bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat Shock Protein-90 Inhibitors Increase MHC Class I-Related Chain A and B Ligand Expression on Multiple Myeloma Cells and Their Ability to Trigger NK Cell Degranulation
Authors: Fionda Cinzia , Soriani Alessandra , Malgarini Giulia , Iannitto Maria Luisa , Santoni Angela , Cippitelli Marco 
Published: September 2009

Abstract
Modulation of the host immune system represents a promising therapeutic approach against cancer, including multiple myeloma. Recent findings indicate that the NK group 2D (NKG2D)- and DNAX accessory molecule-1 (DNAM-1)-activating receptors play a prominent role in tumor recognition and elimination by cytotoxic lymphocytes, suggesting that the levels of NKG2D and DNAM-1 ligand expression on tumor cells may be a critical factor to improve the immune response against cancer. In this study, we tested the effect of 17-allylaminogeldanamycin and radicicol, drugs targeting the heat shock protein-90 (HSP-90) chaperone protein and displaying antimyeloma activity, on the expression of NKG2D and DNAM-1 ligands in human myeloma cell lines. We demonstrate that HSP-90 inhibitors are able to up-regulate both MHC class I chain-related (MIC) A and MICB protein surface and mRNA expression in human myeloma cell lines, without any significant effect on the basal expression of the DNAM-1 ligand poliovirus receptor CD155, or induction of nectin-2 and UL16-binding proteins. Activation of the transcription factor heat shock factor-1 by HSP-90 inhibitors is essential for the up-regulation of MICA/MICB expression and knockdown of heat shock factor-1 using small hairpin RNA interference blocks this effect. Moreover, in vitro and in vivo binding of heat shock factor-1 to MICA and MICB promoters indicates that it may enhance NKG2D ligand expression at the transcriptional level. Finally, exposure to HSP-90 inhibitors renders myeloma cells more efficient to activate NK cell degranulation and a blocking Ab specific for NKG2D significantly reduces this effect. Thus, these results provide evidence that targeting NKG2D ligands expression may be an additional mechanism supporting the antimyeloma activity of HSP-90 inhibitors and suggest their possible immunotherapeutic value.
Applying the Burke–Litwin model as a diagnostic framework for assessing organisational effectiveness
Authors: Martins Nico , Coetzee Melinde 
Published: September 2009

This exploratory study investigated the utility of the Burke–Litwin model as a diagnostic framework for assessing the factors affecting organisational effectiveness. The research setting consisted of an international company, with a population comprising representatives of more than 17 different nationalities. The purposive sampling method was used to involve employee participants (N = 147) in focus groups and executive managers (N = 11) in semi- structured probing interviews. The factors identified related to both the transformational and transactional dimensions of the Burke–Litwin model. The f ndings add to the existing literature on factors causing organisational effectiveness and ineffectiveness in cross-cultural organisational contexts.
Screening for Breast Cancer
Authors: Henderson Jillian T. , Webber Elizabeth M. , Weyrich Meghan S. , Miller Marykate , Melnikow Joy 
Published: April 2024

ImportanceBreast cancer is a leading cause of cancer mortality for US women. Trials have established that screening mammography can reduce mortality risk, but optimal screening ages, intervals, and modalities for population screening guidelines remain unclear.ObjectiveTo review studies comparing different breast cancer screening strategies for the US Preventive Services Task Force.Data SourcesMEDLINE, Cochrane Library through August 22, 2022; literature surveillance through March 2024.Study SelectionEnglish-language publications; randomized clinical trials and nonrandomized studies comparing screening strategies; expanded criteria for screening harms.Data Extraction and SynthesisTwo reviewers independently assessed study eligibility and quality; data extracted from fair- and good-quality studies.Main Outcomes and MeasuresMortality, morbidity, progression to advanced cancer, interval cancers, screening harms.ResultsSeven randomized clinical trials and 13 nonrandomized studies were included; 2 nonrandomized studies reported mortality outcomes. A nonrandomized trial emulation study estimated no mortality difference for screening beyond age 74 years (adjusted hazard ratio, 1.00 [95% CI, 0.83 to 1.19]). Advanced cancer detection did not differ following annual or biennial screening intervals in a nonrandomized study. Three trials compared digital breast tomosynthesis (DBT) mammography screening with digital mammography alone. With DBT, more invasive cancers were detected at the first screening round than with digital mammography, but there were no statistically significant differences in interval cancers (pooled relative risk, 0.87 [95% CI, 0.64-1.17]; 3 studies [n = 130 196]; I2 = 0%). Risk of advanced cancer (stage II or higher) at the subsequent screening round was not statistically significant for DBT vs digital mammography in the individual trials. Limited evidence from trials and nonrandomized studies suggested lower recall rates with DBT. An RCT randomizing individuals with dense breasts to invitations for supplemental screening with magnetic resonance imaging reported reduced interval cancer risk (relative risk, 0.47 [95% CI, 0.29-0.77]) and additional false-positive recalls and biopsy results with the intervention; no longer-term advanced breast cancer incidence or morbidity and mortality outcomes were available. One RCT and 1 nonrandomized study of supplemental ultrasound screening reported additional false-positives and no differences in interval cancers.Conclusions and RelevanceEvidence comparing the effectiveness of different breast cancer screening strategies is inconclusive because key studies have not yet been completed and few studies have reported the stage shift or mortality outcomes necessary to assess relative benefits.
Primary Care Physicians’ Experiences With and Adaptations to Time Constraints
Authors: Nguyen Michelle-Linh T. , Honcharov Vlad , Ballard Dawna , Satterwhite Shannon , McDermott Aoife M. , Sarkar Urmimala 
Published: April 2024

ImportanceThe primary care workforce shortage is significant and persistent, with organizational and policy leaders urgently seeking interventions to enhance retention and recruitment. Time constraints are a valuable focus for action; however, designing effective interventions requires deeper understanding of how time constraints shape employees’ experiences and outcomes of work.ObjectiveTo examine how time constraints affect primary care physicians’ work experiences and careers.Design, Setting, and ParticipantsBetween May 1, 2021, and September 31, 2022, US-based primary care physicians who trained in family or internal medicine were interviewed. Using qualitative analysis of in-depth interviews, this study examined how participants experience and adapt to time constraints during a typical clinic day, taking account of their professional and personal responsibilities. It also incorporates physicians’ reflections on implications for their careers.Main Outcomes and MeasuresThematic analysis of in-depth interviews and a measure of well-being (American Medical Association Mini-Z survey).ResultsInterviews with 25 primary care physicians (14 [56%] female and 11 [44%] male; median [range] age, 43 [34-63] years) practicing in 11 US states were analyzed. Two physicians owned their own practice, whereas the rest worked as employees. The participants represented a wide range of years in practice (range, 1 to ≥21), with 11 participants (44%) in their first 5 years. Physicians described that the structure of their work hours did not match the work that was expected of them. This structural mismatch between time allocation and work expectations created a constant experience of time scarcity. Physicians described having to make tradeoffs between maintaining high-quality patient care and having their work overflow into their personal lives. These experiences led to feelings of guilt, disillusionment, and dissatisfaction. To attempt to sustain long-term careers in primary care, many sought ways to see fewer patients.Conclusions and RelevanceThese findings suggest that organizational leaders must align schedules with work expectations for primary care physicians to mitigate physicians’ withdrawal from work as a coping mechanism. Specific strategies are needed to achieve this realignment, including incorporating more slack into schedules and establishing realistic work expectations for physicians.
Preview controller synthesis for a class of linear parameter periodic systems
Authors: Li Li , Liao Yonglong , Zhang Yaofeng 
Published: April 2024

SummaryIn this study, the problem of preview tracking control (PTC) was considered with regard to the linear parameter periodic systems (LPPSs) subject to previewed signals. First, the difference operator approach was extended to derive an augmented error system (AES). As a result, the PTC problem was transformed into a stabilization problem via state/output feedback. Second, sufficient conditions guaranteeing the closed‐loop stability of the augmented error systems were derived, and the design of a periodic controller with preview actions was proposed through the approach of linear matrix inequalities (LMIs). Finally, a numerical simulation was performed to illustrate the effectiveness of the proposed periodic controller.
The Biological Role of Macrophage in Lung and Its Implications in Lung Cancer Immunotherapy
Authors: Wang Chenyang , Gao Qing , Wu Jinghong , Lu Mingjun , Wang Jinghui , Ma Teng 
Published: April 2024

AbstractThe lungs are the largest surface of the body and the most important organ in the respiratory system, which are constantly exposed to the external environment. Tissue Resident Macrophages in lung constitutes the important defense against external pathogens. Macrophages connects the innate and adaptive immune system, and also plays important roles in carcinogenesis and cancer immunotherapy. Lung cancer is the leading cause of cancer‐related death worldwide, with an overall five‐year survival rate of only 21%. Macrophages that infiltrate or aggregate in lung tumor microenvironment are defined as tumor‐associated macrophages (TAMs). TAMs are the main components of immune cells in the lung tumor microenvironment. The differentiation and maturation process of TAMs can be roughly divided into two different types: classical activation pathway produces M1 tumor‐associated macrophages, and bypass activation pathway produces M2 tumor‐associated macrophages. Studies have found that TAMs are related to tumor invasion, metastasis, and treatment resistance, and show potential as a new target for tumor immunotherapy. Therefore, the biological function of macrophages in lung and the role of TAMs in the occurrence, development, and treatment of lung cancer are discussed in this paper.
Enhanced Silicon Anodes with Robust SEI Formation Enabled by Functional Conductive Binder
Authors: Chen Benqiang , Xu Dongmin , Chai Simin , Chang Zhi , Pan Anqiang 
Published: April 2024

AbstractThe application of silicon (Si) anode is limited by the drastic volume change of silicon in the lithiation/delithiation process, the repeated formation of the solid electrolyte interface (SEI), and the low intrinsic conductivity. In this work, a small amount of poly (3,4‐ethylenedioxythiophene):poly (styrene sulfonic acid) (PEDOT:PSS) (PP), citric acid (CA), isopropyl alcohol (IPA), and silicon nanoparticles (SiNPs) are mixed and vacuum treated at a specific temperature to obtain silicon‐based anode electrode composite Si@PP@CA. The interphase forms a robust elastic network with hydrogen and chemical bonds, which have good mechanical properties and self‐repairing characteristics. The modified PEDOT:PSS as the conductive medium significantly improves the charge transfer rate. Moreover, the rapid formation of SEI by CA on the surface of SiNPs enhances the structural stability of the material. The electrochemical results show that the capacity of Si@PP@CA composite electrode canretain more than 2200 mAh g−1 after 200 cycles at 0.2 A g−1. It still shows a high capacity retention of 89% even at the current density of 1.0 A g−1 after 2000 cycles. More importantly, such excellent performance can be obtained using an electrode with an active material content of up to 90 wt%, which is essential for practical applications.
Femtosecond Laser Maskless Optical Projection Lithography of Cartilage PCM Inspired 3D Protein Matrix to Chondrocyte Phenotype
Authors: Li Teng , Liu Jie , Guo Min , Bin Fan‐Chun , Duan Qi , Dong Xian‐Zi , Jin Feng , Fujita Katsumasa , Zheng Mei‐Ling 
Published: April 2024

AbstractHydrogels containing chondrocytes have exhibited excellent potential in regenerating hyaline cartilage. However, chondrocytes are vulnerable to dedifferentiation during in vitro culture, leading to fibrosis and mechanical degradation of newly formed cartilage. It is proposed to modulate cartilage formation via the developed chondrocyte pericellular matrix (PCM) ‐like scaffolds for the first time, in which the S, M, and L‐sized scaffolds are fabricated by femtosecond laser maskless optical projection lithography (FL‐MOPL) of bovine serum albumin‐glyceryl methacrylate hydrogel. Chondrocytes on the M PCM‐like scaffold can maintain round morphology and synthesize extracellular matrix (ECM) to induce regeneration of hyaline cartilage microtissues by geometrical restriction. A series of M PCM‐like scaffolds is fabricated with different stiffness and those with a high Young's modulus are more effective in maintaining the chondrocyte phenotype. The proposed PCM‐like scaffolds are effective in modulating cartilage formation influenced by pore size, depth, and stiffness, which will pave the way for a better understanding of the geometric cues of mechanotransduction interactions in regulating cell fate and open up new avenues for tissue engineering.
Stretchable Metal Halide Perovskite Color Conversion Layers with Block Copolymer Dispersant
Authors: Cheon Jaehui , Park Jeong‐Min , Son Jeonghyeon , Lee Minsub , Lee Sumin , Park Chanwoo , Kim Hyo Jung , Kim Jae‐Hyuk , Park Jong S. , Jeong Beomjin 
Published: April 2024

AbstractStretchable luminescent nanocomposites with metal halide perovskite (MHP) emitters are in high demand as deformable color‐conversion layers (CCLs) for vivid‐colored form‐factor free displays. However, the immiscibility of the MHP crystals with an elastomeric polymer matrix induces particle aggregation with resultant luminescence quenching, hindering the development of MHP‐based CCLs. Herein, a simple method is proposed to produce highly luminescent MHP nanoparticles (NPs) and stably disperse them in an elastomeric poly(dimethylsiloxane) (PDMS) polymer matrix with block copolymer (BCP) dispersant. The nanocomposites are developed through sequential steps of synthesis of MHP‐NP dispersion solution with BCP and blending with PDMS followed by thermal curing. It is revealed that Lewis basic poly(2‐vinylpyridine)‐block‐poly(dimethylsiloxane) (P2VP‐b‐PDMS) BCP added in the synthesis step promotes crystallization of the MHPs as nanocrystals with an average diameter of 5.9 ± 1.2 nm, whereas MHPs with hundreds of nm are produced without BCP. The resultant MHP‐NPs with P2VP‐b‐PDMS exhibit excellent photophysical properties, such as narrow band emission, high photoluminescence (PL) quantum yield, and long PL lifetime. The MHP‐NPs are stably dispersed in the PDMS matrix by P2VP‐b‐PDMS without particle aggregation, leading to highly deformable and stretchable nanocomposites with stable PL emission upon repetitive stretching, and excellent environmental stability.
Efficacy and Safety of Resveratrol in the Treatment of Bladder Cancer Derived Organoids
Authors: Liu Guang‐Yao , Xiao Kang‐Hua , Li Hong , Chen Xiang , Ye Hai‐Shan , Liu Lin‐Jie , Li Ting‐Ting , Li Sheng , Lu Jun‐Lin , Chen Xu , Liu Jia 
Published: April 2024

AbstractIntravesical instillation is a prevalent approach in bladder cancer (BC) management, yet it often causes adverse reactions and drug resistance. Safer and more effective alternative is therefore in urgent need, and resveratrol (RES) emerges as a promising candidate. However, the effectiveness of RES against BC remains unexplored. In this study, BC‐derived organoids (BCOs) are established to evaluate the efficacy of RES in comparison to conventional anti‐BC drugs (epirubicin (EPI), cisplatin (CDDP), gemcitabine (GEM), and vinorelbine (VNR)). After a 96‐h treatment, RES demonstrates superior anti‐BCOs efficacy (64.00%; 16/25) compared to the other chemotherapeutics (15.38% to 53.85%). Eighteen BCOs are treated with RES, EPI, or a combination of RES and EPI (RES/EPI) in short‐term (3 h per day for four times) to mimic intravesical instillation. RES exhibits the stronger efficacy (44.44%; 8/18) than EPI against BCOs, and the RES/EPI enhances sensitivity of a single drug (50.00%; 9/18). RES inhibits the activation of β‐catenin/CD44 axis in RES‐sensitive BCOs. The organoid‐forming potential of mouse bladder is preserved after intravesical instillation of RES, and 200 × 10−6 m RES demonstrates no adverse effects on patient‐derived bladder urothelial organoids. The findings highlight the potential of RES, particularly in combination with EPI, to improve intravesical instillation outcomes in BC management.
Expansion of the core features of VACTERL association to include genital anomalies
Authors: Forero Laura T. , Henderson Riley , Galarreta Carolina , Swee Steven , Bird Lynne M. 
Published: April 2024

AbstractGenital anomalies have been reported with VACTERL association but not considered a core feature. Acute and chronic complications stemming from unrecognized genital anomalies have been reported in adolescents and young adults with VACTERL association. We sought to determine the frequency and severity of genital anomalies in VACTERL patients and identify which core features were more frequently associated with genital anomalies. A retrospective chart review from January 2010 to October 2021 identified 211 patients with two or more core VACTERL features, 34% of whom had a genital anomaly. The majority of genital anomalies (83% of those in males and 90% in females) were classified as functionally significant (requiring surgical intervention or causing functional impairment). The frequency of genital anomalies in the VACTERL cohort was higher if anorectal malformations or renal anomalies were present in both males and females and if vertebral anomalies were present in females. Due to their functional significance, genital anomalies should be assessed in all patients with two or more core features of VACTERL association, especially in those with anorectal or renal anomalies. Most genital anomalies in males will be detected on physical examination but additional investigation is often needed to detect genital anomalies in females. The timing and type of investigation are subjects for future study.
In vivo validation of late‐onset Alzheimer's disease genetic risk factors
Authors: Sasner Michael , Preuss Christoph , Pandey Ravi S. , Uyar Asli , Garceau Dylan , Kotredes Kevin P. , Williams Harriet , Oblak Adrian L. , Lin Peter Bor‐Chian , Perkins Bridget , Soni Disha , Ingraham Cindy , Lee‐Gosselin Audrey , Lamb Bruce T. , Howell Gareth R. , Carter Gregory W. 
Published: April 2024

AbstractINTRODUCTIONGenome‐wide association studies have identified over 70 genetic loci associated with late‐onset Alzheimer's disease (LOAD), but few candidate polymorphisms have been functionally assessed for disease relevance and mechanism of action.METHODSCandidate genetic risk variants were informatically prioritized and individually engineered into a LOAD‐sensitized mouse model that carries the AD risk variants APOE ε4/ε4 and Trem2*R47H. The potential disease relevance of each model was assessed by comparing brain transcriptomes measured with the Nanostring Mouse AD Panel at 4 and 12 months of age with human study cohorts.RESULTSWe created new models for 11 coding and loss‐of‐function risk variants. Transcriptomic effects from multiple genetic variants recapitulated a variety of human gene expression patterns observed in LOAD study cohorts. Specific models matched to emerging molecular LOAD subtypes.DISCUSSIONThese results provide an initial functionalization of 11 candidate risk variants and identify potential preclinical models for testing targeted therapeutics.Highlights
A novel approach to validate genetic risk factors for late‐onset AD (LOAD) is presented.
LOAD risk variants were knocked in to conserved mouse loci.
Variant effects were assayed by transcriptional analysis.
Risk variants in Abca7, Mthfr, Plcg2, and Sorl1 loci modeled molecular signatures of clinical disease.
This approach should generate more translationally relevant animal models.
Purely Organic Room‐Temperature Phosphorescence Molecule for High‐Performance Non‐Doped Organic Light‐Emitting Diodes
Authors: Peng Xiaoluo , Zou Peng , Zeng Jiajie , Wu Xing , Xie Dian , Fu Yan , Yang Dezhi , Ma Dongge , Tang Ben Zhong , Zhao Zujin 
Published: April 2024

AbstractPurely organic molecules with room‐temperature phosphorescence (RTP) are potential luminescent materials with high exciton utilization for organic light‐emitting diodes (OLEDs), but those exhibiting superb electroluminescence (EL) performances are rarely explored, mainly due to their long phosphorescence lifetimes. Herein, a robust purely organic RTP molecule, 3,6‐bis(5‐phenylindolo[3,2‐a]carbazol‐12(5H)‐yl)‐xanthen‐9‐one (3,2‐PIC‐XT), is developed. The neat film of 3,2‐PIC‐XT shows strong green RTP with a very short lifetime (2.9 μs) and a high photoluminescence quantum yield (72 %), and behaviors balanced bipolar charge transport. The RTP nature of 3,2‐PIC‐XT is validated by steady‐state and transient absorption and emission spectroscopies, and the working mechanism is deciphered by theoretical simulation. Non‐doped multilayer OLEDs using thin neat films of 3,2‐PIC‐XT furnish an outstanding external quantum efficiency (EQE) of 24.91 % with an extremely low roll‐off (1.6 %) at 1000 cd m−2. High‐performance non‐doped top‐emitting and tandem OLEDs are also achieved, providing remarkable EQEs of 24.53 % and 42.50 %, respectively. Delightfully, non‐doped simplified OLEDs employing thick neat films of 3,2‐PIC‐XT are also realized, furnishing an excellent EQE of 17.79 % and greatly enhanced operational lifetime. The temperature‐dependent and transient EL spectroscopies demonstrate the electrophosphorescence attribute of 3,2‐PIC‐XT. These non‐doped OLEDs are the best devices based on purely organic RTP materials reported so far.
Electrochemically‐Driven 1,4‐Aryl Migration via Radical Fluoromethylation of N‐Allylbenzamides: a Straightforward Access to Functionalized β‐Arylethylamines
Authors: Derat Etienne , Masson Géraldine , Claraz Aurélie 
Published: April 2024

AbstractAn electrochemical radical Truce Smiles rearrangement of N‐allylbenzamides is documented herein. The selective 1,4‐aryl migration was triggered by the radical fluoromethylation of the alkene providing a direct route to fluoro derivatives of the highly privileged β‐arylethylamine pharmacophore. This practical transformation utilizes readily available starting materials and employs an electrical current to drive the oxidative process under mild reaction conditions. It accommodates a variety of migratory aryl groups with different electronic properties and substitution patterns. Careful selection of the protecting group on the nitrogen atom of the N‐allylbenzamide is crucial to outcompete the undesired 6‐endo cyclization and achieve high level of selectivity towards the 1,4‐aryl migration. DFT calculations support the reaction mechanism and unveil the origin of selectivity between the two competitive pathways.