bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences of Organizational Practices That Advance Women in Health Care Leadership
Authors: Mousa Mariam , Garth Belinda , Boyle Jacqueline A. , Riach Kathleen , Teede Helena J.
Published: March 2023

Importance

Women are underrepresented in health care leadership positions. Organizational practices and culture play a key role in mitigating this disparity.

Objective

To explore the experiences of women in leadership roles and inform how health care organizations can support the advancement of women into leadership.

Design, Setting, and Participants

This qualitative study used a constructivist grounded theory approach applied over a 1-year period (May 1, 2021, to May 31, 2022) in a large private health care network in Australia. Women were eligible if they had been in leadership positions for more than 5 years. Purposive and theoretical sampling guided recruitment of 28 women, representing medical, nursing, and allied health specialties. Interviews lasted 1 hour, producing 500 pages of transcripts for analysis.

Main Outcomes and Measures

The primary outcome was a model of organizational practices and conditions that advance women in health care leadership, extrapolated from the collective experiences of women in leadership. Key elements pertained to organizational patterns of interaction and group norms and behaviors that contributed toward women’s experiences of career advancement.

Results

Overall, 28 women (23 [82%] White; 3 [11%] Southeast Asian) participated in the study, 10 (36%) of whom were in nursing, 9 (32%) of whom were in allied health, and 9 (32%) of whom were in medical disciplines. Organizational practices that advance women in health care leadership were highly dependent on conducive organizational culture enhancing women’s credibility and capability as leaders. Four interrelated elements were identified that create the necessary conditions for an organizational culture to advance women in health care leadership, including (1) identifying and actively addressing systemic barriers, (2) challenging gendered assumptions and expectations of leadership behaviors, (3) providing mentorship to shape career opportunities, and (4) determining how these conditions all contribute toward raising women’s credibility to enable internalizing a leadership identity. For women, advancing to leadership involved organizations moving away from ad hoc, inconsistent applications of gender equity practices and generating supportive practices that reinforced a workforce culture of credibility, collaboration, and continuous improvement to support women.

Conclusions and Relevance

In light of persisting inequity in health care leadership, women’s experiences were captured in this qualitative study to identify organizational practices that support their advancement. Insights into factors that influence efficacy of these practices, including building a supportive culture and mentoring, are discussed. This research informs a National Health and Medical Research Council initiative with international collaborators to support organizations in advancing women in health care leadership.
Incidence of Interstitial Lung Disease in Patients With Rheumatoid Arthritis Treated With Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs
Authors: Baker Matthew C. , Liu Yuhan , Lu Rong , Lin Janice , Melehani Jason , Robinson William H.
Published: March 2023

Importance

Current data are lacking regarding the risk of biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use on the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA).

Objective

To determine the risk of developing ILD in patients with RA undergoing treatment with different b/tsDMARDs.

Design, Setting, and Participants

Retrospective cohort study using claims data from the Optum Clinformatics Data Mart between December 2003 and December 2019. Adult patients with RA, 1 year or more of continuous enrollment, treatment with a b/tsDMARD of interest, and without preexisting ILD were included. Data were analyzed from October 2021 to April 2022.

Exposures

New administration of adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib.

Main Outcomes and Measures

Crude incidence rates (IRs) for the development of ILD were calculated. The risk of ILD across different b/tsDMARDs was compared using Cox-regression models. A sensitivity analysis using a prevalent new-user cohort design compared patients treated with tofacitinib and adalimumab.

Results

A total of 28 559 patients with RA (mean [SD] age 55.6 [13.7] years; 22 158 female [78%]) were treated with adalimumab (13 326 patients), abatacept (5676 patients), rituximab (5444 patients), tocilizumab (2548 patients), or tofacitinib (1565 patients). Crude IRs per 1000 person-years for ILD were 3.43 (95% CI 2.85-4.09) for adalimumab, 4.46 (95% CI 3.44-5.70) for abatacept, 6.15 (95% CI 4.76-7.84) for rituximab, 5.05 (95% CI 3.47-7.12) for tocilizumab, and 1.47 (95% CI 0.54-3.27) for tofacitinib. After multiple adjustments, compared with patients treated with adalimumab, patients treated with tofacitinib had a lower risk of ILD (adjusted hazard ratio [aHR] 0.31; 95% CI, 0.12-0.78; P = .009). In a prevalent new-user cohort analysis, patients treated with tofacitinib had 68% reduced risk of ILD compared with adalimumab (aHR 0.32; 95% CI 0.13-0.82; P < .001). In an adjusted model, there was a 69% reduced risk of ILD in patients treated with tofacitinib compared with patients treated with adalimumab.

Conclusions and Relevance

In this retrospective cohort of patients with RA, patients treated with tofacitinib had the lowest incidence of ILD compared with patients treated with all bDMARDs evaluated, and patients treated with tofacitinib had a reduced risk of ILD compared with patients treated with adalimumab after adjusting for important covariates. Additional prospective studies are needed to better understand the role tofacitinib may play in preventing ILD in patients with RA. These results, while significant, should be interpreted with caution given the fairly small sample size of the tofacitinib group.
Association Between Magnitude of Differential Blood Pressure Reduction and Secondary Stroke Prevention
Authors: Hsu Chia-Yu , Saver Jeffrey L. , Ovbiagele Bruce , Wu Yi-Ling , Cheng Chun-Yu , Lee Meng
Published: March 2023

Importance

The degree to which more intensive blood pressure reduction is better than less intensive for secondary stroke prevention has not been delineated.

Objective

To perform a standard meta-analysis and a meta-regression of randomized clinical trials to evaluate the association of magnitude of differential blood pressure reduction and recurrent stroke in patients with stroke or transient ischemic attack (TIA).

Data Sources

PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 1980, to June 30, 2022.

Study Selection

Randomized clinical trials that compared more intensive vs less intensive blood pressure lowering and recorded the outcome of recurrent stroke in patients with stroke or TIA.

Data Extraction and Synthesis

The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. Risk ratio (RR) with 95% CI was used as a measure of the association of more intensive vs less intensive blood pressure lowering with primary and secondary outcomes. The univariate meta-regression analyses were conducted to evaluate a possible moderating effect of magnitude of differential systolic blood pressure (SBP) and diastolic blood pressure (DBP) reduction on the recurrent stroke and major cardiovascular events.

Main Outcomes and Measures

The primary outcome was recurrent stroke and the lead secondary outcome was major cardiovascular events.

Results

Ten randomized clinical trials comprising 40 710 patients (13 752 women [34%]; mean age, 65 years) with stroke or TIA were included for analysis. The mean duration of follow-up was 2.8 years (range, 1-4 years). Pooled results showed that more intensive treatment compared with less intensive was associated with a reduced risk of recurrent stroke in patients with stroke or TIA (absolute risk, 8.4% vs 10.1%; RR, 0.83; 95% CI, 0.78-0.88). Meta-regression showed that the magnitude of differential SBP and DBP reduction was associated with a lower risk of recurrent stroke in patients with stroke or TIA in a log-linear fashion (SBP: regression slope, −0.06; 95% CI, −0.08 to −0.03; DBP: regression slope, −0.17; 95% CI, −0.26 to −0.08). Similar results were found in the association between differential blood pressure lowering and major cardiovascular events.

Conclusions and Relevance

More intensive blood pressure–lowering therapy might be associated with a reduced risk of recurrent stroke and major cardiovascular events. These results might support the use of more intensive blood pressure reduction for secondary prevention in patients with stroke or TIA.
Engaging European society at the forefront of cancer research and care
Authors: Baumann Michael , Celis Julio , Ringborg Ulrik , Heitor Manuel , Berns Anton , Albreht Tit , Arabadjiev Jeliazko , Boutros Michael , Brandenburg Mario , Canhao Helena , Carneiro Fatima , Chomienne Christine , De Lorenzo Francesco , Eggermont Alexander M. M. , Font Angel , Garralda Elena , Goulart Margarida , Henrique Rui , Lawler Mark , Maier‐Hein Lena , Meunier Francoise , Oberst Simon , Oliveira Pedro , Papatriantafyllou Maria , Schüz Joachim , Solary Eric , Valencia Alfonso , Vargas Rosalia , Weiderpass Elisabete , Wilking Nils
Published: March 2023

European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (EBCP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research. This meeting report presents all discussions that shed light on how infrastructures can be effectively shaped for translational, prevention, clinical and outcomes cancer research, with a focus on implementation and sustainability and while engaging patients and the public. In addition, we summarize recommendations on how to introduce frameworks for the digitalization of European cancer research. Finally, we discuss what structures, commitment, and resources are needed to establish a collaborative cancer research environment in Europe to achieve the scale required for innovation.
Low‐Threshold, External‐Cavity‐Free Flexible Perovskite Lasers
Authors: Cao Xuhui , Xing Shiyu , Lai Runchen , Lian Yaxiao , Wang Yaxin , Xu Jiying , Zou Chen , Zhao Baodan , Di Dawei
Published: March 2023

A distinct advantage of halide perovskite semiconductors is their potential as gain media in high‐performance, all‐solution‐processed flexible lasers. However, most perovskite microlasers employ external optical resonators with rigid and high‐temperature/vaccum‐processed structures unsuitable for flexible applications. Here, low‐threshold, external‐cavity‐free perovskite lasers (≈550 nm, linewidth: ≈0.3 nm, quality factor: ≈1900, room temperature), prepared with excellent reproducibility using simple one‐step spin‐coating and low‐temperature annealing, are demonstrated. Exceptionally low lasing thresholds of 9.3 and 14.6 µJ cm−2 are achieved for external‐cavity‐free perovskite lasers on rigid and flexible substrates, respectively. The thresholds and quality factors are on par with that of high‐performance perovskite microlasers with well‐designed external cavities. The lasers exhibit good operational stability, showing half‐life of >1.8 × 108 pulses under optical pumping in air. Transient optical experiments reveal that the low thresholds stem from enhanced band‐to‐band spontaneous and stimulated emission processes in the high‐quality microcrystalline perovskite, effectively out‐pacing trap‐mediated and Auger processes detrimental to the lasing action. The flexible perovskite lasers retain >95% of the initial intensity after 10000 bending cycles, showing outstanding mechanical durability. As these lasers can be produced from solution within minutes at low costs, the findings are expected to enable high‐throughput, scalable fabrication of perovskite lasers for emerging applications.
Host Material for Multi‐Color Display with High and Stable Electro‐Phosphorescent Efficiencies: Meta‐Linkage for Balanced Hole and Electron Injection
Authors: Liu Chaoke , Li Tengyue , Sun Mizhen , Xie Mingliang , Zhou Yannan , Feng Wenjuan , Sun Qikun , Zhang Shi‐Tong , Xue Shanfeng , Yang Wenjun
Published: March 2023

Novel host materials and their molecular design methods for phosphorescent materials are crucial for the application of phosphorescent organic light emitting diodes (PhOLEDs), which require balanced carrier injection and sufficient triplet energy levels (ET). Herein, two host materials, namely PPI22PPPBO and PPI33PPPBO, are designed by varying the linkage of benzoxazole (PBO) and phenanthroimidazole (PPI) groups with appropriate ET for green, yellow, and red phosphors. The meta‐link PPI33PPPBO is not only of smaller π‐conjugation, but also of more ordered face‐to‐face stacking for enhanced and more balanced carrier mobility. As a result, the green, yellow, and red PhOLEDs utilizing PPI33PPPBO as host materials show low turn‐on voltages of 2.8 V. The maximum external quantum efficiency (EQEmax) of the corresponding devices reaches 22.8%, 26.7%, and 17.6%, which is superior to that of the traditional host materials CBP and mCP, showing great application potential. More importantly, when the luminance is 1000 cd m−2, their EQE can still be as high as 21.9%, 25.5%, and 16.4%, corresponding to negligible efficiency roll‐offs of only 3.9%, 4.5%, and 6.8%. To the best of authors knowledge, it is the first time that PBO is applied to PhOLED host materials using a twisted connection method.
Seamless Feedthroughs for Neurotechnologies Using Diffusion Processes
Authors: Rudmann Linda , Huber Sebastian D. , Stieglitz Thomas
Published: March 2023

Electrical feedthroughs are a major part of active implantable medical devices. They are responsible for connecting the implants’ active sites with the processing electronics that are usually hermetically packaged. They deliver conductive pathways through the package wall and have to avoid premature device failure due to ingressing humidity. With decreasing device size, the requirements on the single parts increase, including the electrical feedthroughs. As conventional electrical feedthroughs rely on opening the hermetic bulk material of the package that introduce leak paths, they always raise the potential that water enters the package inside alongside these interfaces. Therefore, a proof‐of‐concept study of a new hermetic electrical feedthrough design that leaves the hermetic bulk material, that is, silicon, intact is presented. The concept is based on diffusing noble metals, Pt and Au, into the semiconductor bulk, resulting in a quasi‐localized resistance increase of the silicon. It is shown that by variation of diffusion temperature, time, the substrate cooling, and others, a parameter combination is found with which optoelectronic components can be driven through an intact silicon substrate.
Efficient Fully‐Sprayed Organic Solar Cells with Coffee‐Ring‐Free Photoactive Layer and Alloy Top‐Electrode
Authors: Chang Kai , Yu Boyang , Liu Linna , Fang Dong , Zhao Xinyan , Mi Baoxiu , Huang Wei , Deng Weiwei
Published: March 2023

Depositing all functional layers (including the top electrode) with spray methods is highly desirable and challenging for the eventual commercialization of organic solar cells (OSCs). This work addresses two key challenges toward fully‐sprayed OSCs: i) the printing of a high‐quality photoactive layer free of coffee rings and ii) the spray of the top electrode without the need of evaporation nor solvents. To eliminate coffee rings caused by individual droplets, the photoactive layer is deposited by electrospray on the cooled substrate. The reduced temperature slows down the solvent evaporation, promotes merging of individual droplets, and suppresses the formation of coffee rings. By optimizing the drying temperature, homogeneous films without coffee rings are obtained. The improved active‐layer morphology facilitates charge transport and reduces recombination. The device prepared by the coldplate‐assisted electrospray reaches a power conversion efficiency (PCE) of 17.13%. In addition, an alloy with the melting point of 62 °C is spray‐printed as the top electrode using an airbrush. The spray process is optimized by the trade‐off between the coverage rate and the film thickness. OSCs with the alloy electrode achieve the highest PCE of 16.26%. The fully‐sprayed OSCs exhibit PCEs up to 15.09%, demonstrating a viable route toward fully‐sprayed OSCs with high‐performance.
Visualization of Surface Charge Carrier Diffusion Lengths in Different Perovskite Crystal Orientations Using 4D Electron Imaging
Authors: Nughays Razan O. , Yang Chen , Nematulloev Sarvarkhodzha , Yin Jun , Harrison George T. , Zhao Jianfeng , Fatayer Shadi , Bakr Osman M. , Mohammed Omar F.
Published: March 2023

Understanding charge carrier dynamics on the surface of materials at the nanometer and femtosecond scales is one of the key elements to optimizing the performance of light‐conversion devices, including solar cells. Unfortunately, most of the pump‐probe characterization techniques are surface‐insensitive and obtain information from the bulk due to the large penetration depth of the pulses. However, ultrafast scanning electron microscopy (USEM) is superior in visualizing carrier dynamics at the surface with high spatial‐temporal resolution. Here, the authors successfully used USEM to uncover the tremendous effect of surface orientations and termination on the charge carrier of MAPbI3 perovskite single crystals. Time‐resolved secondary electrons snapshots and density functional theory calculations clearly demonstrate that charge carrier diffusion, surface trap density, surface work function, and carrier concentration are strongly facet‐dependent. The results display a diffusion length of 22 micrometers within 6.0 nanoseconds along (001) orientation. While (100) facet forms defect states that prevent carrier diffusion and shows an increase in the surface work function leading to dark contrast and fast charge carrier recombination. These findings provide a new key component to optimizing the surface of perovskites, thus paving the way for even more efficient and stable solar‐cell devices based on perovskite single crystals.
Advanced and Readily‐Available Wireless‐Powered Blue‐Light‐Implant for Non‐Invasive Peri‐Implant Disinfection
Authors: Zhang Ludan , Li Yamin , Yuan Lintian , Zhang Qianyi , Yan Yuqing , Dong Fan , Tang Jun , Wang Yuguang
Published: March 2023

Non‐invasive light‐based antibacterial therapy has a good prospect in non‐surgical treatment of peri‐implant infections. However, its applications are severely limited by poor penetration of light into human tissues, leading to unsatisfying outcomes. Moreover, as an essential prerequisite for traditional light therapy, lasers can no longer meet the patients’ needs for convenient treatment at any time. To break through the spatial and temporal limitations of traditional light therapy, a wireless‐powered blue‐light zirconia implant for readily available treatment of peri‐implant infection is proposed. In space, complete irradiation to complex peri‐implant structure is realized by the built‐in wireless‐powered light source, thus improving the efficacy. In time, wireless‐powering allows timely and controllable anti‐infection treatment. Blue micro‐light emitting diodes are used as therapeutic light sources, which effectively kill peri‐implant infection‐related bacteria without exogenous photosensitive agents. Porphyromonas gingivalis biofilm on implant surface can be completely killed after 20 min irradiation in vitro. The bactericidal rate of peri‐implant methicillin‐resistant Staphylococcus aureus infection reaches 99.96 ± 0.03% under 30 min per day blue light exposure in vivo. Within the scope of this study, the treatment of peri‐implant infection with blue‐light implant has preliminary feasibility, giving a new approach to non‐invasive treatment of deep oral infections, including peri‐implant infections.
Among men, androgens are associated with a decrease in Alzheimer's disease risk
Authors: Kusters Cynthia D. J. , Paul Kimberly C. , Romero Tahmineh , Sinsheimer Janet S. , Ritz Beate R.
Published: March 2023

INTRODUCTION

Increased levels of sex hormones have been hypothesized to decrease Alzheimer's disease (AD) risk. We assessed the association between sex steroid hormones with AD using a Mendelian randomization (MR) approach.

METHODS

An inverse‐variance weighting (IVW) MR analysis was performed using effect estimates from external genome‐wide association study (GWAS) summary statistics. We included independent variants (linkage disequilibrium R2 < 0.001) and a p‐value threshold of 5 × 10−8.

RESULTS

An increase in androgens was associated with a decreased AD risk among men: testosterone (odds ratio [OR]: 0.53; 95% confidence interval [CI]: 0.32–0.88; p‐value: 0.01; false discovery rate [FDR] p‐value: 0.03); dehydroepiandrosterone sulfate (DHEAS; OR: 0.56; 95% CI: 0.38–0.85; p‐value: 0.01; FDR p‐value: 0.03); and androsterone sulfate (OR: 0.69; 95% CI: 0.46–1.02; p‐value: 0.06; FDR p‐value: 0.10). There was no association between sex steroid hormones and AD among women, although analysis for estradiol had limited statistical power.

DISCUSSION

A higher concentration of androgens was associated with a decreased risk of AD among men of European ancestry, suggesting that androgens among men might be neuroprotective and could potentially prevent or delay an AD diagnosis.

Highlights

Sex hormones are hypothesized to play a role in developing Alzheimer's disease (AD).

The effect of sex hormones on AD was assessed using Mendelian randomization (MR) analysis.

Among women, genetically determined effects of sex hormones were limited or null.

Among men, a higher concentration of androgens decreased AD risk.

This study suggests a causal relationship between androgens and AD among men.
Selective Neuronal Knockout of STAT3 Function Inhibits Epilepsy Progression, Improves Cognition, and Restores Dysregulated Gene Networks in a Temporal Lobe Epilepsy Model
Authors: Tipton Allison E. , Cruz Del Angel Yasmin , Hixson Kathryn , Carlsen Jessica , Strode Dana , Busquet Nicolas , Mesches Michael H. , Gonzalez Marco I. , Napoli Eleonora , Russek Shelley J. , Brooks‐Kayal Amy R.
Published: March 2023

Objective

Temporal lobe epilepsy (TLE) is a progressive disorder mediated by pathological changes in molecular cascades and hippocampal neural circuit remodeling that results in spontaneous seizures and cognitive dysfunction. Targeting these cascades may provide disease‐modifying treatments for TLE patients. Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) inhibitors have emerged as potential disease‐modifying therapies; a more detailed understanding of JAK/STAT participation in epileptogenic responses is required, however, to increase the therapeutic efficacy and reduce adverse effects associated with global inhibition.

Methods

We developed a mouse line in which tamoxifen treatment conditionally abolishes STAT3 signaling from forebrain excitatory neurons (nSTAT3KO). Seizure frequency (continuous in vivo electroencephalography) and memory (contextual fear conditioning and motor learning) were analyzed in wild‐type and nSTAT3KO mice after intrahippocampal kainate (IHKA) injection as a model of TLE. Hippocampal RNA was obtained 24 h after IHKA and subjected to deep sequencing.

Results

Selective STAT3 knock‐out in excitatory neurons reduced seizure progression and hippocampal memory deficits without reducing the extent of cell death or mossy fiber sprouting induced by IHKA injection. Gene expression was rescued in major networks associated with response to brain injury, neuronal plasticity, and learning and memory. We also provide the first evidence that neuronal STAT3 may directly influence brain inflammation.

Interpretation

Inhibiting neuronal STAT3 signaling improved outcomes in an animal model of TLE, prevented progression of seizures and cognitive co‐morbidities while rescuing pathogenic changes in gene expression of major networks associated with epileptogenesis. Specifically targeting neuronal STAT3 may be an effective disease‐modifying strategy for TLE. ANN NEUROL 2023;94:106–122
Interaction between Divalent Copper Fluoride and Carboxamide Group Enabling Stereoretentive Fluorination of Tertiary Alkyl Halides
Authors: Tsuchiya Naoki , Yamamoto Tetsuhiro , Akagawa Hiroki , Nishikata Takashi
Published: March 2023

Herein, we report a copper‐catalyzed stereospecific fluorination involving CsF and α‐bromocarboxamides as tertiary alkyl sources that, unlike traditional stereospecific routes involving stereoinversive SN2 reactions, proceeds with retention of stereochemistry. The developed stereospecific Cu‐catalyzed reaction is among the most efficient methods for synthesizing fluorinated molecules that possess highly congested stereogenic carbon centers. Mechanistic studies revealed that the combined reactivity of CuF2 and Cs salt is essential for completing the catalytic cycle. Our catalytic system underwent fluorination exclusively with tertiary alkyl bromides and did not react with primary alkyl bromides, indicating that this stereospecific fluorination methodology is suitable for synthesizing fluorinated building blocks possessing stereo‐defined F‐containing tertiary carbon stereogenic center.
Glutathione‐Induced In Situ Michael Addition between Nanoparticles for Pyroptosis and Immunotherapy
Authors: Zhen Wenyao , Liu Yang , An Shangjie , Jiang Xiue
Published: March 2023

Most tumor treatments will fail when ignoring competition and cooperation between each cancer cell and its microenvironment. Inspired by game theory, therapeutic agents can be introduced to compete for intracellular molecules to disrupt the cooperation between molecules and cells. Biomineralized oxidized (−)‐epigallocatechin‐3‐o‐gallate (EGCG)–molybdenum ion coordination nanoparticles were prepared for disrupting redox equilibria and simultaneously reacting with intracellular GSH in a Michael addition to form large aggregates that can mechanically disrupt endosomal and plasma membranes, stimulating pyroptosis and anti‐tumor immunological responses for versatile inhibition of different types of tumors. This design disrupts the cooperation between molecules and between cancer and immune cells, achieving an optimal payoff in competition and cooperation in cancer therapy.
The relationship between obstructive sleep apnea and circulating tau levels: A meta‐analysis
Authors: Huang Zhi‐Wei , Zeng Hui‐Xue , Huang Ya‐Ping , Wang Tie‐Zhu , Huang Wen‐Sen , Huang Yan‐Fei , Lin Li , Li Hao
Published: March 2023

Background

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that impairs memory, thinking, language, and, eventually, the ability to carry out the simplest of tasks. Tau protein, the major component of neurofibrillary tangles, is considered a key mediator of AD pathogenesis. The association between obstructive sleep apnea (OSA) and circulating tau remains unclear. The aim of the present meta‐analysis was to evaluate the relationship between OSA and circulating tau via quantitative analysis.

Methods

A systematic search of Pubmed, Embase, and Web of Science were performed. The mean values of circulating total tau (T‐tau) and phosphorylated tau (P‐tau) in OSA and control groups were extracted. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by using a random‐effect model or fixed‐effect model.

Results

A total of seven studies comprising 233 controls and 306 OSA patients were included in this study. The meta‐analysis showed that the circulating T‐tau level was significantly higher in OSA patients than those in the control group (SMD = 1.319, 95% CI = 0.594 to 2.044, z = 3.56, p < .001). OSA patients also had significantly higher circulating P‐tau level than control group (SMD = 0.343, 95% CI = 0.122 to 0.564, z = 3.04, p = .002).

Conclusions

The present meta‐analysis demonstrated that both circulating T‐tau and P‐tau levels were significantly increased in OSA subjects when compared with non‐OSA subjects. Larger sample‐size studies on the association between OSA and circulating tau are still required to further validate our results.
Antecedents of consumers' online apparel purchase intention through Virtual Try On technology: A moderated moderated‐mediation model
Authors: Chidambaram Vijayabanu , Rana Nripendra P. , Parayitam Satyanarayana
Published: March 2023

The study aims to empirically examine the consumers' online apparel purchasing behavior using the constructs from the technology acceptance model (UTAUT). The complex interrelationships between perceived usefulness, perceived risk, perceived enjoyment, and virtual try‐on (VTO) technology were explored using a moderated moderated‐mediation model. Most importantly, this research focuses on how VTO, one of the frequently used disruptive technologies, influences consumer behavior. Using a structured survey instrument, the data was collected from 288 millennial respondents and has been analyzed using Hayes's PROCESS macros. The results reveal that attitude towards VTO mediated the relationship between perceived usefulness and behavioral intention of customers to engage in online shopping. Perceived risk (first moderator) negatively moderated the relationship between perceived usefulness and attitude towards VTO, and perceived enjoyment (second moderator) has positively moderated the relationship between perceived usefulness and perceived risk and behavioral intention mediated through attitude towards VTO. The theoretical and practical implications were also discussed.
C‐Dimethylated Flavones as Possible Potential Anti‐Tubercular and Anticancer Agents.
Authors: Bollikolla Hari Babu , Anandam Rambabu , Chinnam Sampath , Varala Ravi , Khandapu Bala Murali Krishna , Kapavarapu Ravikumar , Syed Khasim Sharif , Dubasi Narasimhaswamy , Syed Mastan Ali
Published: March 2023

The present investigation describes an intramolecular Oxa‐Michael addition of penta‐substituted phenols to the enone of the tether in the presence of iodine as the oxidizing agent. TenC‐Dimethylated flavones with moderate to good yields (10a–j, 60–89 %) were isolated by heating the correspondingC‐dimethylated chalcones using iodine in DMSO. Using the Microplate Alamar Blue test (MABA) technique, the drugs′ quantitative drug susceptibility against the H37Rv strain of replicating Mycobacterium TB was determined. The sensitivity of two of the developed compounds (10e,10h) was up to 6.25 g/mL. The human lung adenocarcinoma cell lines (A549) were used in the anticancer study, which was carried out using the MTT cell proliferation assay. In A549 cell lines, four flavones demonstrated anticancer activity with IC50values between 39 and 48 μM. TheC‐dimethylated flavones,10b(3,4‐dimethoxy),10c(2,3,4‐trimethoxy),10e(p‐fluoro) and10g (N‐methyl indole) substitutions on ring ‘B’ showed good anticancer activity with IC50values 39.17, 39.21, 48.43 and 43.48 μM, respectively. The compounds10b,10c,10d,10e, and10ihad improved binding and interaction profiles among all the compounds examined during the currentIn Silicoresearch, as shown by the docking simulations against two targets EGFR and MTB MurI.
Continuous local intravenous heparin infusion after re‐exploration for venous congestion in free‐flap breast reconstruction: A case series
Authors: Kubo Kazuyuki , Kirita Miho , Hamahata Atsumori , Sakurai Hiroyuki
Published: March 2023

We demonstrated local intravenous heparin infusion to salvage flaps after re‐exploration for postoperative venous congestion after free‐flap breast reconstruction. All flaps were salvaged using local intravenous heparin infusion without major complications. Local intravenous heparin infusion is an effective and safe procedure.
A rare tonsillar metastasis of Merkel cell carcinoma: A case report
Authors: Okonkwo Precious C. , Henning Ania , Plaza Jose , Agrawal Amit , Contreras Carlo M.
Published: March 2023

Merkel cell carcinoma (MCC) metastasis to the tonsil is extremely rare with five published cases. We report the case of a patient with palatine tonsillar MCC metastasis, who presented without oropharyngeal symptoms, which contrast prior reported cases.
Trimethoprim/sulfamethoxazole‐induced methemoglobinemia in pediatric patient: A case report
Authors: Alotaibi Sultan , Mously Alaa , Alnujaimy Zainab , Alotaibi Abdulansir , Alharthi Abdullah
Published: March 2023

In this report, a case of high dose of sulfamethoxazole/trimethoprim‐induced methemoglobinemia and is reported in a young boy with ventilator‐associated pneumonia and was treated successfully with methylene blue and cessation of the offending agent.
Comminution of Wood: Single‐Particle Breakage
Authors: Eisenlauer Moritz , Steinhauer Daniel , Klotz Alexander , Jost-Kovács Alma , Wolf Sebastian , Teipel Ulrich
Published: March 2023

An essential element for the sustainable use of renewable resources is an efficient comminution process. For efficient comminution processes, detailed knowledge of the fracturing processes is necessary. Therefore, single‐particle comminution under impact stress was investigated, and the influence of the moisture content and the particle size in single‐particle comminution of beech wood is described. The extent of applicability of the existing models to wood, for modeling the breakage probability function for brittle materials, was investigated.
Immediate exacerbation of atopic dermatitis after switching from upadacitinib to dupilumab: A report of two cases
Authors: Ito Makoto , Kamata Masahiro , Uchida Hideaki , Egawa Shota , Fukaya Saki , Hayashi Kotaro , Fukuyasu Atsuko , Tanaka Takamitsu , Ishikawa Takeko , Tada Yayoi
Published: March 2023

Janus kinase (JAK) inhibitors are efficacious for atopic dermatitis (AD). However, some patients receiving JAK inhibitors develop acne, especially younger patients, or herpes zoster, especially elderly patients, and desire to switch to dupilumab. We experienced two patients with immediate exacerbation of AD after switching from upadacitinib to dupilumab, and herein report these cases. This phenomenon is attributed to the difference in elimination half‐life of the two drugs and a slower onset of efficacy of dupilumab than upadacitinib. When switching from a JAK inhibitor to dupilumab, short‐term concomitant use, intensifying topical treatment, and/or rescue with cyclosporine should be considered.
Evaluating Diff‐Quik cytology smears for large‐panel mutation testing in lung cancer—Predicting DNA content and success with low‐malignant‐cellularity samples
Authors: Fielding David I. , Dalley Andrew J. , Singh Mahendra , Nandakumar Lakshmy , Lakis Vanessa , Chittoory Haarika , Fairbairn David , Patch Ann‐Marie , Kazakoff Stephen H. , Ferguson Kaltin , Bashirzadeh Farzad , Bint Michael , Pahoff Carl , Son Jung Hwa , Hodgson Alan , Sharma Sowmya , Waddell Nicola , Lakhani Sunil R. , Hartel Gunter , Nones Katia , Simpson Peter T.
Published: March 2023

Background

Cytology smears are commonly collected during endobronchial ultrasound–guided transbronchial needle aspiration (EBUS TBNA) procedures but are rarely used for molecular testing. Studies are needed to demonstrate their great potential, in particular for the prediction of malignant cell DNA content and for utility in molecular diagnostics using large gene panels.

Methods

A prospective study was performed on samples from 66 patients with malignant lymph nodes who underwent EBUS TBNA. All patients had air‐dried, Diff‐Quik cytology smears and formalin‐fixed, paraffin‐embedded cell blocks collected for cytopathology and molecular testing. One hundred eighty‐five smears were evaluated by microscopy to estimate malignant cell percentage and abundance and to calculate smear size and were subjected to DNA extraction. DNA from 56 smears from 27 patients was sequenced with the TruSight Oncology 500 assay (Illumina).

Results

Each microscopy parameter had a significant effect on the DNA yield. An algorithm was developed that predicted a >50‐ng DNA yield of a smear with an area under the curve of 0.86. Fifty DNA samples (89%) with varying malignant yields were successfully sequenced. Low‐malignant‐cell content (<25%) and smear area (<15%) were the main reasons for failure. All standard‐of‐care mutations were detected in replicate smears from individual patients, regardless of malignant cell content. Tier 1/2 mutations were discovered in two cases where standard‐of‐care specimens were inadequate for sequencing. Smears were scored for tumor mutation burden.

Conclusions

Microscopy of Diff‐Quik smears can triage samples for comprehensive panel sequencing, which highlights smears as an excellent alternative to traditional testing with cell blocks.
Safety, Tolerability, and Pharmacokinetics of IMU‐935, a Novel Inverse Agonist of Retinoic Acid Receptor–Related Orphan Nuclear Receptor γt: Results From a Double‐Blind, Placebo‐Controlled, First‐in‐Human Phase 1 Study
Authors: Polasek Thomas M. , Leelasena Indika , Betscheider Irina , Marolt Marija , Kohlhof Hella , Vitt Daniel , Fliegert Frank , Muehler Andreas R.
Published: March 2023

Retinoic acid receptor–related orphan nuclear receptor (ROR)γt regulates the transcription of interleukin‐17 and other cytokines implicated in inflammatory and autoimmune diseases. We assessed the safety, tolerability, and pharmacokinetics (PK) of IMU‐935, an inverse agonist of RORγt, in a first‐in‐human phase 1 study. This was a double‐blind, placebo‐controlled trial that randomly assigned healthy subjects single ascending doses (25–400 mg) or multiple ascending doses (150 mg once or twice daily for 14 days) of IMU‐935 or placebo. Dose escalation was determined by the safety, tolerability, and PK. Twenty‐four and 70 subjects received placebo or IMU‐935, respectively. Of the 70 subjects who received IMU‐935, 59 received a single dose and 11 received multiple doses. Treatment‐emergent adverse events (TEAEs) occurred in 21 subjects (88%) and 58 (83%) given any dose of placebo or IMU‐935, respectively. Treatment‐related TEAEs occurred in 6 (30%) and 25 (42%) subjects given a single dose of placebo and IMU‐935, respectively. All treatment‐related TEAEs were mild except for 2 moderate TEAEs and 1 moderate TEAE in the IMU‐935 group and placebo group, respectively. No treatment‐related discontinuations or serious adverse events occurred. The PK of IMU‐935 were dose proportional with a half‐life of ≈24 hours. In conclusion, IMU‐935 was safe with no dose‐limiting toxicities and had a PK profile that supports once‐daily dosing.
Optical Properties and Metal‐Dependent Charge Transfer in Iodido Pentelates
Authors: Möbs Jakob , Stuhrmann Gina , Wippermann Stefan , Heine Johanna
Published: March 2023

Lead‐free heavy halogenido metalates are currently under intense investigation, as they show similarly promising semiconducting properties as their famous but toxic lead relatives. A major interest in this regard is the understanding and control of optical properties with the goal of designing highly efficient photoconducting materials. Here, we present two isostructural iodido pentelates (Hpyz)3E2I9 ⋅ 2H2O (pyz=pyrazine; E=Sb, Bi). Both compounds are stable up to 100 °C. We observe an inverted order of band gap sizes, 1.91 eV and 1.98 eV for the antimony and bismuth compound, respectively, compared to similar pairs of compounds. We use DFT calculations to confirm that this surprising finding can be traced back to the presence of charge transfer excitations in both compounds.
Magnetic Isolation, RNA Extraction, and Nanostring Analysis of Human Peripheral Blood Leukocytes Subsets
Authors: McFarlin Brian K. , Bridgeman Elizabeth A. , Sass Tatum N.
Published: March 2023

Advancements in multiplexed molecular biology techniques have allowed for blood samples and specific circulating blood leukocytes to be a useful sample source when examining systemic changes associated with changes in body weight, muscle injury, disease onset/progression, and other common conditions. One gap in the current scientific knowledge relates to the impact of changes in individual leukocyte subsets on the overall systemic response. While many studies have published data related to changes observed in a mixed population of circulating leukocytes (i.e., whole blood sample), few studies have identified which cell(s) are responsible for the overall change. Since it is established that leukocyte subsets respond differently to various experimental challenges, it may be possible to gain new insight regarding overall biological state. This has application to a variety of health, nutrition, and exercise intervention models. Despite the need to examine changes in mRNA expression levels in individual leukocyte subsets they are not always easy to isolate and perform mRNA analysis on. In this report we describe a method to magnetically isolate, stabilize RNA, and analyze 800+ mRNA in a single sample analysis. Further we compared total leukocyte and leukocyte subset (i.e., granulocytes, monocytes, and T‐cells) mRNA expression to better understand how subset changes contribute to overall response. Examination of subset responses may provide targets for future intervention studies. © 2023 Wiley Periodicals LLC.

Basic Protocol 1: Automated magnetic isolation of granulocytes, monocytes, and T‐cells

Basic Protocol 2: RNA extraction from magnetically sorted granulocytes, monocytes, and T‐cells

Basic Protocol 3: Nanostring analysis of RNA extracted from magnetically sorted granulocytes, monocytes, and T‐cells
What to do when it is hard to fire someone in the academy
Authors: Schwebel David C.
Published: March 2023

Before his presidency, Donald Trump popularized the reality TV show tagline, “You're fired!” on the show The Apprentice. In television‐land, the act of firing an employee is quick, simple, and even entertaining.
Breaking down re‐enrollment barriers for adult learners improves experience for all
Authors: Sutton Halley
Published: March 2023

CHICAGO — Re‐engaging your stopped‐out adult learners can be a dramatic tool in your arsenal for boosting completion rates, as well as changing the lives of the students in your community. “We know who [these students] are: when they stopped out, why they stopped out. It's rarely that they failed out, but more likely they ‘lifed’ out in some way,” Tony Sheppard, Professor and Program Coordinator of Hospital Management & Tourism at Sacramento State University, said.
Degree attainment rose during the pandemic, though racial gaps persist
Authors: Sutton Halley
Published: March 2023

The national share of working‐age Americans who hold college degrees increased across racial and ethnic groups, and rose in all states between 2019 and 2021. That finding comes from new data from the Lumina Foundation on college degree or credential attainment rates for American adults.
Longtime official recognized for her leadership during COVID‐19
Authors: D'Orio Wayne
Published: March 2023

When COVID‐19 shut down Cornell in 2020, like colleges across the country, officials had to reinvent how they were able to help students. Suddenly, Lisa M. Clark, the school's deputy university registrar, found herself working at home with a Zoom screen full of other officials she had never interacted with before.
Evaluating the potential role of human papilloma virus infection in breast carcinogenesis via real‐time polymerase chain reaction analyzes of breast fine needle aspiration samples from Greek patients
Authors: Mareti Evangelia , Vavoulidis Eleftherios , Papanastasiou Anastasios , Maretis Theodoros , Tsampazis Nikolaos , Margioula‐Siarkou Chrysoula , Chatzinikolaou Fotios , Giasari Sofia , Nasioutziki Maria , Daniilidis Angelos , Zepiridis Leonidas , Dinas Konstantinos
Published: March 2023

Background

Human papilloma virus (HPV), in addition to its known clinical contribution to cervical cancer is probably actively involved in the development of breast tumors in various populations worldwide. Predominant HPV types in breast cancer patients vary geographically. The present study further examines HPV incidence in Greece, based on molecular analysis of clinical cytological samples.

Methods

Greek patient fine needle aspiration (FNA) biopsy samples were examined using RT‐PCR and immunohistological staining. FNA biopsy samples were collected from 114 female patients, diagnosed between the years 2018 and 2021, 57 with C5 diagnosed breast cancer lesions and 57 diagnosed with benign diseases.

Results

A total of three different HPV types were identified within the patient sample. HPV‐39 was found only in the control group, in 1.8% of patients, while HPV‐59 was present in both control and study groups in 1.8% and 3.5% respectively. HPV‐16, on the other hand, was present only in the study group in 12.3% of cases. HPV type presence was statistically differentiated between histological groups. HPV‐16 was exclusively in IDC, HPV‐39 was present in one cyst diagnosed sample and HPV‐59 was present in 3 samples that included fibroadenoma, IDC and LN diagnosis.

Conclusion

More international comparative studies are required to investigate population differences and HPV genotype distribution to offer definite answers to the effect that certain HPV types might have a role in breast cancer, as this study also supports, albeit in a cofactory role.
Historic and contemporary biogeographic perspectives on range‐wide spatial genetic structure in a widespread seagrass
Authors: Sinclair Elizabeth A. , Hovey Renae K. , Krauss Siegfried L. , Anthony Janet M. , Waycott Michelle , Kendrick Gary A.
Published: March 2023

Historical and contemporary processes drive spatial patterns of genetic diversity. These include climate‐driven range shifts and gene flow mediated by biogeographical influences on dispersal. Assessments that integrate these drivers are uncommon, but critical for testing biogeographic hypotheses. Here, we characterize intraspecific genetic diversity and spatial structure across the entire distribution of a temperate seagrass to test marine biogeographic concepts for southern Australia. Predictive modeling was used to contrast the current Posidonia australis distribution to its historical distribution during the Last Glacial Maximum (LGM). Spatial genetic structure was estimated for 44 sampled meadows from across the geographical range of the species using nine microsatellite loci. Historical and contemporary distributions were similar, with the exception of the Bass Strait. Genetic clustering was consistent with the three currently recognized biogeographic provinces and largely consistent with the finer‐scale IMCRA bioregions. Discrepancies were found within the Flindersian province and southwest IMCRA bioregion, while two regions of admixture coincided with transitional IMCRA bioregions. Clonal diversity was highly variable but positively associated with latitude. Genetic differentiation among meadows was significantly associated with oceanographic distance. Our approach suggests how shared seascape drivers have influenced the capacity of P. australis to effectively track sea level changes associated with natural climate cycles over millennia, and in particular, the recolonization of meadows across the Continental Shelf following the LGM. Genetic structure associated with IMCRA bioregions reflects the presence of stable biogeographic barriers, such as oceanic upwellings. This study highlights the importance of biogeography to infer the role of historical drivers in shaping extant diversity and structure.