bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical–striatal network functional connectivity markers in poststroke fatigue: a single-centre fMRI case–control study protocol
Authors: Tang Wai Kwong , Hui Edward Sai Kam , Leung Wai H
Published: August 2024

Introduction

Structural and functional abnormalities in the cortical–striatal network (CSN) are hypothesised to play a key role in the pathogenesis of neurological disease-associated fatigue. Some small-scale functional MRI (fMRI) studies have suggested that poststroke fatigue (PSF) is related to focal functional connectivity (FC) changes. To date, there has been no published large-scale fMRI study on PSF. This planned study will examine the role of the CSN FC on PSF.

Methods and analysis

The planned study will be a prospective cohort study conducted at the Neurology Unit of the Prince of Wales Hospital. We will recruit 738 participants. The project duration will be 36 months. A psychiatrist will administer the Fatigue Severity Scale (FSS) at 3 months (P1) following the index stroke. PSF is defined as an FSS Score≥4.0. PSF severity will be defined by the FSS total score at P1. Participants with PSF at P1 will undergo two follow-up assessments at 9 (P2) and 15 (P3) months post stroke. PSF remission at P2 or P3 will be defined as a 50% reduction in FSS. Participants will undergo MRI examinations within 2 weeks of the 3-month poststroke assessment. Structural MRI, resting-state fMRI and diffusion tensor imaging will be performed. FC, structural connectivity, infarcts, cerebral microbleeds and white matter hyperintensities will be analysed. For the primary analysis, the effect of PSF on the FC, structural connectivity and diffusion metrics of CSN of stroke survivors, voxel-wise two-sample t-tests will be performed with FDR correction for multiple comparison and significance level set at p<0.05.

Ethics and dissemination

Ethical approval was obtained from the Joint Chinese University of Hong Kong–New Territories East Cluster clinical research ethics committee. The study findings will be shared through peer-reviewed journal publications, national and international conferences and social media platforms.
How to distinguish promotion, prevention and treatment trials in public mental health? Study protocol for the development of the VErona-LUgano Tool (VELUT)
Authors: Purgato Marianna , Albanese Emiliano , Papola Davide , Prina Eleonora , Tedeschi Federico , Gross Alden , Sijbrandij Marit , Acarturk Ceren , Annoni Anna Maria , Silva Manuela , Jordans Mark J D , Lund Crick , Tol Wietse A , Cuijpers Pim , Barbui Corrado
Published: August 2024

Introduction

Promoting mental health, preventing and treating mental disorders are critically important in public health, and many randomised controlled trials (RCTs) evaluate intervention strategies for these objectives. However, distinguishing promotion from prevention and from treatment RCTs is challenging. A tool to place studies along the promotion-to-treatment continuum in mental health research does not exist, leaving it to researchers and policymakers to decide on how to classify individual RCTs, which hinders evidence synthesis.

Methods and analysis

We present a protocol for the development of a new tool to assist researchers in distinguishing RCTs along the promotion-to-treatment continuum. We will establish a Tool Development Group, and use the Population, Intervention, Comparison and Outcome framework to define constructs. We will generate, define, categorise and reduce the items in the tool using qualitative methods, including cognitive interviews and a Delphi exercise. Psychometric evaluation—including unidimensionality, local independence, monotonicity and item homogeneity—will include data collection, scoring, internal consistency checks and factor analysis of the tool’s indicators for available RCTs. We will use standard Cohen’s kappa statistics to assess the reliability of the tool.

Ethics and dissemination

This study involves data collection from the already published literature. However, this protocol has been approved by the ethics committee of the Università della Svizzera Italiana (CE 2024 04). The results of the present project will be disseminated in peer-reviewed journals and at international and national scientific meetings. Training materials for the application of the tool will also be developed and disseminated to the scientific community. The tool and all related implementation materials will be published on a website and will be freely accessible to the public.
Characteristics of effective parent-mediated interventions for parents of children with neurodevelopmental disorders in rural areas: a systematic review protocol
Authors: Cullenward Julia , Curtin Michael , Dos Santos Vagner
Published: August 2024

Introduction

Parent-mediated interventions are therapeutic approaches that use parent training to enable parents to provide primary support and intervention to their child through the development of necessary skills, knowledge, and resources.

Parent-mediated interventions can be broadly divided into two stages: (1) Clinicians educating, training and coaching parents in the implementation of an intervention and relevant information regarding their child’s condition and (2) Parent(s) mediating and implementing the intervention based on the coaching and education received. These interventions can act as the primary intervention for children or supplement clinical interventions. This review will include both stages of the implementation process as well as both primary and supplementary interventions. Outcomes of parent-mediated interventions include long-term symptom reduction, improved prognosis for a wide range of behavioural and brain functions and enhanced parent–child dyadic social communication.

Methods and analysis

This systematic review aims to synthesise existing evidence and identify the characteristics of effective parent-mediated intervention for parents of children with neurodevelopmental disorders residing in rural areas. Systematic searches of CINAHL, PsycINFO, ProQuest allied health and nursing database, Ebscohost Psych and Behavioural database and SocINDEX were conducted twice with the latest completed on 5 March 2024 using preidentified search terms. Citations will be imported into EndNote V.20.6 (Clarivate Analytics, Pennsylvania, USA) to organise and de-duplicate and then Covidence to complete screening and extraction. The articles will be screened and reviewed following the Joanna Briggs Institute (JBI) guidelines for systematic reviews of Mixed methods. The JBI appraisal tools for systematic reviews will be used to assess the trustworthiness, relevance and results of qualitative, quantitative and mixed-methods studies. The scope of the literature analysed will include articles published between 2013 and 2024 in English. Literature was limited to the last 10 years to ensure the relevance of results as the intention is to report on current evidence. The start date of the study was March 2023 and the planned completion date is October 2024.

Ethics and dissemination

This study will neither involve human nor animal subjects and does not require ethics approval. Results will be disseminated to relevant groups in peer-reviewed journal(s) and at relevant children and parent health conferences or rural conferences. The key outcomes will also be shared on social media to support access for non-research audiences.
Beach Sprints Rowing: Injury and Illness Prevalence at the 2022 World Championships
Authors: DeLeo Joseph Michael , Ackerman Kathryn , Verhagen Evert , Fry Andrew C , Wilson Fiona
Published: August 2024

Background

Injury and illness surveillance helps establish the infrastructure to provide adequate medical support at regattas and is the foundation for developing prevention strategies.

Objective(s)

To assess the prevalence and characteristics of injuries in the 4 weeks before the start of the 2022 World Rowing Beach Sprints Finals (WRBSF) (the ‘Prevalence Survey’) and describe the incidence and nature of new-onset injuries and illnesses incurred during the WRBSF (the ‘Incidence Survey’).

Methods

Athletes completed: (1) a prevalence survey recording injuries the 4 weeks before the WRBSF and (2) a recording of injuries and illnesses that occurred during the 3-day regatta.

Results

Fifty-nine of 152 eligible WRBSF athletes completed the prevalence injury survey. Twenty-three (38.9%) reported experiencing at least one injury within the 4 weeks before the WRBSF. The most prevalent anatomical injury sites were the forearm (11.86%), lumbar spine (10.17%), knee (8.47%), ankle (6.78%) and hand/fingers (6.78%). During the competition, only two illness occurrences were reported; both were respiratory infections. Two athletes reported injuries: a hamstring strain and a concussion.

Conclusion

Rowers presenting to the WRBSF described injuries leading up to the event that were similar to those common in classic rowing. Rowers at the event suffered injuries of the lower limb that were different from classic rowing and may be related to the addition of running to this event. An event concussion should be considered as a more likely injury in this type of rowing and future events should be prepared to manage such an injury.
Case report of fatal immune-mediated myocarditis following treatment with davoceticept (ALPN-202), a PD-L1-dependent CD28 costimulator and dual PD-L1/CTLA-4 checkpoint inhibitor, in combination with pembrolizumab
Authors: Cavalcante Ludimila , Chandana Sreenivasa , Lakhani Nehal , Enstrom Amanda , LeBlanc Heidi , Schmalz Joseph , Lengyel Krisztina , Schneider Frank , Thomas Heather , Chisamore Michael J , Peng Stanford L , Naumovski Allison , Davar Diwakar
Published: August 2024

Engagement of programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) can interfere with the CD28 signaling requisite for T-cell activation. While immune checkpoint inhibitors (ICIs) can relieve this suppression, they are unable to drive CD28 costimulation that may mechanistically contribute to ICI resistance. Thus, CD28 costimulation in the context of checkpoint inhibition may activate immunosuppressed T-cells in the tumor microenvironment. Davoceticept (ALPN-202) is an Fc fusion of a CD80 variant immunoglobulin domain (vIgD) designed to mediate PD-L1-dependent CD28 costimulation while inhibiting the PD-L1 and CTLA-4 checkpoints. PD-L1-restriction of davoceticept’s CD28 costimulatory activity may minimize systemic T-cell activation and avoid untoward systemic toxicities. At the same time, preclinical studies have suggested that treatment with davoceticept during PD-1 inhibition may enhance antitumor activity by upregulating PD-L1, potentially synergizing with davoceticept’s PD-L1-dependent costimulatory mechanism. This report details two cases of fatal cardiac events following treatment with davoceticept in combination with pembrolizumab (anti-PD-1) in the phase 1 study, NEON-2. Both events occurred in females in their 60s; one with choroidal melanoma and prior immunotherapy, the other with ICI-naïve microsatellite stable colorectal cancer. The clinical courses were fulminant with symptom onset at 2 weeks, followed by rapid decline. Cardiac autopsy from one patient confirmed immune-related myocarditis, and immunosequencing revealed expansion of a single T-cell clone that was not present in the pretreatment tumor. These cases highlight the importance of understanding risk factors that may contribute to immune-related myocarditis and other severe immune-related adverse events when CD28 agonism is targeted in the context of checkpoint inhibition.Trial registration number: NEON-2 (NCT04920383).
ALOX5 contributes to glioma progression by promoting 5-HETE-mediated immunosuppressive M2 polarization and PD-L1 expression of glioma-associated microglia/macrophages
Authors: Chen Tao , Liu Jiangang , Wang Chenci , Wang Zhengwei , Zhou Jiayi , Lin Jiani , Mao Jie , Pan Tingzheng , Wang Jianwei , Xu Hongchao , He Xiaosheng , Wu Dinglan , Liu Zhuohao
Published: August 2024

Background

Oxylipin metabolism plays an essential role in glioma progression and immune modulation in the tumor microenvironment. Lipid metabolic reprogramming has been linked to macrophage remodeling, while the understanding of oxylipins and their catalyzed enzymes lipoxygenases in the regulation of glioma-associated microglia/macrophages (GAMs) remains largely unexplored.

Methods

To explore the pathophysiological relevance of oxylipin in human glioma, we performed Ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) analysis in human glioma and non-tumor brain tissues. To comprehensively investigate the role of arachidonate lipoxygenase 5 (ALOX5) in glioma, we performedin vivobioluminescent imaging, immunofluorescence staining and flow cytometry analysis on tumors from orthotopic glioma-bearing mice. We developed an ALOX5-targeted nanobody, and tested its anti-glioma efficacy of combination therapy with α-programmed cell death protein-1 (PD-1).

Results

In this study, we found that ALOX5 and its oxylipin 5-hydroxyeicosatetraenoic acid (5-HETE) are upregulated in glioma, accumulating programmed death-ligand 1 (PD-L1)+M2-GAMs and orchestrating an immunosuppressive tumor microenvironment. Mechanistically, 5-HETE derived from ALOX5-overexpressing glioma cells, promotes GAMs migration, PD-L1 expression, and M2 polarization by facilitating nuclear translocation of nuclear factor erythroid 2-related factor 2. Additionally, a nanobody targeting ALOX5 is developed that markedly suppresses 5-HETE efflux from glioma cells, attenuates M2 polarization of GAMs, and consequently ameliorates glioma progression. Furthermore, the combination therapy of the ALOX5-targeted nanobody plus α-PD-1 exhibits superior anti-glioma efficacy.

Conclusions

Our findings reveal a pivotal role of the ALOX5/5-HETE axis in regulating GAMs and highlight the ALOX5-targeted nanobody as a potential therapeutic agent, which could potentiate immune checkpoint therapy for glioma.
Determining cold strain in cold air: a comparison of two methods of partitional calorimetry to calculate heat storage and debt in cold air with mild hypothermia
Authors: Wallace Phillip J. , Hartley Geoffrey L. , Cheung Stephen S.
Published: August 2024

We compared two methods of partitional calorimetry to calculate heat storage and heat debt during cold air (0°C) exposure causing mild core cooling. Twelve participants performed a 5 min baseline in thermoneutral conditions (∼22.0°C, ∼50% relative humidity) followed by cold air exposure (∼0°C) until rectal temperature was reduced by ∆−0.5°C. Partitional calorimetry was used to calculate avenues of heat exchange (radiative, convective, and evaporative), heat storage, and heat debt continuously throughout cold exposure. We compared deriving these variables using prediction equations based on environmental and participant characteristics (PCALEquation Method) versus using measurement tools such as humidity sensors and heat flux discs (PCALHeat Flux Method). There were significant differences between methods (all p ≤ 0.001) for determining heat exchange, heat storage, and heat debt. At ∆−0.5°C, PCALHeat Flux Method had greater levels of radiative and convective heat exchange (PCALHeat Flux Method: −143.0 ± 16.8 W∙m2 vs PCALEquation Method: −123.0 ± 12.9 W∙m2, p ≤ 0.001), evaporative heat exchange (PCALHeat Flux Method: −9.0 ± 1.7 W∙m2 vs PCALEquation Method: −4.1 ± 0.0 W∙m2, p ≤ 0.001), heat storage (PCALHeat Flux Method: −15.0 ± 31.0 W∙m2 vs PCALEquation Method: +6.0 ± 25.9 W∙m2, p = 0.020), and heat debt (PCALHeat Flux Method: −692.0 ± 315.0 kJ vs PCALEquation Method: −422.0 ± 136.0 kJ, p ≤ 0.001). Overall, this study found the largest discrepancies between the two methods were when the environmental conditions and skin temperature were in high flux, as well as when core temperature was reduced by ∆−0.5°C. The use of PCALHeat Flux Method may be more advantageous to use in the cold to provide a higher resolution measurement of cold strain.
Consistent excesses in the search for $$\varvec{\tilde{\chi }_{2}^0\tilde{\chi }_{1}^\pm :}$$ wino/bino vs. Higgsino dark matter
Authors: Chakraborti Manimala , Heinemeyer Sven , Saha Ipsita
Published: August 2024

The quest for supersymmetric (SUSY) particles is among the main search channels currently pursued at the LHC. Particularly, electroweak (EW) particles with masses as low as a few hundred GeV are still viable. Recent searches for the “golden channel”, $$pp \rightarrow \tilde{\chi }_{2}^0 \tilde{\chi }_{1}^\pm \rightarrow \tilde{\chi }_{1}^0 Z^{(*)} \, \tilde{\chi }_{1}^0 W^{\pm (*)}$$

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show consistent excesses between ATLAS and CMS in the 2 lepton, 3-lepton and mono-jet searches, assuming "Equation missing" and $$\Delta m:= m_{\tilde{\chi }_{2}^0} - m_{\tilde{\chi }_{1}^0} \approx 20 \,\, \textrm{GeV}$$

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, as a DM candidate is in good agreement with the observed limits on the DM content of the universe, as well as with negative results from Direct Detection (DD) experiments. We analyze these two scenarios with respect to the observed excesses, taking into account all relevant experimental constraints. We show that in particular wino/bino DM with different signs of the SU(2) and U(1) soft SUSY-breaking parameters can describe well the experimental excesses, while being in agreement with all other constraints.
Polarized image of a synchrotron emitting ring around a static hairy black hole in Horndeski theory
Authors: Shi Han-Yu , Zhu Tao
Published: August 2024

In this paper, we investigate the polarization images of a synchrotron-emitting fluid ring surrounding a static hairy black hole within the framework of Horndeski’s theory. Our findings indicate that the characteristics of these polarization images are predominantly influenced by the hairy parameter, alongside the magnetic field near the black hole, the fluid’s velocity, and the observer’s inclination angle. Specifically, the hairy parameter primarily affects the polarized intensity and the apparent radius of the ring in the images. Conversely, the impacts of the magnetic field, fluid velocity, and inclination angle on the polarization images are found to be independent of the hairy parameter and closely resemble those observed in the context of Schwarzschild black holes. Additionally, the polarization direction is significantly influenced by the magnetic field orientation, while the inclination angle crucially determines the apparent flatness of the images. Variations in the fluid velocity direction also markedly affect the trend in polarized intensity. Furthermore, we explore how these parameters influence the Stokes $$Q-U$$

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loops, revealing distinct behaviors in response to changes in the aforementioned variables. This comprehensive analysis enhances our understanding of the intricate dynamics and observational signatures of black holes within alternative gravitational theories.
FISCAL ASPECTS OF THE EQUITY-EFFICIENCY TRADE-OFF
Authors: DALAMAGAS BASIL , LEVENTIDES JOHN , TANTOS STEFANOS
Published: August 2024

This study makes an attempt to trace out the extent to which (in)direct taxation distorts consumers’ behavior, thus being a hindrance towards achieving an optimal allocation of resources between equity and efficiency targets. To substantiate our argument, a utility maximization model is built to examine whether fiscal policy restores public confidence in attaining equilibrium between the marginal rate of substitution (MRS) and the marginal rate of transformation (MRT). The validity of our model is then tested by using a sample of eleven countries. Comparing actual with optimal (in)direct tax rates, we find that the tax system of eight countries tends to favor equity over efficiency (actual direct (indirect) tax rates higher (lower) than optimal direct (indirect) tax rates) and the tax system of three countries tends to apply the efficiency principle.
Comprehensive assessment of A-type granite from south Sinai, Egypt: geochemistry, zircon geochemistry and geochronology
Authors: Abu Anbar Mohamed , Ghoneim Mohamed F. , Abu-Alam Tamer S. , Hamdy Dina , Dong YunPeng , Wang Bo , Liu Xiaoming , Masoud Ahmed E.
Published: August 2024

The A-type granites are an important component of the Earth's continental crust and play a significant role in understanding crustal evolution and tectonic processes. This study presents a comprehensive assessment of A-type granites from Ataitir El Dehami granites (ADG), which are located in the northwestern part of the Wadi Seih area in South Sinai, using geochemistry, zircon geochemistry and geochronology characteristics. The geochemical analysis reveals that ADG are characterized by high silica content, relatively high FeO* and high alkali concentration, consistent with A-type granites derived from the melting of tonalite sources. Zircons from Ataitir El Dehami granites have high REE contents with Ce enrichment and depletion of Eu, which, together with the high U/Yb ratios, suggest that the studied granites were generated from melting of continental crustal rocks. Zircon U–Pb geochronological data indicate that the granite emplacement occurred around 575–603 Ma throughout continuous exhumation pulses. The isotopic analyses also indicate the presence of inherited zircon grains (735 ± 9 Ma). The present data suggest that the studied granites were formed in a post-collisional setting, and represent the transition stage from convergence to extension that occurred at 600 Ma.
On the Inference of Original Graph Information from Graph Embeddings
Authors: Li Yantao , Li Xinyang , Lei Xinyu , Qin Huafeng , Hu Yiwen , Zhou Gang
Published: August 2024

Graph embedding converts a graph data into a low dimensional space to preserve the original graph information. However, graph data can be reconstructed by malicious adversaries to train machine learning models from graph embeddings. This paper studies to what extent an adversary (without the original graph data) can recover the original graph data from graph embeddings. To quantify the original graph information leakage from graph embeddings, we develop a deep neural network model InferNet that can be used by adversaries to infer the original graph information from an adversary-accessible graph embedding database. More specifically, we propose the data-free reversed knowledge distillation technique to support the InferNet training even if the original graph dataset is absent. To ensure the performance of InferNet, we design two cycle-consistency loss functions to have an interactive training of InferNet over three series of datasets. To further enhance the performance of InferNet, we provide a joint training algorithm that simultaneously trains the pseudo-sample generator and InferNet, which significantly reduces the storage space. We evaluate the performance of InferNet on three datasets, and the intensive experiments demonstrate that InferNet can infer the original graph information from the graph embedding dataset with high accuracy.
Taming Consensus in the Wild (with the Shared Log Abstraction)
Authors: Balakrishnan Mahesh
Published: August 2024

The shared log is an abstraction for building layered consensus systems that are simple to develop, deploy, evolve, and operate. Shared logs emerged from systems research and have seen significant traction in industry over the past decade. In this paper, we describe some design principles for consensus-based systems, based on our experience building and operating real-world shared log databases in the wild.
Niche Theory and Species Range Limits Along Elevational Gradients: Perspectives and Future Directions
Authors: Chen I-Ching , Shen Sheng-Feng , Chan Shih-Fan
Published: August 2024

Despite two centuries of research, the mechanisms underlying the formation of species’ elevational range limits remain poorly understood. The climatic variability hypothesis highlights the role of climatic conditions in shaping species’ thermal tolerance and distribution ranges, while the species interactions–abiotic stress hypothesis underscores the relative importance of biotic factors and abiotic stress along environmental gradients. We emphasize Darwin's perspective on the ubiquity of interspecific competition across climatic gradients and the importance of understanding how climate modulates biotic interactions to shape species distributions. Niche theory provides a comprehensive framework, combined with empirical research, to explore how environmental gradients influence species traits, leading to context-dependent species interactions that constrain distributions. In particular, the application of the concept of environmentally weighted performance can further elucidate these complex ecological mechanisms. Future research should integrate multiple approaches, including field and laboratory manipulative experiments, theoretical modeling, and interdisciplinary collaboration, to improve our understanding of species distributions in mountain regions and to inform biodiversity conservation strategies in the face of rapid environmental change.
Geographic Gradients in Species Interactions: From Latitudinal Patterns to Ecological Mechanisms
Authors: Hargreaves Anna L.
Published: August 2024

The idea that species interactions are more ecologically and evolutionarily important toward lower latitudes underpins seminal theories in ecology and evolution. Recent global studies have found the predicted latitudinal gradients in interactions, particularly predation. However, latitudinal patterns alone do not reveal why interactions vary geographically and so do not provide strong predictions in space (e.g., for specific ecosystems) or time (e.g., forecasting responses to global change). Here, I review theory to identify a clearer, mechanistic, and testable framework for predicting geographic variation in the importance of species interactions. I review competing metrics of importance, proximate mechanisms that can increase interaction importance, and environmental gradients that could generate predictable geographic patterns (climate extremes and stability, warmer temperatures, productivity, and biodiversity). Strong empirical tests are accumulating thanks to the rise of global experiments and datasets; renewed focus on testing why interactions vary spatially will help move the field from identifying latitudinal patterns to understanding broader mechanisms.
Biogenesis and Functionality of Sortase-Assembled Pili in Gram-Positive Bacteria
Authors: Chang Chungyu , Ramirez Nicholas A. , Bhat Aadil H. , Nguyen Minh T. , Kumari Poonam , Ton-That HyLam , Das Asis , Ton-That Hung
Published: August 2024

A unique class of multimeric proteins made of covalently linked subunits known as pili, or fimbriae, are assembled and displayed on the gram-positive bacterial cell surface by a conserved transpeptidase enzyme named pilus-specific sortase. Sortase-assembled pili are produced by a wide range of gram-positive commensal and pathogenic bacteria inhabiting diverse niches such as the human oral cavity, gut, urogenital tract, and skin. These surface appendages serve many functions, including as molecular adhesins, immuno-modulators, and virulence determinants, that significantly contribute to both the commensal and pathogenic attributes of producer microbes. Intensive genetic, biochemical, physiological, and structural studies have been devoted to unveiling the assembly mechanism and functions, as well as the utility of these proteins in vaccine development and other biotechnological applications. We provide a comprehensive review of these topics and discuss the current status and future prospects of the field.
Extraordinary Hydrogen Evolution and Oxygen Evolution Reaction Activity From PPy@FeCo-LDH/NF Bifunctional Electrocatalyst in Alkaline Solution
Authors: Zhang Boxuan , Cui Jinxing , Li Zhifang , Yang Changlong , Dong Weiwei , Li Ke , Ma Yuanyuan , Nan Zheng
Published: August 2024

Alkaline water electrolysis is a promising technique for the production of hydrogen and oxygen. Nevertheless, the development of low-cost, high-activity metal-based electrocatalysts that can effectively catalyze the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) remains a significant challenge. Herein, we polymerized Polypyrrole (PPy) with FeCo layered double metal hydroxide grown in situ on nickel foam (NF) (FeCo-LDH/NF) by electrochemical polymerization to acquire composite material PPy@FeCo-LDH/NF. As a promising electrocatalyst with dual functionality for the HER and OER, the HER overpotential of PPy@FeCo-LDH/NF was 153 mV, and the OER overpotential was 245 mV at a current density of 10 mA·cm−2. It was because that PPy increased the number of active adsorption sites, which in turn regulated the ion transfer rate between the electrolyte and the prepared catalyst. At the same time, after 24 h of stability testing, the HER and OER capacitance retention rates were 96.7% and 97.1%, respectively.
Smooth and Vertical Sidewall Formation for AlGaN-Based Electronic and Optoelectronic Devices
Authors: Ghosh Arnob , Dominic Merwin Xavier Agnes Maneesha , Rajan Siddharth , Arafin Shamsul
Published: August 2024

We report a two-step etching process involving inductively coupled plasma (ICP) etching followed by wet chemical etching to achieve smooth and vertical sidewalls, being beneficial for AlGaN-based electronic and optoelectronic devices. The influence of ICP power on the roughness of etched sidewalls is investigated. It is observed that ICP etching alone does not produce smooth sidewalls, necessitating subsequent wet chemical etching using tetramethyl ammonium hydroxide (TMAH) to enhance sidewall smoothness and reduce tilt angle. The morphological evolution of the etched sidewalls with wet etch time for the device structures is also thoroughly investigated. Consistent etch results are achieved for AlxGa1-xN alloys with Al compositions up to 70%, indicating the effectiveness of our etching process.
Maintenance of thermogenic adipose tissues despite loss of the H3K27 acetyltransferases p300 or CBP
Authors: Gamu Daniel , Cameron Makenna S. , Gibson William T.
Published: August 2024

The role of transcriptionally activating H3K27ac epigenetic mark has yet to be examined in mouse thermogenic fats specifically, which we achieved here via Ucp1-Cre-driven knockdown of the histone acetyltransferases (HAT) p300 or CBP under several metabolic contexts. Despite successful knockdown of either HAT, brown adipose tissue was maintained at room temperature. As such, knockout mice were indistinguishable to controls when fed an obesogenic diet or when given a β3-adrenergic receptor agonist to induce browning of white fat. Unlike other tissues, thermogenic fats are resilient to p300 or CBP ablation, likely due to sufficient functional overlap between them.
Hierarchical differences in the encoding of amplitude modulation in the subcortical auditory system of awake nonhuman primates
Authors: Mackey Chase A. , Hauser Samantha , Schoenhaut Adriana M. , Temghare Namrata , Ramachandran Ramnarayan
Published: August 2024

In everyday environments, the brain is tasked with extracting information from sound envelopes, which involves both sensory encoding and perceptual decision-making. Different neural codes for envelope representation have been characterized in midbrain and cortex, but studies of brainstem nuclei such as the cochlear nucleus (CN) have usually been conducted under anesthesia in nonprimate species. Here, we found that subcortical activity in awake monkeys and a biologically plausible perceptual decision-making model accounted for sound envelope discrimination behavior.
Preparation and Application of Novel Power Semiconductor Chips
Authors: Yang Zhiwei , Abas Asim
Published: August 2024

This study aims to improve the triggering current and dynamic characteristics of thyristor chips by designing new gate structures and multilayer semiconductor structures. Thyristor chips are essential components in power electronic devices, widely used in fields such as power transmission, motor control, and energy conversion systems. Trigger current is a key factor in the performance of thyristor chips, which is responsible for initiating the conduction state of the thyristor and carrying high current under high voltage conditions. This study improved the triggering current and dynamic characteristics of thyristor chips by optimizing the chip structure, especially by introducing multilayer P/N semiconductor design and improving the gate structure. The research results provide important guidance for the future development of thyristor chips and also contribute to the advancement of semiconductor technology.
Safety and Efficacy Assessment of a Cross‐linked Hyaluronic Acid Dermal Filler for Correction of Moderate‐to‐Severe Nasolabial Folds in Skin Types III and IV
Authors: Yazdanparast Taraneh , Ahmad Nasrollahi Saman , Samadi Aniseh , Kafi Hamidreza , Nassiri Kashani Mansour , Ayatollahi Azin , Firooz Alireza
Published: August 2024

Introduction. Hyaluronic acid fillers are widely used to correct nasolabial folds. This treatment provides favorable aesthetic outcomes. The aim of this study was the safety and efficacy evaluation of Lunaphil Ultra intradermal filler for correcting nasolabial folds in the Iranian population with Fitzpatrick skin types III and IV. Methods. In this before and after clinical study, Lunaphil Ultra dermal filler was injected in nasolabial folds of 24 female and 6 male volunteers (mean age: 43.36 and SD: 11.55). Two independent physicians assessed the severity of nasolabial folds before injection and 2, 12, and 24 weeks later, according to the Allergan scale. The volume, depth, and area of both nasolabial folds and the thickness and density of the dermis in the right nasolabial fold were also measured. Adverse events and subject satisfaction were also recorded. Results. One grade or more improvement was detected in 81%, 57%, and 65% of participants at weeks 2, 12, and 24, respectively. The median score for the Allergan scale decreased significantly in all follow‐up visits. The median value of the area of nasolabial folds significantly reduced in all follow‐up visits. Two weeks after injection, dermis density showed a significant increase. The mean score for pain level during the injection was 1.96 out of 10. Adverse events were mild and transient. The median satisfaction scores were 9‐10 out of 10 at different visits. Conclusion. The findings showed that cross‐linked hyaluronic acid dermal filler containing lidocaine could be applied in clinical practice for correction of nasolabial folds in skin types III and IV, with high safety and efficacy. More comprehensive future research could approve these results. This trial is registered with IRCT20150101020514N11.
Figure 3 from Clinical Efficacy of the HIV Protease Inhibitor Indinavir in Combination with Chemotherapy for Advanced Classic Kaposi Sarcoma Treatment: A Single-Arm, Phase II Trial in the Elderly
Authors: Sgadari Cecilia , Scoppio Biancamaria , Picconi Orietta , Tripiciano Antonella , Gaiani Francesca Maria , Francavilla Vittorio , Arancio Angela , Campagna Massimo , Palladino Clelia , Moretti Sonia , Monini Paolo , Brambilla Lucia , Ensoli Barbara
Published: August 2024

Active MMP-2, CEC, and EPC levels and NK activity in participants that entered the maintenance phase (n = 16). Shown are the levels (cells/mL) at enrolment, upon induction, during maintenance, and post-therapy follow-up of active MMP-2 (A), CEC (B), and EPC (C), and NK-cell activity against K562 (D) or BCBL-1 targets (E) as % of lysis. Data are presented as box plots. Wilcoxon signed rank sum test for paired data and Mann–Whitney test were used for the analyses. P values assess the changes from enrolment and from baseline of maintenance within responders and progressors and differences between responders and progressors at each time point.
Figure 2 from Clinical Efficacy of the HIV Protease Inhibitor Indinavir in Combination with Chemotherapy for Advanced Classic Kaposi Sarcoma Treatment: A Single-Arm, Phase II Trial in the Elderly
Authors: Sgadari Cecilia , Scoppio Biancamaria , Picconi Orietta , Tripiciano Antonella , Gaiani Francesca Maria , Francavilla Vittorio , Arancio Angela , Campagna Massimo , Palladino Clelia , Moretti Sonia , Monini Paolo , Brambilla Lucia , Ensoli Barbara
Published: August 2024

Immunological parameters in participants that entered the maintenance phase (n = 16). Levels at enrolment, upon induction and during maintenance and post-therapy follow-up of total lymphocytes absolute number (103 cells/μL; A), CD4+ (B) CD8+, and (C) T-cell number (cells/μL), CD4+/CD8+ ratio (D), B- (E), and NK- (F) cell number (cells/μL). Data are presented as box plots. Wilcoxon signed rank sum test for paired data and Mann–Whitney test were used for the analyses. P values assess the changes from enrolment and from baseline of maintenance within responders and progressors and differences between responders and progressors at each time point.
Data from A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors
Authors: Vernet Rémi , Fernandez Eugenio , Migliorini Denis , Ancrenaz Virginie , Charrier Emily , Belkouch Marie-Claude , Von Rohr Olivier , Urwyler Muriel , De Vito Claudio , Renaux Jessica , Villard Jean , Rubin Olivier , Grogg Julien , Mach Nicolas
Published: August 2024

Abstract
Over two decades, most cancer vaccines failed clinical development. Key factors may be the lack of efficient priming with tumor-specific antigens and strong immunostimulatory signals. MVX-ONCO-1, a personalized cell-based cancer immunotherapy, addresses these critical steps utilizing clinical-grade material to replicate a successful combination seen in experimental models: inactivated patient’s own tumor cells, providing the widest cancer-specific antigen repertoire and a standardized, sustained, local delivery over days of a potent adjuvant achieved by encapsulated cell technology. We conducted an open-label, single-arm, first-in-human phase I study with MVX-ONCO-1 in patients with advanced refractory solid cancer. MVX-ONCO-1 comprises irradiated autologous tumor cells coimplanted with two macrocapsules containing genetically engineered cells producing granulocyte–macrophage colony-stimulating factor. Patients received six immunizations over 9 weeks without maintenance therapy. Primary objectives were safety, tolerability, and feasibility, whereas secondary objectives focused on efficacy and immune monitoring. Data from 34 patients demonstrated safety and feasibility with minor issues. Adverse events included one serious adverse event possibly related to investigational medicinal product and two moderate-related adverse events. More than 50% of the patients with advanced and mainly nonimmunogenic tumors showed clinical benefits, including partial responses, stable diseases, and prolonged survival. In recurrent/metastatic head and neck squamous cell carcinoma, one patient achieved a partial response, whereas another survived for more than 7 years without anticancer therapy for over 5 years. MVX-ONCO-1 is safe, well tolerated, and beneficial across several tumor types. Ongoing phase IIa trials target patients with advanced recurrent/metastatic head and neck squamous cell carcinoma after initial systemic therapy.
Significance:
This first-in-human phase I study introduces a groundbreaking approach to personalized cancer immunotherapy, addressing limitations of traditional strategies. By combining autologous irradiated tumor cells as a source of patient-specific antigens and utilizing encapsulated cell technology for localized, sustained delivery of granulocyte–macrophage colony-stimulating factor as an adjuvant, the study shows a very good safety and feasibility profile. This innovative approach holds the promise of addressing tumor heterogeneity by taking advantage of each patient's antigenic repertoire.
Data from Acetalax (Oxyphenisatin Acetate, NSC 59687) and Bisacodyl Cause Oncosis in Triple-Negative Breast Cancer Cell Lines by Poisoning the Ion Exchange Membrane Protein TRPM4
Authors: Mizunuma Makito , Redon Christophe E. , Saha Liton Kumar , Tran Andy D. , Dhall Anjali , Sebastian Robin , Taniyama Daiki , Kruhlak Michael J. , Reinhold William C. , Takebe Naoko , Pommier Yves
Published: August 2024

Abstract
Triple-negative breast cancer (TNBC) is clinically aggressive and relatively unresponsive to current therapies. Therefore, the development of new anticancer agents is needed to satisfy clinical needs. Oxyphenisatin acetate (Acetalax), which had been used as a laxative, has recently been reported to have anticancer activity in murine models. In this study, we demonstrate that Acetalax and its diphenolic laxative structural analogue bisacodyl (Dulcolax) exhibit potent antiproliferative activity in TNBC cell lines and cause oncosis, a nonapoptotic cell death characterized by cellular and nuclear swelling and cell membrane blebbing, leading to mitochondrial dysfunction, ATP depletion, and enhanced immune and inflammatory responses. Mechanistically, we provide evidence that transient receptor potential melastatin member 4 (TRPM4) is poisoned by Acetalax and bisacodyl in MDA-MB468, BT549, and HS578T TNBC cells. MDA-MB231 and MDA-MB436 TNBC cells without endogenous TRPM4 expression as well as TRPM4-knockout TNBC cells were found to be Acetalax- and bisacodyl-resistant. Conversely, ectopic expression of TRPM4 sensitized MDA-MB231 and MDA-MB436 cells to Acetalax. TRPM4 was also lost in cells with acquired Acetalax resistance. Moreover, TRPM4 is rapidly degraded by the ubiquitin–proteasome system upon acute exposure to Acetalax and bisacodyl. Together, these results demonstrate that TRPM4 is a previously unknown target of Acetalax and bisacodyl and that TRPM4 expression in cancer cells is a predictor of Acetalax and bisacodyl efficacy and could be used for the clinical development of these drugs as anticancer agents.
Significance:
Acetalax and bisacodyl kill cancer cells by causing oncosis following poisoning of the plasma membrane sodium transporter TRPM4 and represent a new therapeutic approach for TNBC.
Influencia del nivel socioeconómico en la percepción familiar de los riesgos en línea
Authors: López-Martínez Adela , Sádaba Charo , Feijoo Beatriz , Zozaya Luisa
Published: August 2024

(analytical)The use of social networks among children and adolescents has modified the need for parental mediation. The personal nature of these devices requires strategies that place more importance on trust and support, such as child-focused mediation. In the current digital context where families are concerned about the risks faced by their children, this qualitative research brings together 40 interviews of parent-child dyads living in Spain who are asked about mediation, risk perception, and their ability to face these risks. The findings have a direct correlation with socioeconomic status: fathers and mothers with high socioeconomic status are more aware of possible risks than those with low socioeconomic status. Children from wealthier families believe they are better able to manage these risks.
Perfusion Imaging‐Based Triage for Acute Ischemic Stroke: Trends in Use and Impact on Clinical Outcomes
Authors: Lee Jeong‐Yoon , Kim Do Yeon , Kim Jun Yup , Kang Jihoon , Kim Beom Joon , Han Moon‐Ku , Kim Yong Soo , Kang Kyusik , Kim Jae Guk , Lee Soo Joo , Kim Dae‐Hyun , Cha Jae‐Kwan , Choi Jin‐Kyo , Park Sang‐Soon , Park Tai Hwan , Lee Kyungbok , Kwon Doo Hyuk , Lee Jun , Park Hong‐Kyun , Cho Yong‐Jin , Hong Keun‐Sik , Lee Minwoo , Oh MI Sun , Yu Kyung‐Ho , Lee Byung‐Chul , Kim Hyunsoo , Choi Kangho , Kim Joon‐Tae , Gwak Dong‐Seok , Kim Dong‐Eog , Kang Chul‐Hoo , Kim Joong‐Goo , Choi Jay Chol , Yum Kyu Sun , Shin Dong‐Ick , Kim Wook‐Joo , Kwon Jee‐Hyun , Park Hyungjong , Hong Jeong‐Ho , Sohn Sungil , Lee Sang‐Hwa , Kim Chulho , Park Chan‐Young , Jeong Hae‐Bong , Park Kwang‐Yeol , Lee Dongwhane , Park Jong‐Moo , Lee Keon‐Joo , Han Jung Hoon , Kim Chi Kyung , Oh Kyungmi , Woo Ho Geol , Heo Sung Hyuk , Kim Jonguk , Lee Juneyoung , Lee Ji Sung , Gorelick Philip B. , Bae Hee‐Joon ,   and on behalf of the CRCS‐K‐NIH investigators
Published: August 2024

Background

Perfusion imaging (PI) serves as a valuable tool for triaging patients with acute ischemic stroke for endovascular treatment (EVT). This study aims to investigate trends in PI use and its impacts on EVT rates and clinical outcomes, particularly focusing on variations across different time windows.

Methods

Data from a prospective, nationwide, acute stroke registry in South Korea were analyzed retrospectively. PI was regarded as treatment‐decision imaging when conducted either (1) prior to EVT, or (2) within 3 hours from hospital arrival in patients not receiving EVT. The study spanned 3 epochs: 2011–2014, 2015–2017, and 2018–2021. Based on the time from onset to arrival, patients were categorized into 2 time windows: early (0–6 hours) and late (6–24 hours). We evaluated EVT rates and clinical outcomes in patients with anterior large vessel occlusion.

Results

From 2011 to 2021 among 49 449 patients with acute ischemic stroke presenting within 24 hours of onset, PI use rates declined from 36.9% to 30.1%. In the early window, rates dropped from 48.4% to 32.4%, whereas in the late window, they increased from 23.5% to 27.8%. Factors such as older age, atrial fibrillation, anterior large vessel occlusion, and severe stroke were associated with higher rates in the late window. Conversely, younger age and male sex were associated with higher rates in the early window. For patients with anterior large vessel occlusion, PI use increased the likelihood of receiving EVT in the late window and minimized the risk of symptomatic intracranial hemorrhage in the early window. However, 3‐month functional outcomes and mortality were. unaffected.

Conclusion

The study revealed distinct trends in PI use across early and late time windows, indicating varying roles of PI in these time frames. However, the definitive value and necessity of PI in guiding EVT decision‐making remain unclear, underscoring the need for further research
The influence of calibration on bias in quality control and patient results for TSH on Vitros XT 7600 analyzer
Authors: Boreyko Jill , Ivica Josko
Published: August 2024

IntroductionThyroid-stimulating hormone (TSH) is a glycoprotein secreted by the anterior pituitary gland and is regulated by negative feedback from the serum free thyroid hormones. In this study we aimed to quantitate the relative bias caused by calibration drifting as seen in our TSH Levey-Jennings quality control (QC) charts and assess the magnitude of bias on patients’ samples.
Materials and methodsIn the period from October 2021 to August 2022 we looked at the QC results of ten 28-days’ calibration time intervals and calculated relative bias compared to the mean. For each time interval the mean from three QC points before and after calibration was calculated. The average from 10 pre- and post-calibration means was calculated and the relative bias, pre- and post-calibration, was then calculated. We used 5 patient samples with low, normal and high TSH concentrations and calculated relative bias pre- and post-calibration. The allowed relative bias for TSH is ± 6.7%.
ResultsAt both QC levels, with the respective means of 5.14 mIU/L (coefficient of variation, CV% = 3.1%) and 27.80 mIU/L (CV% = 3.2%) had their respective relative bias - 8.2% and - 7.9%. The patient samples with low (0.586 mIU/L), normal (2.89 mIU/L and 5.19 mIU/L) and high (20.5 mIU/L and 39.8 mIU/L) TSH had - 4.1%, - 4.0%, - 3.5%, - 5.1% and - 4.1%, respectively.
ConclusionEven though the relative bias exceeded allowable criteria for the QC samples, this was not manifested on the patients’ samples.