bluuebunny/crossref_metadata_2025 huggingface dataset:
Hubungan Pengetahuan HIV/AIDS dengan Stigma terhadap Orang dengan HIV/AIDS di Kalangan Remaja 15-19 Tahun di Indonesia (Analisis Data SDKI Tahun 2012)
Authors: Situmeang Berliana , Syarif Syahrizal , Mahkota Renti
Published: February 2019

Stigma terhadap ODHA menjadi salah satu hambatan paling besar dalam pencegahan, perawatan, pengobatan, dan dukungan HIV/AIDS. Pengetahuan tentang HIV/AIDS mempengaruhi terjadinya stigma terhadap ODHA. Tujuan penelitian ini untuk mengetahui hubungan pengetahuan tentang HIV/AIDS dengan stigma terhadap ODHA di kalangan remaja usia 15-19 tahun di Indonesia. Penelitian ini menggunakan data Survei Demografi dan Kesehatan Indonesia (SDKI) Tahun 2012 dengan disain cross-sectional. Sampel penelitian sebanyak 8.316 orang. Hasil studi menunjukkan 71,63% remaja mempunyai stigma terhadap ODHA, 49,10% remaja mempunyai pengetahuan yang kurang tentang HIV. Pengetahuan yang kurang tentang HIV/AIDS berhubungan dengan stigma terhadap ODHA (PR= 1,210 95% CI: 1,149-1,273) setelah dikontrol oleh keterpaparan media massa. Perlu dilakukan peningkatan pengetahuan tentang HIV/AIDS pada remaja guna mengurangi stigma terhadap ODHA.
Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs
Authors: Kern David M , Oh SeCheol , Hite Richard K , Brohawn Stephen G
Published: February 2019

Hypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here, we present single-particle cryo-electron microscopy structures of Mus musculus LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction. Constricted and expanded structures reveal coupled dilation of cytoplasmic LRRs and the channel pore, suggesting a mechanism for channel gating by internal stimuli. Conformational and symmetry differences between LRRC8A structures determined in detergent micelles and lipid bilayers related to reorganization of intersubunit lipid binding sites demonstrate a critical role for the membrane in determining channel structure. These results provide insight into LRRC8 gating and inhibition and the role of lipids in the structure of an ionic-strength sensing ion channel.
Analysis of the genetic diversity and population structure of Salix psammophila based on phenotypic traits and simple sequence repeat markers
Authors: Hao Lei , Zhang Guosheng , Lu Dongye , Hu Jianjun , Jia Huixia
Published: February 2019

Salix psammophila (desert willow) is a shrub endemic to the Kubuqi Desert and the Mu Us Desert, China, that plays an important role in maintaining local ecosystems and can be used as a biomass feedstock for biofuels and bioenergy. However, the lack of information on phenotypic traits and molecular markers for this species limits the study of genetic diversity and population structure. In this study, nine phenotypic traits were analyzed to assess the morphological diversity and variation. The mean coefficient of variation of 17 populations ranged from 18.35% (branch angle (BA)) to 38.52% (leaf area (LA)). Unweighted pair-group method with arithmetic mean analysis of nine phenotypic traits of S. psammophila showed the same results, with the 17 populations clustering into five groups. We selected 491 genets of the 17 populations to analyze genetic diversity and population structure based on simple sequence repeat (SSR) markers. Analysis of molecular variance (AMOVA) revealed that most of the genetic variance (95%) was within populations, whereas only a small portion (5%) was among populations. Moreover, using the animal model with SSR-based relatedness estimated of S. psammophila, we found relatively moderate heritability values for phenotypic traits, suggesting that most of trait variation were caused by environmental or developmental variation. Principal coordinate and phylogenetic analyses based on SSR data revealed that populations P1, P2, P9, P16, and P17 were separated from the others. The results showed that the marginal populations located in the northeastern and southwestern had lower genetic diversity, which may be related to the direction of wind. These results provide a theoretical basis for germplasm management and genetic improvement of desert willow.
Potential antidiabetic effect of ethanolic and aqueous-ethanolic extracts ofRicinus communisleaves on streptozotocin-induced diabetes in rats
Authors: Gad-Elkareem Mohamed A.M. , Abdelgadir Elkhatim H. , Badawy Ossama M. , Kadri Adel
Published: February 2019

Recently, herbal drugs and their bioactive compounds have gained popularity in the management of diabetes mellitus (DM), which has become an epidemic disease all over the world and is especially prevalent in the Kingdom of Saudi Arabia (KSA). This study aimed to investigate the antidiabetic effect of ethanolic and aqueous-ethanolic extracts of wildRicinus communis(R. communis) leaves in streptozotocin (STZ) induced diabetic rats. Diabetic rats were administered orally with the mentioned extracts at doses of 300 and 600 mg/kg/BW for 14 days, and the obtained results of different biochemical parameters were compared with normal control, diabetic control and standard drug glibenclamide (5 mg/kg/BW). The obtained results revealed a remarkable and significantly (P < 0.05) reverse effect of the body weight loss, observed when diabetic rats were treated with ethanol and aqueous-ethanol extracts at 300 mg/kg/BW. Administration of the ethanol extract at 600 mg/kg/BW significantly (P < 0.05) reduced the blood glucose level. A significant increase in the AST, ALT and ALP levels (P < 0.05) was observed in the diabetic control and in the experimental groups with glibenclamide which was also significantly (P < 0.05) lowered after treatment with extracts at special doses. Total proteins, albumin, total bilirubin, direct bilirubin, creatinine and urea were also investigated and compared to the corresponding controls. We showed that administration ofR. communisextract generally significantly (P < 0.05) ameliorated the biochemical parameters of diabetic rats. Also, the changes in serum electrolyte profile were assessed and the results demonstrate that administration of extracts at concentration of 600 mg/kg/BW generally inhibits the alteration maintain their levels. The obtained data imply the hypoglycemic effects of this plant, which may be used as a good alternative for managing DM and therefore validating its traditional usage in KSA.
ST-Segment Elevation in the Stress Laboratory
Authors: Galeano-Lovera Santiago F. , Kusumoto Fred , Allison Thomas G.
Published: November 2024

This case report describes a woman in her early 60s who went into cardiac arrest immediately after administration of an echocardiogram contrast agent.
A Clinical Update on MASLD
Authors: Zhang Grace Y. , Brandman Danielle
Published: November 2024

This Clinical Insights discusses new diagnostic criteria, risk stratification, and emerging treatments of metabolic dysfunction–associated steatotic liver disease (MASLD; formerly nonalcoholic fatty liver disease).
Antihypertensive Deprescribing and Cardiovascular Events Among Long-Term Care Residents
Authors: Odden Michelle C. , Graham Laura A. , Liu Xiaojuan , Dave Chintan V. , Lee Sei J. , Li Yongmei , Jing Bocheng , Fung Kathy , Peralta Carmen A. , Steinman Michael A.
Published: November 2024

Importance

The practice of deprescribing antihypertensive medications is common among long-term care residents, yet the effect on cardiovascular outcomes is unclear.

Objective

To compare the incidence of hospitalization for myocardial infarction (MI) or stroke among long-term care residents who are deprescribed or continue antihypertensive therapy.

Design, Setting, and Participants

This comparative effectiveness research study used target trial emulation with observational electronic health record data from long-term care residents aged 65 years or older admitted to US Department of Veterans Affairs community living centers between October 1, 2006, and September 30, 2019, and taking at least 1 antihypertensive medication. Analyses were conducted between August 2023 and August 2024.

Exposure

A reduction in the number of antihypertensive medications or dose (by ≥30%), assessed using barcode medication administration data.

Main Outcome and Measures

Incidence of MI and stroke hospitalization up to 2 years was assessed using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. A pooled logistic regression model with inverse probability of treatment weighting (IPTW) and inverse probability of censoring weighting (IPCW) was used to estimate per-protocol effects.

Results

Of 13 096 long-term care residents (97.4% men; median age, 77 years [IQR, 70-84 years]) taking antihypertensive medication, 17.8% were deprescribed antihypertensive medication over a period of 12 weeks. The estimated unadjusted cumulative incidence of stroke or MI hospitalization over 2 years was similar among residents who were and were not deprescribed antihypertensives in per-protocol analyses (11.2% vs 8.8%; difference, 2.4 percentage points [95% CI, −2.3 to 7.1 percentage points]). Participant characteristics were balanced after applying IPTW and IPCW; all standardized mean differences were less than 0.05. After full adjustment for confounding and informative censoring, the per-protocol analysis results showed no association of antihypertensive deprescribing with MI or stroke hospitalization (hazard ratio, 0.93; 95% CI, 0.70-1.26).

Conclusions and Relevance

In this comparative effectiveness research study, deprescribing antihypertensive medication was not associated with risk of hospitalization for MI or stroke in long-term care residents. These findings may be informative for long-term care residents and clinicians who are considering deprescribing antihypertensive medications.
Obesity and Outcomes in Adoptive Cellular Therapy in Solid Tumors
Authors: Tao Derrick L. , Nardo Mirella , Leung Cheuk Hong , Lin Heather Y. , Kang Lei , Le Hung , Dumbrava Ecaterina E. , Hong David S.
Published: November 2024

This cohort study investigates the association of obesity with adoptive cell therapy outcomes in patients with solid tumors.
Outcomes in Randomized Clinical Trials Testing Changes in Daily Water Intake
Authors: Hakam Nizar , Guzman Fuentes Jose Luis , Nabavizadeh Behnam , Sudhakar Architha , Li Kevin D. , Nicholas Catherine , Lui Jason , Tahir Peggy , Jones Charles P. , Bent Stephen , Breyer Benjamin N.
Published: November 2024

Importance

Several public recommendations exist regarding the amount of daily water intake, yet the supporting evidence is not clear, and benefits of increasing water consumption are not well-established.

Objective

To summarize evidence from randomized clinical trials (RCTs) pertaining to the health-related outcomes associated with increased or decreased daily water consumption.

Evidence Review

A systematic search of PubMed, Web of Science, and Embase was performed up to April 6, 2023. Studies were included if they aimed to assess the impact of daily water consumption by any defined amount on any health-related outcome.

Findings

Of 1464 records screened, 18 (1%) eligible studies were included in the review. Among eligible studies, 15 (83%) were parallel group RCTs, and 3 (16%) were crossover studies. Interventions in these studies consisted of a recommendation to alter the daily amount of water intake by a specific amount for a predefined period ranging between 4 days and 5 years, while the control groups were mostly asked to maintain their usual intake habits. The studies assessed various populations. Recurring primary end points included weight loss, fasting blood glucose level, headache, urinary tract infection, and nephrolithiasis. Consuming additional water was associated with greater weight loss (range, 44%-100% more than control conditions) and fewer nephrolithiasis events (15 fewer events per 100 participants over 5 years). Single studies suggested benefits related to migraine prevention, urinary tract infection, diabetes control, and hypotension. Ten studies (55%) reported at least 1 positive result, and 8 studies (44%) reported negative results.

Conclusions and Relevance

This systematic review found that there is a limited number of clinical trials in the literature assessing the benefits of increasing water intake related to a large variety of health outcomes. While the quality and quantity of evidence is limited, a small number of studies suggested benefits of water intake on weight loss and nephrolithiasis, while single studies raised the possibility of benefits for patients with migraine, urinary tract infection, diabetes, and hypotension. Given the low cost and low adverse-effect profile of water, further well-designed studies should assess benefits in these specific conditions.
Current and Future Roles of Chimeric Antigen Receptor T-Cell Therapy in Neurology
Authors: Ismail Fatme Seval , Gallus Marco , Meuth Sven G. , Okada Hideho , Hartung Hans-Peter , Melzer Nico
Published: November 2024

Importance

Advancements in molecular engineering have facilitated the creation of engineered T cells that express synthetic receptors, termed chimeric antigen receptors (CARs). This is promising not only in cancer treatment but also in addressing a spectrum of other conditions. This review provides a comprehensive overview of the current approaches and future potential of CAR T-cell therapy in the field of neurology, particularly for primary brain tumors and autoimmune neurological disorders.

Observations

CAR T-cell therapy for glioblastoma is promising; however, first-in-human trials did not yield significant success or showed only limited success in a subset of patients. To date, the efficacy of CAR T-cell therapies has been demonstrated in animal models of multiple sclerosis, but larger human studies to corroborate the efficacy remain pending. CAR T cells showed efficacy in treatment of patients with relapsed or refractory aquaporin 4–immunoglobulin G–seropositive neuromyelitis optica spectrum disorders. Further studies with larger patient populations are needed to confirm these results. Success was reported also for treatment of cases with generalized myasthenia gravis using CAR T cells. Chimeric autoantibody receptor T cells, representing a modified form of CAR T cells directed against autoreactive B cells secreting autoantibodies, were used to selectively target autoreactive anti–N-methyl-d-aspartate B cells under in vitro and in vivo conditions, providing the basis for human studies and application to other types of autoimmune encephalitis associated with neuronal or glial antibodies.

Conclusions and Relevance

CAR T cells herald a new era in the therapeutic landscape of neurological disorders. While their application in solid tumors, such as glioblastoma, has not universally yielded robust success, emerging innovative strategies show promise, and there is optimism for their effectiveness in certain autoimmune neurological disorders.
Consideration of Children in Naloxone Coprescribing Laws
Authors: Hunt Ava , Trella Jeanette , Chaiyachati Barbara H.
Published: November 2024

This Viewpoint advocates for more careful consideration of families and children in policymaking surrounding naloxone coprescribing or accessibility.
Understanding brain cancer and exploiting its vulnerabilities
Authors: Salomoni Paolo
Published: November 2024

Brain cancer is one of the most devastating neoplasms affecting both children and adults. Its dismal prognosis has for long‐time discouraged research in this area. However, in the last 10–15 years remarkable progress has been made in our understanding of brain cancer biology, thus showing promise for the identification of new ways to treat these tumors towards the improvement of patients' survival and quality of life. This Thematic Issue on Brain cancers offers a much needed and timely critical overview of the fundamental discoveries in this area of research and which of those are more promising for effective translation into the clinic. Critically, many Reviews from this Issue also provide discussion points on why the field has not progressed as much as it had hoped to. It is important to emphasize however that we are living in exciting times with regards to our ability to translate fundamental findings into the clinic thanks to the enormous technological advances facilitating the study of cancer genomes and the development of new drugs or repurposing existing agents.
Spatial Coupling of Photocatalytic CO2 Reduction and Selective Oxidation on Covalent Triazine Framework/ZnIn2S4 Core–Shell Structures
Authors: Li Qi , Li Xiang , Zheng Mang , Luo Fanqi , Zhang Liping , Zhang Bin , Jiang Baojiang
Published: November 2024

Photocatalytic CO2 reduction coupled with alcohol oxidation to aldehyde presents a promising strategy for the simultaneous production of fuels and valuable chemicals. The efficiency of the coupled photocatalytic reactions remains low due to poor charge separation, difficulty in CO2 activation, and uncontrolled compatibility between reactions. This work presents S‐bridged covalent triazine framework (SCTF) core‐ZnIn2S4 shell photocatalysts for simultaneous CO2 reduction and selective furfural synthesis at distinct active sites. As evidenced by in situ X‐ray photoelectron spectroscopy and Kelvin probe force microscopy, photogenerated electrons in the composite photocatalysts transfer from the ZnIn2S4 shell to the SCTF core, improving charge separation. Experimental and theoretical results confirm that the presence of pyridine N atoms (Lewis basic sites) in SCTF enhances CO2 adsorption, thereby reducing the energy barrier for *COOH generation and promoting *CO production. Meanwhile, furfuryl alcohol oxidation and deprotonation occur on ZnIn2S4 by consuming photogenerated holes, which in turn benefits the conversion of CO2 to CO. As a result, the optimized SCTF/ZnIn2S4‐0.2 core/shell photocatalyst exhibited a superior CO production yield of 263.5 µmol g−1 and 95% conversion of furfuryl alcohol to aldehyde under simulated sunlight irradiation.
Effects of Physical Exercise Breaks on Executive Function in a Simulated Classroom Setting: Uncovering a Window into the Brain
Authors: Yu Qian , Zhang Zhihao , Ludyga Sebastian , Erickson Kirk I. , Cheval Boris , Hou Meijun , Pindus Dominika M. , Hillman Charles H. , Kramer Arthur F. , Falck Ryan S. , Liu‐Ambrose Teresa , Kuang Jin , Mullen Sean P. , Kamijo Keita , Ishihara Toru , Raichlen David A. , Heath Matthew , Moreau David , Werneck André O. , Herold Fabian , Zou Liye
Published: November 2024

Acknowledging the detrimental effects of prolonged sitting, this study examined the effects of an acute exercise break during prolonged sitting on executive function, cortical hemodynamics, and microvascular status. In this randomized crossover study, 71 college students completed three conditions: (i) uninterrupted sitting (SIT); (ii) SIT with a 15 min moderate‐intensity cycling break (MIC); and (iii) SIT with a 15 min vigorous‐intensity cycling break (VIC). Behavioral outcomes, retinal vessel diameters (central retinal artery equivalents [CRAE], retinal vein equivalents [CRVE], arteriovenous ratio [AVR]), cortical activation, and effective connectivity were evaluated. Linear mixed models identified significant positive effects of exercise conditions on behavioral reaction time (RT), error rate, and inverse efficiency score (β = −2.62, −0.19, −3.04: ps < 0.05). MIC and VIC conditions produced pre‐to‐post‐intervention increases in CRAE and CRVE (β = 4.46, 6.34), frontal activation, and resting‐state and task‐state causal density (β = 0.37, 0.06) (ps < 0.05) compared to SIT; VIC was more beneficial for executive function and neurobiological parameters. The effect of AVR on average RT was mediated through task‐based causal density (indirect effect: −0.82). Acutely interrupting prolonged sitting improves executive function, microvascular status, and cortical activation and connectivity, with causal density mediating the microvascular‐executive function link.
Identification of Nicotinic Acetylcholine Receptor for N‐Acetylcysteine to Rescue Nicotine‐induced Injury Using Beating Cilia in Primary Tissue Derived Airway Organoids
Authors: Zheng Yichao , Tian Qinyong , Yang Haowei , Cai Yongde , Zhang Jiaxin , Wu Yifen , Zhu Shuo , Qiu Zuocheng , Lin Yimin , Hong Jiangquan , Zhang Yi , Dockrell David , Ma Shaohua
Published: November 2024

Smoking is one of the major contributors to airway injuries. N‐acetylcysteine (NAC) has been proposed as a treatment or preventive measure for such injuries. However, the exact nature of the smoking‐induced injury and the protective mechanism of NAC are not yet fully understood. Here, patient tissue‐derived airway organoids for modeling smoking‐induced injury, therapeutic investigation, and mechanism studies are developed. Airway organoids consist mainly of ciliated cells, together with basal cells, goblet cells, and myofibroblast‐like cells. The organoids display apical‐out and basal‐in polarity and are enriched in beating cilia, which are sensitive to smoking challenge and NAC treatment. An algorithm is developed to measure ciliary beating activity by analyzing the altered beating pattern of cilia in response to nicotine challenge and NAC treatment. Nicotinic acetylcholine receptors (nAChRs) expressed by airway organoids are involved in the mechanisms of nicotine‐induced injury through the nicotine‐nAChR pathway. In contrast to the common understanding that NAC has an antioxidative effect that mitigates airway damage, it is elucidated that NAC binding to nicotine can abolish the binding capacity of nicotine to nAChRs and thus prevent nicotine‐induced injury. This study focuses on the advances and potential of humanized organoids in understanding biological processes, mechanisms, and identifying therapeutic targets.
Nematic and Smectic Phases with Proper Ferroelectric Order
Authors: Strachan Grant J. , Górecka Ewa , Szydłowska Jadwiga , Makal Anna , Pociecha Damian
Published: November 2024

A material showing a sequence of three ferroelectric liquid crystalline phases below the paraelectric nematic phase is synthesized and studied. The polar order of molecules appearing due to the dipole–dipole interactions in the ferroelectric nematic, NF, phase is preserved also in the smectic phases: orthogonal SmAF and tilted SmCF. The ferroelectric ground state of both smectic phases is confirmed by their second harmonic generation (SHG) activity and polarization switching. In the SmCF phase the polarization becomes oriented to the electric field by decreasing the tilt angle to zero. Although both smectic phases are ferroelectric in nature, their dielectric response is found to be very different.
Decoherence Effects on Local Quantum Fisher Information and Quantum Coherence in a Spin‐1/2$1/2$ Ising‐XYZ$XYZ$ Chain
Authors: Carrion Hector L. , Rojas Onofre , Filgueiras Cleverson , Rojas Moises
Published: November 2024

This research explores the effects of decoherence on local quantum Fisher information and quantum coherence dynamics in a spin‐1/2 Ising‐XYZ chain model with independent reservoirs at zero temperature. Contrasting these effects with those in the spin‐1/2 Heisenberg XYZ model reveals intricate interactions among quantum coherence, entanglement, and environmental decoherence in spin systems. Analysis of coherence dynamics highlights differences between the original and hybrid models, showcasing increased entanglement due to Ising interactions alongside reduced coherence from environmental redistribution. proves more resilient than coherence in specific scenarios, emphasizing decoherence's varying impacts on quantum correlations. This research underscores the complexity of quantum coherence dynamics and the crucial role of environmental factors in shaping quantum correlations, providing insights into entanglement and coherence behavior under environmental influences and guiding future studies in quantum information processing and correlation dynamics.
Nicht‐Kanonische C16 Homoterpen‐Biosynthese Weitverbreitet in Actinobakterien
Authors: Reuter Tatjana , Dieminger Lars , Steidle Sarah , Zoller Katrin , Holocher Maximilian , Zhou Lin , Hanauska Dominik Matthias , Racz Katharina , Barra Lena
Published: November 2024

Ein neuartiger Biosyntheseweg zur seltenen und wenig Erforschten nicht‐kanonischen Familie der Homoterpene wurde in Actinobakterien durch gezieltes Genome‐Mining und enzymatische In vitro‐Rekonstitution entdeckt. Der Weg umfasst eine anfängliche methylierungsinduzierte Doppelbindungsisomerisierung von Farnesyldiphosphat (FPP) zu (2E,7E)‐6‐Methylfarnesyldiphosphat, katalysiert durch eine neuartige Familie von Methyltransferasen mit dualer Funktion. Das resultierende lineare C16‐Doppelbindungsisomer von FPP stellt das spezifische Substrat für eine neue Familie von Typ‐I‐Terpenzyklasen dar, die diverse Zyklisierungsreaktionen katalysieren. Funktionelle Charakterisierung von neun Enzympaaren führte zur Entdeckung von fünf bisher unbeschriebenen Homoterpen‐Naturstoffen. Die entdeckte Enzymologie ermöglicht die Entwicklung biokatalytischer und genetisch programmierbarer Systeme zur Herstellung methylierter Terpene mit potenziell neuartigen Eigenschaften („Magic‐Methyl‐Effekt“).
Switching Residues: A Platform for the Synthesis of Fidaxomicin Antibiotics
Authors: Jung Erik , Griesser Tizian , Costafrolaz Jordan , Duverger Ondine , Mattenberger Yves , Dittmann Silvia , Dorst Andrea , Major Alexander , Dailler David , Schäfle Daniel , Sievers Susanne , Brodolin Konstantin , Viollier Patrick H. , Sander Peter , Gademann Karl
Published: November 2024

Peripheral modification is often the main approach to optimize natural products for improved biological activity or desired physicochemical properties. This procedure inevitably increases molecular weight, often accompanied by undesired increased lipophilicity. Removing structural elements from natural products is not always tolerated. This is also the case for the antibiotic fidaxomicin (Fdx), where every structural component has been shown to be crucial for antibiotic activity. In this work, we demonstrate how the residue switching approach can maintain biological activity of Fdx derivatives by replacing the rhamnoside‐dichlorohomoorsellinate moiety of Fdx with smaller, more polar building blocks. We used palladium‐catalysed allylic substitution to selectively install N‐nucleophiles on the core of Fdx. The new derivatives were designed to mimic the binding of Fdx to the bacterial RNA polymerase. Evaluation against Mycobacterium tuberculosis, Clostridioides difficile, and the Gram‐negative model organism Caulobacter crescentus demonstrated that the newly introduced residues can restore antibiotic activity, which was further supported by on‐target RNA polymerase assays. We combined the allylic substitution with an organocatalysed novioside acylation protocol to enable the functionalisation of two vectors on Fdx in one pot. This platform greatly expands the accessible chemical space for Fdx derivatives and enables the future development of systemic Fdx antibiotics.
Role of Aralkylamine N‐Acetyltransferase in the Response to Antioxidative Stress in the Fruit Fly Drosophila Melanogaster Adults
Authors: Rodríguez‐Illamola Arnau , Sidorov Roman , Čapková‐Frydrychová Radmila , Kodrík Dalibor
Published: November 2024

In multicellular organisms, the indole melatonin synthesized by aralkylamine N‐acetyltransferase (AANATI) serves as an antioxidant. To test this, sex‐mixed 3‐day‐old mated fly adults bw1 and AANAT1 homozygous recessive loss‐of‐function mutant (bw AANAT1lo) of Drosophila melanogaster were fed by a standard diet or by one containing paraquat (PQ, 1,1′‐dimethyl‐4,4′‐bipyridilium dichloride hydrate) at a final concentration of 15.5 mM. Experiment lasted 8 h and began at 11 a.m. In bw1 flies the paraquat treatment resulted in a significant (evaluated by Student's t‐tests) decrease of the superoxide dismutase (SOD) activity and an increase the catalase (CAT) and glutathione S‐transferase (GST) activities. Meanwhile, in these flies, total Antioxidative capacity (TAC) was significantly curbed by the paraquat presence. Importantly, these changes were not observed in the AANAT1‐mutants. Thus, melatonin seems to play an important defence role against the oxidative stress elicited by paraquat.
Compositional Dynamic Modelling for Counterfactual Prediction in Multivariate Time Series
Authors: Li Kevin , Tierney Graham , Hellmayr Christoph , West Mike
Published: November 2024

Theoretical developments in sequential Bayesian analysis of multivariate dynamic models underlie new methodology for counterfactual prediction. This extends the utility of existing models with computationally efficient methodology, enabling routine exploration of post‐intervention analyses with multiple time series in putatively casual studies. Methodological contributions also define the concept of outcome adaptive modelling to monitor and respond to changes in experimental time series following interventions. The benefits of sequential analyses with time‐varying parameter models for such investigations are inherited in this broader setting. A case study in forecasting retail revenue following marketing interventions highlights the methodological advances.
Fully Aqueous‐Processed Li‐Ion Electrodes with Ultra‐High Loading and Potential for Roll‐to‐Roll Processing
Authors: Nagler Felix , Gronbach Andreas , Flegler Andreas , Giffin Guinevere A.
Published: November 2024

In this study, high‐ and ultra‐high‐loading NMC622‐based cathodes (7.0 and 18.0 mAh/cm2) and graphite‐based anodes (9.0 and 22.5 mAh/cm2) were prepared by using a porous carbon structure as current collector. All electrodes in this work were prepared by an NMP‐free, PFAS‐free and scalable process. Full cells with areal capacities of 7 mAh/cm2 and 18 mAh/cm2 were assembled and tested. The results show an excellent cycling stability, reaching up to 950 cycles at 10 mA/cm2 for the cells with ultra‐high‐loading electrodes (capacity 18 mAh/cm2) and 650 cycles at 8 mA/cm2 for the cells with high‐loading electrodes (capacity of 7 mAh/cm2). The influence of cathode porosity on the electrochemical performance in cells capacity of 7 mAh/cm2 showed that a lower porosity leads to a poorer rate capability as well as a worse cycling capability (400 cycles at 6 mA/cm2). Post‐mortem analysis reveal that the anode aging is more pronounced during full cell cycling. Further the scalability of the production process was demonstrated by using a padder tool. With that, cathodes with a loading of 5 mAh/cm2 were produced in a roll‐to‐roll process.
Prevalence of Congenital Ocular Anomalies in 15 Countries of Europe: Results From the Medikeye Study
Authors: Dubucs Charlotte , Caillet Anthony , Frémont Félix , Delteil Laurane , N'Go Van , Neville Amanda Julie , Ballardini Elisa , Dolk Helen , Loane Maria , Garne Ester , Khoshnood Babak , Lelong Nathalie , Rissmann Anke , O'Mahony Mary , Pierini Anna , Gatt Miriam , Bergman Jorieke , Krawczynski Maciej Robert , Latos Bielenska Anna , Echevarría González de Garibay Luis Javier , Cavero‐Carbonell Clara , Addor Marie‐Claude , Tucker David , Jordan Sue , Den Hond Elly , Nelen Vera , Barisic Ingeborg , Rouget Florence , Randrianaivo Hanitra , Hoareau Jonathan , Perthus Isabelle , Hurault‐Delarue Caroline , Courtade‐Saïdi Monique , Damase‐Michel Christine
Published: November 2024

Background

Congenital ocular anomalies (COA) are among the most common causes of visual impairment in children in high‐income countries. The aim of the study is to describe the prevalence of the various COA recorded in European population‐based registries of CA (EUROCAT) participating in the EUROmediCAT consortium.

Methods

Data from 19 EUROmediCAT registries and one healthcare database (EFEMERIS) were included in this descriptive epidemiological study. Cases of COA included live births, FD from 20 weeks gestational age (GA), and termination of pregnancy for fetal anomaly.

Results

The prevalence of total COA was 3.47/10,000 births (95% CI [3.61–3.82]), ranging from 1.41 to 13.46/10,000 depending on the registry. Among COA cases, congenital lens anomalies were the most frequent anomalies (31%), of which over half were single ocular anomalies (presenting with only one ocular anomaly). An/microphthalmia was the second most frequent COA (24%) of which three‐quarters were multiply malformed (associated to extraocular major anomalies). Among single COA cases, 58 were prenatally diagnosed (4%), of which, 58% were diagnosed in the second trimester. Known genetic causes of COA explained 2.5%–25% of COA depending on their class.

Conclusions

This is the first European study describing COA. The detailed prevalence data offered in this study could improve screening and early diagnosis of different classes of COA. As COA are rare, epidemiological surveillance of large populations and accurate clinical descriptions are essential.
Free Online Multiplayer Games as Inclusive Tools for Teaching Ecology
Authors: Erfanian Mohammad Bagher
Published: November 2024

Teaching ecology is the primary way of communicating the current knowledge in the discipline to future generations. Besides general tools (e.g., lectures, videos, simulations, and having students read published literature), experimenting and field practices are two principal ways to teach ecology. However, funding shortages along with the fact that some phenomena occur in large spatial and long temporal scales, hinder the use of experiments and fieldwork in pedagogy. Computer‐based games are interactive digital tools that were initially designed to be entertaining and engaging. In addition, they are effective motivational educational tools that are already being used in the pedagogy of various majors. Still, few studies have assessed the application of games in teaching ecology. Although those studies reported positive feedback from the students, they reported that making these games is expensive and time‐consuming. Therefore, educators would benefit from using free and globally accessible games. Here, I introduce the application of online multiplayer games in teaching ecology. Recently, I explored a snake game in which its environment resembles artificial ecosystems. Each player (i.e., each snake) can be regarded as an individual of a population or a species within a community. Then, a couple of general ecological rules, phenomena, and analyses can be easily inferred from these games. I asked the undergraduate students to play these games, collect the data, and write a report on their analysis. The students deduced different ecological phenomena from their in‐game experience and reported these games are useful and fun to play. Many games have been produced to increase global awareness of human actions on the environment. These games are geared toward various age groups, including children, young adults, and adults. Two obstacles hinder the use of these games in pedagogy. First, most of the games are not globally accessible, and second, their effectiveness in teaching has not been assessed yet. I envision a future where online games are integrated as part of the pedagogy in ecology. These games are globally accessible, therefore, no barriers exist to test the application of these games. I encourage the readers to conduct a global survey on their usefulness. This might be a step toward reaching a globally inclusive pedagogy in ecology.
Multi‐Omic Analysis Reveals the Impact of Bortezomib in Hyperleukocytic Acute Myeloid Leukemia
Authors: Wu Jinxian , Li Xinqi , Xiong Bei , Yin Wanyue , Li Ruihang , Chen Guopeng , Ma Linlu , Tong Xiqin , Liu Xiaoyan , Zhou Fuling
Published: November 2024

Background

Hyperleukocytic acute myeloid leukemia (HL‐AML) is associated with early complications and high mortality rates, highlighting the urgent need for more effective therapeutic strategies.

Methods

This study conducted label‐free proteomic analysis on serum from HL‐AML and non‐HL AML (NHL‐AML) patients, integrating the data with the OHSU transcriptomic database. Flow cytometry was used to evaluate the in vitro impact of bortezomib. The in vivo effectiveness of bortezomib was assessed using the patient‐derived xenograft (PDX) model of HL‐AML.

Results

Through integrated analysis of serum proteomics and transcriptomics, we observed an abnormal enrichment of the NF‐kappa B pathway in HL‐AML, suggesting its potential as a novel therapeutic target. Given that bortezomib is an inhibitor of the NF‐kappa B pathway, HL‐AML bone marrow cells were treated with varying concentrations of bortezomib (0, 5, 10, and 20 nM) in vitro. The results indicated a significant cytotoxic effect of bortezomib on HL‐AML cells, accompanied by increased apoptosis rates and decreased proliferation. Co‐administration of bortezomib with the frontline clinical chemotherapeutic regimen of daunorubicin and cytarabine (DA regimen) significantly extended mouse survival. Bone marrow immunophenotyping showed reductions in CD45+ and CD33+ cell populations, indicating disease amelioration. Immunohistochemical analysis further confirmed the inhibitory effect on the NF‐kappa B pathway, as evidenced by reduced levels of P‐IKBα and P‐p65 proteins, validating the proposed therapeutic mechanism.

Conclusions

These data suggest that combination therapy involving bortezomib and the DA regimen may represent a promising strategy for HL‐AML.
Bringing Theory Into Action: Justice‐Oriented Practices for the Classroom
Authors: Suh Emily K. , Unruh Kendra
Published: November 2024

Like other postsecondary educators, community college faculty face challenges from conservative politicians seeking to eliminate equity perspectives in college teaching and educational stakeholders who overapply the label of equity, rendering it devoid of meaning. Through a content analysis of literacy class‐focused equity practices from recent works we ground recommended practices in the larger body of community college and university literacy scholarship. In so doing, we seek to amplify practitioner‐scholar expertise and present four stages of an equity‐to‐justice praxis; awakening, making informed policy and practice changes, enacting culturally sustaining and responsive pedagogy. We offer concrete strategies for action and ultimately to reconceptualize the work of community colleges as liberation.
MnO2 Nanowire Thin Mesh With Enhanced Mass Transfer as Hydroxide Exchange Membrane Fuel Cell Cathode
Authors: Xin Dongyue , Liu Xuerui , Chen Chengjin , Wang Haiyong , Chen Bowen , Zhang Shuxin , Fang Jinjie , Deng Chen , Zhu Wei , Zhuang Zhongbin
Published: November 2024

Hydroxide exchange membrane fuel cells (HEMFCs) are promising due to the potential use of nonprecious metal catalysts. However, the performance of HEMFCs based on nonprecious catalysts is still unsatisfactory, and one reason for this is hindered mass transfer in the catalyst layer. In this study, we employ a hydrothermal method to grow in situ a MnO2 nanowire thin mesh (NTM) catalytic layer on the gas diffusion electrode. The HEMFC prepared with MnO2 NTM cathode achieves a peak power density of 425 mW cm−2, surpassing the performance of the HEMFC prepared using the traditional powder catalyst spraying method by four times. High‐frequency resistance and limiting current tests indicate that the MnO2 NTM reduces ohmic resistance and improves mass transfer, thereby enhancing the HEMFC performance. Furthermore, the peak power density of the HEMFC is increased to 626 mW cm−2 by depositing additional active Co3O4 nanoparticles on the MnO2 NTM. These findings demonstrate that an interconnected and porous catalyst layer structure is beneficial for improving mass transfer properties, which in turn enhances HEMFC performance.
Stimuli Induced Reversible Switching Between a Self‐Assembled 2‐Catenane and the Constituent Coordination Rings
Authors: Soni Raveena , Bardhan Devjanee , Krishnaswamy Shobhana , Chand Dillip Kumar
Published: November 2024

A pair of comparable sized C‐shaped bis‐monodentate ligands (L1 and L22+) and a linear bis‐monodentate ligand (L3) complementing to the terminal‐lengths of the C‐shaped ligands have been identified. One‐pot combination of cis‐Pd(tmeda)2+, L1 and L3 (2 : 1 : 1 ratio) in water resulted an octa‐cationic 2‐catenane, [Pd2(tmeda)2(L1)(L3)]28+ in which two identical tetra‐cationic macromonocyclic coordination rings are interlocked; however, a guest bound coordination ring was formed in presence of a selected di‐anionic guest. Complexation of cis‐Pd(tmeda)2+ with a mixture of L22+ and L3 (2 : 1 : 1 ratio) in water resulted the hexa‐cationic macromonocyclic coordination ring, [Pd2(tmeda)2(L2)(L3)]6+ whereas a guest bound coordination ring was formed in the presence of the di‐anionic guest. Addition of the guest to the preformed octa‐cationic catenane caused ring separation to favour the guest‐bound ring. This guest bound ring could be reverted to the 2‐catenane by sequestering the bound guest using the relatively electron deficient hexa‐cationic coordination ring. Thus, a design principle for reversible switching between a 2‐catenane and the constituent macromonocyclic‐rings using anion‐binding/‐sequestering as the core concept has been established.
Yb(OTf)3‐Catalyzed Asymmetric [3+3] Cycloaddition of N‐Vinyl Nitrones with Activated Cyclopropanes to Prepare 1,2‐Oxazines
Authors: Wu Yu‐Zheng , Leng Yue , Chen Yi‐Xin , Huang Shi‐Qiu , Zou Ning , Chen Chun‐Hua , Mo Dong‐Liang
Published: November 2024

Comprehensive Summary

We described a Yb(OTf)3 combined with Pybox ligand catalyzed asymmetric [3+3] cycloaddition of N‐vinyl cinnamaldehyde nitrones with activated cyclopropanes to prepare various functionalized 1,2‐oxazines in 24%—95% yields and 22%—96% ee. Experimental results revealed that the reaction underwent a domino [3+3] cycloaddition, dealkenylation, and aza‐1,4‐addition in three steps. The chiral 1,2‐oxazine could be obtained in gram scales and easily converted into various 1,2‐oxazine scaffolds. The present method features broad substrate scope, good functional group compatibility, three‐component domino reaction, and asymmetric [3+3] cycloaddition of N‐vinyl nitrones with activated cyclopropanes.
Mental Pain Questionnaire: Clinimetric Properties of a Potential Global Person‐Centred Outcome Measure
Authors: Cosci Fiammetta , Carrozzino Danilo , Patierno Chiara , Romanazzo Sara , Berrocal Carmen , Chiarugi Alberto , De Cesaris Francesco , Guiducci Serena , Mansueto Giovanni , Christensen Kaj Sparle , Sensky Tom
Published: November 2024

Introduction

The Mental Pain Questionnaire (MPQ) was developed using a clinimetric approach to bring together the key features of mental pain into a single, brief, transdiagnostic scale. The present study aims at extending the validation of the MPQ to people from three different clinical settings.

Methods

A multicentre, cross‐sectional study on adults diagnosed with migraine (n = 256), systemic sclerosis (n = 219), or mental disorders (n = 138) was conducted. The MPQ was administered; Rasch and Mokken analyses were performed to assess clinimetric validity.

Results

The overall fit to the Rasch model indicated a misfit, improved by the exclusion of a single item. MPQ showed to be unidimensional. MPQ total score and individual items scalability were optimal except for the same item. The total MPQ score showed an optimal scalability for the systemic sclerosis sample and an acceptable scalability for the migraine and mental disorders samples. Local dependency was found between two pairs of items. Person separation reliability indices (PSI 0.45) showed that the MPQ could not distinguish between groups with different levels of mental pain.

Conclusion

Mental pain has the potential to serve as a truly generic patient‐centred outcome measure. Recommendations are made for revisions of the original MPQ, but these will require testing in further validation studies.
Bulk Layering Effects of Ag and Cu for Tandem CO2 Electrolysis
Authors: Sassenburg Mark , Iglesias van Montfort H. P. , Kolobov Nikita , Smith Wilson A. , Burdyny Thomas
Published: November 2024

The electrochemical reduction of carbon dioxide (CO2) presents an opportunity to close the carbon cycle and obtain sustainably sourced carbon compounds. In recent years, copper has received widespread attention as the only catalyst capable of meaningfully producing multi‐carbon (C2+) species. Notably carbon monoxide (CO) can also be reduced to C2+ compounds on copper, motivating tandem systems that combine copper and CO‐producing species, like silver, to enhance overall C2+ selectivities. In this work, we examine the impact of layered‐combinations of bulk Cu and Ag by varying the location and proportion of the CO‐producing Ag layer. We report an effective increase in the C2+ oxygenate selectivity from 23 % with a 100 nm Cu to 38 % for a 100 : 15 nm Cu : Ag layer. Notably, however, for all co‐catalyst cases there is an overproduction of CO vs Cu alone, even for 5 nm Ag layers. Lastly, due to restructuring and interlayer mobility of the copper layer it is clear that the stability of copper limits the locational advantages of such tandem solutions.
Molecular Electrocatalysts in Lithium‐Sulfur Batteries
Authors: Wang Zhihua , Ke Junru , Rui Zixin , Xu Li , Li Gaoran , Ji Hua , Zhu He , Lan Si
Published: November 2024

Lithium‐sulfur (Li−S) batteries face challenges due to the sluggish reaction kinetics of sulfur species, which reduces sulfur utilization and thus lowers performance. Molecular electrocatalysts, with their clear and adequately exposed active sites, offer a reliable way to enhance reaction kinetics in lithium‐sulfur batteries. This review elaborates on the reaction processes and mechanisms of molecular electrocatalysts, focusing on both the sulfur reduction reaction (SRR) and sulfur evolution reaction (SER) to explore their potential working principles. Additionally, we analyze the design strategies for novel catalysts aimed at inhibiting the diffusion of lithium polysulfides (LiPSs). This paper aims to design molecular electrocatalysts that facilitate the multiphase conversion of sulfur species, providing guidance for the commercialization of Li−S batteries.
Trends in the Detection of Erythropoietin Receptor Agonists (ERAs) in Anti‐Doping: An Analysis of Recent Adverse Analytical Findings (AAFs)
Authors: Equey Tristan , Broséus Julian , Baume Norbert , Aikin Reid
Published: November 2024

Anti‐doping efforts aim to reduce the prevalence of doping through a combination of education, deterrence, and detection. Detection of doping practices, for example through testing and/or investigations, aims both to catch committed dopers and deter potential dopers. To date, little empirical evidence is available examining the ability of detection strategies to deter athletes from doping. Here, trends in adverse analytical findings (AAFs) for EPO or other EPO‐Receptor Agonists (ERAs) were examined over an 8‐year period in order to assess the impact of ERA testing and detection on athlete behavior. It was observed that the majority (62.8%) of ERA AAFs occur on samples collected on the day of a competition. Evidence is also presented that the largest fraction of ERA AAFs occurs on the first sample ever taken from an athlete (43.2%), and that the ERA AAF rates decline steadily as athletes continue to be tested. These findings provide evidence of a deterrent effect of testing on ERA use in sport.