis, genu valgum, and malpositioned toes. Two other individuals from the extended family with similar clinical features are also described. Array‐CGH did not reveal any pathological copy number variation. Exome sequencing failed to find any causal variants. Differential diagnoses and the possibility that we might be reporting a hitherto unknown syndrome are discussed.
One‐pot synthesis of 1,4‐dihydropyridines and N‐arylquinolines in the presence of copper complex stabilized on MnFe2O4 (MFO) as a novel organic–inorganic hybrid material and magnetically retrievable catalyst
Authors: Ahadi Najmieh , Mobinikhaledi Akbar , Bodaghifard Mohammad Ali
Published: July 2020

In this work, the design and synthesis of a heterogeneous catalyst based on functionalization of manganese ferrite nanoparticles encapsulated in a silica layer with Schiff base and subsequent incorporation of copper is presented. The fabricated hybrid material was characterized by employing Fourier‐transform infrared spectroscopy, X‐ray powder diffraction, field emission scanning electron microscopy, transmission electron microscopy, energy‐dispersive X‐ray spectroscopy, differential thermal gravimetric analysis, vibrating sample magnetometry and inductively coupled plasma‐optical emission spectrometry techniques. The prepared organic–inorganic hybrid material was successfully used as an efficient and recoverable catalyst for the synthesis of 1,4‐dihydropyridines and N‐arylquinolines under mild and green reaction conditions. The results showed that the catalyst exhibited excellent catalytic activity under optimum reaction conditions and the desired products were obtained in good to excellent yields. The new 1,4‐dihydropyridines and N‐arylquinolines were characterized by Fourier‐transform infrared spectroscopy, 1H NMR and Elemental analysis of Carbon, Hydrogen and Nitrogen (CHN) analyses. Study of the catalyst reusability confirmed that the catalyst could be recycled for five reaction runs with slight loss of the catalytic activity and negligible copper leaching.
Newly designed Mn (III)–W(V) bimetallic assembly built by manganese (III) Schiff–base and octacyanotungstate(V) building blocks: Structural topologies, and magnetic features
Authors: Muddassir Mohd. , Alarifi Abdullah , Afzal Mohd , Sepay Nayim
Published: July 2020

New complex [Mn (SB)2(DMF)2] [W (CN)8] hereafter referred to as complex 1, which was prepared by self–assembly of [Mn (SB)2(DMF)2]3+ and [W (CN)8]3− and structurally characterized by elemental analysis, infrared (IR) and single crystal X–ray techniques (H2SB is Schiff base derived from the condensation of salicylaldehyde and N,N–diethylethylenediamine and DMF is dimethylformamide). The structure consists of 1–D supramolecular chains and further stacks to give a 3–D supramolecular architecture whose molecular fragments are linked by hydrogen bond as well as C − H···π interactions between [Mn (SB)2(DMF)2]3+ and [W (CN)8]3−. An underlying net for the representation consists of two types of fragments with 1,4 M5–1 and 1,8 M9–1 topologies and further illustration of the molecular network in terms of a graph−theory approach using simplification procedure resulted in the underlying net of 2C1topological type in the complex 1. Magnetic susceptibility measurements of complex 1 was carried out in the temperature range 2–300 K, indicates the presence of either magnetic anisotropy zero field splitting, the effect of intramolecular interactions, or both. Complex 1 follows the Curie–Weiss law with Curie constant value of 3.43 cm3mol−1K, and the slight negative Weiss constant (−0.60 K) value indicates the predominant antiferromagnetic magnetic exchange interactions.

The magnetic properties of Title complex was investigated thoroughly and showed that ferromagnetic interaction between W(V) and Mn (III) operate via the intramolecular H–bonding interaction between cyanide nitrogens and a hydrogen atom.
Assessment of poly(L‐lactide) as an environmentally benign CO2 capture and storage adsorbent
Authors: Stelitano Sara , Lazzaroli Victor , Conte Giuseppe , Pingitore Valentino , Policicchio Alfonso , Agostino Raffaele Giuseppe
Published: July 2020

Carbon capture and storage (CCS) in conjunction with an increasing use of renewables provides a clean pathway to sustainable development and climate change mitigation. In selecting a low temperature CCS adsorbent, parameters such as selectivity, regeneration energy, and economicity play a crucial role. Poly(L‐lactide) (PLA) is one of the most promising materials in science and engineering, not only because it is a green polymer progressively replacing petrobased plastics, but also for its carbon dioxide (CO2)‐philic nature that makes it a suitable candidate for greenhouse gas capture and climate change mitigation. Literature data point to PLA as a valid CCS candidate, although no direct gaseous CO2 adsorption investigation or with mild preparation/regenerative energy was reported. In the present experimental work, a deeper investigation of the adsorption/desorption properties of PLA in presence of gaseous CO2 at room temperature was undertaken by means of a home‐made Sievert‐type apparatus. The effects of pressure (0–15 bar), morphology (commercial pellets, powder, and flakes), and regenerative energy (303 and 333 K) were investigated. PLA samples were also characterized by helium picnometry to obtain skeletal density and by XRD and SEM to obtain morphological and structural information. Results show that PLA represents a valid and ecological alternative among the materials for the capture of CO2. The PLA absorption capacity reaches 16 wt% at 15 bar and 303 K, and is closely linked to the thermal treatment, morphology, and crystalline structure of the material.
Comparison of telescopic and naked‐eye sunspots for the very small spots on February 15, 1900 and January 30, 1911
Authors: Neuhäuser Ralph , Geymeier Michael , Arlt Rainer , Chapman Jesse
Published: July 2020

In a recent discussion of the Maunder Minimum, two sunspot observations by Chinese court astronomers on February 15, 1900 and January 30, 1911 (±1 day) – presumably made with the unaided eye – were considered false detections because the spot areas of the largest spot on those days (±1 day) as recorded by the Royal Greenwich Observatory, would be too small for naked‐eye detection, namely 11 and 13 millionths of a solar disk (msd), respectively (Usoskin et al. 2015). We revisit this issue here. First, we review theoretical and empirical considerations of the lower limit for the sunspot area detectable by the naked eye: under optimal conditions, very good observers can detect spots as small as ∼100 msd (and we present one example, where an observer reported a spot, when the largest spot on that day was only 65 msd, but being part of a longish group facilitating the detection). Then, we review all known sunspot observations on and around February 15, 1900 and January 30, 1911, including full‐disk drawings. For February 15, 1900, Kalocsa observatory, Hungary, shows a feature close to the western limb with an area of 134 msd, but it is not clear whether it was a spot or faculae or pores (as spot, it could have been detectable even by naked‐eye). The two spot groups detected in Kodaikanal, India, on January 31, 1911 and February 1 with 18.5 to 33.0 msd area would be too small for detection by the naked eye. However, the Chinese records for February 15, 1900 and January 30, 1911 do not even mention whether the observations were performed with a telescope or by the unaided eye. We conclude that there is no convincing evidence that these two – or even all – Chinese sunspot records are unreliable.
Recent Advances on Graphene Quantum Dots as Multifunctional Nanoplatforms for Cancer Treatment
Authors: Iannazzo Daniela , Celesti Consuelo , Espro Claudia
Published: July 2020

Graphene quantum dots (GQDs), the latest member of the graphene family, have attracted enormous interest in the last few years, due to their exceptional physical, chemical, electrical, optical, and biological properties. Their strong size‐dependent photoluminescence and the presence of many reactive groups on the graphene surface allow their multimodal conjugation with therapeutic agents, targeting ligands, polymers, light responsive agents, fluorescent dyes, and functional nanoparticles, making them valuable agents for cancer diagnosis and treatment. In this review, the very recent advances covering the last 3 years on the applications of GQDs as drug delivery systems and theranostic tools for anticancer therapy are discussed, highlighting the relevant factors which regulate their biocompatibility. Among these factors, the size, kind, and degree of surface functionalization have shown to greatly affect their use in biological systems. Toxicity issues, which still represent an open challenge for the clinical development of GQDs based therapeutic agents, are also discussed at cellular and animal levels.
Anaplastic lymphoma kinase–positive anaplastic large cell lymphoma presenting as diffuse pulmonary infiltrates
Authors: Sato Shuku , Tamai Yotaro
Published: July 2020

Anaplastic large cell lymphoma has a characteristic sinusoidal growth pattern that presents as pulmonary lymphangitic involvement causing respiratory distress. Recognition and prompt treatment of this entity can result in dramatic response to therapy.
Insights into the production of upgraded biofuels using Mg‐loaded mesoporous ZSM‐5 zeolites
Authors: Sanahuja‐Parejo Olga , Veses Alberto , López José Manuel , Callén María Soledad , Solsona Benjamín , Richards Nia , Taylor Stuart H. , García Tomás
Published: July 2020

Bio‐oil catalytic upgrading has been performed using mesoporous Mg‐loaded ZSM‐5. The presence of Mg modifies both textural and acidic properties, which do not only depend on the Mg content (1 and 5 wt. %) but also on the Si/Al ratio of the parent zeolite (25 and 40). Mg impregnation over mesoporous acidic zeolites has been shown to be essential for further deoxygenation of the raw bio‐oil. Thus, remarkable deoxygenation rates have been achieved, exceeding 68 % for a 5 wt. % Mg‐loaded ZSM‐5 (Si/Al=25). For this catalyst, decarboxylation reactions at MgO active sites seem to be predominant, promoting the upgrading of phenols towards the formation of phenolic compounds with lower oxygen content. As in the case of acidic mesoporous ZSM‐5, the formation of aromatics for Mg‐loaded mesoporous ZSM‐5 samples could be mainly related to the promotion of decarbonylation reactions of phenolic compounds over Brønsted acidic sites at the external surface. Interestingly, the presence of strong Lewis acidic sites created by the interaction between (Mg2+OH−)+ species and extra framework alumina jointly with the remaining Brønsted acidic sites at the external surface could enhance the formation of aromatics through cascade reactions involving ketonization and further aldol condensation and dehydration reactions.
The Bioequivalence of Two Peficitinib Formulations, and the Effect of Food on the Pharmacokinetics of Peficitinib: Two‐Way Crossover Studies of a Single Dose of 150 mg Peficitinib in Healthy Volunteers
Authors: Shibata Mai , Toyoshima Junko , Kaneko Yuichiro , Oda Kazuo , Kiyota Tsuyoshi , Kambayashi Atsushi , Nishimura Tetsuya
Published: July 2020

The marketed tablet formulation of peficitinib differs from the tablet used during the clinical trials. The bioequivalence of the marketed formulation and developmental tablet, and the food effect on the marketed formulation, were analyzed in 2 Japanese open‐label, randomized, 2‐way crossover studies in healthy male volunteers. Volunteers received a single oral dose of the marketed 150‐mg peficitinib tablet under fasted conditions (bioequivalence), and under fed or fasted conditions (food effect). Bioequivalence was compared with the developmental 150‐mg tablet. Samples for pharmacokinetic analysis were collected before dose and ≤72 hours after dose. Safety assessments included adverse events, vital signs, and laboratory variables. In total, 40 and 18 subjects were randomized to the bioequivalence and food effect studies, respectively. The 2 peficitinib formulations were bioequivalent (90% confidence intervals of the geometric mean ratios for Cmax and AUCt of peficitinib were within predefined limits of 0.8 to 1.25). The AUClast and the Cmax of the marketed tablet were 36.8% and 56.4% higher, respectively, under fed versus fasted conditions. Peficitinib was well tolerated. The marketed 150‐mg tablet formulation of peficitinib was bioequivalent to the developmental 150‐mg formulation, with no discernible safety differences. Bioavailability increased under fed conditions with the marketed tablet formulation.
Quantitative Analysis of Protein Self‐Association by Sedimentation Velocity
Authors: Zhao Huaying , Li Wenqi , Chu Wendan , Bollard Mary , Adão Regina , Schuck Peter
Published: July 2020

Sedimentation velocity analytical ultracentrifugation is a powerful classical method to study protein self‐association processes in solution based on the size‐dependent macromolecular migration in the centrifugal field. This technique can elucidate the assembly scheme, measure affinities ranging from picomolar to millimolar Kd, and in favorable cases provide information on oligomer lifetimes and hydrodynamic shape. The present step‐by‐step protocols detail the essential steps of instrument calibration, experimental setup, and data analysis. Using a widely available commercial protein as a model system, the protocols invite replication and comparison with our results. A commentary discusses principles for modifications in the protocols that may be necessary to optimize application of sedimentation velocity analysis to other self‐associating proteins. ©2020 Wiley Periodicals LLC.

Basic Protocol 1: Measurement of external calibration factors

Basic Protocol 2: Sedimentation velocity experiment for protein self‐association

Basic Protocol 3: Sedimentation coefficient distribution analysis in SEDFIT and isotherm analysis in SEDPHAT
Modeling the Effect of DAV132, a Novel Colon‐Targeted Adsorbent, on Fecal Concentrations of Moxifloxacin and Gut Microbiota Diversity in Healthy Volunteers
Authors: Guk Jinju , Guedj Jérémie , Burdet Charles , Andremont Antoine , de Gunzburg Jean , Ducher Annie , Mentré France
Published: July 2020

To prevent antibiotic‐induced perturbations on gut microbiota, DAV132, a novel colon‐targeted adsorbent, which sequesters antibiotic residues in the lower gastrointestinal tract, was developed. We built an integrated pharmacological model of how DAV132 reduces fecal free moxifloxacin and preserves gut microbiota. We used plasma and fecal free moxifloxacin concentrations, and Shannon diversity index from 16S ribosomal RNA gene metagenomics analysis of fecal microbiota, of 143 healthy volunteers assigned randomly to receive moxifloxacin only, or with 10 DAV132 dose regimens, or to a control group. We modeled reduced fecal moxifloxacin concentrations using a transit model for DAV132 kinetics and a Michaelis‐Menten model with an effect of the amount of activated charcoal on adsorption efficacy. Changes in moxifloxacin‐induced perturbations on gut microbiota diversity were then quantified through a turnover model with the Emax model. With the developed model, the efficiency of pharmacokinetic antagonism and its consequences on gut microbiota diversity were quantified.
Synthesis and Characterization of Push‐Pull Aza‐BODIPY Dyes Towards Application in NIR‐II Photothermal Therapy
Authors: Rattanopas Sopita , Chansaenpak Kantapat , Siwawannapong Kittipan , Ngamchuea Kamonwad , Wet‐osot Sirawit , Treekoon Jongjit , Pewklang Thitima , Jinaphon Thanachit , Sagarik Kritsana , Lai Rung‐Yi , Cheng Liang , Kamkaew Anyanee
Published: July 2020

A new series of aza‐BODIPYs (CN−X) with significantly red‐shifted absorbances were designed and synthesized by installation of various electron‐donating groups on the para‐positions of 3,5‐phenyl groups while strong electron‐withdrawing groups (nitrile groups) were fixed on the para‐positions of 1,7‐phenyl moieties. Interestingly, strong electron‐donating groups such as N'N‐dimethylaniline (CN−NMe2) could provide strong NIR absorption up to 857 nm and weak fluorescence emission up to 967 nm, whereas strong evidence supported heat production via non‐radiative decay after excitation. Electrochemical studies revealed that the substituents on the dyes showed strong effects on the oxidation potentials where the oxidation wave of CN−NMe2 occurred at the lowest overpotential, followed by CN−OMe, CN−Me, CN−Br and CN−H, respectively. Calculations were also performed to understand the push‐pull effect of the substituents on the aza‐BODIPY systems. Finally, applications of dyes in NIR cancer cell imaging and the NIR‐II photothermal effect were also investigated.
Mass cytometry reveals immune signatures associated with cytomegalovirus (CMV) control in recipients of allogeneic haemopoietic stem cell transplant and CMV‐specific T cells
Authors: McGuire Helen M , Rizzetto Simone , Withers Barbara P , Clancy Leighton E , Avdic Selmir , Stern Lauren , Patrick Ellis , Fazekas de St Groth Barbara , Slobedman Barry , Gottlieb David J , Luciani Fabio , Blyth Emily
Published: July 2020

Objectives

Cytomegalovirus (CMV) is known to have a significant impact on immune recovery post‐allogeneic haemopoietic stem cell transplant (HSCT). Adoptive therapy with donor‐derived or third‐party virus‐specific T cells (VST) can restore CMV immunity leading to clinical benefit in prevention and treatment of post‐HSCT infection. We developed a mass cytometry approach to study natural immune recovery post‐HSCT and assess the mechanisms underlying the clinical benefits observed in recipients of VST.

Methods

A mass cytometry panel of 38 antibodies was utilised for global immune assessment (72 canonical innate and adaptive immune subsets) in HSCT recipients undergoing natural post‐HSCT recovery (n = 13) and HSCT recipients who received third‐party donor‐derived CMV‐VST as salvage for unresponsive CMV reactivation (n = 8).

Results

Mass cytometry identified distinct immune signatures associated with CMV characterised by a predominance of innate cells (monocytes and NK) seen early and an adaptive signature with activated CD8+ T cells seen later. All CMV‐VST recipients had failed standard antiviral pharmacotherapy as a criterion for trial involvement; 5/8 had failed to develop the adaptive immune signature by study enrolment despite significant CMV antigen exposure. Of these, VST administration resulted in development of the adaptive signature in association with CMV control in three patients. Failure to respond to CMV‐VST in one patient was associated with persistent absence of the adaptive immune signature.

Conclusion

The clinical benefit of CMV‐VST may be mediated by the recovery of an adaptive immune signature characterised by activated CD8+ T cells.
A compact skull‐shaped defected ground super wideband microstrip monopole antenna for short‐distance wireless communication
Authors: Rahman MD Atiqur , Singh Mandeep Singh Jit , Samsuzzaman MD , Islam Mohammad Tariqul
Published: July 2020

In this paper, a human skull‐shaped miniaturized super wideband microstrip monopole antenna is presented. The shape of the microstrip radiator is optimized and designed by combining different sizes of semicircular‐ and rectangular‐shaped radiating elements along with a microstrip feed line. On the other hand, a defected ground structure as the ground is placed at the opposite side of the radiator, which is fabricated on Rogers 5880 substrate. The electrical length of the proposed antenna is 0.240 × 0.200 × 0.016 λ at 3 GHz. The CST microwave studio is used for all the required simulations regarding antenna prototype design and optimization. The complete outcomes demonstrate that the proposed miniaturized antenna has a bandwidth of 24.5 GHz (3 to 27.5 GHz) having a radiation pattern in the form of nearly omnidirectional. The measured fractional bandwidth of the antenna is 160.66%, and the bandwidth dimension ratio is 3346.99, which is the highest among the literature review. The maximum calculated gain and efficiency are 6.3 dBi and 93%, respectively. For the time domain analysis, the antenna shows a decent performance in terms of the system group delay and fidelity factor. The numerical and experimental data are investigated throughout the study, which represents that the proposed antenna is suitable for short‐distance wireless communication like wireless local area network/Wi‐Fi/Worldwide Interoperability for Microwave Access (WiMAX)/ultra‐wideband and some other applications.
Trophic response to ecological conditions of habitats: Evidence from trophic variability of freshwater fish
Authors: Choi Bohyung , Lee Changhwa , Takizawa Yuko , Chikaraishi Yoshito , Oh Hye‐Ji , Chang Kwang‐Hyeon , Jang Min‐Ho , Kim Hyun‐Woo , Lee Kyung‐Lak , Shin Kyung‐Hoon
Published: July 2020

To adapt to ecological and environmental conditions, species can change their ecological niche (e.g., interactions among species) and function (e.g., prey‐predation, diet competition, and habitat segregation) at the species and guild levels. Stable isotope analysis of bulk carbon and nitrogen of organisms has conventionally been used to evaluate such adaptabilities in the scenopoetic and bionomic views as the isotopic niche width.

Compound‐specific stable isotope analysis (CSIA) of nitrogen within amino acids provides trophic information without any disruption of scenopoetic views in the isotope ratios, unlike conventional bulk isotope analysis provides both information and therefore frequently hinders its usefulness for trophic information.

We performed CSIA of amino acids to understand the trophic variability of the pike gudgeon Pseudogobio esocinus and largemouth bass Micropterus salmoides as representative specialist and generalist fish species, respectively, from 16 ecologically variable habitats in the four major rivers of Korea.

There was little variation (1σ) in the trophic position (TP) among habitats for P. esocinus (± 0.2); however, there was considerably large variation for M. salmoides (± 0.6). The TP of M. salmoides was negatively correlated with the benthic invertebrate indices of the habitats, whereas the TP of P. esocinus showed no significant correlation with any indices. Thus, these two representative fish species have different trophic responses to ecological conditions, which is related to known differences in the trophic niche between specialists (i.e., small niche width) and generalists (i.e., large niche width).

Over the past four decades, the conventional bulk isotope analysis has not been capable of deconvoluting “scenopoetic” and “bionomic” information. However, in the present study, we demonstrated that the CSIA of amino acids could isolate trophic niches from the traditional ecological niche composed of trophic and habitat information and evaluated how biological and ecological indices influence the trophic response of specialists and generalists.
Advances in accelerometry for cardiovascular patients: a systematic review with practical recommendations
Authors: Vetrovsky Tomas , Clark Cain C.T. , Bisi Maria Cristina , Siranec Michal , Linhart Ales , Tufano James J. , Duncan Michael J. , Belohlavek Jan
Published: July 2020

Aims

Accelerometers are becoming increasingly commonplace for assessing physical activity; however, their use in patients with cardiovascular diseases is relatively substandard. We aimed to systematically review the methods used for collecting and processing accelerometer data in cardiology, using the example of heart failure, and to provide practical recommendations on how to improve objective physical activity assessment in patients with cardiovascular diseases by using accelerometers.

Methods and results

Four electronic databases were searched up to September 2019 for observational, interventional, and validation studies using accelerometers to assess physical activity in patients with heart failure. Study and population characteristics, details of accelerometry data collection and processing, and description of physical activity metrics were extracted from the eligible studies and synthesized. To assess the quality and completeness of accelerometer reporting, the studies were scored using 12 items on data collection and processing, such as the placement of accelerometer, days of data collected, and criteria for non‐wear of the accelerometer. In 60 eligible studies with 3500 patients (of those, 536 were heart failure with preserved ejection fraction patients), a wide variety of accelerometer brands (n = 27) and models (n = 46) were used, with Actigraph being the most frequent (n = 12), followed by Fitbit (n = 5). The accelerometer was usually worn on the hip (n = 32), and the most prevalent wear period was 7 days (n = 22). The median wear time required for a valid day was 600 min, and between two and five valid days was required for a patient to be included in the analysis. The most common measures of physical activity were steps (n = 20), activity counts (n = 15), and time spent in moderate‐to‐vigorous physical activity (n = 14). Only three studies validated accelerometers in a heart failure population, showing that their accuracy deteriorates at slower speeds. Studies failed to report between one and six (median 4) of the 12 scored items, with non‐wear time criteria and valid day definition being the most underreported items.

Conclusions

The use of accelerometers in cardiology lacks consistency and reporting on data collection, and processing methods need to be improved. Furthermore, calculating metrics based on raw acceleration and machine learning techniques is lacking, opening the opportunity for future exploration. Therefore, we encourage researchers and clinicians to improve the quality and transparency of data collection and processing by following our proposed practical recommendations for using accelerometers in patients with cardiovascular diseases, which are outlined in the article.
Inulin as a Promising Alternative Feedstock for Docosahexaenoic Acid Production by Schizochytrium sp. ATCC 20888
Authors: Dai Kexin , Zhao Jing , Cheng Yan , Tian Chang , Zhang Chunzhi , Chen Ming
Published: July 2020

Schizochytrium sp. is considered as a promising alternative commercial source of docosahexaenoic acid (DHA), but the production is hindered by the high feedstock cost. In this study, inulin is used as a cheap and readily available feedstock for Schizochytrium sp. ATCC 20888 to produce DHA. The strain could not utilize inulin directly and therefore inulin first needed to be hydrolyzed. Compared with the acidic hydrolyzate by HCl and hydrolyzate by endo‐inulinase, the hydrolyzate by exo‐inulinase serves as the most effective carbon source for microalgal growth. Hydrolysis of inulin by exo‐inulinase is further optimized, and up to 97.8% of inulin conversion is obtained under the optimal conditions of 40 °C, pH 7.0, substrate concentration of 80 g L−1 and exo‐inulinase loading of 2 g kg−1 substrate for 12 h. The resulting hydrolyzate containing mainly fructose is used for the DHA production by the microalga. The lipid content in biomass, DHA content in total fatty acids, DHA yield, and DHA productivity at 72 h reach 45.26%, 35.59%, 5.64 g L−1 and 1.88 g L−1 d−1, respectively. The results suggest that inulin is an excellent feedstock for Schizochytrium sp. suitable for commercial DHA production.

Practical Applications: DHA is an essential nutrient for human health and is widely used in infant formula and functional food. As a reserve carbohydrate, inulin present in plants represents a cheap, abundant, and readily available bioresource. This study describes the suitability of inulin as a promising alternative to glucose for DHA production by Schizochytrium sp. Hence, a practical bioprocess for commercial DHA production from inulin by Schizochytrium sp. could be developed. As far as it is known, this is the first report of inulin as a feedstock for Schizochytrium sp. to produce DHA.
ANGUISH: Security attack in narrowband‐Internet of Things (NB‐IoT) using game theory and hardware analysis
Authors: Kumar Vinod , Kumar Jha Rakesh , Jain Sanjeev
Published: July 2020

In recent years, the Internet of Things (IoT) plays a vital role in our daily life. IoT is dominating in many areas like industries, health care, smart home, social network, defense sector, and the education sector. In the last couple of years, users are facing different challenges like security issues related to social network and defense sector. In this article, our prime focus is to secure the social and defense network associated with narrowband‐Internet of Things. This article proposes the artificial intelligence (AI)‐based defense security attacks using unmanned aerial vehicle (UAV). In the first part of the article, we have proposed attack modeling on smart home scenario and finalize the critical parameter for performance analysis. In the next section, the performance analysis based on game theory (GT) (AI based) approach is attained, using different techniques like nash equilibrium and Prisoner's dilemma. In the last section, detailed hardware analysis has been carried out for analyzing attack in real‐time scenario and is illustrated with the help of step‐by‐step process. Our proposed model proves that UAV‐based router can spoof by the intruder with the probability of 0.4 using GT and hardware analysis.
Trends in parotidectomy over 30 years in an Australian tertiary care center
Authors: Subramaniam Narayana , Gao Kan , Gupta Ruta , Clark Jonathan Robert , Low Tsu‐Hui (Hubert)
Published: July 2020

Background

Nomenclature, classification, and management of parotid tumors are constantly evolving; this study was performed to identify temporal trends in histology and facial nerve sacrifice in parotidectomy during a 30‐year period (1987‐2018).

Methods

Retrospective analysis of patients treated in a single tertiary‐care institution during this time period was performed with analysis of temporal trends.

Results

Two thousand eight hundred and fifty‐seven parotidectomies were performed; pleomorphic adenoma was the most common histology (34.3%), followed by skin cancer metastases (32.3%). Significant trends noted were increasing age (P < .001), fewer parotidectomies for inflammatory lesions (P < .001), reduced incidence of mucoepidermoid carcinoma (P = .048), increasing incidence of parotidectomy for cutaneous malignancies (P < .001), and reduced facial nerve sacrifice (P = .034).

Conclusion

In this contemporary series of parotid pathology, metastatic cutaneous malignancies accounted for a third of cases. Despite reducing facial nerve sacrifice in parotid disease, it is still required in approximately 15% of malignancy and needs to be discussed with all patients preoperatively.
Characterization and Proteome of Circulating Extracellular Vesicles as Potential Biomarkers for NASH
Authors: Povero Davide , Yamashita Hirokazu , Ren Wenhua , Subramanian Mani G. , Myers Robert P. , Eguchi Akiko , Simonetto Douglas A. , Goodman Zachary D. , Harrison Stephen A. , Sanyal Arun J. , Bosch Jaime , Feldstein Ariel E.
Published: July 2020

Nonalcoholic fatty liver disease (NAFLD) is currently one of most common forms of chronic liver disease globally. NAFLD represents a wide spectrum of liver involvement from nonprogressive isolated steatosis to nonalcoholic steatohepatitis (NASH), characterized by liver necroinflammation and fibrosis and currently one of the top causes of end‐stage liver disease and hepatocellular carcinoma. At present, there is a lack of effective treatments, and a central barrier to the development of therapies is the requirement for an invasive liver biopsy for diagnosis of NASH. Discovery of reliable, noninvasive biomarkers are urgently needed. In this study, we tested whether circulating extracellular vesicles (EVs), cell‐derived small membrane‐surrounded structures with a rich cargo of bioactive molecules, may serve as reliable noninvasive “liquid biopsies” for NASH diagnosis and assessment of disease severity. Total circulating EVs and hepatocyte‐derived EVs were isolated by differential centrifugation and size‐exclusion chromatography from serum samples of healthy individuals, patients with precirrhotic NASH, and patients with cirrhotic NASH. EVs were further characterized by flow cytometry, electron microscopy, western blotting, and dynamic light scattering assays before performing a proteomics analysis. Our findings suggest that levels of total and hepatocyte‐derived EVs correlate with NASH clinical characteristics and disease severity. Additionally, using proteomics data, we developed understandable, powerful, and unique EV‐based proteomic signatures for potential diagnosis of advanced NASH. Conclusion: Our study shows that the quantity and protein constituents of circulating EVs provide strong evidence for EV protein–based liquid biopsies for NAFLD/NASH diagnosis.
Hall effects on MHD couple stress fluid flow through a vertical microchannel subjected to heat generation: A numerical study
Authors: Roja A. , Gireesha B. J.
Published: July 2020

The present study analyzes the irreversibility in an electrically conducting couple stress fluid between two vertical channel plates with the aspects of exponential space and temperature‐dependent, radiative heat flux, heat generation, and Joule heating. A reduced system of the governing equations is obtained via applying suitable nondimensional variables. To determine the solutions of velocity, thermal field, irreversibility, and irreversibility ratio, the Runge‐Kutta‐Fehlberg method along with the shooting technique has been employed. The various pertinent parameters that are involved in the problem have been discussed in detail through graphs. The results show that the entropy production can improve with the viscous dissipation, Joule heating, exponential space and temperature‐dependent, and radiative heat flux. Furthermore, it is clear that the entropy enhances with wall ambient temperature difference, radiation parameter, and the effect is reversed with higher estimations of the fluid wall interaction parameter, couple stress parameter, and rarefaction. The present numerical results are compared with the existing results that are in good agreement.
Development and Application of a Predictive Model for Treated Wastewater Irrigation Management in a Semiarid Area
Authors: Dragonetti Giovanna , Khadra Roula , Daccache André , Oubelkacem Abdellah , Choukr-Allah Redouane , Lamaddalena Nicola
Published: July 2020

The use of treated wastewater (TWW) as an alternative resource to fresh water (FW) for irrigation purposes is becoming increasingly important, especially in semiarid and arid regions. However, achieving success in crop production largely depends on the adoption of appropriate on-farm management strategies aimed at optimizing crop yields, maintaining soil productivity and safeguarding the environment. For this purpose, predictive models are of particular interest. A safe irrigation management (SIM) model developed and tested in this research was used to schedule irrigation under controlled management tailored to the use of 1) TWW and 2) FW and to reproduce farmers' strategies. These management strategies aim to improve actual irrigation practices, accounting for water quality, soil characteristics, and crop yield. The results of the application of SIM on a citrus farm in Souss-Massa, Morocco, show that the management strategy adopted by farmers withdraws considerable amounts of water and results in substantial drainage volumes compared to those in the SIM strategy. In the specific case of TWW, the strategy simulated by the SIM model resulted in a decrease in yield of approximately 4%, compared to the 23% decrease derived from the farmers' traditional strategy. Moreover, SIM allowed for great savings in terms of fertilizing elements and for the reduction in the movement of water and salts beyond the root zone, usually considered the main source of groundwater contamination. These results confirm the appropriateness of using prediction models and the accuracy of the SIM model in adapting irrigation strategies to TWW, which will be an integral part of the strategies that encourage their use in irrigated agriculture. Integr Environ Assess Manag 2020;16:910–919. © 2020 SETAC
Phenotypically defined subpopulations of circulating follicular helper T cells in common variable immunodeficiency
Authors: Yesillik Sait , Gupta Sudhir
Published: July 2020

Background

Common variable immunodeficiency (CVID) is characterized by low immunoglobulin G and IgA/IgM, decreased switched memory B cells, impaired response to vaccine, and an increased susceptibility to infections and autoimmunity. TFH cells play an important role in germinal center reaction where it supports isotype switching, somatic hypermutation, generation of memory B cells, and differentiation of B cells to plasma cells. The objective was to study the distribution of three subsets of TFH cells and their relationship with autoimmune diseases associated with CVID.

Methods

TFH cells have been divided into TFH1 (interleukin 21 [IL‐21] and interferon γ), TFH2 (IL‐21 and IL‐4), and TFH17 (IL‐21 and IL‐17) cells. Mononuclear cells from 25 patients with CVID and age and gender‐matched controls were stained with various monoclonal antibodies (anti‐CD4 APC, anti‐CXCR5 FITC, anti‐CCR6 PerCP, and anti‐CXCR3 PE) and isotype controls and analyzed for TFH1 (CD4+CXCR5+CXCR3+CCR6−), TFH2 (CD4+CXCR5+CXCR3−CCR6−), and TFH17 (CD4+CXCR5+CXCR3−CCR6+) cells by multicolor flow cytometry. Twenty thousand cells were acquired and analyzed by FlowJo software. Statistical analysis of comparison of patients and healthy controls was performed by paired t test using PRISM 7 software.

Results

TFH2 and TFH17 cells subpopulations of TFH cells were significantly decreased (P < .003 and P < .006, respectively) in CVID as compared with controls. No significant difference was observed in any of TFH cell subpopulations between CVID with and those without autoimmunity group.

Conclusion

Alterations in TFH cell subpopulation may play a role in defects in B cell compartment in CVID.