bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of die materials and pressure-dependent slip on the extrusion of linear low-density polyethylene
Authors: Person Timothy J. , Denn Morton M.
Published: July 2002

The flow of linear low-density polyethylene through stainless-steel slit dies occurred at shear rates approximately 12% higher than in identical α-brass dies at the same wall shear stresses, indicating near-wall slip. The flow curves were independent of gap spacing. We show through the slip theory of Hill and co-workers [J. Rheol. 34, 891–918 (1990)] that a measurable gap dependence of the flow curve is not a necessary consequence of wall slip; the flow curves for both stainless steel and α-brass dies can be fit with the same rheological parameters, with a difference in the work of adhesion accounting for the differences in the flow curves. X-ray photoelectron spectroscopy revealed differences in the chemistry of brass surfaces with different pretreating, corresponding to small differences in flow curves. Fluorocarbon-coated die surfaces showed no more slip than stainless steel, while the flow curve with gold-coated surfaces followed stainless steel at intermediate stress and brass at high stress.
Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients With Cancer
Authors: Cella Chiara A. , Knoedler Maren , Hall Marcia , Arcopinto Michele , Bagnardi Vincenzo , Gervaso Lorenzo , Pellicori Stefania , Spada Francesca , Zampino Maria G. , Ravenda Paola S. , Frassoni Samuele , Passaro Antonio , Milano Monica , Laffi Alice , Fazio Nicola , Lordick Florian
Published: February 2023

Importance

The assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event.

Objective

To validate the ONKOTEV score as a novel RAM to assess the risk of VTE among outpatients with cancer.

Design, Setting, and Participants

ONKOTEV-2 is a noninterventional prognostic study conducted in 3 European centers located in Italy, Germany, and the United Kingdom among a prospective cohort of 425 ambulatory patients with a histologically confirmed diagnosis of a solid tumor who were receiving active treatments. The total study duration was 52 months, with an accrual period of 28 months (from May 1, 2015, to September 30, 2017) and an overall follow up-period of 24 months (data were censored September 30, 2019). Statistical analysis was performed in October 2019.

Exposures

The ONKOTEV score was calculated for each patient at baseline by collecting clinical, laboratory, and imaging data from tests performed for routine practice. Each patient was then observed to detect any thromboembolic event throughout the study period.

Main Outcomes and Measures

The primary outcome of the study was the incidence of VTE, including deep vein thrombosis and pulmonary embolism.

Results

A total of 425 patients (242 women [56.9%]; median age, 61 years [range, 20-92 years]) were included in the validation cohort of the study. The cumulative incidences for the risk of developing VTE at 6 months were 2.6% (95% CI, 0.7%-6.9%), 9.1% (95% CI, 5.8%-13.2%), 32.3% (95% CI, 21.0%-44.1%), and 19.3% (95% CI, 2.5%-48.0%), respectively, among 425 patients with an ONKOTEV score of 0, 1, 2, and greater than 2 (P < .001). The time-dependent area under the curve at 3, 6, and 12 months was 70.1% (95% CI, 62.1%-78.7%), 72.9% (95% CI, 65.6%-79.1%), and 72.2% (95% CI, 65.2%-77.3%), respectively.

Conclusions and Relevance

This study suggests that, because the ONKOTEV score has been validated in this independent study population as a novel predictive RAM for cancer-associated thrombosis, it can be adopted into practice and into clinical interventional trials as a decision-making tool for primary prophylaxis.
Next-Generation Alternative Payment Models in Oncology—Will Precision Preclude Participation?
Authors: Mullangi Samyukta , Parikh Ravi B. , Schleicher Stephen M.
Published: February 2023

This Viewpoint proposes 3 changes to the Enhancing Oncology Model of the US Centers for Medicare & Medicaid Services.
Association of Human Papillomavirus Status With Suicide Risk Among Patients With Head and Neck Cancer
Authors: Chakoma Tatenda , Moon Peter K. , Osazuwa-Peters Oyomoare L. , Megwalu Uchechukwu C. , Osazuwa-Peters Nosayaba
Published: February 2023

Importance

Human papillomavirus (HPV) is strongly associated with head and neck cancer, and HPV status is considered a prognostic factor. Being a sexually transmitted infection, HPV-related cancers may have greater risk of stigma and psychological distress; however, the potential association of HPV-positive status with psychosocial outcomes, such as suicide, is understudied in head and neck cancer.

Objective

To investigate the association between HPV tumor status and suicide risk among patients with head and neck cancer.

Design, Setting, and Participants

This population-based retrospective cohort study included adult patients with clinically confirmed cases of head and neck cancer based on HPV tumor status from the Surveillance, Epidemiology, and End Results database from January 1, 2000, to December 31, 2018. Data analysis was conducted from February 1 to July 22, 2022.

Main Outcomes and Measures

The outcome of interest was death by suicide. Primary measure was HPV status of tumor site, dichotomized as positive or negative. Covariates included age, race, ethnicity, marital status, cancer stage at presentation, treatment modality, and type of residence. Cumulative risk of suicide among patients with HPV-positive and HPV-negative head and neck cancer was assessed using Fine and Gray competing risk models.

Results

Of 60 361 participants, the mean (SD) age was 61.2 (13.65) years, and 17 036 (28.2%) were women; there were 347 (0.6%) American Indian, 4369 (7.2%) Asian, 5226 (8.7%) Black, 414 (0.7%) Native Hawaiian or Other Pacific Islander, and 49 187 (81.5%) White individuals. A competing risk analysis showed a significant difference in the cumulative incidence of suicide between HPV-positive cancers (5-year suicide-specific mortality, 0.43%; 95% CI, 0.33%-0.55%) and HPV-negative cancers (5-year suicide-specific mortality, 0.24%; 95% CI, 0.19%-0.29%). Tumor status that was HPV positive was associated with increased suicide risk in the unadjusted model (hazard ratio [HR], 1.76; 95% CI, 1.28-2.40), but not the fully adjusted model (adjusted HR, 1.18; 95% CI, 0.79-1.79). Among people with oropharyngeal cancer only, HPV status was associated with increased suicide risk, but the width of the confidence interval prevented definitive conclusion (adjusted HR, 1.61; 95% CI 0.88-2.94).

Conclusions and Relevance

The results of this cohort study suggest that patients with HPV-positive head and neck cancer have similar risk of suicide as patients with HPV-negative cancer, despite differences in overall prognosis. Early mental health interventions may be associated with reduced suicide risk in all patients with head and neck cancer and should be assessed in future work.
MicroRNA signature and integrative omics analyses define prognostic clusters and key pathways driving prognosis in patients with neuroendocrine neoplasms
Authors: Soldevilla Beatriz , Lens‐Pardo Alberto , Espinosa‐Olarte Paula , Carretero‐Puche Carlos , Molina‐Pinelo Sonia , Robles Carlos , Benavent Marta , Gomez‐Izquierdo Lourdes , Fierro‐Fernández Marta , Morales‐Burgo Patricia , Jimenez‐Fonseca Paula , Anton‐Pascual Beatriz , Rodriguez‐Gil Yolanda , Teijo‐Quintans Ana , La Salvia Anna , Rubio‐Cuesta Beatriz , Riesco‐Martínez Maria C. , Garcia‐Carbonero Rocio
Published: February 2023

Neuroendocrine neoplasms (NENs) are mutationally quiet (low number of mutations/Mb), and epigenetic mechanisms drive their development and progression. We aimed at comprehensively characterising the microRNA (miRNA) profile of NENs, and exploring downstream targets and their epigenetic modulation. In total, 84 cancer‐related miRNAs were analysed in 85 NEN samples from lung and gastroenteropancreatic (GEP) origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N = 63) and methylomics (N = 30) were performed to predict miRNA target genes, signalling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas cohorts and in NEN cell lines. We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5‐year survival of 80%, 66% and 36%). Expression of the eight‐miRNA gene signature correlated with 71 target genes involved in PI3K–Akt and TNFα–NF‐kB signalling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. In brief, we identified an 8‐miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patients.
Analysis of CyberKnife intracranial treatment plans using ICRU 91 dose reporting: A retrospective study
Authors: Conlon Dion , Connolly James , Galal Mohamed , Ahmed Ismail , Foley Mark , Kleefeld Christoph
Published: February 2023

ICRU 91, published in 2017, is an international standard for prescribing, recording, and reporting stereotactic treatments. Since its release, there has been limited research published on the implementation and impact of ICRU 91 on clinical practice. This work provides an assessment of the recommended ICRU 91 dose reporting metrics for their use in clinical treatment planning. A set of 180 intracranial stereotactic treatment plans for patients treated by the CyberKnife (CK) system were analyzed retrospectively using the ICRU 91 reporting metrics. The 180 plans comprised 60 trigeminal neuralgia (TGN), 60 meningioma (MEN), and 60 acoustic neuroma (AN) cases. The reporting metrics included the planning target volume (PTV) near‐minimum dose (), near‐maximum dose (), and median dose (), as well as the gradient index (GI) and conformity index (CI). The metrics were assessed for statistical correlation with several treatment plan parameters. In the TGN plan group, owing to the small targets, was greater than in 42 plans, whereas both metrics were not applicable in 17 plans. The metric was predominantly influenced by the prescription isodose line (PIDL). The GI was significantly dependent on target volume in all analyses performed, where the variables were inversely related. The CI was only dependent on target volume in treatment plans for small targets. The ICRU 91 and metrics breakdown in plans for small target volumes below 1 cm3; the Min and Max pixel should be reported in such cases. The metric is of limited use for treatment planning. Given their volume dependence, the GI and CI metrics could potentially serve as plan evaluation tools in the planning of the sites analyzed in this study, which would ultimately improve treatment plan quality.
KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine
Authors: Müller Peter , Takacs Danielle S. , Hedrich Ulrike B. S. , Coorg Rohini , Masters Laura , Glinton Kevin E. , Dai Hongzheng , Cokley Jon A. , Riviello James J. , Lerche Holger , Cooper Edward C.
Published: February 2023

Precision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage‐gated K+ channel subunit KV1.1. So far, loss‐of‐function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain‐of‐function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4‐aminopyridine. Clinical use of 4‐aminopyridine was associated with reduced seizure burden, enabled simplification of co‐medication and prevented rehospitalization.
Regulation of Chirality Transfer and Amplification from Chiral Cysteine to Gold Nanorod Assemblies using Nonchiral Surface Ligands
Authors: Zhang Chenqi , Gao Xinshuang , Li Hanbo , Ji Yinglu , Cai Rui , Hu Zhijian , Wu Xiaochun
Published: February 2023

Owing to large chiroptical activity and high tunability, dynamic chiral superstructures of plasmonic nanoparticles have attracted great attention. A useful strategy has been developed to obtain strong plasmonic chiroptical responses (plasmonic circular dichroism, PCD) by adding small chiral thiols on achiral side‐by‐side assemblies of gold nanorods (AuNRs). Despite the critical role of chiral thiols, the impact of achiral surface ligands is yet to be revealed. Herein, the effects of achiral surface ligands are systematically investigated from the viewpoints of counter ion, hydrocarbon chain length, and head group of surfactants. A well‐packed ligand shell is found to be beneficial for the chirality transfer and amplification from adsorbed chiral thiols to rod assemblies. The PCD temperature amplification effect is observed by using different surfactant ligands and reflects the energy cost of rod‐twisting in the assemblies. This study deepens the understanding of chiral plasmonic assemblies driven by small chiral molecules and provides rational design to fabricate such assembly structures.
A Senomorphic‐Conjugated Scaffold for Application of Senescent Cells in Regenerative Medicine
Authors: Deng Wenqi , Jo Jun‐ichiro , Tanaka Tomonari , Morikuni Hidetoshi , Hashimoto Yoshiya , Matsumoto Naoyuki , Honda Yoshitomo
Published: February 2023

Procuring a sufficient amount of cells is essential for cell‐based regenerative therapy. However, the application of senescent cells replicated using cell culture is limited because the cells have lost their regenerative ability or produce deleterious senescence‐associated secretory phenotypes (SASPs). In this study, using a senomorphic (epigallocatechin gallate [EGCG]), which could modulate SASP secretion from senescent cells, nonsenescent and senescent dedifferentiated fat cells from rats (rDFAT cells), and congenital cleft‐jaw defects in rats, the authors show that the senomorphic (EGCG)‐conjugated cellular scaffold restores the bone regenerative ability of senescent multipotent progenitor cells, even in vivo. In this osteogenic process, the EGCG‐conjugated scaffold attenuates the production of representative SASPs (i.e., interleukin [IL]‐6 and tumor necrosis factor‐α) and reactive oxygen species in vivo and in vitro. In polymerase chain reaction arrays in vitro, the EGCG‐conjugated cellular scaffold suppresses the expression of genes associated with deleterious SASP factors for bone formation (e.g., Csf2, IL‐1a, and others) from senescent rDFAT cells and elevates the expression of potential osteogenesis‐ and bone remodeling‐ related gene (e.g., Cxcl13 and Spp1). These results provide insights to expand the application of senomorphics and senescent stem/multipotent progenitor cells in cell‐based regenerative medicine.
Pixelating Responsive Structural Color via a Bioinspired Morphable Concavity Array (MoCA) Composed of 2D Photonic Crystal Elastomer Actuators
Authors: Pan Yi , Li Chang , Hou Xiaoyu , Yang Zhenyu , Li Mingzhu , Shum Ho Cheung
Published: February 2023

Stimuli‐responsive structural coloration allows the color change of soft substrates in response to environmental stimuli such as heat, humidity, and solvents. Such color‐changing systems enable smart soft devices, such as the camouflageable skin of soft robots or chromatic sensors in wearable devices. However, individually and independently programmable stimuli‐responsive color pixels remain significant challenges among the existing color‐changing soft materials and devices, which are crucial for dynamic display. Inspired by the dual‐color concavities on butterfly wings, a morphable concavity array to pixelate the structural color of two‐dimensional photonic crystal elastomer and achieve individually and independently addressable stimuli‐responsive color pixels is designed. The morphable concavity can convert its surface between concave and flat upon changes in the solvent and temperature, accompanied by angle‐dependent color‐shifting. Through multichannel microfluidics, the color of each concavity can be controllably switched. Based on the system, the dynamic display by forming reversibly editable letters and patterns for anti‐counterfeiting and encryption are demonstrated. It is believed that the strategy of pixelating optical properties through locally altering surface topography can inspire the design of new transformable optical devices, such as artificial compound eyes or crystalline lenses for biomimetic and robotic applications.
Design of Flame‐Made ZnZrOx Catalysts for Sustainable Methanol Synthesis from CO2
Authors: Pinheiro Araújo Thaylan , Morales‐Vidal Jordi , Zou Tangsheng , Agrachev Mikhail , Verstraeten Simon , Willi Patrik O. , Grass Robert N. , Jeschke Gunnar , Mitchell Sharon , López Núria , Pérez‐Ramírez Javier
Published: February 2023

Mixed zinc‐zirconium oxides, ZnZrOx, are highly selective and stable catalysts for CO2 hydrogenation to methanol, a pivotal energy vector. However, their activity remains moderate, and descriptors to design improved systems are lacking. This work applies flame spray pyrolysis (FSP), a one‐step and scalable method, to synthesize a series of ZnZrOx catalysts, and systematically compares them to coprecipitated (CP) analogs to establish deeper synthesis–structure–performance relationships. FSP systems (up to 5 mol%) generally display a threefold higher methanol productivity compared to their CP counterparts. In‐depth characterization and theoretical simulations show that, unlike CP, FSP maximizes the surface area and formation of atomically dispersed Zn2+ sites incorporated in lattice positions within the ZrO2 surface, which is key to improving performance. Analysis by in situ electron paramagnetic resonance (EPR) spectroscopy reveals that the specific architecture of the flame‐made catalyst markedly fosters the generation of oxygen vacancies. Together with surrounding Zn and Zr‐O atoms, the oxygen vacancies create active ensembles that favor methanol formation through the formate path while suppressing undesired CO production, as confirmed by kinetic modeling. This study elucidates the nature of active sites and their working mechanism, pushing forward ZnZrOx‐catalyzed methanol synthesis by providing a new benchmark for this cost‐effective and earth‐abundant catalyst family.
The clinical impact of COVID‐19 on endoscopic surgery in Japan: Analysis of data from the National Clinical Database
Authors: Shiroshita Hidefumi , Endo Hideki , Inomata Masafumi , Akagi Tomonori , Yamamoto Hiroyuki , Yamaguchi Shigeki , Eguchi Susumu , Wada Norihito , Kurokawa Yukinori , Seki Yosuke , Sakai Yoshiharu , Miyata Hiroaki , Kakeji Yoshihiro , Kitagawa Yuko , Taketomi Akinobu , Mori Masaki
Published: February 2023

Aim

This study aimed to evaluate the impact of the coronavirus disease (COVID‐19) pandemic on elective endoscopic surgeries in Japan using the National Clinical Database.

Methods

We retrospectively analyzed the clinicopathological factors and surgical outcomes of laparoscopic cholecystectomy (LC), laparoscopic distal gastrectomy (LDG), and laparoscopic low anterior resection (LLAR) and compared the monthly numbers of each procedure performed in 2020 with those in 2018 and 2019. The degree of infection in prefectures was classified into low and high groups.

Results

In 2020, the number of LCs (except for acute cholecystitis) was 76 079 (93.0% of that in 2019), the number of LDGs was 14 271 (85.9% of that in 2019), and the number of LLARs was 19 570 (88.1% of that in 2019). Although the number of robot‐assisted LDG and LLAR cases increased in 2020, the growth rate was mild compared with that in 2019. There was little difference in the number of cases in the degree of infection in the prefectures. The numbers of LC, LDG, and LLAR cases decreased from May to June and recovered gradually. In late 2020, the proportion of T4 and N2 cases of gastric cancer and the number of T4 cases of rectal cancer increased compared with those in 2019. There was little difference between the proportions of postoperative complications and mortality in the three procedures between 2019 and 2020.

Conclusion

The number of endoscopic surgeries decreased in 2020 as a result of the COVID‐19 pandemic. However, the procedures were performed safely in Japan.
Cyclic extrusion synthesis of mesoporous carbon‐supported metal catalysts for selective hydrogenation
Authors: Xu Jialu , Hou Shengtai , Niu Qiang , Zhang Pengfei , Luo Zheng‐Hong
Published: February 2023

The mesoporous carbon‐supported metal catalysts are important materials in heterogeneous catalysis. From the standpoint of process intensification, the current synthesis methods still suffer from several issues, such as the excessive use of toxic solvents, the time‐consuming self‐assembly process, and the difficulty of continuous production. Herein, we report a solvent‐free and continuous route to synthesize mesoporous carbon‐supported metal catalysts. Interestingly, the use of cyclic extrusion could promote mixing, coordination, and assembly of catalyst precursors (tannin‐metal salts‐additives) by shearing and squeeze force. The as‐made mesoporous carbon‐supported nickel materials showed high surface areas (up to 512 m2 g−1), narrow pore size distribution (~10 nm), and good performance in the selective hydrogenation of nitrobenzene to aniline (Conv. >99%; Sel. >99%). In addition, the fluid property of catalyst precursors and the geometry of the twin‐screw extrusion channel were studied, and the essence of this cyclic extrusion process is also discussed.
Expanding the reproductive organ phenotype of CHD7‐spectrum disorder
Authors: Nomakuchi Tomoki T. , Danowitz Melinda , Stewart Blythe , Leonard Jacqueline , Izumi Kosuke , Krantz Ian , Kolon Thomas F. , Langdon David , Skraban Cara , Van Batavia Jason , Zackai Elaine , Jiao Kai , Linn Rebecca , Alexander Caitlin , Zaontz Mark , Vogiatzi Maria G. , Pyle Louise C.
Published: February 2023

CHD7 disorder is a multiple congenital anomaly syndrome with a highly variable phenotypic spectrum, and includes CHARGE syndrome. Internal and external genital phenotypes frequently seen in CHD7 disorder include cryptorchidism and micropenis in males, and vaginal hypoplasia in females, both thought to be secondary to hypogonadotropic hypogonadism. Here, we report 14 deeply phenotyped individuals with known CHD7 variants (9 pathogenic/likely pathogenic and 5 VOUS) and a range of reproductive and endocrine phenotypes. Reproductive organ anomalies were observed in 8 of 14 individuals and were more commonly noted in males (7/7), most of whom presented with micropenis and/or cryptorchidism. Kallmann syndrome was commonly observed among adolescents and adults with CHD7 variants. Remarkably, one 46,XY individual presented with ambiguous genitalia, cryptorchidism with Müllerian structures including uterus, vagina and fallopian tubes, and one 46,XX female patient presented with absent vagina, uterus and ovaries. These cases expand the genital and reproductive phenotype of CHD7 disorder to include two individuals with genital/gonadal atypia (ambiguous genitalia), and one with Müllerian aplasia.
Carbon‐Carbon Bond Formation from Carbon Monoxide and Hydride: The Role of Metal Formyl Intermediates**
Authors: Parr Joseph M. , Crimmin Mark R.
Published: February 2023

Current examples of carbon chain production from metal formyl intermediates with homogeneous metal complexes are described in this Minireview. Mechanistic aspects of these reactions as well as the challenges and opportunities in using this understanding to develop new reactions of CO and H2 are also discussed.
Microstructuring process in oleogels formulated with vegetable oils and monoglycerides: A comparison of non‐isothermal nucleation kinetics by spectrophotometric and DSC analysis
Authors: Contreras‐Ramírez Javier Isaac , Acosta‐Gurrola Esperanza , Rosas‐Flores Walfred , Gallegos‐Infante José Alberto , Toro‐Vázquez Jorge Fernando
Published: February 2023

The initial oleogelation process (microstructuring) as well as the formulation are determinant to obtain the desired characteristics in oleogels with potential application in the industry. The microstructuring process in oleogels has been extensively studied by means of techniques highly sensitive to thermal variations, such as differential scanning calorimetry (DSC). However, there are other readily available techniques and equipment that can be employed to perform similar evaluations. Non‐isothermal nucleation kinetics by spectrophotometric methods can be used as alternatives to basic crystallization studies in oleogels. Therefore, in this research a comparison of both techniques is presented, highlighting their similarities, advantages and limitations, in the study of the microstructure of oleogels. Oleogels were obtained with a minimum concentration of gelator and another saturated one, using vegetable oils of different degrees of saturation. The crystallization profiles of the oleogels were obtained by DSC, a non‐isothermal nucleation kinetics was performed from the molten system and the final microstructure was evaluated by optical microscopy. The Fisher‐Turnbull and Avrami model was used to evaluate the behavior during microstructuring. A gap was observed during the crystallization process by DSC which can be evaluated by spectrophotometry. Differences in the microstructuring process were found in both methods due to the temperature ramp used and formulation variables. The results obtained by spectrophotometry indicate that it can be a good alternative, easily accessible in oleogel crystallization studies, when high sensitivity or very specific thermal parameters are not required.
Simulation and optimized design of cure cycle for three‐dimensional polymer‐matrix composite component
Authors: Yang Wenkai , Zhao Che , Jia Yunlong , Lu Shihong
Published: February 2023

The cure cycle plays a crucial role in manufacturing polymer‐matrix composite component. Unreasonable design of cure cycle can easily lead to thermal gradients during curing process, which will generate residual stress and seriously affect the quality of component. Meanwhile, the cure cycle of the three‐dimensional composite component is difficult to optimized, due to the complicated distribution of temperature and curing degree. In this paper, numerical simulation is applied to research the curing process of the polymer‐matrix composite. The change rules of temperature and curing degree are explored. An optimum design method for the cure cycle of three‐dimensional composite component is proposed. Meanwhile, numerical simulation is applied in this method to design the cure cycle by referring to the change rules of temperature and curing degree of the component, in which the internal and external thermal gradients can be balanced during the curing process. The results show that the optimized cure cycle can significantly reduce the thermal gradients for three‐dimensional composite component, which provide guidance for cure cycle design in the manufacturing of polymer‐matrix composite.
Enhanced mechanical, tribological, and acoustical behavior of polyphenylene sulfide composites reinforced with zero‐dimensional alumina
Authors: Natarajan Elango , Ramesh S. , Markandan Kalaimani , Saravanakumar N. , Dilip A. Anto , Batcha Abdul Rahim Sadiq
Published: February 2023

Polyphenylene sulfide (PPS) is a semicrystalline thermoplastic which can pass UL94V‐0 standard without adding flame retardant. In the present study, effect of alumina (Al2O3) addition on the mechanical, tribological, and acoustical behavior of PPS polymer were investigated. Experimental findings indicate that elastic modulus, tensile strength, and flexural strength were enhanced by 21.4%, 7.7%, and 6.9%, respectively. The highest tensile strength was obtained when PPS was reinforced with 5 wt% Al2O3 while highest bending strength and toughness were obtained with 20 wt% Al2O3. Reinforced composites encountered <5% and <14% mass loss when heated to 420 and 500°C, respectively. Lower filler concentrations (<5 wt%) had insignificant effect on the glass transition temperature (Tg) of the composite. Experimental results agreed well to Hashin–Shtrikman and Suquet predictions at lower filler concentrations since filler particles could be easily dispersed in the interstitial sites of PPS matrix without significant agglomeration. Besides, significant acoustic emission (AE) characteristic such as higher absolute energy rate was witnessed in Al2O3 reinforced PPS composites. The insights derived from this study are expected to open a new avenue of producing composites with high stiffness, strength, and significant AE events by using zero‐dimensional fillers.
Wildfire damage and contamination to private drinking water wells
Authors: Jankowski Caroline , Isaacson Kristofer , Larsen Madeline , Ley Christian , Cook Myles , Whelton Andrew J.
Published: February 2023

Following the 2021 Marshall Fire in Colorado, this study was conducted to better understand private well and plumbing damage and to develop public health guidance. More than 20 post‐fire drinking water well guidance documents with varied recommendations were found. Approximately 227 wells were located in the fire footprint. Seventeen properties were visited, and a subset of wells were sampled for organic and inorganic contaminants. Property debris was also collected. Benzene, toluene, and 19 semi‐volatile organic compounds (SVOCs) were detected in water extracts of property debris. No wells contained volatile organic compound contamination. Two shallow wells (12 and 15 ft) had debris contamination; one well contained notable SVOC contamination. One multi‐home unregulated well system was extensively damaged, lost pressure, and had not been repressurized 11 months after the fire due to financial and technical challenges. Study results highlight the need for follow‐up work to understand well system damage and household response.
microRNA‐221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease
Authors: Yao Yufang , Zhao Zhiyue , Zhang Fubo , Miao Na , Wang Nan , Xu Xin , Yang Chaoping
Published: February 2023

Background

Parkinson's disease (PD) is one of the most common systemic neurodegenerative diseases and is related to the loss of dopaminergic neurons in the substantia nigra. Several studies verified that microRNA (miRNAs) targeting the Bim/Bax/caspase‐3 signaling axis is involved in the apoptosis of dopaminergic neurons in substantia nigra. In this study, we aimed to explore the role of miR‐221 in PD.

Methods

To examine the function of miR‐221 in vivo, we used a well‐established 6‐OHDA‐induced PD mouse model. Then we conducted adenovirus‐mediated miR‐221 overexpression in the PD mice.

Results

Our results showed that miR‐221 overexpression improved motor behavior of the PD mice. We demonstrated that overexpression of miR‐221 reduced the loss of dopaminergic neurons in the substantia nigra striatum by promoting their antioxidative and antiapoptosis capacities. Mechanistically, miR‐221 targets Bim, thus inhibiting Bim and Bax caspase‐3 mediated apoptosis signaling pathways.

Conclusion

Our findings suggest miR‐221 participates in the pathological process of PD and might be a potential drug target and provide new insight into PD treatment.
Impedimetric nanoimmunosensor platform for aflatoxin B1 detection in peanuts
Authors: Barbieri Gilcelia J. L. S. , Simão Estéfani P. , Avelino Karen Y. P. S. , Oliveira Maria D. L. , Andrade Cesar A. S.
Published: February 2023

This article developed a novel electrochemical immunosensor for the specific detection of aflatoxin B1 (AFB1). Amino‐functionalized iron oxide nanoparticles (Fe3O4‐NH2) were synthesized. Fe3O4‐NH2 were chemically bound on self‐assembly monolayers (SAMs) of mercaptobenzoic acid (MBA). Finally, polyclonal antibodies (pAb) were immobilized on Fe3O4‐NH2‐MBA. The sensor system was evaluated through atomic force microscopy (AFM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). A reduction in the anodic and cathodic peak currents was observed after the assembly of the sensor platform. The charge transfer resistance (Rct) was increased due to the electrically insulating bioconjugates. Then, the specific interaction between the sensor platform and AFB1 blocks the electron transfer of the [Fe(CN)6]3−/4− redox pair. The nanoimmunosensor showed a linear response range estimated from 0.5 to 30 μg/mL with a limit of detection (LOD) of 9.47 μg/mL and a limit of quantification (LOQ) of 28.72 μg/mL for AFB1 identification in a purified sample. In addition, a LOD of 3.79 μg/mL, a LOQ of 11.48 μg/mL, and a regression coefficient of 0.9891 were estimated for biodetection tests on peanut samples. The proposed immunosensor represents a simple alternative, successfully applied in detecting AFB1 in peanuts, and therefore, represents a valuable tool for ensuring food safety.
Monocyte chemoattractant protein 1 as a potential biomarker for immune checkpoint inhibitor‐associated neurotoxicity
Authors: Möhn Nora , Mahjoub Susann , Duzzi Laura , Narten Emily , Grote‐Levi Lea , Körner Gudrun , Seeliger Tabea , Beutel Gernot , Bollmann Benjamin‐Alexander , Wirth Thomas , Huss André , Tumani Hayrettin , Grimmelmann Imke , Gutzmer Ralf , Ivanyi Philipp , Skripuletz Thomas ,   ICOG‐CCCH (Immune Cooperative Oncology Group; Comprehensive Cancer Center Hannover)
Published: February 2023

Background

Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors (ICI). However, there is a growing awareness of immune‐related adverse events (irAE). Especially ICI‐mediated neurological adverse events (nAE(+)), are tough to diagnose and biomarkers to identify patients at risk are missing.

Methods

A prospective register with prespecified examinations was established for ICI treated patients in December 2019. At the time of data cut‐off, 110 patients were enrolled and completed the clinical protocol. Herein, cytokines and serum neurofilament light chain (sNFL) from 21 patients were analyzed.

Results

nAE of any grade were observed in 31% of the patients (n = 34/110). In nAE(+) patients a significant increase in sNFL concentrations over time was observed. Patients with higher‐grade nAE had significantly elevated serum‐concentrations of monocyte chemoattractant protein 1 (MCP‐1) and brain‐derived neurotrophic factor (BDNF) at baseline compared to individuals without any nAE (p < 0.01 and p < 0.05).

Conclusion

Here, we identified nAE to occur more frequently than previously reported. Increase of sNFL during nAE confirms the clinical diagnosis of neurotoxicity and might be a suitable marker for neuronal damage associated with ICI therapy. Furthermore, MCP‐1 and BDNF are potentially the first clinical‐class nAE predictors for patients under ICI therapy.
Facile Synthesis of Palladium‐Silver Dilute Alloy Catalyst for Acetylene Hydrogenation
Authors: Chai Shanshan , Gao Denglei , Xia Jing , Yang Yanpeng , Wang Xi
Published: February 2023

Selective hydrogenation of acetylene (C2H2) to ethylene (C2H4) has been recognized as an important strategic reaction for the removal of trace acetylene from ethylene. Palladium‐based alloys are one of the most commonly used catalysts for this reaction but bear a high price and unsatisfactory catalytic performance. Here, we develop a feasible strategy toward the synthesis of a palladium‐silver dilute alloy catalyst (PdxAg/Al2O3), which contains the Pd1Ag single‐atom‐alloy (SAA) and Pd2Ag dimer‐alloy (DA) species. This catalyst exhibits a high ethylene (C2=) yield of 90.1 % even after 100 hours at 60 °C, which is 11.9 times higher than that of the PdAg/Al2O3 alloy catalyst. Based on in‐situ spectroscopic investigations and theoretical calculations, both Pd1Ag SAA and Pd2Ag DA species in PdxAg/Al2O3 are easier to desorb C2H4 compared with PdAg/Al2O3, and they experience the possible hydrogenation paths with the low energy barriers to yield C2=. Furthermore, PdxAg/Al2O3 is beneficial to restraining coking due to the endothermic C−H bond cleavage. Thus, these combined merits contribute to the superior catalytic performance for PdxAg/Al2O3.
Development of Enterovirus Antiviral Agents That Target the Viral 2C Protein
Authors: Kejriwal Rishabh , Evans Tristan , Calabrese Joshua , Swistak Lea , Alexandrescu Lauren , Cohen Michelle , Rahman Nahian , Henriksen Niel , Charan Dash Radha , Hadden M. Kyle , Stonehouse Nicola J. , Rowlands David J. , Kingston Natalie J. , Hartnoll Madeline , Dobson Samuel J. , White Simon J.
Published: February 2023

The Enterovirus (EV) genus includes several important human and animal pathogens. EV‐A71, EV‐D68, poliovirus (PV), and coxsackievirus (CV) outbreaks have affected millions worldwide, causing a range of upper respiratory, skin, and neuromuscular diseases, including acute flaccid myelitis, and hand‐foot‐and‐mouth disease. There are no FDA‐approved antiviral therapeutics for these enteroviruses. This study describes novel antiviral compounds targeting the conserved non‐structural viral protein 2C with low micromolar to nanomolar IC50 values. The selection of resistant mutants resulted in amino acid substitutions in the viral capsid protein, implying these compounds may play a role in inhibiting the interaction of 2C and the capsid protein. The assembly and encapsidation stages of the viral life cycle still need to be fully understood, and the inhibitors reported here could be useful probes in understanding these processes.
Bimetallic Metal‐Organic Frameworks (BMOF) and BMOF‐ Incorporated Membranes for Energy and Environmental Applications
Authors: Chithra K. R. , Rao Shashank M. , Varsha M. V. , Nageswaran Gomathi
Published: February 2023

Bimetallic metal organic frameworks (BMOFs) are a class of crystalline solids and their structure comprises two metal ions in the lattice. BMOFs show a synergistic effect of two metal centres and enhanced properties compared to MOFs. By controlling the composition and relative distribution of two metal ions in the lattice the structure, morphology, and topology of BMOFs could be regulated resulting in an improvement in the tunability of pore structure, activity, and selectivity. Thus, developing BMOFs and BMOF incorporated membranes for applications such as adsorption, separation, catalysis, and sensing is a promising strategy to mitigate environmental pollution and address the looming energy crisis. Herein we present an overview of recent advancements in the area of BMOFs and a comprehensive review of BMOF incorporated membranes reported to date. The scope, challenges as well as future perspectives for BMOFs and BMOF incorporated membranes are presented.
High Entropy Oxide (CrMnFeNiMg)3O4 with Large Compositional Space Shows Long‐Term Stability as Cathode in Lithium‐Sulfur Batteries
Authors: Chung Sheng‐Heng , Wu Yi‐Hsuan , Tseng Yu‐Hsun , Nguyen Thi Xuyen , Ting Jyh‐Ming
Published: February 2023

The repeated formation and irreversible diffusion of liquid‐state lithium polysulfides (LiPSs) are the primary challenges in the development of high‐energy‐density lithium‐sulfur battery (LSB). An effective strategy to alleviate the resulting polysulfide loss is critical for the stability of LSBs. In this regard, high entropy oxides (HEOs) appear as a promising additive for the adsorption and conversion of LiPSs owing to the diverse active sites, offering unparalleled synergistic effects. Herein, we have developed a (CrMnFeNiMg)3O4 HEO as a functional polysulfide trapper in LSB cathode. The adsorption of LiPSs by the metal species (i. e., Cr, Mn, Fe, Ni, and Mg) in the HEO takes place through two different paths and leads to enhanced electrochemical stability. We demonstrate that the optimal sulfur cathode with the (CrMnFeNiMg)3O4 HEO attains a high peak and reversible discharge capacities of 857 mAh g−1 and 552 mAh g−1, respectively, at a cycling rate of C/10, a long cycle life of 300 cycles, and a high rate performance at the cycling rates from C/10 to C/2.
pMOS‐only pW‐power voltage reference with sub‐10 ppm/°C trimmed temperature coefficient and sub‐100 ppm/V line sensitivity
Authors: Azimi Mohammad , Habibi Mehdi , Crovetti Paolo
Published: February 2023

In this paper, a new ultra‐low‐power voltage reference based on a two‐stage, all‐pMOS topology operating in the subthreshold region is proposed to uniquely meet the pW‐power range power consumption requirements of emerging Internet‐of‐Things applications without significantly compromising the temperature coefficient (TC) and the line sensitivity (LS) performance. The proposed circuit consists of the LS regulator, TC corrector, and TC trimming sections. Based on post‐layout Monte Carlo simulations in 180‐nm CMOS, the proposed circuit operates with 0.8‐ to 2.4‐V supply potential and generates a reference voltage of 206 mV with a process spread of 7.8%, achieving an average calibrated TC of 4.4 ppm/°C in the temperature range of −20°C to 80°C, and an average LS of 51.5 ppm/V with a power consumption of 25.9 pW at 25°C (469.1 pW at 80°C).
ALKBH5‐mediated m6A demethylation of TIRAP mRNA promotes radiation‐induced liver fibrosis and decreases radiosensitivity of hepatocellular carcinoma
Authors: Chen Yuhan , Zhou Peitao , Deng Yixun , Cai Xinni , Sun Mingrui , Sun Yining , Wu Dehua
Published: February 2023

Background

Radiation‐induced hepatic stellate cell (HSC) activation promotes radiation‐induced liver fibrosis (RILF), a complication for hepatocellular carcinoma (HCC) radiotherapy. The demethylase alpha‐ketoglutarate‐dependent dioxygenase alkB homolog 5 (ALKBH5) decreases N6‐methyladenylate methylation (m6A) modification of RNA, while its role in regulating RILF pathogenesis and HCC radiosensitivity remains unknown.

Methods

Methylated RNA immunoprecipitation sequencing (MeRIP‐seq) and RNA‐sequencing (RNA‐seq) were used to screen target genes regulated by ALKBH5. HSC with altered ALKBH5 expression was used to assess irradiation‐induced HSC activation and the effect of HSC on recruitment and polarisation of monocytes. Key cytokines in medium from irradiated HSC‐educated monocytes were identified by cytokine array detection. The effects of blocking ALKBH5 and key cytokines on RILF and HCC radiosensitivity were also evaluated.

Results

Radiation‐induced ALKBH5 expression in HSC mediated m6A demethylation of toll‐interleukin 1 receptor domain containing adaptor protein (TIRAP) mRNA and activated its downstream NF‐κB and JNK/Smad2 pathways to promote HSC activation. Additionally, ALKBH5 regulated CCL5 secretion by irradiated HSC to promote monocyte recruitment and M2 macrophage polarisation. Notably, polarised monocytes secreted CCL20 to up‐regulate ALKBH5 expression in HSC, and reduce HCC radiosensitivity by activating ALKBH5/TIRAP axis in HCC cells. ALKBH5 knockdown‐combined CCR6 (CCL20 receptor) inhibitor significantly alleviated RILF and improved HCC radiosensitivity in mice. HCC patients with high ALKBH5 and TIRAP expression were prone to radiation‐induced liver injury and poor tumour response to radiotherapy.

Conclusions

Collectively, irradiation up‐regulates ALKBH5 in HSC to mediate monocyte recruitment and M2 polarisation and form positive feedback to promote RILF and reduce HCC radiosensitivity. The dual roles of ALKBH5 as a microenvironmental regulator and radiosensitisation target provide new ideas for RILF prevention and radiosensitisation of HCC.
Underlying geology and climate interactively shape climate change refugia in mountain streams
Authors: Ishiyama Nobuo , Sueyoshi Masanao , García Molinos Jorge , Iwasaki Kenta , Negishi Junjiro N. , Koizumi Itsuro , Nagayama Shigeya , Nagasaka Akiko , Nagasaka Yu , Nakamura Futoshi
Published: February 2023

Identifying climate‐change refugia is a key adaptation strategy for reducing global warming impacts. Knowledge of the effects of underlying geology on thermal regime along climate gradients and the ecological responses to the geology‐controlled thermal regime is essential to plan appropriate climate adaptation strategies. In the present study, the dominance of volcanic rocks in the watershed is used as a landscape‐scale surrogate for cold groundwater inputs to clarify the importance of underlying geology in stream ecosystems along climate gradients. First, using hundreds of monitoring stations distributed across multiple catchments, we explored the relationship between watershed geology and the mean summer water temperature of mountain streams along climate gradients in the Japanese archipelago. Mean summer water temperature was explained by the interaction between the watershed geology and climate in addition to independent effects. The cooling effect supported by volcanic rocks reached up to 3.3°C among study regions, which was more pronounced in streams with less summer precipitation or lower air temperatures. Next, we examined the function of volcanic streams as cold refugia under contemporary and future climatic conditions. Community composition analyses revealed that volcanic streams hosted distinct stream communities composed of more cold‐water species compared with nonvolcanic streams. Scenario analyses based on multiple global climate models and Representative Concentration Pathways (RCPs) revealed a geology‐related pattern of thermal habitat loss for cold‐water species. Nonvolcanic streams rapidly declined in thermally suitable habitats for lotic sculpins even under the lowest emission scenario (RCP 2.6). In contrast, most volcanic streams will be sustained below the thermal threshold, especially for low‐ and mid‐level emission scenarios (RCP 2.6, 4.5). However, the distinct stream community in volcanic streams and geology‐dependent habitat loss for lotic sculpins was not uniform and were more pronounced in streams with less summer precipitation or lower air temperatures. These findings highlight that underlying geology, climate variability, and their interaction should be considered simultaneously for the effective management of climate‐change refugia in mountain streams.