bluuebunny/crossref_metadata_2025 huggingface dataset:
Significant Incidental Findings in the National Lung Screening Trial
Authors: Gareen Ilana F. , Gutman Roee , Sicks JoRean , Tailor Tina D. , Hoffman Richard M. , Trivedi Amal N. , Flores Efren , Underwood Ellen , Cochancela Jerson , Chiles Caroline
Published: May 2023

Importance

Low-dose computed tomography (LDCT) lung screening has been shown to reduce lung cancer mortality. Significant incidental findings (SIFs) have been widely reported in patients undergoing LDCT lung screening. However, the exact nature of these SIF findings has not been described.

Objective

To describe SIFs reported in the LDCT arm of the National Lung Screening Trial and classify SIFs as reportable or not reportable to the referring clinician (RC) using the American College of Radiology’s white papers on incidental findings.

Design, Setting, and Participants

This was a retrospective case series study of 26 455 participants in the National Lung Screening Trial who underwent at least 1 screening examination with LDCT. The trial was conducted from 2002 to 2009, and data were collected at 33 US academic medical centers.

Main Outcomes and Measures

Significant incident findings were defined as a final diagnosis of a negative screen result with significant abnormalities that were not suspicious for lung cancer or a positive screen result with emphysema, significant cardiovascular abnormality, or significant abnormality above or below the diaphragm.

Results

Of 26 455 participants, 10 833 (41.0%) were women, the mean (SD) age was 61.4 (5.0) years, and there were 1179 (4.5%) Black, 470 (1.8%) Hispanic/Latino, and 24 123 (91.2%) White individuals. Participants were scheduled to undergo 3 screenings during the course of the trial; the present study included 75 126 LDCT screening examinations performed for 26 455 participants. A SIF was reported for 8954 (33.8%) of 26 455 participants who were screened with LDCT. Of screening tests with a SIF detected, 12 228 (89.1%) had a SIF considered reportable to the RC, with a higher proportion of reportable SIFs among those with a positive screen result for lung cancer (7632 [94.1%]) compared with those with a negative screen result (4596 [81.8%]). The most common SIFs reported included emphysema (8677 [43.0%] of 20 156 SIFs reported), coronary artery calcium (2432 [12.1%]), and masses or suspicious lesions (1493 [7.4%]). Masses included kidney (647 [3.2%]), liver (420 [2.1%]), adrenal (265 [1.3%]), and breast (161 [0.8%]) abnormalities. Classification was based on free-text comments; 2205 of 13 299 comments (16.6%) could not be classified. The hierarchical reporting of final diagnosis in NLST may have been associated with an overestimate of severe emphysema in participants with a positive screen result for lung cancer.

Conclusions and Relevance

This case series study found that SIFs were commonly reported in the LDCT arm of the National Lung Screening Trial, and most of these SIFs were considered reportable to the RC and likely to require follow-up. Future screening trials should standardize SIF reporting.
Perspectives of Rare Disease Experts on Newborn Genome Sequencing
Authors: Gold Nina B. , Adelson Sophia M. , Shah Nidhi , Williams Shardae , Bick Sarah L. , Zoltick Emilie S. , Gold Jessica I. , Strong Alanna , Ganetzky Rebecca , Roberts Amy E. , Walker Melissa , Holtz Alexander M. , Sankaran Vijay G. , Delmonte Ottavia , Tan Weizhen , Holm Ingrid A. , Thiagarajah Jay R. , Kamihara Junne , Comander Jason , Place Emily , Wiggs Janey , Green Robert C.
Published: May 2023

Importance

Newborn genome sequencing (NBSeq) can detect infants at risk for treatable disorders currently undetected by conventional newborn screening. Despite broad stakeholder support for NBSeq, the perspectives of rare disease experts regarding which diseases should be screened have not been ascertained.

Objective

To query rare disease experts about their perspectives on NBSeq and which gene-disease pairs they consider appropriate to evaluate in apparently healthy newborns.

Design, Setting, and Participants

This survey study, designed between November 2, 2021, and February 11, 2022, assessed experts’ perspectives on 6 statements related to NBSeq. Experts were also asked to indicate whether they would recommend including each of 649 gene-disease pairs associated with potentially treatable conditions in NBSeq. The survey was administered between February 11 and September 23, 2022, to 386 experts, including all 144 directors of accredited medical and laboratory genetics training programs in the US.

Exposures

Expert perspectives on newborn screening using genome sequencing.

Main Outcomes and Measures

The proportion of experts indicating agreement or disagreement with each survey statement and those who selected inclusion of each gene-disease pair were tabulated. Exploratory analyses of responses by gender and age were conducted using t and χ2 tests.

Results

Of 386 experts invited, 238 (61.7%) responded (mean [SD] age, 52.6 [12.8] years [range 27-93 years]; 126 [52.9%] women and 112 [47.1%] men). Among the experts who responded, 161 (87.9%) agreed that NBSeq for monogenic treatable disorders should be made available to all newborns; 107 (58.5%) agreed that NBSeq should include genes associated with treatable disorders, even if those conditions were low penetrance; 68 (37.2%) agreed that actionable adult-onset conditions should be sequenced in newborns to facilitate cascade testing in parents, and 51 (27.9%) agreed that NBSeq should include screening for conditions with no established therapies or management guidelines. The following 25 genes were recommended by 85% or more of the experts: OTC, G6PC, SLC37A4, CYP11B1, ARSB, F8, F9, SLC2A1, CYP17A1, RB1, IDS, GUSB, DMD, GLUD1, CYP11A1, GALNS, CPS1, PLPBP, ALDH7A1, SLC26A3, SLC25A15, SMPD1, GATM, SLC7A7, and NAGS. Including these, 42 gene-disease pairs were endorsed by at least 80% of experts, and 432 genes were endorsed by at least 50% of experts.

Conclusions and Relevance

In this survey study, rare disease experts broadly supported NBSeq for treatable conditions and demonstrated substantial concordance regarding the inclusion of a specific subset of genes in NBSeq.
Insights into Phase Evolution and Mechanical Behavior of the Eutectoid Ti–6.4(wt%)Ni Alloy Modified with Fe and Cr
Authors: Pfaffinger Verena , Staufer Ella , Edtmaier Christian , Arnoldt Aurel , Schmitz-Niederau Martin , Horky Jelena , Klein Thomas
Published: May 2023

Titanium alloys gain increasing importance in industry due to the expansion of advanced manufacturing technologies such as additive manufacturing. Conventional titanium alloys processed by such technologies suffer from formation of large primary grains and anisotropy of mechanical properties. Therefore, novel alloys are required. Herein, the effect of ternary alloying elements Fe and Cr on the Ti–6.4(wt%)Ni eutectoid system is investigated. Both elements act as eutectoid formers. Fe and Cr show sluggish transformation behavior, whereas Ni is an active eutectoid‐forming element. Thereby, sluggish refers to slow and active to fast transformation kinetics. The focus of this work is on the combined addition of such elements studied under different heat‐treatment conditions. It is shown in the results that largely varying microstructures can be generated resulting in hardness values ranging from 239 to 556 HV0.1. Moreover, the formation of a substructure within the α phase of direct aged alloys is observed. The formation mechanism of this substructure is investigated in detail. The mechanical properties are discussed based on the microstructural characteristics. The presence of intermetallic Ti2Ni phase increases the Young's modulus, whereas the presence of ω phase results in embrittlement. The results shed light upon the complex phase formation and decomposition behavior of titanium alloys based on Ti–6.4Ni.
Design, Preparation, and Mechanical Property Investigation of Ti–Ta 3D‐Auxetic Structure by Laser Powder Bed Fusion
Authors: Gao Mu , He Dingyong , Wu Xu , Tan Zhen , Guo Xingye
Published: May 2023

In recent years, Ti–Ta alloy has become a hot material in orthopedic implants. At the same time, the metal lattice structure with a negative Poisson's ratio has a great prospect in the application of implants due to its unique mechanical properties. Herein, an antichiral three‐dimensional polyhedron (A3P) lattice structure with negative Poisson's ratio is designed. This lattice structure is prepared by laser powder bed fusion (LPBF) technology using Ti–Ta alloy as the feedstock material. The surface morphology and relative density of the Ti–Ta samples built with different laser scanning speeds are compared for the optimization of the Ti–Ta's LPBF parameter. Then, the A3P structure of the Ti–Ta alloy is fabricated using the optimized LPBF parameters. The negative Poisson's ratio effect of the A3P structure is verified by finite element analysis (FEA) and compared with experimental results. The compression test results show that the yield strength and elastic modulus of the A3P structure are 9.2 MPa and 0.14 GPa, respectively, which is suitable for the orthopedics application. A3P structure has higher fracture energy compared with diamond structure, indicating it can absorb more energy in the fracture process. A3P shows a promising prospect in the application of orthopedics implantation.
In Situ Growth of Imine‐Bridged Anion‐Selective COF/AAO Membrane for Ion Current Rectification and Nanofluidic Osmotic Energy Conversion
Authors: Chen Mengyuan , Yang Kun , Wang Jin , Sun Hanjun , Xia Xing‐Hua , Wang Chen
Published: May 2023

Facing the energy crisis, using the salinity gradient between seawater and freshwater for osmotic energy conversion is a direct way to obtain energy. So far, most nanofluidic membranes utilized for osmotic energy generation are cation‐selective. Given that both anion‐ and cation‐selective membranes have the identical importance for energy conversion devices, it is of great significance to develop anion‐selective membranes. Herein, an anion‐selective membrane is synthesized by in situ growth of imine‐bridged covalent organic framework (COF) on ordered anodic aluminum oxide (AAO) at room temperature. The imine groups and residual amino groups of COF can combine with protons in neutral solution, enabling the COF positively charged and efficiently transport of anions. Particularly, due to the asymmetry in the charge and structure of COF/AAO, the as‐prepared membrane exhibits excellent ionic current rectification property, which can inhibit ion concentration polarization effectively and possess high ion selectivity and permeability. Using the present COF/AAO membrane, salinity gradient energy can be successfully harvested from solutions with high salt content, and the output power density reached 17.95W m−2 under a 500‐fold salinity gradient. The study provides a new avenue for construction and application of anion‐selective membranes in the smart ion transport and efficient energy conversion.
Biomimetic Antithrombotic Tissue‐Engineered Vascular Grafts for Converting Cholesterol and Free Radicals into Nitric Oxide
Authors: Yang Dongcheng , Li Yanzhao , Tan Ju , Li Wenya , Xu Zilu , Xu Jianhua , Xu Wenhui , Hou Chunli , Zhou Jingting , Li Gang , Yang Mingcan , Liu Yong , Tang Qiaorui , Zhang Xiaohan , Zeng Wen , Feng Xuli , Zhu Chuhong
Published: May 2023

Small‐diameter tissue‐engineered vascular grafts (sdTEVGs) are essential materials used in bypass or replacement surgery for cardiovascular diseases; however, their application efficacy is limited because of patency rates, especially under hyperlipidemia, which is also clinically observed in patients with cardiovascular diseases. In such cases, improving sdTEVG patency is challenging because cholesterol crystals easily cause thrombosis and impede endothelialization. Herein, the development of a biomimetic antithrombotic sdTEVG incorporating cholesterol oxidase and arginine into biomineralized collagen–gold hydrogels on a sdTEVG surface is described. Biomimetic antithrombotic sdTEVGs represent a multifunctional substrate for the green utilization of hazardous substances and can convert cholesterol into hydrogen peroxide, which can react with arginine to generate nitric oxide (NO). NO is a vasodilator that can simulate the antithrombotic action of endothelial cells under hyperlipidemic conditions. In vivo studies show that sdTEVGs can rapidly produce large amounts of NO via a cholesterol catalytic cascade to inhibit platelet aggregation, thereby improving the blood flow velocity and patency rates 60 days after sdTEVG transplantation. A practical and reliable strategy for transforming “harmful” substances into “beneficial” factors at early transplantation stages is presented, which can also promote vascular transplantation in patients with hyperlipidemia.
Multiscale Anisotropic Scaffold Integrating 3D Printing and Electrospinning Techniques as a Heart‐on‐a‐Chip Platform for Evaluating Drug‐Induced Cardiotoxicity
Authors: Liu Sitian , Wang Zihan , Chen Xinyi , Han Mingying , Xu Jie , Li Ting , Yu Liu , Qin Maoyu , Long Meng , Li Mingchuan , Zhang Hongwu , Li Yanbing , Wang Ling , Huang Wenhua , Wu Yaobin
Published: May 2023

Cardiac safety assessments are significant in drug discovery, as drug‐induced cardiotoxicity (DIC) is the primary cause of drug attrition. Despite heart‐on‐a‐chip (HoC) technology becoming an increasingly popular tool for evaluating DIC, its development remains a challenge owing to the anisotropic cardiac structure of the native myocardium. Herein, an anisotropic multiscale cardiac scaffold is presented via a hybrid biofabrication method by combining 3D printing with electrospinning technology, where the 3D‐printed micrometer‐scale scaffold frames enable mimicking the interwoven myocardium anatomical structure and the branched‐aligned electrospun nanofibers network is able to directionally guide cellular arrangements. The in vitro 3D bioengineered cardiac tissues are then fabricated by encapsulating three‐layer multiscale scaffolds within a photocurable methacrylated gelatin hydrogel shell. It is demonstrated that such an anisotropic multiscale structure could contribute to enhancing cardiomyocyte maturation and synchronous beating behavior. More attractively, with the integration of 3D bioengineered cardiac tissues and a self‐designed microfluidic perfusion system, a 3D anisotropic HoC platform is established for evaluating DIC and cardioprotective efficacy. Collectively, these results indicate that the HoC model developed by integrating the 3D bioengineered cardiac tissues could effectively recapitulate the clinical manifestations, thereby highlighting their efficacy as a valuable preclinical platform for testing drug efficacy and cardiotoxicity.
Enhancing Prosthetic Control through High‐Fidelity Myoelectric Mapping with Molecular Anchoring Technology
Authors: Pan Liang , Wang Hui , Huang Pingao , Wu Xuwei , Tang Zihan , Jiang Ying , Ji Shaobo , Cao Jinwei , Ji Baohua , Li Guanglin , Li Dechang , Wang Zhiming , Chen Xiaodong
Published: May 2023

Myoelectric control utilizes electrical signals generated from the voluntary contraction of remaining muscles in an amputee's stump to operate a prosthesis. Precise and agile control requires low‐level myoelectric signals (below 10% of maximum voluntary contraction, MVC) from weak muscle contractions such as phantom finger or wrist movements, but imbalanced calcium concentration in atrophic skin can distort the signals. This is due to poor ionic–electronic coupling between skin and electrode, which often causes excessive muscle contraction, fatigue, and discomfort during delicate tasks. To overcome this challenge, a new strategy called molecular anchoring is developed to drive hydrophobic molecular effectively interact with and embed into stratum corneum for high coupling regions between ionic fluxes and electronic currents. The use of hydrophobic poly(N‐vinyl caprolactam) gel has resulted in an interface impedance of 20 kΩ, which is 1/100 of a commercial acrylic‐based electrode, allowing the detection of ultralow myoelectric signals (≈1.5% MVC) that approach human limits. With this molecular anchoring technology, amputees operate a prosthesis with greater dexterity, as phantom finger and wrist movements are predicted with 97.6% accuracy. This strategy provides the potential for a comfortable human–machine interface when amputees accomplish day‐to‐day tasks through precise and dexterous myoelectric control.
Catalyst Development for High‐Temperature Polymer Electrolyte Membrane Fuel Cell (HT‐PEMFC) Applications
Authors: Seselj Nedjeljko , Alfaro Silvia M. , Bompolaki Eftychia , Cleemann Lars N. , Torres Tomas , Azizi Kobra
Published: May 2023

A constant increase in global emission standard is causing fuel cell (FC) technology to gain importance. Over the last two decades, a great deal of research has been focused on developing more active catalysts to boost the performance of high‐temperature polymer electrolyte membrane fuel cells (HT‐PEMFC), as well as their durability. Due to material degradation at high‐temperature conditions, catalyst design becomes challenging. Two main approaches are suggested: (i) alloying platinum (Pt) with low‐cost transition metals to reduce Pt usage, and (ii) developing novel catalyst support that anchor metal particles more efficiently while inhibiting corrosion phenomena. In this comprehensive review, the most recent platinum group metal (PGM) and platinum group metal free (PGM‐free) catalyst development is detailed, as well as the development of alternative carbon (C) supports for HT‐PEMFCs.
Hiltonol, a dsRNA Mimic, Promotes NK Cell Anticancer Cytotoxicity Through TAZ Cytoplasmic Sequestration
Authors: Wong Darren Chen Pei , Xia Zekun , Shao Nandi , Yow Ivan , Thivakar T. , Yeo Jin Ye , Salazar Andres M. , Liou Yih‐Cherng , Low Boon Chuan , Ding Jeak Ling
Published: May 2023

The evolutionarily conserved YAP/TAZ mechanoresponsive transcription cofactors regulate development and tumorigenesis. Here, it is shown for the first time that human natural killer (NK) cells specifically express TAZ but not YAP, and TAZ serves to limit NK cytotoxicity. The synthetic double‐stranded RNA, hiltonol, is able to trigger cytoplasmic compartmentalization of TAZ, which increases NK cytotoxicity. Mechanistically, a low dose of hiltonol enhances the actin‐based intracellular contractility of NK cells accompanied by an increase in active RhoA and myosin light chain phosphorylation, conceivably through an increase in ERK1/2 activation‐dependent ROS production. Importantly, it is showed that the dissociation of LATS1 from actin upon activation of contractility is associated with TAZ cytoplasmic localization. Functionally, hiltonol also reduces the NK cell surface inhibitory receptors, e.g., KIR3DL1, through c‐Myc inhibition. Direct inhibition of c‐Myc promotes NK cytotoxicity against K562 lymphoblast. The findings are corroborated by coculturing hiltonol‐pretreated NK cells with breast and lung cancer cells, and increased NK‐mediated cancer killing is demonstrated, which conceivably occurs via compartmentalization of TAZ to the cytoplasm which facilitates NK cytotoxicity. The findings pave the way for ex vivo rejuvenation of NK cells for in vivo immunotherapies, which can involve a cocktail of low dose hiltonol and c‐Myc inhibitor.
Machine Learning‐Enabled Virtual Screening with Multiple Protein Structures toward the Discovery of Novel JAK3 Inhibitors: Integration of Molecular Docking, Pharmacophore, and Naïve Bayesian Classification
Authors: Zhu Jingyu , Sun Jingyu , Jia Lei , Xu Lei , Cai Yanfei , Chen Yun , Jin Jian
Published: May 2023

Extensive research has accumulated suggesting that Janus kinase 3 (JAK3) is closely related to the occurrence and development of various human diseases, making JAK3 a highly potential drug target. However, JAK3 has high homology with other members of the JAK family, making the development of JAK3 inhibitors full of challenges. Thus, here, a naïve Bayesian classification (NBC) model based on multiple JAK3 protein conformations, which integrates molecular docking, pharmacophore, and molecular descriptors, is developed to find novel JAK3 inhibitors. First, the validation set is used to prove whether molecular docking or pharmacophore, integrating multiple JAK3 conformations always has higher prediction accuracy than that of any single conformation. Second, external prediction reveals that the NBC model combining molecular docking, pharmacophore, and important molecular features could significantly improve the enrichment of active JAK3 inhibitors. Finally, the optimal NBC model is utilized for virtual screening against a large chemical database and some compounds with high Bayesian scores are identified. Altogether, the machine learning‐based virtual screening protocol not only has strong efficiency but also has high screening accuracy. It is hoped that the developed virtual screening strategy could provide valuable guidance for the discovery of novel JAK3 inhibitors.
Kinetics of cellular and humoral immunogenicity and effectiveness of SARS‐CoV‐2 booster vaccination in hematologic neoplasms
Authors: Jiménez Moraima , Fernández‐Naval Candela , Navarro Víctor , Novoa Sandra , Martinez‐Gallo Mónica , Medina Daniel , Andrés Cristina , Antón Andrés , Peralta Soraya , Pujadas Gemma , Hernández Cristina , Pagès Carlota , Roldán Elisa , Pumarola Tomás , Gironella Mercedes , Ruiz‐Camps Isabel , Martínez‐Gómez Xavier , Valcárcel David , Hernández Manuel , Bosch Francesc , Crespo Marta , Esperalba Juliana , Abrisqueta Pau
Published: May 2023

Data on the effect of booster SARS‐CoV‐2 vaccination are mainly focused on humoral immunogenicity, while the kinetics of vaccine‐induced cellular response and its correlation with effectiveness in hematologic patients are less explored. Our aim was to evaluate the longitudinal cellular and humoral immunogenicity induced by two and three doses of the mRNA‐1273 SARS‐CoV‐2 vaccine in 270 patients with hematologic malignancies, and its relationship with the severity of breakthrough SARS‐CoV‐2 infection. Results indicate that at 23 weeks after the second dose, the seroconversion rate declined from 68.5% to 59.3%, with a reduction in median anti‐S titers from 1577 to 456 BAU/mL, mainly in patients over 65 years of age or chronic lymphocytic leukemia (CLL) patients undergoing active therapy. Cellular immunogenicity, however, remained positive in 84.4% of cases. A third vaccine dose seroconverted 42.7% (41/96) and triggered cellular response in 36.7% (11/30) of previously negative patients. Notably, only 7.2% (15/209) of patients failed to develop both humoral and cellular response. Active therapy, anti‐CD20 antibodies, lymphopenia, hypogammaglobulinemia, and low CD19+ cell count were associated with poor humoral response, while active disease, GvHD immunosuppressive therapy, lymphopenia, and low CD3+, CD4+, CD56+ cell count determined an impaired cellular response. After 13.8 months of follow‐up, the incidence of SARS‐CoV‐2 infection was 24.8% (67/270), including 6 (9%) severe/critical cases associated with a weaker cellular (median interferon gamma (IFN‐γ) 0.19 vs. 0.35 IU/mL) and humoral response (median anti‐S titer <4.81 vs. 788 BAU/mL) than asymptomatic/mild cases. In conclusion, SARS‐CoV‐2 booster vaccination improves humoral response and COVID‐19 severity is associated with impaired vaccine‐induced immunogenicity.
Humanization for neurological disease modeling: A roadmap to increase the potential of Drosophila model systems
Authors: Katanaev Vladimir L.
Published: May 2023

Neuroscience and neurology research is dominated by experimentation with rodents. Around 75% of neurology disease‐associated genes have orthologs in Drosophila melanogaster, the fruit fly amenable to complex neurological and behavioral investigations. However, non‐vertebrate models including Drosophila have so far been unable to significantly replace mice and rats in this field of studies. One reason for this situation is the predominance of gene overexpression (and gene loss‐of‐function) methodologies used when establishing a Drosophila model of a given neurological disease, a strategy that does not recapitulate accurately enough the genetic disease conditions. I argue here the need for a systematic humanization approach, whereby the Drosophila orthologs of human disease genes are replaced with the human sequences. This approach will identify the list of diseases and the underlying genes that can be adequately modeled in the fruit fly. I discuss the neurological disease genes to which this systematic humanization approach should be applied and provide an example of such an application, and consider its importance for subsequent disease modeling and drug discovery in Drosophila. I argue that this paradigm will not only advance our understanding of the molecular etiology of a number of neurological disorders, but will also gradually enable researchers to reduce experimentation using rodent models of multiple neurological diseases and eventually replace these models.
Investigation of selective retinoic acid receptor alpha antagonist ER‐50891 and related analogs for male contraception
Authors: Kyzer Jillian L. , Noman Md Abdullah Al , Cuellar Rebecca A. D. , Chung Sanny S. W. , Maitra Soma , Naqvi Tahmina , Hawkinson Jon E. , Wolgemuth Debra J. , Georg Gunda I.
Published: May 2023

Retinoic acid receptor alpha (RARα) antagonist ER‐50891 and 15 analogs were prepared and tested in vitro for potency and selectivity at RARα, RARβ, and RARγ using transactivation assays. Minor modifications to the parent molecule such as the introduction of a C4 tolyl group in place of the C4 phenyl group on the quinoline moiety slightly increased the RARα selectivity but larger substituents significantly decreased the potency. Replacement of the pyrrole moiety of ER‐50891 with triazole, amides, or a double bond produced inactive compounds. ER‐50891 was found to be stable in male mouse liver microsomes and was tested in male mice to assess its effects on spermatogenesis. Characteristic, albeit modest and transient, effects on spermatogenesis were observed.
Synthesis and Antifungal Activity of Curcumol Derivatives
Authors: Gao Fu‐Tian , Jin Jun , Jian Jun‐You , Chen Liang , Gu Wei , Yuan Chun‐Mao , Hao Xiao‐Jiang , Huang Lie‐Jun
Published: May 2023

To discover novel and effective antifungal candidates, a series of new curcumol derivatives were designed, synthesized, and evaluated their antifungal activity against five phytopathogenic fungi by the mycelium growth rate method. Derivatives c4, c22 and c23 exhibited excellent antifungal activity against Phomopsis sp. with EC50 values of 3.06, 3.07, and 3.16 μM, respectively. Specifically, compound c4 exhibited the strongest antifungal activity against Phomopsis sp., which was 44 times that of pyrimethanil (EC50=134.37 μM). The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicated that compound c4 could cause cell senescence and death of Phomopsis sp. by changing the normal hyphal morphology and disrupting the normal metabolism of hyphal cells. Moreover, compound c4 showed excellent curative effect against Phomopsis sp. on kiwifruit. These findings confirmed that compound c4 has great potential as a potent antifungal agent.
Advances in immune response to pulmonary infection: Nonspecificity, specificity and memory
Authors: Xu Jianqiao , Xie Lixin
Published: May 2023

The lung immune response consists of various cells involved in both innate and adaptive immune processes. Innate immunity participates in immune resistance in a nonspecific manner, whereas adaptive immunity effectively eliminates pathogens through specific recognition. It was previously believed that adaptive immune memory plays a leading role during secondary infections; however, innate immunity is also involved in immune memory. Trained immunity refers to the long‐term functional reprogramming of innate immune cells caused by the first infection, which alters the immune response during the second challenge. Tissue resilience limits the tissue damage caused by infection by controlling excessive inflammation and promoting tissue repair. In this review, we summarize the impact of host immunity on the pathophysiological processes of pulmonary infections and discuss the latest progress in this regard. In addition to the factors influencing pathogenic microorganisms, we emphasize the importance of the host response.
Y‐Shaped D‐A Type Thioxanthone Derivatives: Mechano‐Induced Thermally Activated Delayed Fluorescence and High‐Contrast Mechano‐Responsive Luminescence
Authors: Mu Yingxiao , Liao Liyun , Li Wenlang , Yang Zhiyong , Zhang Yi , Huo Yanping , Chi Zhenguo
Published: May 2023

High‐contrast mechano‐responsive luminescence (MRL) materials with mechano‐induced emission enhancement properties are fascinating candidates but few, for applications in rewritable media and recording devices. Here, an interesting design strategy of “Y‐shape” donor‐acceptor (D−A) type molecules for high‐contrast MRL materials was presented, based on substituted diphenylamine donor and planar acceptor. Interestingly, their D−A torsion angles are small in crystals but increased after ground, resulted in planar and twist intramolecular charge transfer (PICT and TICT) states, respectively. Therefore, high‐contrast MRL switching between weak blue (450 nm) fluorescence and bright yellow (552 nm) thermally activated delayed fluorescence (TADF) can be achieved for compound TXDO (4,4′‐dimethoxydiphenylamine donor), which photoluminescence quantum yield increased from 2.8 % to 54.7 % after ground. Most importantly, the two independent D−A conjugation dihedral angles are actually independent in the “Y‐shape” molecules. Especially for compound TXDT (4,4′‐di‐tert‐butyldiphenylamine donor), its crystal exhibited both PICT and TICT processes inside, resulted from the different dihedral angles of 11.8° and 35.5°, respectively. The TXDT crystal thus showed dual‐peak emission, including both TICT fluorescence and PICT room‐temperature phosphorescence. Therefore, this strategy of “Y‐shape” D−A type molecules provide a new approach to design advanced luminescent materials with mechano‐induced TADF feature, for high‐contrast MRL and single‐component white luminescence.
Cooperatively Catalyzed Activation of Thioglycosides That Bypasses Intermediacy of Glycosyl Halides
Authors: Dent Ashley , Escopy Samira , Demchenko Alexei V.
Published: May 2023

Reported herein is the development of a novel method for activating thioglycosides without a glycosyl halide intermediate. This has been achieved through the use of a silver salt coupled with an acid additive and molecular iodine. The enhanced stereocontrol was achieved via the H‐bond mediated aglycone delivery (HAD) method, and the extended trisaccharide synthesis was achieved via iteration of deprotection and glycosylation steps.
Polymer‐Stabilized Liquid Crystal Films Containing Dithienyldicyanoethene‐Based Chiral Photoswitch: Multi‐Modulation for Environment‐Adaptative Smart Windows
Authors: Lin Siyang , Zhang Yiyu , Guo Dekang , Song Chunfeng , Guo Jinbao
Published: May 2023

A polymer‐stabilized liquid crystal (PSLC)‐based environment‐adaptative smart window with multi‐modulations is demonstrated. This PSLC system contains a right‐handed dithienyldicyanoethene‐based chiral photoswitch and a chiral dopant, S811, with opposite handedness, of which the reversible cis‐trans photoisomerization of the switch can drive self‐shading of the smart window under UV light stimulus because of the transition from nematic phase to cholesteric one. With the assistance of solar heat, the opacity of the smart window can be deepened because the heat promotes the isomerization conversion rate of the switch. This switch has no thermal relaxation at room temperature, therefore, the smart window exhibits dual stabilization: transparent state (cis‐isomer) and opaque state (trans‐isomer). Moreover, the incident intensity of sunlight can be regulated by an electric field, which allows the smart window to adapt to some specific situations. Such an energy‐saving device can be used in buildings and vehicles to control indoor temperature and adapt to the required ambiance.
Metal‐Free Electrocatalysts for the Selective 2 e−Oxygen Reduction Reaction: A Never‐Ending Story?
Authors: Tuci Giulia , Rossin Andrea , Zhang Xiong , Truong‐Phuoc Lai , Berretti Enrico , Liu Yuefeng , Pham‐Huu Cuong , Ali Sajjad , Jan Faheem , Poggini Lorenzo , Giambastiani Giuliano
Published: May 2023

Hydrogen peroxide (H2O2) electrosynthesis via the 2e−Oxygen Reduction Reaction (ORR) represents a highly challenging, environmentally friendly and cost‐effective alternative to the current anthraquinone‐based technology. Various lightweight element hetero‐doped carbon nanostructures are promising and cheap metal‐free electrocatalysts for H2O2synthesis, particularly those containing O‐functionalities. The exact role of O‐containing functional groups as electroactive sites for the process remains debated if not highly controversial. Herein, we have reported on the covalent exohedral functionalization of the outer surface of extra‐pure multi‐walled carbon nanotubes (MWCNTs) with discrete O‐functional groups as a unique approach to prepare selective electrocatalysts for the process. This kind of decoration has added fundamental tiles to the puzzling structure/reactivity relationship of O‐containing carbon‐based catalysts for ORR, clearing doubts on the controversial role of hydroxyl/phenol groups as key functionalities for the design of more performing 2e−ORR electrocatalysts.
Thienoindolizines and their Benzo‐Fused Derivatives: Synthesis and Physical Properties
Authors: Ausekle Elina , Ehlers Peter , Villinger Alexander , Argüello Cordero Miguel Andre , Lochbrunner Stefan , Langer Peter
Published: May 2023

A series of thienoindolizine structural isomers have been synthesized in a one‐pot, two‐step procedure starting from easily accessible gem‐difluoroalkene functionalized bromothiophenes. The developed method gives easy access to a range of thienoindolizine products containing thieno[3,2‐g]‐, thieno[3,4‐g]‐ and thieno[2,3‐g]indolizine core structures. The described synthesis strategy consists of a base mediated, transition metal free nucleophilic substitution of fluorine atoms by nitrogen containing heterocycles followed by a Pd catalyzed intramolecular cyclization. A series of 22 final product examples has been obtained with yields ranging from 29 % to 95 %. UV/Vis absorption, fluorescence spectroscopy, fluorescence lifetime measurements and cyclic voltammetry were carried out with selected final products to evaluate structural effects on photophysical and electrochemical properties. (TD)DFT and NICS calculations were performed to provide insight into the electronic properties of the four core molecular structures.
Tf2O‐Catalyzed Tandem Cyclization/Trifluoromethylselenolation of Alkynes for Synthesis of CF3Se‐Containing Heterocycles
Authors: Zhang Shangbiao , Gao Yan , Xiao Rui , Li Yang , Wang Yanan , Yuan Zheliang
Published: May 2023

Herein, the tandem synthesis of various CF3Se‐containing heterocyclic compounds has been developed, using Tf2O as the catalyst and trifluoromethyl selenoxides as the electrophilic trifluoromethylselenolation reagents. This process is characterized by its mild conditions, ease of operation, and good functional group compatibility. A variety of alkynes could be transferred into CF3Se‐containing indoles, benzofurans, benzothiophenes, isoquinolines and chromenes in good yields. A key step involving the formation of the electrophilic CF3Se species was proposed.
Clinical outcomes of chemotherapy in cancer patients with different ethnicities
Authors: Pathak Suhrud , Zajac Kelsee K. , Annaji Manjusha , Govindarajulu Manoj , Nadar Rishi M. , Bowen Dylan , Babu R. Jayachandra , Dhanasekaran Muralikrishnan
Published: May 2023

Background

Choosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti‐cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.

Recent findings

Pharmacogenomics, the study of how an individual's genes impact the processing and action of a drug, can optimize drug responsiveness and reduce toxicities by creating a customized medication regimen. However, these differences are rarely considered in the initial determination of standardized chemotherapeutic protocols and treatment algorithms. Because pharmacoethnicity is influenced by both genetic and nongenetic variables, clinical data highlighting disparities in the frequency of polymorphisms between different ethnicities is steadily growing.  Recent data suggests that ethnic variations in the expression of allelic variants may result in different pharmacokinetic properties of the anti‐cancer medication. In this article, the clinical outcomes of various chemotherapy classes in patients of different ethnicities were reviewed.

Conclusion

Genetic and nongenetic variables contribute to the interindividual variability in response to chemotherapeutic drugs. Considering pharmacoethnicity in the initial determination of standard chemotherapeutic protocols and treatment algorithms can lead to better clinical outcomes of patients of different ethnicities.
Gelation Mechanism Revealed in Organometallic Gels: Prevalence of van der Waals Interactions on Oligomerization by Coordination Chemistry
Authors: Wang Yinping , Coppel Yannick , Fitremann Juliette , Massou Stéphane , Mingotaud Christophe , Kahn Myrtil L.
Published: May 2023

Shaping of nanomaterials is a necessary step for their inclusion in electronic devices and batteries. For this purpose, the formulation of a moldable material including these nanomaterials is desirable. Organomineral gels are a very interesting option, since the components of the nanomaterial itself form a gel without the help of a binder. As a consequence, the properties of the nanomaterial are not diluted by the binder. In this article we studied organometallic gels based on a [ZnCy2] organometallic precursor and a primary alkyl amine which together forms spontaneously gels after few hours. We identified the main parameters controlling the gel properties monitored by rheology and NMR measurements The experiments demonstrate that the gelation time depends on the length of the alkyl chain of the amine and that the gelation mechanism derived firstly from the rigidification of the aliphatic chains of the amine, which takes precedence over the oligomerization of the inorganic backbone. This result highlights that the control of the rheological properties of organometallic gels remains mainly governed by the choice of the amine.
Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Properties of Rozibafusp Alfa, a Bispecific Inhibitor of BAFF and ICOSL: Analyses of Phase I Clinical Trials
Authors: Abuqayyas Lubna , Chen Po‐Wei , dos Santos Marcia Teixeira , Parnes Jane R. , Doshi Sameer , Dutta Sandeep , Houk Brett E.
Published: May 2023

Rozibafusp alfa (AMG 570) is a first‐in‐class bispecific IgG2‐peptide fusion designed to inhibit inducible T‐cell costimulator ligand (ICOSL) and B‐cell activating factor (BAFF). The pharmacokinetics (PK) and pharmacodynamics (PD) of rozibafusp alfa were investigated in two randomized, placebo‐controlled clinical studies: a phase Ia single ascending‐dose study (7–700 mg subcutaneously (s.c.)) in healthy subjects and a phase Ib multiple ascending‐dose study (70–420 mg s.c. every 2 weeks (q2w)) in patients with rheumatoid arthritis. Rozibafusp alfa exhibited nonlinear PK and dose‐related and reversible dual‐target engagement. Maximal reduction of naïve B cells from baseline (> 40%), reflective of BAFF inhibition, was achieved with rozibafusp alfa exposure (area under the concentration‐time curve from time 0 to time infinity (AUCinf) and AUC within a dosing interval from day 0 to day 14 (AUCtau)) above 51 and 57 days•μg/mL for the single‐dose (≥ 70 mg) and multiple‐dose studies (≥ 70 mg q2w), respectively. ICOSL receptor occupancy on circulating B cells, a surrogate PD end point for ICOSL inhibition, was directly related to drug concentration. PK/PD analysis showed > 90% RO at rozibafusp alfa ≥ 22.2 μg/mL (≥ 420‐mg single dose or ≥ 210 mg q2w multiple dose), with saturation occurring at higher drug concentrations. These results informed the design and dose selection of a phase IIb study assessing the safety and efficacy of rozibafusp alfa in patients with active systemic lupus erythematosus.
Analysis and control of partial power processing nonisolated bidirectional DC‐DC converter
Authors: Hu Wei , Tao Jintong , Ding Zekang , Yang Hong
Published: May 2023

A partial power processing non‐isolated bidirectional DC‐DC converter is proposed, which is composed of non‐isolated bidirectional DC‐DC converter and direct power flow path. Part of the power of the system is transmitted from the power stage to the load through the non‐isolated bidirectional DC‐DC converter, while the other part is transferred via the direct path without processing by the non‐isolated bidirectional DC‐DC converter. This topology not only enhances the energy conversion efficiency but also has the remarkable advantages of high energy density, simple design, small volume, light weight, and low electromagnetic interference. It can be applied in various two‐way energy management scenarios such as photovoltaic, fuel cell, and super capacitor energy storage. The analysis of the operating principle reveals that the converter can realize the increase and decrease of input voltage and the bidirectional flow of current. When the bidirectional DC‐DC converter steps the voltage down, the partial power converter is in the step‐up mode of reverse transmission. As the bidirectional DC‐DC converter is steps input voltage up, the partial power converter is in step‐down mode of forward transmission. The differential equations and mathematical models of each operating mode are established, and the appropriate voltage feedback control strategy is proposed. Finally, a prototype is constructed and experiments verify the analysis.
Nuclear export of BATF2 enhances colorectal cancer proliferation through binding to CRM1
Authors: Zhou Jie , Lei Zengjie , Chen Jianfang , Liao Shengbo , Chen Yanrong , Liu Chengxiang , Huang Shuo , Li Liuli , Zhang Yan , Wang Pei , Huang Yinghui , Li Jianjun , Liang Houjie
Published: May 2023

Background

During the tumourigenesis and development of colorectal cancer (CRC), the inactivation of tumour suppressor genes is closely involved, although detailed molecular mechanisms remain elusive. Accumulating studies, including ours, have demonstrated that basic leucine zipper transcription factor ATF (activating transcription factor)‐like 2 (BATF2) is a capable tumour suppressor that localises in the nucleus. However, its different subcellular localisation, potential functions and underlying mechanisms are unclear.

Methods

The translocation of BATF2 and its clinical relevance were detected using CRC samples, cell lines and xenograft nude mice. Candidate BATF2‐binding proteins were screened using co‐immunoprecipitation, quantitative label‐free liquid chromatography–tandem mass spectrometry proteomic analysis, Western blotting and immunofluorescence. Recombinant plasmids, point mutations and siRNAs were applied to clarify the binding sites between BATF2 and chromosome region maintenance 1 (CRM1).

Results

The present study found that BATF2 was mainly localised in the cytoplasm, rather than nucleus, of CRC cells in vitro and in vivo, while cytoplasmic BATF2 expression was inversely correlated with the prognosis of CRC patients. Furthermore, we identified the nuclear export and subsequent ubiquitin‐mediated degradation of BATF2 in CRC cells. Mechanistically, a functional nuclear export sequence (any amino acid) was characterised in BATF2 protein, through which BATF2 bound to CRM1 and translocated out of nucleus, ultimately enhancing CRC growth via inducing activator protein 1 (AP‐1)/cyclin D1/phosphorylated retinoblastoma protein (pRb) signalling pathway. Additionally, nuclear export of BATF2 can be retarded by the mutation of NES in BATF2 or the knockdown of CRM1, whereas CRM1 expression was negatively associated with nuclear BATF2 expression and the prognosis of CRC patients.

Conclusion

These findings revealed the biological effects and underlying mechanisms of cytoplasmic localisation of BATF2. Furthermore, suppressing nuclear export of BATF2 via mutating its NES region or inhibiting CRM1 expression may serve as a promising therapeutic strategy against CRC.
EUS‐guided FNAC in intra‐abdominal lesions: Technique of tissue acquisition, ancillary testing, pearls and perils, and prospects
Authors: Kundu Reetu , Rana Surinder Singh , Suneel Rachagiri , Dey Pranab
Published: May 2023

Endoscopic ultrasound enables visualization of lesions within and in the vicinity of the gastrointestinal tract. Endoscopic ultrasound guided fine needle aspiration cytology (EUS‐FNAC) helps in targeting various luminal and extraluminal lesions both diagnostically and therapeutically. Various intra‐abdominal organs amenable to EUS‐FNA include the gastrointestinal tract (GIT), pancreas, kidney, adrenal gland, liver, bile duct, gallbladder, spleen, and lymph nodes. EUS‐FNAC is mostly done for pancreatic and intra‐abdominal lymph nodal lesions. In the present review, we have discussed various aspects of EUS‐FNAC.
Toad venom bufadienolides and bufotoxins: An updated review
Authors: Asrorov Akmal M. , Kayumov Muzaffar , Mukhamedov Nurkhodja , Yashinov Ansor , Mirakhmetova Ziyoda , Huang Yongzhuo , Yili Abulimiti , Aisa Haji Akber , Tashmukhamedov Mugrajitdin , Salikhov Shavkat , Mirzaakhmedov Sharafitdin
Published: May 2023

Bufadienolides, naturally found in toad venoms having steroid‐like structures, reveal antiproliferative effects at low doses. However, their application as anticancer drugs is strongly prevented by their Na+/K+‐ATPase binding activities. Although several kinds of research were dedicated to moderating their Na+/K+‐ATPase binding activity, still deeper fundamental knowledge is required to bring these findings into medical practice. In this work, we reviewed data related to anticancer activity of bufadienolides such as bufalin, arenobufagin, bufotalin, gamabufotalin, cinobufotalin, and cinobufagin and their derivatives. Bufotoxins, derivatives of bufadienolides containing polar molecules mainly belonging to argininyl residues, are reviewed as well. The established structures of bufotoxins have been compiled into a one‐page figure to review their structures. We also highlighted advances in the structure‐modification of the structure of compounds in this class. Drug delivery approaches to target these compounds to tumor cells were discussed in one section. The issues related to extraction, identification, and quantification are separated into another section.
Analyses of cytokine gene expression and fecal microbiota in a patient with Cronkhite‐Canada syndrome successfully treated with prednisolone
Authors: Honjo Hajime , Masuta Yasuhiro , Otsuka Yasuo , Masaki Sho , Minaga Kosuke , Kudo Masatoshi , Watanabe Tomohiro
Published: May 2023

Although prednisolone treatment is effective in Cronkhite–Canada syndrome (CCS), its mechanisms of action are poorly understood. We performed analyses of cytokine expression and fecal microbiota in a patient with the concurrent occurrence of CCS and rectal cancer, in whom regression of polyposis was achieved by prednisolone. Regression of CCS polyps was accompanied by downregulation of proinflammatory cytokine expression and alterations in microbiota composition; a decrease in Bacteroides fragilis and Peptostreptococcus anaerobius with the promotion of inflammation. We could not completely exclude the possibility that alterations in fecal microbiota composition might be influenced by the presence of advanced cancer. However, this case suggests that the administration of PSL might lead to the regression of CCS polyps through alterations in gut microbiota composition and suppression of proinflammatory cytokine responses.