bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between glioblastoma location and O6-methylguanine-DNA methyltransferase promoter methylation percentage
Authors: Sansone Giulio , Lombardi Giuseppe , Maccari Marta , Gaiola Matteo , Pini Lorenzo , Cerretti Giulia , Guerriero Angela , Volpin Francesco , Denaro Luca , Corbetta Maurizio , Salvalaggio Alessandro
Published: December 2024

A large literature assessed the relationships between the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and glioblastoma location with inconsistent results. Studies assessing this association using the percentage of methylation are lacking. This cross-sectional study aimed at investigating relationships between glioblastoma topology and MGMT promoter methylation, both as categorical (presence/absence) and continuous (percentage) status. We included patients with diagnosis of isocitrate dehydrogenase wild-type glioblastoma [World Health Organization (WHO) 2021 classification], available pre-surgical MRI, known MGMT promoter methylation status. Quantitative methylation assessment was obtained through pyrosequencing. Several analyses were performed for categorical and continuous variables (χ2, t-tests, ANOVA and Pearson’s correlations), investigating relationships between MGMT methylation and glioblastoma location in cortex/white matter/deep grey matter nuclei, lobes, left/right hemispheres and functional grey and white matter network templates. Furthermore, we assessed at the voxel-wise level location differences between (i) methylated and unmethylated glioblastomas and (ii) highly and lowly methylated glioblastomas. Lastly, we investigated the linear relationship between glioblastoma-voxel location and the MGMT methylation percentage. Ninety-three patients were included (66 males; mean age: 62.3 ± 11.3 years), and 42 were MGMT methylated. The mean methylation level was 33.9 ± 18.3%. No differences in glioblastoma volume and location were found between MGMT-methylated and MGMT-unmethylated patients. No specific anatomical regions were associated with MGMT methylation at the voxel-wise level. MGMT methylation percentage positively correlated with cortical localization (R = 0.36, P = 0.021) and negatively with deep grey matter nuclei localization (R = −0.35, P = 0.025). To summarize, we investigated relationships between MGMT methylation status and glioblastoma location through multiple approaches, including voxel-wise analyses. In conclusion, MGMT promoter methylation percentage positively correlated with cortical glioblastoma location, while no specific anatomical regions were associated with MGMT methylation status.
Efficacy and Safety of Switching from Baricitinib to Ritlecitinib in Severe Alopecia Areata
Authors: Chen Ying , Xu Qiuyun , Lv Xiaoqing , Zhuang Zeyu , Bao Siyi , Mao Jing , Gong Ting , Ji Chao
Published: December 2024

This study investigates the efficacy and safety of ritlecitinib, a JAK3/TEC inhibitor, in patients with severe alopecia areata (AA) inadequate or no response to baricitinib, a JAK1/2 inhibitor. Our results indicate that treatment with ritlecitinib not only leads to significant improvements in hair regrowth and quality of life but also positively impacts the psychological well-being of patients with severe AA. our study highlights an inadequate or no response to one JAKi does not necessarily predict failure with another.
Perspectives on Contraception, Pregnancy, and Reproductive Health Counseling from Young Women With Inflammatory Bowel Disease
Authors: Brenner Erica J , Grewe Mary E , Berenblum Tobi Catalina , Bryant Amy G , Dubinsky Marla C , Zhang Xian , Long Millie D , Kappelman Michael D , Buchbinder Mara
Published: December 2024

Background/Aims

Active inflammatory bowel disease (IBD) increases the risk of pregnancy complications and contraceptive side effects, and contraceptive use may impact the clinical course of IBD. Although young people are at elevated risk for unintended pregnancy, those with IBD receive minimal disease-specific contraceptive guidance. We characterized perspectives and preferences on contraception and reproductive health counseling from young cis-women with IBD.

Methods

We conducted 60-min semi-structured interviews with cis-women with IBD ages 18-30 (recruited nationwide and from North Carolina IBD clinics; February–June 2023). Interview guides included questions about reproductive health and preferences for receiving reproductive health information. Audio-recordings were professionally transcribed and coded using an inductive, thematic approach and Dedoose software.

Results

Participants included 30 cis-women with IBD (ages 18-30, 77% White, 7% Hispanic, and 55% Crohn’s disease). Some participants shared that IBD increased their menstrual symptom burden, prompting contraceptive use to control menses. Participants discussed the impact of IBD on their contraceptive decision-making, including concerns regarding blood clots. For a participant subset, IBD did not impact contraceptive decision-making. Participants discussed how IBD impacted their perspectives on childbearing, including concerns about IBD heritability, infertility, and peripartum IBD flares. Participants wanted their gastroenterology provider to proactively address reproductive health, provide appropriate resources, and coordinate care with reproductive health providers.

Conclusions

Young cis-women with IBD may have IBD-specific concerns about contraceptives, pregnancy, and menstrual symptoms and desire better IBD-related reproductive health counseling. Inflammatory bowel disease providers can improve reproductive health counseling by proactively addressing IBD-specific reproductive health questions, providing reproductive health resources, and coordinating care.
Success rate and factors affecting stability of infrazygomatic miniscrew implants: a systematic review and meta-analysis
Authors: Katyal Sakshi , Bhatia Navleen Kaur , Sardana Rinkle , Singh Surjit , Chugh Ankita , Shamim Muhammad Aaqib , Anil Abhishek , Negi Anurag , Chugh Vinay Kumar
Published: December 2024

Background

The infrazygomatic miniscrew implants (IZC-MSI) serve as innovative temporary anchorage devices placed parallel to the roots of molars in the infrazygomatic crest region, leveraging their extra-radicular location to support the en masse distalization and intrusion of the maxillary dentition. The efficacy and stability of these screws are crucial for their application in contemporary orthodontic practices.

Objectives

This systematic review aimed to estimate the success rate and factors affecting the stability of IZC-MSI.

Search methods

An electronic search was conducted on 7 February 2024 across the following databases: PubMed, Scopus, EMBASE, and Cochrane databases without any restriction on language and time of publication.

Selection criteria

The review included clinical trials (both randomized and non-randomized) and retrospective cohort studies that utilized infrazygomatic miniscrew anchorage for orthodontic tooth movement in human participants.

Data collection and analysis

The proportion of success rate was calculated and factors affecting stability (patient and implant-related factors) such as age, sex, implant position, and loading characteristics were subjected to subgroup analysis and meta-regression. The quality assessment of studies was done using the Cochrane risk-of-bias tools for randomized (RoB 2.0) and non-randomized trials (ROBINS-I).

Results

Fourteen studies (n = 1683 IZC-MSI) were included in the meta-analysis revealing a 92% success rate of IZC-MSI (C.I. 87%–95%; prediction interval: 66%–99%; I2 = 80%). Studies with sample size > 100 presented a 94% success rate (C.I. 91%–96%; I2 = 63%) and moderate heterogeneity. Meta-regression analysis revealed no significant relation between age and success rate. Significant heterogeneity was observed in the subgroup analysis of host-, implant- and other related risk factors affecting stability and limited correlation was found. The risk-of-bias assessment revealed high risk in five, moderate in five, and low in four studies.

Conclusions

IZC-MSI have shown a good success rate for their clinical application. Although some factors appear to influence IZC-MSI stability, the majority of them necessitate additional investigation due to the low quality of evidence. Furthermore, high-quality studies are needed to confirm the results of this meta-analysis and address other important factors such as operator’s experience, insertion torque, and sinus penetration that could not be analysed due to limited data.

Registration

CRD42024469048.
Co-regulation of cooperative and private traits by PsdR in Pseudomonas aeruginosa
Authors: Qiu Huifang , Dandekar Ajai A , Dai Weijun
Published: December 2024

Social interactions profoundly shape the dynamics and functionality of microbial populations. However, mechanisms governing the regulation of cooperative or individual traits have remained elusive. Here, we investigated the regulatory mechanisms of social behaviors by characterizing the fitness of transcriptional regulator PsdR mutants in cooperating Pseudomonas aeruginosa populations. In a canonical model described previously, PsdR was shown to solely have a nonsocial role in adaptation of these populations by controlling the intracellular uptake and processing of dipeptides. In addition to these known private traits, we found that PsdR mutants also enhanced cooperation by increasing the production of quorum sensing (QS)-regulated public goods. Although private dipeptide utilization promotes individual absolute fitness, it only partially accounts for the growth advantage of PsdR mutants. The absence of the QS master regulator LasR delayed the appearance of PsdR variants in an evolution experiment. We also demonstrated that the growth fitness of PsdR mutants is determined by a combination of the QS-mediated cooperative trait and the dipeptide metabolism-related private trait. This dual trait is co-regulated by PsdR, leading to the rapid spread of PsdR variants throughout the population. In conclusion, we identified a new social model of co-regulating cooperative and private traits in PsdR variants, uncovering the social and nonsocial roles of this transcriptional regulator in cooperating bacterial populations. Our findings advance the fundamental understanding of bacterial social interactions and provide insights into population evolution, pathogen infection control and synthetic biotechnology.
Effects of a Physical Activity Intervention on Perceived Stress, Fatigue, and Depressive Symptoms in Older Adults: A Secondary Analysis of the LIFE Study
Authors: Smail Emily J , Kaufmann Christopher N , King Abby C , Espeland Mark A , Anton Stephen , Manini Todd M
Published: December 2024

Background

Engaging in physical activity is critical for maintaining well-being in older adults, particularly those at heightened risk for mobility disability. We assessed the effects of a physical activity (PA) intervention on perceived stress, fatigue, and depressive symptoms compared to a health education (HE) program in older adults with mobility challenges and evaluated differential effects of the interventions among those with the poorest self-rated mental health at baseline.

Methods

Secondary data analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study, a single-blinded, parallel randomized controlled trial conducted between February 2010 and December 2013. The PA intervention included walking, strength exercises, balance training, and flexibility activities. The HE intervention consisted of workshops on health topics for older adults. The main outcomes for our analysis included standardized scales with participants self-reporting their stress, fatigue, and depressive symptoms at baseline, 12 months, and 24 months postrandomization.

Results

Results from the 1 495 participants (Mage = 78 years; 66% female in both groups) showed no significant between-group differences in perceived stress, fatigue, or depressive symptom scores over time. However, in both intervention groups, participants with worse baseline scores showed a steady improvement in symptom scores over time compared to the remaining participants, who showed some decline (p value for interaction < .05).

Conclusions

Among mobility-impaired individuals, a long-duration, group-based PA intervention had no more impact on stress, fatigue, or depressive symptoms compared to a group-based HE intervention. However, participants with higher symptoms at baseline showed improvement over time in both intervention groups.
The Fifth Annual Symposium of the Midwest Aging Consortium
Authors: Reader Brenda F , Rosas Lorena , Knopf Bailey Anna , Liu Yang , Alzate-Correa Diego , Bhat Ajay , Carey Anna , Cuervo Ana Maria , Dayal Sanjana , Demarco Rafael S , Elliehausen Christian J , Englund Davis A , Hamilton Haylee L , Johnston Matthew , Kang Ping , Konopka Adam R , Lepola Noah , Presley Carolyn J , Schafer Marissa J , Serrano Joan , Singer Benjamin D , Song Min-Ae , Stanford Kristin I , Taylor Jackson , Wei Wei , Yeh Chung-Yang , Zhang Lei , Zhang Lei , Anderson Rozalyn M , Bai Hua , Robbins Paul D , Lamming Dudley W , Mihaylova Maria M , Rojas Mauricio , Mora Ana L
Published: December 2024

As the healthcare burden caused by an increasingly aging population rapidly rises, a pressing need exists for innovative geroscience research that can elucidate aging mechanisms and precipitate the development of therapeutic interventions to support healthy aging. The Fifth Annual Midwest Aging Consortium Aging Research symposium, held from April 28 to 30, 2024, was hosted by The Ohio State University in Columbus, Ohio, and featured presentations from investigators across the Midwestern United States. This report summarizes the research presented at the symposium, whose topics included cellular senescence and the aging brain, metabolism and metabolic interventions, nutrition, redox mechanisms and biomarkers, and stress mechanisms. Abstract presentations and short talks highlighted early-stage and young investigators, whereas 2 keynote presentations anchored the symposium. Overall, this symposium showed the robustness of aging research in the Midwest and underscored the advantages of a collaborative approach to geroscience research.
scGraph2Vec: a deep generative model for gene embedding augmented by graph neural network and single-cell omics data
Authors: Lin Shiqi , Jia Peilin
Published: December 2024

Background

Exploring the cellular processes of genes from the aspects of biological networks is of great interest to understanding the properties of complex diseases and biological systems. Biological networks, such as protein–protein interaction networks and gene regulatory networks, provide insights into the molecular basis of cellular processes and often form functional clusters in different tissue and disease contexts.

Results

We present scGraph2Vec, a deep learning framework for generating informative gene embeddings. scGraph2Vec extends the variational graph autoencoder framework and integrates single-cell datasets and gene–gene interaction networks. We demonstrate that the gene embeddings are biologically interpretable and enable the identification of gene clusters representing functional or tissue-specific cellular processes. By comparing similar tools, we showed that scGraph2Vec clearly distinguished different gene clusters and aggregated more biologically functional genes. scGraph2Vec can be widely applied in diverse biological contexts. We illustrated that the embeddings generated by scGraph2Vec can infer disease-associated genes from genome-wide association study data (e.g., COVID-19 and Alzheimer's disease), identify additional driver genes in lung adenocarcinoma, and reveal regulatory genes responsible for maintaining or transitioning melanoma cell states.

Conclusions

scGraph2Vec not only reconstructs tissue-specific gene networks but also obtains a latent representation of genes implying their biological functions.
Quantum With an Eye on ROI
Authors: Runciman Brian
Published: December 2024

Brian Runciman MBCS talked to Stefano Mensa, Advanced Computing and Emerging Technology Lead at the Science and Technology Facilities Council (STFC) Hartree Centre, about practical uses of quantum computing and where it may lead in the next two to three years.
Soil pH modulates the activity of low-affinity methane oxidation in soils from the Amazon region
Authors: Fonseca de Souza Leandro , Nakamura Fernanda Mancini , Kroeger Marie , Obregon Dasiel , de Moraes Moacir Tuzzin , Vicente Mariana Gomes , Moreira Marcelo Zacharias , Pellizari Vivian Helena , Tsai Siu Mui , Nüsslein Klaus
Published: December 2024

Aims

In the Amazon region, pastures are the main land use subsequent to deforestation and this change can result in soil acidification and degradation. Liming is a management practice to increase soil pH, important to recover degraded lands and increase soil fertility, but its impacts on soil methane cycling in tropical soils are unknown. Here we investigate the role of soil pH on methane uptake under high concentrations of the gas, manipulating pasture and forest soils pH by liming and evaluating the active methane cycling microbial community.

Methods and Results

Top layer of forest and pasture soils were subjected to liming treatment and incubated with ∼10 000 ppm of 13CH4. Soil DNA was evaluated with Stable Isotopic Probing (SIP-DNA), methanotrophic abundance was quantified (pmoA gene), and high throughput sequencing of 16S rRNA was performed. Liming increased the methane uptake in both forest (∼10%) and pasture (∼25%) soils. Methanotrophs Methylocaldum spp. (type I) and potential methanotrophs in Beijerinckiaceae (type II) were identified to actively incorporate carbon from methane in limed pasture soils. In limed forest soils, Nitrososphaeraceae were identified as 13C-enriched taxa, indicating that ammonia oxidizers can oxidize methane in these soils.

Conclusions

Liming Amazonian pasture soils not only contributes to the fertility and recovery of degraded areas but also has the potential to improve the oxidation of methane at high concentrations of this gas.
Effects of antioxidants on in vitro growth of Thecaphora frezzii
Authors: Figueroa Ana Cristina , Díaz María Soledad , Turco Mauricio , Fernández Trotta Andrea , Marino Bibiana , Soria Néstor Walter , Beltramo Dante Miguel , Alasino Roxana Valeria
Published: December 2024

Abstracts

Aims

Thecaphora frezzii, the causal agent of peanut smut, causes significant grain losses in Argentina. Current control strategies are insufficient to manage this pathogen. We investigate the effect of antioxidants on the in vitro development of T. frezzii hyphae, to identify compounds with antifungal activity, also evaluate protein and lipid profiles as potential targets for these compounds.

Methods and results

The antifungal activity was evaluated in both, solid and liquid media, and minimum inhibitory concentration and minimum fungicidal concentration were calculated. The protein profile was assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis, while lipids were analyzed by thin-layer chromatography (TLC) and gas chromatography with flame ionization detection, both before and after hyphal treatment. Lipase activity was analyzed using agar Tween 20 and TLC, while lipid peroxidation was evaluated by the thiobarbituric acid-reactive substance (TBARS)assay. Microscopy was used to observe morphological and metabolic changes. Butylated hydroxyanisole, methylparaben, and lipoic acid showed inhibitory effects on T. frezzii. Lipoic acid was chosen for further study due to its lack of environmental toxicity. Lipoic acid induced the loss of cytosolic proteins, hydrolysis of triglycerides, and increased levels of free fatty acids, monoacylglycerols, and diacylglycerols. It also caused a decrease in ergosterol levels and alterations in the fungal cell wall and membrane, ultimately leading to cell death.

Conclusions

This study demonstrates the efficacy of lipoic acid in inhibiting the in vitro development of T. frezzii.
Etomoxir suppresses the expression of PPARγ2 and inhibits the thermogenic gene induction of brown adipocytes through pathways other than β-oxidation inhibition
Authors: Shimura Hiroki , Yamamoto Sota , Shiiba Isshin , Oikawa Mami , Uchinomiya Shohei , Ojida Akio , Yanagi Shigeru , Kadowaki Hisae , Nishitoh Hideki , Fukuda Toshifumi , Nagashima Shun , Yamaguchi Tomoyuki
Published: December 2024

Brown adipocytes are characterized by a high abundance of mitochondria, allowing them to consume fatty acids for heat production. Increasing the number of brown adipocytes is considered a promising strategy for combating obesity. However, the molecular mechanisms underlying their differentiation remain poorly understood. In this study, we demonstrate that etomoxir, an inhibitor of Carnitine Palmitoyltransferase 1 (CPT1), inhibits their differentiation through mechanisms independent of β-oxidation inhibition. In the presence of etomoxir during brown adipocyte differentiation, reduced expression of the thermogenic gene UCP1 and decreased lipid droplets formation were observed. Furthermore, a transient reduction in the expression of PPARγ2, a critical factor in adipocyte differentiation, was also observed in the presence of etomoxir. These findings suggest the presence of a regulatory mechanism that specifically enhances PPARγ2 expression during brown adipocyte differentiation, thereby modulating thermogenic gene expression.
Restoring the Regulated: The EU’s Nature Restoration Law
Authors: Lees Emma , Pedersen Ole W
Published: December 2024

To halt the decline of the natural environment, attention is increasingly directed towards nature restoration. A recent example of this is the EU’s Nature Restoration Law (NRL). This article presents an assessment of the NRL, arguing that the NRL is ambitious but that this ambition comes with a risk of it becoming a performative body of law. To test the NRL’s application in Member States, this article identifies four key ‘interpretive puzzles’: the relative priorities between the different obligations in the NRL; the correct approach to timescales and the concept of natural range; the ‘climate change causation defence’ and the interaction between the definition of restoration measures and pre-emptive measures. The article then articulates the central theme in relation to these four puzzles—the tension in the relationship between the mandated ‘plan-led’ approach, and a potential lack of Member State discretion in the contents of that plan.
Real-world treatment patterns and survival in extensive stage small-cell lung cancer in Japan
Authors: Horinouchi Hidehito , Chang Chia-Hsien Suzu , Shaw Jaime , Archangelidi Olga , Balasubramanian Akhila , Pundole Xerxes
Published: December 2024

Objective

To describe standard of care and inform the evolving unmet need among extensive stage small-cell lung cancer (ES-SCLC) patients in Japan since approval of first-line anti-PD-L1 therapies, we describe treatment patterns and overall survival by line of therapy.

Methods

We conducted a descriptive analysis of adult ES-SCLC patients in Japan using de-identified patient data within the MDV database (hospital-based claims) to describe treatment patterns and DeSC database (payer-based claims linked to mortality of municipality records) to describe both treatment patterns and real-world overall survival (rwOS).

Results

The study population of MDV and DeSC cohorts included 6302 and 903 patients, respectively. First-line anti-PD-L1 therapy-based regimens grew since their approval in 2019 and were used in ~35% and ~59% of patients in 2022, in the MDV and DeSC cohorts, respectively. Amrubicin monotherapy was the most common second-line (2 L) regimen before and after 1 L anti-PD-L1 approvals. No clear standard of care was identified in third-line (3 L) and fourth-line (4 L). Median rwOS following 1 L therapy was 10.6 months (95% CI: 9.0, 11.8) and 9.3 months (95% CI: 8.3, 10.3) in patients who did and did not receive anti-PD-L1 therapy, respectively. Following 2 L, 3 L, and 4 L therapy, median rwOS was 6.7 months (95% CI: 5.9, 7.4), 5.5 months (95% CI: 4.4, 6.4), and 4.7 months (95% CI: 3.4, 6.9), respectively.

Conclusions

Anti-PD-L1 therapies have become part of first-line standard of care but survival in treated Japanese ES-SCLC patients remains poor, highlighting the unmet medical need in the post anti-PD-L1 era.
Beyond the normative impasse of environmental migration: From regimes to infrastructures in a Latin American key
Authors: Hoffmann Florian F , dos Reis Santos Leilane Nascimento
Published: December 2024

The article draws on the concept of legal infrastructures and infrastructuring processes in the context of the ongoing discussion on the (legal) framing of environmental migration. It lays out why the entanglement of empirical and normative indeterminacy in environmental migration forces opens the door to a transdisciplinary and multidimensional perspective. It explores how framing environmental migration in terms of legal mobility infrastructures or, rather, of the legal infrastructuring of (global) mobility can help transcend the legal impasse that currently still surrounds it. It draws on previous work on entangled mobility regimes in Latin America, most notably in the context of the Venezuelan refugee crisis as of 2015 and on the impact of the Covid-19 pandemic on the border regime in Brazil. Some of the phenomena observed in these contexts provide valuable insights into the logic of the legal infrastructuring of mobility and into how the environment/displacement nexus might be infrastructured in a region that is one of the hotspots of the climate crisis.
The relationship between sexual health literacy and sexual function of women with diabetes mellitus: a cross-sectional study
Authors: Çakmak Betül , Abay Halime , Doğanay Ceren Atilgan , Çelik Nazan , Özel Yasemin , Üstün Yusuf
Published: December 2024

Background

Sexual dysfunction (SD) is a complication of poorly managed diabetes mellitus (DM). To prevent SD, patients should develop sexual health literacy (SHL).

Objective

This study investigated the relationship between SHL and SD in women with DM.

Methods

This cross-sectional study was performed between 1 October 2023 and 1 June 2024. The sample comprised 400 participants. The inclusion criteria were (1) being 18-65 years of age, (2) having been diagnosed with DM, and (3) having a sex partner. Data were collected using a personal information form, the Female Sexual Function Index (FSFI), and the Sexual Health Literacy Scale (SHLS).

Outcomes

The data were analyzed using the Mann–Whitney test, Kruskal–Wallis H test, Spearman correlation coefficients, and binary logistic regression.

Results

Over half of the participants experienced SD (68,2%). Participants with higher education, those whose partners had higher education, those who did not have any chronic disease other than DM, and those who did not take hormone replacement therapy had a lower rate of SD (P < 0.05). Participants with higher income, those who used family planning, those with DM I, and non-menopausal participants had lower SD and higher SHL (P < 0.05). Insulin-only participants had higher SD and lower SHL than those who were on other types of medications (P < 0.05). There was a significant negative correlation between scale scores (FSFI and SHLS) and age (r = -0.388; P < 0.001 r = -0.326; P < 0.001, respectively), age of partner (r = -0.383; P < 0.001, r = -0.274; P < 0.001, respectively), duration of romantic relationship (r = -0.326; P < 0.001, r = -0.328; P < 0.001, respectively), number of children (r = -0.109; P < 0.001, r = -0.290; P < 0.001, respectively), and duration of DM (r = -0.254; P < 0.001, r = -0.125; P < 0.013, respectively). There was a significant positive correlation between scale scores (FSFI and SHLS) and number of sexual intercourse (r = 0,493; P < 0.001, r = 0.127; P < 0.011, respectively). A one-unit increase in DM duration resulted in a 3.7% increase in SD rate (OR = 1.037). A one-unit increase in the number of sexual intercourses reduced the SD rate by 35.5% (OR = 0.645).

Clinical Implication

The data show that the prevalence of SD in diabetic women is directly affected by the number of sexual intercourses per week, menopausal status, and duration of DM.

Strengths and limitations

This is the first study to examine the relationship between SHL and SD in women with DM. Second, the results are sample-specific and cannot be generalized to all women with DM.

Conclusion

Healthcare professionals should ensure that women with DM have high levels of SHL to prevent SD and improve their quality of sexual life.
Evaluation of a commercial Histoplasma antigen detection enzyme immunoassay for the follow-up of histoplasmosis treatment in people living with HIV from Argentina
Authors: Messina Fernando A , Marin Emmanuel , Caceres Diego H , Romero Mercedes , Manrique Mariela , Santiso Gabriela Maria
Published: December 2024

Histoplasmosis poses a significant risk to HIV patients, particularly in regions with limited access to antiretroviral therapy. Antigen detection assays are crucial in these settings for timely diagnosis and treatment, which can reduce mortality. While commercial antigen detection kits have performed well in diagnosing histoplasmosis, their effectiveness in monitoring treatment remains unclear. This study aimed to evaluate the correlation between urine antigen levels and clinical response using the clarus Histoplasma Galactomannan (GM) enzyme immunoassays (EIA) kit. The study followed 27 HIV patients diagnosed with histoplasmosis over 24 weeks, measuring urinary Histoplasma antigen (Ag) levels and clinical outcomes. Patients received amphotericin B as induction therapy, followed by maintenance with itraconazole. Results showed a significant decrease in Ag levels over time, with clinical scores improving in correlation with the decline in Ag levels. Four patients exhibited atypical Ag patterns due to immune reconstitution inflammatory syndrome or issues with itraconazole bioavailability. Despite these challenges, all patients showed improvement by week 24. The findings suggest that the clarus Histoplasma GM EIA kit could be a valuable tool for monitoring and evaluating the response to antifungal therapy in histoplasmosis patients.
Clumps as multiscale structures in cosmic noon galaxies
Authors: Kalita Boris S , Suzuki Tomoko L , Kashino Daichi , Silverman John D , Daddi Emanuele , Ho Luis C , Ding Xuheng , Mercier Wilfried , Faisst Andreas L , Sheth Kartik , Valentino Francesco , Puglisi Annagrazia , Saito Toshiki , Kakkad Darshan , Ilbert Olivier , Khostovan Ali Ahmad , Liu Zhaoxuan , Tanaka Takumi , Magdis Georgios , Zavala Jorge A , Tan Qinghua , Kartaltepe Jeyhan S , Yang Lilan , Koekemoer Anton M , McKinney Jed , Robertson Brant E , Jin Shuowen , Hayward Christopher C , Hirschmann Michaela , Franco Maximilien , Shuntov Marko , Gozaliasl Ghassem , Kaminsky Aidan , Rich R Michael
Published: December 2024

Star-forming clumps have been found to significantly influence the star formation of gas-rich $z\gt 1$ galaxies. Using public data from JWST/NIRCam (Cosmic Evolution Survey; COSMOS-Web) and Atacama Large (sub-)Millimeter Array (ALMA; Fiber-Multi Object Spectrograph or FMOS-COSMOS survey), we study a sample of 32 massive ($\gt 10^{10.5}\, \rm {\rm M}_{\odot }$) main-sequence galaxies at $z_{\rm spec}\sim 1.5$ with $\sim 0.3\, \rm kpc$ resolution. We create composite morphological models consisting of bulge, disc, and clumps to fully ‘deconstruct’ the galaxy images. With the resulting measurements of the flux and size of these components, we find the following: (i) the combined contribution of clumps is 1–30 per cent towards the net star formation of the host while contributing 1–20 per cent to its stellar mass. The clumps show a correlation between their stellar mass and star formation rate (SFR), but have an increased specific SFR relative to the star formation main-sequence, with offsets ranging from $0 \lesssim \Delta \log \rm sSFR \lesssim 0.4$. They feature star formation surface densities of $10^{-2}-10^{2}\, \rm {\rm M}_{\odot }\, yr^{ -1}\, kpc^{-2}$, consistent with values observed in both local star-forming and starburst galaxies. (ii) The detected clumps span a large range of characteristic sizes ($r_{e} \sim 0.1 - 1\, \rm kpc$) and stellar masses ($\sim 10^{8.0-9.5}\, \rm {\rm M}_{\odot }$). We estimate a mass–size relation ($r_{e} \propto \rm M_{\star }^{\, 0.52 \pm 0.07}$) along with a stellar mass function (slope, $\alpha = - 1.85 \pm 0.19$), both suggesting a hierarchical nature similar to that expected in star-forming regions in local galaxies. (iii) Our measurements agree with the properties of stellar clumps in $z\gtrsim 1$ lensed systems, bridging the gap between lensed and unlensed studies by detecting structures at sub-kpc scales. (iv) Clumps are found to be preferentially located along spiral features visible primarily in the residual rest frame near-IR images. In conclusion, we present an observation-based, coherent picture of star-forming clumps in galaxies at $z \gt 1$.
Cloud-scale elemental abundance variations and the CO-to-dust-mass conversion factor in M31
Authors: Bosomworth Chloe , Forbrich Jan , Lada Charles J , Caldwell Nelson , Kobayashi Chiaki , Viaene Sébastien
Published: December 2024

From a spectroscopic survey of candidate H ii regions in the Andromeda Galaxy (M31) with MMT/Hectospec, we have identified 294 H ii regions using emission line ratios and calculated elemental abundances from strong-line diagnostics (values ranging from subsolar to supersolar) producing both oxygen and nitrogen radial abundance gradients. The oxygen gradient is relatively flat, while the nitrogen gradient is significantly steeper, indicating a higher N/O ratio in M31’s inner regions, consistent with recent simulations of galaxy chemical evolution. No strong evidence was found of systematic galaxy-scale trends beyond the radial gradient. After subtracting the radial gradient from abundance values, we find an apparently stochastic and statistically significant scatter of standard deviation 0.06 dex, which exceeds measurement uncertainties. One explanation includes a possible collision with M32 200–800 Myr ago. Using the two-point correlation function of the oxygen abundance, we find that, similar to other spiral galaxies, M31 is well-mixed on sub-kpc scales but less so on larger (kpc) scales, which could be a result of an exponential decrease in mixing speed with spatial scale, and the aforementioned recent merger. Finally, the MMT spectroscopy is complemented by a dust continuum and CO survey of individual giant molecular clouds, conducted with the Submillimeter Array (SMA). By combining the MMT and SMA observations, we obtain a unique direct test of the oxygen abundance dependence of the $\alpha ^{\prime }(^{12}{\rm CO})$ factor which is crucial to convert CO emission to dust mass. Our results suggest that within our sample there is no trend of the $\alpha ^{\prime }(^{12}{\rm CO})$ with oxygen abundance.
Assessing metal-induced glycation in French fries
Authors: Nobert Seth , Wolgien-Lowe Haley , Davis Tamara , Paterson Emma , Wilson-Rawlins Thérèse , Golizeh Makan
Published: December 2024

Non-enzymatic glycation is the chemical reaction between the amine group of an amino acid and the carbonyl group of a reducing sugar. The final products of this reaction, advanced glycation end-products (AGEs), are known to play a key role in aging and many chronic diseases. The kinetics of the AGE formation reaction depends on several factors, including pH, temperature, and the presence of prooxidant metals, such as iron and copper. In this study, the effect of iron and copper on the rate and outcome of non-enzymatic glycation was examined in the test tube and a food model, using chromatography and spectrometry methods. Binding efficiencies of several chelating agents to selected metals were also assessed. Phytic acid was the most efficient of the tested chelating agents. The effect of phytic acid on AGE formation in French fries was evaluated. While phytic acid treatment increased the amounts of UV-absorbing compounds in fries, a food ingredient rich in phytic acid showed the opposite effect. This study suggests that prooxidant metals can affect the rate, outcome, and yield of the non-enzymatic glycation reaction and that they do so differently when free or chelated. Moreover, despite being an excellent iron chelator, phytic acid can promote AGE formation in fried food potentially via mechanisms other than metal-induced glycation.
Genome-wide phenotypic profiling of transcription factors and identification of novel targets to control the virulence of Vibrio vulnificus
Authors: Sung Dayoung , Choi Garam , Ahn Minji , Byun Hokyung , Kim Tae Young , Lee Hojun , Lee Zee-Won , Park Ji Yong , Jung Young Hyun , Han Ho Jae , Choi Sang Ho
Published: December 2024

For successful infection, the life-threatening pathogen Vibrio vulnificus elaborately regulates the expression of survival and virulence genes using various transcription factors (TFs). In this study, a library of the V. vulnificus mutants carrying specific signature tags in 285 TF genes was constructed and subjected to 16 phenotypic analyses. Consequently, 89 TFs affecting more than one phenotype of V. vulnificus were identified. Of these, 59 TFs affected the in vitro survival including growth, stress resistance, biofilm formation and motility, and 64 TFs affected the virulence of V. vulnificus. Particularly, 27 of the 64 TFs enhanced the in vitro hemolytic or cytotoxic activities, and 8 of the 27 TFs also increased the in vivo brine shrimp or murine infectivities of V. vulnificus. Among the eight TFs, HlyU, IscR, NagC, MetJ and Tet2 did not affect the growth of V. vulnificus but still regulated the expression of major exotoxin genes, including rtxA, vvhA and plpA, thereby emerging as potential drug targets for anti-virulence therapies with low selective pressure for developing resistance. Altogether, this study characterized the functions of TFs at a genome-wide scale and identified novel targets to control the virulence of V. vulnificus.
The interplay of the translocase activity and protein recruitment function of PICH in ultrafine anaphase bridge resolution and genomic stability
Authors: Kong Nannan , Chen Kun , Chanboonyasitt Primrose , Jiang Huadong , Wong Ka Yan , Ma Hoi Tang , Chan Ying Wai
Published: December 2024

Incomplete sister centromere decatenation results in centromeric ultrafine anaphase bridges (UFBs). PICH (PLK1-interacting checkpoint helicase), a DNA translocase, plays a crucial role in UFB resolution by recruiting UFB-binding proteins and stimulating topoisomerase IIα. However, the involvement of distinct PICH functions in UFB resolution remains ambiguous. Here, we demonstrate that PICH depletion in non-transformed diploid cells induces DNA damage, micronuclei formation, p53 activation, G1-phase delay and cell death. Whole-genome sequencing reveals that segregation defects induced by PICH depletion cause chromosomal rearrangements, including translocations and inversions, emphasizing its significance in preserving genomic integrity. Furthermore, a PICH mutant that impairs UFB recruitment of BLM and RIF1 partially inhibits UFB resolution while a translocase-inactive mutant (PICHK128A) fails to resolve UFBs. Notably, expression of PICHK128A inhibits single-stranded UFB formation and induces hypocondensed chromosomes. We propose that PICH’s translocase activity plays a dual role in promoting UFB resolution by facilitating the generation of single-stranded UFBs and stimulating topoisomerase IIα.
Engagement in Preexposure Prophylaxis Care at 1 Year Among Men Who Have Sex With Men Enrolled in the French ANRS PREVENIR Cohort Study
Authors: Liegeon Geoffroy , Assoumou Lambert , Béniguel Lydie , Palich Romain , Pialoux Gilles , Slama Laurence , Surgers Laure , Duvivier Claudine , Ohayon Michel , Mouhim Hannane , Pavie Juliette , Vu Duc-Hoan , Michels David , Ben Mechlia Mohamed , Spire Bruno , Ghosn Jade , Molina Jean-Michel , Costagliola Dominique
Published: December 2024

Background

We evaluated 1-year engagement in pre-exposure prophylaxis (PrEP) care and associated factors among gay, bisexual, and other men who have sex with men (GBMSM) in a large cohort of oral PrEP users in the Paris region, France.

Methods

We included in this analysis cisgender GBMSM enrolled in the ANRS PREVENIR cohort study from 3 May 2017 to 28 February 2019. We categorized 1-year PrEP engagement into 4 categories: high (consistent visits, attendance, and prescription refills at months 3, 6, 9, and 12), low (missed visits or no prescription refills), disengagement (PrEP discontinuation), and lost to follow-up. We used a logistic regression model to identify sociodemographic and behavioral factors associated with high engagement in PrEP care.

Results

Of 3211 participants, 2685 GBMSM were included in the analysis. At enrollment, participants had a median age of 36 years, with 88% born in Europe and 52.4% already undergoing PrEP. At month 12, 1612 (60.0%) participants met the high engagement definition, 438 (16.3%) exhibited low engagement, 459 (17.1%) disengaged from PrEP care, and 176 (6.6%) were lost to follow-up. In multivariable analysis, high engagement in PrEP care at 1 year was associated with older age (P < .001), being born in Europe (P = .01), having a higher education level (P = .05), already undergoing PrEP at enrollment (P < .001), having a bacterial sexually transmitted infection in the prior year (P = .01), earlier enrollment in the study (P = .04), and using PrEP daily or switching between PrEP regimens within the first year (P < .001).

Conclusions

Younger GBMSM, those born outside Europe, and those who were PrEP naive had lower engagement rates in the cohort, requiring tailored support.
Incidence of patient-reported fatigue developing on palbociclib and endocrine therapy for advanced HR+ HER2− breast cancer
Authors: Rahman Shadab A , Poort Hanneke , Schrag Deborah , Tung Stephanie C , Zhou Eric S , Wiley Aleta , Finkelstein Lauren B , Elguenaoui Elkhansaa , Nolan Moira , Mayer Erica L , Joffe Hadine
Published: December 2024

Objectives

Fatigue is a common nonhematologic toxicity of the CDK4/6 inhibitor palbociclib in metastatic breast cancer (MBC) patients with prevalence rates of clinician-rated all-grade and grade 3/4 fatigue of 39.2% and 2.5%, respectively. We prospectively assessed the incidence of fatigue emerging on palbociclib using patient-reported measures and explored potential predictors.

Methods

Eighty-eight patients with HR+ HER2− MBC without fatigue initiating palbociclib with endocrine therapy were assessed before and monthly across the initial 6 cycles. Clinically meaningful levels of patient-reported fatigue (Functional Assessment of Chronic Illness Therapy Fatigue Scale, FACIT-F < 34), severity of, and functional interference due to fatigue (NCI Patient-Reported Outcomes for CTCAE, PRO-CTCAE) were assessed. Hematologic and nonhematologic predictors were examined pretreatment and concurrent with fatigue assessments.

Results

Patient-reported fatigue emerged in 21/88 patients [incidence rate 23.9% (95%CI, 15.4%-34.1%)] within 2.8 ± 1.7 treatment cycles. PRO-CTCAE-rated incidence rate of severe fatigue and fatigue interference was 14.8% (95%CI, 8.1%-23.9%) and 10.2% (95%CI, 4.8%-18.5%), respectively. Lower pretreatment absolute neutrophil count (ANC) levels predicted treatment-emergent fatigue (P =.01), but ANC levels on treatment did not (P =.78). Other pretreatment predictors were long sleep duration (P =.02) and low physical activity (trend, P =.07). Treatment-emergent fatigue was associated with objectively measured long sleep duration on treatment (P =.02), but not other measures (P ≥.35).

Conclusions

One-quarter of patients with HR+ HER2− MBC initiating palbociclib report rapidly emergent clinically meaningful fatigue, often with severe symptoms and functional interference. Treatment-emergent fatigue is associated with both pretreatment (lower ANC levels, longer sleep duration) and on-treatment (long sleep duration) hematologic and nonhematologic profiles.
Racial differences in real-world outcomes of first-line therapies for advanced renal cell carcinoma
Authors: Geynisman Daniel M , John William S , Miller Taavy A , Asgarisabet Parisa , Guttenplan Sarah B , Yin Xin , Savill Kristin M Zimmerman , McAllister Lindsay , Rosenblatt Lisa
Published: December 2024

Background

Given the historical underrepresentation of racial minorities in clinical trials, little is known about racial differences in outcomes of first-line therapies for advanced renal cell carcinoma (aRCC). This study described patient characteristics and clinical outcomes of first-line therapies for aRCC, including nivolumab + ipilimumab, pembrolizumab + axitinib, and tyrosine kinase inhibitors, by race in the real-world setting.

Methods

We conducted a retrospective medical chart review of patients with intermediate/poor-risk clear-cell aRCC. Treating physicians abstracted patient data from electronic medical charts.

Results

Among 346 patients with intermediate/poor-risk aRCC, a higher proportion of African-American/Black (n = 78) versus White (n = 268) patients had poorer baseline functional performance (ECOG-PS ≥ 2: 37.2% versus 21.3%). African-American/Black patients trended toward numerically lower overall response rates and shorter overall survival for nivolumab + ipilimumab or pembrolizumab + axitinib than White patients.

Conclusions

These findings provide important insights into racial differences in first-line aRCC treatment outcomes within real-world settings. Additional research with larger sample sizes is warranted.
Impact of cryopreservation on immune cell metabolism as measured by SCENITH
Authors: Luscombe Curtis , Jones Eben , Gregorova Michaela , Jones Nicholas , Rivino Laura
Published: December 2024

The dynamic functioning of immune cells is regulated by cellular metabolic processes, and there is growing interest in the study of immunometabolic correlates of dysfunctional immune responses. SCENITH is a novel flow cytometry-based technique that allows for ex vivo metabolic profiling of immune cells within heterogeneous samples. Cryopreservation of clinical samples is frequently undertaken to facilitate high throughput processing and longitudinal analyses of immune responses, but is thought to lead to cellular metabolic dysfunction. We aimed to investigate the impact of cryopreservation on immune cell metabolism, harnessing SCENITH’s unique ability to describe the divergent bioenergetic characteristics of distinct immune cell subsets. We demonstrate that upon activation, T cells are unable to sufficiently/readily undergo metabolic reprogramming. Additionally, we find that cryopreservation introduces a time-dependent metabolic artefact that favours glycolysis and impairs oxidative phosphorylation, suggesting that cryopreservation results in mitochondrial dysfunction. Despite this artefact, SCENITH was still able to reveal the distinct bioenergetic profiles of contrasting immune cells populations following cryopreservation. Whilst SCENITH can provide valuable information about immune cell metabolism even in cryopreserved samples, our findings have important implications for the design of future studies. Investigators should carefully consider how to process and store clinical samples to ensure that cryopreservation does not confound analyses, particularly where longitudinal sampling is required.
‘Racism without racists’: A clarification and refutation of the hypothesis
Authors: Urquidez Alberto G
Published: December 2024

Sally Haslanger's notion of ‘pure structural oppression’ is the idea of an institution or structure that is unjust independent of any and all agential wrongdoing, and for which no agent is liable. Haslanger argues that pure structural oppression is possible, but she does not defend it as a viable phenomenon in the actual world. The rough equivalent of ‘pure structural oppression’ in the racial domain is the ‘racism without racists hypothesis’. This is the claim that institutional racism without racist agents is not just logically possible but probable under some set of viable circumstances. My aim in this paper is to clarify and assess two arguments for the racism without racists hypothesis. These are Haslanger's and Joshua Glasgow's arguments. I explain the limitations of their arguments as well as the general limitations of the hypothesis for a theory of racism.