bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing Donor Acceptor Interactions of Chalcogenide Supported Fluorophosphonium Ions Using peri‐substituted Acenaphthyl Scaffolds
Authors: Heuermann Isabell , Mostaghimi Farzin , Lork Enno , Mebs Stefan , Hupf Emanuel , Beckmann Jens
Published: November 2024

The fluorination of the peri‐substituted acenaphthyl scaffolds 5‐PhE‐Ace‐6‐PPh2 (1E, E=O, S, Se, Te) using XeF2 afforded the difluorinated products 5‐PhE‐Ace‐6‐PF2Ph2 (2E, E=O, S, Se, Te) and tetrafluorinated products 5‐PhEF2‐Ace‐6‐PF2Ph2 (3E, E=Se, Te) depending on the stoichiometry applied. Fluoride abstraction of 2E using Me3SiOTf gave rise to the chalcogenide supported fluorophosphonium ions [5‐PhE‐Ace‐6‐P(F)Ph2](OTf) (4O and 5E, E=S, Se, Te). The molecular structure of 4O features a tetrahedral P atom, whereas those of the heavier analogues (5E, E=S, Se) contain trigonal bipyramidal P atoms that arise from intramolecular LP(E)→σ*(P−F) interactions.
Effect of Perilla Seeds Pretreatment on the Volatile Profile and Flavor Characteristics of Perilla Oil: Comparison of Oven, Infrared, and Microwave Heating
Authors: Yao Ling , Huang Jianhua , He Hongying , Song Zhihua , Wang Xingguo , Wang Xiaosan
Published: November 2024

The effects of microwave (MW), infrared (IF), and oven heating (OH) on the volatile profile and flavor of perilla oil were investigated in this study. Physicochemical properties and Maillard reaction products of perilla oil were measured to investigate the potential pathway of flavor formation. Sensory evaluation, combined with headspace‐solid‐phase microextraction‐gas chromatography‐mass spectrometry (HS‐SPME‐GC‐MS) and electronic nose (E‐nose) techniques, was employed to determine the categories and contents of volatile compounds in perilla oil. Three heating treatments all effectively increased the content of odor‐active volatile compounds in perilla oil. Samples treated by MW contained higher concentration of heterocyclics, while samples treated using IF and OH contained more aldehydes. The content of (E,E)‐2,4‐heptadienal were highly correlated to P‐AV. The contents of pyrazines and furans were positively correlated with A420nm, particularly 2,5‐dimethyl‐pyrazine, trimethyl‐pyrazine, and 2‐pentylfuran. The content of hexanal and (E)‐2‐hexenal showed a negative correlation with the content of heterocyclic compounds. Consequently, the volatile compounds in perilla oils were generated through three potential mechanisms: lipid oxidation, the Maillard reaction, and their synergistic effect.
Scandium‐Catalyzed Fischer Indole Synthesis: A Highly Efficient Construction of Complicated Indoles
Authors: Thorat Vijaykumar H. , Chao Hao‐Yu , Yang Po‐Han , Hsieh Jen‐Chieh
Published: November 2024

Herein, we report an efficient scandium‐catalytic reaction protocol for the classical Fischer indole synthesis, which can tolerate a wide variety of polycyclic substrates and allow us to easily construct complex indole structures in high yields for most cases. Moreover, in order to demonstrate the reaction efficacy, we also synthesized two quinazolinone‐containing natural alkaloids, their analog, as well as an anticancer indenoindolone compound.
Ribes khorasanicum: A Potent Antioxidant Against Organ Toxicity by Effect on the NF‐κB Pathway
Authors: Shafei Mohammad Naser , Shabab Sadegh , Entezari Heravi Nazanin , Mohebbati Reza
Published: November 2024

Acetaminophen (APAP) is a well‐known drug that, in high doses, induces hepatotoxicity and nephrotoxicity. This study has investigated the preventive effect of the extract and fractions of Ribes khorasanicum on APAP‐induced liver and kidney damage. In this experiment, after analysis of the extract using FTIR, toxicity was induced by APAP on the 7th day. Before that, the extract and their aqueous, ethyl acetate, and n‐hexane fractions were administrated orally. 24 h after APAP administration, the animals were sacrificed. The liver and kidney were removed for the evaluation of oxidation and biochemical markers, including SGOT, SGPT, ALP, LDH, albumin, urea, creatinine, and bilirubin and also for histopathological evaluations. The safety of the extract was evaluated based on the MTT. Also, expression of the NF‐kB is done. Administration of Ribes khorasanicum significantly decreased the biochemical parameters compared to the APAP. Oxidative parameters, as well as histopathological changes in preventive groups, were improved compared to the APAP in both tissues. The results showed that the aqueous and ethyl acetate fractions of the extract had a better effect than the whole extract and n‐hexane fraction against APAP toxicity.
Causes of death among patients diagnosed with chronic lymphocytic leukemia: A population‐based study in the Netherlands, 1996–2020
Authors: van der Straten Lina , Levin Mark‐David , Dinnessen Manette A. W. , Visser Otto , Posthuma Eduardus F. M. , Doorduijn Jeanette K. , Langerak Anton W. , Kater Arnon P. , Dinmohamed Avinash G.
Published: November 2024

Chronic lymphocytic leukemia (CLL) manifests heterogeneously with varying outcomes. This population‐based study examined causes of death (CODs), as registered by the physician who established the death, among 20,588 CLL patients diagnosed in the Netherlands between 1996 and 2020. Utilizing cause‐specific flexible parametric survival models, we estimated cause‐specific hazard ratios (HRs) and cumulative incidences of death due to CLL, solid malignancies, other hematological malignancies, infections, and other causes. Our findings reveal CLL as the predominant COD, contributing to around 40% of relative mortality, with a declining 5‐year death probability from 16.8% in 1996–2002 to 7.6% in 2010–2020. Also, deaths attributed to solid malignancies, other hematological malignancies, and other COD diminished over time, as evidenced by respective HRs (95% confidence interval) of 0.68 (0.60%–0.77%), 0.45 (0.38%–0.53%), and 0.77 (0.66%–0.90%). In summary, our comprehensive, population‐based analysis underscores a noticeable reduction in CLL‐attributed deaths and other competing causes over the studied period. Nonetheless, CLL is registered as the most prevalent cause of mortality among contemporary diagnosed patients with CLL, emphasizing the continued relevance of CLL‐centric clinical strategies and research.
Understanding COVID‐19 Vaccine Acceptance Among Iranian Pregnant Women: Insights From a Multicenter Cross‐Sectional Study
Authors: Fathnezhad‐Kazemi Azita , Hadipour Lila , Pirami Raziyeh , Khazaeian Somayyeh
Published: November 2024

Background and Aims

Despite significant advancements in COVID‐19 vaccine research and development, hesitancy in its acceptance, particularly among pregnant women, is recognized as a health threat. Based on the Health Belief Model, this study aimed to identify the factors influencing vaccine nonacceptance among pregnant women in the cities of Zahedan and Tabriz, Iran.

Methods

The present research was a multicenter cross‐sectional study conducted among pregnant women in two Iranian provinces, Zahedan and Tabriz, covering both high and low fertility regions. The study was conducted from February 2022 to August 2022. The sample size comprised 650 pregnant women attending selected healthcare centers. Data collection tools included questionnaires on sociodemographic characteristics, awareness, vaccine acceptance, and health beliefs related to vaccination. Data were analyzed using descriptive and analytical methods, including Analysis of variance (ANOVA), Independent t‐test, and multivariable logistic regression.

Results

Among the 650 pregnant women, the vaccine acceptance rate was 47.4% and 52.6% of pregnant women reported vaccine nonacceptance during pregnancy. The logistic regression model indicated that the odds of vaccine acceptance increase with maternal employment (OR = 11.53, 95% CI: 4.81–27.63), higher maternal education levels (OR = 6.97, 95% CI: 3.11–15.63), higher income (OR = 1.60, 95% CI: 1.07–2.55), and increased awareness levels (OR = 1.37, 95% CI: 1.03–1.52). Additionally, the odds of vaccine acceptance increase with increased perceived susceptibility (OR = 2.55, 95% CI: 0.47–3.76), increased perceived benefits (OR = 2.22, 95% CI: 1.06–4.61), increased perceived barriers (OR = 0.42, 95% CI: 0.18–1.12), and increased cues to action (OR = 2.01, 95% CI: 1.03–3.92).

Conclusion

Our study underscores the multifaceted nature of COVID‐19 vaccine acceptance among pregnant women, with socioeconomic, awareness‐related, and psychological factors all playing pivotal roles. These findings can inform targeted interventions and strategies aimed at increasing vaccine acceptance in this vulnerable population, ultimately contributing to enhanced maternal and fetal health during the ongoing pandemic.
Early Versus Delayed Usage of Paxlovid in Severe Omicron‐Infected Patients With Hypoxemia: A Prospective Multiple‐Center Cohort Study
Authors: Wang Yu‐Ji , Ma Xi‐Yan , Wei Xiao‐Ying , Zhang Meng‐Lan , Su Nan , Jiang Jun‐Hong , Xu Guo‐Peng , Wang Ran , Zeng Da‐Xiong
Published: November 2024

Background and Aims

Early stage administration of Paxlovid has been shown to improve the prognosis of mild to moderate COVID‐19 patients with high risk. However, few evidence was validated in severe COVID‐19 patients with hypoxemia. It is also unclear whether delayed usage of Paxlovid affected prognosis in COVID‐19 patients or not.

Methods

In this multiple‐centers prospective study, we collected the clinical data in hospitalized severe adult Omicron infection patients with hypoxemia. All patients were divided into two groups according to the time of Paxlovid usage after the symptom onset: early group (Paxlovid administration in 5 days after symptom onset) and delayed group (Paxlovid administration beyond 5 days after symptom onset). The 28‐day composite outcomes were evaluated.

Results

Totally 198 hospitalized severe omicron‐infected subjects with hypoxemia were enrolled. There was no difference between the two groups about the baseline characteristics and laboratory parameters, except for leukocytes (5.29 × 109 vs. 7.90 × 109/L, p = 0.01) and albumin levels (35 vs. 31 g/L, p = 0.04). The 28‐day composite outcomes in early group were slightly lower than that in delayed group but with no difference (12.8% vs. 16.67%, p = 0.602). The viral clearance ratio at Day 7 after Paxlovid treatment in early group was higher than that in delayed group (79.48% vs. 58.33%, p = 0.029). The medium hospitalized duration in early group was shorter than that in delayed group (11.31 vs. 15.32 days, p = 0.005). Logistic analysis showed the independent risk factors of prognosis including underlying diseases ≥ 3 kinds (ORR = 1.72), d‐dimer ≥ 2.0 μg/mL (ORR = 1.35), and MODS (ORR = 14.01).

Conclusions

In Omicron‐infected subjects with hypoxemia, early usage of Paxlovid received benefits in hospitalized time and viral clearance, but delayed usage did not result in a worse composite prognosis. This result might provide direct evidence of antiviral strategy in severe Omicron infection subjects with hypoxemia.
A Retrospective Analysis of Universal Health Insurance Policy‐Making Process in Iran: A Qualitative Study
Authors: Kabir Mohammad Javad , Heidari Alireza , Lotfi Mansoureh , Khatirnamani Zahra , Golpira Reza
Published: November 2024

Background and Aims

Universal Health Insurance (UHI) coverage began in 2014, after the implementation Health Transformation Plan (HTP) to reduce out‐of‐pocket payments and improve access to health services in Iran Health Insurance Organization (IHIO). The purpose of this study was to analyze the UHI policy‐making process in Iran.

Methods

This study was performed using Walt and Gilson's (1994) policy triangle framework and Kingdon's multiple streams model. Data were collected through document review, in‐depth individual interviews (constituting 17 policymakers and top, middle, and operational level managers), and one round‐table discussion (constituting 10 top managers and senior policymakers). The majority of the participants were MD and MPH (47.07%). Document review data were analyzed using thematic content analysis. Interviews and discussions were analyzed using framework analysis.

Results

The high‐level documents of Iran emphasize the need for insurance coverage. The commitment of the new government to enforce the laws, concurrent implementation of the UHI and the HTP, the new government's approach to enforcing civil rights, and media pressure to speed up the implementation process. UHI was initiated in 2014 and about 11 million people across the country were covered by free health insurance but the budget did not change in proportion to the increase in insured population, and increased IHIO's debt to contracting centers.

Conclusions

To achieve continuity and effectiveness of UHI in Iran, all stakeholders should be involved. Political will and commitment and sustainable financing are needed for it.
Nipah Virus Outbreaks in Kerala: An Impending Doom?
Authors: Sanker Vivek , Vellekkat Faheem , Dave Tirth
Published: November 2024

Background and Aims

The resurgence of Nipah virus (NiV) in Kerala, India, represents a significant public health challenge. This paper aims to explore ongoing challenges associated with NiV transmission, focusing on environmental factors, healthcare responses, and shifts in clinical manifestations. We also highlight the critical need for proactive management strategies to prevent future outbreaks, given the virus's zoonotic nature and evolving transmission dynamics.

Methods

A search was conducted using keywords such as “Nipah virus,” “Kerala,” and “bats” in PubMed, Scopus, Google Scholar, and trusted news sources. Articles and reports were selected based on their relevance to NiV transmission, clinical presentation, and containment efforts, particularly concerning recent outbreaks in Kerala.

Results

Recent outbreaks have shown atypical respiratory presentations, complicating early detection and increasing the importance of healthcare containment. The virus's clustering within specific regions and the emergence of a new genotype underscore the need for enhanced surveillance.

Conclusion

The frequent NIV outbreaks in Kerala demand a multifaceted approach to prevention. Early detection systems, public awareness campaigns, and rigorous environmental management are essential. Collaborative efforts between government and public health entities are paramount to mitigate the impact of this deadly virus. Continuous research is imperative to safeguard public health.
Numerical Investigation of Pyramid Solar Stills with PCM‐Nanoparticles and Absorber Fins: Enhanced Thermal Performance for Sustainable Water Desalination
Authors: Abed Angham Fadil , Alshukri Mohammed J. , Alsayah Ahmed Mohsin , Rasheed Rassol Hamed , Khaled Mahmoud
Published: November 2024

In arid regions facing challenges of limited access to potable water and electricity, solar desalination stands out as a promising solution for producing clean water from brackish sources. This research intends to examine and enhance an innovative and sustainable solar desalination system. A computational study is conducted on a pyramid solar still (PSS) combined with a phase‐change material incorporated with nanoparticles, with a variety of absorber fins. The study investigates three configurations: a traditional pyramid–shaped solar still, one with square absorber fins, and another with circular fins. Paraffin wax mixed with Al2O3 nanoparticles is used beneath the absorber fins. Conservation equations are solved using COMSOL Multiphysics. Simulation outcomes demonstrate that the incorporation of finned absorbers, coupled with elevated water temperatures, significantly enhances the yield of the improved PSS compared with its conventional counterpart. The square‐finned absorber PSS exhibits a substantial increase in total accumulated productivity over the conventional design. Moreover, the PSS with square‐finned absorbers demonstrates an impressive average peak daily thermal efficiency improvement of 49.19% compared with a conventional solar still. This study highlights the effectiveness of the modified PSS as a superior option for household water generation.
Immunogenicity of two‐dose sinopharm BBIB‐CorV vaccine in Morocco: One‐year follow‐up and neutralizing activity against severe acute respiratory syndrome coronavirus 2 variants of concern
Authors: Ouarab Maha , Bouaiti Elarbi , Rhazzar Zineb , El Annaz Hicham , kochri Safae el , Hemlali Mouhssine , Ghammaz Hamza , Nyabi Omar , Bakkouri Karim el , Touil Nadia , Elouennass Mostafa , Belayachi Lamiae , Gala Jean Luc , Ennibi Khalid , El Fahime Elmostafa
Published: November 2024

Background

This study aimed to evaluate the immunogenicity of a two‐dose Sinopharm BBIB‐CorV (Vero cells) vaccine against SARS‐CoV‐2, at 28 days, 6 months, and 1‐year postvaccination. And assess the capacity of two‐dose vaccine recipients to neutralize SARS‐CoV‐2 strains B.1 (Wuhan/D614G), B.1.1.7 (Alpha), AY.33 (Delta), or BA.5.2.2 (Omicron) variants of concern (VOCs).

Methods

A prospective matched case–control cohort study was conducted at the Military Hospital of Rabat, Morocco between February 2021 and 2022. Immunogenicity was evaluated by standard Microneutralization (MN) assay against four variants (Wuhan D614G, Alpha, Delta, and Omicron).

Results

The overall positive neutralizing rates for vaccine recipients against B.1 D614G were 72.09%, 74.82%, and 75.19% on 28‐, 180‐, 365‐ day respectively. The proportion of NAbs targeting the Wuhan D614G, and Alpha variants under the BBIBP‐CorV vaccination was high on Day 28‐ and 6 months postvaccination.

Conclusion

The immunogenic response to the newly emerging SARS‐CoV‐2 variants of concern (VOCs), such as Delta and Omicron was comparatively reduced. As a result, it is recommended that additional boost vaccinations be considered.
Profiles of intergenerational and digital solidarity between middle‐aged parents and young adult children during the COVID‐19 pandemic: Associations with parents' psychological well‐being
Authors: Hwang Woosang , Hadi Narges , Lee Seonhwa , Brown Maria T. , Silverstein Merril
Published: November 2024

We uncovered latent profiles of intergenerational and digital solidarity between middle‐aged parents and their oldest young adult children during the COVID‐19 pandemic. Furthermore, we investigated whether solidarity latent profiles were related to middle‐aged parents' psychological well‐being. We used data from the 2022 survey of the Longitudinal Study of Generations (LSOG), which involved 234 middle‐aged parents providing information about their oldest young adult children. Using latent profile analysis, we uncovered five solidarity profiles (Tight‐knit traditional, distant‐but‐digitally connected, obligatory, sociable, and conflictual) in relationships between middle‐aged parents and their oldest young adult children during the pandemic. Furthermore, we found that middle‐aged parents belonging to the distant‐but‐digitally connected and tight‐knit traditional profiles had enhanced psychological well‐being than those in the conflictual profile during the pandemic. These findings indicate that middle‐aged parents' use of digital communication with young adult children benefited their psychological well‐being during the pandemic. Moreover, using digital communication may be related to strong solidarity between middle‐aged parents and young adult children when they live independently.
Feasibility Study of Label‐Free Raman Spectroscopy for Parathyroid Gland Identification
Authors: Wang Hao , Guo Sisi , Zhang Ruoyu , Yao Jing , Tian Wen , Wang Jianfeng
Published: November 2024

We aim to evaluate the feasibility of Raman spectroscopy for parathyroid gland (PG) identification during thyroidectomy. Using a novel side‐viewing handheld Raman probe, a total of 324 Raman spectra of four tissue types (i.e., thyroid, lymph node, PG, and lipid) commonly encountered during thyroidectomy were rapidly (< 3 s) acquired from 80 tissue sites (thyroid [n = 10], lymph node [n = 10], PG [n = 40], lipid [n = 20]) of 10 euthanized Wistar rats. Two partial least‐squares (PLS)‐discriminant analysis (DA) detection models were developed, differentiating the lipid and nonlipid (i.e., thyroid, lymph node, and PG) tissues with an accuracy of 100%, and PG, lymph node, and thyroid could be detected with an accuracy of 98.4%, 93.9%, and 95.4% respectively. This work demonstrates the feasibility of Raman spectroscopy technique for PG identification and protection during thyroidectomy at the molecular level.
Patient and public involvement in HIV research: a mapping review and development of an online evidence map
Authors: Jackson‐Perry David , Cart‐Richter Ellen , Haerry David , Ahmeti Lindrit , Bieri Annatina , Calmy Alexandra , Ballif Marie , Pasin Chloé , Notter Julia , Amstutz Alain ,   the Swiss HIV Cohort Study Young Researchers’ Group, and the Swiss HIV Cohort Study
Published: November 2024

Introduction

Increasing evidence indicates the benefits of patient and public involvement (PPI) in medical research, and PPI is increasingly expected by funders and publishers. We conducted a mapping review of studies reporting examples of PPI implementation in HIV research, and developed an online evidence map to guide HIV researchers.

Methods

We systematically searched Medline and Embase up until 18 August 2024, including search terms with variations for PPI and HIV. We extracted information from identified studies in duplicate and analysed the data descriptively and qualitatively to describe types of PPI models and reported benefits, challenges, and mitigation strategies. This study was co‐initiated and co‐led by people living with HIV.

Results

We identified 17 studies reporting PPI in HIV research between 1992 and August 2024. Most PPI examples informed prospective clinical studies, but also qualitative research, questionnaire development, research priority setting and surveys. Ten studies described the number and characteristics of PPI members involved. We observed four PPI models, from a model that solely engaged PPI members for a specific task to a model whereby PPI representatives were integrated into the study team with decision‐making authority. Benefits reported included wider dissemination of research results, better understanding of research material and results, and higher levels of trust and learning between researcher and communities. The most commonly reported challenges were the lack of specific resources for PPI, differing levels of knowledge and expertise, concern about HIV status disclosure, and lack of diversity of the PPI team. Uneven power dynamics, tensions, and differing expectations between stake‐holder groups were also frequently noted.

Conclusions

This mapping review summarizes published examples of PPI in HIV research for various phases of research. There is a clear need to strengthen the reporting on PPI processes in HIV research, for example by following the Guidance for Reporting Involvement of Patients and the Public (GRIPP) 2 guidelines, and developing guidance on its hands‐on implementation. We embedded PPI from study inception onwards, which potentially pre‐empted some of the challenges reported in the reviewed examples. The resulting online evidence map is a starting point to guide researchers on integrating PPI into their own research.
Novel Intertypic Recombinant Coxsackievirus A2 Containing Specific Amino Acid Mutations in the RNA‐Dependent RNA Polymerase Potentially Associated With Its Emergence
Authors: Xie Zhenfeng , Khamrin Pattara , Maneekarn Niwat , Kumthip Kattareeya
Published: November 2024

Coxsackievirus A2 (CVA2), a member of enterovirus A species (EV‐A), is associated with diverse human diseases and occasionally causes acute gastroenteritis (AGE). In Thailand, CVA2 emerged as the predominant genotype in 2019. The increasing incidence of CVA2, coupled with the limited availability of full‐length genomes, highlights the need for more complete genome sequence analysis to facilitate molecular epidemiology study. This study aimed to investigate the molecular epidemiology, evolutionary dynamics, and recombination characteristics of CVA2 associated with AGE in Thailand from 2013 to 2022. A total of 19 full‐genome sequences of CVA2 isolated from stool samples of AGE patients in Thailand were characterized and analyzed together with the reference sequences available in the GenBank database. A novel lineage of CVA2 (subgenotype C5) was detected with the potential recombination with CVA10 within the P2 and P3 regions. Specific consensus amino acid mutations, A61S in the VP3 gene and R136K in the 3D (RdRp) gene, were identified in all CVA2 recombinant strains. Additionally, the S45G mutation in the RdRp gene was found to be potentially associated with the emergence of CVA2 infection in 2019. In conclusion, this study reveals potential intertypic recombinant events and specific mutations in CVA2 strains isolated from AGE patients and provides a broader understanding of its evolutionary epidemiology.
Bifurcation and Controller Design of 5D BAM Neural Networks With Time Delay
Authors: Cui Qingyi , Xu Changjin , Xu Yiya , Ou Wei , Pang Yicheng , Liu Zixin , Shen Jianwei , Baber Muhammad Zafarullah , Maharajan Chinnamuniyandi , Ghosh Uttam
Published: November 2024

All the time delayed dynamical system plays a vital role in describing the dynamical phenomenon of neural networks. In the current article, we study a class of 5D delayed bidirectional associative memory (BAM) neural networks that conform to objective reality. First of all, we prove that the solution of the delayed 5D BAM neural networks exists and is unique by virtue of fixed point theorem and some inequality techniques. Secondly, the Hopf bifurcation and stability of the delayed 5D BAM neural networks are investigated by exploiting the stability criterion and bifurcation theory. Once more, Hopf bifurcation control strategy of the delayed 5D BAM neural networks is explored by virtue of two different hybrid controllers. By adjusting the parameters of the controllers, we can control the stability domain and Hopf bifurcation onset. Eventually, the correctness of the theoretical results was verified through numerical simulations. The conclusions obtained in this paper are new and have important theoretical value in neural network area.
A Perspective of Multi‐Reflecting TOF MS
Authors: Verenchikov A. N. , Makarov V. V. , Vorobyev A. V. , Kirillov S. N.
Published: November 2024

Time‐of‐flight mass spectrometry (TOF MS) excels in rapid and high‐sensitivity analysis, making it a cornerstone of analytical chemistry. But as sample complexity explodes in omics studies, so does the need for higher resolving power to ensure accurate results. Traditional TOF instruments face a challenge: achieving high resolution often requires a very large instrument. To overcome this limitation, scientists developed alternative designs for TOF analyzers called multi‐pass TOF analyzers (MPT). These MPT analyzers come in two main configurations: multi‐turn (MTT) and multi‐reflecting (MRT). Drawing on the authors’ extensive experience, this review describes two decades of MPT advancements. It highlights the critical development of optimized analyzer designs, tracing the evolution towards mirror‐based MRT instruments, generally providing superior resolution and spatial acceptance compared to MTT. While the manuscript attempts to overview MTT advances, it primarily focuses on MRT technology. Additionally, the review explores the role of orthogonal accelerators and trap pulse converters, comparing their efficiency and the dynamic range limits imposed by space charge effects. By comparing various MRT configurations and commercially available instruments, the review sets out to inform and empower researchers so they can make informed decisions about MRT mass spectrometers.
Metabolomics‐driven approaches for identifying therapeutic targets in drug discovery
Authors: Pan Shanshan , Yin Luan , Liu Jie , Tong Jie , Wang Zichuan , Zhao Jiahui , Liu Xuesong , Chen Yong , Miao Jing , Zhou Yuan , Zeng Su , Xu Tengfei
Published: November 2024

Identification of therapeutic targets can directly elucidate the mechanism and effect of drug therapy, which is a central step in drug development. The disconnect between protein targets and phenotypes under complex mechanisms hampers comprehensive target understanding. Metabolomics, as a systems biology tool that captures phenotypic changes induced by exogenous compounds, has emerged as a valuable approach for target identification. A comprehensive overview was provided in this review to illustrate the principles and advantages of metabolomics, delving into the application of metabolomics in target identification. This review outlines various metabolomics‐based methods, such as dose–response metabolomics, stable isotope‐resolved metabolomics, and multiomics, which identify key enzymes and metabolic pathways affected by exogenous substances through dose‐dependent metabolite–drug interactions. Emerging techniques, including single‐cell metabolomics, artificial intelligence, and mass spectrometry imaging, are also explored for their potential to enhance target discovery. The review emphasizes metabolomics' critical role in advancing our understanding of disease mechanisms and accelerating targeted drug development, while acknowledging current challenges in the field.
Simultaneous monitoring of glycogen, creatine, and phosphocreatine in type II glycogen storage disease using saturation transfer MRI
Authors: Bie Chongxue , Bo Shaowei , Yadav Nirbhay N. , van Zijl Peter C. M. , Wang Tao , Chen Lin , Xu Jiadi , Zou Chao , Zheng Hairong , Zhou Yang
Published: November 2024

Purpose

There is a need for non‐invasive approaches to assess the progression of glycogen storage diseases (GSD). Here, we use saturation transfer (ST) MRI via relayed nuclear Overhauser effects (glycoNOE) to detect abnormal changes in muscle glycogen of a GSD II mouse model. In addition to glycogen, the energy metabolites phosphocreatine (PCr) and creatine (Cr) were studied to assess the muscle disease.

Methods

Water saturation (Z‐spectra) and 1H MRS were acquired at 9.4 T on the skeletal muscle of healthy control mice and homozygous acid ‐glucosidase (GAA) knock‐out mice (ages of 2–48 weeks). The glycoNOE (−1 ppm), total creatine (tCr)* (+2 ppm, = a × [Cr] + b × [PCr]), and PCr (+2.5 ppm) from Z‐spectra and the ratio between tCr and taurine signals (tCr/Tau) from 1H MRS spectra were quantified by using multi‐pool Lorentzian fitting methods. The concentrations of the metabolites were also measured via tissue assays.

Results

The postnatal GSD II mice (age <12 weeks) showed a continued accumulation of muscle glycoNOE signal. GlycoNOE in adult GSD II mice (age ≥12 weeks) reached a plateau, at a level above 400% of that in normal mice. PCr, tCr*, and tCr/Tau gradually decreased in GSD II mice during the postnatal stage, then stabilized at levels comparable to adult control, yet PCr in adult GSD II mice was lower than that in controls.

Conclusion

This study demonstrates that ST MRI of glycogen can provide in situ non‐invasive biomarkers for GSD II disease progression, with the potential to study the progression and treatment response of GSDs.
Design and operation of a whole‐body MRI scanner without RF shielding
Authors: Biber Stephan , Kannengiesser Stephan , Nistler Juergen , Braun Markus , Blaess Stefan , Gebhardt Matthias , Grodzki David , Ritter Dieter , Seegerer Georg , Vester Markus , Schneider Rainer
Published: November 2024

Purpose

To investigate how a clinical MRI system can be operated without an RF cabin. Receive interference cancellation via signal processing and active transmit emission suppression are evaluated for mitigating image artifacts and achieving electromagnetic compatibility.

Methods

A clinical whole‐body MR scanner with B0 = 0.55 T was placed in an environment without RF shielding. The signals of 16 additional auxiliary receive antenna elements outside the scanner bore were used to remove interference from the wanted MR signal via a dedicated sidelobe cancellation algorithm. In vivo measurements with different MR sequences were performed in the presence of ambient RF noise and additional artificial interferers, covering brain and abdominal applications. To investigate the transmit electromagnetic compatibility, simulations with different auxiliary transmit antenna arrangements and body coil loading conditions were performed, and their emission suppression performance in the far field was evaluated.

Results

The MR sidelobe cancellation algorithm successfully removed interference artifacts up to more than 3 times of the wanted MR image energy; difference images carried little to no visibly removed wanted signal. According to the simulations, electromagnetic compliance can be achieved with 32 or more auxiliary transmit antennas. The number and placement of sensor points are essential.

Conclusions

A whole‐body 0.55T MR scanner can be operated without RF shielding. Image artifacts from external interference can be removed, requiring only a modest number of auxiliary antennas. Electromagnetic compliance appears to be achievable using active transmit cancellation, but the required hardware efforts may not be practical.
Gibberellin action‐based strategies show promise in the control of Striga—A major threat to global agriculture
Authors: Chen Jiazheng , Takahashi Ikuo , Nakajima Masatoshi , Asami Tadao
Published: November 2024

Societal Impact Statement

The root‐parasitic plant Striga hermonthica can cause severe crop failure, leading to significant agricultural and economic losses in Africa. Despite the promising target offered by the Striga seed germination mechanism for developing control methods, effective control methods have yet to be established. For seed germination, Striga must undergo an incubation under warm and humid conditions, a process termed conditioning, which allows it to germinate. Here, we report that the plant hormone gibberellin stimulates the conditioning process in Striga seeds. Our findings suggest that the quantitative control of gibberellin in plants is a promising approach for controlling Striga infestations and may help alleviate substantial threats to food security.

The root‐parasitic plant S. hermonthica is a serious agricultural threat in Africa. Although a number of control methods have been employed to combat Striga, there is still a need to develop more effective control methods. Striga seeds germinate only in the presence of host plants, owing to the need for host‐released stimulants, primarily strigolactone. To detect signals from the host, Striga seeds must be exposed to a specific warm, dark, and moist environment, which is known as conditioning. Gibberellin directly promotes germination in many nonparasitic plants, but Striga seeds are insensitive to exogenous gibberellin. Consequently, the role of gibberellin in the germination of Striga seeds is unclear.

We demonstrated that the effect of the gibberellin biosynthesis inhibitor paclobutrazol was higher in seeds during the conditioning, compared with those already conditioned, suggesting that gibberellin primarily regulates conditioning rather than germination. The content of an active form gibberellin, gibberellin A4 (GA4) exhibited an increase throughout the conditioning period, and we quantified the elevated expression levels of some gibberellin biosynthesis genes. The GA4 treatment shortened the conditioning period required for strigolactone‐induced seed germination.

We also discovered that gibberellin upregulated ShACO1, the gene responsible for ethylene synthesis, during conditioning, and that the inhibition of GR24‐induced germination by the ethylene biosynthesis inhibitor α‐aminoisobutyric acid was gradually alleviated by GA4.

Our findings demonstrate that gibberellin is critical for conditioning and germination processes but acts as a minor stimulant in Striga seeds. This study demonstrates the potential of quantitative endogenous gibberellin control for Striga management, providing valuable insights for alleviating food security issues.
Local depletion of large molecule drugs due to target binding in tissue interstitial space
Authors: Zasedateleva Tatiana , Schaller Stephan , de Lange Elizabeth C. M. , de Witte Wilhelmus E. A.
Published: November 2024

Drug–target binding determines a drug's pharmacodynamics but can also have a profound impact on a drug's pharmacokinetics, known as target‐mediated drug disposition (TMDD). TMDD models describe the influence of drug–target binding and target turnover on unbound drug concentrations and are frequently used for biologics and drugs with nonlinear plasma pharmacokinetics. For drug targets expressed in tissues, the effect of TMDD may not be detected when analyzing plasma concentration curves, but it might still affect tissue concentrations and occupancy. This review aimed to investigate the likeliness of such a scenario by reviewing the literature for a typical range of TMDD parameter values and their impact on local drug concentrations and target occupancy in a whole‐body PBPK model with TMDD. Our analysis demonstrated that tissue drug concentrations are impacted and significantly depleted in many physiological scenarios. In contrast, the effect on plasma concentrations is much lower, specifically for smaller organs with lower perfusion. Moreover, in scenarios with fast internalization of the drug–target complex, the distribution of large molecules from plasma to tissue interstitial space emerges as a rate‐limiting step for the drug–target interaction. These factors may lead to overpredicting local drug concentrations when considering only plasma pharmacokinetics. A sensitivity analysis revealed the high and not always intuitive impact of drug‐specific parameters, including the drug molecule hydrodynamic radius, dissociation constant (Kd), drug–target complex internalization rate constant (kint), and target dissociation rate constant (koff), on the drug's pharmacokinetics. Our analysis demonstrated that tissue TMDD needs to be considered even if plasma pharmacokinetics are linear.
Promising 2D Carbon Allotropes with Intrinsic Bandgaps Based on Bilayer α‐Graphyne
Authors: Li Wentao
Published: November 2024

2D carbon allotropes with moderated electronic bandgaps are highly desirable for next‐generation carbon‐based nanoelectronics beyond graphene. Herein, the structural and electronic properties of bilayer α‐graphyne have been systematically investigated by using first‐principles calculations. Consequently, in addition to typical van der Waals (vdW) stacks of single‐layer α‐graphyne, new 2D carbon allotropes with purely sp2 or sp3 hybridizations can be achieved, arising from the absence of intralayer acetylene linkages during structural relaxation. Compared to the Dirac semimetallic behavior of monolayer α‐graphyne, the electronic structure of vdW bilayer α‐graphyne can be further modulated by stacking patterns, yet retains metallic characteristics. In contrast, intrinsic semiconducting characteristics can be observed in the proposed new 2D carbon allotropes with tunable bandgaps dependent on the in‐plane biaxial strain. Correspondingly, a pristine 2D carbon sheet with only sp2 hybridization exhibits a promising direct bandgap of 1.062 eV, while the sp3‐hybridized carbon network possesses an indirect bandgap of 1.708 eV, which can be further converted to the direct type under small compressive strains, implying great potential in future carbon‐based nanoelectronic applications beyond graphene. Also, this work provides a new approach for developing novel carbon allotropes via the vertical stacking of graphyne with acetylenic linkages.
Mushrooms and Colorectal Cancer: Unveiling Mechanistic Insights and Therapeutic Innovations
Authors: Kurl Samridhi , Kaur Snimmer , Mittal Neeraj , Kaur Gurpreet
Published: November 2024

Nature has bestowed us with an abundant reservoir of resources that besides having nutritional value, are prolific mines of bioactive constituents with a plethora of medicinal activities. Mushrooms have been used since centuries in traditional system of medicine for their purported health benefits including anticancer activities. Thorough research, spanning over centuries in Japan, China, Korea, and the USA, has established the unique properties of mushrooms and their extractives in the prevention and treatment of various types cancer. The aim of the review article is to provide a comprehensive overview of the existing literature highlighting the potential relationship between mushrooms and colorectal cancer. Different databases such as PubMed, Web of Science, Google Scholar, and ScienceDirect were searched and a total of 62 articles and two book chapters were reviewed, and data were extracted. Multiple studies have demonstrated that mushrooms exhibit anticancer activities, effectively reducing adverse side effects such as nausea, myelosuppression, anemia, and sleeplessness. Furthermore, they have been shown to mitigate drug resistance following chemotherapy and radiation therapy. Certain species such as Antrodia, Pleurotus, Ganoderma, Lentinula, Hericium, Cantharellus, Clitocybe, Coprinopsis, Trametes, Sparassis, Lactarius, and so on manifest anticancer activity in colon. The article can help improve the scientific understanding of the co‐relationship between mushrooms and colorectal cancer. This may help in advancing the research directions and integrating the mushroom‐based strategies into current treatment protocols of colorectal cancer.
Constrained Control of Autonomous Underwater Gliders Based on Disturbance Estimation and Tracking Back Calculation
Authors: Lei Ming , Jia Fuxin , Chai Haoruo , Ding Shuoshuo , Zhang Tiedong
Published: November 2024

This article presents an anti‐disturbance constrained control scheme for the pitch channel of autonomous underwater gliders subject to internal and external disturbances, as well as actuator saturation. First, the integral control technique is employed to develop a disturbance observer to estimate the overall effect of possible uncertainties and disturbances on the nominal vehicle model, which is referred to as the mismatched lumped disturbance. Then, a disturbance rejection control law is constructed based on the disturbance observer. Following that, a straightforward anti‐windup modification is proposed to handle potential input constraints by using the tracking back calculation technique. Specifically, the difference between saturated and unsaturated control input signals is utilized to create a feedback signal that addresses the disturbance observer input, thereby alleviating system windup during actuator saturation events. Furthermore, the stability of the overall closed‐loop system is established in term of the Lyapunov stability theorem, demonstrating that the tracking error is ultimately bounded. Compared with some existing anti‐windup control schemes, the suggested approach offers intuitive design guidelines, resulting in a simple controller that can be easily implemented. Finally, the effectiveness and robustness of the proposed control scheme are verified through simulation results.
Dispersion on the Complete Graph
Authors: De Ambroggio Umberto , Makai Tamás , Panagiotou Konstantinos
Published: November 2024

We consider a synchronous process of particles moving on the vertices of a graph , introduced by Cooper et al. Initially,  particles are placed on a vertex of . At the beginning of each time step, for every vertex inhabited by at least two particles, each of these particles moves independently to a neighbor chosen uniformly at random. The process ends at the first step when no vertex is inhabited by more than one particle. Cooper et al. showed that when the underlying graph is the complete graph on  vertices, then there is a phase transition when the number of particles . They showed that if for some fixed , then the process finishes in a logarithmic number of steps, while if , an exponential number of steps are required with high probability. Here we provide a thorough asymptotic analysis of the dispersion time around criticality, where , and describe the transition from logarithmic to exponential time. As a consequence of our results we establish, for example, that the dispersion time is in probability and in expectation in when , and provide qualitative bounds for its tail behavior.
Effects of entrepreneurship and governance quality on global and regional economic performance: A pathway to sustainable development
Authors: Ogbuabor Jonathan E. , Emeka Ekene ThankGod , Ogbuabor Chukwunweike A.
Published: November 2024

This study investigated the effects of entrepreneurship and governance quality on global and regional economic performance, and the moderating influence of governance quality on the entrepreneurship‐economic performance nexus. The study used a panel of 109 countries from 2010 to 2022. Prais‐Winsten regression, standard Fixed Effects regression with robust standard errors, Fixed Effects regression with Driscoll and Kraay standard errors, and the dynamic system GMM regression were used. We find that the unconditional effect of entrepreneurship on global economic performance is mainly negative, while governance quality predominantly exerts positive effect on global economic performance, but generally failed to moderate the adverse effect of entrepreneurship. Interestingly, we find regional disparities indicating that the patterns in Europe and Asia align with the global results, while the dynamics in the Americas show that the unconditional effect of entrepreneurship on economic performance is mainly positive and significant, with governance quality also exerting significant positive influence and reinforcing the positive effect of entrepreneurship. For Africa, we find that entrepreneurship is a potent driver of economic performance when it is measured using Total Early‐stage Entrepreneurial Activity and Entrepreneurial Employee Activity. We discussed the policy implications of these findings in relation to the sustainable development goals.
Synergistic Electronic Interaction in PdCu Alloy/TiO2‐NSs for Ambient Efficient Dehydrogenation of Formic Acid
Authors: Ashraf Saima , Liu Yanyan , Liu Shuling , Mehdi Sehrish , Zhang Huanhuan , Shen Ruofan , Guo Xianji , Wu Xianli , Jiang Jianchun , Wang Yongfeng , Li Baojun
Published: November 2024

Palladium‐based catalysts are remarkable in endorsing hydrogen (H2) generation through formic acid (HCOOH, FA) dehydrogenation under near‐ambient conditions. Hydrogen energy efficiency depends on high‐performance catalyst design. In this study, Pd‐Cu nanoalloy catalysts with mutable atomic ratios are successfully fabricated on TiO2 nanosheets (TiO2‐NSs).The synergistic electronic interactions between Palladium (Pd) and copper (Cu) are revealed through a density of states (DOS) analysis of alloy supported over a mixed valence state of Ti linked to oxygen vacancies (Vo) in TiO2‐NSs, Enhanced adsorption of target molecules reveals novel active sites for Formic acid dehydrogenation (FAD), with O─H bond cleavage via HCOO formate intermediate preceding C─H and C─O bond cleavage. Experimental and theoretical research demonstrates that the Pd‐Cu/TiO2‐NSs (3:7) catalyst d electron redistribution and d‐band center shift lower the activation energy for O─H bond cleavage, exhibit superior H2 production than pure Pd and Cu, increasing Pd electron density due to synergistic effects from reactive crystal facets, defects, and strong metal support interactions (SMSI), lowering the activation energy for HCOOH dissociation step, generating carbon dioxide (CO2) and H2 with a unprecedented high turnover frequency (TOF) of 6268 molH2.h−1.molPd−1 at 303K with activation energy (Ea) of 15 KJ mol−1. This attempt models an efficient HCOOH‐to‐hydrogen catalyst.