bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation and Management of Deficiency of Adenosine Deaminase 2
Authors: Lee Pui Y. , Davidson Brad A. , Abraham Roshini S. , Alter Blanche , Arostegui Juan I. , Bell Katherine , Belot Alexandre , Bergerson Jenna R. E. , Bernard Timothy J. , Brogan Paul A. , Berkun Yackov , Deuitch Natalie T. , Dimitrova Dimana , Georgin-Lavialle Sophie A. , Gattorno Marco , Grimbacher Bodo , Hashem Hasan , Hershfield Michael S. , Ichord Rebecca N. , Izawa Kazushi , Kanakry Jennifer A. , Khubchandani Raju P. , Klouwer Femke C.C. , Luton Evan A. , Man Ada W. , Meyts Isabelle , Van Montfrans Joris M. , Ozen Seza , Saarela Janna , Santo Gustavo C. , Sharma Aman , Soldatos Ariane , Sparks Rachel , Torgerson Troy R. , Uriarte Ignacio Leandro , Youngstein Taryn A. B. , Zhou Qing , Aksentijevich Ivona , Kastner Daniel L. , Chambers Eugene P. , Ombrello Amanda K. ,   DADA2 Foundation, Makley Mary K. , Hayner Kristen L. , Kling Bridget E. , Cowsert Lex M. , Williams Julie S.
Published: May 2023

Importance

Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited disease characterized by systemic vasculitis, early-onset stroke, bone marrow failure, and/or immunodeficiency affecting both children and adults. DADA2 is among the more common monogenic autoinflammatory diseases, with an estimate of more than 35 000 cases worldwide, but currently, there are no guidelines for diagnostic evaluation or management.

Objective

To review the available evidence and develop multidisciplinary consensus statements for the evaluation and management of DADA2.

Evidence Review

The DADA2 Consensus Committee developed research questions based on data collected from the International Meetings on DADA2 organized by the DADA2 Foundation in 2016, 2018, and 2020. A comprehensive literature review was performed for articles published prior to 2022. Thirty-two consensus statements were generated using a modified Delphi process, and evidence was graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence.

Findings

The DADA2 Consensus Committee, comprising 3 patient representatives and 35 international experts from 18 countries, developed consensus statements for (1) diagnostic testing, (2) screening, (3) clinical and laboratory evaluation, and (4) management of DADA2 based on disease phenotype. Additional consensus statements related to the evaluation and treatment of individuals with DADA2 who are presymptomatic and carriers were generated. Areas with insufficient evidence were identified, and questions for future research were outlined.

Conclusions and Relevance

DADA2 is a potentially fatal disease that requires early diagnosis and treatment. By summarizing key evidence and expert opinions, these consensus statements provide a framework to facilitate diagnostic evaluation and management of DADA2.
Smoking Cessation and Changes in Anxiety and Depression in Adults With and Without Psychiatric Disorders
Authors: Wu Angela Difeng , Gao Min , Aveyard Paul , Taylor Gemma
Published: May 2023

Importance

Although many people report a desire to quit smoking, concerns about mental health worsening after quitting are often raised by clinicians and people who smoke.

Objective

To assess changes in mental health following smoking cessation using 3 confirmatory coprimary analytical approaches.

Design, Setting, and Participants

This cohort study was conducted using data from a large, randomized clinical trial, the Evaluating Adverse Events in a Global Smoking Cessation Study. Analytical approaches included multivariable Tobit regression, propensity score adjustment, and instrumental variable regressions conducted from August to October 2022. Missing data were imputed for sensitivity analysis. The trial occurred in 16 countries at 140 centers between 2011 and 2015. Only data from participants who completed the trial collected in the US were available for this secondary analysis. Participants included adults with or without a psychiatric disorder who smoked.

Exposure

Smoking abstinence between weeks 9 through 24.

Main Outcomes and Measures

Anxiety and depression scores were measured using the Hospital Anxiety and Depression Scale at 24 weeks, where a lower score indicates better mental health (range, 0-21).

Results

Of the 4260 participants included (mean [SD] age, 46.5 [12.4] years; 2485 women [58.3%]; 3044 White individuals [71.5%]), 2359 (55.4%) had a history of mental illness. The mean (SD) baseline Hospital Anxiety and Depression Scale score was 4.25 (3.68) (median [IQR], 3 [1-6]) for anxiety and 2.44 (2.91) (median [IQR], 1 [0-4]) for depression. After adjustment for demographics and baseline variables, smoking cessation was associated with a decrease in scores for both anxiety (−0.40 point; 95% CI, −0.58 to −0.22 point) and depression (−0.47 point; 95% CI, −0.61 to −0.33 point) compared with continuing smoking. Similarly, propensity score–adjusted models indicated that smoking cessation was associated with reduced scores for anxiety (β = −0.32; 95% CI, −0.53 to −0.11) and depression (β = −0.42; 95% CI, −0.60 to −0.24). Instrumental variable analysis was underpowered, and estimates were imprecise. Findings were robust to planned sensitivity and subgroup analyses, with larger effect sizes in people with a history of mental illness.

Conclusions and Relevance

In this cohort study of people with and without psychiatric disorders, smoking cessation, sustained for at least 15 weeks, was associated with improved mental health outcomes in observational analyses, but the instrumental variable analysis provided inconclusive evidence. Findings like these may reassure people who smoke and their clinicians that smoking cessation likely will not worsen and may improve mental health.
Standard Restrictions vs Expedited Activity After Pelvic Organ Prolapse Surgery
Authors: O’Shea Michele , Siddiqui Nazema Y. , Truong Tracy , Erkanli Alaattin , Barber Matthew D.
Published: May 2023

Importance

Restrictions on postoperative activity following pelvic organ prolapse (POP) surgery are not evidence based. Nonetheless, many pelvic surgeons place lifting and activity restrictions on patients following surgery.

Objective

To evaluate whether expedited activity results in noninferior anatomic and symptomatic outcomes compared with standard activity restrictions after POP surgery.

Design, Setting, and Participants

This randomized noninferiority clinical trial included patients undergoing vaginal or laparoscopic apical reconstructive surgery for POP between July 1, 2020, and October 31, 2021, at a single academic tertiary referral center in Durham, North Carolina. Anatomic outcomes were assessed by masked examiners, and subjective outcomes were assessed via validated surveys, both completed at 3 months postoperatively. Patients meeting minimum physical activity criteria with at least stage II bothersome POP were eligible. A total of 218 patients were approached, of whom 123 were randomly assigned and 107 had complete outcome data and were included in the analysis.

Interventions

Patients were randomly assigned to receive standard restrictions vs expedited postoperative activity instructions.

Main Outcomes and Measures

The anatomic coprimary outcome was maximum anatomic POP support loss (SLmax), which is the most distal point of pelvic organ support loss according to the Pelvic Organ Prolapse Quantification System (noninferiority margin, 1.0 cm). The symptomatic coprimary outcome was the Pelvic Organ Prolapse Distress Inventory (POPDI) symptom score (noninferiority margin, 34.3 points). Differences between outcomes were assessed using linear regression models controlling for baseline SLmax and POPDI, respectively.

Results

Of 123 participants randomized, 107 had complete 3-month outcome data and were included in the analysis. Mean (SD) age was 62.8 (10.1) years. At 3 months, mean (SD) SLmax was −1.7 (1.4) cm in the expedited group and −1.5 (1.4) cm in the standard group (P = .44). After adjusting for baseline SLmax, the mean maximum support loss was 0.18 cm higher within the vaginal canal in the expedited group (95% CI, −0.68 to 0.33 cm). The coprimary outcome of POPDI score was a mean (SD) 23.7 (41.8) points in the expedited group vs 25.7 (39.3) points in the standard group (P = .80). After adjusting for baseline scores, mean POPDI scores were 5.79 points lower in the expedited group (95% CI, −20.41 to 8.84).

Conclusions and Relevance

The findings demonstrate that expedited activity after prolapse surgery results in noninferior anatomic and symptomatic prolapse outcomes. It is reasonable to instruct patients undergoing minimally invasive prolapse surgery to resume physical activities ad lib postoperatively.

Trial Registration

ClinicalTrials.gov Identifier: NCT04329715
Peptide Hydrogels as Immunomaterials and Their Use in Cancer Immunotherapy Delivery
Authors: Falcone Natashya , Ermis Menekse , Tamay Dilara Goksu , Mecwan Marvin , Monirizad Mahsa , Mathes Tess Grett , Jucaud Vadim , Choroomi Auveen , de Barros Natan Roberto , Zhu Yangzhi , Vrana Nihal Engin , Kraatz Heinz‐Bernhard , Kim Han‐Jun , Khademhosseini Ali
Published: May 2023

Peptide‐based hydrogel biomaterials have emerged as an excellent strategy for immune system modulation. Peptide‐based hydrogels are supramolecular materials that self‐assemble into various nanostructures through various interactive forces (i.e., hydrogen bonding and hydrophobic interactions) and respond to microenvironmental stimuli (i.e., pH, temperature). While they have been reported in numerous biomedical applications, they have recently been deemed promising candidates to improve the efficacy of cancer immunotherapies and treatments. Immunotherapies seek to harness the body's immune system to preemptively protect against and treat various diseases, such as cancer. However, their low efficacy rates result in limited patient responses to treatment. Here, the immunomaterial's potential to improve these efficacy rates by either functioning as immune stimulators through direct immune system interactions and/or delivering a range of immune agents is highlighted. The chemical and physical properties of these peptide‐based materials that lead to immuno modulation and how one may design a system to achieve desired immune responses in a controllable manner are discussed. Works in the literature that reports peptide hydrogels as adjuvant systems and for the delivery of immunotherapies are highlighted. Finally, the future trends and possible developments based on peptide hydrogels for cancer immunotherapy applications are discussed.
Heterostructures Regulating Lithium Polysulfides for Advanced Lithium‐Sulfur Batteries
Authors: Wang Tao , He Jiarui , Zhu Zhi , Cheng Xin‐Bing , Zhu Jian , Lu Bingan , Wu Yuping
Published: May 2023

Sluggish reaction kinetics and severe shuttling effect of lithium polysulfides seriously hinder the development of lithium‐sulfur batteries. Heterostructures, due to unique properties, have congenital advantages that are difficult to be achieved by single‐component materials in regulating lithium polysulfides by efficient catalysis and strong adsorption to solve the problems of poor reaction kinetics and serious shuttling effect of lithium‐sulfur batteries. In this review, the principles of heterostructures expediting lithium polysulfides conversion and anchoring lithium polysulfides are detailedly analyzed, and the application of heterostructures as sulfur host, interlayer, and separator modifier to improve the performance of lithium‐sulfur batteries is systematically reviewed. Finally, the problems that need to be solved in the future study and application of heterostructures in lithium‐sulfur batteries are prospected. This review will provide a valuable reference for the development of heterostructures in advanced lithium‐sulfur batteries.
Highly Atom‐Economic and Efficient Electrochemical Selenylative Annulation of 2‐Alkynyl Biaryls
Authors: Mukherjee Nilanjana , Chatterjee Tanmay
Published: May 2023

A catalyst‐ and oxidant‐free, highly efficient, scalable, and sustainable synthetic method is developed for the selenylative annulation of 2‐alkynyl biaryls or 2‐heteroaryl‐substituted alkynyl benzenes with readily available diselenides under electrochemical conditions to synthesize a wide variety of selanyl polycyclic aromatic hydrocarbons and polycyclic heteroaromatics in high to excellent yield up to 99% at room temperature in a short time (2‐5 h). The transformation required only electricity as a green reagent and produces hydrogen gas as the only innocuous byproduct. Notably, the green chemistry metrics of the protocol are found excellent. Mechanistic studies revealed a radical pathway being initiated by the in situ generation of the corresponding selenyl radical from diselenides under electrochemical conditions. Significantly, a direct comparison of the electrochemical approach with that of our previously developed iodine‐catalyzed chemical approach revealed that the electrochemical approach is not only catalyst‐ and oxidant‐free, but also more energy‐efficient, high‐yielding, sustainable, and practical.
A Fe Single Atom Seed‐Mediated Strategy Toward Fe3C/FeNC Catalysts with Outstanding Bifunctional ORR/OER Activities
Authors: Chang Jiangwei , Zhang Qi , Yu Jingkun , Jing Wen , Wang Siyang , Yin Guangchao , Waterhouse Geoffrey I. N. , Lu Siyu
Published: May 2023

The discovery of low‐cost and high‐performance bifunctional oxygen electrocatalysts is vital to the future commercialization of rechargeable zinc‐air batteries (ZABs). Herein, a Fe single atom seed‐mediated strategy is reported for the fabrication of Fe3C species closely surrounded by FeN4C active sites with strong electronic interactions built between them and more importantly, creating optimized coordination environment, via subtly adjusting their ratio, for favorable adsorption energies of oxygen intermediates formed during oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Concretely, the voltage difference (ΔE) between the ORR half‐wave and OER potential at a current density of 10 mA cm−2 for the compositionally‐optimized FeNC/Fe3C‐op electrocatalyst is only 0.668 V, endowing itself one of the best bifunctional OER/ORR benchmarks. As a demo, ZABs assembled with FeNC/Fe3C‐op as the air cathode deliver a remarkable specific capacity (818.1 mAh gZn−1) and a power density (1013.9 mWh gZn−1), along with excellent long‐term durability (>450 h). This work extends the methodology to modulate the activity of FeN4C atomic site, undoubtedly inspiring wide explorations on the precise design of bifunctional oxygen electrocatalysts.
Expert Panel Curation of 113 Primary Mitochondrial Disease Genes for the Leigh Syndrome Spectrum
Authors: McCormick Elizabeth M. , Keller Kierstin , Taylor Julie P. , Coffey Alison J. , Shen Lishuang , Krotoski Danuta , Harding Brian ,   NICHD ClinGen U24 Mitochondrial Disease Gene Curation Expert Panel, Gai Xiaowu , Falk Marni J. , Zolkipli‐Cunningham Zarazuela , Rahman Shamima
Published: May 2023

Objective

Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene–disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes.

Methods

The Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP standardized gene curation for LSS by refining the phenotypic definition, modifying the ClinGen Gene–Disease Clinical Validity Curation Framework to improve interpretation for LSS, and establishing a scoring rubric for LSS.

Results

The GDR with LSS across the nuclear and mitochondrial genomes was classified as definitive for 31 of 114 GDRs curated (27%), moderate for 38 (33%), limited for 43 (38%), and disputed for 2 (2%). Ninety genes were associated with autosomal recessive inheritance, 16 were maternally inherited, 5 were autosomal dominant, and 3 were X‐linked.

Interpretation

GDRs for LSS were established for genes across both nuclear and mitochondrial genomes. Establishing these GDRs will allow accurate variant interpretation, expedite genetic diagnosis of LSS, and facilitate precision medicine, multisystem organ surveillance, recurrence risk counseling, reproductive choice, natural history studies, and determination of eligibility for interventional clinical trials. ANN NEUROL 2023;94:696–712
Hidden Lives. Early Childhood Care as an Academic: The Slow Burn
Authors: Shenvi Ryan A.
Published: May 2023

As the inaugural entry in the new series Hidden Lives, this Viewpoint Article highlights challenges in early childhood care faced by academicians. Research centers must adapt to societal shifts in family structure, uncertainty around research funding, expanded job responsibilities and upheavals brought about by the pandemic. These problems represent opportunities for change at the technological, cultural and policy levels. It is crucial that we recognize those in need and help where we can.
Construction of Asymmetrical Dual Jahn–Teller Sites for Photocatalytic CO2 Reduction
Authors: Liu Huanhuan , Chen Yanxu , Li Huiyi , Wan Guanglin , Feng Yafei , Wang Wentao , Xiao Chong , Zhang Genqiang , Xie Yi
Published: May 2023

Photocatalytic CO2 reduction (PCR) expresses great attraction to convert useless greenhouse gas into valuable chemical feedstock. However, the weak interactions between catalytic sites and PCR intermediates constrains the PCR activity and selectivity. Herein, we proposed a new strategy to match the intermediates due to the maximum orbital overlap of catalytic sites and C1 intermediates by establishing dual Jahn–Teller (J–T) sites, in which, the strongly asymmetric J–T sites can break the nonpolar CO2 molecules and self‐adapt the different structure of C1 intermediates. Taking cobalt carbonate hydroxide as an example, the weakly symmetric dual cobalt (Co2) dual J–T sites, weakly asymmetric Fe&Co sites and strongly asymmetric Cu&Co sites were assembled. After illumination, the interaction between dual J–T sites and the CO2 molecules enhances J–T distortion, which further modulates the PCR activity and selectivity. As a result, the Cu&Co sites exhibited CO yield of 8137.9 μmol g−1, about 2.3‐fold and 4.2‐fold higher than that of the Fe&Co and Co2 sites within 5‐hour photoreaction, respectively. In addition, the selectivity achieved as high as 92.62 % than Fe&Co (88.67 %) and Co2 sites (55.33 %). This work provides a novel design concept for the construction of dual J–T sites to regulate the catalytic activity and selectivity.
Coupled Solar Battery with 6.9 % Efficiency
Authors: Jiao Lei , Zhang Xiang , Feng Yangyang , Lin Jing , Yuan Daqiang , Wang Yaobing
Published: May 2023

Solar‐to‐electrochemical energy storage in solar batteries is an important solar utilization technology comparable to solar‐to‐electricity (solar cells) and solar‐to‐fuel (photocatalytic cells) conversion. Unlike the indirect approach of integrated solar flow batteries combining photoelectrodes with redox‐electrodes, coupled solar batteries enable direct solar energy storage, but are hampered by low efficiency due to rapid charge recombination of materials and misaligned energy levels between electrodes. Herein, we propose a design for a coupled solar battery that intercouples two photo‐coupled ion transfer (PCIT) reactions through electron‐ion transfer upon co‐photo‐pumping of photoelectrochemical storage cathode and anode. We used a representative covalent organic framework (COF) to achieve efficient charge separation and directional charge transfer between two band‐matched photoelectrochemical storage electrodes, with a photovoltage sufficient for COF dual‐redox reactions. By pumping these electrodes, the coupled solar battery stores solar energy via two synergistic PCIT reactions of electron‐proton‐relayed COF oxidation and reduction, and the stored solar energy is released as electrochemical energy during COF regeneration in discharge while interlocking the loops. A breakthrough in efficiency (6.9 %) was achieved, adaptive to a large‐area (56 cm2) tandem device. The presented photo‐intercoupled electron‐ion transfer (PIEIT) mechanism provides expandable paths toward practical solar‐to‐electrochemical energy storage.
Total Synthesis of Thiamyxins A–C and Thiamyxin E, a Potent Class of RNA‐Virus‐Inhibiting (Cyclo)depsipeptides
Authors: Bauer Kevin , Kazmaier Uli
Published: May 2023

We present the first total synthesis of the thiamyxins A–C and the now fully characterized thiamyxin E, an interesting class of thiazole‐ and thiazoline‐rich depsipeptides with diverse antiviral activity. The synthesis features a parallel closing of two methyl thiazoline units, with low epimerization of the very labile adjacent stereocenter. It also includes the three‐step synthesis of an uncommon hydroxy acid and the oxidation‐free elimination of a phenylselenide to form a dehydroalanine moiety. The exploitation of the acid‐labile stereocenter at the isoleucine moiety and the reopening of the macrolactones gave access to the four thiamyxins with good yields and diastereomeric purities from a single precursor. The modular total synthesis allows further testing of the biological activity and gives opportunities to explore the pharmacophore and antiviral target through derivatization.
Synergistic modification of short‐chain fluoro‐alcohol and siloxane end‐capping agents endowing an enhanced superhydrophobic waterborne polyurethane coating
Authors: Wang Bolin , Zhao Nana , Wu Jiawei , Pan Zhicheng , Zhao Cheng , Pan Mingwang
Published: May 2023

Waterborne polyurethane (WPU) is an environmentally friendly product that can replace organic solvents with water. Still, its linear molecular chain structure and the presence of hydrophilic groups greatly affect water resistance and mechanical properties, limiting its wide application in the field of coatings. Herein, a series of fluorosilicone modified waterborne polyurethanes (FSiWPUs) were prepared by introducing tridecafluoro‐nonanol (TFN) and (3‐aminopropyl) triethoxysilane (APTES) into the ends of molecular chains of WPUs. These chains were constituted by different soft segments, including polybutylene adipate glycol, polycarbonate diol, or polytetramethylene ether glycol. Then fluorine element in TFN migrates and aggregates onto the surface during FSiWPU film‐forming to reduce the surface energy. Meanwhile, the hydrolytic condensation of APTES forms a Si–O–Si micro‐crosslinking structure. As a result, the two capping agents enable the modified FSiWPU to have better hydrophobicity, water resistance, and mechanical properties. The research results show that when the TFN:APTES molar ratio of capping agents introduced is 8:2, the static water contact angles of FSiWPUs with different soft sections reach 161.4°–165.3° and the maximum water absorption rate reduce to 8.9%–13.78%. Due to the simultaneous improvement of hydrophobic, water resistance, and mechanical properties, the modified FSiWPUs become the most promising candidates for superhydrophobic coatings.
Measurement invariance of the Domain‐Specific Risk‐Taking (DOSPERT) scale
Authors: Welindt Dillon , Condon David M. , Weston Sara J.
Published: May 2023

Group‐level risk attitudes are often studied across psychology domains (e.g., binge drinking among college students, and driving risk by gender). In measuring these differences by self‐report, such work relies on the assumption that those measures of risk attitude function equivalently across demographic groups—that is, that the measure employed has the property of measurement invariance. Here, we examine the measurement invariance properties of a widely used risk measure, the Domain‐Specific Risk‐Taking (DOSPERT) scale across different demographic groups. A secondary goal was to determine whether a hierarchical or bifactor model better fits the data. Data were collected from Prolific using a stratified sampling approach to ensure sufficient and unconfounded sampling of sex, socioeconomic status (SES), and race (N = 412). Sample groups consisted of approximately 50 participants each, based on the intersection of three dichotomized demographic groups (high vs. low SES, White vs. non‐White, and female vs. male). Subjects completed the 30‐item form of the DOSPERT assessing likelihood, perceived benefit, and riskiness of the same 30 behaviors. The bifactor models showed a superior fit to the hierarchical models and were used in subsequent analyses. These analyses demonstrated that no models fit generally acceptable criteria for configural fit, and many models additionally fail cutoffs for metric and scalar invariance. This study adds to findings that the DOSPERT does not perform equivalently across demographic groups. We suggest development of a scale of risk that is invariant across commonly assessed demographic factors.
What is an enhancer?
Authors: Thomas Henry Fabian , Buecker Christa
Published: May 2023

Tight control of the transcription process is essential for the correct spatial and temporal gene expression pattern during development and in homeostasis. Enhancers are at the core of correct transcriptional activation. The original definition of an enhancer is straightforward: a DNA sequence that activates transcription independent of orientation and direction. Dissection of numerous enhancer loci has shown that many enhancer‐like elements might not conform to the original definition, suggesting that enhancers and enhancer‐like elements might use multiple different mechanisms to contribute to transcriptional activation. Here, we review methodologies to identify enhancers and enhancer‐like elements and discuss pitfalls and consequences for our understanding of transcriptional regulation.
New insights from modelling studies and molecular dynamics simulations of the DIS5‐S6 extracellular linker of the skeletal muscle sodium channel NaV1.4
Authors: Robinson Anna , Tao Elaine , Neeman Teresa , Kaehler Benjamin , Corry Ben
Published: May 2023

In the CryoEM‐structure of the hSkMNaV1.4 ion channel (PDB:6AGF), the 59‐residue DIS5‐S6 linker peptide was omitted due to absence of electron density. This peptide is intriguing – comprised of unique sequence and found only in mammalian skeletal muscle sodium ion channels. To probe potential physiological and evolutionary significance, we constructed an homology model of the complete hSkMNaV1.4 channel. Rather than a flexible random coil potentiating drift across the channel, the linker folds into a compact configuration through self‐assembling secondary structural elements. Analogous sequences from 48 mammalian organisms show hypervariability with between 40% and 100% sequence similarity. To investigate structural implications, sequences from 14 representative organisms were additionally modelled. All showed highly conserved N‐and C‐terminal residues closely superimposed, suggesting a critical functional role. An optimally located asparagine residue within the conserved region was investigated for N‐linked glycosylation and MD simulations carried out. Results suggest a complex glycan added at this site in the linker may form electrostatic interactions with the DIV voltage sensing domain and be mechanistically involved in channel gating. The relationship of unique sequence, compact configuration, potential glycosylation and MD simulations are discussed relative to SkMNaV1.4 structure and function.
Aptamer‐based strategies against SARS‐CoV‐2 viruses
Authors: Huang Yihao , Chen Ximing , Zhang Jialu , Tian Wenhai , Liu Siwen , Chun‐Yee Tam Rachel , Yang Chaoyong , Song Yanling
Published: May 2023

The COVID‐19 pandemic, caused by SARS‐CoV‐2, has seriously threatened human life and security in recent years and has had a serious impact on economic development. A range of strategies, including antibodies, small‐molecule agents and vaccines, have been developed and widely used to combat SARS‐CoV‐2. However, the uncertain development and susceptibility to mutation of SARS‐CoV‐2 pose challenges to these approaches, making it necessary to develop a broader range of strategies to complement and expand the diversity of attacks against SARS‐CoV‐2. As promising tools against SARS‐CoV‐2, aptamers have attracted wide attention due to their unique molecular properties. In this review, we survey SARS‐CoV‐2 aptamers and aptamer‐based detection tools as well as aptamer‐based therapeutics. In addition, we analyze the potential value of aptamers in the investigation of SARS‐CoV‐2 infection mechanism and vaccine design. Finally, we look forward to the future development direction of aptamers against SARS‐CoV‐2 or other viruses.
Oxygenated Cembrane Diterpenes from the South China Sea Soft Coral Sinularia tumulosa**
Authors: Zhu Sheng‐Hui , Yu Dan‐Dan , Su Ming‐Zhi , Luo Hui , Yao Li‐Gong , Gu Feifei , Liang Lin‐Fu , Wang Hong , Guo Yue‐Wei
Published: May 2023

The chemical investigation of the rarely studied soft coral Sinularia tumulosa resulted in the discovery of five oxygenated cembrane diterpenes 1–5, including two new compounds situmulins A (1) and B (2). The structures of 1 and 2 were established through the extensive analyses of 1D and 2D NMR spectral data together with the comparisons with the known compounds. Furthermore, the absolute configuration of 1 was determined by the time‐dependent density functional theory (TDDFT) ECD approach, while the relative configuration of 2 was assigned via the quantum mechanical‐NMR (QM‐NMR) calculations. It might be worth to point out it is the first time to disclose the presence of cembrane diterpenes in the title species. In the bioassays, compound 2 not only showed strong antibacterial activities against fish pathogenic bacteria Streptococcus parauberis FP KSP28 and Phoyobacterium damselae FP2244 with both minimum inhibitory concentration for 90 % (MIC90) values of 25 μM, but also demonstrated substantial inhibitory efficacy against vancomycin‐resistant Enterococcus faecium bacteria G1, G4, G7, G8 and G13 from several individuals, with MIC90 values of 25, 50, 100, 50 and 25 μM, respectively.
Design, Synthesis, and Antitumor Activities of Isomers of Artemisinin Dimer Derivatives
Authors: Yue Lingyun , Pan Yanna , Wang Jiaoying , Yue Lin , Luo Yuxuan , Lv Fang , Lv Jiagang , Chen Jianping , Zhao Qingjie , Lin Haixia
Published: May 2023

In recent years, numerous studies have reported on the anti‐tumor properties of artemisinin and its derivatives. However, the relationship between their artemisinin chirality and activity remains unknown. In this study, we synthesized a series of artemisinin dimer derivatives with three different chiral structures and tested their antiproliferative activity in MCF‐7 and HepG2 cells using the CCK‐8 assay. Interestingly, we discovered that artemisinin dimer derivatives with β, β and α, β conformations at C‐10 exhibited stronger anti‐tumor activity than those with an α, α configuration in MCF‐7 and HepG2 cells. Notably, compound 4 showed an activity of 0.06 μM in MCF‐7 cells. This study demonstrates the relationship between the conformation and activity of artemisinin dimer derivatives, and these derivatives have the potential to be developed into anti‐cancer drugs.
Analytical Methods for the Rapid Determination of Solid Biofuel Quality
Authors: Endriss Felix , Kuptz Daniel , Hartmann Hans , Brauer Stefan , Kirchhof Rainer , Kappler Andreas , Thorwarth Harald
Published: May 2023

Fuel properties of solid biofuels are essential aspects for the energy‐efficient and low‐emission operation of biomass heat and power plants. Hence, fuel quality parameters are often defined and used for pricing in supply contracts. To simplify and accelerate analytical approaches, rapid analysis devices are required to determine fuel properties such as water‐ and ash content, calorific value, and chemical composition on‐site. This article gives an overview about available technologies and, if applicable, their current state of use as rapid analysis devices for solid biofuels.
Building climate resilience through crop residue utilization: Experiences of Ghanaian smallholder farmers
Authors: Antwi‐Agyei Philip , Atta‐Aidoo Jonathan , Guodaar Lawrence , Dougill Andrew
Published: May 2023

A major limiting factor affecting the uptake of conservation agriculture practices in smallholder farming systems in sub‐Saharan Africa is the limited availability of sufficient crop residues for use as surface mulch. This paper assesses the trade‐offs in crop residue utilization among smallholder farmers and its implications for soil management in the face of climate change risks in northern Ghana. The paper triangulated data from 350 household surveys with participatory key informant interviews from seven selected communities in three districts of northern Ghana. The problem confrontation index (PCI) was adopted to identify and rank the challenges associated with farmers’ decision to use crop residues, while a multivariate probit model was used to analyse and predict the factors that influence farmers’ choice of crop residue management practices. Results showed that crop residues were used as cooking fuel in households (21%), livestock feed (21%), left on the farm to decompose as mulch (34%) or burned to clear the land (24%). Key challenges identified included high labour cost (PCI = 404), high labour intensity (PCI = 388), the cost and transport for collection and storage of externally sourced crop residue (PCI = 383) and the low benefit from crop residue to farm output/soil fertility (PCI = 339). Results from the multivariate probit model revealed that household and farm variables, institutional and socio‐psychological factors, and experience of some climate shocks all influence farmers’ choice of crop residue management practices. Crop residue use and management practices adopted were determined by factors including the crops being grown, challenges faced by farmers and the management options available. The study recommends the need for the Government of Ghana to empower farmers through the provision of technical knowledge and machinery for the sustainable utilization of crop residues due to the high labour intensity and cost associated with such practices.
Systematic review and meta‐analysis: Prognostic impact of time from diagnosis to treatment in patients with acute myeloid leukemia
Authors: Franco Stephanie , Geng Xue , Korostyshevskiy Valeriy , Karp Judith E. , Lai Catherine
Published: May 2023

Background

Acute myeloid leukemia (AML) has been considered an oncologic emergency that requires initiation of chemotherapy immediately after diagnosis. With the introduction of novel targeted therapies, there is a potential benefit associated with delaying definitive treatment for identification of actionable therapeutic targets. Unfortunately, cytogenetic/molecular testing can take >7 days to return, and there is not a consensus regarding the prognostic impact of time from diagnosis to treatment (TDT) in AML.

Methods

A literature review and meta‐analysis of studies done to date that evaluate TDT was conducted. Studies that reported baseline characteristics, TDT, and outcomes for patients with AML were selected. Outcomes included overall survival (OS), complete remission (CR), and mortality. Studies that measured CR rates within each TDT range and data to calculate odds ratios were included in the meta‐analysis. The remaining outcomes were synthesized descriptively for literature review.

Results

Thirteen studies were identified, which comprised a total of 14,946 patients. Median TDT values were between 1 and 8 days. Several studies found a significant association between prolonged TDT and older age and lower proliferation burden. Four of 11 studies did not detect a significant relationship between TDT and OS. No studies found a significant association between TDT and early death. Six of eight studies did not find a significant association between TDT and CR rate. The meta‐analysis found a significant association between prolonged TDT and decreased achievement of CR (p < .05).

Conclusions

Results were highly variable but suggest it may be feasible to pursue cytogenetic/molecular testing in patients who are clinically stable, particularly in those aged 60 years and older.
Exploring the Self‐Cleaning Facets of Fluorinated Graphene Nanoarchitectonics: Progress and Perspectives
Authors: Datta K. K. R.
Published: May 2023

The development of graphene nanoarchitectonics, including their synthesis, surface modification, interfaces, conductivity and porosity, has moved forward rapidly and attracted attention from interdisciplinary research fields. Fluorinated graphene (FG), a rising star and a fascinating member of graphene family has been identified as a promising material for multiple applications, such as sensors, optics, catalysis and self‐cleaning technologies. In this review, we highlight the important aspects of FG pertinent to physiochemical stability and self‐cleaning technologies. We discuss the precise functionalization of FG surfaces with organic functionalities, which are promising for creating high‐performance graphene derivatives. Also, by utilizing the reactivity of few‐layered FG nanosheets, it is possible to develop coatings based on dispersions of functionalized FG inks coupled with porous solids and tubular nanomaterials with super‐wetting functions. The functional groups of the resultant hybrids are connected to innovative substrates including meshes and macroporous sponges that can be useful for super‐wetting containers and oleophilic sorbents. Furthermore, we discuss hydrophobic FG‐porphyrin hybrids with metal coordination and hydrophobicity dependent photoluminescence. Finally, the self‐cleaning action and anti‐corrosion features of FG hybrids are explored, with potential applications in triboelectric nanogenerators and water harvesting. Future development of these materials should focus on new designs, porosity control, batch uniformity, durable self‐cleaning membranes, smart textiles, eco‐compatible coatings and disposability.
Investigating genes associated with cardiovascular disease among heart failure patients for translational research and precision medicine
Authors: Ahmed Zeeshan , Zeeshan Saman , Persaud Nicholas , Degroat William , Abdelhalim Habiba , Liang Bruce T.
Published: May 2023

Background

Cardiovascular disease (CVD) is a leading cause of premature mortality in the United States and the world. CVD comprises several complex and mostly heritable conditions, which range from myocardial infarction to congenital heart disease. The risk factors contributing to the development of CVD and response to therapy in an individual patient are highly variable. Here, we report our findings from an integrative analysis of gene expression, disease‐causing gene variants and associated phenotypes among CVD populations, with a focus on high‐risk heart failure (HF) patients.

Methods

We built a cohort using electronic health records of consented patients with available samples and then performed high‐throughput whole genome and RNA sequencing of key genes responsible for HF and other CVD pathologies. Our in‐depth gene expression analysis revealed differentially expressed genes associated with HF and other CVDs. We performed a variant analysis of whole genome sequence data of CVD patients and identified genes with altered gene expression with functional and non‐functional mutations in these genes.

Results

Our results highlight the importance of investigating the mechanisms of CVD progression through multi‐omics datasets. Next, we performed splice mutation and variant distribution analysis of genes associated with HF and other CVD. We implemented Jensen–Shannon divergence (JSD)‐based method and identified HBA1, FADD, ADRB2, NPPB, ADRB1, ADB and NPPC genes with the greatest variance based on their JSD scores. Our study provided evidence that applying integrative data analysis approach involving genomics and transcriptomics data will not only help understand the pathophysiology of CVD diseases but also reduce heterogeneity in disease subtypes.
OMIP‐94: Twenty‐four‐color (thirty‐marker) panel for deep immunophenotyping of immune cells in human peripheral blood
Authors: Pierzchalski Arkadiusz , Zenclussen Ana C. , Herberth Gunda
Published: May 2023

This newly established 24‐color (30‐marker) panel focuses on the characterization of the main human immune cell subtypes and was optimized for the analysis of human whole blood using a full spectrum flow cytometer. The panel covers all main leukocyte populations: neutrophils, eosinophils and basophils, monocytes (with additional subsets), dendritic cells, innate lymphoid cells and lymphocytes. As for lymphocytes, this panel includes CD4+ T helper, Treg cells, and CD8+ cytotoxic T cells. Further T cells subsets are included with special focus on invariant T cells: γδ T cells (including δ2TCR variant), invariant NKT cells and MAIT (mucosal‐associated invariant T cells) cells. Additionally, total B cells (including Bregs and plasmocytes), NK cells, and NKT cells are included. For the overall check of activation status of the analyzed immune cells we used HLA‐DR, CD38, CD57, CD69, PD‐1, and CD94. In addition, we used CD62L, CD45RA, CD27, and CD39 to describe the differentiation status of these cells. The panel was designed to maximize the information that can be obtained from surface markers in order to avoid the need for fixation and permeabilization steps. The presented multimarker panel offers the possibility to discover new immune cell subtypes which in patients and in cohort studies may lead to the identification of altered immune phenotypes and might give a link to immune system based or to certain other diseases. This panel was developed for a full spectrum flow cytometer equipped with a minimum of three lasers. We developed this panel using healthy human fresh blood, however it was also successfully used for staining of isolated human peripheral blood mononuclear cells (PBMC).
Assessment of self‐stigma in epilepsy: Validation of the German version Epilepsy Self‐Stigma Scale (ESSS‐G)
Authors: Kuramochi Izumi , Iwayama Takayuki , Brandt Christian , Yoshimasu Haruo , Bien Christian G. , Hagemann Anne
Published: May 2023

Objective

Self‐stigma is the internalization of unfavorable public perceptions, which people with epilepsy (PWE) frequently experience. PWE with strong self‐stigma have low self‐esteem and are less likely to engage in treatment behavior. The Epilepsy Self‐Stigma Scale (ESSS) has been developed and validated in Japan. We translated the ESSS into German for this study to examine its reliability and validity.

Methods

We created the German version of ESSS (ESSS‐G) based on the original Japanese version. From May to October 2022, we recruited out‐ and inpatients from Bethel Epilepsy Centre, University Hospital for Epileptology, for psychometric evaluation. Inclusion criteria were an age of ≥18 years, sufficient reading and speaking skills in German, and the ability to comprehend the German questionnaires. Participants also completed the Rosenberg Self‐Esteem Scale (RSES), Neurological Disorders Depression Inventory for Epilepsy (NDDI‐E), Generalized Anxiety Disorder 7 (GAD‐7), Epilepsy Knowledge Scale, and items on “overall quality of life (QOL)” and “overall health” (items from QOLIE‐31).

Results

One hundred twenty‐eight of 146 patients asked to participate granted informed consent and completed the study questionnaire (87.7% response rate). 115 cases were analyzed since 13 did not match the inclusion criteria. The analysis revealed a single factor explaining 49.2% of the total variance. All factor loadings were >0.40, and the reliability was high (Cronbach's α = 0.80). Higher ESSS total scores were associated with higher anxiety (GAD‐7, r = 0.54, P < 0.001) and depression (NDDI‐E, r = 0.45, P < 0.001), lower self‐esteem (RSES, r = −0.41, P < 0.001), overall QOL (r = −0.40, P < 0.001), and overall health (r = −0.35, P < 0.001), but not with knowledge about epilepsy (r = 0.03, P = 0.770). In Germany, females, younger individuals, patients with earlier seizure onset, and those with generalized epilepsy had significantly higher self‐stigma.

Significance

The German version of the ESSS proved reliable and valid. It allows to evaluate the efficacy of treatment strategies in lowering self‐stigma and conducting intercultural comparisons of epilepsy self‐stigma.
Food‐borne polyphenols: A biocompatible anchor recuperating iron homeostasis
Authors: Li Yonglu , Feng Xinyu , Zheng Xiaodong , Zhu Jiajin , Gu Qing
Published: May 2023

Food‐borne polyphenols have long contributed to human health via multifaceted mechanisms, while emerged studies especially those published in recent 10 years have witnessed the close relevance between the bioactivity of polyphenols with iron homeostasis. Polyphenols are involved in various physiological processes of iron and manifest with multidirectional regulative effects. The diversiform polyphenols–iron interactions have extended the cognition of various disorders and diseases. This review aims to present a comprehensive scope of polyphenols–iron interactions, and the structural property, biological effects, and molecular mechanism of polyphenols on iron homeostasis were systematically illustrated, categorized, exemplified, and discussed. Multiple related disorders and diseases were focused on, and the specific polyphenols–iron interactions were elucidated during the processes of pathogenesis, development, intervention, and treatment. Present shortages such as bidirectional effects, unclear mechanism, clinical challenges, and extraction efficiency of polyphenols were also analyzed, and some innovative techniques adopted for polyphenols–iron‐based systems or therapies explorations were discussed, inspiring future perspectives for the understandings, exploitations, and correlations of both iron homeostasis and polyphenols. This review brings the polyphenols–iron interactions on the stage, telling the full story of how polyphenols anchor iron to achieve beneficial bioactivities, enlightening ideas for polyphenols–iron interactions‐based understanding of diseases, and illumining strategies for polyphenols as dietary adjuvant or future therapeutic agents for iron‐related physiological abnormality.
How to use AI in pathology
Authors: Schüffler Peter , Steiger Katja , Weichert Wilko
Published: May 2023

AI plays an important role in pathology, both in clinical practice supporting pathologists in their daily work, and in research discovering novel biomarkers for improved patient care. Still, AI is in its starting phase, and many pathology labs still need to transition to a digital workflow to be able to enjoy the benefits of AI. In this perspective, we explain the major benefits of AI in pathology, highlight key requirements that need to be met and example how to use it in a typical workflow.
The efficient CO2 fixation catalyzed by K‐doped g‐C3N4 catalyst for synthesizing benzimidazoles at atmospheric pressure
Authors: Tu Xuewei , Zhang Luping , Chen Yutong , Zhu Shouxin , Sun Can , Jin Jiali , Liu Min , Zheng Hui
Published: May 2023

The conversion of CO2 into valuable chemicals to reduce greenhouse gas emissions has received extensive attention. Converting CO2 into pharmaceutical intermediates via graphitic carbon nitride (CN) at atmospheric pressure is a challenge. In this work, a series of novel graphitic carbon nitrides (K‐CN) catalysts with different doping ratios of K were synthesized by post‐treatment of CN with KOH as a dopant under magnetic stirring. Herein, substrates of o‐phenylenediamine with different electron‐donating/withdrawing groups were employed to convert CO2 into high‐value heterocyclic benzimidazoles. The optimal reaction conditions were determined by a single factor optimization approach. A series of benzimidazole derivatives were synthesized with a yield of up to 96% under atmospheric pressure, indicating that the catalyst can efficiently fix CO2. This work not only designs a simple and low‐cost K‐CN catalyst but also provides a new pathway for converting CO2 into valuable benzimidazole derivatives at atmospheric pressure. © 2023 Society of Chemical Industry and John Wiley & Sons, Ltd.