bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing Early Clinical Investigations in Cancer Immunotherapy: The Translational Journey of RG6292, a Novel, Selective Treg‐Depleting Antibody
Authors: Belli Sara , Amann Maria , Hutchinson Lucy , Pousse Laurène , Abdolzade‐Bavil Afsaneh , Justies Nicole , Jacobsen Bjoern , Ploix Corinne , Tselempi Eleni , Tosevski Vinko , Koll Hans , Schnetzler Gabriel , Boetsch Christophe , Marrer‐Berger Estelle
Published: May 2024

The multifaceted IL‐2/IL‐2R biology and its modulation by promising therapeutic agents are highly relevant topics in the cancer immunotherapy field. A novel CD25‐Treg‐depleting antibody (Vopikitug, RG6292) has been engineered to preserve IL‐2 signaling on effector T cells to enhance effector activation and antitumor immunity, and is currently being evaluated in the clinic. The Entry into Human‐enabling framework described here investigated the characteristics of RG6292, from in vitro quantification of CD25 and RG6292 pharmacology using human tissues to in vivo assessment of PK/PD/safety relationships in cynomolgus monkeys as non‐human primate species (NHP). Fundamental knowledge on CD25 and Treg biology in healthy and diseased tissues across NHP and human highlighted the commonalities between these species in regard to the target biology and demonstrated the conservation of RG6292 properties between NHP and human. The integration of in vitro and in vivo PK/PD/safety data from these species enabled the identification of human relevant safety risks, the selection of the most appropriate safe starting dose and the projection of the pharmacologically‐relevant dose range. The first clinical data obtained for RG6292 in patients verified the appropriateness of the described approaches as well as validated the full clinical relevance of the projected safety, PK, and PD profiles from animal to man. This work shows how the integration of mechanistic non‐clinical data increases the predictive value for human, allowing efficient transition of drug candidates and optimizations of early clinical investigations.
Promoting Water Oxidation by Proton Acceptable Groups Surrounding Catalyst on Electrode Surface
Authors: Li Yingzheng , Sun Bin , Liu Chang , Zhao Ziqi , Ning Hongxia , Zhang Peili , Li Fei , Sun Licheng , Li Fusheng
Published: May 2024

Large‐scale hydrogen production through water splitting represents an optimal approach for storing sustainable but intermittent energy sources. However, water oxidation, a complex and sluggish reaction, poses a significant bottleneck for water splitting efficiency. The impact of outer chemical environments on the reaction kinetics of water oxidation catalytic centers remains unexplored. Herein, chemical environment impacts were integrated by featuring methylpyridinium cation group (Py+) around the classic Ru(bpy)(tpy) (bpy=2,2’‐bipyridine, tpy=2,2′ : 6′,2′′‐terpyridine) water oxidation catalyst on the electrode surface via electrochemical co‐polymerization. The presence of Py+ groups could significantly enhance the turnover frequencies of Ru(bpy)(tpy), surpassing the performance of typical proton acceptors such as pyridine and benzoic acid anchored around the catalyst. Mechanistic investigations reveal that the flexible internal proton acceptor anions induced by Py+ around Ru(bpy)(tpy) are more effective than conventionally anchored proton acceptors, which promoted the rate‐determining proton transfer process and enhanced the rate of water nucleophilic attack during O−O bond formation. This study may provide a novel perspective on achieving efficient water oxidation systems by integrating cations into the outer chemical environments of catalytic centers.
A 0.012‐mm2 0.244‐pJ/bit successive approximation register analog‐to‐digital converter‐based true random number generator for Internet of Things applications in a 65‐nm complementary metal–oxide–semiconductor
Authors: Cheng Kai , Chen Yong , Stefano Crovetti Paolo , Martins Rui P. , Mak Pui‐In
Published: May 2024

This paper proposes a true random number generator (TRNG) based on a successive approximation register (SAR) analog‐to‐digital converter (ADC). A top‐plate sampling SAR ADC structure and a new MSB‐isolation switch scheme (MISS) are combined to achieve low‐power operation and small area occupancy at the same time. When the SAR ADC has completed its conversion, a secondary firing of the comparator measures the remaining signal. This 1‐bit quantized residue serves as the true random sequence, thus eliminating the need for extra circuitry in the TRNG. A 65‐nm prototype of the proposed TRNG was found to occupy an area of 0.012 mm2 and successfully passed all the National Institute of Standards and Technology (NIST) tests without post‐processing. It achieved a figure‐of‐merit of 0.244 pJ/bit for a 1 Mb/s random sequence with a 0.8‐V power supply. Its resilience to power noise injection attacks was also verified.
A diminutive perivascular epithelioid cell tumor in the colon
Authors: Sugimura Naoki , Hirata Daizen , Iwatate Mineo , Hattori Santa , Fujita Mikio , Sano Wataru , Fujimori Takahiro , Sano Yasushi
Published: May 2024

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor. Some papers have reported that colonoscopy could be used to treat PEComa with a predominantly pedunculated polyp, whereas surgical intervention is often required for cases with submucosal‐type tumors. These findings suggest that the morphology of PEComa changes dramatically with disease progression. Because of the rapid progression of PEComa, endoscopic treatment remains challenging, and early‐stage PEComa morphology is not well understood. A 64‐year‐old man presented to our hospital for a follow‐up colonoscopy after undergoing multiple polypectomies. He had a medical history of colorectal adenoma and prostate cancer. A 4‐mm pale blue elevated but not pedunculated lesion was observed in the transverse colon, an area where he had not had polyps previously. Since no epithelial change was observed, the presence of a submucosal tumor, such as a gastrointestinal stromal tumor, was suspected. Cold snare polypectomy was performed, and the lesion was completely resected. Histological evaluation using hematoxylin and eosin staining identified that the submucosal tumor included thickened vascular walls and adipose tissue. Although fragmented due to significant degeneration, spindle‐shaped cells staining positive for smooth muscle actin were observed within and surrounding the unstructured hyalinized tissue with calcifications. Based on these findings, the lesion was diagnosed as angiomyolipoma, a subtype of PEComa. Complete resection was confirmed by histopathology. To our knowledge, this PEComa is the smallest of any PEComa reported in the literature. Our finding provides valuable insights into the very early stage of colorectal PEComas.
Self‐smoothing lithium metal anode based on screen‐printed Cu‐mesh current collector for long‐term safety of lithium metal batteries
Authors: Li Dongdong , He Yue , Chen Bin , Xu Jun , Liu Qingyi , Yang Shengchen , Lai Wen‐Yong
Published: May 2024

Lithium metal is an attractive anode candidate to enable high‐energy lithium battery systems. However, nonideal dendrite growth at the anode/separator interface hinders the safe application of lithium metal batteries (LMBs). Three‐dimensional (3D) current collectors (CCs) with high specific surface area could afford a crucial effect on suppressing dendrites, yet still subject to large thickness/weight and limited scalability for large‐area fabrication. Here, we show an industry‐compatible screen‐printing technique to prepare ultrathin (∼1.5 μm) and ultralight (∼0.54 mg cm−2) Cu mesh on commercial Cu foil to realize a long‐term safety of LMBs. In contrast to conventional laboratory level techniques, the screen‐printed Cu‐mesh CCs (∼8.3 mg cm−2), which are even lighter than the original Cu foil (∼8.84 mg cm−2), show a high compatibility for large‐area fabrication. Meanwhile, the periodic Cu mesh can be also used to regulate the homogeneous distribution of Li‐ion flux and thus, be in favor of realizing self‐smoothing anodes at even deep and fast plating/stripping of lithium. The resulting lithium anodes demonstrate a long‐term cyclic life of ∼840 h at 1 mA cm−2 with a high Coulombic efficiency of 97.5%. LMBs with Cu‐mesh CCs exhibit outstanding capacity retentions of ∼87% after 350 cycles at 1 C and ∼80% after 200 cycles at 5 C, suggesting a significant step of printable 3D CCs toward practical application of high‐energy LMBs.
Selective online model updating in hybrid simulation of a full‐scale steel moment frame
Authors: Sepulveda Claudio , Cheng Mao , Becker Tracy , Mosqueda Gilberto , Wang Kung‐Juin , Huang Po‐Chia , Huang Cheng‐Wei , Uang Chia‐Ming , Chou Chung‐Che
Published: May 2024

This study presents the implementation of an online model updating algorithm within a full‐scale hybrid simulation (HS) of a six story, four bay steel moment frame. The experimental substructure consists of a cruciform subassembly generating critical data on the nonlinear behavior of the first story column and two beams with reduced beam sections (RBSs) on each side. The updating algorithm focuses on the modeling parameters of plastic hinge elements representing the RBSs in the numerical model. A smooth plasticity model is utilized for beam plastic hinges with updating parameters identified from on‐line experimental data through a modified version of the unscented Kalman filter. The HS shows that the numerical beam hinges based on simple hysteretic model with updated parameters are able to capture the characteristic behavior observed in experiments. Due to fracture of beam flanges is observed in the experiments, a selective updating concept is proposed to allow for updating multiple numerical components accounting for asymmetric behavior and variability in the response. The selective updating method is validated through virtual HSs that are better able to identify and isolate the effects of fracture and other behavioral characteristics. The combination of results from physical and virtual tests highlights the benefits of model updating on the local and overall system‐level response.
The pulsed effects of reintroducing wolves on the carnivore community of Isle Royale
Authors: Rodriguez Curras Mauriel , Romanski Mark C , Pauli Jonathan N
Published: May 2024

Large carnivores are being globally reintroduced with the goal of restoring ecological interactions. However, the extent that competitive interactions are restored within communities is often unclear. In a before–after study within Isle Royale National Park (in the US state of Michigan), we quantified the spatial, behavioral, trophic, and demographic effects of the reintroduction of a large carnivore (gray wolf; Canis lupus) on meso‐carnivores (red fox; Vulpes vulpes) and small carnivores (American marten; Martes americana). The wolf reintroduction produced a phase‐dependent pulse perturbation: wolves constrained the distribution of foxes, thereby benefiting martens, yet foxes altered their behavior, notably using human‐provided resource subsidies (campsites and food) more frequently, which buffered demographic consequences. Once wolf packs coalesced, all observed changes subsided, and competitive interactions returned to their pre‐wolf values. Our results show that some predicted—and often desired—consequences of large carnivore reintroductions may not be permanent due to the transitory dynamics of social carnivores and the presence of humans, even within a “pristine wilderness”.
Monascus red pigments alleviate high‐fat and high‐sugar diet‐induced NAFLD in mice by modulating the gut microbiota and metabolites
Authors: Gao Wenyan , Chen Xinghao , Wu Shaokang , Jin Lu , Chen Xu , Mao Genxiang , Wan Xiaoqing , Xing Wenmin
Published: May 2024

Monascus red pigments (MRP) may have benefits against NAFLD with an unclear mechanism. This study aimed to explore the protective effect of MRP supplementation against NAFLD through regulation of gut microbiota and metabolites. The C57BL/6 mice animals were randomly allocated into the normal diet (NC), HFHS diet‐induced NAFLD model, and MRP intervention group fed with HFHS diet. Serum lipid profiles and liver function parameters were measured. Liver and colon histopathology analysis was conducted to determine the injury in the liver and colon. 16S rRNA gene sequencing was employed to analyze gut microbial composition from fecal samples. Untargeted metabonomics was performed to analyze changes in metabolites in serum and fecal samples. MRP supplementation significantly improved the HFHS‐induced alterations in body weight, lipid profiles, and liver function (p < .01). MRP supplementation decreased the abundance of Akkermansia, Candidatus saccharimonas, Dubosiella, and Oscillibacter, while increasing Lactobacillus, Lachnospiraceae NK4A136 group, and Rikenella in mice fed the HFHS diet. Furthermore, MRP supplementation improved the serum and fecal metabolic profiles induced by the HFHS diet, primarily involving the arachidonic acid metabolism, unsaturated fatty acid biosynthesis, and adipocyte lipolysis pathways. Liver function and lipid profiles were closely associated with the abundance of Lactobacillus, Streptococcus, Oscillibacter, Akkemansia, and Desulfovibrio (p < .01). These findings revealed that MRP supplementation may help restore gut microbiota composition and balance its metabolites, thereby improving NAFLD. This study presents a novel outlook on the potential benefits of MRP supplementation in ameliorating NAFLD and supports the application of MRP as a new functional food.
Living methods for living guidelines: Changes to evidence synthesis methods in the Australian National Clinical Evidence Taskforce COVID‐19 living guidelines
Authors: White Heath , Turner Tari , Beecher Claire , Poole Alex , McDonald Steve , Hewitt Jessie , Chakraborty Samantha , Fraile‐Navarro David , Cheyne Saskia , Vogel Joshua , Jeppesen Britta Tendal , McGloughlin Steve ,   National Clinical Evidence Taskforce
Published: May 2024

Living evidence methods, such as those used to produce living guidelines, can evolve over time as the context or evidence changes. In Australia, the National Clinical Evidence Taskforce has been developing living guidelines for the management and care of people with coronavirus disease 2019 (COVID‐19) since March 2020, undertaking daily searches, and producing over 130 updates of more than 200 recommendations. Over the 3 years of the guidelines, the methods have also been ‘living’. In this paper, we describe why, how and with what impact changes to our methods have been made. When changes were required to the methods, the Taskforce Evidence Team developed a ‘Methods Brief’ outlining the proposed changes, rationale and any risks. This was presented to the Guidelines Leadership Group for approval and to the Steering Committee for noting. Changes were then reflected in the online, publicly available description of our methods. Methods to develop the living guidelines evolved through five phases, reflecting changes in the availability of evidence, the degree and nature of clinical uncertainty and resource availability. Largely these changes were to the criteria we used to select evidence for inclusion, and our expected level of responsiveness to new evidence. In the initial phases, inclusion criteria were very broad, and as the evidence base stabilised our focus narrowed to areas of high clinical importance and evidence certainty. The rapidly evolving nature of the pandemic, understanding of the illness, clinical questions and evidence base during development of the living COVID‐19 guidelines, necessitated multiple changes to the methods used to produce the guidelines. In this context, the ongoing revision of the methods for living guideline production was a necessity and a strength of the living approach. Questions remain about how best to ensure rigour is maintained while methods evolve.
Hypoxia‐induced SENP3 promotes chemosensitivity and mitochondrial fission via deSUMOylation of Drp1
Authors: Mao Yuanyuan , Liu Keyue , Yang Yaocheng , Liang Yiran , Gong ZhaoJian , Wu Kun
Published: May 2024

Objective

The study aimed to investigate the effect of the SUMOylation status of Drp1 on mitochondrial fission in CDDP‐treated HNSCC cells cultured under hypoxic conditions.

Materials and methods

The effect of hypoxia on the chemosensitivity of HNCC cells was evaluated by flow cytometry and CCK‐8 assays. The biological function of SUMO‐specific peptidase 3 (SENP3) was evaluated by loss‐of‐function assays both in vitro and in vivo. SENP3‐regulated deSUMOylation of Drp1 were performed with co‐IP assays.

Results

SENP3 expression correlated with chemosensitivity in clinical HNSCC samples subjected to hypoxic conditions. Hypoxia‐induced ROS increased HIF‐1α/SENP3 expression and mitochondrial fission in CDDP‐treated HNSCC cells, and these effects were reversed by NAC treatment. SENP3 knockdown reversed hypoxia‐induced mitochondrial fission and inhibited HNSCC cell apoptosis, which decreased CDDP sensitivity. Furthermore, hypoxia‐induced SENP3 deconjugated SUMO2 from Drp1.

Conclusion

Our findings revealed that hypoxia‐induced SENP3 facilitates CDDP sensitivity and mitochondrial fission via deSUMOylation of Drp1.
Influence of donor–recipient sex on engraftment of normal and leukemia stem cells in xenotransplantation
Authors: Mian Syed A. , Ariza‐McNaughton Linda , Anjos‐Afonso Fernando , Gurung Remisha , Jackson Sophie , Kizilors Aytug , Gribben John , Bonnet Dominique
Published: May 2024

Immunodeficient mouse models are widely used for the assessment of human normal and leukemic stem cells. Despite the advancements over the years, reproducibility, as well as the differences in the engraftment of human cells in recipient mice remains to be fully resolved. Here, we used various immunodeficient mouse models to characterize the effect of donor–recipient sex on the engraftment of the human leukemic and healthy cells. Donor human cells and recipient immunodeficient mice demonstrate sex‐specific engraftment levels with significant differences observed in the lineage output of normal CD34+ hematopoietic stem and progenitor cells upon xenotransplantation. Intriguingly, human female donor cells display heightened sensitivity to the recipient mice's gender, influencing their proliferation and resulting in significantly increased engraftment in female recipient mice. Our study underscores the intricate interplay taking place between donor and recipient characteristics, shedding light on important considerations for future studies, particularly in the context of pre‐clinical research.
‘Nostalgic food heals for us’: A qualitative exploration of experiences with nostalgia, food, and mood
Authors: Simpson Kate , Angus Douglas J. , Lee Megan F.
Published: May 2024

Issue Addressed

Nostalgia—the bittersweet reliving of the past—has been linked to social connection and psychological wellbeing. Although food consumption is often an intrinsically social experience, relatively little research has examined how individuals experience and understand how food consumption relates to feelings of nostalgia, food and mood.

Methods

In the current study, semi‐structured interviews were conducted with eight Australians from varying cultural backgrounds to explore their experiences with nostalgia, food and mood.

Results

Reflexive thematic analysis identified three key themes from the data: (i) The bittersweet experiences of food‐evoked nostalgia—individuals' descriptions of food‐evoked nostalgia and how it impacted their mood both positively and negatively (ii) social connection and identity continuity—participants' description of food‐evoked nostalgia and how this provides an opportunity for social connection and identity continuity throughout life, which positively influences mood, and (iii) the role and relationship of food‐evoked nostalgia and mood—individual descriptions of the important role that nostalgic food plays in their life, in addition to their relationship with food, and how this impacts mood.

Conclusions

Understanding the positive component of nostalgic foods allowed individuals to bolster positive mood states with food‐evoked nostalgia, increasing their quality of life.

So What?

Understanding the link between food‐evoked nostalgia and mood has significant implications, suggesting that negative mood states altered by nostalgic foods may result in positive mood states. Appropriate use of food‐evoked nostalgia may increase the quality of life for individuals experiencing low mood states.
Quantitative study of rainfall lag effects and integration of machine learning methods for groundwater level prediction modelling
Authors: Wang Yinan , Guo Fei , Chen Shubao , Zhang Hong , Zhang Zhuo , Li Anbo
Published: May 2024

Groundwater level (GWL) is a significant indicator for quantifying groundwater availability. Currently, hydrologists worldwide are actively engaged in modelling and predicting GWL. In karst regions, GWL exhibit varying responses to rainfall events across different locations and the impact of rainfall events on GWL within the same location also varies. Despite incorporating rainfall as an input variable, most existing data‐driven GWL prediction models inadequately account for the spatio‐temporal heterogeneity of karst water areas. Therefore, this study proposes a new analysis method to investigate the response patterns of GWL to rainfall events in karst regions with typical spatio‐temporal variations, known as the sensitivity analysis of rainfall‐GWL response. The method introduces the rainfall response coefficient to describe the response characteristics of GWL to rainfall. Through the rainfall response coefficient, the rainfall response variable (RR) is calculated and incorporates it as an input in the RR‐long short‐term memory (LSTM) GWL prediction model. The effectiveness of proposed method was validated by GWL prediction in karst aquifers located in Jinan City, China, renowned for its spatial–temporal heterogeneity in karst development. Through the analysis and validation conducted by integrating geographical multi‐feature, the study revealed a significant improvement in the accuracy of the RR‐LSTM model after integrating RR as a variable, particularly during significant rainfall events. These findings affirm that the method proposed in this study is highly effective in karst regions characterized by anisotropic karst features.
Advances in a measurement method of rainfall kinetic power and momentum affecting soil erosion processes
Authors: Carollo F. G. , Serio M. A. , Pampalone V. , Ferro V.
Published: May 2024

Rainfall is one of the factors affecting soil erosion, and rainfall kinetic energy or momentum is used to represent the capability of the precipitation to erode soil, named rainfall erosivity. Accurate measurements of rainfall erosivity are useful for a reliable prediction of soil loss. Rainfall momentum and kinetic energy, both calculated per unit time and area, can be obtained using terminal raindrop velocity and the drop size distribution (DSD) measured by disdrometers, which are instruments expensive and not suitable for large scale use. An innovative patented method to measure the rainfall energy is based on the estimation of DSD by simultaneous detection, in a given time interval, of the rainfall intensity I and the number N of raindrops that hit a specific piezoelectric surface. In this paper, advances of this method are presented. In particular, two new theoretical procedures to estimate the parameters μ and Λ of Ulbrich's distribution, that allow for the calculation of the rainfall kinetic energy and momentum, are proposed. Both procedures (Scenario 1 and 2) are based on the frequency distribution of the momentum M(D) of raindrops detected in a sampling time interval. Specifically, in the Scenario 1, μ and Λ are estimated by using I, N and the standard deviation, s(D), of the drop diameters obtained from the measured momentum distribution. In the Scenario 2 the parameters are estimated using I, N and the mean value, m(D), of the drop diameters deriving from the momentum distribution. The reliability of the proposed procedures was tested using DSD measurements recorded in three different experimental sites. The developed analysis demonstrated that Scenario 2 is the best method to estimate μ and Λ, and to reproduce the DSD, accordingly. The proposed method, associated with a patented device, not yet build, will allow the direct measurement of the rainfall energy characteristics, which are usually roughly estimated from rainfall intensity. The possibility to easily measure these energy variables can support the development of research in the field of soil erosion and, in general, of hydrogeological instability. In particular, the proposed measurement method and the construction of the device could stimulate the scientific community to deepen the study of the effect of the rainfall energy on soil erosion for improving the predictive capability of water erosion models.
Development of a probabilistic risk model for pharmaceuticals in the environment under population and wastewater treatment scenarios
Authors: Welch Samuel A. , Grung Merete , Madsen Anders L. , Jannicke Moe S.
Published: May 2024

Preparing for future environmental pressures requires projections of how relevant risks will change over time. Current regulatory models of environmental risk assessment (ERA) of pollutants such as pharmaceuticals could be improved by considering the influence of global change factors (e.g., population growth) and by presenting uncertainty more transparently. In this article, we present the development of a prototype object-oriented Bayesian network (BN) for the prediction of environmental risk for six high-priority pharmaceuticals across 36 scenarios: current and three future population scenarios, combined with infrastructure scenarios, in three Norwegian counties. We compare the risk, characterized by probability distributions of risk quotients (RQs), across scenarios and pharmaceuticals. Our results suggest that RQs would be greatest in rural counties, due to the lower development of current wastewater treatment facilities, but that these areas consequently have the most potential for risk mitigation. This pattern intensifies under higher population growth scenarios. With this prototype, we developed a hierarchical probabilistic model and demonstrated its potential in forecasting the environmental risk of chemical stressors under plausible demographic and management scenarios, contributing to the further development of BNs for ERA. Integr Environ Assess Manag 2024;20:1715–1735. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Key Points

We constructed a prototype object-oriented Bayesian network to predict the environmental risks of six key pharmaceuticals in Norwegian surface waters under 36 plausible future scenarios. Object-oriented design paradigms allowed efficient modular construction of a pharmaceutical consumption-to-pollution probabilistic environmental risk assessment (ERA) network. Our initial predictions indicated that, of the pharmaceuticals considered, ethinylestradiol presented by far the highest risk quotients, followed by ibuprofen; risk was greatest in rural areas, without effective wastewater treatment, and under high population growth scenarios. Our prototype sets the stage for Bayesian network-based ERA of pharmaceuticals; however, there are several technical limitations that still hold the approach back.
Online photography intervention reduces internet addiction during COVID‐19: A randomised controlled trial
Authors: Ma Jinjin , Zhu Huanya , He Wenqi , Qiang Xiaowei , Li Fanshu , Gan Yiqun
Published: May 2024

The COVID‐19 pandemic has escalated concerns regarding internet addiction. This study investigated the impact of an online photograph intervention on internet addiction and identified its effectiveness mechanisms. Individuals diagnosed with internet addiction (internet addiction test score > 36, Mage = 22.85, 78.6% women) were randomly allocated to either the intervention (n = 64) or control (n = 81) groups. For 10 days, the intervention group was tasked with photographing “things that make you feel a sense of control in life” and writing 100‐word descriptions explaining the reason for the sense of control elicited by the image. Meanwhile, the control group participated only in the assessments. Assessments were conducted before the intervention, immediately afterward and 7 days later. A significant interaction between group and time was observed, with the intervention group showing a notable reduction in internet addiction and an increase in sense of control. The sense of control at post‐test significantly mediated the intervention's effect on reducing internet addiction at follow‐up, but only among individuals with high perceived social support. The findings indicate that online photography interventions can effectively diminish internet addiction, with a sense of control acting as a potent mechanism for intervention, particularly in individuals with substantial perceived social support.
Cover Image
Authors: Zhong Chengquan , Zhang Jingzi , Wang Yuelin , Long Yanwu , Zhu Pengzhou , Liu Jiakai , Hu Kailong , Chen Junjie , Lin Xi
Published: May 2024

The image highlights our artificial intelligence framework, named Supercon‐Diffusion, for the inverse design of high‐temperature superconductors.

image
Instant clot forming and antibacterial wound dressings: Achieving hemostasis in trauma injuries with S‐nitroso‐N‐acetylpenicillamine—tranexamic acid—propolis formulation
Authors: Nguyen Dieu Thao , Pant Jitendra , Sapkota Aasma , Goudie Marcus James , Singha Priyadarshini , Brisbois Elizabeth J , Handa Hitesh
Published: May 2024

Wound infection and excessive blood loss are the two major challenges associated with trauma injuries that account for 10% of annual deaths in the United States. Nitric oxide (NO) is a gasotransmitter cell signaling molecule that plays a crucial role in the natural wound healing process due to its antibacterial, anti‐inflammatory, cell proliferation, and tissue remodeling abilities. Tranexamic acid (TXA), a prothrombotic agent, has been used topically and systemically to control blood loss in reported cases of epistaxis and combat‐related trauma injuries. Its properties could be incorporated in wound dressings to induce immediate clot formation, which is a key factor in controlling excessive blood loss. This study introduces a novel, instant clot‐forming NO‐releasing dressing, and fabricated using a strategic bi‐layer configuration. The layer adjacent to the wound was designed with TXA suspended on a resinous bed of propolis, which is a natural bioadhesive possessing antibacterial and anti‐inflammatory properties. The base layer, located furthest away from the wound, has an NO donor, S‐nitroso‐N‐acetylpenicillamine (SNAP), embedded in a polymeric bed of Carbosil®, a copolymer of polycarbonate urethane and silicone. Propolis was integrated with a uniform layer of TXA in variable concentrations: 2.5, 5.0, and 7.5 vol % of propolis. This design of the TXA–SNAP–propolis (T‐SP) wound dressing allows TXA to form a more stable clot by preventing the lysis of fibrin. The lactate dehydrogenase‐based platelet adhesion assay showed an increase in fibrin activation with 7.5% T‐SP as compared with control within the first 15 min of its application. A scanning electron microscope (SEM) confirmed the presence of a dense fibrin network stabilizing the clot for fabricated dressing. The antibacterial activity of NO and propolis resulted in a 98.9 ± 1% and 99.4 ± 1% reduction in the colony‐forming unit of Staphylococcus aureus and multidrug‐resistant Acinetobacter baumannii, respectively, which puts forward the fabricated dressing as an emergency first aid for traumatic injuries, preventing excessive blood loss and soil‐borne infections.
Unveiling myricetin's pharmacological potency: A comprehensive exploration of the molecular pathways with special focus on PI3K/AKT and Nrf2 signaling
Authors: Goyal Ahsas , Sikarwar Om , Verma Aanchal , Solanki Kunal , Agrawal Neetu , Dubey Nandini , Yadav Harlokesh Narayan
Published: May 2024

Myricetin can be found in the traditional Chinese medicinal plant, Myrica rubra. Myricetin is a flavonoid that is present in many vegetables, fruits, and plants and is considered to have strong antioxidant properties as well as a wide range of therapeutic applications. Growing interest has been piqued by its classification as a polyphenolic molecule because of its potential therapeutic benefits in both the prevention and management of numerous medical conditions. To clarify myricetin's traditional medical uses, modern research has investigated various pharmacological effects such as antioxidant, anticancer, anti‐inflammation, antiviral, antidiabetic, immunomodulation, and antineurodegenerative effects. Myricetin shows promise as a nutritional flavonol that could be beneficial in the prevention and mitigation of prevalent health conditions like diabetes, cognitive decline, and various types of cancer in humans. The findings included in this study indicate that myricetin has a great deal of promise for application in the formulation of medicinal products and nutritional supplements since it affects several enzyme activities and alters inflammatory markers. However, comprehensive preclinical studies and research studies are necessary to lay the groundwork for assessing myricetin's possible effectiveness in treating these long‐term ailments. This review summarizes both in vivo and in vitro studies investigating myricetin's possible interactions through the nuclear factor‐E2‐related factor 2 (Nrf2) as well as PI3K (phosphatidylinositol 3‐kinase)/AKT (protein kinase B) signaling pathways in an attempt to clarify the compound's possible clinical applicability across a range of disorders.
Block‐transitive triple systems with sporadic or alternating socle
Authors: Ding Suyun , Zhang Yilin , Zhan Xiaoqin , Chen Guangzu
Published: May 2024

This paper is a contribution to the classification of all pairs , where is a triple system and is a block‐transitive but not flag‐transitive automorphism group of . We prove that if the socle of is a sporadic or alternating group, then one of the following holds:

is a and ;

is a and ;

is a and or ;

is a with and .
The Oberwolfach problem with loving couples
Authors: Rinaldi Gloria
Published: May 2024

We generalize the well‐known Oberwolfach problem posed by Ringel in 1967. We suppose to have couples (here is an even integer) and suppose that they have to be seated for several nights at round tables in such a way that each person seats next to his partner exactly times and next to every other person exactly once. We call this problem the Oberwolfach problem with loving couples. When , the problem coincides with the so‐called spouse‐avoiding variant, which was introduced by Huang, Kotzig, and Rosa in 1979. While if either or equals the number of nights, it corresponds to the spouse‐loving variant or to the Honeymoon variant, which was recently studied by Bolohan et al. and by Lepine and Sajna, respectively. In this paper, for each possible choice of , we construct many classes of solutions to the Oberwolfach problem with loving couples. We also obtain new solutions to the Honeymoon variant.
Ablation of Sam50 is associated with fragmentation and alterations in metabolism in murine and human myotubes
Authors: Shao Bryanna , Killion Mason , Oliver Ashton , Vang Chia , Zeleke Faben , Neikirk Kit , Vue Zer , Garza‐Lopez Edgar , Shao Jian‐qiang , Mungai Margaret , Lam Jacob , Williams Qiana , Altamura Christopher T. , Whiteside Aaron , Kabugi Kinuthia , McKenzie Jessica , Ezedimma Maria , Le Han , Koh Alice , Scudese Estevão , Vang Larry , Marshall Andrea G. , Crabtree Amber , Tanghal Janelle I. , Stephens Dominique , Koh Ho‐Jin , Jenkins Brenita C. , Murray Sandra A. , Cooper Anthonya T. , Williams Clintoria , Damo Steven M. , McReynolds Melanie R. , Gaddy Jennifer A. , Wanjalla Celestine N. , Beasley Heather K. , Hinton Antentor
Published: May 2024

The sorting and assembly machinery (SAM) Complex is responsible for assembling β‐barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block‐face‐scanning electron microscopy and computer‐assisted 3D renderings were employed to compare mitochondrial structure and networking in Sam50‐deficient myotubes from mice and humans with wild‐type (WT) myotubes. Furthermore, autophagosome 3D structure was assessed in human myotubes. Mitochondrial metabolic phenotypes were assessed using Gas Chromatography‐Mass Spectrometry‐based metabolomics to explore differential changes in WT and Sam50‐deficient myotubes. The results revealed increased mitochondrial fragmentation and autophagosome formation in Sam50‐deficient myotubes compared to controls. Metabolomic analysis indicated elevated metabolism of propanoate and several amino acids, including ß‐Alanine, phenylalanine, and tyrosine, along with increased amino acid and fatty acid metabolism in Sam50‐deficient myotubes. Furthermore, impairment of oxidative capacity was observed upon Sam50 ablation in both murine and human myotubes, as measured with the XF24 Seahorse Analyzer. Collectively, these findings support the critical role of Sam50 in establishing and maintaining mitochondrial integrity, cristae structure, and mitochondrial metabolism. By elucidating the impact of Sam50‐deficiency, this study enhances our understanding of mitochondrial function in skeletal muscle.
Venous thromboembolism performance measurement in the United States: An evolving landscape with many stakeholders
Authors: Braun Barbara I. , Kolbusz Karen M. , Bozikis Michele R. , Schmaltz Stephen P. , Abe Karon , Reyes Nimia L. , Dardis Michelle N.
Published: May 2024

Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a life‐threatening, costly, and common preventable complication associated with hospitalization. Although VTE prevention strategies such as risk assessment and prophylaxis are available, they are not applied uniformly or systematically across US hospitals and healthcare systems. Hospital‐level performance measurement has been used nationally to promote standardized approaches for VTE prevention and incentivize the adoption of guideline‐based care management. Though most measures reflect care processes rather than outcomes, certain domains including diagnosis, treatment, and continuity of care remain unmeasured. In this article, we describe the development of VTE prevention measures from various stakeholders, measure strengths and limitations, publicly reported rates, the impact of technology and health policy on measure use, and perspectives on future options for surveillance and performance monitoring.
Improving Microstructural Estimation in Time‐Dependent Diffusion MRI With a Bayesian Method
Authors: Liu Kuiyuan , Lin Zixuan , Zheng Tianshu , Ba Ruicheng , Zhang Zelin , Li Haotian , Zhang Hongxi , Tal Assaf , Wu Dan
Published: May 2024

Background

Accurately fitting diffusion‐time‐dependent diffusion MRI (td‐dMRI) models poses challenges due to complex and nonlinear formulas, signal noise, and limited clinical data acquisition.

Purpose

Introduce a Bayesian methodology to refine microstructural fitting within the IMPULSED (Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion) model and optimize the prior distribution within the Bayesian framework.

Study Type

Retrospective.

Population

Involving 69 pediatric patients (median age 6 years, interquartile range [IQR] 3–9 years, 61% male) with 41 low‐grade and 28 high‐grade gliomas, of which 76.8% were identified within the brainstem or cerebellum.

Field Strength/Sequence

3 T, oscillating gradient spin‐echo (OGSE) and pulsed gradient spin‐echo (PGSE).

Assessment

The Bayesian method's performance in fitting cell diameter (), intracellular volume fraction (), and extracellular diffusion coefficient () was compared against the NLLS method, considering simulated and experimental data. The tumor region‐of‐interest (ROI) were manually delineated on the b0 images. The diagnostic performance in distinguishing high‐ and low‐grade gliomas was assessed, and fitting accuracy was validated against H&E‐stained pathology.

Statistical Tests

T‐test, receiver operating curve (ROC), area under the curve (AUC) and DeLong's test were conducted. Significance considered at P < 0.05.

Results

Bayesian methodology manifested increased accuracy with robust estimates in simulation (RMSE decreased by 29.6%, 40.9%, 13.6%, and STD decreased by 29.2%, 43.5%, and 24.0%, respectively for , , and compared to NLLS), indicating fewer outliers and reduced error. Diagnostic performance for tumor grade was similar in both methods, however, Bayesian method generated smoother microstructural maps (outliers ratio decreased by 45.3% ± 19.4%) and a marginal enhancement in correlation with H&E staining result (r = 0.721 for compared to r = 0.698 using NLLS, P = 0.5764).

Data Conclusion

The proposed Bayesian method substantially enhances the accuracy and robustness of IMPULSED model estimation, suggesting its potential clinical utility in characterizing cellular microstructure.

Evidence Level

3

Technical Efficacy

Stage 1
Empowering or burdening? The short‐term benefits and costs of upward networking at work
Authors: Wang Song , Luan Kun , Qin Xin
Published: May 2024

Research on social networking primarily focuses on the long‐term benefits of upward networking on career success. However, how it influences employees in the short term is largely overlooked. Integrating conservation of resources theory and self‐control strength model, we developed a moderated dual‐pathway model that simultaneously examines the immediate benefit and cost of upward networking and investigates how trait self‐control moderates the dual‐pathway mechanism. Based on two experiments and a time‐lagged experience sampling study, we examined the moderated effects of trait self‐control, as well as the conditionally indirect relationship between upward networking and work engagement through the resource gain of perceived impact at work and the resource loss of ego depletion. We found that, on the one hand, for employees high in trait self‐control, engaging in upward networking is likely to be related to perceived impact at work and indirectly affects work engagement. On the other hand, for employees with low trait self‐control, engaging in upward networking is likely to increase ego depletion and indirectly affects work engagement. Overall, our findings contribute to theories of social networking and self‐control and specifically highlight the complexity of upward networking, which both empowers and burdens employees in terms of immediate work outcomes.
Enhanced polysaccharide production through quorum sensing system in Cordyceps militaris
Authors: Qiao Huang , Chen Jianshu , Yang Shengli
Published: May 2024

This study aimed to enhance extracellular polysaccharide (EPS) production in Cordyceps militaris by constructing a quorum sensing (QS) system to regulate the expression of biosynthetic enzyme genes, including phosphoglucomutase, hexokinase, phosphomannomutase, polysaccharide synthase, and UDP‐glucose 4‐epimerase genes. The study found higher EPS concentrations in seven recombinant strains compared to the wild‐type C. militaris, indicating that the overexpression of key enzyme genes increased EPS production. Among them, the CM‐pgm‐2 strain exhibited the highest EPS production, reaching a concentration of 3.82 ± 0.26 g/L, which was 1.52 times higher than the amount produced by the wild C. militaris strain. Additionally, the regulatory effects of aromatic amino acids on the QS system of the CM‐pgm‐2 strain were investigated. Under the influence of 45 mg/L tryptophan, the EPS production in CM‐pgm‐2 reached 4.75 ± 0.20 g/L, representing a 1.90‐fold increase compared to wild C. militaris strains. This study provided an effective method for the large‐scale production of EPSs in C. militaris, and opened up new avenues for research into fungal QS mechanisms.
Semiautomated electronic medical record based system for monitoring delayed adverse events in pediatric endoscopy and sedation
Authors: Wong Jonathan , Abazi Tea , Thielke Rob , Lerner Diana
Published: May 2024

Objective

To develop a semiautomated electronic medical record (EMR) system to track pediatric endoscopic procedural adverse event (AE) at a tertiary referral children's hospital.

Methods

We developed an automated EMR based query for postprocedure AEs. Main outcome measurements within 30 days of procedure: return to emergency department, return to surgery, unplanned admissions and admissions with longer than intended stays. Events were graded using a recently described classification system for postendoscopy events and tracked for a 36‐month period, from January 2017 to December 2019.

Results

Development of a semi‐automated system was successful in comprehensive identification of endoscopy and sedation related AE. A total of 193 AEs (2%) were identified in all three categories. Seventy cases (0.7%) were noted to be a direct result of an endoscopic procedure. Of these cases, 31 (44%) were noted to be Grade 3, 5 cases (7%) Grade 4, and no Grade 5 AE occured. Higher rates of AE were observed after therapeutic procedures versus diagnostic (2.6% vs. 0.3%, p = <0.00001). AEs related to sedation occurred in 0.5% of procedures with the majority (84%) reported in patients with American Society of Anesthesia classification of 3 or greater.

Conclusions

Diagnostic endoscopy remains a safe procedure and risk of both endoscopy and sedation related AE are low. Therapeutic procedures carry a higher risk but are still overwhelmingly safe. Institutional investment in this EMR based system allowed for sustainability and comprehensive tracking of endoscopy related AE.
Surfactants produced from carbohydrate derivatives: Part 2. A review on the value chain, synthesis, and the potential role of artificial intelligence within the biorefinery concept
Authors: Marquez Ronald , Ortiz Maria S. , Barrios Nelson , Vera Ramon E. , Patiño‐Agudelo Álvaro Javier , Vivas Keren A. , Salas Mariangeles , Zambrano Franklin , Theiner Eric
Published: May 2024

This comprehensive and critical review explores the synthesis and applications of carbohydrate‐based surfactants within the biorefinery concept, focusing on biobased sugar‐head molecules suitable for use across several manufacturing sectors, including cosmetics, pharmaceuticals, household products, detergents, and foods. The main focus relies on sustainable alternatives to conventional surfactants, which could reduce the final manufacturing carbon footprint of several industrial feedstocks and products. A thorough analysis of raw materials, highlighting the significance of feedstock sources, and the current biobased surfactants and rhamnolipid biosurfactants production trends, is presented. Key organic reactions for the production of sorbitan esters, sucrose esters, alkyl polyglycosides, and fatty acid glucamines, such as glycosidation, acylation, and etherification, as well as the production of rhamnolipids through fermentation are described. Given the scarce literature on the characterization of these surfactant types within the hydrophilic–lipophilic deviation (HLD) framework, the surfactant contribution parameter (SCP) in the HLD equation for sugar‐head surfactants is critically assessed. The economic landscape is also discussed, noting the significant growth in the biobased surfactants and biosurfactant market, driven by environmental awareness and regulatory changes, with projections indicating a substantial market increase in the forthcoming years. Finally, the promising potential of generative artificial intelligence (AI) in developing customized surfactant molecules, with optimized properties for targeted applications, is emphasized as a promising avenue for future research.