bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double‐blind, placebo‐controlled trial
Authors: Beghi Ettore , Pupillo Elisabetta , Bianchi Elisa , Bonetto Valentina , Luotti Silvia , Pasetto Laura , Bendotti Caterina , Tortarolo Massimo , Sironi Francesca , Camporeale Laura , Sherman Alexander V. , Paganoni Sabrina , Scognamiglio Ada , De Marchi Fabiola , Bongioanni Paolo , Del Carratore Renata , Caponnetto Claudia , Diamanti Luca , Martinelli Daniele , Calvo Andrea , Filosto Massimiliano , Padovani Alessandro , Piccinelli Stefano Cotti , Ricci Claudia , Dalla Giacoma Stefania , De Angelis Nicoletta , Inghilleri Maurizio , Spataro Rossella , La Bella Vincenzo , Logroscino Giancarlo , Lunetta Christian , Tarlarini Claudia , Mandrioli Jessica , Martinelli Ilaria , Simonini Cecilia , Zucchi Elisabetta , Monsurrò Maria Rosaria , Ricciardi Dario , Trojsi Francesca , Riva Nilo , Filippi Massimo , Simone Isabella Laura , Sorarù Gianni , Spera Cristina , Florio Lucia , Messina Sonia , Russo Massimo , Siciliano Gabriele , Conte Amelia , Saddi Maria Valeria , Carboni Nicola , Mazzini Letizia ,   the RNS60‐ALS Study Group
Published: September 2022

Background and purpose

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials.

Methods

This was a phase II, multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group trial. Participants diagnosed with definite, probable or probable laboratory‐supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non‐infusion days, followed by an additional 24 weeks off‐treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale—Revised), a measure of self‐sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire‐40, ALSAQ‐40) and survival. Tolerability and safety were assessed.

Results

Seventy‐four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ‐40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ‐40, difference –0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60.

Conclusions

The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation.
Gene panel to guide antiseizure medication prescribing: Does the cost justify the benefits?
Authors: Widjaja Elysa
Published: September 2022

Pharmacogenomics hold the potential to identify variants associated with adverse drug reactions and treatment efficacy of anti‐seizure medications. A model‐based cost‐utility analysis by Gordon and colleagues showed that genetically‐guided therapy costs more, yielded higher quality‐adjusted life years outcomes, and was considered to be cost‐effective compared to usual care. The study provided preliminary evidence on the value of pharmacogenetic testing in patients with drug‐resistant epilepsy. However, data input for the model was based on assumptions that need to be empirically tested. Further, there are many other factors that may affect the cost‐effectiveness of pharmacogenetic testing that need to be considered, including the model of service delivery, its implementation in complex clinical service, whether clinicians will modify treatment decisions based on pharmacogenetic information, and the fidelity with which recommendation on testing is adhered to in the real‐world. The cost‐effectiveness analysis should be repeated when more robust data on the effectiveness of pharmacogenetics are available and conducted alongside a budget impact analysis, incorporating the direct health care resources required to implement widespread testing and potential subsequent changes in treatment.
A Novel, Laser‐Based Microsampling Technique for Texturally Controlled, Combined and Complementary Sr and Nd Isotope Measurements in Silicate Minerals
Authors: Logue Andrew S. , Bybee Grant M. , Tappa Michael J. , Baxter Ethan , Iaccheri Linda
Published: September 2022

The limitations of many in situ microsampling techniques, especially when applied to isotopic analyses, may result in lower measurement precision and limit the ability to compare different isotope systems within the same phase or the same isotope system between phases. High‐precision, combined and complementary isotopic measurements are typically limited to whole‐rock samples or mineral separates at the expense of textural context. We demonstrate that laser ablation instruments could offer an effective, non‐mechanical alternative to micro‐milling for delineating and extracting single crystals, interstitial phases, and sub‐crystal scale features from soluble‐resin thick sections for column chromatography and high precision ID‐TIMS measurement. Systematic testing demonstrated that both modern and legacy laser instruments are capable of ablating through plagioclase, pyroxene and fused glass to depths of 200 μm. Modern instruments offer software benefits to identifying optically‐indistinct petrographic features, chemical zoning and avoiding alteration phases by using overlain high‐resolution datasets. Extracting delineated targets of varying geometry was achieved under binocular microscope using common mineral‐separation tools. Analysis of RM glass used as mineral proxies indicate (a) no significant thermal aureole on ablated margins that could affect measured parent‐daughter ratios, (b) no elevated risk of contamination compared with traditional mineral separation techniques, (c) excellent blanks for low‐yield analyses and (d) high‐precision ID‐TIMS results (87Sr/86Sr and 143Nd/144Nd) for sub‐100 ng Sr loads and sub‐10 ng Nd loads.
Clinically relevant model of oxaliplatin‐induced sinusoidal obstruction syndrome
Authors: Toda Rei , Seo Satoru , Uemoto Yusuke , Morino Koshiro , Nishino Hiroto , Nakamura Naohiko , Okuno Masayuki , Iguchi Kohta , Sato Motohiko , Nakamura Kojiro , Taura Kojiro , Nakagawa Shunsaku , Nakagawa Takayuki , Tsuruyama Tatsuaki , Manabe Toshiaki , Kawaguchi Hiroaki , Iwaisako Keiko , Ikegawa Masaya , Uemoto Shinji , Hatano Etsuro
Published: September 2022

Aim

Sinusoidal obstruction syndrome (SOS) induced by oxaliplatin‐including chemotherapies (OXCx) is associated with impaired hepatic reserve and higher morbidity after hepatic resection. However, in the absence of an appropriate animal experimental model, little is known about its pathophysiology. This study aimed to establish a clinically relevant reproducible model of FOLFOX‐induced SOS and to compare the clinical/histopathological features between the clinical and animal SOS settings.

Methods

We performed clinical/pathological analyses of colorectal liver metastasis (CRLM) patients who underwent hepatectomy with/without preoperative treatment of FOLFOX (n = 22/18). Male micro‐minipigs were treated with 50% of the standard human dosage of the FOLFOX regimen.

Results

In contrast to the monocrotaline‐induced SOS model in rats, hepatomegaly, ascites, congestion, and coagulative necrosis of hepatocytes were absent in patients with CRLM with OXCx pretreatment and OXCx‐treated micro‐minipigs. In parallel to CRLM cases with OXCx pretreatment, OXCx‐challenged micro‐minipigs exhibited deteriorated indocyanine green clearance, morphological alteration of liver sinusoidal endothelial cells, and upregulated matrix metalloproteinase‐9. Using our novel porcine SOS model, we identified the hepatoprotective influence of recombinant human soluble thrombomodulin in OXCx‐SOS.

Conclusions

With distinct differences between monocrotaline‐induced rat SOS and human/pig OXCx‐SOS, our pig OXCx‐SOS model serves as a preclinical platform for future investigations to dissect the pathophysiology of OXCx‐SOS and seek preventive strategies.
Urgent desensitization for severe amiodarone intolerance with a 12‐step protocol
Authors: Purtell Christopher , Mehta Mehek , Steele Ryan , Schoenfeld Mark
Published: September 2022

A 68‐year‐old man with severe nonischemic cardiomyopathy presented with cardiogenic shock and electrical storm. The patient had recently experienced a severe skin reaction to amiodarone and did not respond to alternative antiarrhythmic therapies. He underwent an emergent desensitization protocol and was able to tolerate amiodarone within 12 h. This was effective at suppressing electrical storm and did not lead to any further allergic or hemodynamic issues.
‘It's like being pushed into sea on a boat with no oars’: Breast cancer survivorship and rehabilitation support in Ireland and the UK
Authors: Deery Elizabeth , Johnston Katie , Butler Thomas
Published: September 2022

Background

Cancer survivorship is associated with co‐morbidities including anxiety, depression and cardiovascular disease (CVD). Rehabilitative care post‐treatment is vital for survivors' psychological and physical well‐being. The present study aimed to investigate breast cancer survivors' attitudes towards their health post‐treatment; their awareness of co‐morbidities associated with treatment; and their awareness of support systems available.

Methods

A qualitative research approach was employed, using semi‐structured interviews with breast cancer survivors from the UK and Ireland. Data were analysed using thematic analysis. Eight breast cancer survivors were recruited through purposive sampling.

Results

Two themes emerged from the data: (1) health and rehabilitation post‐treatment, which included mental and physical health and a desire to control one's own health in survivorship as well as a discussion around co‐morbidities, and (2) access to support services in survivorship, which highlighted both positive and negative experiences of accessing support, as well as reasons for not accessing support in survivorship.

Conclusions

Access to rehabilitation support, including diet, exercise and stress management, is key to survivorship. Rehabilitation and support services need to be more readily available for survivors to aid them in this journey and to educate them on the increased risk of conditions such as CVD with cancer treatment. Utilising current cardiac rehabilitation models could be a solution to provide a holistic cancer rehabilitation, thus providing the lifelong support that cancer survivors both want and need.
Elucidating the multiple genetic alterations involved in the malignant transformation of a KRAS mutant neurenteric cyst. A case report
Authors: Saito Shoji , Natsumeda Manabu , Sainouchi Makoto , Takino Toru , Shibuya Kohei , On Jotaro , Kanemaru Yu , Ogura Ryosuke , Okada Masayasu , Oishi Makoto , Shimada Yoshifumi , Wakai Toshifumi , Okuda Shujiro , Ajioka Yoichi , Kakita Akiyoshi , Fujii Yukihiko
Published: September 2022

Neurenteric cyst (NC) shows benign histopathology and rarely demonstrate malignant transformation. We herein describe a case of NC that exhibited malignant transformation. A 65‐year‐old female presented with gait disturbance due to compression by a cystic mass on the dorsal surface of the medulla oblongata. Partial resection was performed twice, leading to improvement of her symptoms. Two years after the second surgery, gadolinium‐perfused T1‐weighted magnetic resonance imaging revealed an invasive lesion with contrast enhancement at the trigone of the left lateral ventricle for which partial resection followed by radiotherapy was performed. However, mass regrowth was observed, with the patient eventually succumbing to her disease 11 months after her third surgery. Histopathological analyses of the first and second surgical specimens identified pseudostratified cuboidal epithelial cells, with no nuclear or cellular atypia resembling gastrointestinal mucosa, lining the inner surface of the cystic wall. Based on these findings the lesion was diagnosed as NC. The third surgical specimen exhibited apparent malignant features of the epithelial cells with elongated and hyperchromatic nuclei, several mitotic figures, small necrotic foci, and a patternless or sheet‐like arrangement. Based on these findings, the lesion was diagnosed as NC with malignant transformation. Next‐generation sequencing revealed KRAS p.G12D mutation in all specimens. Additionally, the third surgical specimen harbored the following 12 de novo gene alterations: ARID1A loss, BAP1 p.F170L, CDKN1B loss, CDKN2A loss, CDKN2B loss, FLCN loss, PTCH1 loss, PTEN loss, PTPRD loss, SUFU loss, TP53 loss, and TSC1 loss. The aforementioned results suggest that KRAS mutation is associated with the development of the NC, and that the additional gene alterations contribute to malignant transformation of the NC.
Orthopox viruses and the safety margins of solvent‐detergent treated plasma‐derived medicinal products
Authors: Kindermann Johanna , Karbiener Michael , Kreil Thomas R.
Published: September 2022

Background

The currently ongoing outbreak of monkeypox virus in many non‐endemic countries around the world has also raised concerns about the safety of plasma‐derived medicinal products. Based on what is known about the poxviridae, that is, that members are exceedingly large and carry a lipid envelope, effective removal and inactivation by plasma product manufacturing processes is expected. For the widely used solvent‐detergent (S/D) treatments, however, poxviruses have been reported as potentially being a bit more resistant.

Study Design and Methods

Using a S/D mixture comprising tri‐n‐butyl‐phosphate, polysorbate 80 and Triton X‐100 (TX‐100), inactivation of vaccinia virus (a model closely resembling monkeypox virus, both within the same genus, i.e., Orthopoxvirus) in a plasma‐derived process intermediate was analyzed over 60 min. As use of Triton X‐100 will, based on environmental concerns, be restricted, similar experiments were conducted with a physicochemically virtually identical alternative, Nereid.

Results

Fast inactivation of vaccinia virus to the assay detection limit, that is, reduction of infectivity by greater than 4 log10 within 10–20 min, was measured for the TX‐100 S/D mixture. The alternative S/D mixture (Nereid instead of TX‐100) was found fully equivalent.

Conclusion

As for other lipid‐enveloped viruses, treatment of process intermediates with S/D mixtures containing TX‐100 or the closely related detergent Nereid are highly effective in inactivating poxviruses. Thus, the current spread of monkeypox virus does not compromise the viral safety margins of plasma‐derived medicines.
Diffusion Bonded Compact Heat Exchanger in Inconel 740H for High Temperature and High-Pressure Applications
Authors: Jia Zhijun , Parlow Thomas , Kuhr Dane , Anderson Mark , Baker Brian
Published: September 2022

It is desired to develop heat exchangers able to be operated at high temperatures (750°C) and pressures (3636 psi) for use in advanced Brayton power cycle. Conventional materials have not had the high strength at temperature required for these applications previously, however a fairly new material Inconel 740H developed by Special Metals for the ultra-supercritical water fossil industry has shown good performance under these conditions. In further efforts to capitalize on these new high strength high temperature alloys CompRex has developed a diffusion bonding procedure capable of alloying compact high effectiveness heat exchangers that can perform under these high temperature and high-pressure conditions. Initial tests of the heat exchanger are being conducted at the University of Wisconsin using supercritical CO2 working fluid. The bonding process has been adjusted such that the strength of the bonded block has achieved over 90% yield and tensile strength of the 740H base material values. Grain size before and after bonding were measured to determine the extent of grain growth and grain diffusion across the interface. A discussion of the heat exchanger design, etching and initial tensile tests on sample bonds will be discussed.
Convective Heat Transfer Potential of Particles/Airflow Through Single Cell Thick Additively Manufactured Octet-Shaped Lattice Frame Material
Authors: Aider Youssef , Cho Heejin , Singh Prashant
Published: September 2022

Particle-to-Supercritical Carbon Dioxide (sCO2) heat exchangers are one of the most critical components of the next-generation Concentrating Solar Power (CSP) plants. There have been several efforts to enhance the overall heat exchanger performance which essentially comprises of thermal resistances offered by sCO2 channel, wall (separating sCO2 with particles) thickness, particle-wall contact resistance and particle-side effective heat transfer coefficient. This study is focused towards reducing the particle side thermal resistance by incorporating single unit cell thick reticulated Octet lattice frame structures on the falling particle side to enhance the effective thermal conductivity of the particle channel and to enhance convective heat transfer between the falling particles and the solid phase of the falling particle channel (endwalls and fibers). Steady-state experiments were conducted to measure the effective thermal conductivity of lattice frame material for two cases: a) when void space was occupied by air, b) when void space was occupied with particles. Further, convective heat transfer experiments have been conducted with both air (steady-state) and particles (quasi steady-state) as “working fluid” for panels sandwiching the Octet array. Three different lattice porosities ranging from 0.75 to 0.9 have been tested for a wide range of air flow rates and a fixed particle flow rate (highest potential).
Analysis of the Heat Transfer and Criterion of Freezing of Molten Salt Startup Flow in Relatively Cold Pipes
Authors: Zhang Ye , Li Peiwen
Published: September 2022

Currently, most of the modern concentrated solar thermal power plants employ molten salts as the heat transfer fluid to carry the thermal energy from solar concentrators and deliver to thermal storage systems or thermal power plants for the need of power generation. For the startup operation of solar concentrators, molten salts need to be pumped to flow into the pipes which may have lower temperature than the molten salt due to cold ambient overnight or over the suspend period of operation. As the freezing point of various molten salts ranges from 220 °C to 430 °C, preventing the freezing of molten salt flowing in cold pipe is a very important requirement for the safe operation of a concentrated solar thermal power plant. In this work, the authors have conducted a basic heat transfer analysis of transient heat exchange between molten salts and the flow pipe to find a criterion or the critical condition of preventing molten salt from freezing. The effects of molten salt flow velocity, heat capacities of molten salt and pipe, dimensions of pipes, and the initial temperatures of salts and cold pipes are all correlated theoretically in the analysis through modeling of transient heat transfer between a pipe and the fluid. The results are very helpful to the understanding and management of a safe startup of hot molten salt flowing in cold pipes on cyclic operations.
Heat Transfer Coefficient Predictions of the Air-Cooled Condenser With Machine Learning Based on the Operation Big Data of the Power Plant
Authors: Chen Kai , Xie Xin , Chu Yan , Leng Meng , Zhang Jinyi , Xu Zhenwei , Huang Feng , Zhang Heming
Published: September 2022

The optimal operation of the air-cooled condenser (ACC) is crucial to the thermal efficiency of the power plant, where the heat transfer capacity of the ACC plays the fundamental role. However, the heat transfer coefficient (HTC) of the ACC is usually unknown due to its complexity under the real operation conditions, and therefore the operation of the ACC relies on the operator’s experience. Here prediction models of HTC of the ACC incorporating the heat transfer mechanisms and the machine learning algorithms are proposed. Approximately 1200 thousand of data records from a thermal power plant of China are reduced and used to train the models. Machine learning algorithms, such as Gaussian Process Regression (GPR), XGBoost (XGB), Multilayer Perceptron (MLP) and Support Vector Machines (SVM) are applied to build the models, which are all evaluated with the records in the test dataset. 17 parameters are treated as the features to train the HTC prediction models. Predictions with all the algorithms reach the level of engineering applications (MAPE < 0.060, R2 > 0.930, δ > 0.930), where XGB performs the best (MAPE = 0.042, R2 = 0.962, δ = 0.972). The feature importance and the correlations among all the parameters are analyzed. The effects of the ACC heat exchanger locations on the heat transfer are also studied based on the variations of the feature importance. In addition, the prediction model of the ACC fan rotation speed ω is studied as well, which is not as good as the HTC prediction model as ω prediction is an inverse problem. This work will benefit the thermal efficiency improvement of the power plant with the historical operating data with low cost.
Topology Optimization Design and Heat Transfer Performance of Cooling Channel Based on Fluid-Solid Coupling
Authors: Duan Zhijian , Xie Gongnan , Ma Xinrong
Published: September 2022

Based on the steady-state incompressible Navier-Stokes equations, a topology optimization strategy for fluid-solid coupling structure was proposed to maximize cooling efficiency. The physical model was established based on the active cooling system for scramjet configuration, and the Galerkin finite element method (FEM) was used to discretize the Navier-Stokes equations. Furthermore, combined with the rational approximation of material properties (RAMP) method, the globally convergent method of moving asymptotes (GCMMA) was used to solve the mathematical optimal model with different boundary conditions and objective functions. Numerical examples were provided to demonstrate the validity and effectiveness of the optimization strategy. The optimal flow passages of scramjet active cooling system under constraints are given successfully. Compared with the initial channel, the performance of the topological channel in reducing average temperature and flow loss is significantly improved, and the temperature of the construction is more uniform to avoid the occurrence of concentrated high temperature areas. In practical engineering application, the preliminary configuration obtained from the topology optimization can be parameterized to further improve the cooling performance of the channel.
Effects of Flow-Induced Vibration on Forced Convection Heat Transfer From Two Tandem Cylinders at Unequal Diameters
Authors: Khan Hamid Hassan , Islam Md Didarul , Fatt Yap Yit , Janajreh Isam
Published: September 2022

The effect of FIV on forced convection heat transfer from two elastically mounted tandem cylinders of unequal diameters has been investigated. The present numerical simulation demonstrates the effect of the diameter ratio (d/D = 0.2–1) on the heat transfer of an upstream cylinder with variable diameter ‘d’ and a downstream cylinder with constant diameter ‘D’. The flow is considered incompressible, two-dimensional, laminar at Re = 150 and Pr = 0.71. The two elastically mounted heated cylinders are allowed to oscillate in the transverse direction with reduced velocity Ur = 4 and 6, mass ratio m* = 2, damping ratio ξ = 0. The gap ratio between cylinders G/D = 1.5 and 3.5 are considered to elucidate the effect of heat transfer in extended body regime (G/D = 1.5) and reattachment regime (G/D = 3.5). The impact of the diameter ratio (d/D = 0.2–1) on flow dynamics and heat transfer characteristics is demonstrated through oscillation amplitude, flow structures and Nusselt number.
Comparison of Micro Fin Array Configurations for Heat Transfer Enhancement in Microchannels
Authors: Frear Colton , Carbajal Gerardo , Romero Edwar
Published: September 2022

An experimental study was conducted to compare several different micro fin array configurations to determine which channel design allows for maximum heat transfer for the largest range of flow conditions. The fin configurations were tested on novel microchannel cooling devices to measure their effectiveness. Three array configurations were tested: a dummy channel, a straight channel, and a hybrid channel. The baseline of which is a simple linear fin array that has previously proven to be effective. The second is a segmented design, in which the arrays of fins are part of a larger array of diamond-shaped segments. The final design is a hybrid between the first two configurations, resembling the straight fin design but cut into larger segments diagonally. A custom cover was made to allow measurements for temperature and pressure to be made at the inlet and outlet of the channel while not impeding the mass flux through the system. Using a scanning electron microscope (SEM), it was found that the average hydraulic diameter of each channel is 155 microns. Each cooling device was tested under a range of flowrate and heat inputs. The temperature change and pressure drop were calculated using temperature and pressure data from the inlet and outlet. This information, along with the mass flux, allows for a wide range of comparisons to be made between configurations. The experimental results revealed that, for single-phase flow, the original segmented fin configuration is the most effective. However, it is believed that the disruptive geometry of the segmented channel will allow for much greater flow mixing for all flow rates. Thus, allowing the design to perform well under a broader range of conditions. It was found during this experiment that the segmented channel design outperformed both the straight fin channel and the dummy channel.
Use of Genetic Algorithms to Extract Fundamental Heat Transfer Performance Parameters From Evaporative Cooler Test Data
Authors: Cabrera Samuel , Carey Van P.
Published: September 2022

To understand the effect of ZnO nanostructures on various metal surfaces, previous experiments have tested the evaporation performance of ZnO coated surfaces through single droplet deposition and pool boiling experiments. Results indicate that applying ZnO superhydrophilic surfaces on metal substrates enhances surface wettability and single droplet vaporization. These superhydrophilic surfaces have the potential to be easily scaled up to larger and more complex heat exchangers and enhance spray cooling processes. Consequently, this study explores the direct evaporative cooling of ZnO coated and non-coated copper wavy fin heat exchangers. The experimental apparatus consists of an airflow and water flow system. The airflow system consists of a variable speed fan and an electric heater that preheats air before it flows into the wavy fins and the water flow system consists of a low volumetric water flow nozzle that sprays droplets into the wavy fins. Experimental results and machine learning tools are used in tandem to characterize the efficiency of the heat exchangers and to extract fundamental heat transfer performance parameters such as the average heat transfer coefficient. Specifically, a genetic algorithm is used to determine how the Colburn heat transfer factor varies with Reynolds number, and how the wetted interfacial area varies with flow conditions. Thus, in addition to providing greater insight into the performance of the heat exchanger and its dependence on system parameters, a genetic algorithm helps attain an optimal design consisting of ZnO coated surfaces that will greatly enhance spray cooling systems.
Single-crystal organometallic perovskite optical fibers
Authors: Zhou Yongfeng , Parkes Michael A. , Zhang Jinshuai , Wang Yufei , Ruddlesden Michael , Fielding Helen H. , Su Lei
Published: September 2022

Semiconductors in their optical-fiber forms are desirable. Single-crystal organometallic halide perovskites have attractive optoelectronic properties and therefore are suitable fiber-optic platforms. However, single-crystal organometallic perovskite optical fibers have not been reported before due to the challenge of one-directional single-crystal growth in solution. Here, we report a solution-processed approach to continuously grow single-crystal organometallic perovskite optical fibers with controllable diameters and lengths. For single-crystal MAPbBr
3
(MA = CH
3
NH
3
+
) perovskite optical fiber made using our method, it demonstrates low transmission losses (<0.7 dB/cm), mechanical flexibilities (a bending radius down to 3.5 mm), and mechanical deformation–tunable photoluminescence in organometallic perovskites. Moreover, the light confinement provided by our organometallic perovskite optical fibers leads to three-photon absorption (3PA), in contrast with 2PA in bulk single crystals under the same experimental conditions. The single-crystal organometallic perovskite optical fibers have the potential in future optoelectronic applications.
A Stk4-Foxp3–NF-κB p65 transcriptional complex promotes T
reg
cell activation and homeostasis
Authors: Cui Ye , Benamar Mehdi , Schmitz-Abe Klaus , Poondi-Krishnan Varsha , Chen Qian , Jugder Bat-Erdene , Fatou Benoit , Fong Jason , Zhong Yuelin , Mehta Stuti , Buyanbat Altantsetseg , Eklioglu Beray Selver , Karabiber Esra , Baris Safa , Kiykim Ayca , Keles Sevgi , Stephen-Victor Emmanuel , Angelini Claudia , Charbonnier Louis-Marie , Chatila Talal A.
Published: September 2022

The molecular programs involved in regulatory T (T
reg
) cell activation and homeostasis remain incompletely understood. Here, we show that T cell receptor (TCR) signaling in T
reg
cells induces the nuclear translocation of serine/threonine kinase 4 (Stk4), leading to the formation of an Stk4–NF-κB p65–Foxp3 complex that regulates Foxp3- and p65-dependent transcriptional programs. This complex was stabilized by Stk4-dependent phosphorylation of Foxp3 on serine-418. Stk4 deficiency in T
reg
cells, either alone or in combination with its homolog Stk3, precipitated a fatal autoimmune lymphoproliferative disease in mice characterized by decreased T
reg
cell p65 expression and nuclear translocation, impaired NF-κB p65–Foxp3 complex formation, and defective T
reg
cell activation. In an adoptive immunotherapy model, overexpression of p65 or the phosphomimetic Foxp3
S418E
in Stk3/4-deficient T
reg
cells ameliorated their immune regulatory defects. Our studies identify Stk4 as an essential TCR-responsive regulator of p65-Foxp3–dependent transcription that promotes T
reg
cell–mediated immune tolerance.
Evolution of the
vls
Antigenic Variability Locus of the Lyme Disease Pathogen and Development of Recombinant Monoclonal Antibodies Targeting Conserved VlsE Epitopes
Authors: Li Li , Di Lia , Akther Saymon , Zeglis Brian M. , Qiu Weigang
Published: September 2022

Current diagnostic protocols of Lyme disease indirectly detect the presence of antibodies produced by the patient upon infection by the bacterial pathogen, not the pathogen itself. These diagnostic tests tend to underestimate early-stage bacterial infections before the patients develop robust immune responses.
Supplemental Material: Major-element geochemistry of pelites
Authors: Forshaw Jacob B. , Pattison David R.
Published: September 2022

Detailed methodology, supplemental figures and tables, and references for studies in the database.  Whole-rock analyses can be found in the EarthChem repository (https://www.earthchem.org). 
Strategies to prevent and manage running-related knee injuries: a systematic review of randomised controlled trials
Authors: Alexander James L N , Culvenor Adam G , Johnston Richard R T , Ezzat Allison M , Barton Christian J
Published: September 2022

Objective

To evaluate the effectiveness of interventions to prevent and manage knee injuries in runners.

Design

Systematic review and meta-analysis.

Data sources

MEDLINE, EMBASE, CINAHL, Web of Science and SPORTDiscus up to May 2022.

Eligibility criteria for selecting studies

Randomised controlled trials (RCTs) with a primary aim of evaluating the effectiveness of intervention(s) to prevent or manage running-related knee injury.

Results

Thirty RCTs (18 prevention, 12 management) analysed multiple interventions in novice and recreational running populations. Low-certainty evidence (one trial, 320 participants) indicated that running technique retraining (to land softer) reduced the risk of knee injury compared with control treadmill running (risk ratio (RR) 0.32, 95% CI 0.16 to 0.63). Very low-certainty to low-certainty evidence from 17 other prevention trials (participant range: 24 –3287) indicated that various footwear options, multicomponent exercise therapy, graduated running programmes and online and in person injury prevention education programmes did not influence knee injury risk (RR range: 0.55–1.06). In runners with patellofemoral pain, very low-certainty to low-certainty evidence indicated that running technique retraining strategies, medial-wedged foot orthoses, multicomponent exercise therapy and osteopathic manipulation can reduce knee pain in the short-term (standardised mean difference range: −4.96 to −0.90).

Conclusion

There is low-certainty evidence that running technique retraining to land softer may reduce knee injury risk by two-thirds. Very low-certainty to low-certainty evidence suggests that running-related patellofemoral pain may be effectively managed through a variety of active (eg, running technique retraining, multicomponent exercise therapy) and passive interventions (eg, foot orthoses, osteopathic manipulation).

PROSPERO registration number

CRD42020150630
IOC consensus statement on recommendations and regulations for sport events in the heat
Authors: Racinais Sebastien , Hosokawa Yuri , Akama Takao , Bermon Stephane , Bigard Xavier , Casa Douglas J , Grundstein Andrew , Jay Ollie , Massey Andrew , Migliorini Sergio , Mountjoy Margo , Nikolic Nebosa , Pitsiladis Yannis P , Schobersberger Wolfgang , Steinacker Juergen Michael , Yamasawa Fumihiro , Zideman David Anthony , Engebretsen Lars , Budgett Richard
Published: September 2022

This document presents the recommendations developed by the IOC Medical and Scientific Commission and several international federations (IF) on the protection of athletes competing in the heat. It is based on a working group, meetings, field experience and a Delphi process. The first section presents recommendations for event organisers to monitor environmental conditions before and during an event; to provide sufficient ice, shading and cooling; and to work with the IF to remove regulatory and logistical limitations. The second section summarises recommendations that are directly associated with athletes’ behaviours, which include the role and methods for heat acclimation; the management of hydration; and adaptation to the warm-up and clothing. The third section explains the specific medical management of exertional heat stroke (EHS) from the field of play triage to the prehospital management in a dedicated heat deck, complementing the usual medical services. The fourth section provides an example for developing an environmental heat risk analysis for sport competitions across all IFs. In summary, while EHS is one of the leading life-threatening conditions for athletes, it is preventable and treatable with the proper risk mitigation and medical response. The protection of athletes competing in the heat involves the close cooperation of the local organising committee, the national and international federations, the athletes and their entourages and the medical team.
Clinical features ofNOTCH2NLC-related neuronal intranuclear inclusion disease
Authors: Tian Yun , Zhou Lu , Gao Jing , Jiao Bin , Zhang Sizhe , Xiao Qiao , Xue Jin , Wang Ying , liang Hui , Liu Yaling , Ji Guang , Mao Chenhui , Liu Caiyan , Dong Liling , Zhang Long , Zhang Shugang , Yi Jiping , Zhao Guohua , Luo Yingying , Sun Qiying , Zhou Yafang , Yi Fang , Chen Xiaoyu , Zhou Chaojun , Xie Nina , Luo Mengchuan , Yao Lingyan , Hu Yacen , Zhang Mengqi , Zeng Qiuming , Fang Liangjuan , Long Hong-Yu , Xie Yuanyuan , Weng Ling , Chen Si , Du Juan , Xu Qian , Feng Li , Huang Qing , Hou Xuan , Wang Junpu , Xie Bin , Zhou Lin , Long Lili , Guo Ji-feng , Wang Junling , Yan Xinxiang , Jiang Hong , Xu Hongwei , Duan Ranhui , Tang Beisha , Shen Lu
Published: September 2022

Background

Abnormal expanded GGC repeats within theNOTCH2HLCgene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID). This cross-sectional observational study aimed to characterise the clinical features ofNOTCH2NLC-related NIID in China.

Methods

Patients withNOTCH2NLC-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy.

Results

In the 247 patients withNOTCH2NLC-related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=−0.196, p<0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p<0.05). In NIID pedigrees, significant genetic anticipation was observed (p<0.05) without repeat instability (p=0.454) during transmission.

Conclusions

NIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum ofNOTCH2NLC-related NIID.
A Median-based Resilient Distributed Optimization Algorithm Against Byzantine Attack
Authors: Xu Chentao , Liu Qingshan
Published: September 2022

Distributed optimization algorithms are widely used for solving science and engineering problems in recent years. However, these algorithms become vulnerable in the face of external attacks, so it is urgent to develop novel resilient distributed optimization algorithms against attacks. In this paper, we design a novel median-based resilient distributed optimization algorithm to defend the Byzantine attack. The existence of transition matrix is proved, and the convergence and optimality of the proposed algorithm are analyzed. Simulation experiments are performed to verify the effectiveness of the proposed algorithm and the results show that it is more effective than the compared one and can get the best possible results against the attack.
From the Editor: What? You’re a human, too?!
Authors: Kelly Rob
Published: September 2022

As you read this latest rant, I am preparing my talk for the Gordon Research Conference (GRC) on Aqueous Corrosion, chaired this year by the illustrious Jamie Noël of Western University (see more about him in People News).
Pennington Corner: “Well, You Certainly Don’t Get That on Zoom!”
Authors: Jannuzzi Christopher J.
Published: September 2022

After two years and seven months, the Society has returned to hosting in-person technical conferences. The 241st ECS Meeting took place from May 29 to June 2 in beautiful Vancouver, British Columbia, Canada. How exciting it was to be back together again after such a very long time apart!
Electric Vehicle Batteries: Past, Present, and Future
Authors: Corrigan Dennis A.
Published: September 2022

Electric vehicles (EVs) were first commercialized over 100 years ago, using lead-acid batteries. Due to low battery energy density limiting the vehicle range, EVs were surpassed by gasoline powered cars that have dominated the auto industry until now. It took electrochemists 100 years to achieve the order of magnitude increase in specific energy needed for electric vehicles to become competitive. The Nobel prize technology of the lithium-ion battery has provided the necessary high energy density together with other excellent performance attributes including high power and long life in an affordable package for the modern EV. This breakthrough has enabled a return to commercialization of electric vehicles this time with excellent performance. Millions of electric vehicles are now being produced and sold globally with huge investments being made in EVs and Li-Ion batteries by the automotive and battery industries.
Role of BH4 deficiency as a mediator of oxidative stress-related endothelial dysfunction in menopausal women
Authors: DuBose Lyndsey E. , Ozemek Cemal , Wick Tyler , Richardson Vanessa , Hildreth Kerry L. , Moreau Kerrie L.
Published: September 2022

Endothelial function is reduced across the menopausal stages related to increased oxidative stress associated with estrogen deficiency. In vitro studies demonstrate that coadministration of VITC with BH4 prevents endothelial nitric oxide synthase (eNOS) uncoupling and reductions in NO by peroxynitrite; however, this remains untested in humans. We demonstrate that the coadministration of BH4 + VITC does not restore endothelial function in perimenopausal and postmenopausal women to the level of premenopausal women, suggesting that other mechanisms contribute.
A Study on Excavation Characteristics of Tunnel with Upper-Soft Lower-Hard Stratum
Authors: Feng Jun , Yang Hui-juan , Zhang Yu
Published: September 2022

In view of the geological environment, in which the upper part is the “soft” layer of completely weathered siliceous rock and the lower part is the “hard” layer of weakly weathered limestone, the rail surface line is designed to pass through the interface between the upper “soft” layer and lower “hard” layer. First, the MIDAS/GTS software was used to comprehensively simulate the stress and deformation law of surrounded rock under three excavation methods, which are the positive benching and retaining core soil method, CRD method, and double side drift method, for selecting the appropriate excavation method. After the excavation method was determined, the rule of change in the stress and deformation of the surrounded rock with time in the actual excavation process was analyzed by field monitoring means. Finally, on the basis of the findings in the numerical analysis as well as the field monitoring, the engineering characteristics, such as the stress and deformation of the surrounded rock during the excavation of deep buried tunnels in the upper-soft lower-hard ground, were analyzed. The results revealed the following: (1) Under all three excavation methods, the tunnel deformation was small and met the requirements for tunnel deformation control. (2) Due to the different excavation support sequence, the distribution of lining bending moment of the three excavation methods was widely different. The bending moment of the lining produced by the positive benching method was far less than that of the other two methods. (3) Due to the difference in lithology, the stress of the tunnel lining in the thick upper “soft” and “hard” strata was mainly concentrated on the upper soft rock area, while the stress in the lower hard rock area was relatively small, and the lining stress value generated using the three excavation methods was relatively large. In general, the deformation and stress in the positive benching method construction were less than those in the other two methods. In addition, the positive benching method was convenient for mechanized operation, the construction progress was fast, and the cost was relatively low. Therefore, the positive benching and retaining core soil method is adoptable for this kind of tunnel. (4) The measured stress and deformation at the rail surface line exhibited a change law of first increase, and subsequently, this tended to be stable. The change in stress-time can be expressed by the Boltzmann function, and the change in deformation with time can be well expressed by exponential functions. (5) The stress value and deformation value detected in the actual excavation were greater than the results of the theoretical numerical analysis. However, the findings in the theoretical numerical analysis still have certain guiding significance for actual excavation.
Effective Analytical Computational Technique for Conformable Time-Fractional Nonlinear Gardner Equation and Cahn-Hilliard Equations of Fourth and Sixth Order Emerging in Dispersive Media
Authors: Al-Smadi Mohammed , Al-Omari Shrideh , Karaca Yeliz , Momani Shaher
Published: September 2022

The aim of this paper is to investigate the approximate solutions of nonlinear temporal fractional models of Gardner and Cahn-Hilliard equations. The fractional models of the Gardner and Cahn-Hilliard equations play an important role in pulse propagation in dispersive media. The time-fractional derivative is observed in the conformable framework. In this orientation, a reliable computationally algorithm is designed and developed by following a residual error and multivariable power series expansion. Basically, the approximate solutions of pulse wave function of the fractional higher-order Gardner and Cahn-Hilliard equations are obtained in the form of a conformable convergent fractional series. Relevant consequences are theoretically and numerically investigated under the conformable sense. Besides, the analysis of the error and convergence of the developed technique are discussed. Some of the unidirectional homogeneous physical applications of the posed models in a finite compact regime are tested to confirm the theoretical aspects, demonstrate different evolutionary dynamics, and highlight the superiority of the novel developed algorithm compared to other existing analytical methods. For this purpose, associated graphs are displayed in two and three dimensions. Growing and decaying modes of the fractional parameters are analyzed for several

α

values. From a numerical viewpoint, the simulations and results declare that the proposed iterative algorithm is indeed straightforward and appropriate with efficiency for long-wavelength solutions of nonlinear partial differential equations.