bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemoradiotherapy and nanomedicine: Drug mechanisms and delivery systems
Authors: Molinaro Matthew , Skrodzki David , Pan Dipanjan
Published: August 2024

Radiotherapy is an invaluable tool in the treatment of cancer. However, when used as a monotherapy, it fails to provide curative outcomes. Chemotherapy drugs are often included to boost the effects of radiation. Key classes of radiosensitizing drugs include platinum compounds, anthracyclines, antimetabolites, taxanes, topoisomerase inhibitors, alkylating agents, and DNA damage repair inhibitors. Chemoradiotherapy suffers from not only systemic toxicities from chemotherapy drugs but also synergistic radiation toxicity as well. It is critical to deliver radiosensitizing molecules to tumor cells while avoiding adjacent healthy tissues. Currently, nanomedicine provides an avenue for tumor specific delivery of radiosensitizers. Nanoscale delivery vehicles can be synthesized from lipids, polymers, or inorganic materials. Additionally, nanomedicine encompasses stimuli responsive particles including prodrug formulation for tumor specific activation. Clinically, nanomedicine and radiotherapy are intertwined with approved formulation including DOXIL and Abraxane. Though many challenges remain, the ongoing progress evidences a promising future for both nanomedicine and chemoradiotherapy.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease

Therapeutic Approaches and Drug Discovery > Emerging Technologies
Holographic $$ \frac{1}{2} $$-BPS surface defects in ABJM
Authors: Lozano Yolanda , Macpherson Niall T. , Petri Nicolò , Ramírez Anayeli
Published: August 2024

Abstract

We study the class of AdS3 × ℂℙ3 solutions to massive Type IIA supergravity with $$ \mathfrak{osp} $$
osp
(6|2) superconformal algebra recently constructed in [1]. These solutions are foliations over an interval preserving $$ \mathcal{N} $$
N
= (0, 6) supersymmetry in two dimensions, that in the massless limit can be mapped to the AdS4 × ℂℙ3 solution of ABJM/ABJ. We show that in the massive case extra NS5-D8 branes, that we interpret as $$ \frac{1}{2} $$

1
2

-BPS surface defect branes within the ABJ theory, backreact in the geometry and turn one of the 3d field theory directions onto an energy scale, generating a flow towards a 2d CFT. We construct explicit quiver field theories that we propose flow in the IR to the (0, 6) SCFTs dual to the solutions. Finally, we show that the AdS3 solutions realise geometrically, in terms of large gauge transformations, an extension to the massive case of Seiberg duality in ABJ theories proposed in the literature.
The (1,0) tensor and hypermultiplets in loop space
Authors: Bak Dongsu , Gustavsson Andreas
Published: August 2024

Abstract

We show that the (1,0) tensor and hypermultiplet supersymmetry variations can be uplifted to loop space. Upon dimensional reduction we make contact with abelian five-dimensional super Yang-Mills, which has a nonabelian generalization that we subsequently uplift back to loop space where we conjecture a nonabelian generalization of the (1,0) supersymmetry variations and demonstrate their on-shell closure.
Association of trauma classifications to long-term outcome in blunt trauma patients
Authors: Kuorikoski Joonas , Heinänen Mikko , Brinck Tuomas , Söderlund Tim
Published: August 2024

Purpose

The impact of major trauma is long lasting. Although polytrauma patients are currently identified with the Berlin polytrauma criteria, data on long-term outcomes are not available. In this study, we evaluated the association of trauma classification with long-term outcome in blunt-trauma patients.

Methods

A trauma registry of a level I trauma centre was used for patient identification from 1.1.2006 to 31.12.2015. Patients were grouped as follows: (1) all severely injured trauma patients; (2) all severely injured polytrauma patients; 2a) severely injured patients with AIS ≥ 3 on two different body regions (Berlin-); 2b) severely injured patients with polytrauma and a physiological criterion (Berlin+); and (3) a non-polytrauma group. Kaplan-Meier survival analysis was performed to estimate differences in mortality between different groups.

Results

We identified 3359 trauma patients for this study. Non-polytrauma was the largest group (2380 [70.9%] patients). A total of 500 (14.9%) patients fulfilled the criteria for Berlin + definition, leaving 479 (14.3%) polytrauma patients in Berlin- group. Berlin + patients had the highest short-term mortality compared with other groups, although the difference in cumulative mortality gradually plateaued compared with the non-polytrauma patient group; at the end of the 10-year follow up, the non-polytrauma group had the greatest mortality due to the high number of patients with traumatic brain injury (TBI).

Conclusion

Excess mortality of polytrauma patients by Berlin definition occurs in the early phase (30-day mortality) and late deaths are rare. TBI causes high early mortality followed by increased long-term mortality.
Migrationshintergrund und Einsamkeit im mittleren und hohen Alter in Deutschland
Authors: Hajek André , König Hans-Helmut
Published: August 2024

Hintergrund

Bisher gibt es nur wenige Erkenntnisse über den Zusammenhang zwischen Migrationshintergrund und Einsamkeit im mittleren und hohen Alter in Deutschland. Ziel war daher, eine Assoziation zwischen Migrationshintergrund und Einsamkeit in dieser Gruppe darzustellen.

Methoden

Die Daten stammen aus dem Deutschen Alterssurvey (Welle 7, November 2020 bis März 2021), einer repräsentativen Stichprobe von zuhause lebenden Personen mittleren und höheren Alters. Die Stichprobe umfasste 4145 Individuen. Das mittlere Alter betrug 63,8 Jahre, 93,2 % der Befragten hatten keinen Migrationshintergrund, wohingegen ungefähr 5,9 % der Befragten einen Migrationshintergrund mit eigener Migrationserfahrung und 0,9 % einen Migrationshintergrund, aber ohne eigene Migrationserfahrung hatten. Zur Quantifizierung der Einsamkeit wurde das etablierte Instrument von De Jong Gierveld verwendet.

Ergebnisse

Multiple lineare Regressionen zeigten, dass Personen mit Migrationshintergrund und eigener Migrationserfahrung im Vergleich zu Personen ohne Migrationshintergrund eine signifikant höhere Einsamkeit aufweisen (β = 0,15, 95 % Konfidenzintervall (KI): 0,004–0,30, p < 0,05), wohingegen Personen mit Migrationshintergrund, aber ohne eigene Migrationserfahrung eine signifikant niedrigere Einsamkeit aufweisen (β = −0,27, 95 % KI: −0,52 bis −0,02, p < 0,05).

Diskussion

Personen mit Migrationshintergrund und eigener Migrationserfahrung scheinen eine Risikogruppe für hohe Einsamkeit im mittleren und hohen Alter in Deutschland darzustellen. Insofern sollte diese Gruppe bei entsprechenden Maßnahmen besonders berücksichtigt werden. Vor dem Hintergrund der aktuellen (und potenzieller künftiger) Migrationsbewegungen sind diese Ergebnisse von großer Relevanz, da insbesondere diese Gruppen von Einsamkeit betroffen sein könnten.
Modifizierte Masquelet-Plastik
Authors: Fischer C. , Schipper S. , Langwald S. , Klauke F. , Kobbe P. , Mendel T. , Hückstädt M.
Published: August 2024

Die Rekonstruktion langstreckiger Knochendefekte infolge von primär traumatischen oder sekundär infektions- oder tumorbedingten Substanzverlusten stellt nach wie vor eine chirurgische Herausforderung dar. Die Kallusdistraktion über Segmenttransport, der vaskularisierte Knochentransfer und die induzierte Membrantechnik (IMT) stellen etablierte Verfahren der Rekonstruktion dar. In den letzten Jahrzehnten erfreut sich die IMT aufgrund ihrer Praktikabilität, Reproduzierbarkeit und Zuverlässigkeit zunehmender Popularität. Gleichsam erfuhr die Originaltechnik eine Vielzahl von Modifikationen. Die Ergebnisse stellen sich als entsprechend heterogen dar. Diese Übersicht soll die wesentlichen Grundprinzipien der IMT darlegen und einen Überblick über die verschiedenen Modifikationen und ihre Komplikationen geben.
Additive manufacturing and mechanical performance of short fiber reinforced PEEK (polyether ether ketone) thermoplastic composites in a vacuum environment
Authors: Vatandaş Bahri Barış , Gümrük Recep
Published: August 2024

Short fiber reinforced thermoplastic composites (SFRTC) have gained popularity in the material extrusion (MEX) method, which is an additive manufacturing (AM) technology, allowing for the simpler and more cost-effective production of polymer composites. However, parts produced using MEX 3D printing technology often exhibit poor mechanical properties and surface quality compared to products manufactured using injection molding, which is one of the main disadvantages of this method. Various methods are used to overcome these challenges, such as production in a vacuum environment, heat-based processes, ultrasonic vibrations, and others. The objective of this study was to achieve parts with lower porosity and improved mechanical properties when printed in a vacuum environment compared to an atmospheric environment. Additionally, an investigation into the optimization of printing parameters was conducted to determine the parameters that yield the highest mechanical properties. For this purpose, SFRTC parts were printed at different vacuum levels (0.5, 10, 100 mbar), and they were subjected to flexural tests to determine their mechanical properties. The results showed that the flexural stress and elastic modulus of the samples produced in a 0.5 mbar vacuum environment increased by 79.75% and 39.41%, respectively, compared to samples produced in an atmospheric environment. Furthermore, the cross-sectional images of the samples were examined using an optical microscope, revealing the lowest porosity in the samples printed in 0.5 mbar vacuum environment.
Combination of low doses of mirtazapine plus venlafaxine produces antidepressant-like effects in rats, without affecting male or female sexual behavior
Authors: Álvarez-Silva Adriana , Rodríguez-Manzo Gabriela , Reyes Rebeca , Fernández-Guasti Alonso
Published: August 2024

Rationale

Pharmacological treatments for depression are not always effective and produce unwanted side effects. Male and female sexual dysfunction is one of these side effects, which can lead to treatment withdrawal. Combination of two antidepressants with different mechanisms of action, like mirtazapine (MTZ) and venlafaxine (VLF) have been shown to be effective for treatment-resistant depression in humans. Combination of low doses of these drugs may still exert antidepressant-like effects without altering sexual behavior.

Objectives

To investigate the potential antidepressant-like effect of the chronic administration of low doses of MTZ plus VLF combined, as well as its impact on male and female sexual behavior in rats.

Methods

The antidepressant-like effect of a 14-day treatment with combinations of MTZ plus VLF (0/0, 2.5/3.75 or 5/7.5 mg/kg) was assessed in young adult male and female rats in the forced swim test (FST). The 5/7.5 mg/kg MTZ/VLF combination was also tested in the chronic mild stress (CMS) test, in both males and females treated for 21 days. The sexual effects of this last treatment were assessed in sexually experienced males and in gonadally-intact females during proestrus.

Results

The 5/7.5 mg/kg MTZ/VLF combination produced an antidepressant-like effect in the FST and reversed the CMS-induced anhedonia in both male and female rats. This combination did not alter male sexual behavior, female proceptive and receptive behaviors or the regularity of the estrous cycle.

Conclusion

The combination of low doses of MTZ and VLF might be a promising therapeutic alternative to treat depression without affecting the sexual response.
Evaluation of the incidence, predictors, risk assessment scores and outcomes of thromboembolism in a cohort of Egyptian NHL patients - Real World Experience
Authors: El-Ashwah Shaimaa , Elashwah Salma , Khaled Omnia , Ghanem Ahmed A. , AboElfarh Hadeer Elsaeed , Selim Ramadan Ayman , Mansour Reham Osama , Shaaban Yasmine
Published: August 2024

Non-Hodgkin’s Lymphoma (NHL) is the most common subtype of lymphoma. The incidence of venous thromboembolism (VTE) in aggressive NHL was estimated recently to be 11%. Several risk assessment scores and factors are available to help identify cancer patients at risk for developing VTE. Patients with a pathologically confirmed diagnosis of NHL were identified at the Oncology Center of Mansoura University. The study included 777 patients: 719 with DLBCL-NOS, 26 with Anaplastic-B-cell, and 32 with T-cell-rich-NHL. Data were retrospectively collected from electronic medical records, including clinical, radiological, and laboratory information related to VTE and NHL. The median age at NHL diagnosis was 53 years, (range: 18–98). There was a male predominance, 51.4% of the cases. At initial lymphoma diagnosis, VTE was identified in 46 (5.9%) patients, and 61 (7.9%) patients experienced VTE while undergoing chemotherapy. According to logistic regression analysis, a PS (performance status) ≥ 2, bulky lesions, and mediastinal masses were significant predictors of VTE at presentation, with P-values of 0.022, 0.002, and < 0.001, respectively. Meanwhile, NHL patients who developed VTE during chemotherapy had significantly poorer PS, higher absolute neutrophilic counts (ANC), neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels than lymphoma patients without VTE, with P-values of 0.003,  0.034, 0.049, 0.01 and 0.007, respectively, as determined by multivariate analysis. The ROC curve identified the cut-off values of 4.875 × 109/L for ANC, 2.985 for NLR, 144.85 for PLR, and 417.5 U/L for LDH as potential markers for predicting VTE in NHL patients. Patients with a PS ≥ 2 and values exceeding these cut-offs for ANC, NLR, and PLR experienced significantly higher incidences of VTE than other groups, with P-values of 0.003, < 0.001, < 0.001, and < 0.001, respectively. At the end of the follow-up, the overall survival was significantly shortened by VTE occurring during chemotherapy, hypoalbuminemia,  intermediate-high and high international prognostic index (IPI) scores (intermediate-high and high), responses other than CR and relapse, all with P-values < 0.05. ECOG PS and Inflammatory markers such as NLR, PLR, and neutrophilic count could serve as predictors of the development of thrombotic events in patients with NHL-DLBCL. Additionally, the occurrence of VTE during chemotherapy is an independent poor prognostic marker for overall survival (OS).
Maximal Colourings for Graphs
Authors: Mulas Raffaella
Published: August 2024

We consider two different notions of graph colouring, namely, the t-periodic colouring for vertices that has been introduced in 1974 by Bondy and Simonovits, and the periodic colouring for oriented edges that has been recently introduced in the context of spectral theory of non-backtracking operators. For each of these two colourings, we introduce the corresponding colouring number which is given by maximising the possible number of colours. We first investigate these two new colouring numbers individually, and we then show that there is a deep relationship between them.
Effects of ∆-9 tetrahydrocannabinol on the small intestine altered by high fructose diet: A Histopathological study
Authors: Isildar Basak , Beydogan Alisa Bahar , Koyuturk Ece , Coskun Yazici Zeynep Mine , Koyuturk Meral , Bolkent Sema
Published: August 2024

The consumption of fructose is increasing day by day. Understanding the impact of increasing fructose consumption on the small intestine is crucial since the small intestine processes fructose into glucose. ∆9-Tetrahydrocannabinol (THC), a key cannabinoid, interacts with CB1 and CB2 receptors in the gastrointestinal tract, potentially mitigating inflammation. Therefore, this study aimed to investigate the effects of the high-fructose diet (HFD) on the jejunum of rats and the role of THC consumption in reversing these effects. Experiments were conducted on Sprague–Dawley rats, with the experimental groups as follows: control (C), HFD, THC, and HFD + THC. The HFD group received a 10% fructose solution in drinking water for 12 weeks. THC groups were administered 1.5 mg/kg/day of THC intraperitoneally for the last four weeks. Following sacrification, the jejunum was evaluated for mucus secretion capacity. IL-6, JNK, CB2 and PCNA expressions were assessed through immunohistochemical analysis and the ultrastructural alterations via transmission electron microscopy. The results showed that fructose consumption did not cause weight gain but triggered inflammation in the jejunum, disrupted the cell proliferation balance, and increased mucus secretion in rats. Conversely, THC treatment displayed suppressed inflammation and improved cell proliferation balance caused by HFD. Ultrastructural examinations showed that the zonula occludens structures deteriorated in the HFD group, along with desmosome shrinkage. Mitochondria were found to be increased due to THC application following HFD. In conclusion, the findings of this research reveal the therapeutic potential of THC in reversing HFD-related alterations and provide valuable insights for clinical application.

Graphical abstract
Tracing a caring transition policy for the German coal region Lusatia
Authors: Walk Paula , Koepchen Marius , Stognief Nora , Probst Johannes
Published: August 2024

Coal mining and generation adversely affect several ecosystems, including climate, water and land. On the other hand, questions of justice and socio-economic considerations of affected regions are crucial for a successful coal phase-out, underlining the need for a nexus perspective. This includes taking a gender perspective, which thus far has received relatively little attention. We contribute to closing this gap through our study on the coal region Lusatia in Germany, where an unprecedentedly high amount of money is spent to shape the regional transition. The allocation of these funds is the subject of a contentious debate about which societal needs are considered most urgent to be met. We conducted a critical discourse analysis examining relevant policy documents and analyzing dominant ideas about what a successful transition in Lusatia should look like. Based on feminist care theory and interviews with locally organized women, we show that concepts of care for humans and nonhumans are severely underdeveloped. To address this gap, we propose based on women’s emerging discourse four pillars of care work as social infrastructure that should be central to transition processes: (1) aftercare for social and ecological residuals of coal mining, (2) social cohesion, (3) democratic care services, and (4) caring democracy: democratic decision-making on how to care.
Brief Report: A population-based study of the impact of the COVID-19 pandemic on benzodiazepine use among children and young adults
Authors: Antoniou Tony , Pajer Kathleen , Gardner William , Penner Melanie , Lunsky Yona , McCormack Daniel , Tadrous Mina , Mamdani Muhammad , Gozdyra Peter , Juurlink David N. , Gomes Tara
Published: August 2024

The COVID-19 pandemic was associated with increases in the prevalence of depression and anxiety among children and young adults. We studied whether the pandemic was associated with changes in prescription benzodiazepine use. We conducted a population-based study of benzodiazepine dispensing to children and young adults ≤ 24 years old between January 1, 2013, and June 30, 2022. We used structural break analyses to identify the pandemic month(s) when changes in prescription benzodiazepine dispensing occurred, and interrupted time series models to quantify changes in dispensing following the structural break and compare observed and expected benzodiazepine use. A structural break occurs where there is a sudden change in the trend of a time series. We observed an immediate decline in benzodiazepine dispensing of 23.6 per 100,000 (95% confidence interval [CI]: -33.6 to -21.2) associated with a structural break in April 2020, followed by a monthly decrease in the trend of 0.3 per 100,000 (95% CI: -0.74 to 0.14). Lower than expected benzodiazepine dispensing rates were observed each month of the pandemic from April 2020 onward, with relative percent differences ranging from − 7.4% (95% CI: -10.1% to – 4.7%) to -20.9% (95% CI: -23.2% to -18.6%). Results were generally similar in analyses stratified by sex, age, neighbourhood income quintile, and urban versus rural residence. Further research is required to understand the clinical implications of these findings and whether these trends were sustained with further follow-up.
Efficiently reconfiguring a connected swarm of labeled robots
Authors: Fekete Sándor P. , Kramer Peter , Rieck Christian , Scheffer Christian , Schmidt Arne
Published: August 2024

When considering motion planning for a swarm of n labeled robots, we need to rearrange a given start configuration into a desired target configuration via a sequence of parallel, collision-free moves. The objective is to reach the new configuration in a minimum amount of time. Problems of this type have been considered before, with recent notable results achieving constant stretch for parallel reconfiguration: If mapping the start configuration to the target configuration requires a maximum Manhattan distance of d, the total duration of an overall schedule can be bounded to $$\mathcal {O}(d)$$

O
(
d
)

, which is optimal up to constant factors. An important constraint for coordinated reconfiguration is to keep the swarm connected after each time step. In previous work, constant stretch could only be achieved if disconnected reconfiguration is allowed, or for scaled configurations of unlabeled robots; on the other hand, the existence of non-constant lower bounds on the stretch factor was unknown. We resolve these major open problems by (1) establishing a lower bound of $$\Omega (\sqrt{n})$$

Ω
(

n

)

for connected, labeled reconfiguration and, most importantly, by (2) proving that for scaled arrangements, constant stretch for connected, labeled reconfiguration can be achieved. In addition, we show that (3) it is -complete to decide whether a makespan of 2 can be achieved, while it is possible to check in polynomial time whether a schedule of makespan 1 exists.
Multi-cycle Direct Numerical Simulations of a Laboratory Scale Engine: Evolution of Boundary Layers and Wall Heat Flux
Authors: Danciu Bogdan A. , Giannakopoulos George K. , Bode Mathis , Frouzakis Christos E.
Published: August 2024

Multi-cycle direct numerical simulations (DNS) of a laboratory-scale engine at technically relevant engine speeds (1500 and 2500 rpm) are performed to investigate the transient velocity and thermal boundary layers (BL) as well as the wall heat flux during the compression stroke under motored operation. The time-varying wall-bounded flow is characterized by a large-scale tumble vortex, which generates vortical structures as the flow rolls off the cylinder wall. The bulk flow is found to strongly affect the development of the BL profiles, especially at higher engine speeds. As a result, the large-scale flow structures lead to alternating pressure gradients near the wall, invalidating the flow equilibrium assumptions used in typical wall modeling approaches. The thickness of the velocity BL and of the viscous sublayer was found to scale inversely with engine speed and crank angle. The thermal BL thickness also scales inversely with engine speed but increases with in-cylinder temperature. In contrast, thermal displacement thickness, which is sometimes used as a proxy for thermal BL thickness, was found to decrease with increasing temperature in the bulk. Examination of the heat flux distribution revealed areas of increased heat flux, particularly at places characterized by strong flow directed towards the wall. In addition, significant cyclic variations in the surface-averaged wall heat flux were observed for both engine speeds. An analysis of the cyclic tumble ratio revealed that the cycles with lower tumble ratio values near top dead center (TDC), indicative of an earlier tumble breakdown, also exhibit higher surface averaged wall heat fluxes. These findings extend previous numerical and experimental results for the evolution of BL structure during the compression stroke and serve as an important step for future engine simulations under realistic operating conditions.
TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema
Authors: Ge Yi-Ling , Li Pei-Jie , Bu Ying-Rui , Zhang Bin , Xu Jin , He Si-Yuan , Cao Qing-Lin , Bai Yun-Gang , Ma Jin , Zhang Lin , Zhou Jie , Xie Man-Jiang
Published: August 2024

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE.
Natural selection requires no teleology in addition to heritable variation in fitness
Authors: Cofnas Nathan
Published: August 2024

According to the standard formulation, natural selection requires variation, differential fitness, and heritability. I argue that this formulation is inadequate because it fails to distinguish natural selection from artificial selection, intelligent design, forward-looking orthogenetic selection, and adaptation via the selection of nonrandom variation. I suggest adding a no teleology condition. The no teleology condition says that the evolutionary process is not guided toward an endpoint represented in the mind of an agent, variation is produced randomly with respect to adaptation, and selection pressures are not forward looking.
Antitumorigenic potential of Lactobacillus-derived extracellular vesicles: p53 succinylation and glycolytic reprogramming in intestinal epithelial cells via SIRT5 modulation
Authors: Zhang Jingbo , Huang Xiumei , Zhang Tingting , Gu Chongqi , Zuo Wei , Fu Lijuan , Dong Yiping , Liu Hao
Published: August 2024

Objective

Colorectal cancer progression involves complex cellular mechanisms. This study examines the effects of Lactobacillus plantarum-derived extracellular vesicles (LEVs) on the SIRT5/p53 axis, focusing on glycolytic metabolic reprogramming and abnormal proliferation in intestinal epithelial cells.

Methods

LEVs were isolated from Lactobacillus plantarum and incubated with Caco-2 cells. Differential gene expression was analyzed through RNA sequencing and compared with TCGA-COAD data. Key target genes and pathways were identified using PPI network and pathway enrichment analysis. Various assays, including RT-qPCR, EdU staining, colony formation, flow cytometry, and Western blotting, were used to assess gene expression, cell proliferation, and metabolic changes. Co-immunoprecipitation confirmed the interaction between SIRT5 and p53, and animal models were employed to validate in vivo effects.

Results

Bioinformatics analysis indicated the SIRT5/p53 axis as a critical pathway in LEVs' modulation of colorectal cancer. LEVs were found to inhibit colorectal cancer cell proliferation and glycolytic metabolism by downregulating SIRT5, influencing p53 desuccinylation. In vivo, LEVs regulated this axis, reducing tumor formation in mice. Clinical sample analysis showed that SIRT5 and p53 succinylation levels correlated with patient prognosis.

Conclusion

Lactobacillus-derived extracellular vesicles play a pivotal role in suppressing colonic tumor formation by modulating the SIRT5/p53 axis. This results in decreased glycolytic metabolic reprogramming and reduced proliferation in intestinal epithelial cells.
Effects of Internal, External, and Neutral Attentional Allocation on Post-Event Processing in Social Anxiety
Authors: Adamis Alexandra M. , Jessup Sarah C. , Olatunji Bunmi O.
Published: August 2024

Purpose

Excessive attentional allocation towards threats has been theorized to play a maintaining role in social anxiety disorder (SAD). However, it is unclear if both heightened attentional focus towards internal threats (i.e., interoceptive signals of anxiety) and external threats (i.e., negative social-evaluative cues) are pathogenic. Further, evidence for the causal pathways by which biased attention maintains SAD is limited. The present study tested the effects of experimentally induced internally and externally oriented attention towards threats relative to a neutral control on state anxiety and post-event processing (PEP) in a highly socially anxious sample.

Methods

During an impromptu speech task, participants (N = 123) were randomized to allocating their attention to their own thoughts, actions, or body sensations (internal condition; n = 41), to an audience member’s reactions and evaluations (external condition; n = 42), or to a neutral object (control condition; n = 40). State anxiety and PEP were assessed immediately following the speech and 24 h later.

Results

Although no differences between the control condition and the external and internal conditions were observed, participants in the internal condition reported significantly higher state anxiety immediately after the speech and higher PEP 24 h later compared to the external condition. State anxiety immediately after the speech mediated heightened PEP 24 h later among the internal condition compared to the external condition.

Conclusions

Findings support the theorized maladaptive role of self-focused attention in the maintenance of SAD and suggest that attending internally may be more harmful than attending externally, despite the presence of socio-evaluative threats in the environment.
Discord-based counterfactual explanations for time series classification
Authors: Bahri Omar , Li Peiyu , Filali Boubrahimi Soukaina , Hamdi Shah Muhammad
Published: August 2024

The opacity inherent in machine learning models presents a significant hindrance to their widespread incorporation into decision-making processes. To address this challenge and foster trust among stakeholders while ensuring decision fairness, the data mining community has been actively advancing the explainable artificial intelligence paradigm. This paper contributes to the evolving field by focusing on counterfactual generation for time series classification models, a domain where research is relatively scarce. We develop, a post-hoc, model agnostic counterfactual explanation algorithm that leverages the Matrix Profile to map time series discords to their nearest neighbors in a target sequence and use this mapping to generate new counterfactual instances. To our knowledge, this is the first effort towards the use of time series discords for counterfactual explanations. We evaluate our algorithm on the University of California Riverside and University of East Anglia archives and compare it to three state-of-the-art univariate and multivariate methods.
Nontrivial t-designs in polar spaces exist for all t
Authors: Weiß Charlene
Published: August 2024

A finite classical polar space of rank n consists of the totally isotropic subspaces of a finite vector space over $$\mathbb {F}_q$$

F
q

equipped with a nondegenerate form such that n is the maximal dimension of such a subspace. A t-$$(n,k,\lambda )$$

(
n
,
k
,
λ
)

design in a finite classical polar space of rank n is a collection Y of totally isotropic k-spaces such that each totally isotropic t-space is contained in exactly $$\lambda $$
λ
members of Y. Nontrivial examples are currently only known for $$t\le 2$$

t
≤
2

. We show that t-$$(n,k,\lambda )$$

(
n
,
k
,
λ
)

designs in polar spaces exist for all t and q provided that $$k>\frac{21}{2}t$$

k
>

21
2

t

and n is sufficiently large enough. The proof is based on a probabilistic method by Kuperberg, Lovett, and Peled, and it is thus nonconstructive.
Examining the impact of ecological deficit on life expectancy in GCC countries: a nonlinear panel data investigation
Authors: Jarallah Shaif , Wirayuda Anak Agung Bagus , Alsamara Mouyad , Barkat Karim , Al-Mahrezi Abdulaziz , Chan Moon Fai
Published: August 2024

The Gulf Cooperation Council (GCC) countries have witnessed remarkable economic growth over recent decades. Arguably, this progress of these major oil and natural gas producers has come to the detriment of the environment in terms of increased CO2 emissions and associated ecological degradation. The effects of these high emissions and environmental challenges on human health, specifically life expectancy (LE), have not been thoroughly explored in the literature. We aim to fill this research gap by assessing the relationship between Ecological footprint deficiency and the diverse and context-specific factors affecting LE in the GCC, highlighting the critical roles of urbanization, economic indicators, and digitization in shaping health outcomes. The study employs panel data for the 2000–2020 period. It utilizes linear and non-linear panel estimation methods to analyze these variables’ long-term and short-term effects. Specifically, we run unit root tests, cointegration analysis to validate our datasets, and OLS, ARDL, and panel threshold regressions to examine said relationships. Our findings reveal a significant relationship between ecological footprint and LE across the GCC countries. The results indicate that a higher ecological deficit is associated with lower LE in our sampled nations. Meanwhile, our panel threshold results highlight more nuanced impacts of our variables of interest, revealing significant threshold effects and intricate dynamics influencing LE. Our results are robust when substituting CO2 emissions for the ecological footprint suggesting and supporting our evidence for a more complex, potentially nonlinear relationship. Our study emphasizes the urgent need for sustainable environmental policies to mitigate health risks and promote long-term well-being in the GCC region. Nuanced approaches are needed to address each GCC country's health and environmental challenges.
Influence of BaTiO3 substitution on structural and thermal response of lead borosilicate glass for ultrasonic applications
Authors: Salah M. , Moustafa El Sayed , Showahy A. A.
Published: August 2024

An extensive examination of the impact of BaTiO3doping on the mechanical and thermal characteristics of lead-borosilicate glasses is provided in this work. The glass density increases noticeably (from 6020 for BaTiO3to 2533 kg/m3for SiO2), and the molar volume decreases, suggesting a denser and more compact structural arrangement. The mechanical properties exhibited a notable improvement upon the addition of BaTiO3. Specifically, the longitudinal ultrasonic velocity (VL) increased from 3927 to 4458 m/s, and the shear velocity (VS) increased from 2317 to 2630 m/s, indicating a reinforced glass network. The bulk modulus increased from 35.71 to 58.06 GPa, and Young’s modulus increased from 57.2 to 92.98 GPa. These significant increases in elastic moduli were attributed to tighter atom packing and higher levels of cross-linking within the glass matrix. Furthermore, the glass structure’s increased rigidity and connectedness were further indicated by the Debye temperature (θD), which increased from 296.8 to 347.3 K. The influence of BaTiO3on the thermal analysis is demonstrated, which revealed that increasing BaTiO3content raises both the glass transition and crystallization temperatures. The results of the experiment demonstrate how much BaTiO3doping can improve the physical characteristics of lead-borosilicate glasses, enabling them to be used in sophisticated optical and structural applications.
On the complexity of minimum maximal acyclic matchings
Authors: Chaudhary Juhi , Mishra Sounaka , Panda B. S.
Published: August 2024

Low-Acy-Matching asks to find a maximal matching M in a given graph G of minimum cardinality such that the set of M-saturated vertices induces an acyclic subgraph in G. The decision version of Low-Acy-Matching is known to be $${\textsf{NP}}$$
NP
-complete. In this paper, we strengthen this result by proving that the decision version of Low-Acy-Matching remains $${\textsf{NP}}$$
NP
-complete for bipartite graphs with maximum degree 6 and planar perfect elimination bipartite graphs. We also show the hardness difference between Low-Acy-Matching and Max-Acy-Matching. Furthermore, we prove that, even for bipartite graphs, Low-Acy-Matching cannot be approximated within a ratio of $$n^{1-\epsilon }$$

n

1
-
ϵ

for any $$\epsilon >0$$

ϵ
>
0

unless $${\textsf{P}}={\textsf{NP}}$$

P
=
NP

. Finally, we establish that Low-Acy-Matching exhibits $$\textsf{APX}$$
APX
-hardness when restricted to 4-regular graphs.
Investigate-Design-Practice-Reflect: An Iterative Community-Engaged Action Process to Improve Population Health
Authors: Rosen Marisa S. , Rogers Ann E. , J. Von Seggern Mary , Grimm Brandon L. , Ramos Athena K. , Schenkelberg Michaela A. , Idoate Regina E. , Dzewaltowski David A.
Published: August 2024

Background

Community-based coalitions are a common strategy for community engagement efforts targeting the improvement of a variety of population health outcomes. The typical processes that coalitions follow to organize efforts include steps that are sequential, slow, and time intensive. These processes also limit local decision-making to the selection of evidence-based policies or programs.

Methods

We present a process control theory-based Community Action Process, Investigate-Design-Practice-Reflect (IDPR), where community hubs (i.e., coalitions) organize agile efforts in a non-sequential, rapid, and efficient manner to harness local assets and data to make decisions regarding the provision and production of population health services. Using qualitative methods, we illustrate and analyze the use of IDPR in a one community case study as part of Wellscapes, a Type 3-hybrid implementation-effectiveness community randomized controlled trial to improve children’s population health physical activity.

Results

We found community members followed the IDPR Community Action Process to rapidly design, organize, deliver, and receive feedback on a community-based, children’s population physical activity prototype, an afterschool Play-in-the-Park opportunity for all children.

Discussion

Following IDPR afforded the community coalition timely learning through feedback within a process that coordinated decisions regarding what community services met community needs (provision decisions) and how to organize the production of the population health services (production decisions).
Uncovering habitat associations and thresholds—insights for managing breeding waterfowl in Eastern Canada
Authors: Frei Barbara , Cox Amelia R. , Brown Andrea , Dyson Matthew E. , Meyer Shawn , Hanson Alan , Hick Kristina , Gilliland Scott G. , Lepage Christine , Tétreault Mathieu , Roy Christian
Published: August 2024

Context

Understanding how habitat influences species abundance is crucial in developing ecologically sound wildlife conservation management plans. Exploring habitat associations and ecological thresholds in species’ responses allows for better conservation and management on a landscape-scale.

Objectives

This work aimed to identify habitat drivers and response thresholds of waterfowl and waterbird species’ densities in eastern Canada to support key landscape-level decisions for habitat conservation and wetland management.

Methods

We developed predictive abundance models for 17 species across eastern Canada from 2001 to 2015 using data from four regional surveys and identified areas where prioritizing enhancement of wetlands would increase the breeding density of five priority waterfowl species.

Results

Habitat associations and spatial abundance patterns varied across species, but most species responded strongly to forest composition, agriculture, and wetland features. Threshold effects occurred and varied among species, yet generally once 14% of a plot was covered in wetlands, positive effects of increased wetland diminished for most species. Our results allow for the targeting of investments in increasing wetland area along portions of eastern Canada that provide the best opportunities to increase breeding densities for priority waterfowl species.

Conclusions

Understanding species-habitat associations and response thresholds allows for landscape management and planning and prioritization of limited resources. We suggest that management and wetland enhancement efforts for waterfowl in eastern Canada should be guided by predictive models and response thresholds of key habitat attributes to best prioritize actions that will have the biggest positive impact on multiple species.
Single- and multiple-trait quantitative trait locus analyses for seed oil and protein contents of soybean populations with advanced breeding line background
Authors: Huynh Tu , Van Kyujung , Mian M. A. Rouf , McHale Leah K.
Published: August 2024

Soybean seed oil and protein contents are negatively correlated, posing challenges to enhance both traits simultaneously. Previous studies have identified numerous oil and protein QTLs via single-trait QTL analysis. Multiple-trait QTL methods were shown to be superior but have not been applied to seed oil and protein contents. Our study aimed to evaluate the effectiveness of single- and multiple-trait multiple interval mapping (ST-MIM and MT-MIM, respectively) for these traits using three recombinant inbred line populations from advanced breeding line crosses tested in four environments. Using original and simulated data, we found that MT-MIM did not outperform ST-MIM for our traits with high heritability (H2 > 0.84). Empirically, MT-MIM confirmed only five out of the seven QTLs detected by ST-MIM, indicating single-trait analysis was sufficient for these traits. All QTLs exerted opposite effects on oil and protein contents with varying protein-to-oil additive effect ratios (-0.4 to -4.8). We calculated the economic impact of the allelic variations via estimated processed values (EPV) using the National Oilseed Processors Association (NOPA) and High Yield + Quality (HY + Q) methods. Oil-increasing alleles had positive effects on both EPVNOPA and EPVHY+Q when the protein-to-oil ratio was low (-0.4 to -0.7). However, when the ratio was high (-4.1 to -4.8), oil-increasing alleles increased EPVNOPA and decreased EPVHY+Q, which penalizes low protein meal. In conclusion, single-trait QTL analysis is adequately effective for high heritability traits like seed oil and protein contents. Additionally, the populations’ elite pedigrees and varying protein-to-oil ratios provide potential lines for further yield assessment and direct integration into breeding programs.
Short-peptide-based enteral nutrition affects rats MDP translocation and protects against gut-lung injury via the PepT1-NOD2-beclin-1 pathway in vivo
Authors: Pang Xiu-feng , Dai Xiao-yong , Zhao Lu-jia , Ye You-wen , Yang Xiao-ying , Wang Huan-huan , Jiang Meng , Zhu Yu-qin , Shi Bin
Published: August 2024

Background

Peptide transporter 1 (PepT1) transports bacterial oligopeptide products and induces inflammation of the bowel. Nutritional peptides compete for the binding of intestinal bacterial products to PepT1. We investigated the mechanism of short-peptide-based enteral nutrition (SPEN) on the damage to the gut caused by the bacterial oligopeptide product muramyl dipeptide (MDP), which is transported by PepT1. The gut-lung axis is a shared mucosal immune system, and immune responses and disorders can affect the gut-respiratory relationship.

Methods and results

Sprague-Dawley rats were gavaged with solutions containing MDP, MDP + SPEN, MDP + intact-protein-based enteral nutrition (IPEN), glucose as a control, or glucose with GSK669 (a NOD2 antagonist). Inflammation, mitochondrial damage, autophagy, and apoptosis were explored to determine the role of the PepT1-nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-beclin-1 signaling pathway in the small intestinal mucosa. MDP and proinflammatory factors of lung tissue were explored to determine that MDP can migrate to lung tissue and cause inflammation. Induction of proinflammatory cell accumulation and intestinal damage in MDP gavage rats was associated with increased NOD2 and Beclin-1 mRNA expression. IL-6 and TNF-α expression and apoptosis were increased, and mitochondrial damage was severe, as indicated by increased mtDNA in the MDP group compared with controls. MDP levels and expression of proinflammatory factors in lung tissue increased in the MDP group compared with the control group. SPEN, but not IPEN, eliminated these impacts.

Conclusions

Gavage of MDP to rats resulted in damage to the gut-lung axis. SPEN reverses the adverse effects of MDP. The PepT1-NOD2-beclin-1 pathway plays a role in small intestinal inflammation, mitochondrial damage, autophagy, and apoptosis.
Evaluation of the seismic response of reinforced concrete buildings in the light of lessons learned from the February 6, 2023, Kahramanmaraş, Türkiye earthquake sequences
Authors: Yön Burak , Dedeoğlu İbrahim Özgür , Yetkin Musa , Erkek Hakan , Calayır Yusuf
Published: August 2024

On 6 February 2023, two significant seismic events occurred in the southeastern region of Türkiye. The seismic activity, which was perceptible in numerous countries beyond Türkiye, resulted in a considerable number of fatalities. A considerable number of individuals lost their lives and were rendered homeless as a result of the disaster. Two of the most significant factors contributing to the occurrence of these tragedies are the magnitude of the earthquake and structural deficiencies. The present study is concerned with a detailed analysis of these two factors. This study initially considers the seismicity of the region where the earthquakes that occurred on 6 February 2023 took place, as well as the seismic characteristics of these earthquakes. Subsequently, the findings of the field studies conducted in Hatay, Adıyaman, Kahramanmaraş and Malatya, the cities where the earthquakes caused the most destruction, are presented. The objective of the field study is to ascertain the collapse patterns, structural damages and the factors influencing these damages in reinforced concrete structures in the region. The primary causes of damage to structures can be attributed to several factors, including the presence of a strong beam-weak column mechanism, the soft story-weak story mechanism, the pounding effect, the short column damage, the long cantilever and overhangs, the short beam damage, the buckling damage, the torsion effect, the quality of the materials, the insufficient transverse reinforcement, the compressive failure due to over-reinforcement, the corrosion effect, the damage to reinforced concrete shear walls, the infill wall damage, and the damage caused by the soil and foundation system. These causes have been evaluated and recommendations have been formulated to prevent structural damage.