bluuebunny/crossref_metadata_2025 huggingface dataset:
The Trifluorooxygenate Anion [OF3]−: Spectroscopic Evidence for a Binary, Hypervalent Oxygen Species
Authors: Meyer Deniz F. , Medel Robert , Riedel Sebastian
Published: October 2024

Experimental evidence for hypervalent compounds of second‐row elements is still scarce in literature. Here, we present the first report of the long‐sought binary, hypervalent trifluorooxygenate anion [OF3]−. It was isolated in solid Ne matrices under cryogenic conditions after reacting oxygen difluoride with free fluoride ions from laser ablation of alkali metal fluorides MF (M=Li−Cs). VSEPR theory and calculations at the CCSD(T) level predict a C2v‐symmetric T‐shape structure with one short and two long O−F bond lengths in [OF3]−. This is confirmed experimentally by FTIR spectroscopy in combination with isotopic labeling. Analysis of the natural local molecular orbitals shows the presence of one 2c–2e and one 3c–4e bond each. Natural resonance theory indicates the importance of the stability of [OF2]⋅− for the stability of [OF3]−. Although free [OF2]⋅− was not detected, the species MOF2 (M=Na−Cs) could be observed in the same experiments, which are best described as contact ion pairs of M+[OF2]⋅−.
Benzylic C−H Radical Sulfation by Persulfates
Authors: Xia Zhen , Ye Zhongyao , Deng Ting , Tan Ze , Song Chunlang , Li Jiakun
Published: October 2024

Sulfation is a highly valuable pathological and physiological process, yet it is often underappreciated considering the rather difficult accessibility of organosulfates. O‐sulfonation (O−SO3), a conventional and still common way to make organosulfates, restricts its applicability to hydroxyl compounds and therein lies a major challenge of library construction. Here, we describe a benzylic C−H radical sulfation with persulfates via C−O bond formation. This strategy leverages modular control over the reactivity of persulfates and the stability of sulfate radicals by coutercations. K+/NH4+ stabilized sulfate radicals act as the oxidant to generate carbon‐centered radicals from substrates, and activation of persulfates by n‐NBu4+ provides O−O resource pool to facilitate C−OSO3− bond formation via a bimolecular homolytic substitution (SH2) process.
Organocatalytic Asymmetric Construction of 2,6‐Diazabicyclo‐[2.2.2]octanes by Harnessing the Potential of an 3‐Oxindolium Ion Intermediate
Authors: Yadav Jyothi , Patel Arun , Dolas Atul Jankiram , Iype Eldhose , Rangan Krishnan , Kumar Indresh
Published: October 2024

Due to its structural complexity and intrinsic sensitivity of bridged aminal junction, 2,6‐diazabicyclo[2.2.2]octane (2,6‐DABCO) has remained a highly desirable target in synthetic chemistry. However, the asymmetric access to this unit is still insufficient and hampered by the need for meticulously created functionalities for intricate double aza‐cyclizations. Herein, we have developed a novel enantio‐ and diastereoselective protocol to access polycyclic chiral 2,6‐DABCOs under metal‐free conditions. This domino process involves the amine‐catalyzed [4+2] annulation between glutaraldehyde and 2‐arylindol‐3‐ones, followed by an acid‐mediated Pictet–Spengler reaction/intramolecular aza‐cyclization cascade sequence with tryptamine by trapping of in situ generated 3‐oxindolium ion intermediate for the first time. Overall, 2,6‐DABCOs fused with medicinally relevant scaffolds were isolated with good yield and excellent stereoselectivity by constructing five new bonds and four stereocenters in a one‐pot operation.
Impact of cellulose enrichment on castor oil polyurethane sheets: A path to greener materials
Authors: Mangal Mangal , Rao Chebrolu Venkateswara , Das Nipu Kumar , Bose Suryasarathi , Banerjee Tamal
Published: October 2024

Due to the growing concern over the depletion of the global crude oil stock and environmental issues, the replacement of petroleum‐based polymers with environmentally benign alternatives derived from renewable resource has attracted great attention. In the current study, four different polyurethane (PU) sheets were synthesized from unmodified castor oil (CO) and hexamethylene diisocyanate (HDI), incorporating cellulose nanofibers (CNF) as a filler. The mixture consisting molar ratio of CO, HDI, and CNF in a ratio of 1:5:0.8 yielded the best results. This formulation achieved a tensile strength of 22.55 MPa and an elongation at break of 55.9%. Additionally, the resulting PU sheets exhibited excellent thermal properties, with a glass transition temperature (Tg) and melting temperature (Tm) that were notably enhanced, further highlighting the effectiveness of this specific mixture in producing high‐performance, bio‐based PUs. Fourier‐transform infrared spectroscopy (FTIR), thermal, and mechanical characterizations indicated that both reinforced and unreinforced PU exhibited properties within acceptable ranges. Given the bio‐based origins of CO and cellulose, the synthesized polymers are biodegradable and suitable for biomaterial applications. The study confirms that the bio‐based origins of CO and cellulose render synthesized polymers biodegradable, suitable for various biomaterial applications.
Exploring the Role of Neutrophil Extracellular Traps in Systemic Lupus Erythematosus: A Clinical Case Study and Comprehensive Review
Authors: Kaplan Mariana J.
Published: October 2024

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Controllability of nonlinear stochastic impulsive switched systems in Hilbert spaces
Authors: Ansari Shahin , Malik Muslim
Published: October 2024

In this paper, nonlinear first order stochastic switched control systems with non‐instantaneous impulses (NIIs) in infinite‐dimensional spaces are considered. Semigroup theory of linear operators and a fixed‐point approach are used to develop the main results. First, we present the mild solution for the proposed system. Then, we derive sufficient conditions to ensure the total controllability and trajectory controllability results. Further, to validate the study, we provide examples.
Characterising core body temperature response of free‐moving C57BL/6 mice to 1.95 GHz whole‐body radiofrequency‐electromagnetic fields
Authors: Sylvester Emma , Deng Chao , McIntosh Robert , Iskra Steve , Frankland John , McKenzie Raymond , Croft Rodney J.
Published: October 2024

The present study investigated the core body temperature (CBT) response of free‐moving adult male and female C57BL/6 mice, during and following a 2‐h exposure to 1.95 GHz RF‐EMF within custom‐built reverberation chambers, using temperature capsules implanted within the intraperitoneal cavity and data continuously logged and transmitted via radiotelemetry postexposure. Comparing RF‐EMF exposures (WBA‐SAR of 1.25, 2.5, 3.75, and 5 W/kg) to the sham‐exposed condition, we identified a peak in CBT within the first 16 min of RF‐EMF exposure (+0.15, +0.31, +0.24, +0.37°C at 1.25, 2.5, 3.75, and 5 W/kg respectively; statistically significant at WBA‐SAR ≥ 2.5 W/kg only), which largely dissipated for the remainder of the exposure period. Immediately before the end of exposure, only the CBT of the 5 W/kg condition was statistically differentiable from sham. Based on our findings, it is apparent that mice are able to effectively compensate for the increased thermal load at RF‐EMF strengths up to 5 W/kg. In addition, the elevated CBT at the end of the exposure period in the 5 W/kg condition was statistically significantly reduced compared to the sham condition immediately after RF‐EMF exposure ceased. This would indicate that measures of CBT following the end of an RF‐EMF exposure period may not reflect the actual change in the CBT of mice caused by RF‐EMF exposure in mice.
A High‐Throughput Drug Repurposing Strategy to Treat TBX2 and/or TBX3 Dependent Cancers
Authors: Bleloch Jenna S. , Lu Sizhu , Khan Saif Feroz , Serala Karabo , Seraia Elena , Millar Val , Ebner Daniel , Goding Colin , Prince Sharon
Published: October 2024

Background

The highly homologous T‐box transcription factors TBX2 and TBX3 are critical for embryonic development, and their overexpression in postnatal tissues contributes to a wide range of malignancies, including melanoma and rhabdomyosarcoma. Importantly, when TBX2 and TBX3 are depleted in cancers where they are overexpressed, the malignant phenotype is inhibited, and they have therefore been regarded as druggable targets. However, the time and costs associated with de novo drug development are challenging and result in drugs that are costly, especially for patients in low‐ and middle‐income countries. In the current study, we therefore combined a targeted and drug repurposing approach to identify drugs that are expected to be more efficacious and cost‐effective with significantly reduced side effects.

Methods

A high‐throughput cell‐based immunofluorescence screen was performed to identify drugs in the Pharmakon 1600 drug library that can negatively regulate TBX2 and/or TBX3 levels. “Hit” drugs were validated for their effect on TBX2/TBX3 levels and cytotoxicity in TBX2/TBX3‐dependent melanoma and rhabdomyosarcoma cells. To this end, immunofluorescence, western blotting, quantitative real‐time PCR, and MTT cell viability assays were performed.

Results

Niclosamide, piroctone olamine, and pyrvinium pamoate, were identified as TBX2 and/or TBX3‐targeting drugs, and they exhibited cytotoxicity in a TBX2/TBX3‐dependent manner. Furthermore, these “Hit” drugs were shown to induce senescence and/or apoptosis.

Conclusions

Niclosamide, piroctone olamine, and pyrvinium pamoate are promising, cost‐effective therapeutic agents for the treatment of TBX2/TBX3‐dependent cancers.
Exploring the Potential of Enhanced Prognostic Performance of NCCN‐IPI in Diffuse Large B‐Cell Lymphoma by Integrating Tumor Microenvironment Markers: Stromal FOXC1 and Tumor pERK1/2 Expression
Authors: Kim Ji‐Ye , Kahttana Ibadullah , Yoon Hyonok , Chang Sunhee , Yoon Sun Och
Published: October 2024

Background

FOXC1 and ERK1‐2 are proteins implicated in aggressive biological behavior of various malignancies including lymphomas.

Material and Methods

We investigate the additive prognostic value of stromal FOXC1 expression and tumor phosphorylated ERK1‐2 (pERK1‐2) expression to the established National Comprehensive Cancer Network International Prognostic Index (NCCN‐IPI), in 92 diffuse large B‐cell lymphoma (DLBCL) cases. Multidimensional analysis using statistics and machine learning (ML) models assessed prognostic value of established clinicopathologic variables with stromal FOXC1 and tumor pERK1‐2 expressions.

Results

Both high FOXC1 stroma group and high pERK1‐2 tumor group were significantly associated with shorter progression‐free survival (PFS) and overall survival (OS) compared with low group (p = 0.015, 0.034 and p = 0.025, 0.025 each respectively). In multivariable analysis, high FOXC1 stromal expression was an independent prognostic factor of OS (p = 0.037). The addition of stromal FOXC1 and tumor pERK1‐2 to the NCCN‐IPI score significantly improved prediction of time to death compared with NCCN‐IPI score alone (Harrell's C‐index = 0.801 vs. 0.764; p = 0.030). ML models reconfirmed the addition of stromal FOXC1 expression and tumor pERK1‐2 to NCCN‐IPI score had the highest C‐index (0.952) among combinations. Stromal FOXC1 and tumor pERK1‐2 were determinants of DLBCL prognosis, whose addition significantly improved prognostic performance of the NCCN‐IPI.
Impacts and Pathways of Behavioral Activation on Psychological Distress Among Patients Diagnosed With Esophageal and Gastric Cancer in China: A Randomized Controlled Trial
Authors: Huang Runze , Li Anlong , Ge Han , Liu Lijun , Cheng Ling , Zhang Mingjun , Cheng Huaidong
Published: October 2024

Objective

The objective of this study is to investigate the efficacy of behavioral activation (BA), a novel psychological intervention, in ameliorating psychological distress and anxiety symptoms among patients diagnosed with esophageal and gastric cancer, as well as the mediating role of self‐efficacy between BA and psychological distress.

Methods

A total of 139 patients diagnosed with esophageal and gastric cancer were recruited in China from March 2023 to October 2023 and randomly assigned to either the BA plus care as usual group (BA+CAU group) or the care as usual group (CAU group). Pre‐ and post‐intervention questionnaires, including the Psychological Distress Thermometer (DT), Generalized anxiety disorder 7‐item (GAD‐7) Scale, General Self‐Efficacy Scale (GSES) and the activation subscale of Behavioral Activation for Depression Scale (BADS‐A), were administered.

Results

Generalized estimating equation analyses revealed that, compared to usual care alone, combining BA with usual care significantly ameliorated psychological distress, anxiety as well as improved self‐efficacy and activation. The mediation analysis revealed that self‐efficacy served as a mediator in the relationship between activation and psychological distress.

Conclusions

BA primarily based on telephone or WeChat can not only directly ameliorates psychological distress and anxiety symptoms in patients with esophageal cancer and gastric cancer but also indirectly alleviates psychological distress by enhancing self‐efficacy. The study also demonstrates the potential of BA in cancer patients, a skill that can be effectively acquired by primary care workers without specialized training and implemented more flexible.

Trial Registration: NCT06348940
Gastric Mucosal Status and Risk of Gastric Cancer in High‐Risk Individuals: A Population‐Based, Multicenter Prospective Study in China
Authors: Liu Han , Song Song , Geng Xianyi , Chen Ru , Zheng Rongshou , Wei Wenqiang , Li Ni , Chen Wanqing , Ren Jiansong
Published: October 2024

Objective

This study explored the distributions of gastric mucosal status and their links to gastric cancer within urban high‐risk individuals in China.

Methods

From 2014 to 2015, a questionnaire survey was administered among individuals aged 40 to 69 years, residing for over 3 years in seven selected cities across China. Utilizing the questionnaire data, high‐risk individuals for gastric cancer were screened. These identified high‐risk individuals were invited to undergo endoscopy, followed by pathological examinations conducted for those with suspicious lesions. Prior cancer patients and those newly diagnosed with gastric cancer were excluded, and the remaining endoscopic participants were prospectively followed up until December 2021.

Results

The prospective study followed 8911 individuals at high risk of gastric cancer for a median duration of 6.77 years. The incidence density of gastric cancer was 58.55 per 100,000 person‐years. At baseline, the distributions of subjects across normal gastric mucosa, gastritis/ulcer/polyp, atrophic gastritis/intestinal metaplasia, and intraepithelial neoplasia groups were 47.09%, 36.27%, 9.57%, and 7.07%, respectively. Compared with normal gastric mucosa, the hazard ratios (HRs) for gastric cancer in the other groups were 0.89 [95% confidence interval (95%CI): 0.38–2.08], 1.52 (95%CI: 0.50–4.66), and 4.63 (95%CI: 1.98–10.82). When using the 40–54 age group as the reference, the HR for 55–69 age group was 3.49 (95%CI: 1.52–7.98).

Conclusion

Among high‐risk individuals with gastric cancer, the proportions of individuals exhibiting different gastric mucosal status inversely correlated with the severity of mucosal lesions, whereas the risk of gastric cancer progressively escalated with the increasing severity of mucosal lesions and advancing age.
Gelation and dough‐forming properties of canary seed protein concentrate in comparison with commercial soy protein concentrate and vital wheat gluten
Authors: Perera Suneru P. , Briggs Connie , Hucl Pierre , L'Hocine Lamia , Nickerson Michael T.
Published: October 2024

Background and Objectives

In this study, a lab‐scale process was developed to aqueously de‐oil canary seed (yellow and brown‐seeded) flour and derive a protein concentrate. The protein concentrates prepared were evaluated for their gelation and bread dough‐forming properties.

Findings

The aqueous process successfully reduced the oil content in both yellow‐seed and brown‐seed roller‐milled flour. The protein concentrate prepared from yellow‐seed flour and brown‐seed flour had 74.9% and 68.6% purity (dry weight basis), respectively. Proteins showed high resistance to thermal denaturation (peak denaturation at 107°C). It was found that the least gelation concentration of both protein concentrates was 16% (w/w). There were no significant differences in viscoelastic properties and water holding capacity between the protein gels of these two canary seed types and the addition of salt did not noticeably improve these properties. Compared to canary seed, commercial soy protein showed better gelation properties. Both yellow and brown canary seed protein showed a good potential for improving bread dough strength when incorporated into a low‐gluten‐strength wheat flour and was comparable to commercial vital wheat gluten at 1%–3% (w/w) inclusion levels.

Conclusions

The new canary seed protein ingredients prepared by the solvent‐free aqueous‐based process hold good potential for application in food formulation based on their gelation and bread dough‐forming properties.

Significance and Novelty

The gelation and dough‐forming properties of canary seed were not previously studied; therefore, this study provides an insight into those properties for potential food applications for canary seed proteins, which is important for canary seed market diversification as a novel protein source.
Monomeric Metal Species for Low‐Temperature Methane Oxidation
Authors: Yu Tao , Jiang Yue , Luo Wenhao
Published: October 2024

Direct oxidation of methane into value‐added chemicals is considered as one of the holy grails in chemistry and catalysis. Considerable efforts have been devoted to developing advanced catalyst systems operated under mild conditions, and mononuclear metal species, which are currently in the spotlight of methane oxidation, have shown great advantages and addressed significant attention. In this concept, we highlight the recent breakthroughs and developments in monomeric metal species for low‐temperature (<100 °C) methane oxidation. Emphasis is put on the identification and validation of monomeric metal species as the intrinsic active sites. Promising characterization approaches for identifying catalytically relevant features of physicochemical properties of monomeric metal species are discussed, as well as the emerging insights on the development of in situ characterization technologies. Finally, the open challenges and outlooks for rational development of monomeric metal catalysts for methane valorization are examined for guiding further developments and inspiring the future work.
Spin Crossover and Its Application in Organometallic Catalysis: Concepts and Recent Progress
Authors: He Peng , Zhu Shou‐Fei
Published: October 2024

Spin crossover is one of the most important properties of open‐shell metal complexes. In organometallic catalytic reactions, catalysts can alter reaction kinetics by spin crossover, i. e., accelerating or hindering the reaction progression, as well as altering reaction pathways, modulating the reaction selectivity or promoting new reactions. This personal account outlines the introduction and development of important concepts such as “two‐state reactivity” involving spin crossover, and proposes a new concept, “spin‐responsive catalysis” to summarize the catalytic processes in which spin effects are present. Finally, the electronic mechanism of spin crossover accelerating the reaction and the role of spin crossover in changing the reaction path and regulating the reaction selectivity are introduced by taking two recent typical iron‐catalyzed reactions recently reported by our group as examples.
Enantioselective Synthesis of 3‐Hydroxy‐2‐Oxindoles via Ni‐Catalyzed Asymmetric Addition of Aromatic Bromides to α‐Ketoamides
Authors: Tian Jiangyan , Li Xuening , Shou Tao , Li Wendian , Lv Hui
Published: October 2024

Nickel‐catalyzed asymmetric intramolecular addition of aryl halides to α‐ketoamides has been achieved to afford chiral 3‐substituted‐3‐hydroxy‐2‐oxindoles in excellent yields and high enantioselectivities (up to 99 % yield and 98 % ee), which provides efficient access to valuable molecules containing 3‐hydroxy‐2‐oxindole core. The gram‐scale reaction proved the potential utility of the methodology.
Protocol: Assessing the outcomes and impact of professional doctorate programmes in health and social care on the individual, their profession, their employing organisation and wider society: A comprehensive systematic review
Authors: Chapman Hazel M. , McSherry Robert , Bettany‐Saltikov Josette , Mohan Mridula , Spencer Debbie
Published: October 2024

This is the protocol for a Campbell systematic review. This review's objectives are to find out (in relation to health and/or social care): (1) What is known about the outcomes and impact of completing (or not completing) a professional doctorate in health and/or social care on the individual professional? (2) What is known about the outcome and impact of completing (or not completing) a professional doctorate in health and/or social care on the employing organisation? (3) What is known about the outcome and impact of completing (or not completing) a professional doctorate in health and/or social care on the profession? (4) What is known about the outcome and impact of completing (or not completing) a professional doctorate in health and/or social care on service users and the wider society? (5) How do we use the findings from this review to inform educators, higher education institutions, professionals, investors in employing organisations and policymakers? (6) What further research will be needed to answer any knowledge gaps or recommendations? (7) Where possible, we will identify and report on any demographic data and discuss their relevance to the impact and outcomes from professional doctorates.
Electric‐Field Controlled Switchable and Efficient Separation of Radioactive Xe/Kr on Borophene: A Theoretical Study
Authors: Zhang Wenxi , Qu Mengnan , Du Aijun , Sun Qiao
Published: October 2024

The efficient and reversible separation of radioactive Xe/Kr during spent fuel reprocessing is important and challenging for the rapid development of nuclear energy. In this study, we firstly report a strategy of applying an electric field on the solid adsorbent borophene to realize efficient and switchable Xe/Kr separation via a density functional theory (DFT) investigation. Based on the calculational results, the adsorption energies for Xe and Kr on borophene without an electric field are −0.25 eV and −0.18 eV, respectively, indicating that Xe and Kr can only form weak adsorption on borophene. However, by applying an electric field (0.006 a.u.) to the systems, the adsorption energies for Xe and Kr on borophene are −0.98 eV and −0.47 eV, respectively, which shows that the interaction between Xe and borophene has increased dramatically compared with that of Kr, so Xe can be separated from radioactive Xe/Kr mixtures. What's more, when the electric field is removed, desorption of Xe from the surface of borophene is exothermic without an energy barrier. The adsorbent is recyclable. In summary, this theoretical study provides novel information for experimental researches, the highly efficient Xe/Kr separation can be controlled by turning on/off the applied electric field.
The Connections Between Alexithymia, Childhood Maltreatment, Impulsivity and Extreme Sensory Processing Patterns in Relation to Bipolar Symptoms in Inpatients With Bipolar Disorder
Authors: Aghaeimazraji Morteza , Khosravani Vahid , Samimi Ardestani Seyed Mehdi , Berk Michael , Najafi Mahmoud
Published: October 2024

Childhood maltreatment, alexithymia and impulsivity are related to bipolar disorder (BD), but the role of potential underlying mechanisms of this link, such as extreme sensory processing, in BD are unclear. This study compared sensory processing patterns between individuals with BD‐I or BD‐II and between those with and without alexithymia and childhood maltreatment. Additionally, the study aimed to examine the role of extreme sensory processing in the relationship between childhood trauma, alexithymia and impulsivity with both depression and mania in a sample of hospitalized individuals with BD (n = 300). Participants completed self‐report and clinician‐rated scales. Patients with BD‐II exceeded those with BD‐I in low registration, sensory sensitivity and sensation avoidance, whereas patients with BD‐I exhibited a more heightened sensation‐seeking pattern. Patients with BD who had alexithymia and a history of childhood maltreatment exhibited more heightened sensory processing patterns, apart from sensory seeking, compared to those without alexithymia and childhood maltreatment. Additionally, the same pattern was more pronounced in individuals with BD who had both alexithymia and childhood maltreatment compared to those with either condition or neither of these conditions. The pathways from childhood maltreatment and alexithymia to depressive symptoms were mediated by low registration and sensation avoidance. Sensory seeking indirectly affected the link between alexithymia and manic symptoms. Childhood maltreatment and challenges in effectively processing emotional information, along with their related hypo‐ and hypersensitivity, may characterize BD individuals and its manifestation of depressive and manic symptoms.
Longitudinal Analysis of Natural History Progression of Rare and Ultra‐Rare Cerebellar Ataxias Using Item Response Theory
Authors: Hamdan Alzahra , Hendrickx Niels , Hooker Andrew C. , Chen Xiaomei , Comets Emmanuelle , Traschütz Andreas , Schüle Rebecca ,   ARCA Study Group,   EVIDENCE‐RND Consortium, Mentré France , Synofzik Matthis , Karlsson Mats O.
Published: October 2024

Degenerative cerebellar ataxias comprise a heterogeneous group of rare and ultra‐rare genetic diseases. While disease‐modifying treatments are now on the horizon for many ataxias, robust trial designs and analysis methods are lacking. To better inform trial designs, we applied item response theory (IRT) modeling to evaluate the natural history progression of several ataxias, assessed with the widely used scale for assessment and rating of ataxia (SARA). A longitudinal IRT model was built utilizing real‐world data from the large autosomal recessive cerebellar ataxia (ARCA) registry. Disease progression was evaluated for the overall cohort as well as for the 10 most common ARCA genotypes. Sample sizes were calculated for simulated trials with autosomal recessive spastic ataxia Charlevoix–Saguenay (ARSACS) and polymerase gamma (POLG) ataxia, as showcased, across multiple design and analysis scenarios. Longitudinal IRT models were able to describe the changes in the latent variable underlying SARA as a function of time since ataxia onset for both the overall ARCA cohort and the common genotypes. The typical progression rates varied across genotypes between relatively high in POLG (~ 0.98 SARA points/year at SARA = 20) and very low in COQ8A ataxia (~ 0.003 SARA points/year at SARA = 20). Smaller trial sizes were required in case of faster progression, longer trials (~ 75–90% less with 5 years vs. 2 years), and larger drug effects (~ 70–80% less with 100% vs. 50% inhibition). Simulating under the developed IRT model, the longitudinal IRT model had the highest power, with a well‐controlled type I error, compared to total score models or end‐of‐treatment analyses. The established longitudinal IRT framework allows efficient utilization of natural history data and ultimately facilitates the design and analysis of treatment trials in rare and ultra‐rare genetic ataxias.
Drug–Drug Interaction Between Dihydroartemisinin–Piperaquine and Sulfadoxine‐Pyrimethamine During Malaria Chemoprevention in Pregnant Women
Authors: Mwebaza Norah , Roh Michelle E. , Geng Yourong Z. , Opio Leonard , Opira Bishop , Marzan Florence , Mwima Moses W. , Ssemukuye Timothy , Guo Kevin , Gingrich David , Fotaki Nikoletta , Kakuru Abel , Kizza Jimmy , Aguti Miriam , Adrama Harriet , Kamya Moses , Dorsey Grant , Rosenthal Philip J. , Aweeka Francesca T. , Huang Liusheng
Published: October 2024

Co‐administration of dihydroartemisinin–piperaquine (DP) and sulfadoxine‐pyrimethamine (SP) for intermittent preventive treatment of malaria in pregnancy (IPTp) may be superior in preventing adverse birth outcomes compared with either therapy alone, but potential drug–drug interactions require investigation. We conducted intensive and sparse pharmacokinetic (PK) studies in a subset of Ugandan women participating in a randomized controlled trial of monthly IPTp with SP vs. DP vs. DP + SP. Intensive PK sampling was performed from day 0 to 23 after dosing at 28 weeks gestation in 87 participants across treatment arms. Sparse sampling was performed on day 28 (trough) after dosing at 20 and 28 gestational weeks in additional 196 participants receiving SP vs. DP + SP. Intensive PK analysis demonstrated that compared with SP alone, co‐administration of DP + SP was associated with lower maximal concentrations, the area under the concentration–time curves (AUC), and day 23 concentrations of sulfadoxine (25%, 25%, and 27%) and pyrimethamine (26%, 34%, and 32%) (P < 0.05 for all comparisons). Sparse PK results demonstrated participants co‐administered DP + SP had lower trough concentrations after dosing at 20 and 28 gestational weeks for sulfadoxine (6%, P = 0.68 and 31%, P = 0.023, respectively) and pyrimethamine (18%, P = 0.032 and 33%, P < 0.001, respectively) compared with SP alone. Co‐administration of DP + SP was associated with a 19% reduction in piperaquine AUC (P = 0.046), but no significant difference in other PK parameters compared with DP alone. In summary, co‐administration of DP + SP was associated with significantly reduced SP exposure, with a greater magnitude during the third vs. second trimester. The clinical consequences of this interaction are yet unknown.
Using Reporter Gene Assays to Screen and Identify Chemical Compounds that Modulate Estrogen Receptor Activity
Authors: Ooka Masato , Sakamuru Srilatha , Furlow J. David , Xia Menghang
Published: October 2024

Estrogen receptor alpha (ERα) is a nuclear receptor that is expressed mainly in the breast, uterus, and ovary, among several other organs. ERα plays important roles in reproduction, mammary gland formation, and glucose homeostasis. Disruption of ERα may result in adverse outcomes, such as cancer, impaired fertility, and abnormal fetal growth. Therefore, identifying compounds that modulate ERα is of great interest due to their potential‐endocrine disrupting capability and pharmaceutical applications. To rapidly test tens of thousands of compounds, high‐throughput screening assays are essential. Here, we describe high‐throughput screening methods, including plating and treatment of cells in 384‐well and 1536‐well plates and analysis of the resulting data. The two cell lines used, MCF7‐VM7Luc4E2 and HEK293‐ERα‐bla, have been described previously. MCF7‐VM7Luc4E2 cells are a stable luciferase reporter gene cell line expressing full‐length endogenous estrogen receptor in the MCF7 cell line background, and HEK293‐ERα‐bla cells stably express an ERα ligand‐binding domain/GAL4 DNA‐binding domain fusion regulating a UAS β‐lactamase reporter gene. These cell lines can be used to identify and confirm ERα modulators. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Establishment of a high‐throughput ERα reporter gene assay with luminescence readout to identify activators and inhibitors of estrogen receptor α

Basic Protocol 2: Use of an orthogonal assay with fluorescence readout to confirm potential estrogen receptor activators or inhibitors
Metal‐Free C−X Functionalization in Solid‐State via Photochemistry in Ball Mills
Authors: Spula Carolina , Becker Valentin , Talajić Gregor , Grätz Sven , Užarević Krunoslav , Borchardt Lars
Published: October 2024

We report the first metal‐ and catalyst‐free protocol for the facile cross‐coupling of aryl halides towards C−B, C−P and C−S bonds under solid‐state ball milling conditions via UV light irradiation. The reactions can be performed in the absence of bulk solvents at room temperature in a mixer mill, yielding up to 99 % and being tolerant towards various functionalized aryl halides (X=I or Br). Furthermore, we developed a novel photoreactor design increasing the light intensity. With this we could demonstrate that our protocol surpasses classical solvent based as well as purely mechanochemical approaches in terms of green metrics and energy efficiency.
Assessing the Effect of Deep Eutectic Solvents on α‐Chymotrypsin Thermal Stability and Activity
Authors: Gajardo‐Parra Nicolás F. , Cea‐Klapp Esteban , Chandra Anshu , Canales Roberto I. , Garrido José Matías , Held Christoph , Guajardo Nadia
Published: October 2024

Optimizing the liquid reaction phase holds significant potential for enhancing the efficiency of biocatalytic processes since it determines reaction equilibrium and kinetics. This study investigates the influence of the addition of deep eutectic solvents on the stability and activity of α‐chymotrypsin, a proteolytic enzyme with industrial relevance. Deep eutectic solvents, composed of choline chloride or betaine mixed with glycerol or sorbitol, were added in the reaction phase at various concentrations. Experimental techniques, including kinetic and fluorometry, were employed to assess the α‐chymotrypsin activity, thermal stability, and unfolding reversibility. Atomistic molecular dynamics simulations were also conducted to assess the interactions and provide molecular‐level insights between α‐chymotrypsin and the solvent. The results showed that among all studied mixtures, adding choline chloride + sorbitol improved thermal stability up to 18 °C and reaction kinetic efficiency up to two‐fold upon adding choline chloride + glycerol. Notably, the choline chloride + sorbitol system exhibited the most substantial stabilization effect, attributed to the surface preferential accumulation of sorbitol, as corroborated by the computational analyses. This work highlights the potential of tailoring liquid reaction phase of α‐chymotrypsin catalyzed reaction using neoteric solvents such as deep eutectic solvents to enhance α‐chymotrypsin performance and stability in industrial applications.
Arithmetic Optimization Algorithm Quantization Optimized With Energy Detection Using Nonparametric Amplitude
Authors: A Darwin Nesakumar , S Rukmani Devi , T M Inbamalar , K N Pavithra
Published: October 2024

The spectrum sensing is a major significant task in cognitive radio networks (CRNs) to avoid the unacceptable interference to primary users (PUs). Here, the threshold value determines the effectiveness of spectrum sensing and regarded as a sensing system. The fixed threshold used by the current energy detection‐based spectrum sensing (SS) techniques does not provide sufficient safety for the main users. The threshold is determined by lowering the complete probability of decision error in addition to these guidelines. Therefore, an energy detection using nonparametric amplitude quantization optimized with arithmetic optimization algorithm for enhanced spectrum sensing in CRNs (ED‐NAQ‐AOA‐SS CRN) is proposed in this paper to acquire the ideal threshold for decreasing the total error probability. The proposed method achieves greater probability of detection of 99.67%, 98.38%, 92.34%, and 97.45%, lower settling time of 98.33%, 89.34%, 83.12%, and 88.96%, and lower error rate of 93.15%, 91.25%, 79.90%, and 92.88% compared with existing techniques, like intelligent spectrum sharing and sensing in CRN with adaptive rider optimization algorithm (AROA), a novel technique for spectrum sensing in CRN utilizing fractional gray wolf optimization with the cuckoo search optimization (GWOCS), and adaptive neuro‐fuzzy inference scheme depending on cooperative spectrum sensing optimization in CRNs (ANFIS).
Facies variations in gravelly cyclic steps deposited from turbidity currents: Miocene fan delta front deposits compared with a modern active fan delta, central Japan
Authors: Nakajima Takeshi , Saito Yoshiki
Published: October 2024

Gravelly cyclic steps formed by turbidity currents have recently been widely recognised in the geological record. However, the comparison between modern and ancient gravelly cyclic steps remains challenging. In this study, the facies variations of gravelly cyclic steps deposited from turbidity currents in an outcrop of Miocene fan delta front deposits in central Japan are compared with the geomorphic evolution of analogous cyclic steps on the active fan delta front in modern geological systems. These cyclic steps share common characteristics in setting, grain size and dimensions, allowing direct comparison between ancient and modern examples. Repeat bathymetric surveys of the modern Kurobe River fan delta have revealed various types of upslope migrating bedforms interpreted as cyclic steps. Most of these are short‐lived due to erosion of thalwegs by powerful surge‐type turbidity currents triggered by slope failures or burial of thalwegs by deposition, possibly from river‐fed hyperpycnal flows. Such erosion and burial events occur annually on the fan delta front, resulting in compensational cycles. Sedimentary facies of the Miocene fan delta front deposits include conglomerate with a gently upslope dipping erosional base, backset‐stratified sandstone and foreset‐stratified sandstone, which are interpreted as deposits of hydraulic jumps in high‐density turbidity currents in scours on the stoss sides of cyclic steps. Parallel‐stratified conglomerate sandstone is an additional component. Although previous facies models of gravelly cyclic steps have focussed on deposits on stoss sides, a comparison of modern and ancient examples suggests that facies on the lee sides could be parallel‐stratified conglomerate sandstone and undulating bedforms, reflecting supercritical flow conditions. The present study also suggests that hyperpycnal and surge‐type high‐density turbidity currents may deposit different types of facies and play different roles in the construction and destruction of cyclic steps. The present study has significant implications for facies models of gravelly cyclic steps.
Male Reproductive Traits Display Increased Phenotypic Variation in Response to Resource Quality and Parental Provisioning in a Tropical Rainforest Dung Beetle, Onthophagus c.f. babirussa
Authors: Yap Sean , Toh Kai Xin , Puniamoorthy Nalini
Published: October 2024

Reproductive traits that mediate differential fitness associated with mate acquisition and fertilisation success are often strongly linked to the overall condition. We investigated the effects of resource quality and parental provisioning in the phenotypic expression of sexual and non‐sexual traits in a rainforest dung beetle, Onthophagus c.f. babirussa (Eschscholtz, 1822) from Singapore. F1 individuals were reared from wild‐caught beetles and paired up to produce offspring (F2), and F2 larvae from the same F1 parents were reared on two dung substrates (herbivore and omnivore) in a full‐sib design. Sexual traits displayed greater phenotypic variation in response to dung resource quality, with the precopulatory trait (horn length) responding more than the postcopulatory trait (testes weight). Notably, genotype‐by‐environment interactions between parental lines (genotype) and dung type (environment) affected male body size and horn length only, suggesting sex‐specific variance in plasticity associated with sexually selected precopulatory traits. Dung type had significant effects on all measured traits. Offspring that were provisioned higher quality resource (omnivore dung) had larger absolute and relative trait values. Parental lines only significantly affected female body size but none of the male traits, suggesting an important role of environment and resource partitioning in determining precopulatory success of male offspring. Parental provisioning of larval resource varied with resource quality and brood sequence. Parents provisioned more dung when herbivore dung was presented than when they were given omnivore dung and provisioned more dung for their earlier broods when using herbivore dung but not omnivore dung. This suggests a trade‐off between early offspring fitness and resource quality. We tested directly for genotype‐by‐environment (G × E) interactions in the expression of several morphological traits relevant to dung beetle fitness and documented that offspring with similar phenotypes may result from completely different parental resource allocation strategies. We discuss the importance of studying parental investment on trait variation and its implications on dung beetle ecology.
Diversity of Orchid in Abies nephrolepis Nature Reserve in Shanxi, China
Authors: Chen Xiaojiang , Li Jiajia , Wei Wenjiao , Fu Qianru , Zheng Qingrong , Li Meihong , Li Xing
Published: October 2024

Abies nephrolepis Nature Reserve has complex habitats and rich species diversity but lacks systematic ecological surveys. We focused on Orchid in Abies nephrolepis Nature Reserve, investigated and analyzed Orchid diversity and changes in community structure according to the characteristics of the alpine valleys in the study area, in terms of altitude gradient and habitat type, using the sample line method and the quadrat method. The results showed that 11 genera and 13 species of Orchidaceae were found in the survey, among which the species richness of Malaxis monophyllos was the highest, Neottia puberula was the second highest, and the species richness of Tulotis ussuriensis was the lowest, and the species with relative plurality ≥ 10% were Malaxis monophyllos (51.69%), Neottia puberula (14.77%), and Cypripedium guttatum (11.15%). The results of diversity analysis showed that Orchidaceae species were rich and the diversity index were the highest in the middle altitude area of 1950–2250 m; the distribution of Orchidaceae in the low altitude area was obviously clustered, and the similarity with the high altitude area was low. With the increase in altitude, the number of species showed an increase and then a decrease, showing a single‐peak state, which was in line with the theory of “Intermediate altitude expansion hypothesis”. The species and number of Orchidaceae in different habitats of Abies nephrolepis Nature Reserve also varied considerably, with Shannon‐Wiener diversity index being the highest in EV4 (Abies nephrolepis + Picea meyeri + Picea wilsonii + Larix gmelinii var. principis‐rupprechtii—Lonicera hispida—Carex lanceolata community) and EV5, and the smallest in EV1 habitats, Pielow evenness index being the highest in EV5 habitats and the lowest in EV1 habitats, and Simpson's index being the highest in EV5 habitats and the lowest in EV1 habitats. This study provides a scientific basis for strengthening regional monitoring of species diversity and protecting biodiversity.
Predator–prey space use and landscape features influence movement behaviors in a large‐mammal community
Authors: Bassing Sarah B. , Satterfield Lauren , Ganz Taylor R. , DeVivo Melia , Kertson Brian N. , Roussin Trent , Wirsing Aaron J. , Gardner Beth
Published: October 2024

Predator hunting strategies, such as stalking versus coursing behaviors, are hypothesized to influence antipredator behaviors of prey and can describe the movement behaviors of predators themselves. Predators and prey may alter their movement in relation to predator hunting modes, yet few studies have evaluated how these strategies influence movement behaviors of free‐ranging animals in a multiple‐predator, multiple‐prey system. We fit hidden Markov models (HMM) with movement data derived from >400 GPS‐collared ungulates and large predators in eastern Washington, USA. We used these models to test our hypotheses that stalking (cougars [Puma concolor]) and coursing (gray wolves [Canis lupus]) predators would exhibit different broad‐scale movement behaviors consistent with their respective hunting strategies in areas that increased the likelihood of encountering or capturing ungulate prey (e.g., habitats selected by deer [Odocoileus spp.]). Similarly, we expected that broadscale movement behaviors of prey would change in response to background levels of predation risk associated with each predator's hunting strategy. We found that predators and ungulate prey adjusted their broadscale movements in response to one another's long‐term patterns of habitat selection but not based on differences in predator‐hunting strategies. Predators changed their movement behaviors based on the type of prey, whereas ungulates generally reduced movement in areas associated with large predators, regardless of the predator's hunting strategy. Both predator and prey movements varied in response to landscape features but not necessarily based on habitat that would facilitate specific hunting behaviors. Our results suggest that predators and prey adjust their movements at broad temporal scales in relation to long‐term patterns of risk and resource distributions, potentially influencing their encounter rates with one another at finer spatiotemporal scales. Habitat features further influenced changes in movement, resulting in a complex combination of movement behaviors in multiple‐predator, multiple‐prey systems.
Effect of inulin on preventing drunkenness and relieving acute alcoholic intoxication of mice and preparation of its hangover beverage
Authors: Lan Honglin , Li Xingguo , Zhang Yunhui , Wan Jiahao , Wang Yanbin , Cao Jintao , Bai Zhouya , Luo Denglin , Han Sihai , Yue Chonghui , Gao Haiyan
Published: October 2024

The aim of this study was to evaluate the effects of different types of inulin on acute alcoholic intoxication (AAI) in mice and prepare its hangover beverage. Basic physical and chemical properties of different types of inulin (short‐chain inulin, long‐chain inulin, and phosphorylated long‐chain inulin) were analyzed and given by gavage at a dose of 400 mg kg−1 day−1 for a continuous period of 7 days through animal behavior experiments, and the inebriation percentage, mortality rate, duration of inebriation, and sobering time were recorded with the righting reflex as the judgment criterion. The results showed that, compared with the control group, the drunkenness and mortality rates of short‐chain inulin decreased by 12% and 100%, respectively, and the sober time decreased by 18%, while alcohol tolerance was also improved. The best formula for a short‐chain inulin hangover drink was determined to be: 0.4% granulated sugar, 0.5% citric acid, and 0.5% pectin. These suggest that short‐chain inulin may have potential in preventing AAI.
Nutritional composition, phytochemical profile, and health benefits of Hylocereus Undatus (pitaya): A comprehensive review
Authors: Bishoyi Ashok Kumar , Saeed Farhan , Shehzadi Umber , Shankar Amar , Balaji Jadhav , Kaur Jaspreet , Afzaal Muhammad , Imran Ali , Rasheed Musarrat , Hussain Bilal , Hussain Muzzamal , Ahmed Aftab , Islam Fakhar , Kinki Abdela Befa
Published: October 2024

Hylocereus undatus, occasionally referred to as the dragon fruit or white‐fleshed pitaya, is a rich in nutrients fruit appreciated because of its colorful look and health benefits. It is inexpensive in calories but packed with minerals like iron, magnesium, and calcium in addition to essential nutrients like vitamin C and B vitamins. Similarly rich in dietary fiber, particularly promotes gut wellness and improves digestion, is pitaya. It additionally contains antioxidants, such as phenolic compounds, flavonoids, and betalains, which help with scavenging free radicals and reducing the detrimental effects of oxidative stress on the human body. The substantial amount of betalains in Hylocereus undatus phytochemical composition is notable because it contributes to the plant's anti‐inflammatory and antioxidant properties. There has been an association among these phytochemicals and a decreased likelihood of contracting long‐term conditions such as diabetes, cancer, and cardiovascular disease. Omega‐3 fatty acids and omega‐6 fatty acids, in particular, that reduce cholesterol levels while improving blood circulation, are plentiful in the fruit's seeds and are beneficial to heart wellness. The objective of this review is to highlight the nutritional profile, phytochemical and health benefits of Hylocereus undatus in detail.