bluuebunny/crossref_metadata_2025 huggingface dataset:
Toripalimab plus chemotherapy in American patients with recurrent or metastatic nasopharyngeal carcinoma: A cost‐effectiveness analysis
Authors: Lian Dai , Gan Yuling , Xiao Dunming , Xuan Dennis , Chen Yingyao , Yang Yi
Published: May 2024

Background

Toripalimab, combined with gemcitabine and cisplatin, has been approved as the first‐line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM‐NPC), representing a significant milestone as the first FDA‐approved innovative therapy for this condition. Despite this achievement, there's a lack of data on the cost‐effectiveness of toripalimab for RM‐NPC patients in the American context.

Methods

To assess the cost‐effectiveness of toripalimab plus chemotherapy versus chemotherapy alone, a 3‐state partitioned survival model was constructed. The study involved participants with characteristics matching those in the JUPITER‐02 trial. Cost and utility inputs were collected from literature. Main outcomes measured were quality‐adjusted life year (QALY), and incremental cost‐effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses were conducted to verify the robustness of results.

Results

The study found that the toripalimab regimen resulted in 4.390 QALYs at a cost of $361,813, while the chemotherapy‐only regimen yielded 1.685 QALYs at a cost of $161,632. This translates to an ICER of $74,004/QALY, below the willingness‐to‐pay threshold of $150,000/QALY. Sensitivity analyses indicated that utility values, discount rate, and the price of toripalimab significantly impact INMB. With an 87.10% probability of being cost‐effective at a $150,000/QALY threshold, the probabilistic sensitivity analysis supports toripalimab plus chemotherapy as a viable option. Scenario analysis showed that toripalimab remains cost‐effective unless its price increases by 125%. Additionally, a simulated 15‐year study period increases the ICER to $88,026/QALY. Subgroup analysis revealed ICERs of $76,538/QALY for PD‐L1 positive and $70,158/QALY for PD‐L1 negative groups.

Conclusions

Toripalimab in combination with chemotherapy is likely to be a cost‐effective alternative to standard chemotherapy for American patients with RM‐NPC. This evidence can guide clinical and reimbursement decision‐making in treating RM‐NPC patients.
Treosulfan is a safe and effective alternative to busulfan for conditioning in adult allogeneic HSCT patients: Data from a single center
Authors: Uzay Ant , Gündoğdu Yasemin , Koşan Barış , Yetiş Tuğba , Kartı S. Sami
Published: May 2024

Introduction

Type of conditioning regimen impacts the outcome of patients who undergo allogeneic HSCT since graft versus host disease (GVHD), infections, regimen related toxicities (RRT) are important causes of post‐transplant mortality. Despite the RRT profile of busulfan, it is frequently used worldwide. Treosulfan has advantages in terms of dose of administration, lower incidence of sinusoidal obstruction syndrome and lower neurotoxicity. We retrospectively investigated outcomes of patients who underwent allogeneic HSCT with treosulfan or busulfan based conditioning regimens in our institution.

Methods

Treosulfan was administered to 94 patients while 85 patients received busulfan. Our outcomes were RRT, chronic and acute GVHD, relapse related mortality (RRM), non‐relapse mortality, and fungal infection. The clinical follow up data, regarding the primary and secondary endpoints of our study, of the patients who received treosulfan or busulfan based conditioning regimens were statistically analyzed.

Results

The median follow‐up was 14 months for the treosulfan group while it was 11 months for the busulfan group (p = 0.16). RRT was 11.7% and 7.1% for treosulfan and busulfan respectively. The incidence of extensive chronic GVHD was less frequent in the treosulfan group compared to the busulfan group (15.7% vs. 32.1%) (p < 0.001). The incidence of acute GVHD (Grade 3 or higher) was 32.2% in the treosulfan group while it was 31.6% in the busulfan group. The RRM was 17% in the treosulfan group while it was 34% in the busulfan group. The non‐relapse mortality was 35.5% and 29.4% in the treosulfan group and in the busulfan group respectively (p = 0.962).

Conclusion

Treosulfan, with a lower RRM, lower chronic GVHD incidence and with a similar RRT profile appears to be a safe alternative to busulfan.
From the Design of Innovative Ti‐Pt Heterometallic Complexes to the Development of Highly Anti‐Proliferative Water‐Soluble Cationic Titanocenes
Authors: Trommenschlager Audrey , Mabrouk Nesrine , Racoeur Cindy , Godard Amélie , Balan Cédric , Dubrez Laurence , Bettaïeb Ali , Husson Jérôme , Le Gendre Pierre , Paul Catherine , Bodio Ewen
Published: May 2024

Two innovative early/late Ti−Pt‐heterobimetallic complexes were synthesized, characterized, and screened in cell‐based assays using several human (SW480 and MDA‐MB‐231) and murine cancer cell lines (CT26 and EMT6) as well as a non‐cancerous cell line (HMEC). The combination of the two metals – titanium(IV) and platinum (IV) – in a single molecule led to a synergistic biological activity (higher anti‐proliferative properties than a mixture of each of the corresponding monometallic complexes). This study also investigated the benefits of associating a metal‐free terpyridine moiety (with intrinsic biological activity) with a water‐soluble titanocene fragment. The present work reveals that these combinations results in water‐soluble titanocene compounds displaying an anti‐proliferative activity down to the submicromolar level. One of these complexes induced an antitumor effect in vivo in CT26 tumor bearing BALB/C mice. The terpyridine moiety was also used to track the complex in vitro by multiphoton microscopy imaging.
Spinal subdural hematoma with sudden onset of paraplegia in a patient on oral anticoagulant therapy
Authors: Ito Hayato , Hirata Hirohito , Yoshihara Tomohito , Tsukamoto Masatsugu , Watanabe Kazuyuki , Egashira Yoshiaki , Mawatari Masaaki , Morimoto Tadatsugu
Published: May 2024

Key Clinical Message

Spinal subdural hematoma is uncommon but may become more prevalent with increasing anticoagulant use. Early diagnosis from symptoms like lower back pain and leg paralysis is crucial for timely intervention.
Linkage‐Mediated Electronic Structure Modulation in Multicomponent Covalent Organic Frameworks for Dramatically Promoted Photocatalytic Hydrogen Evolution
Authors: Yan Yu , Zhao Yanming , Chen Xikai , Lu Zhou , Peng Yunlei , Chen Zongwei , Xu Qun
Published: May 2024

Linkage chemistry is an essential aspect to covalent organic framework (COF) applications; it is highly desirable to precisely modulate electronic structure mediated directly by linkage for efficient COF‐based photocatalytic hydrogen evolution, which however, remains substantially challenging. Herein, as a proof of concept, a collection of robust multicomponent pyrene‐based COFs with abundant donor‐acceptor (D−A) interactions has been judiciously designed and synthesized through molecularly engineering linkage for photogeneration of hydrogen. Controlled locking and conversion of linkage critically contribute to continuously regulating COFs’ electronic structures further to optimize photocatalytic activities. Remarkably, the well‐modulated optoelectronic properties turn on the average hydrogen evolution rate from zero to 15.67 mmol g−1 h−1 by the protonated quinoline‐linked COF decorated with the trifluoromethyl group (TT‐PQCOF‐CF3). Using diversified spectroscopy and theoretical calculations, we show that multiple modifications toward linkage synergistically lead to the redistribution of charge on COFs with extended π‐conjugation and reinforced D−A effect, making TT‐PQCOF‐CF3 a promising material with significantly boosted carrier separation and migration. This study provides important guidance for the design of high‐performance COF photocatalysts based on the strategy of linkage‐mediated electronic structure modulation in COFs.
A Real‐Time LSPR‐Based Study of Metal‐Organic Framework (MOF) Growth
Authors: Steinmüller Lucie , Csáki Andrea , Mertens Florian , Fritzsche Wolfgang
Published: May 2024

MOFs are known for their absorption properties and widely used for accumulation, filtering, sensorics, photothermal, catalytical and other applications. Their combination with plasmonic metal nanoparticles leads to hybrid structures that profit from the stabilizing effect and high porosity of the MOF as well as the optical and electronic properties of the nanoparticles. The growth of MOFs on plasmonic nanoparticles can be monitored in‐situ using LSPR spectroscopy, simultaneously applying microfluidic reaction conditions for the fabrication of NP@MOF structures. Here, a systematic study is conducted using LSPR spectroscopy for the monitoring of the Layer‐by‐Layer deposition of twelve different MOFs, determining the suitability of LSPR spectroscopy for this purpose. In addition to some well‐investigated materials like HKUST‐1, other MOFs such as MIL‐53, MIL‐88 A and Cu‐BDC are deposited successfully. For some MOFs such as Zn‐Fum, the LSPR experiment indicates that no deposition had taken place. The results are confirmed with AFM, SEM and XPS measurements. This work shows that LSPR spectroscopy is suitable for the in‐situ monitoring of LbL MOF growth and the microfluidic setup is a very promising method for the controlled manufacturing of NP@MOF hybrid structures. Further studies may include the optimization of the synthesis process or the transfer to other materials.
Deploying Cray EX systems with CSM at LANL
Authors: Stradling Alden , Johnson Steven L. , Van Heule Graham
Published: May 2024

Los Alamos National Laboratory has deployed (over the last year and a half) a pair of Cray Shasta machines—a development testbed named Guaje and and production machine named Chicoma, which will soon comprise the bulk of LANL's open science research computing portfolio. In the process, we have encountered a number of problems and challenges in several realms—authentication and authorization, cluster health management, image management, and configuration management. Both independently and in collaboration with Cray/HPE, we have found solutions and brought the system into stable production. The presentation will discuss the solutions and how they came about, and issues we are working to resolve in the near future.
Repositioning of Small Molecules through the Inverse Virtual Screening in silico Tool: Case of Benzothiazole‐Based Inhibitors of Soluble Epoxide Hydrolase (sEH)
Authors: Gazzillo Erica , Colarusso Ester , Giordano Assunta , Chini Maria Giovanna , Potenza Marianna , Hofstetter Robert Klaus , Iorizzi Maria , Werz Oliver , Lauro Gianluigi , Bifulco Giuseppe
Published: May 2024

Computational techniques accelerate drug discovery by identifying bioactive compounds for specific targets, optimizing molecules with moderate activity, or facilitating the repositioning of inactive items onto new targets. Among them, the Inverse Virtual Screening (IVS) approach is aimed at the evaluation of one or a small set of molecules against a panel of targets for addressing target identification. In this work, a focused library of benzothiazole‐based compounds was re‐investigated by IVS. Four items, originally synthesized and tested on bromodomain‐containing protein 9 (BRD9) but yielding poor binding, were critically re‐analyzed, disclosing only a partial fit with 3D structure‐based pharmacophore models, which, in the meanwhile, were developed for this target. Afterwards, these compounds were re‐evaluated through IVS on a panel of proteins involved in inflammation and cancer, identifying soluble epoxide hydrolase (sEH) as a putative interacting target. Three items were subsequently confirmed as able to interfere with sEH activity, leading to inhibition percentages spanning from 70 % up to 30 % when tested at 10 μM. Finally, one benzothiazole‐based compound emerged as the most promising inhibitor featuring an IC50 in the low micromolar range (IC50=6.62±0.13 μM). Our data confirm IVS as a predictive tool for accelerating the target identification and repositioning processes.
LPHD: A low power and high diffusion lightweight block cipher
Authors: Xu Ruihan , Li Lang , Huang Xiantong
Published: May 2024

Smart door locks pose a large number of threats such as network attacks. Its storage area and power of cipher are severely limited because the wireless nodes of smart door locks are mostly battery‐powered. Therefore, effective security solutions are urgently needed. In this paper, a new lightweight block cipher with low power named LPHD is proposed to ensure the security of the master control chip of the smart door lock terminal. We design a scheme of low power S‐box and construct the two‐stage permutation layer (TP structure) suitable for LPHD by filtering the sets of 8‐bit permutations. LPHD proposes a variant of the 8‐branch generalized Feistel structure (GFS) to realize that the bits of all branches are affected in one encryption round. The problem of slow diffusion in the standard Feistel structure is solved. The key schedule adopts the nonlinear design and reuses the encryption process of LPHD. It improves the security of the cipher and reduces hardware overhead. Moreover, we evaluate the hardware implementation and security of LPHD. The results show that LPHD for the unified encryption and decryption circuits requires only 1276 Gate Equivalents (GEs) and 1.914
W on UMC 0.18
m, which is better than other lightweight block ciphers such as SKINNY, PRESENT, and IVLBC. In summary, LPHD provides sufficient security for the master control chip of the smart door lock terminal.
Syntheses and Conformations of a Trinuclear Gold(I) System Based on a Triethinyl‐trisilacyclohexane Scaffold
Authors: Heinrichs Peter , Vishnevskiy Yury V. , Neumann Beate , Stammler Hans‐Georg , Mitzel Norbert W.
Published: May 2024

Trisilacyclohexanes and bissilylmethanes with acetylene units attached to silicon sites have been converted into tri‐ and di‐nuclear gold(I)phosphane complexes and characterized by NMR spectroscopy and X‐ray diffraction. The bissilylmethane‐based gold complexes were used as a test system to work out the synthetic routes before transferring them to the trisilacyclohexane scaffolds, because the latter are more difficult to access. The occurrence of aurophilic interactions (short Au ⋅ ⋅ ⋅ Au contacts) depends on the steric bulk of the phosphorus‐bonded alkyl and aryl groups. DFT studies show that dispersion effects play an important role in the ability to form intramolecular Au ⋅ ⋅ ⋅ Au interactions. QTAIM analyses show that a subtle change of the steric bulk of the phosphane groups alters the relative strength of the dispersion and aurophilic interactions. The combination of DFT studies and X‐ray diffraction experiments shows that the conformation of the trisilacyclohexane backbone is also phase dependent.
Predictive validity of the STarT Back screening tool among older adults with back pain
Authors: Vigdal Ørjan Nesse , Flugstad Solveig , Storheim Kjersti , Killingmo Rikke Munk , Grotle Margreth
Published: May 2024

Background

The predictive validity of the STarT Back screening tool among older adults is uncertain. This study aimed to assess the predictive validity of the SBT among older adults in primary care.

Methods

This prospective cohort study included 452 patients aged ≥55 years seeking Norwegian primary care with a new episode of back pain. A poor outcome (persistent disabling back pain) was defined as a score of ≥7/24 on the Roland‐Morris Disability Questionnaire (RMDQ) at 3, 6 or 12 months of follow‐up. The ability of the SBT risk groups to identify persistent disabling back pain was assessed with multivariable logistic regression, area under receiver operating characteristics curve (AUC), and with the accuracy measures sensitivity, specificity, predictive values and likelihood ratios.

Results

The adjusted odds ratios (95% CI) for persistent disabling back pain were 2.40 (1.34–4.30) at 3 months, 3.42 (1.76–6.67) at 6 months and 2.81 (1.47–5.38) at 12 months for the medium‐risk group (n = 118), and 8.90 (1.83–43.24), 2.66 (0.81–8.67) and 4.53 (1.24–16.46) for the high‐risk group (n = 27), compared to the low‐risk group (n = 282). There were no statistically significant differences in odds between the medium‐ and high‐risk groups at any time point. AUC values (95% CI) were 0.65 (0.59–0.71), 0.67 (0.60–0.73) and 0.65 (0.58–0.71) at 3, 6 and 12 months. Accuracy measures were poor at all time points, with particularly poor sensitivity and negative likelihood ratio values.

Conclusion

The predictive validity of the SBT risk groups in predicting persistent disabling back pain in older adults was poor.

Significance Statement

This study found that the STarT Back screening tool had poor predictive validity among older adults and that it may need recalibration or extension before widespread implementation among older adults. Having valid tools for this population may aid clinicians with allocating scarce healthcare resources, which is especially important considering the rapidly ageing population and its expected challenge to the healthcare systems.
DEPDC5 plays a vital role in epilepsy: Genotypic and phenotypic features in cohort and literature
Authors: Gu Chunyu , Wei Xinping , Yan Dandan , Cai Yingzi , Li Dong , Shu Jianbo , Cai Chunquan
Published: May 2024

Objective

DEPDC5 emerges to play a vital role in focal epilepsy. However, genotype–phenotype correlation in DEPDC5‐related focal epilepsies is challenging and controversial. In this study, we aim to investigate the genotypic and phenotypic features in DEPDC5‐affected patients.

Methods

Genetic testing combined with criteria published by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP), was used to identify pathogenic/likely pathogenic variants in DEPDC5 among the cohort of 479 patients with focal epilepsy. Besides, the literature review was performed to explore the genotype–phenotype correlation and the penetrance in DEPDC5‐related focal epilepsies.

Results

Eight unrelated probands were revealed to carry different pathogenic/likely pathogenic variants in DEPDC5 and the total prevalence of DEPDC5‐related focal epilepsy was 1.67% in the cohort. Sixty‐five variants from 28 studies were included in our review. Combined with the cases reported, null variants accounted for a larger proportion than missense variants and were related to unfavorable prognosis (drug resistance or even sudden unexpected death in epilepsy; χ2 = 5.429, p = .020). And, the prognosis of probands with developmental delay/intellectual disability or focal cortical dysplasia was worse than that of probands with simple epilepsy (χ2 = −, p = .006). Besides, the overall penetrance of variants in DEPDC5 was 68.96% (231/335).

Significance

The study expands the variant spectrum of DEPDC5 and proves that the DEPDC5 variant plays a significant role in focal epilepsy. Due to the characteristics of phenotypic heterogeneity and incomplete penetrance, genetic testing is necessary despite no specific family history. And we propose to adopt the ACMG/AMP criteria refined by ClinGen Sequence Variant Interpretation Working Group, for consistency in usage and transparency in classification rationale. Moreover, we reveal an important message to clinicians that the prognosis of DEPDC5‐affected patients is related to the variant type and complications.
How big is a boulder? The importance of boulder definition choice in earth science research and river management
Authors: Mason Richard J. , Polvi Lina E.
Published: May 2024

Boulders are globally widespread and influence processes across many landscapes including hillslopes, coasts, rivers and extra‐terrestrial settings. Boulders are described as particles, sufficiently large, that they have a disproportionate effect on the surrounding landscape. Moving beyond this conceptual definition, however, requires a somewhat arbitrary decision of how to define a minimum boulder size. The implications of boulder definition on study findings are rarely considered. We investigate the suitability of five boulder definitions, two based on fixed sizes: (1) 0.26 m and (2) 1 m, and three definitions which vary based on system characteristics: (3) grain mobility, (4) grain protrusion and (5) surface grain size distribution (> 84th percentile, D84). We consider the impact of definition on calculated boulder metrics, and, for the >1m and >D84 definitions, their association with channel and catchment characteristics across 20 boulder‐bed streams in northern Sweden. We also surveyed river managers responsible for restoring these rivers, to gain a practitioner insight on boulder size definition. We found that boulder definition matters; for metrics relating to the number or density of boulders, the >D84 and >1m size definitions were negatively correlated. Surveys indicated the importance of communicating boulder definition. We conclude that, whilst the best choice of boulder size definition will vary based on the questions of interest and techniques employed, evaluating the implications of the chosen boulder size definition and communicating the reasoning behind boulder definition choice is crucial.
Cascade loop of ferroptosis induction and immunotherapy based on metal‐phenolic networks for combined therapy of colorectal cancer
Authors: Li Yuwei , Duan Yuxi , Li Yunyi , Gu Yuan , Zhou Lu , Xiao Zhongting , Yu Xinying , Cai Yanjun , Cheng Erzhuo , Liu Qianqian , Jiang Yong , Yang Quan , Zhang Feng , Lei Qi , Yang Bin
Published: May 2024

Cancer immunotherapy is the most promising method for tumor therapy, while ferroptosis could activate the immunogenicity of cancer and strengthen the cellular immune response. However, limited by the complex tumor microenvironment, the abundant glutathione (GSH) and low reactive oxygen species (ROS) seriously weaken ferroptosis and the immune response. Herein, the authors report photothermal metal‐phenolic networks (MPNs) supplied with buthionine sulfoximine (BSO) by reducing levels of GSH and then trapping the tumor cells in the ferroptosis and immunotherapy cascade loop to eliminate colorectal cancer (CRC). The MPNs coated with the model antigen ovalbumin can accumulate at the tumor site, mediate immunogenic cell death (ICD) under NIR irradiation, and initiate tumoricidal immunity. Then the activated CD8+ T cells would release IFN‐γ to inhibit GPX4 and promote the immunogenic ferroptosis induced by Fe3+ and BSO. Finally, the tumor cells at intertumoral and intratumoral levels would be involved in the ferroptosis‐dominated cancer‐immunity circle for CRC eradication, resulting in outstanding therapeutic outcomes in both primary and distant tumor models. Overall, this strategy employs a photothermal nanoplatform to rapidly stimulate ICD and restrain the oxidation defense system, which provides a promising approach to significantly amplify the “cascade loop” of ferroptosis induction and immunotherapy for treatment of CRC.
Trends and gaps in sweet potato (Ipomoea batatas L.) improvement in sub‐Saharan Africa: Drought tolerance breeding strategies
Authors: Makhubu F. N. , Laurie S. M. , Rauwane M. E. , Figlan S.
Published: May 2024

The main challenge facing agricultural crop production in the current global climate change scenario is sustainability. Drought, as a yield‐limiting factor, has become a major threat to international food security. Tolerance to drought is a complex trait and its response is carried out by various genes, transcription factors, microRNAs, hormones, proteins, cofactors, ions and metabolites. The complexity of the trait has limited the development of drought‐tolerant sweet potato cultivars by traditional breeding. Advances in sweet potato breeding to exploit the full potential of the crop to contribute to improved and higher performing sweet potato cultivars, adapted to increasingly risky rainfed conditions, mainly drought, are key to making food production systems more efficient and more tolerant to pressure from drought and other stressors. Genetic gain for yield potential in sweet potato has improved mostly in African countries, mainly as a result of an accelerated breeding scheme. The focus on maximising the utilisation of molecular tools for sweet potato improvement and yield has been recently explored in breeding programmes in sub‐Saharan Africa (SSA). This article provides an update on the trends and gaps in sweet potato breeding in SSA, reviewing the relevant strategies used to improve sweet potato in the region. Finally, the perspectives of using new advanced tools including genetic engineering and genome editing, and the challenges associated with climate change for further improvement of the crop are highlighted. Collaborative efforts in African countries are driving advances in breeding methods through the incorporation of molecular tools to develop drought‐tolerant sweet potato varieties that are important to global food security despite challenges posed by the drastic change in climate.
Loneliness and social isolation among informal carers of individuals with dementia: A systematic review and meta‐analysis
Authors: Liao Xinqi , Wang Zhong , Zeng Qinglin , Zeng Yanli
Published: May 2024

Objectives

This systematic review and meta‐analysis aimed to determine the prevalence of loneliness and social isolation among informal carers of individuals with dementia and to identify potential influencing factors.

Methods

We conducted a comprehensive search across 10 electronic databases, including PubMed, Cochrane, Embase, Web of Science, PsycINFO, CINAHL, Scopus, Chinese Biomedical, China National Knowledge Internet, and WANFANG. Our search strategy covered the inception of the databases up to September 16, 2023, with an updated search conducted on March 8, 2024. Prevalence estimates of loneliness and social isolation, presented with 95% confidence intervals, were synthesized through meta‐analysis. Subgroup analyses and meta‐regression were employed to explore potential moderating variables and heterogeneity.

Results

The study encompassed 27 research papers involving 11,134 informal carers from 17 different countries. The pooled prevalence of loneliness among informal carers of individuals with dementia was 50.8% (95% CI: 41.8%–59.8%), while the pooled prevalence of social isolation was 37.1% (95% CI: 26.7%–47.6%). Subgroup analyses and meta‐regression indicated that various factors significantly influenced the prevalence of loneliness and social isolation. These factors included the caregiving setting, study design, the intensity of loneliness, geographical location (continent), data collection time, and the choice of assessment tools.

Conclusions

This study underscores the substantial prevalence of loneliness and social isolation among informal carers of individuals with dementia. It suggests that policymakers and healthcare providers should prioritize the development of targeted interventions and support systems to alleviate loneliness and social isolation within this vulnerable population.
Bioinformatics approach combined with experimental verification reveals OAS3 gene implicated in paclitaxel resistance in head and neck cancer
Authors: Caglar Hasan Onur , Aytatli Abdulmelik , Barlak Neslisah , Aydin Karatas Elanur , Tatar Arzu , Sahin Abdulkadir , Karatas Omer Faruk
Published: May 2024

Background

This study aimed to identify a candidate gene associated with paclitaxel (PTX) resistance and to evaluate functionally its biological role in the PTX‐resistant head and neck squamous cell carcinoma (HNSCC) cell lines and clinical specimens.

Methods

Microarray data series containing samples of different types of cancers resistant to PTX were analyzed and then a candidate gene associated with PTX resistance was identified using various bioinformatics tools. After the suppression of the target gene expression, changes in cell viability and colony‐forming ability were evaluated in PTX‐resistant FaDu and SCC‐9 cell lines.

Results

Bioinformatics analyses of upregulated genes in PTX‐resistant cancer cells indicated that OAS3 was associated with PTX resistance. The downregulation of OAS3 expression significantly reduced the viability and colony‐forming capacity of PTX‐resistant SCC‐9 cells by inducing apoptosis and cell cycle arrest at G0/G1 phase.

Conclusions

The therapeutic targeting of OAS3 may resensitize PTX‐resistant HNSCC cells with high OAS3 expression to PTX treatment.
Breaking barriers, building faculty: A qualitative analysis to exploring faculty development in academic hospital medicine
Authors: Badawy Jack , Sakumoto Matthew , Murphy Elizabeth , Schmit David , Davis Christine , Segon Ankur , Auerbach Andrew , Burden Marisha
Published: May 2024

Background

Hospital medicine (HM) continues to be primarily composed of junior hospitalists and research has highlighted a paucity of mentors and academic output. Faculty advancement programs have been identified as a means to support junior hospitalists in their career trajectories and to advance the field. The optimal approach to supporting faculty development (FD) efforts is not known.

Objective

To understand hospitalist groups' approaches to FD, including efforts that were perceived to be effective, and to identify barriers as well as potential future directions for FD.

Design

Rapid qualitative methods were utilized including templated summaries and matrix analysis to identify major themes.

Setting and Participants

Virtual focus groups with hospitalists in the Hospital Medicine Reengineering Network (HOMERuN).

Main Outcome and Measures

Qualitative themes.

Results

Nineteen individuals from 17 unique institutions from across the United States in May 2022 participated in seven focus groups. Four key themes emerged from the study and included (1) academic hospitalist programs face multifaceted challenges and barriers to FD in HM, (2) groups have embraced a diversity of structures and frameworks, (3) due to clinical volumes, FD programs have had to adapt and evolve to meet FD needs, and (4) participants identified multiple areas for improvement, including defining tangible outcomes of FD programs and creating a repository of FD material which can be shared widely.
Determination of vancomycin and meropenem in serum and synovial fluid of patients with prosthetic joint infections using UPLC–MS/MS
Authors: He Jiawei , Wang Jing , Cao Li , Zhang Xiaogang , Li Guoqing , Xu Boyong , Ji Baochao , Zhao Jun , Huang Junjie , Yang Jianhua
Published: May 2024

Numerous studies have suggested that intra‐articular administration of antibiotics following primary revision surgery may be one of the methods for treating prosthetic joint infection (PJI). Vancomycin and meropenem are the two most commonly used antibiotics for local application. Determining the concentrations of vancomycin and meropenem in the serum and synovial fluid of patients with PJI plays a significant role in further optimizing local medication schemes and effectively eradicating biofilm infections. This study aimed to establish a rapid, sensitive, and accurate ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for determining the concentrations of vancomycin and meropenem in human serum and synovial fluid. Serum samples were processed using acetonitrile precipitation of proteins and dichloromethane extraction, while synovial fluid samples were diluted before analysis. Chromatographic separation was achieved in 6 min on a Waters Acquity UPLC BEH C18 column, with the mobile phase consisting of 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Quantification was carried out using a Waters XEVO TQD triple quadrupole mass spectrometer with an electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) mode was employed to detect the following quantifier ion transitions: 717.95–99.97 (norvancomycin), 725.90–100.04 (vancomycin), 384.16–67.99 (meropenem). The method validation conformed to the guidelines of the FDA and the Chinese Pharmacopoeia. The method demonstrated good linearity within the range of 0.5–50 μg/ml for serum and 0.5–100 μg/ml for synovial fluid. Selectivity, intra‐day and inter‐day precision and accuracy, extraction recovery, matrix effect, and stability validation results all met the required standards. This method has been successfully applied in the pharmacokinetic/pharmacodynamic (PK/PD) studies of patients with PJI.
MiniaturizedIPDband pass filter with low insertion loss based on modifiedT‐section for5Gapplications
Authors: Zhang Qi , Cao Yazi , Wang Gaofeng
Published: May 2024

A miniaturized bandpass filter (BPF) with low insertion loss based on a modified T‐section and a grounded transmission‐zero resonator is proposed. The novel T‐section consists of two resonators, which can achieve the bandpass performance with two transmission zeros (TZs) in the upper band. The grounded transmission‐zero resonator can generate an extra transmission zero in the lower band. Therefore, high frequency selectivity can be achieved by the above three transmission zeros near the passband. The proposed BPF can achieve an insertion loss of 0.8 dB and a return loss of 22 dB covering 3.3–4.2 GHz, and the upper‐stopband attenuation is better than 20 dB up to 12.5 GHz (3.3f0). The proposed BPF with a miniaturized size of 1.2 mm × 0.5 mm × 0.3 mm have been fabricated using Si‐based integrated passive devices (IPDs) technology and measured by on‐wafer probing. The simulated and measured results of the proposed BPF are in reasonably good agreement.
Four‐Dimensional Ultrasound Imaging of Spatial Relationship of Great Arteries in Fetuses With Transposition of Great Arteries
Authors: Karmegaraj Balaganesh
Published: May 2024

The great artery relationship in transposition of great arteries (TGA) is based on the degree of resorption and growth of subsemilunar conus. In transposition of great arteries, the spatial relationship of the great arteries can be variable. Commonly, the aorta will be related right and anterior to pulmonary artery (D‐TGA). Less commonly, the aorta can be related left and anterior (SDL‐TGA), side‐by‐side, and antero‐posterior to pulmonary artery. Four fetuses with concordant atrioventricular and discordant ventriculoarterial connection with various great arteries relationship were presented in this imaging essay.
Ion‐Mediated Gelation of Thermo‐Responsive Cellulose Nanofibril/Poly(N‐isopropylacrylamide) Hybrid Hydrogels with Tunable De‐Swelling Kinetics
Authors: Motloung Bennie , Pfukwa Rueben , Klumperman Bert
Published: May 2024

The tunability of the lower critical solution temperature (LCST) of poly(N‐isopropylacrylamide) (PNIPAM) to lower or higher temperatures, as well as the ease of modulation of the LCST phase transition kinetics broadens the scope of application of PNIPAM‐based materials in biomedical fields. This work reports a facile approach to formulate a smart, injectable cellulose nanofibril (CNF)/PNIPAM hybrid gel. Hofmeister salts are used to induce ion‐mediated gelation of the nanofibrils and PNIPAM chains, resulting in an interpenetrating network (IPN) structure. From rheological measurements, the hybrid material displays excellent structural integrity at room temperature and tunable thermo‐stiffening around body temperature. De‐swelling kinetics can be modulated by varying the nature and concentration of the Hofmeister ion used. The successful realization of the IPN hybrid gel structure is dependent on the molecular weight of PNIPAM used. Moreover, the hybrid gels show good thermo‐reversibility during thermal cycling, as well as excellent injectability and remarkable self‐healing post‐injection, owing to shear‐thinning and thixotropic characters. Since rheology is a crucial technique in the analysis of soft matter and flow behavior is fundamental for the design and synthesis of application‐specific viscoelastic materials, the work reported herein provides a rheological basis for careful design and synthesis of smart gels.
Dynamics of a generalist predator–prey model in closed advective environments
Authors: Wang Qi
Published: May 2024

In this paper, we consider a two‐species generalist predator–prey model in closed advective environments. Compared with the model in open advective environments to the generalist predator–prey model, the dynamics of our system are different. It is easy to verify that the generalist predator can always invade. Meanwhile, we provide the dynamical behaviors of the model in terms of the intrinsic growth rates, the carrying capacity of both species, the predation rate, and the trophic conversion efficiency. More precisely, we establish the local/global stability of the semi‐trivial steady states and a unique positive equilibrium for the model.
An extended isogeometric collocation method for fracture analysis
Authors: Fathi Farshid , Oakley Jeremy E. , de Borst René
Published: May 2024

A collocation method is developed for discrete fracture models in the context of the partition‐of‐unity method. Spline technologies used in isogeometric analysis (IGA) are exploited to provide a smooth inter‐element transition of gradients, thus allowing to get rid of extra flux terms at element boundaries which are generated by Lagrange polynomials. Bézier extraction is utilised to formulate IGA commensurate with a standard finite element data‐structure. The efficacy of the proposed approach is examined through different numerical examples and is compared with other discrete methods for fracture analysis. The proposed approach is competitive in terms of accuracy with the least computational cost, rendering it a suitable candidate for superseding available collocation approaches for fracture simulation. Moreover, the approach naturally assesses the possibility of physics informed neural networks for fracture simulation, to which collocation is central.
Body composition analysis using dual‐energy x‐ray absorptiometry in an Egyptian pediatric sickle cell disease cohort
Authors: Kaddah Ahmed Maher , Ibrahim Rania S. M. , Gamal Seham , Selim Yasmeen M. M.
Published: May 2024

Background

Growth failure is commonly encountered in sickle cell disease (SCD). Tissue compartment growth and development are subsequently likely to be altered in such patients.

Objective

We aimed to analyze body composition in an Egyptian pediatric SCD cohort using dual‐energy x‐ray absorptiometry (DEXA), one of the most comprehensive and noninvasive assessment methods available.

Methods

Forty children with SCD ≤18 years and 40 healthy youngsters age‐ and gender‐matched were enrolled. Patients’ demographic, clinical, and laboratory parameters were obtained from their archived files. All patients and controls were subjected to body composition assessment using a MedixDR—Whole Body DEXA System.

Results

In SCD patients; weight and height relative to age Z scores were significantly lower (p < .001), total body lean was significantly higher (p = .006), and total body fat percentage was lower, yet the difference was not statistically significant (p = .09). There were no statistically significant variations in bone mineral density or content, basal metabolic rate, subcutaneous adipose tissue, android/gynoid fat ratio, and visceral adipose tissue. There were no significant gender disparities between SCD patients and controls.

Conclusion

Faltering growth in children with SCD should be addressed with a multidisciplinary approach including nutritional support, correction of anemia, and proper medical care. Body composition parameters assessed using DEXA were comparable between cases and controls apart from total body lean. Further clinical studies are needed with multicenter cooperation and a larger sample size to assess the usefulness of DEXA as an assessment tool for body composition in children with SCD.
Carbon fiber‐reinforced thermoplastic synthesized by the hypercrosslinking reaction of polyether ether ketone
Authors: Yamamoto Tetsuya , Nakamoto Takumi , Irisawa Toshihira
Published: May 2024

Recently, thermoplastic resins were used as matrix to synthesize carbon fiber‐reinforced thermoplastic (CFRTP) for recycling it easily. In this study, a CFRTP with excellent mechanical properties and heat resistance was synthesized using a polyether ether ketone (PEEK) as a matrix resin. The PEEK resin was modified to form cross‐linked structures through Friedel–Crafts reaction alkylation. The synthesis temperature of CFRTP was optimized considering the mechanical properties of PEEK, and its heat resistance was enhanced because of the cross‐linked structures. Further, the cross‐linked PEEK resin was partially used as a matrix resin, and the mechanical properties of the CFRTP were enhanced. We plan to develop a method for recycling CFRTP using PEEK and crosslinked PEEK for synthesizing C/C composites by focusing on the high heat resistance of the crosslinked PEEK containing a large amount of carbon and reducing mass loss after heat treatment.

Highlights

CC bonds were introduced into the polyether ether ketone (PEEK) resin by Friedel–Crafts reaction alkylation.

Thermal properties of PEEK were enhanced by hypercrosslinking reaction.

Optimization of synthesized temperature was investigated to fabricate carbon fiber‐reinforced thermoplastic (CFRTP).

Mechanical properties were enhanced CFRTP modified with hypercrosslinking reaction.
Effect of Reaction Layers on Internal Stresses in Co‐Fired Multilayers of Calcium Manganate and Calcium Cobaltite
Authors: Stargardt Patrick , Bresch Sophie , Falkenberg Rainer , Mieller Björn
Published: May 2024

A widespread recovery of waste heat requires a cost‐effective production of thermoelectric generators. Thermoelectric oxides are predestined for use at high temperatures. For manufacturing reasons, a multilayer generator design will be easily scalable and cost‐effective. To evaluate the potential of ceramic multilayer technology for that purpose, a multilayer of the promising thermoelectric oxides calcium cobaltite (Ca3Co4O9), calcium manganate (CMO, CaMnO3), and glass–ceramic insulation layers is fabricated. Cracks and reaction layers at the interfaces are observed in the microstructure. The compositions of these reaction layers are identified by energy‐dispersive X‐ray spectroscopy and X‐ray diffraction. Mechanical and thermal properties of all layers are compiled from literature or determined by purposeful sample preparation and testing. Based on this data set, the internal stresses in the multilayer after co‐firing are calculated numerically. It is shown that tensile stresses in the range of 50 MPa occur in the CMO layers. The reaction layers have only a minor influence on the level of these residual stresses. Herein, it is proven that the material system is basically suitable for multilayer generator production, but that the co‐firing process and the layer structure must be adapted to improve densification and reduce the tensile stresses in the CMO.
Adaptive neural tracking control for flexible joint robot including hydraulic actuator dynamics with disturbance observer
Authors: Phan Van Du , Vo Cong Phat , Ahn Kyoung Kwan
Published: May 2024

In this paper, a disturbance observer‐based adaptive neural backstepping integral sliding mode control (BISMC) is developed for a flexible joint robot (FJR) with the integration of an adjustable stiffness rotary actuator (ASRA). This system suffers from unknown system dynamics, external disturbance, and the influence of variable stiffness, which is a challenge for achieving precision tracking performance. Considering the lumped disturbances in FJR generated by the hydraulic system and the stiffness modulation of the ASRA, we investigate the structural dynamics nonlinear model of the FJR system, including hydraulic actuator dynamics. While other linear control strategies are applied for the FJR, the proposed controller uses BISMC, neural networks (NN), and nonlinear disturbance observers to deal with the disadvantages mentioned above. Radial basis function neural networks (RBFNN) are designed to tackle unknown nonlinear functions, and the disturbance observers are introduced to compensate for the influence of the variable stiffness, disturbance, and the approximation error caused by NN. Simulations and experiments are independently implemented to demonstrate the effectiveness and feasibility of the proposed controller. Results exhibit that the integral absolute error‐index is reduced by 20.4% when the proposed method is deployed for the experiment with a multistep trajectory.
Synthesis of Poly(methacrylamide‐co‐methacrylic acid) Nanogels: Effect of Synthesis Parameters on the Nanosize, Characterization and Stimuli‐Sensitive Characteristics
Authors: Sağlam Sağra , Çavuş Selva
Published: May 2024

Poly(methacrylamide‐co‐methacrylic acid) P(MAAm‐co‐MAAc) nanogels were synthesized using emulsion polymerization method and characterized in terms of structure, stimuli‐sensitive behavior and nanosize. The effect of monomer, surfactant (sodium dodecyl sulfate) and cross‐linker (N,N′‐methylenebisacrylamide) concentration on the nanosize of the nanogels was investigated. The hydrodynamic size of nanogels was determined by dynamic light scattering (DLS) and it was found to be in the range of 109.8–146.1 nm. Polydispersity index (PDI) values were lower than 0.3 (in the range of 0.145–0.261) confirming the narrow size distribution of the nanogels. Zeta potential measurements indicated that the nanogels exhibited good stability. Stimuli‐sensitive behavior of the nanogels was evaluated using UV‐visible spectroscopy. Characterization of the nanogels was carried out by Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), X‐ray diffraction (XRD) and scanning electron microscopy (SEM).
Comparative Study on Solvothermal and Sonochemical Synthesis of Zinc Oxide Nanomaterials and Unraveling the Efficacy in Sunscreen Formulations for Enhanced UV Protection
Authors: Veerabhadraiah Srikanth R. , Bhat Sachin A. , Sharma Rohit Kumar , Yelamaggad C. V. , Naik Nagaraja
Published: May 2024

As the demand for highly efficient UV‐protective sunscreens continues to rise, the exploration of advanced materials becomes imperative. This paper introduces a novel approach to synthesizing zinc oxide (ZnO) nanomaterials through one‐step solvothermal (ZnO−A) and sonochemical (ZnO−B) methods, eliminating the need for stabilizers or capping agents. The materials have undergone rigorous characterization, focusing on structural and optical properties, and are subsequently evaluated for their UV shielding efficacy. The synthesized ZnO nanomaterials are seamlessly incorporated into a pure cream matrix at varying concentrations (5, 10 and 15 wt. %), offering a versatile application for skin protection against UVA/UVB irradiation. Remarkably, the cream with 15 wt. % ZnO−A emerges as a standout performer, demonstrating immense UV blocking efficacy with 96.44 % for UVA and 97.22 % for UVB. The in vitro sun protection factor (SPF) value of 30.76 further underscores its exceptional performance. This research not only establishes a comprehensive comparative analysis of ZnO−A and ZnO−B nanomaterials but also emphasizes their potential as active ingredients in next‐generation skin care sunscreen formulations. The findings contribute to the ongoing efforts in advancing UV protection technologies, addressing both efficacy and safety considerations.