bluuebunny/crossref_metadata_2025 huggingface dataset:
Decentralized clinical trials for medications to reduce the risk of dementia: Consensus report and guidance
Authors: Howard Leanne , Abdelnour Carla , Abner Erin L. , Allegri Ricardo F. , Dodge Hiroko H. , Gauthier Serge , Hoyos Camilla M. , Jicha Gregory A. , Kehoe Patrick G. , Mummery Catherine J. , Ogunniyi Adesola , Scarmeas Nikolaos , Chen Xiaoying , Titiner Jodie R. , Weber Christopher R. ,   Clinical Trial Methodology Working review group members, Peters Ruth
Published: June 2024

INTRODUCTION

Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field.

METHODS

A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations.

RESULTS

Overall, the recommendations support the delivery of decentralized trials in dementia prevention provided adequate safety checks and balances are included. A total of 40 recommendations are presented, spanning aspects of decentralized clinical trials, including safety, dispensing, outcome assessment, and data collection.

DISCUSSION

These recommendations provide an accessible, pragmatic guide for the design and conduct of remote medication trials for dementia prevention.

Highlights

Clinical trials of medication have begun adopting decentralized approaches.

Researchers in the field lack guidance on what would be appropriate circumstances and frameworks for what would be appropriate circumstances and frameworks for the use of decentralized trial methods in dementia prevention.

The present report provides consensus‐based expert recommendations for decentralized clinical trials for dementia prevention.
The presenilin 1 mutation P436S causes familial Alzheimer's disease with elevated Aβ43 and atypical clinical manifestations
Authors: Arber Charles , Belder Christopher R. S. , Tomczuk Filip , Gabriele Rebecca , Buhidma Yazead , Farrell Clíona , O'Connor Antoinette , Rice Helen , Lashley Tammaryn , Fox Nick C. , Ryan Natalie S. , Wray Selina
Published: June 2024

INTRODUCTION

Familial Alzheimer's disease (fAD) is heterogeneous in terms of age at onset and clinical presentation. A greater understanding of the pathogenicity of fAD variants and how these contribute to heterogeneity will enhance our understanding of the mechanisms of AD more widely.

METHODS

To determine the pathogenicity of the unclassified PSEN1 P436S mutation, we studied an expanded kindred of eight affected individuals, with magnetic resonance imaging (MRI) (two individuals), patient‐derived induced pluripotent stem cell (iPSC) models (two donors), and post‐mortem histology (one donor).

RESULTS

An autosomal dominant pattern of inheritance of fAD was seen, with an average age at symptom onset of 46 years and atypical features. iPSC models and post‐mortem tissue supported high production of amyloid beta 43 (Aβ43). PSEN1 peptide maturation was unimpaired.

DISCUSSION

We confirm that the P436S mutation in PSEN1 causes atypical fAD. The location of the mutation in the critical PSEN1 proline‐alanine‐leucine‐proline (PALP) motif may explain the early age at onset despite appropriate protein maturation.

Highlights

PSEN1 P436S mutations cause familial Alzheimer's disease.

This mutation is associated with atypical clinical presentation.

Induced pluripotent stem cells (iPSCs) and post‐mortem studies support increased amyloid beta (Aβ43) production.

Early age at onset highlights the importance of the PALP motif in PSEN1 function.
Antiferromagnetic Interactions through the Thirteen Å Metal–Metal Distances in Heterometallic One‐Dimensional Chains
Authors: Uemura Kazuhiro , Adachi Tomonori , Takamori Atsushi , Yoshida Michiyuki
Published: June 2024

A heterometallic and paramagnetic one‐dimensional aligned chain in −Rh(+2)−Rh(+2)− Pt(+2)−Ni(+2)−Pt(+2)− with direct metal−metal bonds was obtained via HOMO–LUMO interactions at the σ* (dz2) orbital between [Rh2(O2CCH3)4] and [Pt2Ni(piam)4(NH3)4] (piam=pivalamidate). The one‐dimensional chains had straight backbones attributed to face‐to‐face stacking of each complex, and the Ni atoms were separated by approximately 13 Å from four different metals. Each Ni atom had two unpaired electrons in the d‐orbitals, which strongly exchanged with J=−37.9 cm−1 through the diamagnetic −Pt−Rh−Rh−Pt− bonds.
A smart L‐alanine modified Cd‐NDI metal‐organic framework crystalline material: Photochromic properties and photocatalytic degradation dye applications
Authors: Gai Shi Ping , Zhang Ting , Sun Ming Yang , Wang Chen , Chi Yu Xian , Xing Yong Heng , Bai Feng Ying
Published: June 2024

1, 4, 5, 8‐naphthalene diimide (NDI)‐based MOFs, due to their tunable structures and properties, have shown promising applications in photochromism, photocatalysis, electrocatalysis, photothermal therapy, etc. Herein, using an L‐alanine modified NDI ligand, i.e. N, N′‐bis(L‐alanine)naphthalenediimide (AlaNDI), a novel Cd‐NDI Cd (AlaNDI)(H2O)]·DMF·H2O (complex 1) was constructed under solvothermal conditions, which has an obvious different structure with the previously reported ones. Structural analysis shows that the packing structure of complex 1 consists of two adjacent Cd atoms sharing two AlaNDI ligands, forming a dimetallic building block [Cd2O8]. Each building block connects a total of four AlaNDI ligands, where two Cd atoms are bridged by two ligands. The building blocks are interconnected by ligands to form a two‐dimensional layered structure. Based on the features of the NDI skeleton, it was found that complex 1 possesses multiple stimulus responses involving sensitivity to light: a reversible photochromism property and good photocatalytic degradation activity against various dyes, especially against cationic dyes crystal violet (CV), methyl violet (MV), and Janus green B (JGB). In addition, the stimulus‐response mechanism was investigated by control experiments. It is revealed that the photocatalytic active species may be related to h+ and •OH.
Adaptive memory event‐triggered fault‐tolerant dissipative control for networked T‐S fuzzy switched systems under denial‐of‐service attacks
Authors: Gao Hui , Ou Yongsheng , Wang Binrui , Shi Kaibo
Published: June 2024

This paper studied the problem of dissipative control for networked T‐S fuzzy switched systems under denial of service (DoS) attacks via a memory‐based adaptive event‐triggered mechanism. Since the system mode and controller mode do not match exactly, the asynchronous control is designed. The memory‐based adaptive event‐triggered mechanism can achieve better performance by using the historical data released. Though constructing a controller mode dependent Lyapunov functional, the dissipative performance of the closed‐loop system can be guaranteed. Finally, a numerical example is proposed to illustrate the superiority of the approach.
A systematic review of barriers to accessing cleft care worldwide
Authors: Cerón‐Zapata Ana María , Manrique‐Hernández Ruben Darío , Mejía‐Ortega Luz Mery
Published: June 2024

Purpose

Patients with cleft lip/palate need an interdisciplinary approach. Delays in the care of these patients and difficulties in accessing health services have been reported in different low‐, middle‐, and high‐income countries. This study aimed to characterize worldwide publications on access to cleft lip and palate health treatment.

Methods

Databases were selected systematically and searched until July 2021. The review process followed standard methods for systematic reviews. The study quality was evaluated using the Strengthening the Reporting of Observational studies in Epidemiology guidelines for observational studies.

Results

A total of 289 publications were identified using our search strategy. After reviewing the titles and reading the abstracts and full text, 16 studies met the inclusion criteria in the review. In one study, financial difficulties obtained the attention of the professionals who attended to cleft lip/palate patients. Ethnic disparities, problems in transportation, and long distances between users and health centers were found. Additionally, there was misinformation about treatment and follow‐up among the caregivers of patients with cleft lip/palate.

Conclusion

When reviewing the literature on access to health services for patients with cleft lip/palate, barriers were reported in access to information, physical access to care centers, financial resources to cover expenses for treatment, and opportunities in care.
Cultural distance and bilateral trade: A transitional economy perspective
Authors: Mostafiz Fahmida , Akter Mansura , Rahman Mahfuzur
Published: June 2024

Cultural differences represent significant trade barriers between transitional economies and their trading partners, which has been overlooked in recent studies. This paper investigates the effect of cultural distance (CD) on bilateral trade from Bangladesh. We conceptualize a research model by employing the extended gravity model as a theoretical base, where we amplify the theory by proposing that linguistic distance (LD) as a part of cultural distance has a profound effect on bilateral trade based on bilateral trade data from 1995 to 2019 and Hofstede's culture indices between Bangladesh and 157 trading partner countries. Using a pseudo‐poisson maximum likelihood model, we find that cultural distance has a significant and negative impact on Bangladesh's trade, with a significance level of 1%. Our empirical results indicate that one unit increase in cultural distance decreases trade by 40.84% and cultural distance has a greater impact on Bangladesh's exports than on its imports. Findings also reveal that the effect is substantial with high‐income nations than with low‐income nations, and for manufacturing products than primary products trade. Further, this study suggests that in addition to cultural distance (CD), linguistic distance (LD) from trading partners has a tantamount effect on bilateral trade, which is significant at 1%. Theoretically, this study suggests that linguistic distance (LD) should be added on gravity model for analyzing effects of cultural distance on bilateral and multilateral trade. Practically, this study contributes by providing valuable insights to policymakers to pay attention to cultural differences, especially during these economic transition periods to increase bilateral trade.
The ISO 14001 standard's effect on agrifood small‐ and medium‐sized enterprises' performance: Literature review and empirical evidence
Authors: Labella Rocio Carrillo , Fort Fatiha , Parras Rosa Manuel
Published: June 2024

A significant part of the literature postulates the importance of economic factors and, in particular, market pressure as the main motivation for the adoption of environmental management systems, such as ISO 14001 (International Organization for Standardization). Most of these studies are based on questionnaire surveys assessing the perceptions or opinions of company managers. Few studies have investigated the relationship between the adoption of the standard and economic and financial performance using objective accounting data. This study aimed to test the link between ISO 14001 adoption and economic and financial performance using accounting data from 374 agrifood small‐ and medium‐sized enterprises (SMEs) in Spain during the period 2013 to 2015. The results showed that ISO 14001 contributes to improved commercial and marketing performance through a positive effect on turnover in domestic markets and especially in export markets. However, no positive relationship could be found between ISO14001 and company results or profits. Therefore, ISO 14001 can be considered more as a means of entering and developing sales, particularly in export markets, than a tool to enhance financial profits.
Environmental innovation and takeover performance
Authors: Hussain Tanveer , Tunyi Abongeh A. , Areneke Geofry
Published: June 2024

Drawing from the resource‐based view (RBV), we examine the effect of environmental innovation on mergers and acquisitions (M&As) announcement returns. Using an international sample of M&As for the period of 2003–2021 and an event study methodology, we document that acquirers with higher environmental innovation—innovative acquirers—earn average deal announcement abnormal returns that are 0.10–0.50 percentage points higher than those earned by their non‐innovative counterparts. These results are consistent across three important forms of environmental innovation (i.e., product, process, and organizational innovation) and are partly explained by the transfer of environmental innovation from the acquirer to the target. We further find that environmentally innovative acquirers are more likely to engage in majority control and cross‐border acquisitions, thus emphasizing the transfer effect. Overall, we contribute to RBV by providing evidence that environmental innovation is a distinctive resource or dynamic capability that is transferable from bidders to targets in the takeover market.
Peripheral blood mononuclear cells show markers of mitochondrial dysfunction in rheumatoid arthritis
Authors: Abbasifard Anahita , Solgi Ghasem , Khodadadi Iraj , Doosti‐Irani Amin , Tayebinia Heidar , Fazaeli Alireza
Published: June 2024

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Metabolic and mitochondrial dysregulation are critical causal factors in the pathogenesis and progression of RA. Mitochondrial dysfunction include abnormal energy metabolism, and excessive production of reactive oxygen species (ROS). This study aimed to investigate the adenosine triphosphate (ATP), mitochondrial membrane potential (ΔΨm), ROS, and mRNA expression level of ROMO1 (as ROS modulator) and OMA1 (as regulator mitochondrial dynamics) of peripheral blood mononuclear cells (PBMC) in RA patients. The study participants were 50 patients with RA and 50 sex‐ and age‐matched healthy volunteers. PBMC of all participant were isolated by Ficoll‐Paque. Alteration in ΔΨm and cellular ROS were measured using flow cytometry, ATP level was also assessed via luminometry, and ROMO1 and OMA1 mRNA expression via qRT‐PCR assay. A significant decrease in ATP (p = .005) and ΔΨm (p < .001) was observed in the PBMC of RA compared to control. The ROS levels were significantly higher in the PBMC of RA compared to the control (p < .001). ROMO1 and OMA1 mRNA expression was also significantly increased in RA patients compared to control (p < .001). The decrease in ATP is strongly associated with ROS increasing in PBMC of RA patients, denoting an inverse and negative relationship between ATP and ROS production. Also, a decrease in ΔΨm was observed. It seems that in line with mitochondrial dysfunction in PBMC, increased expression of ROMO1 and OMA1 genes could also be involved in the development of RA.
Hemicyanine‐Based Highly Water‐Soluble Probe for Extracellular Nitroreductase
Authors: Jiang Shaoli , Xu Le , Zhong Yihong , Zhang Chuangchuang , Yu Xiaoyu , Li Ke , Ding Lin , Wang Xiaojian
Published: June 2024

Nitroreductase (NTR) has long been a target of interest for its important role involved in the nitro compounds metabolism. Various probes have been reported for NTR analysis, but rarely able to distinguish the extracellular NTR from intracellular ones. Herein we reported a new NTR sensor, HCyS‐NO2, which was a hemicyanine molecule with one nitro and two sulfo groups attached. The nitro group acted as the reporting group to respond NTR reduction. Direct linkage of nitro group into the hemicyanine π conjugate system facilitated the intramolecular electron transfer (IET) process and thus quenched the fluorescence of hemicyanine core. Upon reduction with NTR, the nitro group was rapidly converted into the hydroxylamino and then the amino group, eliminating IET process and thus restoring the fluorescence. The sulfo groups installed significantly increased the hydrophilicity of the molecule, and introduced negative charges at physiological pH, preventing the diffusion into bacteria. Both gram‐negative and gram‐positive bacteria were able to turn on the fluorescence of HCyS‐NO2, without detectable diffusion into cells, providing a useful tool to probe the extracellular reduction process.
Experimental and Computational Fluid Dynamics Analysis of Industrial Water Desalination with High Salinity by Adsorption Chlorine on Resin in a Packed Column
Authors: Mahmoodabadi Hamideh , Soltani Goharrizi Ataallah
Published: June 2024

To investigate chlorine adsorption from water onto resins, some batch adsorption tests were considered. The mechanisms and characteristic parameters of the adsorption process were analyzed using isotherm models which revealed the following order (based on the coefficient of determination): Flory–Huggins (0.99) > Fowler‐Guggenheim (0.98) >, and Langmuir (0.38).The experimental data were examined using two kinetic models, including first‐ and second‐order ones with R2 value of 0.88, 0.1 respectively. According to the adsorption isotherm study, the Flory–Huggins isotherm model better fit adsorption on the surface of resin, as compared to other models. Assessing the thermodynamic parameters found out that the adsorption of Cl onto resins became an exothermic and spontaneous process. The results were then obtained. Similarly, the results of the experiment were provided via the computational fluid dynamics evaluation. Moreover, the results obtained by computational fluid dynamics were compared with the experimental data, and their accuracy was proved. Subsequently, the effects of changing the design and operating parameters, including flow rate (3, 6, 10 L min−1) and bed height (10, 20, 40 cm) on the performance of this tower were studied. The results showed that by reducing the adsorbent, the adsorbed Cl increased and a longer bed was required for adsorption, which was not cost‐effective. The amount of adsorption decreased as the flow rate increased, indicating that there was little contact between the Cl and the adsorbent.
Examining Invasion‐Percolation Across the Cathode Layered Assembly in Polymer Electrolyte Membrane Fuel Cells: Oxygen Resistance, Wettability and Cracks
Authors: García‐Salaberri Pablo A.
Published: June 2024

Efficient evacuation of water generated by oxygen reduction reaction is necessary to increase catalyst utilization in polymer electrolyte membrane Fuel Cells. However, analysis of two‐phase transport is challenged by the wide range of pore sizes present in the membrane electrode assembly (MEA), varying from 10–100 nm in the catalyst layer (CL), 10–1000 nm in the microporous layer (MPL) and 10 μm in the gas diffusion layer (GDL). In this work, a novel multiscale invasion‐percolation model accounting for the cathode CL, MPL and GDL is presented. Saturation in the macroporous GDL is modeled through an all‐or‐nothing invasion law (empty/filled), while a macroscopic description in terms of the capillary pressure curve is adopted for the MPL and the CL. The oxygen transport resistance across the cathode MEA is quantified using the computed saturation distributions. Among other conclusions, the results show that MPL addition is crucial to avoid local flooding at the CL/GDL interface, providing localized access points to the GDL rather than massively invading interfacial macropores. However, excessive MPL hydrophobicity can cause CL flooding. Water removal from the CL can be enhanced by using a more hydrophilic MPL, a hydrophobic CL or the addition of a moderate volume fraction of cracks. Oxygen transport can be further improved by modulating the arrangement of water in the GDL with patterned wettability, provided that the number of MPL cracks is low.
Thermally Stable P‐Chiral Supramolecular Phosphines, their Self‐Assembly and Implication in Rh‐Catalyzed Asymmetric Hydrogenation
Authors: Chandanshive Amol C. , Gonnade Rajesh G. , Chikkali Samir H.
Published: June 2024

P‐chiral supramolecular phosphine ligands are crucial for asymmetric transformations, but their synthesis is tedious. We report a one‐step synthesis of thermally stable P‐chiral supramolecular phosphines and their performance in the asymmetric hydrogenation of functionalized alkenes. A rational designing and synthesis of (R, R)‐QuinoxP* ligated palladium complex (Pd‐2) in excellent yield is reported. This Pd‐2 catalyzed a direct P−C coupling of 2,3‐dihydro‐1‐H‐phosphindole (A1)/1,2,3,4‐tetrahydrophosphindoline (A2) with 1‐(3‐iodophenyl)urea (B1)/2‐iodo /6‐hydroxy pyridine (B2) and,produced corresponding ligands L1–L3. The P−C coupling between A1 and B2 produced 6‐(2,3‐dihydro‐1H‐phosphindol‐1‐yl)pyridine‐2(1H)‐one (L2) with an excellent enantiomeric excess of up to 99 %. L2 was found to be remarkably stable even at 150 °C and did not oxidize/hydrolyze for at least 24 hours in open air. Such thermal stability and an impediment to oxidation are unprecedented. L2 self‐assembled and produced L2−C1 (Pt), L2−C2(Pd), and L2−C3(Rh) assemblies. The utility of the self‐assembled P‐chiral ligand was demonstrated in the Rh‐catalyzed asymmetric hydrogenation (AH) of functionalized olefins. The L2−C3 catalyzed AH of functionalized alkenes and delivered chiral products with excellent enantioselectivity of >99 %. A small library of 16 substrates was subjected to AH using L2−C3 to produce chiral compounds with excellent conversion and ee.
Rational Design of Highly Selective Sialyllactose‐Imprinted Nanogels
Authors: Contardi Cecilia , Mavliutova Liliia , Serra Massimo , Rubes Davide , Dorati Rossella , Vistoli Giulio , Macorano Alessio , Sellergren Börje , De Lorenzi Ersilia
Published: June 2024

We describe a facile method to prepare water‐compatible molecularly imprinted polymer nanogels (MIP NGs) as synthetic antibodies against target glycans. Three different phenylboronic acid (PBA) derivatives were explored as monomers for the synthesis of MIP NGs targeting either α2,6‐ or α2,3‐sialyllactose, taken as oversimplified models of cancer‐related sT and sTn antigens. Starting from commercially available 3‐acrylamidophenylboronic acid, also its 2‐substituted isomer and the 5‐acrylamido‐2‐hydroxymethyl cyclic PBA monoester derivative were initially evaluated by NMR studies. Then, a small library of MIP NGs imprinted with the α2,6‐linked template was synthesized and tested by mobility shift Affinity Capillary Electrophoresis (msACE), to rapidly assess an affinity ranking. Finally, the best monomer 2‐acrylamido PBA was selected for the synthesis of polymers targeting both sialyllactoses. The resulting MIP NGs display an affinity constant≈106 M−1 and selectivity towards imprinted glycans. This general procedure could be applied to any non‐modified carbohydrate template possessing a reducing end.
Targeted Endoperoxides Delivering Singlet Oxygen to Cancer Cell Mitochondria: Exploration of the Therapeutic Potential
Authors: Liu Ziang , Wang Lei , Sun Rensong , Wu Hao , Wang Yang , Zhang Shengli , Li Guangzhe , Shao Kun , Akkaya Engin U.
Published: June 2024

The clinical practice of photodynamic therapy of cancer (PDT) is mostly limited to superficial types of cancer. The major reason behind this limited applicability is the need for light in the photogeneration of ROS, and in particular singlet oxygen. In order to circumvent this major roadblock, we designed and synthesized naphthalene‐derived endoperoxides with mitochondria targeting triphenylphosphonium moieties. Here, we show that these compounds release singlet oxygen by thermal cycloreversion, and initiate cell death with IC50<10 μM in cancer cell cultures. The mouse 4T1 breast tumor model study, where the endoperoxide compound was introduced intraperitoneally, also showed highly promising results, with negligible systemic toxicity. Targeted delivery of singlet oxygen to cancer cell mitochondria could be the breakthrough needed to transform Photodynamic Therapy into a broadly applicable methodology for cancer treatment by keeping the central tenet and discarding problematic dependencies on oxygen or external light.
Electronic and Molecular Structures of a Series of Nickel Bis‐1,1‐Dithiolates
Authors: Macleod Cailean I. , Keramidas Odysseas D. , Miras Haralampos N. , Sproules Stephen
Published: June 2024

A series of homoleptic Ni bis‐1,1‐dithiolates, [Ni(S2C2RR′)2]2− (R=CN, R′=CN, CO2Et, CONH2, Ph, Ph‐4‐Cl, Ph‐4‐OMe, Ph‐4‐NO2, Ph‐3‐CF3, Ph‐4‐CF3, Ph‐4‐CN; R=NO2, R′=H; R=R′=CO2Et) have been synthesized from the reaction of the alkali metal salt of the ligand and nickel chloride, and isolated as tetraphenylphosphonium or tetrabutylammonium salts. The complexes were characterized by X‐ray crystallography, high‐resolution mass spectrometry, and infrared (IR), nuclear magnetic resonance (NMR) and electronic absorption spectroscopies. The molecular structures show a rigidly square planar Ni(II) center linking two four‐membered chelate rings whose dimensions are constant across the series. The electronic effect of the ligand substituent is revealed in the 13C NMR and electronic spectra, and corroborated by density functional calculations. Electron withdrawing groups deshield the low‐field CS2 resonance, and the signature charge transfer band in the visible region is red‐shifted. These observables have been accurately reproduced computationally, and revealed the Ni contribution to the ground state diminishes with decreasing electron withdrawing capacity of the ligand substituent. In contrast to 1,2‐dithiolates, the redox inactivity afforded by 1,1‐dithiolates stems from the smaller chelate ring and substantially reduced sulfur content that is key to stabilizing the radical form.
Carborane Conjugates with Ibuprofen, Fenoprofen and Flurbiprofen: Synthesis, Characterization, COX Inhibition Potential and In Vitro Activity
Authors: Sonam Sonam , Jelača Sanja , Laube Markus , Schädlich Jonas , Pietzsch Jens , Maksimović‐Ivanić Danijela , Mijatović Sanja , Kaluđerović Goran N. , Hey‐Hawkins Evamarie
Published: June 2024

The most effective anticancer drugs currently entail substantial and formidable side effects, and resistance of tumors to chemotherapeutic agents is a further challenge. Thus, the search for new anticancer drugs as well as novel therapeutic methods is still extremely important. Non‐steroidal anti‐inflammatory drugs (NSAIDs) can inhibit COX (cyclooxygenase), overexpressed in some tumors. Carboranes are emerging as promising pharmacophores. We have therefore combined both moieties in a single molecule to design drugs with a dual mode of action and enhanced effectiveness. The NSAIDs ibuprofen, flurbiprofen, and fenoprofen were connected with 1,2‐dicarba‐closo‐dodecaborane(12) via methylene, ethylene or propylene spacers. Three sets of carborane‐NSAID conjugates were synthesized and analyzed through multinuclear (1H, 11B, and 13C) NMR spectroscopy. Conjugates with methylene spacers exhibited the most potent COX inhibition potential, particularly conjugates with flurbiprofen and fenoprofen, displaying higher selectivity towards COX‐1. Furthermore, conjugates with methylene and ethylene spacers were more efficient in suppressing the growth of human cancer cell lines than their propylene counterparts. The carborane‐flurbiprofen conjugate with an ethylene spacer was the most efficient and selective toward the COX‐2‐negative cell line HCT116. Its mode of action was basically cytostatic with minor contribution of apoptotic cell death and dominance of cells trapped in the division process.
A variational construction of Hamiltonian stationary surfaces with isolated Schoen–Wolfson conical singularities
Authors: Gaia Filippo , Orriols Gerard , Rivière Tristan
Published: June 2024

We construct using variational methods Hamiltonian stationary surfaces with isolated Schoen–Wolfson conical singularities. We obtain these surfaces through a convergence process reminiscent to the Ginzburg–Landau asymptotic analysis in the strongly repulsive regime introduced by Bethuel, Brezis and Hélein. We describe in particular how the prescription of Schoen–Wolfson conical singularities is related to optimal Wente constants.
FLOLSTM: Fuzzy logic‐driven optimized LSTM for improved malicious traffic detection in hypervisor environments
Authors: Kumar Anumukonda Naga Seshu , Yadav Rajesh Kumar , Raghava Nallanthighal Srinivasa
Published: June 2024

In the ever‐evolving realm of cloud computing, the challenge of intrusion detection has grown increasingly intricate and vital. With the proliferation of cyber‐attacks and the widespread use of virtualized environments, there is a pressing need for network security solutions that are not only innovative and robust but also easily comprehensible. These solutions must possess the ability to effectively detect malicious activities, provide visibility into network operations, adapt to changing requirements, and promptly alert stakeholders to any suspicious behavior. In this study, we introduce a groundbreaking approach known as fuzzy logic‐driven optimized long short‐term memory (LSTM)—FLOLSTM, specifically designed for hypervisor‐based environments. By integrating fuzzy logic with an optimized LSTM neural network, FLOLSTM aims to significantly enhance the detection of attack traffic within hypervisor networks by combining the interpretability and uncertainty management capabilities of fuzzy logic with the temporal pattern recognition prowess of LSTM. The research methodology involves meticulous data collection from hypervisor monitors, followed by rigorous cleaning and preprocessing to enhance data reliability. Subsequently, the preprocessed data is input into the FLOLSTM classifier to identify malicious activities. Furthermore, the performance of the LSTM is fine‐tuned using the waterwheel plant optimization (WPO) algorithm. Experimental evaluations compare the efficiency of the proposed FLOLSTM with existing techniques across various metrics including accuracy, recall, precision, F‐measure, specificity, false‐positive rate (FPR), and false‐negative rate (FNR). Overall, the FLOLSTM model represents a significant advancement in intrusion detection for cloud environments, offering a potent blend of interpretability, accuracy, and efficiency. Its superior performance underscores its capacity to enhance network security and effectively mitigate cyber threats in dynamic and virtualized settings, thereby making a substantial impact on the field of cyber security.
Tailoring Light‐Harvesting in Zn‐Porphyrin and Carbon Fullerene based Donor‐Acceptor Complex through Ethynyl‐Extended Donor π‐Conjugation
Authors: Ahmed Raka , Manna Arun K.
Published: June 2024

Organic photovoltaic efficiency though currently limited for practical applications, can be improved by means of various molecular‐level modifications. Herein the role of extended donor
‐conjugation through ethynyl‐bridged meso‐phenyl/pyridyl on the photoinduced charge‐transfer kinetics is studied in noncovalently bound Zn‐Porphyrin and carbon‐fullerene based donor‐acceptor complex using time‐dependent optimally tuned range‐separated hybrid combined with the kinetic rate theory in polar solvent. Noncovalent dispersive interaction is identified to primarily govern the complex stability. Ethynyl‐extended
‐conjugation results in red‐shifted donor‐localized Q‐band with substantially increased dipole oscillator strength and smaller exciton binding energy, suggesting greater light‐harvesting efficiency. However, the low‐lying charge‐transfer state below to the Q‐band is relatively less affected by the ethynyl‐extended
‐conjugation, yielding reduced driving forces for the charge‐transfer. Detailed kinetics analysis reveals similar order of charge‐transfer rate constants (~1012 s−1) for all donor‐acceptor composites studied. Importantly, enhanced light‐absorption, smaller exciton binding energy and similar charge‐transfer rates together with reduced charge‐recombination make these complexes suitable for efficient photoinduced charge‐separation. These findings will be helpful to molecularly design the advanced organic donor‐acceptor blends for energy efficient photovoltaic applications.
Beyond MABEL: An Integrative Approach to First in Human Dose Selection of Immunomodulators by the Health and Environmental Sciences Institute (HESI) Immuno‐Safety Technical Committee (ITC)
Authors: Matsumoto Mineo , Polli Joseph Ryan , Swaminathan Suresh K. , Datta Kaushik , Kampershroer Cris , Fortin Marie C. , Salian‐Mehta Smita , Dave Rutwij , Yang Zheng , Arora Payal , Hiura Masanori , Suzuki Mizuho , Brennan Frank R. , Sathish Jean
Published: June 2024

Administration of a new drug candidate in a first‐in‐human (FIH) clinical trial is a particularly challenging phase in drug development and is especially true for immunomodulators, which are a diverse and complex class of drugs with a broad range of mechanisms of action and associated safety risks. Risk is generally greater for immunostimulators, in which safety concerns are associated with acute toxicity, compared to immunosuppressors, where the risks are related to chronic effects. Current methodologies for FIH dose selection for immunostimulators are focused primarily on identifying the minimum anticipated biological effect level (MABEL), which has often resulted in sub‐therapeutic doses, leading to long and costly escalation phases. The Health and Environmental Sciences Institute (HESI) – Immuno‐Safety Technical Committee (ITC) organized a project to address this issue through two complementary approaches: (i) an industry survey on FIH dose selection strategies and (ii) detailed case studies for immunomodulators in oncology and non‐oncology indications. Key messages from the industry survey responses highlighted a preference toward more dynamic PK/PD approaches as in vitro assays are seemingly not representative of true physiological conditions for immunomodulators. These principles are highlighted in case studies. To address the above themes, we have proposed a revised decision tree, which expands on the guidance by the IQ MABEL Working Group (Leach et al. 2021). This approach facilitates a more refined recommendation of FIH dose selection for immunomodulators, allowing for a nuanced consideration of their mechanisms of action (MOAs) and the associated risk‐to‐benefit ratio, among other factors.
Clinical Pharmacology of Glucagon
Authors: Kronfol Mohamad M. , Chow Edwin C. , Lau S. W. Johnny , Nounou Mohamed I. , Vaidyanathan Jayabharathi , Seo Shirley K.
Published: June 2024

Glucagon was discovered about a hundred years ago and its role in health and disease is under continuous investigation. Glucagon is a counter regulatory hormone secreted by alpha cells of the pancreas in response to multiple stimuli. Although some of glucagon's actions and its clinical application have been described, clinical experience with glucagon has been historically overshadowed by that of insulin. To date, the role of glucagon's actions in pharmacotherapy has been under explored. Glucagon plays a considerable role as a hormonal regulator via its known actions on the liver. The rise in obesity and diabetes mellitus prevalence is bringing focus to glucagon's known physiological roles and possible clinical applications. Six glucagon products and a glucagon analog are approved for use in the United States. Clinical pharmacology studies provide crucial support of glucagon's actions as evident from comprehensive pharmacokinetics and pharmacodynamics evaluations in humans. Here, we briefly describe the established physiological role of glucagon in humans and its known relationship with disease. We later summarize the clinical pharmacology of available glucagon products with different routes of administration.
The Facile and Controllable Synthesis of Ultrafine Sn Nanocrystals Loaded on Carbon Black for High‐Performance Lithium Storage
Authors: Zhao Ying , Li Gaofu , Kong Xianglong , Zhao Xudong , Liu Liu , Wang Sihao , Li Guoling , Zhang Milin , Liu Zhiliang , Yang Piaoping
Published: June 2024

Sn and C nanocomposites are ideal anode materials for high‐energy and high‐power density lithium ion batteries. However, their facile and controllable synthesis for practical applications is still a critical challenge. In this work, a facile one‐step method is developed to controllably synthesize ultrafine Sn nanocrystals (< 5 nm) loaded on carbon black (Sn@C) through Na reducing SnCl4 by mechanical milling. Different from traditional up‐down mechanical milling method, this method utilizes mechanical milling to trigger bottom‐up reduction reaction of SnCl4. The in‐situ formed Sn nanocrystals directly grow on carbon black, which results in the homogeneous composite and the size control of Sn nanocrystals. The obtained Sn@C electrode is revealed to possesses large lithium diffusion coefficient, low lithiation energy barrier and stable electrochemical property during cycle, thus showing excellent lithium storage performance with a high reversible capacity (942 mAh g−1 at a current density of 100 mA g−1), distinguished rate ability (480 mAh g−1 at 8000 mA g−1) and superb cycling performance (730 mAh g−1 at 1000 mA g−1 even after 1000 cycles).
Si Single‐Atom Sites Anchored Carbon Anode Achieving the Zero‐Strain Feature and Superior Li+ Storage Performance
Authors: Liu Jieqian , Wang Fei , Mao Jian
Published: June 2024

Overcoming the significant volume strain in silicon‐based anodes has been the focus of research for decades. The strain/stress in silicon‐based anodes is inversely proportional to their size. In this study, we design atomic Si sites to achieve the ultimate size effect, which indeed exhibits a zero‐strain feature. Compared with conventional silicon‐based anodes with alloying addition reactions, the lithium‐ion storage mechanism of atomic Si sites is solid‐solution reactions, which brings about the zero‐strain feature. Additionally, the ligand structure of atomic Si sites remains constant during cycling. This zero‐strain feature results in excellent cycling stability. Furthermore, the exposed atomic Si sites enhance the electrochemical reaction kinetics, leading to outstanding rate performance. Moreover, the anode inherits the advantages of silicon‐based anodes, including a low working voltage (~0.21 V) and high specific capacity (~2300 mAh g−1 or ~1203 mAh cm−3). This work establishes a novel pathway for designing low/zero‐strain anodes.
Graphdiyne‐Induced CoN/CoS2 Heterojunction: Boosting Efficiency for Bifunctional Oxygen Electrochemistry in Zinc‐Air Batteries
Authors: Cui Min , Yuan Yanan , Wu Yue , Che Zhongmei , Li Peixuan , Yang Xiaochen , Chen Yuqi , Hu Wei , Wang Jingui , Wang Shuai , Guo Yingshu , Wu Zexing
Published: June 2024

The performance of zinc‐air battery is constrained by the sluggish rate of oxygen electrode reaction, particularly under high current discharge conditions where the kinetic process of the oxygen reduction reaction (ORR) decelerates significantly. To address this challenge, we present a novel phase transition strategy that facilitates the creation of a heteroatom‐doped heterointerface (CoN/CoS2). The meticulously engineered CoN/CoS2/NC electrocatalyst displays a superior ORR half‐wave potential of 0.87 V and an OER overpotential of 320 mV at 10 mA cm−2. Experimental and computational analysis confirm that the CoN/CoS2 heterostructure optimizes local charge distribution, accelerates electron transfer, and tunes active sites for enhanced catalysis. Notably, this heterojunction improves stability by resisting corrosion and degradation under harsh alkaline conditions, thus demonstrating superior performance and longevity in a custom‐made liquid zinc‐air battery. This research provides valuable practical and theoretical foundations for designing efficient heterointerfaces in electrocatalysis applications.
An ecosystemic perspective of the factors affecting the learning experiences of learners with dyslexia in mainstream schools in England
Authors: Nnamani Georgina
Published: June 2024

A systematic literature review (SLR) of seven papers written between 2015 and 2021 explored the educational experiences of learners with dyslexia in mainstream schools in England from an ecosystemic perspective and how to improve the situation. The analysis employed keywords for database searches and followed the PRISMA flow protocol. It synthesised evidence using thematic analysis and identified seven themes: dyslexia challenges; differential treatment; negative stereotypes; early intervention; teachers' training; power dynamics; and collaboration. The results suggest that several factors can influence the learning experiences of learners with dyslexia in English mainstream schools. Similarly, such factors can, in turn, be dependent on education policies. On that premise, this systematic literature review recommends that to promote positive learning experiences for learners with dyslexia, classroom strategies targeting interventions should be supported with broader environmental strategies shaping individuals' learning experience and offer support from different perspectives. A whole‐school approach to providing intervention, teachers' training, parents and school partnerships, and professional collaboration can improve learners' educational experiences. A further recommendation is for learning interventions to target all learners, to prevent differential treatment of learners with dyslexia and to avoid them standing out from their peers and creating a negative experience.
Modes of governance for sustainability transitions: Conceptual definitions
Authors: Massuga Flavia , Doliveira Sérgio Luis Dias , Kuasoski Marli , Mangoni Simone Soares
Published: June 2024

The unsustainability of production and consumption patterns and the socio‐technical systems in the energy, mobility, water, and solid waste sectors highlights the need for sustainability transitions. However, the transition management perspective indicates that these transformations cannot be managed in the traditional hierarchical sense. Therefore, new modes of governance are required to deal with the complexity and nature of sustainability issues. This study seeks to elucidate these matters by bringing the literature on sustainability transitions, transition management, and governance modes closer to each other, generating a better understanding of governance in transitions. In addition to the theoretical discussion on the linked concepts, this study also contributes by presenting and characterizing five modes of governance that can facilitate the paths to transformation. They are participatory, collaborative, multilevel, smart, and network governance. These modes of governance differ according to the actors involved and the nature of their interactions and encompass different political processes, institutional structures, and policy content. The assumption is that the modes of governance addressed, which distance themselves from conventional approaches based on top‐down control, can favor transition initiatives that promote transformative processes toward a more resilient and sustainable society. However, the inherent embeddedness of the public service is recognized, which requires transitions in governance itself through institutional adaptations and changes in the role of actors and public officials.
Magnetocaloric Analysis of Novel Polycrystalline Sm0.5Sr0.4Nd0.1Mn1‐xTixO3(0≤x≤0.2) that Correlates Structural and Magnetic Properties
Authors: Raman Rajesh , I. B. Shameem Banu , Sankar Raman , Moovendran Kalimuthu
Published: June 2024

This article summarizes the impact of the Ti ion at the Mn site of polycrystalline Sm0.5Sr0.4Nd0.1MnO3 samples, exploring the correlation between the structural, microstructural, magnetic, and magnetocaloric properties through the solid‐state route. The Rietveld refinement pattern divulges that all samples are crystallized predominantly in the orthorhombic phase with the Pnma space group. Temperature‐dependent magnetic studies of Sm0.5Sr0.4Nd0.1Mn1‐xTixO3 (x=0, 0.1, 0.2) expose phase separation phenomena in the field cooling curve, where the first peak at 42 K corresponds to the antiferromagnetic charge ordering or spin orientation of spontaneous magnetization, and the second peak at 87 K, 75.91 K, and 74.28 K corresponds to the paramagnetic to ferromagnetic transition. The maximum magnetic entropy changes (ΔSM) at T=110 K are discerned to be 2.5 J Kg−1 K−1, 1.65 J Kg−1 K−1, and 1.31 J Kg−1 K−1, respectively. Normalization of ΔS values in Sm0.5Sr0.4Nd0.1Mn1‐xTixO3 (x=0, 0.1, 0.2) does not overlap the universal behavior at magnetic fields (1T ‐ 7T), confirming the existence of field‐induced second‐order magnetic transitions. The relative cooling power (RCP) values are found to be 777.96 J Kg−1, 255.28 J Kg−1, and 190.58 J Kg−1 respectively. Further, the enhancement of the working span temperature and the broadening of specific heat capacity peaks in Sm0.5Sr0.4Nd0.1Mn1‐xTixO3 (x=0.1, 0.2) samples make these materials a promising candidate to serve as operating substances in magnetic refrigeration.
Perceived general similarity and relationship satisfaction: The role of attributional confidence
Authors: Lee Ting Hin , Ng Ting Kin
Published: June 2024

Even though many studies have examined the link between individuals' perceived general similarity to their romantic partners and their own relationship satisfaction, there are not many studies focusing on the impact of perceived general similarity reported by the partner. The present work uncovers the potential mediating roles of one's and the partner's attributional confidence in the effects of one's and the partner's perceived general similarity on relationship satisfaction. To investigate the mechanisms, two studies were conducted at individual and dyadic levels. A total of 395 individuals (51.4% female) aged 17–67 (M = 22.06, SD = 4.68) in unmarried opposite‐gender relationships were recruited in Study 1 and 227 unmarried opposite‐gender couples were employed in Study 2. Across two studies, the indirect effect of perceived general similarity on relationship satisfaction via attributional confidence was significant. In particular, the actor effects of perceived general similarity on relationship satisfaction were mediated by the actor effects of attributional confidence. Moreover, the partner effects of perceived general similarity on relationship satisfaction were mediated by partner attributional confidence (i.e., one's partner's perceived general similarity on one's relationship satisfaction via one's partner's attributional confidence). The present findings shed light on the mechanisms through which perceived general similarity fosters relationship satisfaction among opposite‐gender relationships.