bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of ligand recognition and activation of melanin-concentrating hormone receptors
Authors: He Qian , Yuan Qingning , Shan Hong , Wu Canrong , Gu Yimin , Wu Kai , Hu Wen , Zhang Yumu , Xu H. Eric , Zhao Li-Hua
Published: November 2023

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 can couple with multiple G-proteins, including Gi/o, Gq/11, and Gs, while MCHR2 only couple to Gq/11. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with Giand MCH-activated MCHR2 with Gqcomplexes, at the global resolutions of 3.01 Å and 2.40 Å, respectively. These structures reveal that MCH adopts a consistent cysteine-mediated hairpin loop configuration in both receptors. A central arginine from the LGRVY core motif between the two cysteines of MCH penetrates deeply into the transmembrane pocket, triggering receptor activation. Integrated with mutational and functional insights, our findings elucidate the molecular underpinnings of ligand recognition and MCH receptor activation, offering a structured foundation for targeted drug design.
A chemically-induced attenuated strain ofCandida albicansgenerates robust protective immune responses and prevents systemic candidiasis development
Authors: Bose Swagata , Sahu Satya Ranjan , Dutta Abinash , Acharya Narottam
Published: November 2023

Despite current antifungal therapy, invasive candidiasis causes >40% mortality in immunocompromised individuals. Therefore, developing an antifungal vaccine is a priority. Here, we could for the first time successfully attenuate the virulence ofCandida albicansby treating it with a fungistatic dosage of EDTA and demonstrate it to be a potential live whole cell vaccine by using murine models of systemic candidiasis. EDTA inhibited the growth and biofilm formation ofC. albicans. RNA-seq analyses of EDTA-treated cells (CAET) revealed that genes mostly involved in metal homeostasis and ribosome biogenesis were up- and down-regulated, respectively. Consequently, a bulky cell wall with elevated levels of mannan and β-glucan, and reduced levels of total monosomes and polysomes were observed. CAET was eliminated faster than the untreated strain (Ca) as found by differential fungal burden in the vital organs of the mice. Higher monocytes, granulocytes, and platelet counts were detected inCa-vsCAET-challenged mice. While hyper-inflammation and immunosuppression caused the killing ofCa-challenged mice, a critical balance of pro- and anti-inflammatory cytokines-mediated immune responses are the likely reasons for the protective immunity in CAET-infected mice.
Modulation of hepatic transcription factor EB activity during cold exposure uncovers direct regulation of bis(monoacylglycero)phosphate lipids byPla2g15
Authors: Davidson Jessica W. , Jain Raghav , Kizzar Thomas , Geoghegan Gisela , Nesbitt Daniel J , Cavanagh Amy , Abe Akira , Nyame Kwamina , Hunger Andrea , Chao Xiaojuan , James Isabella , Von Bank Helaina , Baldwin Dominique A. , Wade Gina , Michorowska Sylwia , Verma Rakesh , Scheuler Kathryn , Hinkovska-Galcheva Vania , Shishkova Evgenia , Ding Wen-Xing , Coon Joshua J , Shayman James A. , Abu-Remaileh Monther , Simcox Judith A.
Published: November 2023

Cold exposure is a selective environmental stress that elicits a rapid metabolic shift to maintain energy homeostasis. In response to cold exposure, the liver rewires the metabolic state shifting from glucose to lipid catabolism. By probing the liver lipids in cold exposure, we observed that the lysosomal bis(monoacylglycero)phosphate (BMP) lipids were rapidly increased during cold exposure. BMP lipid changes occurred independently of lysosomal abundance but were dependent on the lysosomal transcriptional regulator transcription factor EB (TFEB). Knockdown of TFEB in hepatocytes decreased BMP lipid levels and led to cold intolerance in mice. We assessed TFEB binding sites of lysosomal genes and determined that the phospholipase Pla2g15 regulates BMP lipid catabolism. Knockdown of Pla2g15 in mice increased BMP lipid levels, ablated the cold-induced rise, and improved cold tolerance. Knockout of Pla2g15 in mice and hepatocytes led to increased BMP lipid levels, that were decreased with re-expression of Pla2g15. Mutation of the catalytic site of Pla2g15 ablated the BMP lipid breakdown. Together, our studies uncover TFEB regulation of BMP lipids through Pla2g15 catabolism.
A novel stabilization mechanism accommodating genome length variation in evolutionarily related viral capsids
Authors: Podgorski Jennifer M. , Podgorski Joshua , Abad Lawrence , Jacobs-Sera Deborah , Freeman Krista G. , Brown Colin , Hatfull Graham , Luque Antoni , White Simon J.
Published: November 2023

Tailed bacteriophages are one of the most numerous and diverse group of viruses. They store their genome at quasi-crystalline densities in capsids built from multiple copies of proteins adopting the HK97-fold. The high density of the genome exerts an internal pressure, requiring a maturation process that reinforces their capsids. However, it is unclear how capsid stabilization strategies have adapted to accommodate the evolution of larger genomes in this virus group. Here we characterized a novel capsid reinforcement mechanism in two evolutionary-related actinobacteriophages that modifies the length of a stabilization protein to accommodate a larger genome while maintaining the same capsid size. We used cryo-EM to reveal that capsids contained split hexamers of HK97-fold proteins with a stabilization protein in the chasm. The observation of split hexamers in mature capsids was unprecedented, so we rationalized this result mathematically, discovering that icosahedral capsids can be formed by all split or skewed hexamers as long as their T-number is not a multiple of three. Our results suggest that analogous stabilization mechanisms can be present in other icosahedral capsids, and they provide a strategy for engineering capsids accommodating larger DNA cargoes as gene delivery systems.

Significance Statement

How capsids are stabilized and change size is an important part of understanding how to design protein containers and understand viral evolution. We describe a novel capsid stability mechanism that allows the capsid to package a larger genome without changing the capsid architecture and have predicted other capsids using this mechanism. Beyond the evolutionary implications, our findings provide a mechanism to increase the amount of DNA packaged in a capsid, offering a solution to engineer gene delivery systems with larger DNA content, a pressing challenge in gene therapy.
Last in first out: SIV proviruses seeded later in infection are harbored in short-lived CD4+T cells
Authors: Sambaturu Narmada , Fray Emily J. , Wu Fengting , Zitzmann Carolin , Simonetti Francesco R. , Barouch Dan H. , Siliciano Janet D. , Siliciano Robert F. , Ribeiro Ruy M. , Perelson Alan S. , Molina-París Carmen , Leitner Thomas
Published: November 2023

HIV can persist in a latent form as integrated DNA (provirus) in resting CD4+T cells of infected individuals and as such is unaffected by antiretroviral therapy (ART). Despite being a major obstacle for eradication efforts, the genetic variation and timing of formation of this latent reservoir remains poorly understood. Previous studies on when virus is deposited in the latent reservoir have come to contradictory conclusions. To reexamine the genetic variation of HIV in CD4+T cells during ART, we determined the divergence in envelope sequences collected from 10 SIV infected rhesus macaques. We found that the macaques displayed a biphasic decline of the viral divergence over time, where the first phase lasted for an average of 11.6 weeks (range 4-28 weeks). Motivated by recent observations that the HIV-infected CD4+T cell population is composed of short- and long-lived subsets, we developed a model to study the divergence dynamics. We found that SIV in short-lived cells was on average more diverged, while long-lived cells harbored less diverged virus. This suggests that the long-lived cells harbor virus deposited starting earlier in infection and continuing throughout infection, while short-lived cells predominantly harbor more recent virus. As these cell populations decayed, the overall proviral divergence decline matched that observed in the empirical data. This model explains previous seemingly contradictory results on the timing of virus deposition into the latent reservoir, and should provide guidance for future eradication efforts.

Significance statement

HIV can persist in a latent reservoir unaffected by antiretroviral drugs. The genetic variation of this latent virus population is a major obstacle for eradication efforts, but also a clue to when HIV variants are deposited in the reservoirs. Unfortunately, previous studies assessing when the virus was deposited in latent reservoirs have come to contradictory conclusions. Here, we propose SIV proviral DNA exists in both short- and long-lived CD4+T cells, and that these two cell subsets harbor different genetically diverged virus populations. Our model explains the contradictory findings and shows that when CD4+T cells decay under effective drug treatment, which prevents virus replication, the resulting virus divergence decreases and recapitulates observed data. This knowledge should help in improving future eradication efforts.
Tonically active GABAergic neurons in the dorsal periaqueductal gray control the initiation and execution of instinctive escape
Authors: Stempel A. Vanessa , Evans Dominic A. , Pavón Arocas Oriol , Claudi Federico , Lenzi Stephen C. , Kutsarova Elena , Margrie Troy W. , Branco Tiago
Published: November 2023

To avoid predation, animals perform defensive actions that are both instinctive and adaptable to the environment. In mice, the decision to escape from imminent threats is implemented by a feed-forward circuit in the midbrain, where excitatory VGluT2+neurons in the dorsal periaqueductal gray (dPAG) compute escape initiation and escape vigour from threat evidence. Here we show that GABAergic VGAT+neurons in the dPAG dynamically control this process by modulating the excitability of excitatory escape neurons. Usingin vitropatchclamp andin vivoneural activity recordings in freely behaving mice we found that VGAT+dPAG neurons fire action potentials tonically in the absence of synaptic inputs and are a major source of synaptic inhibition to VGluT2+dPAG neurons. Activity in these spontaneously firing VGAT+cells transiently decreases at escape onset and increases during escape, peaking at escape termination. Optogenetically increasing or decreasing VGAT+dPAG activity bidirectionally changes the probability of escape when the stimulation is delivered at the time of threat onset, and the duration of escape when delivered after escape initiation. We conclude that the activity of tonically firing VGAT+dPAG neurons sets a threshold for escape initiation and controls the execution of the flight locomotor action.
Characterization of gene regulatory elements and dynamic antimicrobial immune responses in mosquito cells using PRO-seq
Authors: van Hout Femke A.H. , Himanen Samu V. , Vihervaara Anniina , Miesen Pascal
Published: November 2023

TheAedes aegyptimosquito transmits arboviruses such as dengue, Zika, and chikungunya virus, posing a substantial threat to global health. The mosquito immune response determines virus transmission, yet, insight into the transcriptional regulation of mosquito immunity remains limited. In this study, we optimized the nascent RNA-sequencing method Precision Run-On sequencing (PRO-seq) forAedes aegyptiAag2 cells. PRO-seq enabled profiling the distribution of active RNA polymerases across the mosquito genome at nucleotide precision and identified the exact transcription start nucleotides (TSN) of expressed genes. Based on exact positioning of the TSN, we uncovered core promoter elements, including the Initiator and Downstream Promoter Elements. Notably, RNA polymerase accumulates at the promoter-proximal region of genes, but transcribes into the divergent region to a lesser extent than in vertebrates. To investigate rapid and dynamic immune responses, Aag2 cells were immune-stimulated with heat-inactivatedE. colifor 1 and 4 hours. Differential gene expression analysis revealed different groups of genes to be induced over time. While Clip domain serine proteases and antimicrobial peptides were induced promptly and sustained, a delayed stress response consisting of heat shock-related genes was only seen at 4 hours after stimulation. Strikingly, gene sets with different temporal expression profiles were associated with distinct transcription factor binding motifs. Altogether, our study provides valuable insights into the functional genomics ofAedes aegyptiand indicates that even within a rapid response, different dynamics emerge, potentially regulated by distinct transcription factors. These insights are crucial to gain a better understanding of the mosquito immune response and its regulation.
From Genomics Data to Causality: An Integrated Pipeline for Mendelian Randomization
Authors: Sharma Jyoti , Jangale Vaishnavi , Swain Asish Kumar , Yadav Pankaj
Published: November 2023

Background

Mendelian randomization (MR) has emerged as a valuable tool for causal inference in genetic epidemiology. Existing MR methods have issues related to pleiotropy and offer limited comprehensiveness. Here, we introduce an integrated MR analysis pipeline designed for GWAS summary statistics data. Our pipeline integrates feature selection, harmonization, and checkpoint mechanisms to improve the accuracy and reliability of MR analysis.

Methods

In classical GWAS, the p-value threshold usually does not guarantee to identify causal single-nucleotide polymorphisms (SNPs). In such cases, t-statistics can be considered as imperative and robust criteria for identifying causal SNPs. Therefore, in this study, we computed the t-statistic for all independent SNPs remained after linkage disequilibrium pruning. Next, prior to harmonization, we removed SNPs having a t-statistic below the average t-statistic value. Furthermore, our pipeline incorporates sensitivity analysis tests at each step to reduce the chances of directional pleiotropy.

Result and Conclusion

We applied our pipeline to single-sample and two-sample MR study designs, encompassing diverse populations and a wide range of diseases. Our results demonstrate superior performance compared to existing MR methods. In conclusion, our research presents an integrated MR analysis pipeline that significantly enhances the accuracy and reliability of MR studies. By outperforming existing methods and providing comprehensive validation, this pipeline represents a valuable tool for researchers in genetics and epidemiology.
Applications of Large Language Models (LLMs) in Breast Cancer Care
Authors: Sorin Vera , Glicksberg Benjamin S. , Barash Yiftach , Konen Eli , Nadkarni Girish , Klang Eyal
Published: November 2023

Purpose

Recently introduced Large Language Models (LLMs) such as ChatGPT have already shown promising results in natural language processing in healthcare. The aim of this study is to systematically review the literature on the applications of LLMs in breast cancer diagnosis and care.

Methods

A literature search was conducted using MEDLINE, focusing on studies published up to October 22nd, 2023, using the following terms: “large language models”, “LLM”, “GPT”, “ChatGPT”, “OpenAI”, and “breast”.

Results

Five studies met our inclusion criteria. All studies were published in 2023, focusing on ChatGPT-3.5 or GPT-4 by OpenAI. Applications included information extraction from clinical notes, question-answering based on guidelines, and patients’ management recommendations. The rate of correct answers varied from 64-98%, with the highest accuracy (88-98%) observed in information extraction and question-answering tasks. Notably, most studies utilized real patient data rather than data sourced from the internet. Limitations included inconsistent accuracy, prompt sensitivity, and overlooked clinical details, highlighting areas for cautious LLM integration into clinical practice.

Conclusion

LLMs demonstrate promise in text analysis tasks related to breast cancer care, including information extraction and guideline-based question-answering. However, variations in accuracy and the occurrence of erroneous outputs necessitate validation and oversight. Future works should focus on improving reliability of LLMs within clinical workflow.
The change in the biomass allocation to stems and leaves in young plants of Dimorphandra wilsonii under eCO2 may harm this endangered species in native areas
Authors: Gonçalves Marina Efigenia , Viegas Geane Cristina Eugenio , Melo Nayara Magry Jesus , Souza João Paulo
Published: November 2023

Climate change is among the main threats to ecosystems, affecting biodiversity and ecosystem services. These changes are associated with increased atmospheric carbon dioxide concentration ([CO2]). This study aimed to investigate how [CO2] influences chlorophyll a fluorescence, vegetative growth, biomass production, and the number of root nodules (NRN) of Dimorphandra wilsonii, a critically endangered species. The study was conducted in six open‐top chambers with two CO2 levels, at elevated [CO2] (eCO2, 717 ± 77 ppm) and at ambient [CO2] (aCO2, 539 ± 42 ppm). We monitored vegetative growth weekly, and at the end of the experiment, we measured chlorophyll a fluorescence and biomass production. Dimorphandra wilsonii plants under eCO2 showed higher (p < 0.05) average leaf dry mass, average leaf area, and lower (p < 0.05) root/shoot ratio than plants under aCO2. The greater aerial biomass allocation contributes to maximizing the photosynthesis performance but could also result in the self‐shading of old basal leaves by new distal leaves on branches. This adjustment could be advantageous in the competition for light; however, it would be a disadvantage for below‐ground resource competition (such as water and nutrients), which could result in decreased drought resistance. Also, this adjustment would be unfavorable to D. wilsonii, which occurs in a seasonal climate environment competing with invasive grasses. Thus, it is possible that climate change scenarios with increases in [CO2] and drought periods could negatively influence the establishment of young plants of D. wilsonii in their natural occurrence area, which could worsen the conservation status of the species.
Matter and Method: The Quest for a New‐Materialist Methodology in Management Studies
Authors: Benozzo Angelo , Distinto Marco , Priola Vincenza
Published: November 2023

This paper offers methodological and theoretical contributions to the field of management at the so‐called ‘turn to matter’ postulated within new materialist perspectives. It discusses more‐than‐human perspectives in management research and provides some methodological directions to support new materialist empirical investigations. Theoretically grounded on new materialism and posthumanism, the paper applies the assemblage approach that focuses on understanding the redistribution of agency to the network of people, things and discourses. In developing three exemplars of assemblages, it shows how it is possible to methodologically encompass the entanglement of the material, the organic, the human and the more‐than‐human to explore a phenomenon such as working from home. The paper concludes by reflecting on what new materialist qualitative research in management could become in order to generate new ways of imagining management, organizations and working lives, as more‐than‐human entanglements.
Radiographic age estimation based on degenerative changes of vertebrae
Authors: Adams Bradley J. , Butler Erin , Fuehr Stephanie M. , Olivares‐Pérez Fransheska , Tamayo Alexandra Semma
Published: November 2023

Age estimation is an important component of decedent identification. When assessing adult remains, anthropologists frequently use gross examination of skeletal elements, such as clavicles, ribs, and pubic symphyses. For fleshed bodies, this requires the removal of these elements and maceration prior to analysis. A new method was developed using radiographic imaging to estimate age from degenerative changes of the lower thoracic and upper lumbar vertebrae. This technique will complement anthropological age estimation methods in young and middle‐aged adults and may serve as a stand‐alone method for older individuals. Digital radiographs from 240 medical examiner cases were evaluated. The sample included 120 females and 120 males between the ages of 18 and 101 years. A 3‐phased scoring system was used for the target vertebrae. Transition analysis was conducted on binned average scores and a Bayesian approach was used to assign age intervals. At the 90% credible interval, individuals in Bin 1 were under 36 years of age while those in Bin 3 were over 47 years of age. Individuals in Bin 2 showed too much age variation to be informative. No significant differences were found between males and females. These findings will be especially useful in the age estimation of older adults and may eliminate the need for skeletal sampling in medicolegal cases where advanced degenerative changes are radiographically observed in the lower thoracic and/or upper lumbar vertebrae. This method was developed for use on fleshed individuals but may also be applicable to skeletonized remains.
Protective effects of baicalin on diethyl nitrosamine‐induced liver cirrhosis by suppressing oxidative stress and inflammation
Authors: Wang Hui , Chang Yufei , Liu Xiao , Liu Linan , Hua Mingxi , Li Ang
Published: November 2023

Baicalin (BA) is a natural product extract with anti‐inflammatory, antioxidant, and hepatoprotective properties. Given that the exact underlying mechanisms responsible for the impact of BA on liver cirrhosis remain ambiguous, a detailed investigation is sorely needed. Accordingly, a rat liver cirrhosis model was established via the intraperitoneal injection of diethyl nitrosamine (DEN, 100 mg/kg). Following the modeling, these rats were given BA (100 mg/kg) or N‐acetylcysteine (NAC, 150 mg/kg) alone or in combination. The pathological morphology of rat liver tissues in each group was observed by hematoxylin and eosin staining and Masson's trichrome staining. The expression of fibrosis‐related proteins was evaluated by Western blot, and the levels of liver function‐related biochemical indexes, oxidative stress‐related indexes, and inflammatory factors in the serum by enzyme‐linked immunosorbent assays (ELISA). The level of mitochondrial reactive oxygen species was measured by flow cytometry. The results depicted that in the rat model of DEN‐induced liver cirrhosis, BA reduced the expression of fibrosis‐related proteins (collagen type I alpha 1, α‐smooth muscle actin, and transforming growth factor‐β1), thereby alleviating the structural fibrosis of liver tissue. Furthermore, BA could diminish the level of mitochondrial reactive oxygen species, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), interleukin (IL)‐1β, IL‐6, tumor necrosis factor‐α (TNF‐α), and monocyte chemotactic protein‐1 (MCP‐1), while promoting albumin, superoxide dismutase (SOD), and glutathione peroxidase (GSH‐Px) levels. Notably, all these effects of BA above were strengthened following the combined treatment of BA and NAC. On the whole, BA suppresses liver fibrosis by inhibiting oxidative stress and inflammation, thereby exerting a hepatoprotective effect.
An 8‐year observational study of the death places of patients with COPD in Turkey
Authors: İdikut Aytekin , İnam Maide Gözde , Karadeniz Güven Damla , Ceylan Serdar , Karcioğlu Oğuz
Published: November 2023

Aim

The place of death is one of the indicators of the quality of end‐of‐life care, which has become an essential public health issue with the aging of the population and the increase in life expectancy. There is a lack of data regarding the location of deaths caused by chronic obstructive pulmonary disease (COPD), the third‐leading cause of mortality worldwide. This retrospective, cross‐sectional study aimed to investigate the places of death of patients with COPD in Turkey and their trends over the years.

Methods

The study included patients who had a COPD International Classification of Diseases code in the hospital information system and were provided a medication report for this disease in a university hospital's chest diseases outpatient clinic between January 1, 2014, and December 31, 2021. The place and date of death were obtained from the death notification system and recorded as an in‐hospital or out‐of‐hospital death.

Results

A total of 1402 (77.3%) patients died in the hospital and 412 (22.7%) died outside the hospital, and when comparing the pandemic period and before, no significant difference was observed between the places of death. Sixty‐three (49.6%) of 127 patients over the age of 90 years died outside the hospital, and a significant relationship was observed between advanced age and out‐of‐hospital mortality (P < 0.005).

Conclusion

According to our findings, a substantial number of patients with COPD in Turkey die in hospitals. The insufficiency of nursing homes and lack of hospice care cause more hospital deaths. Our data are expected to guide the development of end‐of‐life care policies for patients with COPD in our country. Geriatr Gerontol Int 2023; 23: 938–944.
Liver abscess after drug‐eluting bead transarterial chemoembolization for hepatic malignant tumors: Clinical features, pathogenesis, and management
Authors: Wang Li‐Jun , Yin Liang , Liu Kai‐Cai , Lv Wei‐Fu , Lu Dong
Published: November 2023

Aim

The study aimed to investigate the clinical features, incidence, pathogenesis, and management of liver abscess after drug‐eluting bead transarterial chemoembolization (DEB‐TACE) for primary and metastatic hepatic malignant tumors.

Methods

From June 2019 to June 2021, patients with liver abscess after DEB‐TACE for primary and metastatic hepatic malignant tumors were reviewed and evaluated at our hospital. Demographic and clinical data, radiological findings, management approaches, and prognosis were retrospectively analyzed.

Results

In total, 419 DEB‐TACE procedures were carried out in 314 patients with primary and metastatic liver tumors at our medical center. Twelve patients were confirmed to have liver abscesses after DEB‐TACE through clinical manifestations, laboratory investigations, and imaging. In this study, the incidence of liver abscess was 3.82% per patient and 2.86% per DEB‐TACE procedure. After percutaneous drainage and anti‐inflammatory treatments, 10 patients recovered, and the remaining 2 patients died due to direct complications of liver abscess, such as sepsis and multiple organ failure. The mortality rate of liver abscesses after DEB‐TACE was 16.7% (2/12).

Conclusion

The incidence of liver abscess after DEB‐TACE is relatively high and can have serious consequences, including death. Potential risk factors could include large tumor size, history of bile duct or tumor resection, history of diabetes, small DEB size (100–300 μm). Sensitive antibiotics therapy and percutaneous abscess aspiration/drainage are effective treatments for liver abscess after DEB‐TACE.
Drug displacement from protein binding: isolation of a redistributional drug interaction in vivo
Authors: McQUEEN E. G. , WARDELL W. M.
Published: November 2023

The pharmacokinetic interaction between phenylbutazone and sulphadoxine has been studied in live sheep.

Intravenous injection of phenylbutazone causes a rapid fall in the concentration of total sulphadoxine together with a simultaneous rise in the concentration of free sulphadoxine in plasma. Both processes are complete within 3 min of the injection of phenylbutazone.

These reciprocal changes in the concentrations of total and free sulphadoxine in plasma do not depend on changes in the absorption, hepatic metabolism or renal excretion of sulphadoxine. By exclusion therefore, it is concluded that the effect of phenylbutazone in this interaction is solely to cause redistribution of the sulphadoxine.
Inhibition of contact sensitivity in the mouse by topical application of corticosteroids
Authors: EVANS D. P. , HOSSACK MARGARET , THOMSON D. S.
Published: November 2023

Topical application of oxazolone to the ears of mice previously sensitized to this hapten resulted in a marked increase in ear weight 24 h later.

Topical application of hydrocortisone, betamethasone 17‐valerate, fluocinolone acetonide or triamcinolone acetonide inhibited this response in a dose dependent manner.

The free alcohols of the three fluorinated compounds were only weakly active.

Activity in this model was truly local. Oral administration of hydrocortisone or fluocinolone acetonide at doses comparable to those used topically failed to inhibit the ear swelling.

Some steroids with poor anti‐inflammatory properties had no significant effect.
The application of a multi‐component reaction peptide as a model regenerative active to enhance skin wound‐healing postlaser procedure in a double‐blinded placebo‐controlled clinical trial
Authors: Liao I‐Chien , He Chunyan , Liu Xue Lucia , Barresi‐Thornton Rebecca , Wangari‐Olivero Janet , Qian Mark Kun , Neo Boonhoe , Betts Richard , Ding Chunmei , Juchaux Franck , Chen Ying , Marat Xavier , Zheng Qian , Bouez Charbel
Published: November 2023

Introduction

Esthetic procedures are currently among the most effective options for consumers seeking to correct aging signs such as fine lines, wrinkles, and skin tone unevenness. Currently, there is a scientific need for an adjunct active to be paired with esthetic procedures to encourage wound recovery and address postprocedure pigmentation concerns.

Objective

Toward that goal, this study assessed the efficacy of a peptide created from a multi‐component reaction (multi‐component peptide, MCP) as a model active for postprocedure care and evaluated its ability to promote skin healing in an ablative laser‐induced wound model on the forearm.

Methods

The mechanism of action of MCP was investigated using tubo assays, 2D melanocyte, and fibroblast cultures, reconstructed skin equivalents, and ex vivo skin explants. The MCP formula and the clinical benchmark formula of Aquaphor were assessed head‐to‐head by applying the products topically in an ablative laser‐induced wound model (n = 20 subjects). The promotion of wound healing was evaluated by the investigator assessment of epithelial confluence, crusting or scabbing, general wound appearance, erythema, and edema.

Results

MCP was determined to be beneficial to postprocedure skin recovery and healing by four main mechanisms of action: barrier repair as determined in an ex vivo tape‐stripping model, reduction of inflammation and postinflammatory hyperpigmentation, reduction of elastase activity, and stimulation of fibroblast through the mTOR pathway. The formula containing 10% MCP enhanced the kinetics of epithelial confluence and improvement of the crusting or scabbing appearance of the laser‐generated wounds in a laser‐induced mini‐zone wound healing study on the forearm.

Conclusion

This study demonstrates the use of MCP as a proof of concept regenerative active that when incorporated into an optimized postprocedure skincare formula can improve skin healing and enhance the appearance of skin after injury with relevance to ablative aesthetic procedures.
L2 grammar‐for‐interaction: Functions of “and”‐prefaced turns in L2 students’ collaborative talk
Authors: Tůma František , Kääntä Leila , Jakonen Teppo
Published: November 2023

This article examines how second language (L2) interactional competence is manifested in students’ use of “and”‐prefaced turns when doing meaning‐focused oral tasks in pairs and small groups. Drawing on video recordings from English‐as‐a‐foreign‐language upper‐secondary classes recorded in Czechia and Finland, 86 sequences involving “and”‐prefaced turns were scrutinized using multimodal conversation analysis, focusing on language, gaze, and material resources. The findings suggest that by producing “and”‐prefaced turns, students orient to task progression. These turns have two functions: task managerial and contribution to the emerging task answer. By using task‐managerial “and”‐prefaced turns, the current speaker invites another student to participate, while in “and”‐prefaced contributions to the task answer, a participant adds to, generalizes, or modifies the previous task answer. The analysis shows that students mobilized their L2 interactional competence in producing “and”‐prefaced turns in close coordination with embodied resources and with respect to the spatio‐material surroundings and the nature of the task. These findings contribute to the multimodal reconceptualization of the grammar–body interface and research on turn‐initial particles within L2 interactional competence.
Prevalence of COVID‐19 anxiety, geriatric anxiety, and related factors among the elderly in Quchan, Iran during the COVID‐19 pandemic: a cross‐sectional study
Authors: Mortazavi Hamed , Sharifian Elham , Hassannejad Mahdi , Rahnama Mozhgan , Abdollahimohammad Abdolghani , Ildarabadi Es‐hagh
Published: November 2023

Background

Anxiety is a prevalent mental disorder among the elderly, leading to discomfort, disability, increased expenses, reduced quality of life, and dysfunction. Consequently, this study was conducted to determine the prevalence of COVID‐19 anxiety and geriatric anxiety, along with the factors influencing anxiety, in the elderly population served by urban healthcare centres in Quchan.

Methods

This cross‐sectional study involved 650 elderly individuals aged 60–95 years. The participants were selected using a two‐stage cluster sampling method. Data were collected through three questionnaires: the Geriatric Anxiety Inventory (GAI), the Corona Disease Anxiety Scale (CDAS), and a questionnaire on factors contributing to anxiety. Data analysis was performed using simple and multiple regression with IBM SPSS 24.

Results

The prevalence of geriatric anxiety among the elderly was 40.3%, while the prevalence of COVID‐19 anxiety (moderate and severe) was 22.8%. Significant relationships were observed between geriatric anxiety and substance abuse, stressful life events, comorbidities, COVID‐19 anxiety, financial support, loneliness, walking habits, and sleep patterns (P < 0.05).

Conclusion

COVID‐19 anxiety and geriatric anxiety are prevalent concerns among the elderly. Factors like substance abuse, stressful life events, COVID‐19‐related anxiety, comorbidity, living alone, lack of financial support, and poor walking and sleeping habits, which affect anxiety in the elderly, it is essential to address these factors in life planning and provide services through relevant organisations, healthcare teams, and initiatives by the elderly themselves.
The Calkin algebra, Kazhdan's property (T), and strongly self‐absorbing C∗$\mathrm{C}^*$‐algebras
Authors: Farah Ilijas
Published: November 2023

It is well known that the relative commutant of every separable nuclear ‐subalgebra of the Calkin algebra has a unital copy of Cuntz algebra . We prove that the Calkin algebra has a separable ‐subalgebra whose relative commutant has no simple, unital, and noncommutative ‐subalgebra. On the other hand, the corona of every stable, separable ‐algebra that tensorially absorbs the Jiang–Su algebra has the property that the relative commutant of every separable ‐subalgebra contains a unital copy of . Analogous result holds for other strongly self‐absorbing ‐algebras. As an application, the Calkin algebra is not isomorphic to the corona of the stabilization of the Cuntz algebra , any other Kirchberg algebra, or even the corona of the stabilization of any unital, ‐stable ‐algebra.
Bin packing problem with restricted item fragmentation: Assignment of jobs in multi-product assembly environment with overtime
Authors: Ustuncelik Mustafa , Koc Cagri , Tunc Huseyin
Published: November 2023

This paper studies the assignment problem of multi product assembly jobs to days. The problem aims to minimize the amount of overtime while avoiding assembly delays for jobs that can be fragmented into smaller sub-tasks. When sequence-dependent setup times are negligible, the problem considered transforms into the bin packing problem with restricted item fragmentation where jobs represent items and days stand for bins. We present a mixed integer programming model of the problem by extending earlier formulations in the literature. Computational experiments show that the mathematical model obtained optimal solutions for majority of instances tested within reasonable computation times.
Scheduling of distributed additive manufacturing machines considering carbon emissions
Authors: Kucukkoc Ibrahim
Published: November 2023

Additive manufacturing is a rapidly growing technology shaping the future of manufacturing. In an increasingly competitive economy, additive manufacturing can help businesses to remain agile, innovative, and sustainable. This paper introduces the multi-site additive manufacturing (AM) machine scheduling problem considering carbon emissions caused by production and transportation. A mixed-integer linear programming model is developed aiming to optimise two separate objectives addressing economic and environmental sustainability in a multiple unrelated AM machine environment. The former is the total cost caused by production, transportation, set-up and tardiness penalty and the latter is the total amount of carbon emissions caused by production and transportation. The model is coded in Python and solved by Gurobi Optimizer. A numerical example is provided to represent the basic characteristics of the problem and show the necessity of the proposed framework. A comprehensive computational study is conducted under 600s and 1800s time limits for two main scenarios and the results have been elaborated. This article introduces the concept of considering both economic and environmental sustainability caused by production and transportation, proposing the first mathematical model and measuring its performance through a comprehensive experimental study.
Aspects of scaling and scalability for flow-based sampling of lattice QCD
Authors: Abbott Ryan , Albergo Michael S. , Botev Aleksandar , Boyda Denis , Cranmer Kyle , Hackett Daniel C. , Matthews Alexander G. D. G. , Racanière Sébastien , Razavi Ali , Rezende Danilo J. , Romero-López Fernando , Shanahan Phiala E. , Urban Julian M.
Published: November 2023

Recent applications of machine-learned normalizing flows to sampling in lattice field theory suggest that such methods may be able to mitigate critical slowing down and topological freezing. However, these demonstrations have been at the scale of toy models, and it remains to be determined whether they can be applied to state-of-the-art lattice quantum chromodynamics calculations. Assessing the viability of sampling algorithms for lattice field theory at scale has traditionally been accomplished using simple cost scaling laws, but as we discuss in this work, their utility is limited for flow-based approaches. We conclude that flow-based approaches to sampling are better thought of as a broad family of algorithms with different scaling properties, and that scalability must be assessed experimentally.
A comprehensive study of Bardeen stars with conformal motion in $$f({\mathcal {G}})$$ gravity
Authors: Rashid Aisha , Malik Adnan , Shamir M. Farasat
Published: November 2023

In this manuscript, we use the conformal killing vectors to solve the Einstein–Maxwell field equations in the background of modified $$f({\mathcal {G}})$$

f
(
G
)

gravity. We consider the observational data for four different stars namely $$PSR~J1614-2230$$

P
S
R

J
1614
-
2230

, $$PSR ~J1930+327$$

P
S
R

J
1930
+
327

, $$Cen~X-3$$

C
e
n

X
-
3

and $$Vela~X-1$$

V
e
l
a

X
-
1

respectively. By using the data, we derive the physical parameters from the matching criteria using conformal killing vectors and the exterior Bardeen geometry. Furthermore, several physical properties of compact stellar structures are examined in order to achieve the physical validity and stability for considered models. The graphical analysis including energy density, pressure components, equation of state parameters, and energy conditions are examined. Moreover, the equilibrium conditions through Tolman–Oppenheimer–Volkoff equation and stability criteria through adiabatic index for the charged stellar structure study are investigated. It is worth noting that all of these compact objects are physically viable and stable under conformal motion in context of Bardeen geometry for two different models of $$f({\mathcal {G}})$$

f
(
G
)

theory of gravity. Conclusively, the results show that f(G) gravity with Bardeen model may provide more massive stellar objects as compared to general relativity.
Group-Aware Graph Neural Network for Nationwide City Air Quality Forecasting
Authors: Chen Ling , Xu Jiahui , Wu Binqing , Huang Jianlong
Published: November 2023

The problem of air pollution threatens public health. Air quality forecasting can provide the air quality index hours or even days later, which can help the public to prevent air pollution in advance. Previous works focus on citywide air quality forecasting and cannot solve nationwide city forecasting problems, whose difficulties lie in capturing the latent dependencies between geographically distant but highly correlated cities. In this article, we propose the group-aware graph neural network (GAGNN), a hierarchical model for nationwide city air quality forecasting. The model constructs a city graph and a city group graph to model the spatial and latent dependencies between cities, respectively. GAGNN introduces a differentiable grouping network to discover the latent dependencies among cities and generate city groups. Based on the generated city groups, a group correlation encoding module is introduced to learn the correlations between them, which can effectively capture the dependencies between city groups. After the graph construction, GAGNN implements message passing mechanism to model the dependencies between cities and city groups. The evaluation experiments on two real-world nationwide city air quality datasets, including the China dataset and the US dataset, indicate that our GAGNN outperforms existing forecasting models.
A Cost–Benefit Analysis of Preparing National Veterinary Services for Transboundary Animal Disease Emergencies
Authors: Gilbert William , Adamson David , Donachie Daniel , Hamilton Keith , Rushton Jonathan
Published: November 2023

The natural, accidental, or deliberate release of pathogens into livestock populations carries with it a range of consequences for society, from zoonotic disease outbreaks, to changes in food security and economic welfare. An important contribution to mitigating the risk of disease outbreaks comes from having well-prepared emergency response plans and agencies with the capacity to put those plans into operation. In the case of animal disease, national Veterinary Services (VS) take a central role. Unknown and uncertain events, such as if, when and where the next disease outbreak will occur makes economic decision-making a challenge. While the costs of preparing for emergencies can be quantified in a conventional manner, the scope, scale, and likelihood of benefits actually accruing are all subject to uncertainty. This study attempts to examine the costs and benefits of preparing national VS for animal disease emergencies, including natural, accidental, or deliberate release of pathogens. Data collected as part of the World Organisation for Animal Health’s Performance of VS program for countries in East and West Africa and South East Asia were used for estimating investment costs. A state-contingent approach is used to constrain the uncertainty space in terms of disease impact. The probability of a disease event occurring and the probability of that event being contained by emergency preparation are used to describe a frontier at which investment breaks-even in a variety of scenarios. An increased probability of breaking-even on investment was found with high livestock numbers per capita and increasing intensification in livestock production systems. The method and findings provide a means to understand the benefits of preparing for uncertain events and are aimed to further the dialogue around policy development for livestock disease emergencies in lower-income countries.
A Modified Latent Dirichlet Allocation Topic Approach for Driving Style Exploration Using Large-Scale Ride-Hailing GPS Data
Authors: Li Ye , Chen Yiqi , Bao Jie , Xing Lu , Tang Jinjun , Dong Changyin , Gu Ruifeng
Published: November 2023

Driving style identification is of vital importance for intelligent driving system design and urban traffic management. This study aims to identify and analyze driving styles using large-scale ride-hailing GPS data taking different time periods, traffic, and weather conditions into account. The large-scale GPS data are collected and preprocessed, and then, the k-means clustering is implemented to acquire driving behavior. The modified latent Dirichlet allocation topic approach is applied to extract the driving states as the latent variables behind driving behaviors and finally recognize driving styles. The results show that driving styles are composed of five driving states with different probability combinations. Different driving styles in different situations are further analyzed and compared. When considering the impact of peak periods on the driving style, it indicates that styles tend to be conservative in the morning peak, free and dispersed in the evening peak, and diverse in the off-peak hours. While comparing styles regarding the influence of workdays, drivers act more cautiously and conservatively on weekdays but freer on weekends without the pressure of peak hours. The weather factor is also explored and rainy days are verified to be the resistance of driving so that most drivers become cautious and conservative. Finally, two aberrant driving styles are discovered and countermeasures are suggested to improve traffic safety.
The Relationship between Healthy Lifestyle, Self‐Esteem, and Subjective Vitality in the Older Adults of Sirjan
Authors: Alizadeh Somayeh , Borhaninejad Vahidreza , Sadeghi Reza , Khanjani Narges , Saber Maryam , Abolghaseminejad Parniya
Published: November 2023

Older adults are a vulnerable group and face a series of problems that are preventable by changing their lifestyle, so it is necessary to understand the healthy lifestyle and its related factors in older adults. This study aimed to determine the relationship between healthy lifestyle, self‐esteem, and subjective vitality in the older adults of Sirjan. This descriptive‐analytical cross‐sectional study included 200 older adults referred to community health centers in Sirjan in 2021. Older adults with inclusion criteria were selected by two‐stage cluster sampling. Data were collected by demographic information questionnaire, the healthy lifestyle questionnaire for elderly, the Rosenberg self‐esteem scale, and the subjective vitality scale. The data were analyzed using SPSS20 and descriptive and inferential statistics (Mann–Whitney U test, Kruskal–Wallis, post hoc tests, and Spearman correlation coefficient). A significance level <0.05 was considered. The study results showed that the mean scores of healthy lifestyle, self‐esteem, and subjective vitality were 134.42 ± 13.78, 36.34 ± 4.62, and 21.80 ± 2.85, respectively. We observed a direct and significant relationship between healthy lifestyle, self‐esteem, and subjective vitality (p < 0.001). Considering the relationship between healthy lifestyle, self‐esteem, and subjective vitality in older adults, managers and planners can help older adults to promote their healthy lifestyles.