bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of dementia in patients with age‐related medical conditions: a retrospective cohort study
Authors: Kim Hee‐Cheol
Published: November 2024

Objective

This retrospective cohort study aimed to investigate the impact of age‐related medical conditions on the incidence of dementia, considering factors such as hypertension, diabetes mellitus, cerebrovascular disease, cardiovascular disease, chronic kidney disease, osteoarthritis, osteoporosis, chronic obstructive pulmonary disease, and hearing difficulties.

Methods

Data from 513 640 patients at Keimyung University Dongsan Hospital were analyzed using the Observational Medical Outcomes Partnership Common Data Model. Patients with and without age‐related medical conditions were assigned to experimental and control groups, respectively, with propensity score matching. Cox proportional hazards models assessed the association between each condition and dementia incidence.

Results

Hypertension, diabetes mellitus, cerebrovascular disease, cardiovascular disease, chronic kidney disease, osteoarthritis, osteoporosis, and hearing difficulties were associated with increased dementia risk. Chronic obstructive pulmonary disease showed no significant association with increased risk of dementia. Incidence rates ranged from 4.52 to 8.05 per 1000 person‐years in the control group and 7.46 to 14.99 per 1000 person‐years in the experimental group. Hazard ratios ranged from 1.38 to 2.36.

Conclusions

The study highlights the importance of managing age‐related medical conditions to mitigate dementia risk. Understanding these risk factors can inform preventive strategies and improve cognitive health outcomes. Problems with deidentification data analysis and the need for further multicentred studies are among the limitations of this study.
Validation of current commercially‐available devices to thaw pooled, solvent/detergent‐treated human plasma
Authors: Heger Andrea , Gareis Michelle
Published: November 2024

Background

Proper thawing procedures are required to preserve the quality of human fresh frozen plasma (FFP). octaplasLG (Octapharma AG, Switzerland) is a frozen solution of solvent/detergent (S/D)‐treated human plasma, produced to improve pathogen safety. This study aimed to validate the S/D plasma thawing process using the latest‐generation of commercially‐available thawing devices and to determine S/D plasma quality after thawing.

Study Design and Methods

Thawing of S/D plasma units was investigated using a microwave oven (Transfusio‐therm 3000) and dry tempering systems (SAHARA 4 and Plasmatherm V). Times to defrost plasma and reach 30°C product temperature, using the 37°C thawing programmes, were defined for all devices. Thawed S/D plasma units were tested against product release parameters, as well as for hemostatic capacity tested indirectly via global coagulation parameters, coagulation factors, protease inhibitors and markers of activated coagulation.

Results

The fastest thawing was observed using the microwave oven; S/D plasma units were defrosted after 2–3 min. All S/D plasma units thawed by the different devices using optimised thawing conditions were clear and free of solid and gelatinous particles, indicating no local overheating or protein denaturation. Coagulation factor and inhibitor activities and hemostatic capacity of S/D plasma were comparable when thawed by the three different devices. With each device, all product parameters were within product release specification levels after thawing.

Conclusions

S/D plasma can be thawed using the Transfusio‐therm 3000, SAHARA 4 or Plasmatherm V thawing devices using the optimised settings defined for this plasma product, with no negative influence on plasma quality.
ERD14 regulation by the HY5‐ or HY5‐MED2 module mediates the cold signal transduction of asparagus bean
Authors: Liang Le , Sui Xiyu , Xiao Jiachang , Tang Wen , Song Xueping , Xu Zeping , Wang Dong , Xie Minghui , Sun Bo , Tang Yi , Huang Zhi , Li Huanxiu
Published: November 2024

Cold stress affects the growth, development, and yield of asparagus bean (Vigna unguiculata subsp. sesquipedalis). Mediator (MED) complex subunits regulate the cold tolerance of asparagus bean, but the underlying regulatory mechanisms remain unclear. Here, VunMED2 positively responds to cold stress of asparagus beans. Under cold acclimation and freezing treatment, the survival rate, ROS scavenging activity, and expression levels of VunMED2 were increased in VunMED2 transgenic plants. Natural variation in the promoter of VunMED2 in two different cold‐tolerant asparagus beans was observed. Under cold stress, the expression of the GUS reporter gene was higher in cold‐tolerant plants than in cold‐sensitive plants, and the expression of the GUS reporter gene was tissue‐specific. VunHY5 positively influenced the expression of VunMED2 by binding to the E‐box motif, and the transcriptional activation of the promoter was stronger in the cold‐tolerant variety than in cold‐sensitive plants. VunHY5 overexpression improved plant freezing resistance by increasing the antioxidant capacity and expression of dehydrin genes. VunHY5 and VunMED2 play a synergistic role in binding to the G‐box/ABRE motif and transcriptionally activating the expression of VunERD14. VunERD14 complemented the med2 mutant, which could positively respond to plant freezing resistance by reducing membrane lipid peroxidation and improving the antioxidant capacity. Therefore, the VunHY5‐VunERD14 module and the VunHY5‐VunMED2‐VunERD14 positive cascade effect are involved in the cold signal transduction in asparagus bean. Our findings have implications for the breeding of asparagus bean varieties with improved cold tolerance.
The miR319‐based repression of SlTCP2/LANCEOLATE activity is required for regulating tomato fruit shape
Authors: Carvalho Airton , Vicente Mateus H. , Ferigolo Leticia F. , Silva Eder M. , Lira Bruno Silvestre , Teboul Naama , Levy Matan , Serrano‐Bueno Gloria , Peres Lazaro E. P. , Sablowski Robert , Schommer Carla , Valverde Federico , Rossi Magdalena , Ori Naomi , Nogueira Fabio T. S.
Published: November 2024

Fruit morphogenesis is determined by the coordination of cell division and expansion, which are fundamental processes required for the development of all plant organs. Here, we show that the regulation of TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) LANCEOLATE (TCP2/LA) by miR319 is crucial for tomato fruit morphology. The loss of miR319 regulation in the semi‐dominant La mutant led to a premature SlTCP2/LA expression during gynoecium patterning, which results in modified cell division during carpel development. As a consequence, La mutants exhibited elongated ovary and fruit shape, and a reduced number of ovules and seeds. Elongated fruit shape in La may be partially due to the SlTCP2/LA‐mediated repression of OVATE activity in young floral buds. Further analysis showed that the de‐repression of SlTCP2/LA decreases auxin responses in young floral buds by directly repressing SlYUCCA4 expression, but SlTCP2/LA also acts in parallel with ENTIRE (E) to orchestrate fruit morphology and seed production. Our study defines a novel miRNA‐based molecular link between the domestication‐associated OVATE gene and auxin responses. Given the striking variation in fruit morphology among members of the Solanaceae family, fine‐tuning regulation of gene expression by miRNA coupled with modulation of auxin dynamics may be a common driver in the evolution of fruit shape diversity.
Piecewise rank‐one approximation of vector fields with measure derivatives
Authors: Babadjian Jean‐François , Iurlano Flaviana
Published: November 2024

This work addresses the question of density of piecewise constant (resp. rigid) functions in the space of vector‐valued functions with bounded variation (resp. deformation) with respect to the strict convergence. Such an approximation property cannot hold when considering the usual total variation in the space of measures associated to the standard Frobenius norm in the space of matrices. It turns out that oscillation and concentration phenomena interact in such a way that the Frobenius norm has to be homogenized into a (resp. symmetric) Schatten‐1 norm that coincides with the Euclidean norm on rank‐one (resp. symmetric) matrices. By means of explicit constructions consisting of the superposition of sequential laminates, the validity of an optimal approximation property is established at the expense of endowing the space of measures with a total variation associated with the homogenized norm in the space of matrices.
The life strategy of bacteria rather than fungi shifts in karst tiankeng island-like systems
Authors: Jiang Cong , Qiu Changchun , Shui Wei
Published: November 2024

Karst tiankeng is a typical terrestrial habitat island-like system, known as an oasis in a degraded karst landscape. However, we know little about the composition, structure, and life strategies of soil microbial communities in the karst tiankeng ecosystem. In this study, we use amplicon sequencing to investigate the soil bacteria and fungi of 26 karst tiankeng in two typical karst tiankeng groups. The results showed that the composition and structure of bacterial and fungal communities were significantly different at two dimensions (among and within the karst tiankeng group). Bacteria showed more sensitivity to variation in the karst tiankeng area and isolation than fungi. With the increase of karst tiankeng area and isolation, the bacterial life strategies shift from
K
-strategist to
r
-strategist, likely due to the changes in soil properties (total phosphorus, Ca, and soil water content). Abundant and rare taxa play different roles in karst tiankeng ecosystems; abundant taxa serve a key role in nutrient cycles and life strategy shifts by occupying the key status in networks. Considering the key role of soil microbes in ecosystems, more attention must be paid to the impact of habitat loss on soil microbial life strategies, particularly in the ecological impact of life strategies change of abundant and rare taxa.

IMPORTANCE

These findings highlight that habitat loss or fragmentation induces a shift in microbial life strategies and improves our understanding of the composition and biogeography of karst ecosystem microorganisms.
Transcription factor-dependent regulatory networks of sexual reproduction in
Fusarium graminearum
Authors: Kim Wonyong , Kim Da-Woon , Wang Zheng , Liu Meng , Townsend Jeffrey P. , Trail Frances
Published: November 2024

Transcription factors (TFs) involved in sexual reproduction in filamentous fungi have been characterized. However, we have little understanding of how these TFs synergize within regulatory networks resulting in sexual development. We investigated 13 TFs in
Fusarium graminearum
, whose knockouts exhibited abortive or arrested phenotypes during sexual development to elucidate the transcriptional regulatory cascade underlying the development of the sexual fruiting bodies. A Bayesian network of the TFs was inferred based on transcriptomic data from key stages of sexual development. We evaluated
in silico
knockout impacts to the networks of the developmental phenotypes among the TFs and guided knockout transcriptomics experiments to properly assess regulatory roles of genes with same developmental phenotypes. Additional transcriptome data were collected for the TF knockouts guided by the stage at which their phenotypes appeared and by the cognate
in silico
prediction. Global TF networks revealed that TFs within the mating-type locus (
MAT
genes) trigger a transcriptional cascade involving TFs that affected early stages of sexual development. Notably,
PNA1
, whose knockout mutants produced exceptionally small protoperithecia, was shown to be an upstream activator for
MAT
genes and several TFs essential for ascospore production. In addition, knockout mutants of
SUB1
produced excessive numbers of protoperithecia, wherein
MAT
genes and pheromone-related genes exhibited dysregulated expression. We conclude that
PNA1
and
SUB1
play central and suppressive roles in initiating sexual reproduction, respectively. This comprehensive investigation contributes to our understanding of the transcriptional framework governing the multicellular body plan during sexual reproduction in
F. graminearum
.

IMPORTANCE

Understanding transcriptional regulation of sexual development is crucial to the elucidation of the complex reproductive biology in
Fusarium graminearum
. We performed gene knockouts on 13 transcription factors (TFs), demonstrating knockout phenotypes affecting distinct stages of sexual development. Using transcriptomic data across stages of sexual development, we inferred a Bayesian network of these TFs that guided experiments to assess the robustness of gene interactions using a systems biology approach. We discovered that the mating-type locus (
MAT
genes) initiates a transcriptional cascade, with
PNA1
identified as an upstream activator essential for early sexual development and ascospore production. Conversely,
SUB1
was found to play a suppressive role, with knockout mutants exhibiting excessive protoperithecia due to abnormally high expression of
MAT
and pheromone-related genes. These findings highlight the central roles of
PNA1
and
SUB1
in regulating other gene activity related to sexual reproduction, contributing to a deeper understanding of the mechanisms of the multiple TFs that regulate sexual development.
Structure and identification of the native PLP synthase complex from
Methanosarcina acetivorans
lysate
Authors: Agnew Angela , Humm Ethan , Zhou Kang , Gunsalus Robert P. , Zhou Z. Hong
Published: November 2024

Many protein-protein interactions behave differently in biochemically purified forms as compared to their
in vivo
states. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here, we apply the bottom-up structural proteomics method,
cryoID
, toward a model methanogenic archaeon. While they are keystone organisms in the global carbon cycle and active members of the human microbiome, there is a general lack of characterization of methanogen enzyme structure and function. Through the
cryoID
approach, we successfully reconstructed and identified the native
Methanosarcina acetivorans
pyridoxal 5′-phosphate (PLP) synthase (PdxS) complex directly from cryogenic electron microscopy (cryo-EM) images of fractionated cellular lysate. We found that the native PdxS complex exists as a homo-dodecamer of PdxS subunits, and the previously proposed supracomplex containing both the synthase (PdxS) and glutaminase (PdxT) was not observed in cellular lysate. Our structure shows that the native PdxS monomer fashions a single 8α/8β TIM-barrel domain, surrounded by seven additional helices to mediate solvent and interface contacts. A density is present at the active site in the cryo-EM map and is interpreted as ribose 5-phosphate. In addition to being the first reconstruction of the PdxS enzyme from a heterogeneous cellular sample, our results reveal a departure from previously published archaeal PdxS crystal structures, lacking the 37-amino-acid insertion present in these prior cases. This study demonstrates the potential of applying the
cryoID
workflow to capture native structural states at atomic resolution for archaeal systems, for which traditional biochemical sample preparation is nontrivial.

IMPORTANCE

Archaea are one of the three domains of life, classified as a phylogenetically distinct lineage. There is a paucity of known enzyme structures from organisms of this domain, and this is often exacerbated by characteristically difficult growth conditions and a lack of readily available molecular biology toolkits to study proteins in archaeal cells. As a result, there is a gap in knowledge concerning the mechanisms governing archaeal protein behavior and their impacts on both the environment and human health; case in point, the synthesis of the widely utilized cofactor pyridoxal 5′-phosphate (PLP; a vitamer of vitamin B6, which humans cannot produce). By leveraging the power of single-particle cryo-EM and map-to-primary sequence identification, we determine the native structure of PLP synthase from cellular lysate. Our workflow allows the (i) rapid examination of new or less characterized systems with minimal sample requirements and (ii) discovery of structural states inaccessible by recombinant expression.
Permanent draft genome sequences of cadmium-resistant isolates of
Cupriavidus
from soils within the Tar Creek Superfund site
Authors: Winn Jordon N. , Wedlock Emily A. , McHugh Emily P. , Monismith, Jr. David , Campbell James H. , Campbell Alisha G.
Published: November 2024

Soil samples taken near the abandoned town of Picher, OK, USA, were used to enrich and isolate bacteria in the presence of cadmium. Isolates reported belong to the genus
Cupriavidus
. Here, we report their permanent draft sequences with an emphasis on genes conferring resistance to cadmium.
Complete genome of
Xanthomonas citri
pv.
anacardii
strain CCRMTAQ13 (causal agent of angular leaf spot in cashew) from Brazil using long-read Nanopore technology
Authors: Silva Hiago Antonio Oliveira da , de Abreu Lucas Magalhaes , da Gama Marco Aurelio Siqueira , Huguet-Tapia Jose , Zhang Peiqi , Buttros Victor Hugo , Mukesh Jain , White Frank , Martins Samuel J.
Published: November 2024

Here, we present a single contiguous genome sequence of
Xanthomonas citri
pv.
anacardii
(
Xca
; strain CCRMTAQ13), the causal agent of angular leaf spot in cashew, an important commodity crop in Brazil. Oxford Nanopore Sequencing Technology was used to assemble the genome of the
Xca
in a single contig of 5,086,757 bp with a 64.53% GC content. This genome sequence will provide a useful resource for studies on virulence mechanisms, including the identification of a single transcription activator-like effector gene of 3,359 bp.
Erratum to: Dissolution of Ta–Nb and Nb Minerals in Granitoid Melts
Authors: Chevychelov V. Yu. , Viryus A. A.
Published: November 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S0016702924190029
Erratum to: Trace Element Composition of Discordant Zircon as a Reflection of the Fluid Regime of Paleoproterozoic Granulite Metamorphism (Khapchan Terrane, Anabar Shield)
Authors: Skublov S. G. , Gusev N. I. , Salimgaraeva L. I. , Romanova L. Yu.
Published: November 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S0016702924190042
Impact of exercise training in combination with dapagliflozin on physical function in adults with type 2 diabetes mellitus: study protocol for the Dapagliflozin, Exercise Training and physicAl function (DETA) randomised controlled trial
Authors: Sargeant Jack A , Ahmad Ehtasham , James Emily , Baker Luke , Bilak Joanna M , Coull Nicole A , Gulsin Gaurav Singh , King James A , Khunti Kamlesh , Redman Emma , Rowlands Alex , Watson Emma , Wormleighton Joanne V , McCann Gerry P , Yates Thomas , Davies Melanie J
Published: November 2024

Introduction

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are associated with weight loss, diverse cardiorenal benefits and improved glycaemic control. However, the effects of SGLT2i on physical function and fitness are uncertain. The Dapagliflozin, Exercise Training and physicAl function trial investigates whether the SGLT2i dapagliflozin, alone or in combination with structured exercise training, improves physical function compared with diet-induced weight loss in adults with type 2 diabetes mellitus (T2DM), overweight/obesity and impaired physical function.

Methods and analysis

This single-centre randomised controlled trial will assign 1:1:1, 135 adults with T2DM and low physical function to receive one of three treatments: (1) dapagliflozin (10 mg once-daily) alone, (2) dapagliflozin (10 mg once-daily) plus structured exercise training or (3) diet control (where participants are supported to achieve 3% weight loss, equivalent to estimated weight loss with dapagliflozin treatment). Primary and secondary outcomes will be assessed at baseline, 12 and 24 weeks. The primary outcome is the difference in physical function, assessed using the modified Physical Performance Test, between the treatment groups and diet control at 24 weeks. Secondary outcomes include MRI-measured cardiac structure and function, maximal aerobic capacity, resting metabolic rate, device-measured physical activity and sleep, body composition, haemoglobin A1c and cardiovascular risk markers.

Ethics and dissemination

The Heath Research Authority (HRA) and the Medicines and Healthcare Products Regulatory Authority (MHRA) Research Ethics Committee have approved the study. The findings of the study will be published in peer-reviewed journals.

Trial registration number

ISRCTN11459997.

EudraCT number

2019-004586-41.
Brown rice attenuates iron-induced Parkinson’s disease phenotypes in male wild-type drosophila: insights into antioxidant and iron metabolism modulation
Authors: Yankuzo Hassan Muhammad , Sulaiman Ismail , Muhammad Suleiman Alhaji , Raji Abdullahi Abdullahi , Uthman Yaaqub Abiodun , Imam Mustapha Umar
Published: November 2024

Parkinson’s disease (PD) is a progressive movement disorder associated with brain iron (Fe) accumulation and free radicals. Brown rice (BR) is antioxidant-rich and has been shown to ameliorate oxidative stress-induced damage. The aim of this study was to investigate the effects of BR compared to white rice (WR) on Fe-induced PD in a fruit fly model. Three-day-old male adult flies were divided into two groups: one on a normal diet and the other on Fe-diet (1 mmol/L) for 10 days to induce PD. After 10 days, the Fe-fed flies were redistributed into four groups: one on normal diet (Fe group), while the others were treated with BR (Fe + BR group), WR (Fe + WR group), or L-3,4-dihydroxyphenylalanine (L-dopa) (Fe + L-dopa group) for 5 days. Similarly, the flies initially on a normal diet were separated into four groups: one on normal diet (Control group), while the others were treated with BR (BR group), WR (WR group), or L-dopa (L-dopa group) for 5 days. Finally, Fe levels, dopamine, malonaldehyde (MDA), and antioxidant enzymes were measured, and the mRNA levels of antioxidant and Fe metabolism genes were assessed. BR significantly improved motor and cognitive functions, decreased fly head MDA and Fe levels, and increased antioxidant enzyme levels in comparison to the Fe and WR groups. Similarly, BR upregulated the mRNA levels of antioxidant genes: catalase, GPx, Nrf2, and DJ-1. The results suggest that BR could potentially reduce morbidities associated with PD possibly due to its bioactive compounds compared to WR.
Associations of circulating T-cell subsets with carotid artery stiffness: the multiethnic study of atherosclerosis
Authors: DeConne Theodore M. , Buzkova Petra , Pewowaruk Ryan , Delaney Joseph A. , Psaty Bruce M. , Tracy Russell P. , Doyle Margaret F. , Sitlani Colleen M. , Landay Alan L. , Huber Sally A. , Hughes Timothy M. , Bertoni Alain G. , Gepner Adam D. , Ding Jingzhong , Olson Nels C.
Published: November 2024

We investigated associations between T-cells and novel measures of structural and load-dependent arterial stiffness in a large multiethnic cohort. The primary analysis revealed that pro-inflammatory, senescence-associated CD4+CD28–CD57+ T-cells were associated with higher load-dependent arterial stiffness. An exploratory analysis revealed that multiple pro-inflammatory CD4+ and CD8+ T-cell subpopulations were associated with both higher structural and load-dependent arterial stiffness. These results suggest that pro-inflammatory T-cells may contribute to arterial stiffness through both arterial remodeling and elevated blood pressure.
Evaluation of a CBT‐Based Program for Mental Health in the General Population During the COVID‐19 Pandemic: A Stepped‐Care Approach Using a Chatbot and Digitized Group Intervention
Authors: Langhammer Till , Hilbert Kevin , Wasenmueller Robert , Praxl Berit , Ertle Andrea , Asbrand Julia , Lueken Ulrike
Published: November 2024

Background: The COVID‐19 pandemic exposed a substantial portion of society to multiple stressors, while access to mental health care was limited. To address this, we introduced a digital stepped‐care program rooted in cognitive–behavioral therapy (CBT) principles, aiming to alleviate mental health distress among the general public seeking help.

Methods: The program comprises a 4‐week digital application using “Aury” the chatbot, followed by an optional 6‐week online group session for those still symptomatic. A 4‐week waiting period separated these steps. Participants entered based on self‐identified mental health concerns. Interventions addressed prevalent pandemic mental health issues: sleep disturbances, anxiety, depression, worry/rumination, interpersonal issues, and resource mobilization. Outcomes focused on depressive, anxiety, and somatic symptoms, assessed by the Patient Health Questionnaire (PHQ).

Results: Of the 1261 initial participants, postchatbot results (N = 142) indicated small to medium effects (d = 0.412 to d = 0.523). Those finishing the entire program (N = 41) saw substantial symptom decline with medium to large effects (d = 0.757 to d = 0.818). No shifts were seen in the waiting phase. At follow‐up 6 months after baseline, both groups—those who only used the chatbot (N = 60; d = 0.284 to d = 0.416) and those who completed the entire program (N = 27; d = 0.854 to d = 0.926)—showed sustained symptom reduction. Comparing groups that received no intervention, used the chatbot only, and completed the entire program, we observed a dose–response effect.

Conclusions: This resource‐efficient and adaptable digital approach effectively reduced pandemic‐induced mental health issues, indicating its potential in crisis periods with limited health resources. Randomized controlled trials are recommended for further validation.

Trial Registration: Clinical Trial Registry identifier: DRKS00023220.
The Combination of Sorafenib and PGV‐1 Inhibits the Proliferation of Hepatocellular Carcinoma Through c‐Myc Suppression in an Additive Manner: In Vitro Studies
Authors: Novitasari Dhania , Nakamae Ikuko , Yoneda-Kato Noriko , Kato Jun-ya , Hippo Yoshitaka , Suenaga Yusuke , Putri Dyaningtyas Dewi Pamungkas , Meiyanto Edy , Ikawati Muthi’
Published: November 2024

Hepatocellular carcinoma (HCC) is one of the most aggressive types of liver cancer, and it is frequently associated with upregulated c‐Myc expression. Sorafenib (Sor) is commonly used to treat HCC, but many patients experienced mild to severe side effects due to prolonged Sor treatment during therapy. It has been known that Pentagamavunone‐1 (PGV‐1) exhibits a remarkable antiproliferative effect on several cancer cells, yet limited studies have reported its cellular activities in HCC. The current study aims to evaluate the anticancer effects of Sor in combination with PGV‐1 on the progression of HCC proliferation. c‐Myc expressing cells, JHH‐7 and Huh‐7, were used for this study, then Sor and PGV‐1 were tested for their effect on the cellular physiology phenomena including cytotoxicity combination assay and colony formation assay, cell cycle profile and reactive oxygen species (ROS) level by flow cytometry, senescence induction by beta‐galactosidase (SA‐β‐gal) assay, and migration inhibition by wound healing assay. The c‐Myc expression was evaluated through Western blot. PGV‐1 was more effective than Sor at inhibiting cell growth, and it showed greater selectivity for HCC over fibroblast cells. The combination of Sor with PGV‐1 exhibited synergistic‐additive cytotoxicity with an irreversible effect in HCC cell lines. The combination induced senescence similarly with Sor alone in JHH‐7 cells, while PGV‐1 enhanced the cellular senescence when combined with Sor in Huh‐7 cells. Furthermore, the combination increased ROS level in the same way as PGV‐1 did in HCC. The combination with PGV‐1 acted better than Sor alone to inhibit JHH‐7 cell migration. In addition, the combination treatment led to the suppression of c‐Myc, particularly in JHH‐7 cells. Taken together, combining Sor with PGV‐1 promotes better efficacy than Sor alone to inhibit HCC cell proliferation, and further evaluation of the efficacy and safety of adding PGV‐1 to Sor in HCC therapy is worthwhile as a potential combination treatment option.
Octanoic Acid and Decanoic Acid Inhibit Tunicamycin‐Induced ER Stress in Rat Aortic Smooth Muscle Cells
Authors: Sukketsiri Wanida , Tipmanee Varomyalin , Rungruang Panlekha , Higashihara Mayo , Sumi Tomoko , Moriyama Tatsuya , Zaima Nobuhiro
Published: November 2024

ER stress is a crucial factor in the progression of vascular cell diseases. Notably, octanoic acid (OA; C8:0) and decanoic acid (DA; C10:0), prominent components of medium‐chain fatty acids (MCFAs), may provide potential health benefits. However, their effects on vascular smooth muscle cells (VSMCs) remain unknown. Given the link between ER stress and vascular cell pathological conditions, the primary goal of this research is to investigate the protective effects of OA and DA against ER stress induction in rat aortic smooth muscle cells (RASMCs). To achieve this objective, RASMCs were pretreated with OA and DA at concentrations of 250 and 500 μM for 24 h. Subsequently, the cells were exposed to 1 μg/mL of tunicamycin, an ER stress inducer, for an additional 24 h. Apoptosis was assessed using DAPI staining, while DCFH2‐DA probe was used to measure ROS levels. Furthermore, the gene expression of ER stress markers, such as CHOP, GRP78, ATF4, and eIF2α, as well as contractile markers like αSMA and MYH11, was assessed using real‐time reverse transcription polymerase chain reaction. Moreover, the αSMA protein level was measured using immunocytochemistry techniques. The study revealed that OA and DA significantly mitigated cell death caused by tunicamycin, decreased ROS production, and inhibited the gene expression of ER stress markers (CHOP, GRP78, and eIF2α). Notably, OA and DA also inhibited the expression of contractile genes (α-SMA and MYH11) and reduced the number of α‐SMA‐positive cells in tunicamycin‐treated RASMCs. These findings indicate that OA and DA offer protection against ER stress–stimulated cell death and ROS generation in VSMCs, thereby supporting their potential therapeutic applications for safeguarding these cells.
Aspergillus Tracheobronchitis With Mediastinal Lymphadenopathy in a Patient With Well‐Controlled HIV Infection
Authors: Singhatiraj Ekachai , Tiengburanatarm Korsin , Pongpirul Krit
Published: November 2024

Background: Aspergillus tracheobronchitis (AT) is an uncommon yet severe form of invasive pulmonary aspergillosis, with a notably low incidence among individuals living with HIV infection—accounting for merely 4.5% (7 out of 156 cases) in recent reviews. The advent of modern antiretroviral therapy (ART) has significantly altered the landscape of opportunistic infections in HIV, rendering conditions like AT rare in well‐controlled cases.

Case Presentation: We present the case of a woman in her mid‐20s with well‐managed HIV infection who experienced a 4‐week history of fever and dyspnea. Diagnostic procedures, including bronchoscopy, revealed granulation tissue obstructing her right main bronchus. Cultures confirmed infection with Aspergillus fumigatus, leading to a diagnosis of AT. Despite initial positive response to voriconazole treatment, the patient developed severe hemoptysis and unfortunately succumbed to the complication.

Conclusion: This case underscores the critical need for healthcare providers to consider AT in the differential diagnosis of respiratory symptoms in HIV‐positive patients, even when HIV is well‐controlled with ART. Early recognition and prompt antifungal therapy are essential for improving outcomes. Clinicians should remain vigilant for severe complications like hemoptysis, which can occur despite appropriate therapy. This report highlights the ongoing necessity for vigilance and proactive intervention in the care of individuals living with HIV.
Planning of Multiregional EV Charging and Battery Swapping Stations Based on Dynamic Weighting Indexes
Authors: Yao Yin , Wang Yehui , Zhou Bo , Lin Shunfu , Li Dongdong
Published: November 2024

The increase in electric vehicle (EV) penetration has triggered a surge in demand for battery charging and swapping infrastructure. However, in diverse urban regions, an unbalanced allocation of charging stations (CSs) and battery swapping stations (BSSs) can lead to inefficient resource utilization and diminished revenue for these facilities. Therefore, it is urgent to set up a system of operational and economic indexes to evaluate the proportional planning of CSs and BSSs. The traditional weighting method of the index system cannot accurately describe the relationship between the indexes. As a result, an evaluation method of CS and BSS operational economy based on dynamic weighting indexes is proposed. Firstly, from the perspectives of EV owners, CSs, BSSs, power grid, traffic, and environment, a social and economic index system of CSs and BSSs is established, and quantifiable indexes related to the operational economy are extracted. Then, the copula entropy (CE) is used to improve the CRITIC objective weighting method, reflect the correlation between indexes, and align it with the objective law. The selected indexes are weighted by the subjective and objective combination weighting method. Finally, the simulation is conducted based on the practical data of the urban power grid in China. The rationality of the proposed operation economic indexes and the effectiveness of the improved weighting method are verified.
Targeting Quorum Sensing in Pseudomonas aeruginosa Using Marine‐Derived Metabolites—An In Silico Approach
Authors: Padiga Seidu Muntawakilu , Adomako Alice , Boakye Aaron , Laryea Michael Konney , Borquaye Lawrence Sheringham
Published: November 2024

Quorum sensing (QS), a cell‐to‐cell communication among bacteria, is one of the leading mechanisms of antibiotic resistance. Opportunistic bacteria such as Pseudomonas aeruginosa employ QS in their pathogenicity. Marine‐derived natural products have been reported to elicit good antimicrobial and anti‐QS properties. In this work, 30 marine‐derived metabolites were screened against the LasR, PqsR, and RhlR QS receptors of P. aeruginosa using molecular docking and dynamics simulation approach. From virtual screening, 11, 9, and 7 compounds had a preferential affinity for the LasR, PqsR, and RhlR receptors, respectively. For LasR, docking scores between −10.2 and −5.1 kcal/mol were obtained for the compounds. Binding scores of −7.3 to −5.6 kcal/mol and −9.1 to −7.1 kcal/mol were also obtained for PqsR and RhlR, respectively. Interaction with Gln 194, Tyr 258, Ile 236, Leu 208, and Leu 207 catalytic residues were observed for PqsR complexes. Molecular dynamics (MD) simulations revealed that all 11 compounds retained their docking poses with LasR, while 6 compounds maintained stable interactions with PqsR and RhlR. MD show that compounds bind to LasR and RhlR by causing high conformational changes in their DNA‐binding domains (DBDs), as demonstrated by a principal component analysis (PCA) of the respective DBDs. In PqsR, the compounds interacted with crucial residues (Gln 194, Tyr 258, Ile 236, Leu 236, and Leu 207) previously reported as residues necessary for the inhibition of PqsR and maintained these interactions during the simulation. Thus, the compounds exhibited their quorum quenching activity by attenuating DNA recognition in LasR and RhlR while competitively targeting the PqsR binding site. The high binding affinities observed suggest that these marine‐derived compounds could effectively inhibit QS in P. aeruginosa, offering a promising strategy for addressing biofilm‐related infections and antibiotic resistance.
Numerical and Experimental Studies of Shallow‐Water Sloshing Motions in a Prismatic Tank
Authors: Su Yan , Yuan Xinyi , Shi Shengbo
Published: November 2024

Shallow‐water sloshing behavior within a prismatic tank has been analyzed utilizing a model of Boussinesq‐type equations. The Boussinesq‐type equations are calculated by the five‐points finite difference method and extrapolating boundary technique are adopted for simulating the runup phenomena around the inclined bottom. The numerical grid points are divided into the wet region which are evaluated by the Boussinesq‐type equations and the dry region which are obtained from extrapolating boundary technique. The experimental studies of sloshing motions in the prismatic tank were carried out based on the six degrees of freedom motion platform. And the free surface profiles on the inclined bottom were compared between the numerical and experimental results. In the vicinity of the lowest natural frequency, the numerical model presents very good performance on nonbreaking sloshing motions. Based on the numerical Boussinesq‐type model, the frequency response of sloshing motion in prismatic tanks with different inclined bottoms is compared and the transformation from hard-spring effect to soft-spring effect can be found. With the angle of inclined bottom decreased the main wave pattern in the prismatic tank change from nonlinear traveling waves to standing waves.
A Potent, Selective, Small-Molecule Inhibitor of DHX9 Abrogates Proliferation of Microsatellite Instable Cancers with Deficient Mismatch Repair
Authors: Castro Jennifer , Daniels Matthew H. , Brennan David , Johnston Brian , Gotur Deepali , Lee Young-Tae , Knockenhauer Kevin E. , Lu Chuang , Wu Jie , Nayak Sunaina , Collins Cindy , Bansal Rishabh , Buker Shane M. , Case April , Liu Julie , Yao Shihua , Sparling Brian A. , Sickmier E. Allen , Silver Serena J. , Blakemore Stephen J. , Boriack-Sjodin P. Ann , Duncan Kenneth W. , Ribich Scott , Copeland Robert A.
Published: November 2024

DHX9 is a multifunctional DExH-box RNA helicase with important roles in the regulation of transcription, translation, and maintenance of genome stability. Elevated expression of DHX9 is evident in multiple cancer types, including colorectal cancer. Microsatellite instable–high (MSI-H) tumors with deficient mismatch repair (dMMR) display a strong dependence on DHX9, making this helicase an attractive target for oncology drug discovery. In this report, we show that DHX9 knockdown increased RNA/DNA secondary structures and replication stress, resulting in cell-cycle arrest and the onset of apoptosis in cancer cells with MSI-H/dMMR. ATX968 was identified as a potent and selective inhibitor of DHX9 helicase activity. Chemical inhibition of DHX9 enzymatic activity elicited similar selective effects on cell proliferation as seen with genetic knockdown. In addition, ATX968 induced robust and durable responses in an MSI-H/dMMR xenograft model but not in a microsatellite stable/proficient MMR model. These preclinical data validate DHX9 as a target for the treatment of patients with MSI-H/dMMR. Additionally, this potent and selective inhibitor of DHX9 provides a valuable tool with which to further explore the effects of inhibition of DHX9 enzymatic activity on the proliferation of cancer cells in vitro and in vivo.

Significance: DHX9 is required in cancer cells with deficient mismatch repair and can be inhibited by ATX968, providing a promising strategy for the development of precision cancer therapeutics.
Climate Change and Cardiovascular Disease: Who Is Vulnerable?
Authors: Khraishah Haitham , Ostergard Robert L. , Nabi Syed R. , De Alwis Donald , Alahmad Barrak
Published: November 2024

Climate change involves a shift in earth’s climate indicators over extended periods of time due to human activity. Anthropogenic air pollution has resulted in trapping heat, contributing to global warming, which contributes to worsening air pollution through facilitating oxidizing of air constituents. It is becoming more evident that the effects of climate change, such as air pollution and ambient temperatures, are interconnected with each other and other environmental factors. While the relationship between climate change components and cardiovascular disease is well documented in the literature, their interaction with one another along with individuals’ biological and social risk factors is yet to be elucidated. In this review, we summarize that pathophysiological mechanisms by ambient temperatures directly affect cardiovascular health and describe the most vulnerable subgroups, defined by age, sex, race, and socioeconomic factors. Finally, we provide guidance on the importance of integrating climate, environmental, social, and health data into common platforms to inform researchers and policies.
An Accessible, Browser-Based Gestural Controller for Web Audio, MIDI, and Open Sound Control
Authors: Lim Monica , Kotsani Natalia
Published: November 2024

Handmate is a browser-based hand gestural controller for Web Audio, MIDI, and Open Sound Control (OSC), using open-source pose-estimation technology from Google MediaPipe. The Web browser was chosen as the platform to execute all computational processes so that users could access the latest computer vision technology for music-making without requiring any specialized hardware, software, or technical expertise. By combining preexisting technologies in a browser environment, we enable accessible, interactive sound-making using hand movement. Three controllers are described: (1) Handmate Effects, which receives microphone or user sound input and provides a choice of audio effects that can be controlled by hand movement; (2) Handmate MIDI, which outputs MIDI notes or control values; and (3) Handmate OSC, which outputs OSC messages for users to access hand-movement data in other applications.
Vibrational signals differ between contests and copulatory courtship in the red milkweed beetle Tetraopes tetrophthalmus (Coleoptera: Cerambycidae)
Authors: DeLong Sage A. , Desjonquères Camille , Cirino Lauren A.
Published: November 2024

Substrate-borne vibrational communication is commonly used by herbivorous insects to communicate intraspecific information. This form of communication is underexplored and many discoveries of the form and functional significance of these vibrations have yet to be made. Here, we add red milkweed beetles, Tetraopes tetrophthalmus (Coleoptera: Cerambycidae) to the record of arthropods that communicate with these plant-borne vibrations. Red milkweed beetles, like other cerambycids, commonly use stridulation to produce audible squeaks when in stressful situations and can also produce plant-borne vibrations when in contact with conspecifics. These beetles engage in fights for territory which ultimately results in mating opportunities (i.e., contests). We placed beetles into three sex-ratio treatments: male–male (contests), male–female (copulatory courtship), or male–male–female (contests and copulatory courtship). We first describe contests and copulatory courtship behaviours. We then used laser vibrometry and found that red milkweed beetles communicate by producing plant-borne vibrational signals composed of low-frequency rumbles and high-frequency clacks during male–male contests and copulatory courtship. We compared the spectral and temporal features of the vibrations between the two pre-copulatory contexts. We found that vibrational signals were shorter and had a higher fundamental and dominant frequencies when beetles engaged in contests compared to copulatory courtship behaviours. Our results show that these beetles use plant-borne vibrations as context-dependent signals that communicate different information under these two pre-copulatory scenarios. Our data suggests that these context-dependent signals may help beetles gain access to mates and prolong copulation.
Agrippa’s First Letter in Context (Jos. Vita 365)
Authors: Eilers Claude
Published: November 2024

Josephus quotes a letter of Agrippa II at Vita 365 as proof of the superiority of his account of the Judean revolt as presented in the Bellum Judaicum to that of his rival, Justus of Tiberias. The article considers how Josephus has crafted the argument in preparation for this letter. Some have noted a similarity of language between Agrippa’s letter and Josephus’ preparatory text and raised the question of authenticity. There are, however, also dissimilarities, and this note argues that Josephus has crafted his argument leading to this letter in a way that might lead a reader to misread it as a criticism of Justus.
Carl Anton Martini and Natural Law at the University of Vienna after 1752
Authors: Cerman Ivo
Published: November 2024

Natural law as a discipline was definitively institutionalized at universities in the Habsburg monarchy during the reforms of Maria Theresia after 1752. The guiding principles of these reforms were set in the instruction for the chair of natural law in Vienna which was given to Carl Anton Martini. It was Catholic in conception, but it ordered the professor to draw on Grotius. Our article reconstructs the elementary structure of Martini’s theory of natural law with a focus on his conception of state. The article proves that Martini did not adopt Wolff’s conception of deducing duties and obligations from the highest principle for that would conflict with the Catholic emphasis on freedom of will. Instead of that, Martini derived duties and rights from the three God-given ends. Martini perceived the state as based on social contract, after the model of Christian Wolff. However, it seems that Martini rejected the two-contract model and acknowledged only the contract of submission as binding. Martini sought to hold the middle ground between Machiavellians arguing that the subjects lose all rights after the social contract, and radical ‘monarchomachs’ who believe that the ‘populus’ retains the supreme power. Martini argues that the ruler is limited by natural laws; the subjects retain rights to life and to property, but they are denied any right to resistance. Since Martini derived the monarch’s powers from the unlimited duty to guarantee security, he admitted even encroachments on religious freedom. He admitted coercion in matters that would threaten salus civitatis, but respected the inner libertas conscientiae. He also acknowledged a peculiar division of powers differentiating between a legislative, an inspectorial and an executive power. Even though the aim of this division was not a system of checks and balances, a precise description of the scope of the executive power helped to delimit a sphere of individual freedom.
Indifferent Wars in International Law? A Hypothesis on Benedetto Conforti’s Legacy Twenty Years Later
Authors: Mauri Diego
Published: November 2024

In an article that appeared in Volume XII (2002) of the IYIL, Benedetto Conforti discussed the quandary of “just wars” in contemporary international law, wondering whether – and on which conditions – wars conducted outside the UN framework can be considered “just”. On that occasion, Conforti unearthed a thesis that he had decades prior put in writing in the first edition of his famous Manuale, according to which any use of force performed outside the UN Charter could not be evaluated legally, for it pertained to the realm of “legal indifference”. He thus concluded that, when it comes to assessing the “justness” of wars, the answer can be given only by taking stock of moral considerations, that is by resorting to “natural law”. The present contribution aims to appraise this provoking position expressed at the beginning of this millennium. It is argued that resort to the category of legal indifference must not be appraised from a purely philosophical standpoint, but rather in two complementary ways: first, as implying that the justness of any war cannot be decided on the basis of positive law; second, as a metalegal tool to comprehend and describe fundamental changes in the international community. Conforti’s theory of legal indifference vis-à-vis the justness of wars maintains its fascinating quality and utility today.