bluuebunny/crossref_metadata_2025 huggingface dataset:
Porosity identification using residual PPTransformer network
Authors: Huang Ke , Cui Shitao , Kan Hongge , Yang Shihe , Zhang Lina , Chen Yajie , Zhang Xiaolin , Zhu Li , Li Huaiyuan
Published: December 2024

Precisely estimating the carbonate’s porosity is essential for subsurface reservoir characterization. However, conventional methods for obtaining porosity using either core measurements or logging interpretation are expensive and inefficient. Considering the sequence data feature of logging curves and the booming development of intelligent networks in geoscience, this study proposes a reliable and low-cost intelligent Porosity Prediction Transformer (PPTransformer) framework for reservoir porosity prediction using logging curves as inputs. PPTransformer network not only extracts global features through convolutional layers but also captures local features using Encoders and self-attention mechanisms. This proposed network is a data-driven supervised learning framework with a superior accuracy and robustness. The testing results demonstrate that compared to the Transformer network, Long Short-Term time series network, and support vector machine method, the PPTransformer framework exhibits the highest average correlation coefficient and determination coefficient indicators and the lowest root mean square error and absolute error indicators. Moreover, adding stratigraphic lithology as geological constraints to the PPTransformer framework further improves the prediction performance. This indicates that geological constraints will enhance network performance.
Utilization of poetry in teaching Turkish to Kyrgyz at c1 level in emphasis and pronunciation
Authors: Barcın Sibel
Published: December 2024

The aim of this study is to use poetry as an effective tool to improve students’ language skills in teaching Turkish to Kyrgyz. In this context, the teaching of emphasis and pronunciation through poetry is emphasized. In this study, action research, one of the qualitative research methods, was used. The study group of the research consists of 10 Kyrgyz students studying at Kyrgyzstan-Turkey Manas University School of Foreign Languages in the academic year 2022–2023 and who voluntarily participated in the study. Based on this information, students were recommended Necip Fazıl Kısakürek’s poem “Kaldırımlar,” Atillâ İlhan’s poem “Ben Sana Mecburum” and Yavuz Bülent Bâkiler’s poem “Şaşırdım Kaldım İşte” on the first day of the study. Students read the poem of their choice and then prepared for it for 4 days. On the 5th day, they read the poem in the classroom. The data obtained during reading were written down and a comparison was made by considering emphasis, intonation and pronunciation. The data were categorized as “errors related to the mispronunciation of /h/ and /k/ sounds,” “errors related to emphasis” and “ignoring the rhythmic element” and themes were formed and students’ mispronunciations were presented in tables. As a result of the comparisons, the differences between the first day and the last day were evaluated. The findings were interpreted by comparing them with the studies in the literature.
Gender-based violence among women and girls in conflict-affected areas of Northeast Amhara, Ethiopia
Authors: Dellie Endalkachew , Salelew Endalamaw , Mihret Fetene Samrawit , Negash Wubshet D. , Kebede Adane , Haile Tsegaye G. , Alemu Melaku Birhanu , Park Jinha , Tefera Selamawit , Alene Bruhtesfa Mouhabew , Atnafu Asmamaw
Published: December 2024

Background

Gender-Based Violence (GBV) is one of the major problems that women and girls encountered during the conflict between the Ethiopian federal government and the Tigray People's Liberation Front (TPLF). However, there is a gap in evidence regarding gender-based violence resulting from the ongoing conflict in these areas. Therefore, this study assessed the prevalence of GBV and its contributing factors in the conflict-affected northeastern Amhara region of Ethiopia.

Methods

A community-based cross-sectional study was conducted from July 7th to September 30th, 2023, among 597 women and girls who lived in the three most conflict-affected districts (Wadla, Lay-Gaynt, and Meket) in northeastern Amhara regional state of Ethiopia. GBV was assessed using the WHO multi-country study on women's health and domestic violence against women questionnaire, which has 13 items and measures three violence domains (emotional, physical, and sexual). A binary logistic regression analysis was conducted. We used Adjusted Odds Ratios (AOR) with their respective 95% Confidence Intervals (CI) and a p-value of <0.05 to identify statistically significant factors.

Results

The overall prevalence of gender-based violence was 39.0% (95%CI: 35.2–43.6); 36.7% were experienced emotional, 15.4% physical, and 8.9% sexual violences. The burden is higher among individuals who are divorced, substance users, have low social support, or have participated in the war.

Conclusions

Two-fifths of women and girls in conflict-affected areas of the northeastern Amhara region experienced violence. Thus, collaboration between healthcare providers and policymakers is needed to enhance care for victims, including the provision of social support and substance use mitigation.
Anti-PD1 therapies induce an early expansion of Ki67+CD8+ T cells in metastatic non-oncogene addicted NSCLC patients
Authors: Gelibter Alain , Tuosto Lucrezia , Asquino Angela , Siringo Marco , Sabatini Arianna , Zizzari Ilaria Grazia , Pace Angelica , Scirocchi Fabio , Valentino Flavio , Bianchini Serena , Caponnetto Salvatore , Paoli Donatella , Bellati Filippo , Santini Daniele , Nuti Marianna , Rughetti Aurelia , Napoletano Chiara
Published: December 2024

Pembrolizumab (an anti-PD1 antibody) alone or combined with chemotherapy represented the standard of care for advanced non-oncogene addicted non-small cell lung cancer (NSCLC) patients. These therapies induced early modifications of the immune response impacting the clinical outcome. Identifying early changes in the immune system was critical to directing the therapeutic choice and improving the clinical outcome. In this study, we aim to analyze the activating and inhibiting immune cells of NSCLC patients before and during therapy to identify patients who will benefit from immunotherapies. Forty-eight NSCLC patients were analyzed before (T0) and after the first cycle of immunotherapy (T1), evaluating several activating (CD137+and PD1+), proliferating (Ki67+) and immunosuppressing immune subsets (Tregs: total, active, resting, and non-suppressive; MDSCs: PMN(Lox1+)-MDSC and M-MDSCs) by cytofluorimetry. Concurrently, 14 soluble immune checkpoints were analyzed by Luminex assay. Immunotherapy significantly increased the levels of Ki67+(total and CD8+) T cells, PMN(Lox1+)-MDSCs, non-suppressive Tregs (nsTregs), and soluble PD1 from T0 to T1 in the entire NSCLC population, while decreased active Tregs. These changes were partially attributed to responding patients who showed an increase of Ki67+ and CD8+T cells and nsTregs at T1. CD137+(total, CD8+, and CD4+) T cells and soluble LAG3 were predictor factors at T0 and T1. A low ratio of Tregs/CD137+ T cells and high levels of Ki67+CD137+ T cells positively correlated with response to therapy at T0 and T1, respectively. Results highlighted that immunotherapy improved the immunological fitness of those patients who benefited from immunotherapy, changing the immunological balance towards immune activation.
Prognostic significance of hemoglobin, albumin, lymphocyte and platelet score in solid tumors: a pooled study
Authors: Li Jinze , Zheng Jing , Wang Puze , Lv Dong
Published: December 2024

Objective

The high hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been reported to be a good prognostic indicator for several malignancies. However, more evidence is needed before it can be introduced into clinical practice. Here, we systematically evaluated the predictive value of HALP for survival outcomes in patients with solid tumors.

Methods

This study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) Guidelines. In March 2024, an electronic literature search was performed for articles regarding the prognostic role of HALP in solid tumors. Data from studies with reported risk ratios (HRs) and 95% confidence intervals (CIs) were pooled in a meta-analysis. Study bias was assessed using the QUIPS tool.

Results

Of the 729 articles reviewed, 45 cohorts including data from 17,049 patients with cancer were included in the pooled analysis. The pooled results demonstrated that elevated HALP score was significantly associated with favorable overall survival (HR = 0.60, 95% CI 0.54-0.67, p < 0.01), cancer-specific survival (HR = 0.53, 95% CI 0.44- 0.64, p < 0.01), progression-free survival (HR = 0.62, 95% CI 0.54-0.72, p < 0.01), recurrence-free survival (HR = 0.48, 95% CI 0.30-0.77, p < 0.01), and disease-free survival (HR = 0.72, 95% CI 0.57-0.82, p < 0.01). Subgroup analyses based on various confounding factors further revealed the consistent prognostic impact of HALP on overall survival in patients with solid tumors.

Conclusions

Our findings suggest that high HALP is associated with better survival outcomes in patients. The HALP score is a potential prognostic biomarker in solid tumors, but it needs to be further studied whether it can improve the established prognostic model.
Maternal immunization impairs lymphoma growth and CNS/ocular metastasis in the offspring
Authors: Braitbard Ori , Bar-Sinai Allan , Hochman Jacob
Published: December 2024

Maternal immunization is an important tool directed against a variety of infectious maladies in the offspring. A complementary, but less explored area is the use of maternal immunization in the prevention and treatment of childhood cancers. This in part stems from the lack of adequate experimental model systems. Lymphomas of the Central Nervous System (CNS) and ocular involvement pose a therapeutic challenge. Ocular lymphoma is a lethal disease caused mainly by two clinically distinct forms of non-Hodgkin’s lymphoma: non-Hodgkin’s lymphoma of the central nervous system, or Primary CNS lymphoma (PCNSL), and systemic lymphoma metastatic to the eye. Previously, we developed an experimental model whereby mouse lymphoma cell variants, derived from the S49 T-cell lymphoma, metastasized to the CNS and eyes following Intraperitoneal inoculation at days 7-10 postnatal. Here, we extended the model to study whether maternal immunization can impede CNS/Ocular metastasis in the offspring exposed to the metastatic lymphoma cells. To that effect, female Balb/C mice were vaccinated with either immunogenic, live, S49 lymphoma cell variants, or with a purified protein antigen: the 98 amino acid signal peptide of the envelop precursor protein of Mouse Mammary Tumor Virus (MMTV) endogenously harbored by the S49 lymphoma. The offspring from both vaccination protocols were immunized against a challenge with the CNS/Ocular metastatic lymphoma cells. Immunity was conferred via milk suckling and was prolonged without further challenge for an extended period of at least 3 months. The abovementioned findings constitute a novel experimental model system whereby CNS/Ocular metastasis of malignant lymphoma in the offspring is impeded through maternal vaccination/immunization and thus, can be followed mechanistically as well as for novel therapeutic modalities.
SARS-CoV-2 immune responses in patients with multiple myeloma and lenalidomide maintenance therapy
Authors: Martac Ioana , Beer Sina A. , Schenk Aileen , Ahmad Osama , Maier Claus-Philipp , Demirel Gülay , Preuß Beate , Klein Reinhild , Stanger Anna M. P. , Besemer Britta , Hensen Luca , Lengerke Claudia
Published: December 2024

Introduction

Multiple myeloma (MM) is an uncontrolled plasma cell proliferation in the bone marrow, leading to immune dysregulation with impaired humoral immune responses. Conversely, cellular-based responses play a vital role in MM patients. However, the extent and duration of cellular-induced protection remain unclear to date. Here, immunomodulatory drugs (IMiDs) like Lenalidomide (Lena) become interesting, as they may have stimulatory effects on T-cell functioning.

Methods

In this study we investigated immune responses elicited by COVID-19 vaccine or infection comparing 43 healthy volunteers (avg. 35y, 72.1% female, 81.4% previously COVID-19 infected), with 41 MM patients under Lena maintenance therapy (avg. 63.8y, 51.2% female, 61% previously COVID-19 infected). Humoral responses to SARS-CoV-2 spike (S), spike-RBD, and nucleocapsid (N) were measured via ELISA in subjects’ plasma. Freshly isolated PBMCs, incubated with SARS-CoV-2 peptides (N, S), activation induced marker (AIM) assays and flow cytometry, allowed us to assess cellular responses (CD8+ T, T(F)H: CD4+ T (follicular) helper).

Results

Whereas healthy controls showed significant better humoral responses (N IgA p<0.001), T cell responses were robust in the MM group (higher S-act. TH, p<0.001). Stratified by COVID-19 status, the MM group showed higher N-act. TH (p=0.03). These results were unchanged comparing a Lena intake with Lena break around vaccination.

Discussion

Taken together, MM patients under Lena therapy exhibit weakened antibody production but present a robust T cell response following SARS-COV-2 infection or vaccination. Our results highlight the importance of vaccination in this subgroup and moreover, argue against a Lena intake break around the time of vaccination.
The association between the body roundness index and the risk of chronic kidney disease in US adults
Authors: Zhang Jiaying , Yu Xiaofeng
Published: December 2024

Aim

We aimed to systematically assess whether the level of body roundness index (BRI) is associated with the risk of developing chronic kidney disease (CKD) in US adults.

Methods

The studied data was extracted from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. A total of 29,062 participants aged ≥20 years with complete information about BRI and CKD were included in this study. Logistic regression analysis, multivariate linear regression analysis, restricted cubic spline (RCS) plots curve, stratified analysis and receiver operating characteristic (ROC) curve were performed to investigate the association between BRI and CKD.

Results

A total of 29,062 patients were included, involving 4,623 individuals with CKD and 24,439 individuals without CKD. A higher BRI level was substantially related to an increased prevalence of CKD in US adults. After adjusting for confounding variables, the BRI in the fourth quartile was correlated to a higher CKD prevalence (OR: 1.36; 95% CI: 1.10–1.70) compared to the lowest quartile. After adjusting for confounding variables, the BRI in the fourth quartile was correlated to a higher CKD prevalence (OR: 1.36; 95% CI: 1.10–1.70) compared to the lowest quartile. However, in the subgroup analysis stratified by race and body mass index (BMI), no significant associations between BRI and CKD were observed among Mexican participants (OR: 1.10; 95% CI: 0.98–1.23) and those with underweight or normal weight (OR: 0.95; 95% CI: 0.81–1.05). Moreover, a non-linear relationship was found between BRI and the prevalence of CKD. In ROC analysis, BRI demonstrated higher discriminating for CKD (area under the curve: 0.6247; 95% CI: 0.6161–0.6333; optimal cutoff value: 5.161) compared with other indices.

Conclusion

In summary, BRI was independently associated with a higher prevalence of CKD in overweight and obese US adults, excluding Mexican. This may be an important therapeutic target and predictor of CKD. Physicians should advise patients with high BRI scores, especially overweight and obese patients, to embrace healthy lifestyle changes, such as maintaining a balanced diet and engaging in regular physical activity. These changes can help them control their body weight and reduce abdominal fat, ultimately lowering the risk of CKD.
Plant and soil microbial composition legacies following indaziflam herbicide treatment
Authors: Bradbury Ember Sienna , Holland-Moritz Hannah , Gill Amy , Havrilla Caroline A.
Published: December 2024

Land stewards in dryland ecosystems across the western U.S. face challenges to manage the exotic grass Bromus tectorum (cheatgrass), which is a poor forage, is difficult to remove, and increases risk of catastrophic fire. Managers may consider using indaziflam (Rejuvra™), a relatively new pre-emergent herbicide, which may reduce cheatgrass cover within drylands. However, few studies have explored the effects of indaziflam on non-target organisms. We tested how indaziflam application impacted cover and biomass of native and exotics within the plant community and composition and diversity of the soil microbiome by comparing untreated and treated arid shrubland sites in Boulder County, Colorado, USA. We found that indaziflam application decreased cheatgrass cover by as much as 80% and increased native plant cover by the same amount. Indaziflam application also was associated with increased soil nitrate (NO3−), decreased soil organic matter, and had a significant effect on the composition of the soil microbiome. Microbial community composition was significantly related to soil NO3−, soil organic matter, soil pH, and native species and cheatgrass biomass. An indicator species analysis suggested that indaziflam application shifted microbial communities. In untreated sites, ammonia-oxidizing bacteria Nitrosomonadaceae and nitrogen-digesting Opitutaceae and the fungi Articulospora proliferata were found. While in treated sites, ammonia-oxidizing archaea which are associated with intact drylands, Nitrososphaeraceae and toxin digesters and acidic-soil species Sphingomonas and Acidimicrobiia were significantly associated. Overall, these results demonstrate that indaziflam application can increase native plant recruitment, while also affecting soil properties and the soil microbiome. The findings from this study can be used to inform decision-making during dryland restoration planning process as indaziflam use may have benefits and unknown long-term consequences for the biogeochemistry and microbial ecology of the system.
The N6-methyladenosine RNA epigenetic modification modulates the amplification of coxsackievirus B1 in human pancreatic beta cells
Authors: Bonfim Maressa Fernandes , Aitchedji Camille , Van Goethem Flore , Sauvage Lionel , Poinsot Thibault , Calonne Emilie , Deplus Rachel , Fuks François , Eizirik Decio L. , Op de Beeck Anne
Published: December 2024

Type 1 diabetes (T1D) is characterized by a prolonged autoimmune attack resulting in the massive loss of insulin-producing beta cells. The initiation and progression of T1D depends on a complex interaction between genetic, immunological and environmental factors. Epidemiological, experimental and clinical evidence suggest a link between viral infections, particularly Coxsackievirus type B (CVB), and T1D development. Specifically, infections by the CVB serotype 1 (CVB1) contribute to the triggering of autoimmunity against beta cells in genetically predisposed individuals, and prolonged and probably non-lytic infections by CVB are associated with the development of T1D. However, the molecular mechanisms underlying CVB1 replication and establishing persistent infections in human pancreatic beta cells remain poorly understood. Here we show that the N6-methyladenosine (m6A) RNA epigenetic modification machinery regulates CVB1 amplification in the human beta cells. Using small interfering RNA (siRNA) targeting m6A writers and erasers, we observed that downregulation of m6A writers increases CVB1 amplification, while the downregulation of m6A erasers decreases it. Notably, the inhibition of Fat Mass and Obesity-associated protein (FTO), a key m6A eraser, reduced by 95% the production of infectious CVB1 in both human insulin-producing EndoC-βH1 cells and in induced pluripotent stem cell (iPSC)-derived islets. The FTO inhibitor reduced CVB1 expression within 6 h post-infection, suggesting a direct regulation of the CVB1 genome by m6A modification. Furthermore, in the absence of viral replication, FTO inhibition also decreased the translation of the incoming CVB1 genome, indicating that m6A plays a critical role in the initial stages of viral RNA translation. In addition, modulation of the m6A machinery affected the type I interferon response after poly-IC transfection, a mimic of RNA virus replication, but did not affect the cellular antiviral response in CVB1-infected cells. Altogether, these observations suggest that m6A directly affects CVB1 production. Our study provides the first evidence that the m6A epigenetic modification machinery controls CVB amplification in human pancreatic beta cells. This suggests that the m6A machinery is a potential target to control CVB infection in T1D and raises the possibility of an epigenetic control in the establishment of persistent CVB infections observed in the pancreas in individuals with type 1 diabetes.
High-throughput screening of dual-target inhibitors for SARS-CoV-2 main protease and papain-like protease from Chebulae Fructus: in silico prediction and experimental verification
Authors: Wang Changjian , Cao Yipeng , Yang Qi , Wang Xinyue , Yang Zhiying , Yang Jingjing , Li Xinru , Li Bin , Wang Yuefei , Zhang Min
Published: December 2024

Background

The unavoidable propagation of the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has underscored the urgent requirement for efficacious therapeutic agents. The dried fruit of Terminalia chebula Retz., namely Chebulae Fructus, is widely used for treating bacterial and viral infectious diseases, which was witnessed to perform anti-SARS-CoV-2 activity in recommended Chinese patent medicine.

Aim

SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) present essential effects on SARS-CoV-2 replication and transcription, considering as the attractive targets for therapeutic intervention. In this study, we focused on the dual-target to obtain broad-spectrum antiviral candidates from Chebulae Fructus.

Methods

The identified compounds from Chebulae Fructus were used to build a library in a previous study, which were evaluated by molecular docking to screen potential antiviral agents. The SARS-CoV-2 Mpro and PLpro were expressed in E. coli cells and purified. Fluorescence resonance energy transfer (FRET) and surface plasmon resonance (SPR) were utilized to verify the affinity with dual targets. SARS-CoV-2 wild-type, Omicron BA.5 and Omicron EG.5 variants were employed to validate their antiviral activities in vitro. Molecular dynamics simulation was conducted via Gromacs 2022 software in 500 ns to unveil the conformation stability.

Results

Targeting on Mpro and PLpro, eight compounds were screened as the potential dual-target inhibitors in molecular docking. In FRET and SPR assays, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) and 1,2,3,6-tetra-O-galloyl-β-D-glucose (TGG) showed good inhibitory activities with IC50 values ranging from 1.33 to 27.37 μM, and affinity with KD values ranging from 0.442 to 0.776 μM. Satisfactorily, both PGG and TGG display antiviral activity in vitro with EC50 values ranging from 3.20 to 37.29 μM, suggesting as the promising candidates against SARS-CoV-2. In molecular dynamics simulation study, the complexes of Mpro-PGG, Mpro-TGG, PLpro-PGG, and PLpro-TGG exhibited stability over 500 ns period, unveiling the potential interactions.

Conclusion

PGG and TGG are the promising dual-target inhibitors of SARS-CoV-2, which may avoid drug resistance and have a good development prospect. The outcomes of this study provide an effective strategy to systematically explore the antiviral bioactive compounds from Chebulae Fructus.
Novel automated method to assess group dynamics reveals deficits in behavioral contagion in rats with social deficits
Authors: Smirnov Kirill , Starkov Ilya , Sysoeva Olga , Midzyanovskaya Inna
Published: December 2024

Behavioral copying is a key process in group actions, but it is challenging for individuals with autism spectrum disorder (ASD). We investigated behavioral contagion, or instinctual replication of behaviors, in Krushinky-Molodkina (KM) rats (n = 16), a new potential rodent model for ASD, compared to control Wistar rats (n = 15). A randomly chosen healthy Wistar male (“demonstrator rat”) was introduced to the homecage of experimental rats (“observers”) 10–14 days before the experiments to become a member of the group. For the implementation of the behavioral contagion experiment, we used the IntelliCage system, where rats can live in a group of 5–6 rats and their water visits can be automatically scored. During the experiment, the demonstrator was taken out of IntelliCage for a pre-test water deprivation and then placed back for the behavioral contagion test. As a result, a drinking behavior of the water-deprived demonstrator rat prompted water-seeking and drinking behaviors in the whole group. Unlike the Wistar controls, KM observers showed fewer visits to the drinking bottles, particularly lacking inspection visits (i.e., visits without drinking). The control group, in contrast, exhibited a dynamic, cascade-like visiting of the water corners. The proportion of activated observers in KM rats was significantly lower, as compared to Wistar ones, and they did not mimic other observer rats. KM rats, therefore, displayed an attenuated pattern of behavioral contagion, highlighting social deficits in this strain. This study suggests that measuring group dynamics of behavioral contagion in an automated, non-invasive setup offers valuable insights into social behavior in rodents.
Trends in exercise therapy research for neurological diseases: a bibliometric and visualization approach from 2000 to 2024
Authors: Zhang Jiacheng , Zhu Lielie
Published: December 2024

Background

Neurological disorders are one of the major global health burdens, and exercise therapy has been widely recognized as a beneficial intervention. However, the existing literature has primarily focused on summarizing the interventions, complications, and influencing factors, with relatively limited systematic comparisons and summaries.

Methods

This study employed a bibliometric analysis approach, using VOSviewer and CiteSpace software to analyze the literature on the application of exercise therapy in neurological disorders from 2000 to 2024, including annual publication volumes, countries/regions, institutions, authors, journals, keyword co-occurrences, keyword clustering, keyword timelines, and keyword bursts.

Results

The study found that the United States is the leading contributor in this field, and the University of Toronto and the University of Illinois are the most active research institutions. Keyword analysis revealed that the research hotspots in this field are concentrated on the role of exercise therapy in the prevention, treatment, rehabilitation, and improvement of quality of life for neurological disorders, and are gradually delving into its potential physiological mechanisms.

Conclusion

This study provides valuable references for subsequent research in this field, helping to track the research frontiers and predict future research directions. Future research could further explore the specific mechanisms and clinical efficacy for different neurological diseases, providing more targeted evidence for clinical practice.
Sensory innervation in the prostate and a role for calcitonin gene-related peptide in prostatic epithelial proliferation
Authors: Xia Hanyu , Jerde Travis J. , Fehrenbacher Jill C.
Published: December 2024

Introduction

The prostate is densely innervated like many visceral organs and glands. However, studies to date have focused on sympathetic and parasympathetic nerves and little attention has been given to the presence or function of sensory nerves in the prostate. Recent studies have highlighted a role for sensory nerves beyond perception of noxious stimuli, as anterograde release of neuropeptides from sensory nerves can affect vascular tone and local immune responses.

Methods

To identify the degree of sensory innervation in the prostate, we utilized state-of-the-art tissue clearing and microscopy to visualize sensory innervation in the different lobes of the mouse prostate. To determine whether sensory nerves have a role in regulating proliferation within the prostate, we used an intersectional genetic and toxin approach to ablate peptidergic sensory nerves systemically.

Results

We found that sensory neurons are abundant in the prostate both in nerve bundles along the vasculature and as independent nerve fibers wrapped around prostatic acini in a net-like fashion. In addition to the dense innervation of the prostate, we found that Calca haploinsufficiency, the genotype control for our intersectional ablation model, results in a diminished level of Ki67 staining in the stromal compartment of the dorsal lobe and a diminishing Ki67 trend in other lobes.

Discussion

These findings suggest that sensory neurons might have developmental or homeostatic effects within the prostate. Further studies are warranted to assess the role of sensory neurons and the sensory neuropeptides on prostatic development and on proliferation in the presence of pro-inflammatory stimuli such as bacterial infection or tumor cells.
Unlocking the epigenetic code: new insights into triple-negative breast cancer
Authors: Mahendran Gowthami , Shangaradas Ann Dharshika , Romero-Moreno Ricardo , Wickramarachchige Dona Nadeeshika , Sarasija S. H. G. Sumudu , Perera Sumeth , Silva Gayathri N.
Published: December 2024

Triple-negative breast cancer (TNBC) is a highly aggressive and clinically challenging subtype of breast cancer, lacking the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2/neu. The absence of these receptors limits therapeutic options necessitating the exploration of novel treatment strategies. Epigenetic modifications, which include DNA methylation, histone modifications, and microRNA (miRNA) regulation, play a pivotal role in TNBC pathogenesis and represent promising therapeutic targets. This review delves into the therapeutic potential of epigenetic interventions in TNBC, with a focus on DNA methylation, histone modifications, and miRNA therapeutics. We examine the role of DNA methylation in gene silencing within TNBC and the development of DNA methylation inhibitors designed to reactivate silenced tumor suppressor genes. Histone modifications, through histone deacetylation and acetylation in particular, are critical in regulating gene expression. We explore the efficacy of histone deacetylase inhibitors (HDACi), which have shown promise in reversing aberrant histone deacetylation patterns, thereby restoring normal gene function, and suppressing tumor growth. Furthermore, the review highlights the dual role of miRNAs in TNBC as both oncogenes and tumor suppressors and discusses the therapeutic potential of miRNA mimics and inhibitors in modulating these regulatory molecules to inhibit cancer progression. By integrating these epigenetic therapies, we propose a multifaceted approach to target the underlying epigenetic mechanisms that drive TNBC progression. The synergistic use of DNA methylation inhibitors, HDACi, and the miRNA-based therapies offers a promising avenue for personalized treatment strategies, aiming to enhance the clinical outcome for patients with TNBC.
Exploring the effect of carbon nanoparticle tracing technique on five-year overall survival and disease-free survival in patients undergoing radical surgery for colorectal cancer: a retrospective study
Authors: Wen Guangxu , Jia Zihao , Wang Yingying , Kang Qingjie , Hu Denghua , Wang Ziwei
Published: December 2024

Background

To investigate the effect of preoperative carbon nanoparticle tracing technique via colonoscopy on the five-year overall survival and disease-free survival rates in patients undergoing radical resection for colorectal cancer.

Methods

A retrospective cohort study was conducted to collect data from patients diagnosed with colorectal cancer who underwent radical resection with complete postoperative pathological information at the First Affiliated Hospital of Chongqing Medical University from March 2013 to February 2017. Patients with multiple primary cancers were excluded, resulting in 2,237 eligible patients in the study. Of these, 368 patients were lost to follow-up within five years after surgery, resulting in a final sample of 1,869 patients. These patients were then divided into two groups: 758 patients who underwent preoperative carbon nanoparticle tracing technique via colonoscopy (CAS group) and 1,111 patients who did not undergo carbon nanoparticle tracing (non-CAS group). Survival curves for both overall survival and disease-free survival were plotted for both groups based on follow-up results. Univariate and multivariate analyses were performed to investigate the effect of carbon nanoparticle tracing technique on the 5-year overall survival and disease-free survival rates in patients, as well as to explore the factors influencing these outcomes.

Results

The results showed that the total number of lymph nodes detected in the tracing group 15(11,19) was significantly higher than that in the non-tracing group 11(7,15), with a statistically significant difference (p<0.05). The 5-year overall survival rates were 90.8% in the CAS group and 87.4% in the non-CAS group, and, while the disease-free survival rate were 88.5% and 83.4%, respectively. However, the differences between 5-year overall survival and disease-free survival between the two groups were not statistically significant (p>0.05). Both univariate and multivariate cox regression analyses demonstrated that patient age, tumor stage, postoperative chemoradiotherapy, postoperative radiotherapy, and postoperative tumor recurrence were independent factors influencing the 5-year overall survival and disease-free survival rates in colorectal cancer patients.

Conclusion

Carbon nanoparticle tracing technique can effectively increase the total detected number of lymph nodes in patients with radical resection for colorectal cancer, but it does not significantly impact the 5-year overall survival and disease-free survival rates in these patients.
Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer
Authors: Lin Feizhi , Chen Xiaojiang , Liang Chengcai , Zhang Ruopeng , Chen Guoming , Zheng Ziqi , Huang Bowen , Wei Chengzhi , Zhao Zhoukai , Zhang Feiyang , Chen Zewei , Ruan Shenghang , Chen Yongming , Nie Runcong , Li Yuangfang , Zhao Baiwei
Published: December 2024

Aim

Programmed cell death (PCD) critically influences the tumor microenvironment (TME) and is intricately linked to tumor progression and patient prognosis. This study aimed to develop a novel prognostic indicator and marker of drug sensitivity in patients with gastric cancer (GC) based on PCD.

Methods

We analyzed genes associated with 14 distinct PCD patterns using bulk transcriptome data and clinical information from TCGA-STAD for model construction with univariate Cox regression and LASSO regression analyses. Microarray data from GSE62254, GSE15459, and GSE26901 were used for validation. Single-cell transcriptome data from GSE183904 were analyzed to explore the relationship between TME and the newly constructed model, named PCD index (PCDI). Drug sensitivity comparisons were made between patients with high and low PCDI scores.

Results

We developed a novel twelve-gene signature called PCDI. Upon validation, GC patients with higher PCDI scores had poorer prognoses. A high-performance nomogram integrating the PCDI with clinical features was also established. Additionally, single-cell transcriptome data analysis suggested that PCDI might be linked to critical components of the TME. Patients with high PCDI scores exhibited resistance to standard adjuvant chemotherapy and immunotherapy but might benefit from targeted treatments with NU7441, Dasatinib, and JQ1.

Conclusion

The novel PCDI model shows significant potential in predicting clinical prognosis and drug sensitivity of GC, thereby facilitating personalized treatment strategies for patients with GC.
Effects of hypoxia on uteroplacental and fetoplacental vascular function during pregnancy
Authors: Arenas Germán A. , Lorca Ramón A.
Published: December 2024

During pregnancy, marked changes in vasculature occur. The placenta is developed, and uteroplacental and fetoplacental circulations are established. These processes may be negatively affected by genetic anomalies, maternal environment (i.e., obesity or diabetes), and environmental conditions such as pollutants and hypoxia. Chronic hypoxia has detrimental effects on the vascular adaptations to pregnancy and fetal growth. The typical pregnancy-dependent rise in uterine blood flow by vascular remodeling and vasodilation of maternal uterine arteries is reduced, leading to increases in vascular tone. These maladaptations may lead to complications such as fetal growth restriction (FGR) and preeclampsia. In this review, the effect of hypoxia on uteroplacental and fetoplacental circulation and its impact on pregnancy outcomes in humans and animal models are discussed. Evidence is provided for several mechanisms that affect pregnancy through hypoxia-induced alterations. Future directions to fill gaps in knowledge and develop therapeutic strategies to prevent or alleviate hypoxia-related pregnancy complications, such as FGR and preeclampsia, are suggested.
Assessment of ipsilateral and contralateral perfusion after contrast compression therapy of upper limb muscles in MMA athletes - a cross-over study
Authors: Trybulski Robert , Stanula Arkadiusz , Muracki Jarosław , Kuczmik Wacław , Kurtoğlu Ahmet , Taradaj Jakub
Published: December 2024

Objective

The primary aim of this study was to compare the immediate effect of contrast compression therapy with the use of Game Ready (GRT) on hyperaemic reactions in the upper limb on the application and contralateral sides, specifically in the context of mixed martial arts (MMA) athletes.

Design

In this experimental, single-blind, randomized crossover study, we recruited 30 male volunteers training in MMA (mean age: 28.33 ± 3.79 years, BMI: 25.25 ± 3.06, training experience: 9.93 ± 3.83). They were randomly assigned to the experimental (n = 15) or control (sham) group (n = 15). The experimental group underwent a 10-minute Game Ready Therapy (GRT) session, while the control group GRS underwent a sham therapy session. After a 2-week break, a cross-over change of therapy in the groups was performed, ensuring a comprehensive evaluation of the contrast compression therapy’s perfusion effects in 30 participants. Main outcome measures: Hyperemic reaction was measured: rest flow (RF - [non-referent unit]); therapeutic flow (TF- [min]), i.e., the average flow recorded during GR or sham therapy: time of recovery (TR - [min]), i.e., the time for perfusion to return to the resting value after the intervention. Measurements were performed on the ipsilateral and contralateral sides.

Results

The mean perfusion during therapy was significantly higher in GRT compared to GRS (24.70 ± 1.45 vs. 12.60 ± 1.37; p < 0.001; ES = 5.7 [large]; △ = 12.10 > MDC). The time from cessation of contrast therapy to the return of blood flow to resting values showed significantly higher values in GRT compared to GRS (3.07 ± 0.45 vs. 16.80 ± 0.91; p < 0.001; ES = 16.27 [large]). No statistically significant difference was noted between the mean resting perfusion value (RF) and the mean perfusion value during therapy (TF) in the contralateral limb (7.74 ± 0.89 vs. 7.66 ± 0.89; p = 0.284; ES = 0.20 [negligible]; △ = 0.09 < MDC.

Conclusion

This study suggests that compression contrast therapy on the ipsilateral side positively affects the intensification of the hyperaemic reaction. However, no statistically significant hyperaemic responses were observed on the contralateral side.
Effect and individual response to inspiratory muscle training program among instrumentalist musicians
Authors: Ibáñez-Pegenaute Ana , Ortega-Moneo María , Ramírez-Vélez Robinson , Antón M. M.
Published: December 2024

In this quasi-experimental before-after trial, we investigated the effects of a high-intensity, low-repetition inspiratory muscle training (HI-LRMT) protocol on respiratory muscle strength in instrumental musicians. In addition, was to estimate the prevalence of “non-responders” (NRs) in terms of muscle force after intervention. Healthy musicians (n = 48) were divided into 2 groups: HI-LRMT (n = 33) and a control group that did not train (CG, n = 15). The intervention training was a high-intensity, low-repetition inspiratory muscle training program using the PowerBreathe® threshold load pressure device, 2 daily sessions of 30 repetitions per session, with a minimum frequency of 5 days per week, for 12 weeks, 5 min per session. The primary outcome measures were maximal inspiratory pressure and expiratory pressure. Change in PImax over 12 weeks for HI-LRMT vs. control was 30.9 (95% CI 25.5–38.3), with the large effect, confirming worthwhile benefits (ηp2 = 0.61). There were significant changes in PEmax 37.3 (95% CI 19.3–48.1), with a large effect size (ηp2 = 0.33). A third of the participants did not demonstrate improvements in terms of muscle force in instrumental musicians. In conclusion, a 12-week high-intensity, low-repetition inspiratory muscle training program using the PowerBreathe® threshold load pressure device, improved inspiratory and expiratory muscle strength in instrumental musicians.
Association between urinary arsenic and hearing threshold shifts in adults in the United States, National Health and Nutrition Examination Survey, 2015–2016
Authors: Long Lili , Jia Zhenchao , Liu Tao
Published: December 2024

Background

Hearing loss (HL) is a common sensory disorder in humans. Studies on the relationship between arsenic, which is a highly toxic and widely distributed heavy metal with a health risk to humans, and hearing status in humans are contradictory and mostly focused on people living in arsenic-contaminated areas. This study investigated the association between urinary arsenic levels and hearing threshold shifts in the general population in the United States.

Methods

Overall, 1,017 adults (aged 20–69 years) from the National Health and Nutrition Examination Survey (2015–2016) were included in this study. HL was defined as pure-tone average (PTA) ≥ 20 dB at frequencies 500, 1,000, 2000, and 4,000 Hz in the better-hearing ear. Total urinary arsenic (uAs) and dimethylarsinic acid (uDMA) levels were analyzed. Multivariate linear regression analyses and smooth curve fitting were performed to evaluate the correlations between uDMA, uAs, and low-, speech-, and high-frequency hearing levels.

Results

The mean age of the participants was 42.13 ± 13.66 years, including weighted 48.67% men and 12.88% participants with sensorineural HL. After adjusting for potential confounders in the multivariate linear regression model, higher uDMA levels were significantly associated with poor low-, and speech-frequency PTAs, with no differences among participants by age or sex. Smooth curve fitting indicated a nonlinear relationship between uAs and high-frequency PTA hearing threshold shifts. The uAs levels were positively associated with high-frequency PTA until the turning point of 1.54 (adjusted β 4.53, 95% CI 1.16, 7.90; p = 0.0085), beyond which this association was not observed (adjusted β −0.43, 95% CI −1.57, 0.71; p = 0.4600).

Conclusion

We found positive associations between urinary arsenic metabolites uDMA, uAs levels and poor hearing threshold shifts in US adults. This study provides new evidence for the association between arsenic exposure and auditory function.
Geo-spatial analysis of high-risk fertility behaviors and child stunting in Ethiopia
Authors: Zewdia Wondaya Fenta , Asmelash Daniel , Asmelash Yemane
Published: December 2024

Background

The process of childbirth involves significant risks, particularly when certain high-risk fertility behaviors (HRFBs) are observed. HRFB of birth includes maternal age below 18 years or above 34 years at the time of childbirth, having a child born after a short birth interval (24 months), and having a high parity (more than three children). The majority of child stunting cases were linked to high-risk reproductive practices. Stunted children are those whose height-for-age Z-score is less than –2SD (standard deviation) from the median of a reference population. This study aimed to investigate the spatial association between HRFB of birth and stunting in under-five children across Ethiopia’s administrative zones.

Method

This study used cross-sectional data from the latest Mini Ethiopian Demographic and Health 2019 Survey, which included a weighted sample of 4,969 under-five children from 64 administrative zones. Spatial model analysis, specifically the spatial Durbin model, was used to examine the association between HRFB of birth and stunting in children. ArcGIS 10.8 was used for mapping and SAS 9.4 was used for model analysis.

Results

The average mean proportion of HRFB of birth to the rate of stunting in children at the zonal level in Ethiopia was observed to be 58 and 36%, respectively, across Ethiopian zones. Children whose mothers displayed HRFB of birth and who were stunted were 24% at all times. The median value of HRFB of birth and stunting were 0.61 and 0.36, respectively. The average vegetable index and the livestock index across Ethiopian zones showed spatial variations of 0.57 and 0.12, respectively. In the selected spatial Durbin model, the deviance value was very small, indicating that the model fit the data well.

Conclusion

The study found a high prevalence and significant spatial variation in both HRFB of birth and stunting across the Ethiopian zones. The spatial distribution of both HRFB of birth and stunting were found to be significantly clustered in the administrative zones of Ethiopia. These results emphasize the need for targeted interventions to address HRFB and stunting, supporting Ethiopia in achieving its Sustainable Development Goals.
Association between brominated flame retardants and periodontitis: a large-scale population-based study
Authors: Jiang Hao , Yin Jingwen , Wang Meixiang , Yuan Aili , Wu Jing , Lu Yi
Published: December 2024

Background

The association between brominated flame retardants (BFRs) and periodontitis has remained unclear.

Methods

This research included adult participants from NHANES cycles 2009–2014. Survey-weighted generalized linear regressions were used to explore the associations between BFR exposure and periodontitis. Ln-transformed BFRs were treated as quantitative variables and then divided into four quartiles for qualitative analysis. Restricted cubic splines (RCSs) were utilized to investigate potential nonlinear relationships. Quantile weighted quantile sum (WQS) regression and quantile g-computation (QGC) analysis were performed to assess the overall effect of BFRs on periodontitis.

Results

A total of 2,445 participants were included in this study. In the fully adjusted model, several ln-transformed BFR components were positively correlated with periodontitis: serum PBDE28, PBDE47, PBDE85, PBDE99, PBDE100, PBDE154, and PBB153. When expressed in quartiles, PBDE28, PBDE85, PBDE100, PBDE154, and PBB153 showed increased odds with periodontitis. We found significant nonlinear correlation between PBDE28, PBDE47, PBDE85, PBDE100, PBDE154, and PBB153 with periodontitis in the RCS regression. The WQS index for mixed BFR exposure was positively associated with periodontitis prevalence (OR: 1.52; 95% CI: 1.30–1.79, p < 0.001). Similarly, the QGC analysis showed a positive association between mixed BFR exposure and periodontitis prevalence (β: 1.29; 95% CI: 1.24–1.36, p < 0.001).

Conclusion

This study indicates that overall exposure to BFRs is positively associated with the prevalence of periodontitis. Further research is needed to investigate the causal relationship and underlying mechanisms between BFRs and periodontitis.