bluuebunny/crossref_metadata_2025 huggingface dataset:
Female shooters less prevalent than male shooters, motivated differently
Authors: Sutton Halley
Published: January 2025

On Dec. 16, 2024, a school shooting in Madison, WI, claimed the lives of two people and injured half a dozen others. The school shooter in that event was allegedly a 15‐year‐old girl. School shootings committed by females are rare, though not unheard of. Recent studies examine how many school shooters have been female.
Mining Silent Biosynthetic Gene Clusters for Natural Products in Filamentous Fungi
Authors: Wang Yi , Mao Xu‐Ming
Published: January 2025

Filamentous fungi are of great interest due to their powerful metabolic capabilities and potential to produce abundant various secondary metabolites as natural products (NPs), some of which have been developed into pharmaceuticals. Furthermore, high‐throughput genome sequencing has revealed tremendous cryptic NPs underexplored. Based on the development of in silico genome mining, various techniques have been introduced to rationally modify filamentous fungi, awakening the silent biosynthetic gene clusters (BGCs) and visualizing the NPs originally cryptic. This review summarizes the key strategies and research advances in the activation of cryptic BGCs in filamentous fungi, including endogenous non‐targeted activation, single‐target activation and heterologous expression. It also provides a critical evaluation of these strategies and offers perspectives on the current state of research.
Structure‐based Virtual Screening and Drug Design Development of Leishmanicidal Pyrimidines
Authors: de Oliveira Gerliny Bezerra , Santos Costa Érick Caique , Severina do Monte Zenaide , de Almeida Gleybson Correia , da Silva Falcão Emerson Peter , Scotti Luciana , Tullius Scotti Marcus , Oliveira Silva Ricardo , de Sousa Oliveira Daniele Santana , Ademar Sales Junior Policarpo , Alves Pereira Valéria Rêgo , José de Melo Sebastião
Published: January 2025

Leishmaniasis is a neglected disease caused by parasites of the genus Leishmania sp. that causes approximately 1 million cases and 650,000 deaths annually worldwide. Its treatment has several limitations mainly due to high toxicity and clinical resistance, and the search for alternatives is highly desirable. The present work aimed to design new antileishmanial compounds through a virtual screening of a small in‐house library of pyrimidine compounds, never tested against Leishmania, using the active site of trypanothione reductase (TR) as a target model. The compounds showed favorable affinity with the amino acid residues of the active site of TR. Pyr 1–9 were synthesized and tested against Leishmania amazonensis strain. Four derivatives demonstrated activity against promastigote (IC50 value between 11.23 and 91.5 µM) and three other compounds demonstrated discreet activity against amastigote, IC50 value between 81.29 and 153.21 µM. Based on the results obtained in the screening, three new pyrimidines Pyr 10–12 were designed to optimize activity, cytotoxicity, and selectivity. Pyr 10 and Pyr 11 demonstrated good activity against promastigotes, with IC50 of 11.38 ± 9.7 and 20.01 ± 13.55 µM, respectively, and improved cytotoxicity and selectivity. No activity was obtained against amastigotes. Thus, this study contributes important information for the development of new pyrimidines active against Leishmania.
Biological Efficiency of Kunzea ericoides Based On Bioactive Compounds and Impact of Extraction
Authors: Devadass Indhuja , Swift Simon , Baroutian Saeid
Published: January 2025

New Zealand is known for its diverse population of flora and fauna, of which 80 % are endemic. Māori, the indigenous people of New Zealand, have profound and holistic knowledge of plants and utilize them in medicinal, spiritual, and ecological practices. Among these, kānuka has traditionally been used for medicinal purposes. Prior in vitro studies on kānuka extracts have demonstrated promising antioxidant, antimicrobial, anti‐inflammatory, and antiproliferative properties. These studies further recommend the translation of these findings into new medicines and commercial products. However, a significant knowledge gap regarding their therapeutic potential hinders their application in various industries. A deeper understanding of the biochemical composition of the extract and the mode of interaction to exert its bioactivity in the host is vital for achieving this. Hence, this review evaluates the bioactivities of kānuka in association with its bioactive compounds (polyphenolics and terpenoids) reported in the current literature. Knowing the critical role of extraction methodologies in determining bioactive composition, we highlighted their efficiency in the bioactivities of kānuka.
Probing Native CB2 Receptor Mobility in Plasma Membranes of Living Cells by Fluorescence Recovery After Photobleaching
Authors: Ciaramellano Francesca , Leuti Alessandro , Kurtz Alexandrine D. E. , Sarott Roman , Westphal Matthias , Pfaff Patrick , Grether Uwe , Carreira Erick M , Maccarrone Mauro , Oddi Sergio
Published: January 2025

In this study, we employed a novel fluorescent probe, RO7304924—which selectively targets cannabinoid 2 receptor (CB2R)—to assess the lateral mobility of CB2R within the plasma membrane of Chinese hamster ovary cells stably expressing a functional, untagged receptor variant. Utilizing confocal fluorescence recovery after photobleaching (FRAP), we quantified the diffusion coefficient and mobile fraction of CB2R, thereby demonstrating the efficacy of RO7304924 as an innovative tool for elucidating the dynamics of this major endocannabinoid‐binding G protein‐coupled receptor. Our present findings highlight the potential of combining advanced ligand‐based fluorescent probes with FRAP for future investigations into the biochemical details of CB2R mobility in living cells, and its impact on receptor‐dependent cellular processes.
Investigating lightweight foamed concrete prepared using selected brands of detergent and cement grades
Authors: Asante‐Amankwa Michael , Andrews Anthony
Published: January 2025

Foamed concrete, a lightweight, cement slurry‐based cellular material, presents a promising solution to economic and environmental challenges in the construction industry. Its versatility spans from structural applications to thermal insulation and soundproofing, offering benefits such as low density, energy efficiency, and affordability. The study explored the feasibility of using locally sourced materials, specifically by utilizing three different powder detergents (K, M, and S) as foaming agents. These detergents were evaluated for their composition, density, and stability and then combined with two cement grades 32.5R and 42.5R. A total of 12 sample foamed concrete groups were manufactured and checked for compressive strength, density, and water absorption. The results demonstrated that all detergents in specific formulations successfully produced foamed concrete that met or exceeded the ASTM requirements of 1.4 MPa. Samples from Detergent K achieved a dry density range of 1.32–1.539 g/cm3 with 28‐day compressive strength ranges of 0.64–14.25 MPa. Samples from Detergent M produced dry densities in the range of 1.255–1.559 g/cm3 with a compressive strength range of 0.41–12.26 MPa and those from Detergent S produced dry density range of 1.061–1.394 g/cm3 with compressive strength range of 1.03–7. 75 MPa. Notably, there were correlations between the detergent's pH, the relevant oxide quantities and the foam's density and stability which together influenced the overall performance of the foamed concrete.
Molecular Structural Control of the Amorphous‐Crystalline Balance in Solids: Structure‐Phase Correlation in DADQs with Enhanced/Switchable Fluorescence
Authors: Maurya Ritesh Singh , Radhakrishnan T. P.
Published: January 2025

The amorphous/crystalline (A/C) assembly in molecular solids has a direct bearing on their attributes and applications, including mechanical, pharmaceutical, electronic and photophysical. A systematic analysis of the molecular features and interactions that determine the predilection towards the A, C or bi‐stable A‐C states is critical. This fundamental problem is addressed through an exhaustive investigation of a large family of alkoxyalkyl diaminodicyanoquinodimethanes (ROR′‐DADQs); enhancement of their fluorescence from the solution, to the A, to the C state serves as an excellent signature of the phase preference and temporal stability. Their thermal characteristics and single crystal structure investigations coupled with Hirshfeld surface analysis of the intermolecular interactions, not only confirm the spectroscopic observations, but also reveal the significant impact of the molecular structural features, key interactions like H‐bonds, and molecular orientations in the lattice, on the phase stability. These explorations lead to a basic structure‐phase correlation; its predictive power is demonstrated by identifying the borderline systems as functional phase change materials, and the subsequent verification through the reversible cycles of fluorescence switching between the A/C states. The factors promoting the A or C forms of molecular solids can guide the design of novel materials exploiting such supramolecular structures and their interconversions.
“Cofactors” for Natural Products
Authors: Chiou Shao‐Lun , Chang Chin‐Yuan , Chu John
Published: January 2025

Cofactors are non‐protein entities necessary for proteins to operate. They provide “functional groups” beyond those of the 20 canonical amino acids and enable proteins to carry out more diverse functions. Such a viewpoint is rarely mentioned, if at all, when it comes to natural products and is the theme of this Concept. Even though the mechanisms of action (MOA) of only a few natural products are known to require cofactors, we believe that cofactor mediated MOA in natural products are far more prevalent than what we currently know. Bleomycin is a case in point. It binds iron cation to form a pseudoenzyme that generates reactive oxygen species. As another example, calcium cations induce laspartomycin to “fold” into the active conformation. Iron and calcium are bona fide cofactors for bleomycin and laspartomycin, respectively, as these natural products do not display their characteristic anticancer and antibacterial activities without Fe(II) and Ca(II). These types of cofactor mediated MOA in natural products were discovered mostly serendipitously, and being conscious of such a possibility is the first step toward identifying more novel chemistry that nature performs.
Expanding the Variety of Pyridinium‐Based Bis‐QACs with Antimicrobial Properties: Investigation into Linker Structure‐Activity Correlation
Authors: Frolov Nikita A. , Tyutin Alexander A. , Tyurina Alexandra N. , Seferyan Mary A. , Detusheva Elena V. , Son Elizabeth , Saverina Evgeniya A. , Vereshchagin Anatoly N.
Published: January 2025

For decades quaternary ammonium compounds (QACs) have served as main component of a top antiseptic and disinfectant compositions. Among them, bis‐QACs are the most prominent and effective class of biocides. Although mono‐QACs still dominate the antiseptic market, their activity against Gram‐negative bacteria is largely inferior to bis‐QACs. Moreover, the new wave of bacterial resistance during the COVID‐19 pandemic is threatening the efficiency of popular antiseptics. Therefore, the requirement for novel biocides is urgent. Reported here is a unified and simple two‐step synthesis to achieve novel biocide's architectures with aromatic linkers. Thus, a series of 14 bis‐QACs have been prepared using an Ullman‐type reaction following by N‐alkylation. The most prominent compounds showed strong bioactivity against a panel of nineteen microbial pathogens, multi‐resistant bacterial ESKAPEE strains, fungi and biofilms, including strains, which acquired resistance during COVID‐19 in 2021. Moreover, significant improvements in antibiofilm action were observed, where bis‐QACs 5 c and 6 a outperformed gold standard pyridinium antiseptic octenidine. These findings will serve as a good basis for further studies of bis‐QACs architectures as highly effective biocides.
Theoretical Study of the Reversible Hydrogenation of Carbon Dioxide to Formate on Mn‐Pincer Complexes
Authors: Yao Lihua , Meng Lingqiang , Gong Pengcheng , Li Jun , Zhou Yu
Published: January 2025

Recently, Beller and coworkers reported a study on the reversible hydrogenation of CO2 to formic acid using a Mn(I)−PN5P complex. In this paper, we performed DFT calculations to understand the mechanism for this reversible reaction occurring on the Mn−PN5P, Mn−PN3P, and Mn−PNP catalysts. Through investigating in detail two possible routes for CO2 hydrogenation to formic acid, we noticed that the production of formic acid is not thermodynamically favorable. The CO2 reversible hydrogenation actually takes place between CO2/H2 and formate rather than formic acid, although in the beginning of the process formic acid is used. By comparing three pincer ligands (PN5P, PN3P, and PNP), it can be found that the Mn−PN3P and Mn−PNP complexes are favorable for the dehydrogenation of formic acid, but relatively unfavorable for the hydrogenation of CO2. Only the PN5P ligand can balance the forward and reverse reactions, showing the best catalytic activity for CO2 reversible hydrogenation to formic acid. Our computational results support the experimental work of Beller and coworkers and can explain the advantage of the PN5P ligand. This paper could be of benefit for promoting the application of the PN5P ligand in realizing the reversible H2 storage‐release cycle.
Congestion Control Scheme for Link Quality Improvement Using Bio‐Inspired Fuzzy Inference System–Based CoAP in IoT
Authors: Yadav Raveena , Kumar Vinod
Published: January 2025

The Internet of Things (IoT) represents the Internet's future by including devices that can connect with one another. IoT devices in IoT networks collect data from their surroundings and send it in bursts to a server in a remote location. The quantity of applications using computer networks causes resource competition, which in turn causes congestion. The most difficult task in enhancing network quality of service (QoS) is IoT congestion control. For IoT items with modest resource requirements, various protocols have arisen. Different shortages and issues affect basic congestion control, which increases bandwidth use, data loss, and delay. Thus, to solve this issue, in this paper, we propose a bio‐inspired fuzzy inference system (FIS)–based constrained application protocol (BIFIS‐CoAP) for avoiding congestion over network. In order to determine the level of congestion, we use the bottleneck bandwidth gradient (BG‐gradient) and round‐trip time gradient (RT‐gradient) as inputs for BIFIS‐CoAP. By using this indication, BIFIS‐CoAP may anticipate impending congestion and alter the sending rate to prevent it. In order to achieve high performance for burst data transfer, BIFIS‐CoAP constantly checks for bandwidth that is available and uses the congestion degree for updating the variable retransmission time out (RTO) for retransmissions. Using the adaptive Tasmanian devil optimization method (ATDO), input parameters like the RT‐gradient and BG‐gradient are modified to enhance the performance of the FIS. Numerous simulation studies have shown that BIFIS‐CoAP is feasible, and the simulation results show that it performs better than basic CoAP and fuzzy CoAP in terms of delay, throughput, delivery ratio, and retransmissions.
Exploring the relationship between melanopsin gene variants, sleep, and markers of brain health
Authors: Milligan Armstrong Ayeisha , O'Brien Eleanor , Porter Tenielle , Dore Vincent , Bourgeat Pierrick , Maruff Paul , Rowe Christopher C. , Villemagne Victor. L. , Rainey‐Smith Stephanie R. , Laws Simon M. ,   the AIBL Research Group
Published: January 2025

INTRODUCTION

Melanopsin is a photopigment with roles in mediating sleep and circadian‐related processes, which are often disrupted in Alzheimer's disease (AD). Melanopsin also impacts cognition and synaptogenesis. This study investigated the associations between melanopsin genetic variants, sleep, and markers of brain health.

METHODS

Linear regression analyses examined the relationship of single‐nucleotide polymorphisms (SNPs) within the melanopsin gene (OPN4), with cortical amyloid beta (Aβ), cognition, brain volumes, and self‐reported sleep traits in cognitively unimpaired older adults. Further analyses assessed whether sleep traits x OPN4 SNP interactions were associated with markers of brain health.

RESULTS

OPN4 SNPs rs2355009 and rs3740334 were associated with attention and processing speed and ventricular volume and language, respectively. Furthermore, rs3740334 and rs1079610 showed significant interactions with sleep traits in association with language.

DISCUSSION

This study shows associations of OPN4 genetic variants with markers of brain health, and suggests that these variants interact with sleep to exacerbate cognitive effects.

Highlights

The relationships between melanopsin gene (OPN4) variants and markers of brain health were examined cross‐sectionally in cognitively unimpaired older individuals.

Variation within OPN4is associated with differences in cognition and ventricular volume.

rs2355009 and rs3740334 show small–moderate associations with differences in attention and processing speed. Further to this, rs2355009 and rs3740334 were associated with ventricular volumes and language performance, respectively.

The interactions between rs3740334 and rs1079610 and sleep traits also showed small–moderate associations with differences in language performance.
Incidence of dementia in the German Heinz Nixdorf Recall study over 20 years
Authors: Schramm Sara , Rinck Charlotte , Krizanovic Nela , Jöckel Karl‐Heinz , Hüsing Anika , Gronewold Janine , Hermann Dirk , Schmidt Börge , Stang Andreas , Jokisch Martha
Published: January 2025

INTRODUCTION

The aim of the study was to estimate the population‐based dementia incidence in Germany over a period of two decades.

METHODS

We analyzed data from 4814 participants of the population‐based Heinz Nixdorf Recall study (49.8% men, 45–75 years at baseline period 2000–2003), who have been monitored for the occurrence of cognitive decline and dementia. We calculated the cumulative incidence of dementia and its major subtypes and the incidence rate per 1000 person‐years over two decades.

RESULTS

During a median follow‐up of 18.2 (Q1–Q3: 11.3–20.6) years, a total of 298 participants (6.2%) developed dementia (22.1% Alzheimer´s disease, 23.5% vascular dementia, 15.1% mixed dementia, 9.1% other dementia, 30.2% unspecified). The overall incidence rate was 3.9 per 1000 person‐years.

DISCUSSION

Our study is the only current population‐based study in Germany that estimates the incidence of dementia. In order to reduce the high proportion of unspecific dementia diagnoses, diagnostics urgently need to be improved.

Highlights

New data on the incidence of dementia in Germany in participants ≥45 years of age.

Participants have been monitored for dementia incidence over two decades.

The overall incidence in our cohort was 3.9 per 1000 person‐years.

Many patients had unspecific dementia diagnoses in their medical records.

Further diagnostic evaluation should be available for all dementia patients.
Comparison of Demographic Life‐History Traits of the Snake‐Eyed Skink: Observations From an Island and a Mainland Population
Authors: Ağdağ Mehtap , Yıldız Mehmet Zülfü , Altunışık Abdullah
Published: January 2025

The life‐history traits of animals are influenced by several factors. It has been proposed that key factors such as competition, predation pressure, and resource availability may differ between mainland and island populations of the same species. In this context, our study focused on an island (Yayla, Cyprus) and mainland (Hassa, Türkiye) populations of the snake‐eyed skink, Ablepharus budaki. This study aimed to reveal both intra‐population and inter‐population relationships in terms of mean age, longevity, age at maturity, body size, and sexual dimorphism. Our results show that lizards in the island population had longer lifespans and higher mean ages than the mainland population. Nevertheless, both populations were comparable in terms of mean body size. We also concluded that island individuals reach sexual maturity approximately 1 year later than their mainland conspecifics, and sexual dimorphism in terms of size is observed only in the mainland population. This study, offering initial demographic insights into the non‐mainland population of the species, provides the reason for additional research in this field.
Reliability Assessment of an Improved Single‐Input Switched‐Capacitor Boost 7/9‐Level Inverter Suitable for Renewable Energies
Authors: Ghelichi Armin , Varesi Kazem , Khoubrooy Eslamloo Milad
Published: January 2025

This paper proposes an improved single‐source switched‐capacitor inverter that can operate either as 7 or 9‐level inverter based on its capacitors' charging scenario. The proposed inverter utilizes single DC supply, two capacitors, ten switches (all unidirectional) and a single diode to provide a triple/quadruple boosting factor in its seven/nine‐level operation mode. In 7‐level (7 L) operation mode, both the capacitors are charged to identical voltage value (equal to the source voltage), but in 9‐level (9 L) mode, the capacitors are charged to different voltages. Any load type with variety of power factors can be supplied by the proposed inverter. The capacitors' impulsive charging current issue has been solved by employing compact (small‐inductor based) and low‐cost soft‐charging L‐D cells. The reliability assessments have also been performed on the proposed 7/9‐level inverter. The superiority of the proposed inverter over its similar counterparts have been verified by comprehensive comparative analysis. The experimental outcomes have also been provided to make sure of correct performance of proposed inverter.
Low‐Carbon Dispatch of Integrated Energy Systems Considering Solar Thermal Coupled Combined Heat and Power Units
Authors: Lv You , Li Zeyang , Deng Dan , Shi Yijun , Sun Hao , Wang Tenghui
Published: January 2025

To reduce carbon emissions of an integrated energy system (IES), and decrease curtailment of wind and solar energy due to the “power determined by heat” characteristics of combined heat and power (CHP) units, this paper proposes a low‐carbon and economic optimal scheduling model of an IES that considers solar thermal coupled with CHP. First, to alleviate the coupling of heat and electric power, a solar thermal collector (STC)‐CHP unit model is developed by integrating an STC unit with the traditional CHP unit in the IES. In addition, hydrogen energy utilization equipment, including hydrogen fuel cell (HFC), hydrogen storage (HS), is introduced based on the traditional power‐to‐gas (P2G) process, to fully exploit the value of hydrogen. Meanwhile, the carbon capture system (CCS) is considered in the IES to reduce the carbon emission. Next, a low‐carbon economic dispatch model of the STC‐CHP‐P2G‐CCS coupled IES is established considering the reward and punishment ladder‐type carbon trading (RPLCT) mechanism, aiming to minimize economic costs. The proposed model is solved by programming the CPLEX solver through the YALMIP toolbox. Finally, two categories of scenarios simulation are set up to evaluate the proposed IES and its dispatch strategy. Results show that the total daily operating cost of the proposed system amounts to 8.6525 million RMB, marking a significant reduction of 8.2695 million RMB compared to the basic system. This substantial saving not only covers but also exceeds the daily investment cost of 1.8561 million RMB required for the new equipment, demonstrating a certain level of economic viability. In addition, the system achieves a 100% renewable energy accommodation rate, and carbon emissions are reduced by 2596.3 tons by incorporating the RPLCT mechanism, achieving negative carbon emissions.
Achieving National Food Security in Sub‐Saharan African Countries: The Role of Foreign Agricultural Aid
Authors: Balcilar Mehmet , Olasehinde‐Williams Godwin , Tokar Berkan
Published: January 2025

African policymakers have astutely prioritized agricultural expenditure as a crucial strategy to address food insecurity in the continent. However, the available financial resources are insufficient to achieve this objective. Foreign agricultural aid has been proposed as a viable supplement to domestic resource mobilization efforts in bridging the resource deficit. This article investigates the food security implications of sector‐specific aid (agricultural aid) between 1990 and 2020, thus broadening the current understanding. By considering the heterogeneous nature of SSA, this study delves deeper into the relationship between foreign agricultural aid and food security in the region. It investigates both panel and country‐specific causal relationships, providing a more nuanced understanding of the subject. Quantile panel‐type regressions are employed. Coefficients from the fixed effects and random effects with Driscoll–Kraay standard errors are also reported. Additionally, causal linkages between foreign agricultural aid and food security are examined through panel causality testing with bootstrapping. Findings show that agricultural aid contributes to closing the resource gap and improving food security. Also, the effectiveness of agricultural aid is greater when food security is relatively poor, and its impact diminishes as food security improves. Causal relationships suggest that agricultural aid is a determinant of food security. The level of food security is also an indicator of agricultural aid inflows. Thus, strategies such as population control, poverty reduction, and increased access to agricultural land can enhance food security.
Housing Relocation and Residential Satisfaction After Relocation: Effects of Dwelling Condition Changes on Older Adults in the Community
Authors: Park Gum‐Ryeong , Seo Bo Kyong , Namkung Eun Ha
Published: January 2025

Background

This study seeks to analyze the trajectories of residential satisfaction among older adults before and after relocation and explore the variability in the relationship between relocation and residential satisfaction based on changes in housing conditions during the relocation process.

Methods

Utilizing a nationally representative longitudinal dataset of older adults (N = 2718), this study employs individual‐level fixed effect regression models to estimate the association between the timing of relocation and residential satisfaction. Stratified analyses are also conducted to explore how this association varies based on changes in housing conditions.

Results

Residential satisfaction tends to decrease before relocation, peaks at the time of relocation, and maintain higher levels as older adults adapt to their new environment. This adaptation process varies depending on changes in dwelling conditions during relocation, with transitions from poor to non‐poor housing conditions positively affecting psychological responses, while moves from non‐poor to poor conditions can lead to increased psychological burden and prolonged adjustment periods.

Discussion

Aging policies can prioritize programs that facilitate adjustment to new environments to improve residential satisfaction of older adults, thereby promoting healthy aging.
Idecabtagene vicleucel or ciltacabtagene autoleucel for relapsed or refractory multiple myeloma: An international multicenter study
Authors: Merz Maximilian , Albici Anca‐Maria , von Tresckow Bastian , Rathje Kristin , Fenk Roland , Holderried Tobias , Müller Fabian , Tovar Natalia , Oliver‐Cáldes Aina , Vucinic Vladan , Kharboutli Soraya , Bärmann Ben‐Niklas , Ayuk Francis , Platzbecker Uwe , Stölzel Friedrich , Schub Nathalie , Schmitz Friederike , Fandrei David , Born Patrick , Khandanpour Cyrus , Hanoun Christine , Hörster Keven , Teichert Marcel , Jeker Barbara , Hoffmann Michele , Kröger Nicolaus , de Larrea Carlos Fernández , Pabst Thomas , Gagelmann Nico
Published: January 2025

Idecabtagene vicleucel (ide‐cel) and ciltacabtagene autoleucel (cilta‐cel) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM), but direct comparisons are lacking. Leveraging an international multicenter RRMM cohort, we compared the outcome of ide‐cel (n = 162) versus cilta‐cel (n = 42). Co‐primary efficacy endpoints of the study were overall response rate (ORR) and progression‐free survival (PFS). Co‐primary safety endpoints were the incidence of cytokine release syndrome (CRS) and immune‐effector cell‐associated neurotoxicity syndrome (ICANS). Median turnaround time between apheresis and infusion was 47 days for ide‐cel versus 68 days for cilta‐cel (p < 0.001). Cilta‐cel showed significantly higher ORR (93% vs. 79%; p < 0.001), with complete response at Day 30 of 48% versus 26% (p < 0.001). The 10‐month PFS and overall survival (OS) was 82% and 90% for cilta‐cel versus 47% and 77% ide‐cel (p < 0.001 and p = 0.06), and improved outcome for cilta‐cel was confirmed after multivariable adjustment. Incidence of CRS and ICANS appeared similar (81% and 19% for cilta‐cel versus 85% and 19% for ide‐cel), while 10% and 7% in the cilta‐cel group versus 4% and 2% in the ide‐cel group showed severe CRS and ICANS grade 3–4, with CRS occurring significantly earlier for ide‐cel (median, 2 days vs. 4 days; p < 0.001). Nonrelapse mortality was 5% for cilta‐cel versus 3% for ide‐cel (p = 0.51). Cilta‐cel showed later peak of CAR‐T expansion at Day 14 versus Day 7 for ide‐cel, while cilta‐cel expansion was associated with ICANS. Our study provides real‐world evidence that cilta‐cel was associated with superior outcomes and distinct cellular dynamics versus ide‐cel in triple‐class exposed RRMM.
Identification of SETD4 as an Onco‐Immunological Biomarker Encompassing the Tumor Microenvironment, Prognoses, and Therapeutic Responses in Various Human Cancers
Authors: Zhong Yuyun , Wang Ruiqi , Huang Zijie , Hu Zhaoting , Peng Bin , Chen Bin , Sun Liyue
Published: January 2025

Background

SET domain‐containing protein 4 (SETD4) is a histone methyltransferase that has been shown to modulate cell proliferation, differentiation, and inflammatory responses by regulating histone H4 trimethylation (H4K20me3). Previous reports have demonstrated its function in the quiescence of cancer stem cells as well as drug resistance in several cancers. A limited number of systematic studies have examined SETD4's role in the tumor microenvironment, pathogenesis, prognosis, and therapeutic response.

Methods

Utilizing The Cancer Genome Atlas database, and other publicly accessible platforms, we comprehensively analyzed SETD4 gene expression, methylation patterns, and prognostic significance. Furthermore, we investigated its association with cancer‐related pathways, the immune microenvironment, immunotherapy markers, and drug resistance signatures of chemotherapy. Additionally, qRT‐PCR was performed to validate SETD4 expression in clinical specimens.

Results

The expression of SETD4 was abnormal across a variety of cancer types and the expression of SETD4 in colorectal cancer tissues was verified in clinical specimens. The upregulation of SETD4 may be a prognostic risk factor predicting poor overall survival and progression‐free survival. The analysis revealed that the mRNA level of SETD4 was modulated by promoter methylation, and patients with lower methylation levels showed shorter survival times. Pathway analysis showed that SETD4 influenced several key cell cycle pathways, including the G2M checkpoint, and mitotic spindle pathways. In addition, SETD4 negatively affects immune cell infiltration in most cancers, including B cells, CD8 T cells, and macrophages. The correlation between SETD4 and cancer stemness as well as homologous recombination deficiency varied across tumor types, suggesting that SETD4 may play a multifaceted role in tumor resistance. Notably, we identified several potential agents targeting SETD4.

Conclusions

This study demonstrates that SETD4 is an immune‐oncogenic molecule in multiple cancers, with the potential to be a diagnosis, prognosis, and targeted therapy marker.
Tinagl1 restores tamoxifen sensitivity and blocks fibronectin‐induced EMT by simultaneously blocking the EGFR and β1‐integrin/FAK signaling pathways in tamoxifen‐resistant breast cancer cells
Authors: Yuan Jie , Yuan Li , Yang Li , Chinnathambi Arunachalam , Alharbi Sulaiman Ali , Huang Jun , Wang Bei , Zhang Shuqi , Wei Changsheng , Luo Chengyu
Published: January 2025

Tamoxifen (TAM) is employed to treat premenopausal ER‐positive breast cancer patients, but TAM resistance is the main reason affecting its efficacy. Thus, addressing TAM resistance is crucial for improving therapeutic outcomes. This study explored the potential role of Tinagl1, a secreted extracellular matrix protein, whose expression is compromised in TAM‐resistant MCF‐7 breast cancer cells (MCF‐7R). We discovered that Tinagl1 plays a pivotal role in countering TAM resistance by inhibiting the EGFR and β1‐integrin/focal adhesion kinase (FAK) signaling pathways, both of which are abnormally activated in MCF‐7R cells and contribute to the resistance mechanism. Our data showed that the expression level of Tinagl1 in MCF‐7R cells was lower compared to their wild‐type counterparts, and TAM could further reduce Tinagl1 expression in MCF‐7R cells, which was consistent with our microarray results. Moreover, Tinagl1 could restore the sensitivity of MCF‐7R cells to TAM and inhibit the motility of MCF‐7R cells by regulating epithelial‐mesenchymal transition (EMT) in vitro and in vivo experiments. In addition, the level of Tinagl1 in TAM‐resistant breast cancer samples was significantly lower than that in their matched primary tumors. Analysis of an online database further indicated that high Tinagl1 expression correlates with better recurrence‐free survival (RFS), particularly in patients with ER‐positive, HER2‐negative breast cancer. Overall, this study positions Tinagl1 not only as a potential prognostic marker but also as a promising therapeutic target.
Deciphering the Role of Calcium Signaling Pathway‐Associated Single Nucleotide Variants in Susceptibility to Hypertension
Authors: Sharifi Armin , Azimi Azam , Alibakhshi Reza , Rahimi Zohreh , Jalilian Nazanin
Published: January 2025

Background

As a complex disease, hypertension (HTN) is influenced by both genetic and environmental factors and their interaction. The calcium signaling pathway is known to be involved in the regulation of blood pressure, and dysfunction in this pathway may contribute to the development of hypertension. Genome‐wide association studies (GWAS) have identified several genes in the calcium signaling pathway associated with susceptibility to HTN, including PLCB1, ATP2B1, and ADRB1. The aim of this study was to investigate the possible association between single nucleotide variants (SNVs) in the calcium signaling pathway and HTN.

Methods

We genotyped three SNVs: rs1801253 (ADRB1), rs6108168 (PLCB1), and rs17249754 (ATP2B1) in a population of 131 patients with hypertension and 115 healthy controls from Kermanshah province, Iran.

Results

Our results showed a strong and significant association between the G allele and the GG and CG genotypes of the rs1801253 variant in the ADRB1 gene and susceptibility to hypertension. However, no significant association was found for the other two SNVs. In addition, the presence of the GCG haplotype (alleles from left to right: rs1801253, rs6108168, and rs17249754) appeared to confer a protective role against HTN.

Conclusion

This study has made a significant contribution towards enhancing the comprehension of hypertension development, as well as the early identification of individuals who are at risk.
Weight and Blood‐Based Markers of Cachexia Predict Disability, Hospitalization and Worse Survival in Cancer Immunotherapy Patients
Authors: Tran Steven D. , Forrest Noah J. , Guggilla Vijeeth , Perottino Geovanni M. , Johnson Jodi L. , Sosman Jeffrey , Roy Ishan , Walunas Theresa L.
Published: January 2025

Background

Cancer‐associated cachexia can inhibit immune checkpoint inhibitor (ICI) therapy efficacy. Cachexia's effect on ICI therapy has not been studied in large cohorts of cancer patients aside from lung cancer. We studied associations between real‐world routinely collected clinical cachexia markers and disability‐free, hospitalization‐free and overall survival of cancer patients.

Methods

A retrospective study was conducted of electronic health records (EHR) of patients with lung, renal cell, melanoma and other cancers treated with ICI therapy at Northwestern Medicine of Chicago, IL, United States, between March 2011 and January 2022. Weight, body mass index, absolute neutrophil and lymphocyte counts, albumin and C‐reactive protein (CRP) measures were analysed to calculate the Fearon consensus criteria for cachexia, weight loss grading system (WLGS) score, neutrophil‐lymphocyte ratio (NLR), Prognostic Nutritional Index (PNI) and modified Glasgow Prognostic Score (mGPS) at ICI therapy initiation. Kaplan–Meier and Cox proportional hazards analyses were used to determine associations between these metrics and disability‐free, hospitalization‐free and overall survival.

Results

EHR analysis uncovered 3285 cancer patients on ICI therapy (54% > 65 years of age, 50.7% male, 77.7% White). At ICI therapy initiation, 1282 (39.0%) patients had cachexia (consensus criteria), 1641 (50.0%) had a WLGS score ≥ 2, 1806 (55.0%) had an NLR > 3, 1087 (33.1%) had albumin < 3.5 g/dL and 1318 (40.1%) had a PNI < 44. Missing measurements included CRP missing for 98.2% and mGPS missing for 98.6% of patients. Disability‐free (n = 1373), hospitalization‐free (n = 2374) and overall survival (n = 1599) events were analysed with 1‐year rates of 65% (64%–67%), 35% (34%–37%) and 65% (63%–66%), respectively. Multivariate Cox model analyses showed hazard ratios (HR) for cachexia at 1.58 (95% CI 1.38–1.80), 1.47 (95% CI 1.33–1.63) and 1.97 (95% CI 1.75–2.23) for disability, hospitalization and death, respectively. HRs for WLGS ≥ 2 were 1.45 (95% CI 1.28–1.66), 1.37 (95% CI 1.24–1.51) and 1.91 (95% CI 1.69–2.17). HRs for NLR > 3 were 1.57 (95% CI 1.35–1.83), 1.40 (95% CI 1.25–1.58) and 1.95 (95% CI 1.67–2.27). HRs for albumin < 3.5 g/dL were 1.33 (95% CI 1.15–1.54), 1.67 (95% CI 1.50–1.86) and 2.09 (95% CI 1.84–2.36). HRs for PNI < 44 were 1.60 (95% CI 1.39–1.84), 1.46 (95% CI 1.31–1.63) and 2.07 (95% CI 1.80–2.37).

Conclusions

Fearon consensus criteria, WLGS, NLR, albumin and PNI were routinely collected at ICI initiation in regular clinical practice and predictive of worse disability‐free, hospitalization‐free and overall survival in cancer patients receiving ICI therapy. These routine clinical measures may aid prognostication and decision‐making in cancer patients with cachexia.
Helminth extracellular vesicles co‐opt host monocytes to drive T cell anergy
Authors: Borup Anne , Sharifpour Mohammad Farouq , Rossen Litten S. , Whitehead Bradley , Boysen Anders T. , Olesen Rikke , Bohn Anja B. , Ridolfi Andrea , Brucale Marco , Valle Francesco , Paolini Lucia , Radeghieri Annalisa , Bergese Paolo , Miles Kim , Veitch Margaret , Thomas Tamara , Ruscher Roland , Wangchuk Phurpa , Giacomin Paul , Loukas Alex , Nejsum Peter
Published: January 2025

Parasitic helminths secrete extracellular vesicles (EVs) into their host tissues to modulate immune responses, but the underlying mechanisms are poorly understood. We demonstrate that Ascaris EVs are efficiently internalised by monocytes in human peripheral blood mononuclear cells and increase the percentage of classical monocytes. Furthermore, EV treatment of monocytes induced a novel anti‐inflammatory phenotype characterised by CD14+, CD16−, CC chemokine receptor 2 (CCR2−) and programmed death‐ligand 1 (PD‐L1)+ cells. In addition, Ascaris EVs induced T cell anergy in a monocyte‐dependent mechanism. Targeting professional phagocytes to induce both direct and indirect pathways of immune modulation presents a highly novel and efficient mechanism of EV‐mediated host‐parasite communication. Intra‐peritoneal administration of EVs induced protection against gut inflammation in the dextran sodium sulphate model of colitis in mice. Ascaris EVs were shown to affect circulating immune cells and protect against gut inflammation; this highlights their potential as a subject for further investigation in inflammatory conditions driven by dysregulated immune responses. However, their clinical translation would require further studies and careful consideration of ethical implications.
Evidence‐Based De‐Escalation of Radiotherapy in Locally Advanced Rectal Cancer
Authors: Ballal Devesh S. , Saklani Avanish P.
Published: January 2025

Advancements in cancer care have significantly extended the life expectancy of rectal cancer patients and the impact of treatment‐related toxicity on long‐term quality of life has become a crucial factor in determining the most suitable type of neoadjuvant therapy, particularly for patients who are likely to undergo surgery. While radiotherapy has traditionally been regarded as the cornerstone for achieving improved local control in rectal cancer, it is accompanied by a range of associated complications, including bowel and bladder dysfunction, gonadal ablation, and Low Anterior Resection Syndrome. De‐escalation of treatment is undoubtedly beneficial for many patients, and this approach should be tailored to consider their expectations while prioritizing patient care in decision‐making. Although there is inadequate data to support the oncologic safety of a watch‐and‐wait approach without radiation or to omit radiation in patients with suspicious lateral pelvic lymph nodes, sufficient evidence exists to justify de‐escalation by avoiding radiation before surgery in many other patients who respond well to chemotherapy.
A Packaged MISL Dual‐Band Unequal‐Order Bandpass Filter Using Hybrid Resonant Cells
Authors: Wu Yi , Ma Kaixue , Yin Ming
Published: January 2025

In this paper, we present an unequal‐order bandpass filter (BPF) using packaged multilayer metal‐integrated suspended line (MISL) technology. Our proposed multimode hybrid resonant cells combine high‐ patches and slotline modes, allowing for the achievement of three independent controllable frequencies and compact sizes. The key advantage of this resonator is the ability to collect and utilize different resonance modes, enabling the design of unequal‐order dual‐band BPFs. To validate the effectiveness of the proposed concept, a series of filters with unequal orders were simulated. Additionally, a filter (third‐order for the first passband and sixth‐order for the second passband) was designed, simulated, and tested. The test results demonstrated that the unequal‐order filters proposed by us possess advantages of wide bandwidth, low loss, and unequal‐order filtering responses.
Compact/Deep and Wide Harmonic Suppressed Filtering Wilkinson Power Divider
Authors: Kumar Mukesh , Sen Gobinda , Parui S. K. , Das S.
Published: January 2025

This letter presents a filtering Wilkinson power divider (WPD) with good in‐band and out‐of‐band performance based on a filtering impedance inverter (FII). The FII consists of a high‐pass filter (HPF) and a low‐pass filter (LPF). This FII is capable to produce a required value of phase shift at the designed frequency and matched with any impedance value. To validate this, the quarter wavelength lines of conventional WPD having an impedance of 70.7 Ω are replaced by FII. Therefore, the proposed power divider provides bandpass response and power division simultaneously within a small circuit area. The physical area of the proposed power divider occupies only 30% (0.12λg × 0.16λg, where λg is guided wavelength) circuit area of the conventional WPD. Moreover, the in‐band return loss and isolation were better than 30 dB and the out‐of‐band rejection level was better than −25 dB up to 6.5f0 obtained.
Three‐dimensional high‐isotropic‐resolution MR fingerprinting optimized for 0.55 T
Authors: Cao Xiaozhi , Liao Congyu , Zhu Zheren , Li Zhitao , Bhattacharjee Rupsa , Nishmura Mark , Wang Zhixing , Wang Nan , Zhou Zihan , Chen Quan , Abraham Daniel , Majumdar Sharmila , Villanueva‐Meyer Javier , Yang Yang , Setsompop Kawin
Published: January 2025

Purpose

To provide a fast quantitative imaging approach for a 0.55T scanner, where signal‐to‐noise ratio is limited by the field strength and k‐space sampling speed is limited by a lower specification gradient system.

Methods

We adapted the three‐dimensional spiral projection imaging MR fingerprinting approach to 0.55T scanners, with additional features incorporated to improve the image quality of quantitative brain and musculoskeletal imaging, including (i) improved k‐space sampling efficiency, (ii) Cramér‐Rao lower bound optimized flip‐angle pattern for specified T1 and T2 at 0.55 T, (iii) gradient trajectory correction, (iv) attention‐based denoising, and (v) motion estimation and correction.

Results

The proposed MRF acquisition and reconstruction framework can provide high‐quality 1.2‐mm isotropic whole‐brain quantitative maps and 1‐mm isotropic knee quantitative maps, each acquired in 4.5 min. The proposed method was validated in both phantom and in vivo brain and knee studies.

Conclusion

By proposing novel methods and integrating advanced techniques, we achieved high‐isotropic‐resolution MRF on a 0.55T scanner, demonstrating enhanced efficiency, motion resilience, and quantitative accuracy.
The Rule Rather Than the Exception! Multi‐Predator Actualistic Accumulations From Cau del Duc (Lleida, Spain) and Their Implications for the Interpretation of the Archaeopaleontological Record
Authors: Mignino Julián , Rufà Anna , Alonso Goizane , Arilla Maite , Blasco Ruth
Published: January 2025

Numerous zooarchaeological cases have reported the presence of more than one type of predator as causal agents in the formation of the bone record in karstic contexts. However, modern analogs capable of supporting these interpretations from actualistic cases are practically nonexistent. In this paper, we present the analysis of a leporid assemblage accumulated in a cave where the action of different non‐human predators converged. The exhaustive taphonomic analyses suggest that these remains were accumulated by more than one type of predator as the majority product of non‐ingested remains. In comparison with other studies carried out at the same site, we could affirm that the genesis of this assemblage is due to the predatory action of nocturnal birds of prey and carnivorous mammals that carried their prey to this cave. We discuss these results and provide information to enrich archaeological and paleontological studies in contexts with combined taphonomic problems.