bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction and Validation of Mechanical Flexibility in Molecular Crystals: Dispersion Interactions Dictate Bending
Authors: Singh Ashi , Rahman Atiqur , Mondal Srijan , Spackman Mark A , Iversen Bo B , Thomas Sajesh Pynadath
Published: February 2025

Mechanically flexible crystals are a rapidly growing class of functional molecular materials. Typically, such flexible crystals are discovered by serendipity. Herein, we have predicted mechanical flexibility in a series of molecular crystals based on a structure screening approach that combines interaction topology and the presence of nitrile×××nitrile interactions – a supramolecular motif hitherto not associated with bending property. Further, we have experimentally validated plastic/elastic bending properties in a series of crystal structures thus predicted. However, four out of five of these crystals showed the bending direction along π∙∙∙π stacking despite the fact that the direction of strongest interaction anisotropy was rendered by the nitrile∙∙∙nitrile interaction motifs. This is contrary to the commonly perceived anisotropy model and underscores the dominant role of dispersion forces over the electrostatically stabilized motifs in dictating the bending phenomena in molecular crystals. The interaction energies of these motifs have been evaluated using accurate structures from X‐ray quantum crystallography. Analyses combining elastic tensors, interaction anisotropy indices, thermal expansion studies, and high‐pressure simulations quantify the relative roles of the nitrile∙∙∙nitrile motif and π∙∙∙π stacking in mechanical flexibility. Our results point to the possibility of expanding the realm of flexible molecular materials by predictive computational models.
Facilitating OH* Generation on Atomic Pd–Cu Dual Sites towards Efficient Glycerol Electrooxidation to Formate
Authors: Li Junjun , Zhang Yizhen , Zhang Liya , Zhou Qi , Yang Jiangrong , Fu Yu , Yu Le , Sun Yuanmiao , Li Zhenhua , Qin Yuchen , Yi Ding , Zhang Hui , Wang Dingsheng , Zhang Zhicheng
Published: February 2025

The electrocatalytic glycerol oxidation reaction (GOR) represents a mild and sustainable pathway to produce value‐added chemicals such as formate. However, the rational design and controlled synthesis of efficient catalysts to achieve highly selective C−C bond cleavage of glycerol towards formate remains a great challenge. Herein, atomic Pd doped Cu3N hollow nanocubes with Pd−Cu dual sites were prepared via the unique Kirkendall process, exhibiting superior electrocatalytic GOR activity and selectivity towards formate with a maximum Faraday efficiency of 91.6 %. In situ spectroscopic characterization and theoretical calculations reveal that Pd atoms located in partial Cu substituent sites could facilitate the generation of active *OH and enhance the adsorption of glycerol molecule on adjacent Cu sites, while Pd atoms located in Cu3N unit center could effectively reduce the energy barrier of C−C bond cleavage for the rate determining step. Our work provides new insights into the development of well‐defined dual‐site catalysts to boost glycerol electrooxidation to formate.
An Efficient and Eco‐Friendly Protocol for Synthesis of 2‐Substituted Benzimidazole and Quinoxaline Derivatives by Using Nanostructured Cu2O as Recyclable Catalyst
Authors: Kusuma Suman , Manjunath Hemavathi , Narayana Venkat V. , Torrejos Rey Eliseo , Norrrahim Mohd Nor Faiz , Jadhav Arvind H.
Published: February 2025

Reconnoitre the use of earth‐abundant metals for an essential organic reaction was extremely provocative from an industrial vantage point. In this study, the fundamental and energy‐efficient co‐precipitation approach was employed to aid the Cu2O cubed nanostructured catalyst in the generation of benzimidazole and quinoxaline derivatives. The developed Cu2O cubed nanostructured catalyst was thoroughly evaluated by world‐class analytical and spectroscopic techniques. The Cu2O cube catalyst exhibited exceptional crystallinity, a cubic shape, a large specific surface area and uniformly distributed active sites on its surface. The obtained astounding structural and physico‐chemical characteristics successfully enabled the catalytic activity for the synthesis of benzimidazole and quinoxaline. The recognised vital structural and physical attributes substantially improved the catalytic activity for the production of benzimidazole and quinoxaline derivatives over mild reaction conditions. Employing a cubic Cu2O catalyst, diverse reaction parameters have been examined, encompassing the effects of catalyst dosage, temperature, time, solvent, yield and substrate scope. As a result, the designed catalyst was used to synthesise heterocyclic 2‐substituted benzimidazole and quinoxaline derivatives via the condensation of o‐phenylenediamine, aldehydes and 1,2‐diketone. The reported results showed 100% conversion in both aimed products, with 90% selectivity for 2‐substituted benzimidazole and 95% selectivity for quinoxaline derivatives, respectively. The obtained yield for 2‐substituted benzimidazole and quinoxaline derivatives was 85 and 98 at 60°C for 3 and 4 h, individually. The catalytic activity was fully based on the inherent properties of cubic Cu2O. On top of that, all synthesised compounds were structurally validated by 1H NMR, 13C NMR and mass spectrum data. Remarkably, the efficient cubic Cu2O catalyst demonstrated impressive recyclability for up to six consecutive cycles with minimal loss of its initial catalytic activity. The spent cubic Cu2O catalyst's characteristic results revealed evidence for its stable structural and physico‐chemical features. In addition, we endeavoured to propose and describe a plausible reaction mechanism utilizing the developed nanostructured Cu2O cubes for the synthesis of benzimidazole and quinoxaline derivatives.
Shape Memory Polymers With High Response Temperature and Application in Wellbore Stability
Authors: Liu Zhendong , Sun Tengfei , Li Gongrang , Xu Hai , Lv Jianren
Published: February 2025

This study focuses on the preparation and characterization of high glass transition temperature shape memory polymers (HTSMP) for leak plugging applications. The HTSMP was synthesized through a curing reaction and characterized using FTIR spectroscopy, which confirmed the occurrence of a ring‐opening reaction resulting in the formation of hydroxyl groups. The glass transition temperature of HTSMP reached up to 136°C, and it maintained a modulus of over 10 MPa at 200°C. Shape memory performance tests showed that HTSMP samples exhibited a recovery rate ranging from 80% to 95%, with a higher recovery rate observed with increased curing agent content. In sealing performance tests, the addition of HTSMP‐1 significantly improved the plugging effect of conventional plugging agents, with a pressure‐bearing capacity of up to 9.28 MPa at elevated temperatures. These results demonstrate the potential of HTSMP in sealing applications, particularly for addressing fractured leakage in high‐temperature deep wells.
Genomic Evaluation of Recombination in Small Highly Inbred Beef Cattle Populations
Authors: Hay E. , Ling A. S.
Published: February 2025

Meiotic recombination is key for genetic diversity, but its dynamics are underexplored in small inbred beef cattle populations. This study examines recombination in closed beef cattle populations and identifies related genomic regions. Using genotypic data from 1020 Line 1 Hereford and 3420 Composite Gene Combination (CGC) cattle, recombination rates were estimated through offspring and progenitor haplotypes. The CGC composite displayed a higher recombination rate (27.24 events) than the Line 1 population (26.38 events), with reduced rates in Line 1 potentially due to extended homozygous segments. Recombination varied by autosome length, increasing with longer autosomes. A genome‐wide association study revealed novel genomic regions associated with recombination: significantly associated SNP markers were found on Bos taurus autosome (BTA) 1, 7, 13, 15, and 19 in the Line 1 population, and numerous others in the CGC population, indicating complex polygenic influences.
Sensorimotor Behavior in Individuals With Autism Spectrum Disorder and Their Unaffected Biological Parents
Authors: Bojanek Erin K. , Kelly Shannon E. , Schmitt Lauren M. , Pulver Stormi L. , Sweeney John A. , Sprenger Andreas , Unruh Kathryn E. , Mosconi Matthew W.
Published: February 2025

Sensorimotor impairments are common in autism spectrum disorder (ASD) and evident in unaffected first‐degree relatives, suggesting that they may serve as endophenotypes associated with inherited autism likelihood. We tested the familiality of sensorimotor impairments in autism across multiple motor behaviors and effector systems and in relation to parental broader autism phenotypic (BAP) characteristics. Fifty‐seven autistic individuals (probands), 109 parents, and 89 neurotypical control participants completed tests of manual motor and oculomotor control. Sensorimotor tests varied in their involvement of rapid, feedforward control and sustained, sensory feedback control processes. Subgroup analyses compared families with at least one parent showing BAP traits (BAP+) and those in which neither parent showed BAP traits (BAP−). Results show that probands with BAP− parents (BAP− probands) showed atypical control of rapid oculomotor behaviors, while BAP+ probands showed impairments of sustained manual motor and oculomotor behaviors compared to controls. BAP− parents showed impaired rapid oculomotor and sustained manual motor abilities relative to BAP+ parents and controls. Rapid oculomotor behaviors were highly intercorrelated among probands and their biological parents. These findings indicate that rapid oculomotor behaviors are selectively impacted in BAP− probands and their parents and may reflect a familial likelihood for autism independent of parental autistic traits. In contrast, sustained sensorimotor behaviors were affected in BAP+ probands and BAP− parents, suggesting separate familial pathways associated with autism. Finally, atypical saccade dynamics may serve as strong endophenotypes for autism. These findings provide new evidence that rapid and sustained sensorimotor alterations represent strong but separate familial pathways of inherited likelihood for autism.
Metalations on 2,2′‐bipyridine‐functionalized metal–organic frameworks for catalytic platforms
Authors: Kang Jiwon , Cha Seungheon , Ryu Jihun , An Byeongho , Lim Chaewon , Heo Yoonji , Choi Isaac , Kim Min
Published: February 2025

2,2′‐Bipyridine (BPY) is a versatile organic ligand, well known for its strong metal‐chelating properties, which make it a crucial component in coordination chemistry. When integrated into metal–organic frameworks (MOFs), BPY significantly enhances the material's properties, particularly in catalysis, due to its ability to coordinate with a wide range of metal ions. This review focuses on the metalation of BPY‐incorporated MOFs (MOF‐BPYs), with an emphasis on the coordination of secondary metal cations at BPY sites. The metals are categorized into first‐, second‐ and third‐row transition metals, and other metals, highlighting key examples such as Pd, Mo, Cu, and Fe. The synergistic interactions between the metal centers and the MOF framework, which contribute to the enhanced catalytic performance of MOF‐BPYs, are explored in detail. The review also addresses mixed‐metal systems, emphasizing their unique properties and applications. Furthermore, strategies for metalation, including the pre‐functionalization of BPY prior to MOF synthesis and post‐synthetic modification, are critically examined. Finally, the stability of parent MOFs—particularly Zr‐based frameworks, known for their robustness—is discussed in relation to the overall performance of MOF‐BPY materials.
Unveiling the complexity of cellular senescence in cancers: From mechanism to therapeutic opportunities
Authors: Pan Qiuming , Zhu Ye , Ye Zhi , Zhang Huayang , Wang Junxi , Yi Guozhong , Li Zhiyong , Xu Rongyang , Wang Luyao , Wu Zhenzhen , Qi Songtao , Huang Guanglong , Qu Shanqiang
Published: February 2025

Cellular senescence is characterized by a sustained and irreversible cessation of cell proliferation in response to diverse environmental stimuli. However, senescent cells exhibit strong metabolic activity and release a range of cytokines and inflammatory mediators into the tumor microenvironment, collectively referred to as the senescence‐associated secretory phenotype (SASP). In recent years, to develop new therapies for cancers, researchers have conducted extensive studies on the mechanism of cancer cell senescence and revealed that induction of cancer cell senescence could effectively suppress cancer progression. However, it has been documented that cellular senescence not only inhibits cancer initiation but also contributes significantly to cancer progression in some cases. Hence, it is imperative to comprehend the correlation between cellular senescence and tumorigenesis, and discuss the potential utilization of cellular senescence mechanisms to suppress cancer progression, which lays a theoretical foundation for new drugs to treat cancers. In this review, we first provide an overview of the discovery of cellular senescence and its key milestone events. Meanwhile, this review examines the major stimulus for the induction of senescence, and provides an overview of the categorization of cellular senescence. Subsequently, an examination of the primary regulatory mechanisms of cellular senescence is discussed, followed by a summary of the control of the SASP expression and its dual biological roles in cancers. Additionally, we also provide an overview of common biomarkers utilized in the identification of cellular senescence. Finally, this review investigates the efficacy of the “One‐Two punch” sequential treatment approach for cancers, and examines the emerging challenges of this novel approach.
Cognitive Impairment in Chronic Kidney Disease Across Different Stages: The Role of Structural and Perfusion‐Driven Functional Connectivity Changes
Authors: Bai Xiaoyan , Song Lijun , Liu Xu , Yang Wenbo , Li Mingan , Xu Boyan , Yang Zhenghan , Wang Zhen‐Chang , Wang Hao
Published: February 2025

Introduction

Chronic kidney disease (CKD) is associated with cognitive impairment (CI), yet the exact pathophysiological mechanisms remain unclear. This study aims to investigate the alterations in gray matter volume (GMV) and cerebral blood flow (CBF) across CKD stages, identify co‐changed brain regions, explore abnormal seed‐based functional connectivity (FC) in patients with CKD, and investigate the correlation between the abnormal brain regions and neuropsychological test scores.

Methods

Two hundred and eight participants (66 healthy controls, 70 CKD Stages 1–3a, and 72 CKD Stages 3b–5) were consecutively recruited and underwent high‐resolution T1‐weighted imaging, arterial spin labeling, and functional MR imaging. The imaging parameters were compared among three groups, and correlations with MoCA scores were analyzed.

Results

Compared to CKD 1–3a group, the bilateral fusiform gyrus (FFG.L and FFG.R) exhibited reduced GMV, increased CBF, and decreased FFG.L‐FC with bilateral inferior frontal gyrus, triangular part (IFGtriang.L and IFGtriang.R), left middle occipital gyrus (MOG.L), and left hippocampus (HIP.L), as well as decreased FFG.R‐FC with bilateral median cingulate and paracingulate gyri (DCG.L and DCG.R), left superior frontal gyrus, medial (SFGmed.L), IFGtriang.L, and right middle temporal gyrus (MTG.R) in CKD 3b–5 group. A negative correlation was observed between the MoCA scores and FFG.L‐FC with right middle frontal gyrus (MFG.R), IFGtriang.L, IFGtriang.R, HIP.L, and left putamen in patients with CKD 1–3a.

Conclusion

Brain structural and perfusion alterations may underlie the reduced FC between fusiform gyrus and cognitive‐related regions, providing potential neuroimaging evidence for the neuropathological mechanisms of CI in patients with different stages CKD.
Fractional Anisotropy of Cingulum Cingulate Mediates the Relationship Between Happiness and Work Performance in Healthy Individuals
Authors: Kokubun Keisuke , Nemoto Kiyotaka , Yamakawa Yoshinori
Published: February 2025

Introduction

As competition among companies around the world intensifies, the nature of work and the performance required are becoming more complex. In parallel with this, there is growing attention on happiness and well‐being as factors related to improving employee performance. However, little is known about the relationship between happiness and the brain and work performance in healthy people.

Methods

Therefore, we analyzed the correlations between the nine categories of work role performance (WRP), the subjective happiness scale (SHS), and four regions of fractional anisotropy (FA), an index reflecting brain microstructure that has been shown to be related to apathy in previous studies.

Results

It was shown that the cingulum cingulate (CCI) and the superior longitudinal fasciculus (SLF) correlated with the WRP and its facets in a manner consistent with their respective functions. In particular, the CCI was found to be extensively correlated with the facets of the WRP and to have a partially mediating effect on the relationship between the SHS and the WRP.

Conclusion

This study is the first to show that indicators reflecting healthy individuals’ happiness and brain microstructure, which are related to a variety of nonwork factors, are positively correlated with the diverse roles and performance that characterize modern work.
Quinones as Multifunctional Scaffolds for Oxidative, Reductive, and HAT Photocatalysis
Authors: Müller Lea , Poll Jonas , Ghosh Indrajit , Nuernberger Patrick , König Burkhard
Published: February 2025

Photoredox catalysis, which enables both electron and hydrogen atom transfer, has become a powerful tool for activating chemical bonds and synthesizing complex molecules under mild conditions. Typically, photocatalysts
are optimized either for oxidative or reductive reactions within a limited redox window (less than 3.1 V) and for
hydrogen atom transfer (HAT) reactions, with few frameworks capable of mediating both pathways for high redox‐demanding reactions (covering more than a 5 V redox window) without requiring special conditions. Herein, we report the use of quinones as multifunctional scaffolds in light‐driven redox transformations, offering access to a redox window of approximately 5 V using visible light. The quinone scaffold's versatility facilitates a wide range of radical and ionic processes under both oxidative and reductive conditions, in addition to enabling HAT reactions. By keeping the parameters, i.e. the reaction partners, constant, such transformations can be carried out under just two reaction conditions. Oxidative transformations and HAT reactions occur under ambient air, while activation of the chromophore for reductive transformations can be achieved using an inorganic base (Cs2CO3) via a simple acid‐base deprotonation event. This dual capability highlights the potential of quinones as scaffolds to extend their utility in photoredox catalysis.
Pharmacological Inhibition of β Myosin II Disrupts Sarcomere Assembly in Human iPSC‐Derived Cardiac Myocytes
Authors: Hayes James B. , Burnette Dylan T.
Published: February 2025

Sarcomeres are the fundamental contractile units of striated muscle. The functional roles of the cardiac‐specific myosin heavy chains, MYH6 (α myosin II) and MYH7 (β myosin II) during sarcomere assembly remain controversial. To address this, we utilized a selective MYH7 inhibitor, mavacamten, in combination with siRNA‐mediated knockdown of MYH6 or MYH7 in human induced pluripotent stem cell‐derived cardiomyocytes (hiCMs). Our results demonstrate that sarcomere assembly proceeds when either MYH6 or MYH7 is independently depleted, suggesting functional redundancy. However, pharmacological inhibition of MYH7 contractility by mavacamten disrupts sarcomere assembly in a concentration‐dependent manner. Sensitivity to mavacamten correlated with the relative abundance of MYH6 and MYH7: sarcomere assembly by MYH7‐enriched (i.e., MYH6‐depleted) hiCMs was more sensitive to mavacamten (IC50 = 0.1 μM), while assembly by MYH6‐enriched (i.e., MYH7‐depleted) hiCMs was less sensitive (IC50 = 0.5 μM). These findings suggest that MYH7‐mediated contractility is required for sarcomere assembly, but only when MYH7 is present within a cardiac myocyte. We conclude that the MYH7/MYH6 ratio impacts the susceptibility of sarcomere assembly to pharmacological inhibition.
Planning Post‐Launch Evidence Generation: Lessons from France, England and Spain
Authors: Kent Seamus , Meyer Francois , Pavel Alina , Saborido Carlos Martin , Austin Catrin , Williamson Steve , Ray Joshua , Facey Karen
Published: February 2025

Technological developments and innovations in regulatory pathways have meant medicinal products are increasingly associated with substantial clinical and economic uncertainties at launch. This has increased the focus on continuous evidence generation to assess the real‐world value of new medicines post‐launch. This paper examines Post‐Launch Evidence Generation (PLEG) systems in France, Spain, and England, drawing on insights from a series of multistakeholder roundtables hosted by RWE4Decisions. These discussions provided a platform to compare national approaches to PLEG considering PLEG planning and operationalization. The roundtable events included presentations by representatives of the HTA bodies and payers in France, Spain, and England, an industry response, and multistakeholder discussions. The events highlighted that while there are differences in the products to which PLEG is applied and the way it is operationalized, there are many common challenges experienced across systems and by all stakeholders. First, there is a recognition that evidentiary needs must be anticipated earlier to avoid PLEG where possible and better plan for PLEG where needed. Second, there is a need to streamline data collection. This includes trying to make greater use of existing data sources vs. primary data collection, prioritizing collection of a small number of outcomes that directly address key uncertainties, and by improving international collaborations to streamline data collection and evidence generation across borders. Our findings suggest value in improving scientific advice processes and international collaboration to discuss key data gaps early and ensure efficient and effective evidence collection that improves the speed and quality of reimbursement and pricing decisions.
Is There a Key Primer for Amplification of Core Land Plant DNA Barcode Regions (rbcL and matK)?
Authors: Corvalán Leonardo C. J. , de Melo‐Ximenes Amanda A. , Carvalho Larissa R. , e Silva‐Neto Carlos de M. , Diniz‐Filho José A. F. , Telles Mariana P. de C. , Nunes Rhewter
Published: February 2025

The DNA barcode is a technique for molecular identification of species. Two core genes, matK and rbcL, are widely used for land plants. In this technique, the selection of primers is a fundamental step for the success of amplification. Then, we aim to evaluate the primer amplification capability for the DNA barcode regions rbcL and matK. We extracted primer sequences from DNA barcode studies in the Web of Science and used chloroplast genome sequences from NCBI for in silico PCR tests using OpenprimeR. Physicochemical properties of in silico PCR were evaluated using OpenprimeR. Our literature review resulted in 366 and 489 different rbcL and matK primers. These were tested in 8665 sequences, 8463 species from 98 orders. Evaluating only the primer and sequence match, the primers with the highest number of sequences covered were 96.39% and 93.81% forward and reverse for rbcL, and 91.56% and 61.62% forward and reverse for matK. No universal primer for all land plants was found, but two rbcL primer pairs could amplify > 99% of the sequences. In contrast to the results obtained for the matK region, the 10 pairs optimized for the greatest coverage of sequences were not covered by > 85% of the sequences. Therefore, it is advisable to pay attention when selecting primers for the matK region and the need to develop new primers. Here, we recommend a set of primers to cover the largest number of sequences and orders.
Urban Snowmelt Runoff Responses to the Temperature‐Hydraulic Conductivity Relation in a Cold Climate
Authors: Feng Youcan , Ma Donghe , Ma Zhenjie , Tian Lin , Gao Jinhua , Huang Xin , Xue Lijun
Published: February 2025

Urban winter runoff management was mainly regulated by temperature variations and the snow‐removing measures, but the underlying mechanism of the temperature‐hydraulic conductivity (T‐K) relation was seldom studied for urban environments and far from clearly understood. It is imperative to consider the T‐K relation for snowmelt runoff calculation especially when the compound effects with the snow‐removing measures and low impact development (LID) need to be considered. This work investigated the temperature regulation on urban infiltration and snowmelt runoff by a proposed modelling framework. A series of hydrologic model experiments revealed a crucial link between the hydraulic conductivity and snowmelt runoff emphasising the role of temperature in the partitioning between percolation and runoff. The inclusion of a T‐K relation in the SWMM model resulted in a 26.0%–37.1% decrease in infiltration and a 12.7%–25.8% increase in runoff. The effects of the T‐K relation were found to become more significant when the anthropogenic interventions such as snow‐clearing measures and LID were applied. After the T‐K mechanism was modelled, the infiltration and the runoff caused by the snow‐clearing measures were reduced by 33.7%–48.2% and raised by 19.7%–35.6%, respectively, and LID would further reduce infiltration by 46.2%–65.2% and increase runoff by 71.0%–105.2%. This study serves as one of the first a few attempts to improve the understanding of the freeze–thaw cycles of land surface in urban environments.
Identification of Natural Killer Cell‐Associated Clusters in Skin Melanoma and the Impact on Prognosis and Drug Sensitivity
Authors: Zhou Jun , Cai Renhui , Zhang Danqun , Chen Caifeng
Published: February 2025

Background

Skin melanoma exhibits significant heterogeneity in clinical outcomes and treatment responses among patients. This study aimed to investigate natural killer (NK) cell clusters in skin melanoma, their impact on patient prognosis, and their value as biomarkers for tailoring treatment.

Methods

We used data from TCGA, GSE19234, GSE65904, GSE244982, and GSE78220. A gene classifier was developed to identify two distinct clusters of melanoma patients. Survival analysis, NK cell infiltration levels, and responses to immune and targeted therapies were evaluated.

Results

Unsupervised clustering revealed two distinct melanoma patient clusters with significant differences in NK cell activity and clinical outcomes. Cluster 1 showed higher NK cell infiltration, better overall survival (OS) (p < 0.0001), and greater activity in NK‐cell‐related pathways. In contrast, Cluster 2, characterized by lower NK cell activity and higher exhaustion markers, had poorer OS. Drug sensitivity analysis indicated that Cluster 1 was more responsive to most melanoma treatments, whereas Cluster 2 had higher sensitivity to trametinib (p < 0.001). The developed gene classifier had an AUC of 0.913 and effectively differentiated between clusters. Additionally, Cluster 1 showed better responses to immunotherapy with a higher rate of complete and partial responses (p < 0.001). These findings were validated in external databases.

Conclusion

This study identifies two distinct NK‐cell‐related clusters in melanoma with differential prognoses and treatment responses. These findings underscore the importance of integrating NK‐cell‐related profiles into personalized treatment strategies, offering a pathway to optimize therapeutic outcomes based on specific immune profiles.
Deciphering the Molecular Mechanisms of HAART‐Induced Hepatotoxicity
Authors: Ezhilarasan Devaraj , Karthick Munusamy , Sharmila Muthusethupathi , Sanjay Somasundaram , Mani Uthirappan
Published: February 2025

Highly active antiretroviral therapy (HAART), consisting of three or more antiretroviral drugs, is recommended for patients with HIV infection. HAART effectively reduces HIV RNA levels, lowers the risk of opportunistic infections, and improves immune function and survival rates. However, it is also associated with an increased risk of liver injury in HIV‐infected individuals. This review aims to summarize the mechanisms underlying HAART‐induced liver injury. A comprehensive search was conducted in PubMed and EMBASE using keywords such as “Antiretroviral/ARV drugs and drug‐induced liver injury (DILI),” “HAART and DILI,” “Antiretroviral therapy and DILI,” and “HIV infection and DILI.” Relevant papers published before March 2024 were included. Experimental studies have demonstrated that zidovudine and efavirenz can cause structural alterations in mitochondria, impair the respiratory chain, generate free radicals, and deplete mitochondrial DNA, leading to oxidative and endoplasmic reticulum stress, as well as the accumulation of advanced glycation end products in liver tissue. Zidovudine disrupts lipid homeostasis by increasing fatty acid synthesis and reducing metabolism. Efavirenz and its metabolite, 8‐hydroxyefavirenz, induce hepatocellular death and activate proapoptotic markers through c‐Jun N‐terminal kinase signaling. Additionally, lamivudine has been shown to induce liver injury and oxidative stress in rats. Clinically, approximately 50% of HIV patients on HAART regimens containing non‐nucleoside reverse transcriptase inhibitors experience mild to moderate liver injury. HAART regimens that include efavirenz, lamivudine, and tenofovir impair glucose and lipid homeostasis in rats, highlighting the need for caution in HIV patients with fatty liver disease. Patients with viral hepatitis coinfection, those taking antitubercular drugs or cotrimoxazole, and those on nevirapine‐containing regimens are at particularly high risk. Regular monitoring of liver function is essential to prevent liver damage associated with HAART in HIV‐infected patients. While HAART significantly improves survival rates in HIV patients, it also poses a considerable risk of liver injury, necessitating careful monitoring and management.
Efficacy of Lactobacillus reuteri Probiotic in the Bowel Preparation Regimen of Children Candidates for Colonoscopy
Authors: Rahmani Parisa , Ebrahimi Maryam , Rohani Pejman , Sohouli Mohammad Hassan , Magalhães Elma Izze da Silva
Published: February 2025

Objective

Bowel preparation can directly affect the final outcome of a colonoscopy. However, limited studies have been conducted regarding the effect of probiotics on intestinal preparation. Thus, the present study aims to investigate the effect of Lactobacillus reuteri probiotics in the bowel preparation regimen of children who are candidates for colonoscopy.

Methods and Materials

In this double‐blind, placebo‐controlled, randomized clinical trial, 84 colonoscopy candidate pediatric patients were enrolled. Patients were divided into two equal groups of 42 individuals. One group of patients underwent the bisacodyl, polyethylene glycol regimen 48 h before colonoscopy, as along with a placebo. The other group was administered L. reuteri 10 days before colonoscopy and also received bisacodyl and polyethylene glycol 48 h before the procedure. Then, the bowel preparation of the patients was assessed using the Boston Bowel Preparation Scale (BBPS).

Results

The mean age of patients in the placebo and probiotic groups was 94.1 ± 43.8 and 111.2 ± 48.8 months, respectively (p = 0.10). The preparation of the left colon was not significantly different between the placebo and probiotic groups (p = 0.075). The effect of L. reuteri probiotic on the preparation of the right colon was excellent in 18 patients (42.86%) and good in 17 patients (40.47%). The preparation of the right colon was significantly different between the placebo and probiotic groups (p = 0.007). Based on the results, there was a significant association between the consumption of L. reuteri and placebo in the preparation of the transverse colon (p = 0.015).

Conclusion

Probiotic pretreatment as part of bowel preparation significantly improves visualization of the colonic mucosa during colonoscopy.
Number needed to treat for net clinical benefit of oral anticoagulants in Asian patients with atrial fibrillation
Authors: Krittayaphong Rungroj , Pumprueg Satchana , Yindeengam Ahthit , Lip Gregory Y. H.
Published: February 2025

Background

Oral anticoagulants (OAC) can reduce ischemic stroke/systemic embolism (SSE) in patients with non‐valvular atrial fibrillation (AF) while increasing the risk of major bleeding. We aimed to analyze the number needed to treat for the net benefit (NNTnet) of warfarin and non‐vitamin K antagonist oral anticoagulants (NOACs).

Methods

We analyzed the results from multicenter national AF registry from 27 hospitals in Thailand. Follow‐up data were collected every 6 months until 3 years. Main outcomes were SSE, major bleeding, and intracranial hemorrhage (ICH). NNT was calculated from the absolute risk reduction (ARR) of SSE or absolute risk increase (ARI) of major bleeding or ICH. We compared NNTnet of warfarin versus no OAC, NOACs versus no OAC, and NOACs versus warfarin. Warfarin was also categorized into time in therapeutic range (TTR) < and ≥65%.

Results

We studied a total of 3405 patients (mean age 67.8 ± 11.3 years, 1424 (41.8%) were female). The incidence rates of SSE, major bleeding, and ICH were 1.51, 2.25, and 0.78 per 100 person‐years, respectively. Warfarin had negative NNTnet −37 compared to no OAC. NOACs had positive NNTnet 101 and 27 compared to no OACs and warfarin. Warfarin with TTR 65% had positive NNTnet 42 compared to no OAC. NOACs had comparable NNTnet as warfarin with TTR ≥65%.

Conclusion

Warfarin had a negative NNTnet compared to no OAC. Only warfarin with TTR 65% has positive NNTnet. NOACs had positive NNTnet compared to no OAC and when compared to warfarin.
Development of Reliable and High‐Throughput Human Biomimetic Cartilage and Bone Models to Explore Senescence and Personalized Osteoarthritis Treatment Options
Authors: Boone Ilja , Houtman Evelyn , Tuerlings Margo , van den Berg Jim J. , Lehmann Johannes , de Keizer Peter L. J. , Nelissen Rob G. H. H. , Meulenbelt Ingrid
Published: February 2025

To facilitate effective preclinical testing of senescence treatments for osteoarthritis (OA), we have created reliable biomimetic and high‐throughput models using aged human joint tissues. Moreover, concerns regarding scalability led to the concurrent development of a high‐throughput human in vitro senescence cartilage organoid model. Osteochondral explants and cells for the cartilage organoid model were isolated from patients undergoing joint replacement surgery due to OA. To induce senescence, explants and organoids were subjected to radiation and/or mechanical loading. Samples were harvested; gene expression of relevant senescent and cartilage genes was measured using RT‐qPCR, and protein expression was evaluated using histology. A general senescence phenotype was induced by the perturbations, as shown by senescence‐associated β‐galactosidase staining. In‐depth gene expression analysis revealed that hyperphysiological mechanical loading upregulated gene expression of IL8 and SERPINE1, representing aspects of a senescence‐associated secretory phenotype (SASP) profile. Irradiation upregulated CDKN1A, encoding p21, and downregulated LMNB1, representing a cell cycle arrest profile with the absence of a SASP response. Combining the two perturbations showed upregulation of CDKN1A, IL8, and SERPINE and downregulation of LMNB1, representing a complementary senescence model. The high‐throughput human in vitro cartilage organoid senescence model showed similar effects to the irradiation explant model. In this study, we present a variety of senescence models of human aged chondrocytes that allows for rapid initial screening of anti‐senescence compounds in high‐throughput, as well as in‐depth, characterization of post‐mitotic aged chondrocytes prone to OA pathophysiology. This research advances the development of essential therapeutics for OA.
Data‐informed selection of evidence‐based treatments for posttraumatic stress disorder and co‐occurring symptoms
Authors: Torres Victoria Alicia , Coe Elizabeth , Jackson Jalisa , Leonard Kiara , Rostockyj Jessica , Swensen Kira , Meyer Eric , Gulliver Suzy Bird , Jones Stephanie
Published: February 2025

Posttraumatic stress disorder (PTSD) commonly co‐occurs with other disorders. Although there are several evidence‐based treatments available for PTSD and co‐occurring disorders, including cognitive processing therapy (CPT), prolonged exposure (PE), acceptance and commitment therapy (ACT), and the unified protocol for transdiagnostic treatment of emotional disorders (UP), limited findings clarify the use of baseline symptom data to help providers and patients choose among treatments. To address this, the current study examined baseline symptoms and treatment trajectories among 90 veterans and veteran family members with probable PTSD (based on PCL‐5) receiving either trauma‐focused (CPT, PE) or transdiagnostic (ACT, UP) treatment via telehealth, with the aim of assisting providers in recognizing patterns to inform data‐driven treatment selection. Overall, there was no difference in the likelihood of clinically meaningful improvement in PTSD symptoms between transdiagnostic and trauma‐focused treatments, relative risk (RR) = 0.92, 95% confidence interval (CI) [0.63, 1.34]. When stratified by probable substance use disorder (SUD) and major depressive disorder (MDD) status, the results revealed a pattern suggesting that transdiagnostic treatment may be more effective for reducing PTSD symptoms among individuals with probable co‐occurring SUD and MDD, RR = 1.50, 95% CI [0.27, 8.34], whereas trauma‐focused treatment may be more effective for those without probable co‐occurring SUD or MDD, RR = 0.56, 95% CI [0.31, 1.00]. Studies with larger samples and randomization are needed to confirm patterns. This work could be extended by comparing outcomes from other treatments and by assessing functional outcomes such as posttraumatic growth and quality of life.
Subelliptic p$p$‐Laplacian spectral problem for Hörmander vector fields
Authors: Karazym Mukhtar , Suragan Durvudkhan
Published: February 2025

Based on variational methods, we study the spectral problem for the subelliptic ‐Laplacian arising from smooth Hörmander vector fields. We derive the smallest eigenvalue, prove its simplicity and isolatedness, establish the positivity of the first eigenfunction, and show Hölder regularity of eigenfunctions with respect to the control distance. Moreover, we determine the best constant for the ‐Poincaré–Friedrichs inequality for Hörmander vector fields as a byproduct.
Properties and Filtration Performance of Porous Clay Membrane Fabricated at Various Sintering Temperatures
Authors: Zulkifli Rumaizah Che , Azaman Fazureen , Razali Mohd Hasmizam , Ali Asmadi , Hassan Mohd Faiz , Nor Mohd Al Amin Muhamad
Published: February 2025

A porous clay membrane is fabricated using natural ball clay and sintered at various temperatures ranging from 800 to 1100 °C. The properties of the porous clay membrane are characterized, including shrinkage, water absorption, porosity, density, compressive strength, pure water permeation, and turbidity removal from aquaculture wastewater. A clear trend is observed from the findings. As the sintering temperature increases, the water absorption, porosity, and membrane permeation decreases from 62.25% to 43.67%, 57% to 43%, and 4356 to 2235 L h−1 m−2 bar−1, respectively. Conversely, shrinkage, density, compressive strength, and turbidity removal show an opposite correlation, increasing from 9.09% to 18.18%, 0.84 to 1.0 kg m−3, 0.95 to 4.11 MPa, and 79% to 94%, respectively. In summary, the sample sintered at 1000 °C emerges as the optimal choice for aquaculture wastewater filtration. It strikes a balance between the desired density and strength while maintaining an appropriate porosity level and exceptional turbidity removal capacity. This cost‐effective ceramic filter exhibits promising properties in producing clear effluent.
Enhancing Public Awareness: Media Sensitization about Polymers in Daily Life for Sustainable Living
Authors: Martolia Mukta , Srivastava Sonali , Singh Shishir Kumar , Upadhyaya Shrinkhala , Kumar Ankit
Published: February 2025

Considering the widespread presence of polymers in everyday life, it is crucial to have a comprehensive understanding of their effects on the environment, health, and the promotion of sustainable living. The current study aims to investigate and assess the efficacy of media in raising awareness among the general population regarding the widespread existence and importance of polymers in everyday life. Given the wide range of uses in modern living, such as packaging materials and medical equipment, it is vital to have a thorough grasp and appreciation of the function that polymers play in the daily life. The study aims to evaluate the influence of media in boosting awareness, correcting misunderstandings, breaking myths related to the use of, and encouraging responsible utilization of polymer‐based products. The study also attempts to get insights into the influence of media on public attitudes and behaviors related to polymer usage.
Polyaniline‐Based Nanocomposites for Wastewater Treatment
Authors: A Chithra , Arora Isha , Garg Seema , Bhandari Hema , Sagadeven Suresh , Chandra Amrish
Published: February 2025

Over the past few decades, the removal of heavy metals and dyes from the water has become an important concern. Various research studies are focused for the treatment of wastewater and removal of such toxic metals and organic/inorganic dyes from water streams. The process of adsorption and photocatalysis has shown remarkable results in regard for the removal of metals and dyes from the aqueous solution. This paper provides an overall overview of different methods for the synthesis of nanoparticle, synthesis of polyaniline (PANI), and composites based on the PANI combined with nanomaterial. Also, this paper provides an insight on the efficiency of the fabricated nanocomposites for the adsorption of heavy metals and their photocatalytic efficiency for the degradation of dyes from the aqueous solution.
Utilization of Nickel‐Modified Natural Zeolite in Catalytic Structural Reforming of Iraqi Naphtha
Authors: Ismael Khalil Mohsen , Yousif Ghazal Raghed , Jamal Ayed Nabeel
Published: February 2025

This research focuses on the utilization of abundant natural mineral resources in Iraq to prepare both unmodified natural zeolite and nickel‐modified zeolite. These zeolites are employed in the catalytic thermal structural reforming process of naphtha distillates (35–200 °C) under initial temperature conditions (100, 150, 200, 250, 300, 350 °C) using a constant catalyst ratio. The zeolites, prepared in two forms, 1% by weight, and with a reaction time of 1 h, are first tested to determine the optimal temperature. Subsequently, the catalyst ratio and reaction time are adjusted based on the initial conditions for each catalyst, to establish the optimum conditions for unmodified zeolite at a temperature of 350 °C, a catalyst ratio of 3%, and a reaction time of 3 h. For nickel‐modified zeolite, the optimal conditions are found to be a temperature of 300 °C, a catalyst ratio of 3%, and a reaction time of 3 h. The catalysts exhibited the ability to form rings and facilitate hydrogenation reactions, resulting in the preparation of aromatic compounds that reach threefold their original concentration. Specifically, the concentration increases from 7.1% to 23.61% in the nickel‐modified catalyst.
Synthesis, Characterization, and Biological Activity of 5‐Chloroquinolin‐8‐ol Complexes
Authors: Abdalrazaq Sakar Mubarak , Suleiman Hamad Iyad , Saber Shihab Afraa
Published: February 2025

This study involves the preparation of various organic compounds. Ethyl2‐((5‐chloroquinolin‐8‐yl)oxy)acetate compound (S1) is synthesized by the addition of potassium carbonate to 5‐chloroquinolin‐8‐ol and ethylchloroacetate. 2‐((5‐chloroquinolin‐8‐yl)oxy)acetohydrazide (S2) are prepared by the reaction compound S1with hydrazine. Several complexes of Mannich bases are obtained by the reaction equimolar amounts of compound (S2) with the metal salt solution of cobalt and cadmium (MCln.XH2O) (S3‐S5), using ethanol as the solvent. The synthesized compounds and complexes are characterized using various spectroscopic techniques, including Fourier‐Transform Infrared (FT‐IR) spectroscopy, and nuclear magnetic resonance (1H, 13C‐NMR) spectroscopy. Additionally, their melting points, purity, molar conductivity, and magnetic susceptibility are determined. The impact of some prepared compounds and complexes on the growth of two antibiotic‐resistant bacterial strains, namely the gram‐negative Staphylococcus and the ram‐positive Escherichia coli, is studied. Amoxicillin, is used as control antibiotic. Some of the synthesized compounds exhibited significant inhibitory activity against the tested bacterial strains.
Synthesis, Characterization, and Hydrogen Storage of Novel MWCNTs–Organic Nanohybrid
Authors: Hasan Haifaa A. , Karim Muhammad Ghazi Abdul
Published: February 2025

This work included the preparation of the compound 3‐(1‐(4‐(5‐(4‐(methylthio)phenyl)‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)phenyl)‐4,5‐dihydro‐1H‐tetrazol‐5‐yl)‐1H‐indole (MPT) via a series of reactions on the indole. The prepared compound is characterized by FTIR, 1HNMR, CHN, and melting point. The final product (MPT) is used to prepare a new composite with multiwalled carbon nanotubes, the formation of which is proven by FTIR, SEM, EDX, and TEM, and which appeared in the form of nanotubes covered with nanomaterials in irregular shapes, which is the organic compound. The final nanohybrid (MPT@MWCNTs) is used to test its ability to store hydrogen, which proved that the prepared compound can store hydrogen at a weight percentage of 5 wt.% at a pressure of 100 bar.
Characteristics of the Facial Canal–Lateral Canal Dehiscence: The Under‐recognized Third Window
Authors: Garvis William J. , Johnson Blake A. , Kluesner Katherine E. , Garvis Stephanie M.
Published: February 2025

Objective

We aimed to establish normative data on the bony partition between the facial canal (FC) and the lateral semicircular canal (LSCC) and present our initial series of cases in which an FC‐LSCC dehiscence was identified based on these anatomic criteria, with or without other third window pathologies.

Study Design

Normative data: Analysis of archival otopathological human temporal bone specimens and computed tomography (CT) scans. Clinical data: Case studies.

Setting

An otopathology laboratory and a specialized otolaryngology, head and neck surgery outpatient clinic.

Methods

We measured the bony partition thickness between the FC‐LSCC in human temporal bone otopathological specimens and CT scans. The clinical study involved a series of reviews of patients with FC‐LSCC, presenting clinical data and CT images.

Results

The average thickness of the bony partition measured via CT was 0.6 mm ± 0.2 mm, whereas in otopathological specimens it was 0.56 mm ± 0.17 mm. We identified 34 patients with FC‐LSCC dehiscence. The most frequently reported symptoms were hearing loss (44%), dizziness/vertigo (44%), and tinnitus (41%). Of the patients, 15 (44%) had more than 1 site of bone dehiscence and 21 (62%) had bilateral FC‐LSCC dehiscence. We then identified 36 patients in whom only FC‐LSCC dehiscences were found and provided characteristics for this population.

Conclusion

Our study provides normative characteristics on the bony partition between the FC‐LSCC and the signs and symptoms of this third window abnormality. FC‐LSCC should be included in differential diagnoses of patients presenting with third window syndrome symptoms.