bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of therapeutic exercise for primary dysmenorrhea: a systematic review and meta-analysis
Authors: Xiang Yi , Li Qinhai , Lu Zengao , Yu Zemin , Ma Guanglin , Liu Siqi , Li Yingkui
Published: February 2025

Objective

A growing number of research papers have looked at the influence of exercise on pain severity in people with primary dysmenorrhea, but the findings have been inconsistent. The purpose of this research was to thoroughly evaluate the impact of exercise on pain severity in individuals with primary dysmenorrhea and to find the best exercise regimen for these patients.

Methods

All randomized controlled trials (RCTs) of exercise for patients with primary dysmenorrhea were searched in the Embase, PubMed, Cochrane, Web of Science, EBSCO, and CINAHL databases. The search time limit was set from the establishment of each database to 28 January 2025. Control groups included those receiving usual care, only providing health education, or no intervention at all. The outcome measure was pain intensity. The effect size was aggregated using the mean difference (MD) and 95% confidence interval (CI). The methodological quality of the included studies was evaluated using the Cochrane risk-of-bias tool. Stata 15 software was used for meta-analysis, sensitivity analysis, and assessment of potential publication bias. R 4.4.1 software was used for network meta-analysis, area under curve ranking (SUCRA), league plot, and meta-regression.

Results

The analysis included a total of 29 studies that satisfied the criteria. Exercise decreased the visual analog scale (VAS, WMD = −2.62, 95% CI [−3.29, −1.95], p < 0.001) score in individuals with primary dysmenorrhea. Strength training (WMD = −1.76, 95% CI [−2.03, −1.48], p < 0.001), exercise duration of ≥8 weeks (WMD = −1.77, 95% CI [−1.87, −1.66], p < 0.001), frequency of >3 times per week (WMD = −1.60, 95% CI [−1.75, −1.45], p < 0.001), session length of >30 min (WMD = −2.20, 95% CI [−2.38, −2.02], p < 0.001), and a total of ≥90 min per week (WMD = −2.04, 95% CI [−2.19, −1.89], p < 0.001) showed superior efficacy in enhancing VAS (subgroup analyses).

Conclusion

Engaging in physical activity may reduce the intensity of discomfort encountered by individuals afflicted with primary dysmenorrhea, with strength training potentially emerging as the most efficacious alternative. The meta-analysis presents evidence that supports clinicians’ advice to patients with primary dysmenorrhea, recommending that they exercise for a minimum of 8 weeks, with sessions occurring more than three times weekly and lasting longer than 30 min each. The goal is to achieve a minimum weekly total of 90 min by increasing the frequency of workouts.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024581879, CRD42024581879.
Riverine antibiotic resistome along an anthropogenic gradient
Authors: Wang Gangan , Haenelt Sarah , Corrêa Felipe Borim , da Rocha Ulisses Nunes , Musat Florin , Zhang Junya , Müller Jochen A. , Musat Niculina
Published: February 2025

The introduction of antibiotic-resistant bacteria into riverine systems through the discharge of wastewater treatment plant (WWTP) effluent and agricultural waste poses significant health risks. Even when not pathogenic, these bacteria can act as reservoirs for antibiotic resistance genes (ARGs), transferring them to pathogens that infect humans and animals. In this study, we used fluorescence in situ hybridization, qPCR, and metagenomics to investigate how anthropogenic activities affect microbial abundance and the resistome along the Holtemme River, a small river in Germany, from near-pristine to human-impacted sites. Our results showed higher bacterial abundance, a greater absolute and relative abundance of ARGs, and a more diverse ARG profile at the impacted sites. Overall, the ARG profiles at these sites reflected antibiotic usage in Germany, with genes conferring resistance to drug classes such as beta-lactams, aminoglycosides, folate biosynthesis inhibitors, and tetracyclines. There were also variations in the ARG profiles of the impacted sites. Notably, there was a high abundance of the oxacillin resistance gene OXA-4 at the downstream site in the river. In the metagenome assembly, this gene was associated with a contig homologous to small plasmids previously identified in members of the Thiotrichaceae. The likely in-situ host of the putative plasmid was a close relative of Thiolinea (also known as Thiothrix) eikelboomii, a prominent member of WWTP microbiomes worldwide. Our results show that the effluent from WWTPs can introduce bacteria into the environment that act as shuttle systems for clinically relevant ARG.
Size matters: larger fragments of riparian forest in urban areas support functional diversity of soil bacteria more than smaller ones
Authors: Koster Gabriela , Jaźwa Małgorzata , Przemieniecki Sebastian Wojciech , Musielok Łukasz , Azarbad Hamed , Klimek Beata
Published: February 2025

Soil microorganisms are relatively poorly studied in urban ecosystems, particularly within unmanaged woodlands that form island-like patches of vegetation. We surveyed soil bacteria on Salix spp. dominated riparian-like forest patches in Kraków, the second largest city in Poland, to find out which environmental factors influence their activities and functional diversity, measured using Biolog® ECO plates. Our results showed that soil bacterial alpha functional diversity, including substrate richness (number of substrates decomposed) and Shannon diversity, were positively correlated with patch area and number of vascular plant species in the forest floor vegetation layer. However, soil bacterial beta functional diversity (substrate use pattern, CLPP – community level physiological profiles) was primarily driven by patch area and soil physicochemical properties. Our results suggest that the positive effect of patch area (biogeographic effect) on soil bacterial functional diversity may be primarily through stabilisation of environmental conditions, as the amplitude of environmental fluctuations is reduced on larger plots compared to smaller ones. Taken together, our study provides important insights into the relationship between patch area, soil properties, vegetation characteristics, soil bacteria activity, and functional diversity in urban riparian forests, highlighting the importance of considering soil microbes when managing urban ecosystems.
Genomic characterization and antifungal properties of Paenibacillus polymyxa YF, a promising biocontrol agent against Fusarium oxysporum pathogen of codonopsis root rot
Authors: Li Ying , Su Xu , Xi Wenjie , Zheng Yanli , Liu Yang , Zheng Wangshan , Wei Shiyu , Leng Yan , Tian Yongqiang
Published: February 2025

Root rot, a destructive soil-borne disease, poses a significant threat to a wide range of economically important crops. Codonopsis, a high-value medicine plant, is particularly susceptible to substantial production losses caused by Fusarium oxysporum-induced root rot. In this study, we identified a promising biocontrol agent for codonopsis root rot, Paenibacillus polymyxa YF. In vitro assay demonstrated that the strain YF exhibited a 70.69% inhibition rate against F. oxysporum and broad-spectrum antifungal activities against the selected six postharvest pathogens. Additionally, the strain YF demonstrated significant plant growth-promoting properties. Subsequent in vivo inoculation assays revealed that the strain YF effectively mitigated disease symptoms of F. oxysporum-induced root rot in codonopsis, even achieving a complete disease prevention efficacy rate of 100%. Our findings further elucidated that the robust biocontrol capacity of the strain YF against F. oxysporum is mediated through multiple mechanisms, including inhibition of fusaric acid secretion, downregulation of virulence-associated genes in F. oxysporum, and the production of multiple hydrolytic enzymes. Genomic analysis showed that the strain YF has a 5.62-Mb single circular chromosome with 5,138 protein-coding genes. Comprehensive genome mining of the strain YF also identified numerous genes and gene clusters involved in bio-fertilization, resistance inducers synthesis, plant colonization, biofilm formation, and antimicrobial activity. These findings provide insights into the biocontrol mechanisms of the strain YF and offer substantial potential for its further exploration and application in crop production.
Identifying potential biomarkers and molecular mechanisms related to arachidonic acid metabolism in vitiligo
Authors: Li Xiaoqing , Yang Li , Zhu Longfei , Sun Jingying , Xu Cuixiang , Sun Lijun
Published: February 2025

Background

Numerous studies have reported that dysregulation of fatty acid metabolic pathways is associated with the pathogenesis of vitiligo, in which arachidonic acid metabolism (AAM) plays an important role. However, the molecular mechanisms of AAM in the pathogenesis of vitiligo have not been clarified. Therefore, we aimed to identify the biomarkers and molecular mechanisms associated with AAM in vitiligo using bioinformatics methods.

Methods

The GSE75819 and GSE65127 datasets were used in this study as the training and validation sets, respectively, along with 58 AAM-related genes (AAM-RGs). The differentially expressed genes (DEGs) between the lesional and control groups in the training set were identified through differential expression analysis. A biomarker-based nomogram was constructed to predict the risk of vitiligo.

Results

15 overlapping candidate genes were obtained between the DEGs and AAM-RGs. Machine-learning algorithms were used to identify six key genes as PTGDS, PNPLA8, FAAH, ABHD12, PTGS1, and MGLL. In both the training and validation sets, PTGDS, PNPLA8, and MGLL. In both the training and validation sets, PTGDS, PNPLA8, and MGLL were regarded as biomarkers. A nomogram based on these biomarkers showed potential for predicting the risk of vitiligo. Functional enrichment, immune cell infiltration, and regulatory network analyses were used to elucidate the molecular mechanisms.

Conclusion

In conclusion, PTGDS, PNPLA8, and MGLL were implicated in AAM to influence the pathogenesis of vitiligo. These findings offer insights into vitiligo treatment, although further research is needed for a comprehensive understanding.
Neutrophil-related immune-inflammatory biomarkers influence the early progression of medial medullary infarction
Authors: Li Li-Min , Cai Hao
Published: February 2025

Background

Medial medullary infarction (MMI) is a rare type of posterior circulation stroke for which accurate prognostication remains a challenge because of the limited predictive ability of the current models. Blood-derived biomarkers may provide valuable insights that extend beyond established prognostic factors. The aim of this study was to identify rapid and accessible biomarkers for predicting the early progression of MMI.

Methods

Seventy patients with MMI and 83 sex- and age-matched healthy controls (HCs) were recruited for this study. Among them, 20 patients were allocated to the early progression cohort, and 50 patients were assigned to the nonprogression cohort. The laboratory blood indices were subsequently compared across these different cohorts. Receiver operating characteristic (ROC) curves were used to evaluate the predictive values of blood-derived indicators.

Results

The white blood cell (WBC) count, neutrophil count, monocyte count, low-density lipoprotein cholesterol (LDL-C) level, total cholesterol (TC) concentration, WBC-to-high-density lipoprotein cholesterol (HDL-C) ratio (WHR), neutrophil-to-HDL-C ratio (NHR), monocyte-to-HDL-C ratio (MHR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly greater in patients with MMI than in HCs (p < 0.05). The WBC count, neutrophil count, monocyte count, WHR, NHR, MHR, MLR, NLR and PLR were markedly higher in MMI patients with progression than in MMI patients without progression (p < 0.05). ROC curve analysis revealed that the WBC count, neutrophil count, monocyte count, MLR, NLR, PLR, NHR, and WHR were significant predictors of early progression. However, among these factors, the WBC count (AUC = 0.854, p < 0.001), neutrophil count (AUC = 0.878, p < 0.001), NLR (AUC = 0.861, p < 0.001), and NHR (AUC = 0.848, p < 0.001) had the highest levels of accuracy for predicting early progression in patients with MMI.

Conclusion

The efficacy of the WBC count, neutrophil count, NLR and NHR is superior in predicting progression in patients with MMI. The current findings suggest that these indicators may serve as reliable, cost-effective, and innovative prognostic markers for MMI.
Sex differences in the prediction of metabolic abnormalities via body mass index in an Eastern Chinese population
Authors: Gao Yingjie , Jin Kaimeng , Chen Jin , Chen Ben , Guo Yan , Lu Jin
Published: February 2025

Objective

Body mass index (BMI) is important for predicting the occurrence of metabolic abnormality, but sex differences exist. We aimed to investigate potential sex differences in the predictive value of BMI for metabolic abnormality and to calculate the optimal BMI cut-offs for predicting metabolic abnormality for each sex.

Methods

Participants (n = 4,623) who attended a health check-up centre continuously in Eastern China between January 2022 and December 2023 were evaluated for metabolic abnormalities. We calculated the proportions of different metabolic abnormalities in different sexes. Receiver operating characteristic (ROC) curves were calculated to determine the optimal BMI cut-off values for predicting metabolic abnormality in males and females. The recognition rate of each metabolic abnormality using different BMI cut-off values for men and women were evaluated.

Results

Among 4,623 participants (2,234 men and 2,389 women), the age-adjusted prevalence of all metabolic abnormalities was significantly greater among males than among females (p < 0.001). The optimal cut-off values for predicting metabolic abnormalities were 23.5 kg/m2 (males) and 21.8 kg/m2 (females). When BMI ≥24 kg/m2 was used as the cut-off value the recognition rates of each abnormal metabolic factor in the male group were all above 50%, while they were mostly below 50% in the female group, except for the recognition of hyperglycaemia and hypertriglyceridemia. However, in females, when BMI ≥22 kg/m2 was used as the cut-off value, the recognition rates for each abnormal metabolic factor were all above 50%, greater than that when BMI ≥24 kg/m2 was used (p < 0.001).

Conclusion

There were sex differences in the BMI thresholds for predicting metabolic abnormalities in the health check-up population.
Machine learning-driven insights into lipid metabolism and inflammatory pathways in knee osteoarthritis
Authors: Man Tian-Ming , Ma Yun , Zhao Yu-Gang , He Qian-Song , Li Guo-Shuai , Wu Xin-Fang
Published: February 2025

Knee osteoarthritis (KOA) is a multifactorial degenerative joint disease influenced by lipid metabolism, systemic inflammation, and dietary factors. This study integrates clinical data, biochemical markers, and machine learning models to identify key predictors of KOA severity and develop personalized dietary strategies for disease management. A cohort of 600 KOA patients was analyzed, revealing significant correlations between dyslipidemia (low HDL, high LDL) and inflammatory biomarkers (CRP, IL-6). Machine learning models identified BMI, CRP, and IL-6 as critical predictors of pain severity (AUC = 0.93). Based on these findings, we propose targeted dietary recommendations, including increased omega-3 fatty acid intake and reduced saturated fat consumption, to modulate inflammation and improve clinical outcomes. This study highlights the potential of precision nutrition approaches in addressing the metabolic and inflammatory underpinnings of KOA.
AI models for the identification of prognostic and predictive biomarkers in lung cancer: a systematic review and meta-analysis
Authors: AlOsaimi Hind M. , Alshilash Aseel M. , Al-Saif Layan K. , Bosbait Jannat M. , Albeladi Roaa S. , Almutairi Dalal R. , Alhazzaa Alwaleed A. , Alluqmani Tariq A. , Al Qahtani Saud M. , Almohammadi Sara A. , Alamri Razan A. , Alkurdi Abdullah A. , Aljohani Waleed K. , Alraddadi Raghad H. , Alshammari Mohammed K.
Published: February 2025

Introduction

This systematic review and meta-analysis aim to evaluate the efficacy of artificial intelligence (AI) models in identifying prognostic and predictive biomarkers in lung cancer. With the increasing complexity of lung cancer subtypes and the need for personalized treatment strategies, AI-driven approaches offer a promising avenue for biomarker discovery and clinical decision-making.

Methods

A comprehensive literature search was conducted in multiple electronic databases to identify relevant studies published up to date. Studies investigating AI models for the identification of prognostic and predictive biomarkers in lung cancer were included. Data extraction, quality assessment, and meta-analysis were performed according to PRISMA guidelines.

Results

A total of 34 studies met the inclusion criteria, encompassing diverse AI methodologies and biomarker targets. AI models, particularly deep learning and machine learning algorithms demonstrated high accuracy in predicting biomarker status. Most of the studies developed models for the prediction of EGFR, followed by PD-L1 and ALK biomarkers in lung cancer. Internal and external validation techniques confirmed the robustness and generalizability of AI-driven predictions across heterogeneous patient cohorts. According to our results, the pooled sensitivity and pooled specificity of AI models for the prediction of biomarkers of lung cancer were 0.77 (95% CI: 0.72 – 0.82) and 0.79 (95% CI: 0.78 – 0.84).

Conclusion

The findings of this systematic review and meta-analysis highlight the significant potential of AI models in facilitating non-invasive assessment of prognostic and predictive biomarkers in lung cancer. By enhancing diagnostic accuracy and guiding treatment selection, AI-driven approaches have the potential to revolutionize personalized oncology and improve patient outcomes in lung cancer management. Further research is warranted to validate and optimize the clinical utility of AI-driven biomarkers in large-scale prospective studies.
Real-life evidence of encorafenib plus binimetinib in patients with unresectable advanced or metastatic BRAFV600-mutant melanoma in Spain: the BECARE (GEM-2002) trial
Authors: Soria Ainara , Sanchez Mauriño Pedro , Serrano Domingo Juan José , García Galindo Regina , Sequero Silvia , Gutiérrez Sanz Lourdes , Crespo Guillermo , Díaz-Beveridge Roberto , Puértolas Teresa , López Pedro , Fra Rodríguez Joaquín , López Castro Rafael , Aguayo Cristina , Valdivia Javier , Cunquero-Tomás Alberto Jacobo , Benítez Gretel , Ayala de Miguel Pablo , Espinosa Enrique , Muñoz-Couselo Eva , Campos Begoña , García Sánchez Lourdes , Cerezuela-Fuentes Pablo
Published: February 2025

Purpose

Combined BRAF/MEK inhibition with encorafenib (E) plus binimetinib (B) has demonstrated efficacy and tolerability in phase III clinical trials, and is the standard of care for advanced/metastatic BRAFV600-mutant melanoma. However, real-life evidence is limited, particularly in patients pre-treated with immune checkpoint inhibitors (ICI).

Patients and methods

BECARE GEM 2002 was a retrospective, non-interventional study aimed at investigating the real-world effectiveness and tolerability of EB in patients with unresectable or metastatic BRAFV600-mutant melanoma conducted at 21 sites in Spain. The primary objective of this study was to characterise the population of patients receiving EB and assess the efficacy and tolerability of EB in real life. The study included patients treated according to standard clinical practice with EB as the 1st line or 2nd line after progression to ICI for an unresectable or metastatic stage. Patients who previously received treatment with BRAF and/or MEK inhibitor, other than as adjuvants, that ended ≥ 6 m before EB were not eligible

Results

From September 2021 to March 2023, 117 patients were included; 89 (76.1%) and 28 (23.9%) patients received EB as 1st line and 2nd line, respectively. The median follow-up was 13.8 months (95% CI: 12.0-17.4). In patients with EB as 1st line treatment, ORR and median PFS were 75% and 12 months (95% CI: 9.4-18.6), respectively. In patients with EB as 2nd line treatment after ICI, ORR and median PFS were 77.8% and 12.5 months (95% CI: 6.6-NA), respectively. In patients with brain metastasis ORR and median PFS were 70.8% and 6.3 months (95% CI: 6.1-10.3). Treatment-related adverse events of grade ≥3 were reported in 17 (14.5%) patients; transaminitis (9.4%) and diarrhoea (2.6%) were the most frequent adverse events.

Conclusion

In this real-world study, EB treatment demonstrated effectiveness and a consistent safety profile in patients with BRAFV600-mutant melanoma treated according to standard clinical practice, including in those with prior ICI treatment and of brain metastasis; therefore, EB is a feasible treatment option for unresectable and metastatic melanoma.

Clinical trial identification: REec: 0004-2021-OBS

Clinical trial identification

REec: 0004-2021-OBS.
Significance of mouse xenograft tumor model using patient-derived cancer organoids for clinical drug development
Authors: Ogawa Hisataka , Yoshida Keiichi , Hasegawa Shinichiro , Wada Hiroshi , Yasui Masayoshi , Tahara Hideaki
Published: February 2025

Background

In vitro and in vivo preclinical examinations of cancer cell lines are performed to determine the effectiveness of new drugs before initiating clinical trials. However, there is often a significant disparity between the promising results observed in preclinical evaluations and actual outcomes in clinical trials. Therefore, we hypothesized that this inconsistency might be due to the differences between the characteristics of cell lines and actual cancers in patients. Therefore, we screened drugs for bile duct cancer to test our hypotheses.

Methods

We established patient-derived cancer organoids (PDCOs) from the surgical samples of patients with bile duct cancer and conducted multiple in vitro drug screening tests.

Results

We identified proteasome inhibitors (Bortezomib and Carfilzomib) as promising drugs in the screening. Bortezomib has demonstrated a significant antitumor effect on bile duct cancer cell-derived xenografts, as previously reported in preclinical trials. However, although Bortezomib showed significant proliferation inhibition in PDCOs in three-dimensional culture in vitro, it did not exhibit significant anti-tumor effects in mouse xenograft tumor models using our PDCOs. Bile duct cancer cell-line-derived xenografts are characterized by structurally uniform, irregular glandular structures surrounded by simple and sparse stromal components. However, organoid-derived xenografts exhibit a spectrum of differentiation levels within irregular glandular structures and consist of a complex and rich stromal microenvironment similar to those observed in surgical specimens.

Conclusion

These findings suggest that in vivo studies using PDCO xenograft tumor models may be more suitable than conventional mouse tumor models for determining the clinical development of drugs.
Feasibility study of 4D-online monitoring of density gradients induced by lung cancer treatment using carbon ions
Authors: Reidel Claire-Anne , Pierobon Enrico , Horst Felix , Gesson Lévana , Paz Athena , Graeff Christian , Steinsberger Timo , Zink Klemens , Witt Matthias , Senger Yannick , Finck Christian , Vanstalle Marie , La Tessa Chiara , Durante Marco , Weber Uli , Schuy Christoph
Published: February 2025

Tumor motion is a major challenge for scanned ion-beam therapy. In the case of lung tumors, strong under- and overdosage can be induced due to the high density gradients between the tumor- and bone tissues compared to lung tissues. This work proposes a non-invasive concept for 4D monitoring of high density gradients in carbon ion beam therapy, by detecting charged fragments. The method implements CMOS particle trackers that are used to reconstruct the fragment vertices, which define the emission points of nuclear interactions between the primary carbon ions and the patient tissues. A 3D treatment plan was optimized to deliver 2 Gy to a static spherical target volume. The goodness of the method was assessed by comparing reconstructed vertices measured in two static cases to the ones in a non-compensated moving case with an amplitude of 20 mm. The measurements, performed at the Marburg Ion-Beam Therapy Center (MIT), showed promising results to assess the conformity of the delivered dose. In particular to measure overshoots induced by high density gradients due to motion with 83.0 ± 1.5% and 92.0 ± 1.5% reliability based on the ground truth provided by the time-resolved motor position and depending on the considered volume and the iso-energy layers.
Efficacy of anlotinib and chemotherapy combination as neoadjuvant therapy in the treatment of pulmonary artery intimal sarcoma: a case report
Authors: Liang Gai , Zhang Qu , Luo Yan , Zhao Yuanhua , Luo Bo
Published: February 2025

Pulmonary arterial intimal sarcoma (PAIS) is a rare malignant mesenchymal tumor often associated with an unfavorable prognosis and lacks a standardized treatment approach to date. This report presents a notable case of PAIS treated with neoadjuvant therapy involving anlotinib concomitantly administered with chemotherapy of ifosfamide and pirarubicin, which resulted in a favorable outcome. A 38-year-old man was admitted to our hospital with chest tightness, cough, and dyspnea, all of which had persisted for more than a week. Initial evaluation via chest computed tomography (CT) revealed a sizable posterior mediastinal tumor measuring 11.9 × 7.6 cm. A CT-guided biopsy was performed, and pathological findings confirmed the diagnosis of PAIS. Efficacy evaluation showed slow progress after one cycle of chemotherapy with ifosfamide and pirarubicin. To enhance treatment outcomes, we incorporated anlotinib as a neoadjuvant therapy alongside ifosfamide and pirarubicin. Subsequent CT imaging demonstrated a significant reduction in tumor size, and the patient experienced notable alleviation of symptoms. The patient then underwent surgery, radiation, and subsequently, maintenance treatment with anlotinib for one year. No severe drug-related side effects were observed. The patient achieved progression-free survival of 25 months following administration of anlotinib. Thus, the combination of anlotinib with ifosfamide and pirarubicin demonstrated significant efficacy and safety. This approach holds promise as an effective therapeutic strategy for managing unresectable, locally advanced, or advanced PAIS. However, further clinical studies are necessary to validate these findings.
Clinical factors influencing residual subcutaneous tissue after skin-sparing and nipple-sparing mastectomy with immediate breast reconstruction
Authors: Turna Menekse , Caglar Hale Basak
Published: February 2025

Background

Skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have emerged as increasingly preferred alternatives to traditional mastectomy, largely due to their enhanced cosmetic outcomes and elevated levels of patient satisfaction. Nonetheless, the oncological safety and implications associated with residual breast tissue in these surgical procedures continue to raise significant concerns. The objective of this study is to evaluate the influence of various clinical and surgical factors on residual subcutaneous tissue in patients undergoing SSM and NSM.

Methods

This retrospective cohort study encompassed breast cancer patients who underwent postoperative radiotherapy following SSM and NSM with immediate breast reconstruction from November 2020 to April 2024. Clinical and demographic data, including age, tumor size, axillary staging, molecular subtype, genetic analysis, and surgical details, were systematically collected. Additionally, radiation treatment planning CT scans were assessed to measure residual subcutaneous tissue thickness at multiple anatomical regions. The correlation between residual subcutaneous tissue thickness and clinical factors was subsequently analyzed.

Results

The median age was 45 years (range, 31-61). Among the total patients, 20 underwent SSM (52.63%), and 18 underwent NSM (47.37%). An acceptable residual subcutaneous tissue distance (≤5 mm) was observed in 21 breasts (55.26%), while 17 breasts (44.74%) did not meet this criterion. Analysis demonstrated a statistically significant but modest positive correlation between RFT thickness and age (r = 0.38, p = 0.02), minimal positive correlation was observed between RFT thickness and clinical tumor size (r = 0.08, p = 0.042). A significant effect of contralateral breast surgery on residual subcutaneous tissue thickness was noted (F = 8.38, p < 0.001). Additionally, the results also revealed a statistically significant inverse correlation between RFT thickness and axillary involvement (r = -0.18, p = 0.005), suggesting that thicker flaps are associated with reduced axillary involvement. There was no significant difference in RFT thickness between NSM and SSM groups (Chi² = 0.47, p = 0.491).

Conclusion

A significant proportion of patients undergoing SSM and NSM exhibit residual subcutaneous tissue thickness that exceeds acceptable limits, which may vary based on clinical and pathological factors. Further research involving larger cohorts and prospective designs is essential to identify additional contributing factors and optimize indications for postoperative radiotherapy.
Prognostic impact of initial platelet count and post-induction platelet recovery in elderly AML patients: associated with circulating cytokines
Authors: Ling Chun , Cao Neng-Neng , Niu Xiao-Wei , Xu Shi-Yun , Gong Wen-Yu , Bao Wen-Qiang , Jin Qi-Chuan , Wang Yin , Wu Jing , Zhao Chang-Zhi , Fu Wen-Jing , Zhang Qi-Guo , Feng Shan-Shan , Li Dao-Yuan
Published: February 2025

Objective

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy, with various clinical features influencing its prognosis. The aim of this study to evaluate the impact of platelet count at diagnosis and platelet recovery after induction chemotherapy on the survival outcomes of elderly AML patients.

Methods

A total of 109 elderly patients with AML who were treated in our center between 2017 and 2023 were evaluated. According to the median platelet counts at the time of new diagnosis, the cases were divided into a low platelet counts group (≤40×109/L, n=54) and a high platelet count group (>40×109/L, n=55). Platelet recovery times were accepted as the periods from the beginning of induction chemotherapy to a platelet count of ≥20×109/L 3 days in a row, respectively. The median time to platelet recovery was 25 days (range12-47) for all patients. Therefore, platelet recovery in the first 25 days was defined as early platelet recovery and at >25 days it was defined as late platelet recovery.

Results

Low platelet counts at diagnosis and early recovery of platelet counts after induction therapy indicate longer overall survival (OS) and Leukemia-free survival (LFS). Patients with high platelet counts at diagnosis and those with delayed platelet recovery after induction therapy exhibited elevated levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Additionally, patients with high platelet counts at diagnosis also had relatively higher levels of interleukin-8 (IL-8).

Conclusion

Platelets can be used as a prognostic biomarker for elderly AML and may be associated with circulating cytokines.
SATB2 promotes radiation resistance of esophageal squamous cell carcinoma by regulating epithelial-to-mesenchymal transition via the Wnt/β-catenin pathway
Authors: Lin Chen , Wu Youyi , Qian Yuchen , Li Jiayi , He Youdi , Yu Huang , Xie Congying , Su Huafang
Published: February 2025

Purpose

Radioresistance remains a predominant factor contributing to local recurrence in esophageal squamous cell carcinoma (ESCC). SATB2, as a transcriptional co-gene, may affect the radioresistance of cancer cells. Consequently, this study aims to elucidate the mechanism by which SATB2 modulates radiotherapy resistance in esophageal cancer.

Methods

We identified highly expressed genes associated with radioresistance in ESCC using the MSigDB database and conducted survival correlation analysis. A radioresistant esophageal squamous cell carcinoma cell line (KYSE150R) was established using the gradient dose method, and RT-qPCR was used to detect the expression of SATB2 in KYSE150 and KYSE150R cells. CCK-8, Transwell, colony formation assay, and cell scratching were performed to determine and evaluate cell proliferation, cell migration, and cell invasion. Furthermore, the expression levels of mRNA and protein were correlated using WB and RT-qPCR. Mitochondrial membrane potential and apoptosis detection kits were used to evaluate the level of apoptosis. Finally, a mouse subcutaneous xenograft tumor model was employed to elucidate the role of SATB2 on the radiotherapy resistance of ESCC in vivo.

Results

Bioinformatics analysis indicated that SATB2 is linked to increased drug resistance in esophageal cancer. The results demonstrated that suppression of SATB2 decelerates cell proliferation and migration, accelerates apoptosis, inhibits the GSK-3β (Ser9) phosphorylation, and reduces β-catenin and target gene C-myc. The addition of the Wnt/β-catenin signaling pathway agonist (CHIR-99021) reversed these effects. Xenograft studies in mice revealed that knockdown of SATB2 reduced ESCC radioresistance.

Conclusion

We concluded that SATB2 may dysregulate the Wnt/β-catenin pathway, thereby facilitating EMT progression and conferring radioresistance.
The impact of a virtual wound on pain sensitivity: insights into the affective dimension of pain
Authors: Koopmans Ingrid , Doll Robert-Jan , Hagemeijer Maurice , van Barneveld Robert , de Kam Marieke , Groeneveld Geert Jan
Published: February 2025

Background

The perception of pain is difficult to assess due to the complex combination of various components related to nociception, experience, and cognition. There are currently no biomarkers to assess the affective component of pain in healthy volunteers. Using Virtual Reality (VR), it may be possible to assess changes in pain perception when adding an affective component to painful stimulation.

Methods

In this two-visit feasibility study, we assess the effect of a simulated wound in VR on the electrical pain detection (PDT) and tolerance (PTT) threshold in 24 healthy male study participants. The VR simulation presented a copy of the research room from first person view. Prior to each VR assessment, study participants were primed by interacting with the VR environment. Two conditions were assessed: (1) VR-Wound: a burn-wound, smoke, and electrical sparks become visible and audible with increasing stimulus intensity, and (2) VR-neutral: no additional aspects. The PDT and PTT to electrical stimuli were recorded during both VR conditions and outside of VR. VAS-Questionnaires were used to assess unpleasantness and fear.

Results

The PDT decreased when a virtual wound is presented compared to a neutral condition. Study participants experienced the electrical stimulation as more painful and more intense during the wound simulation than during the neutral condition. The effect was more pronounced during the second visit.

Conclusion

VR enhanced the perception of pain, thereby providing new insights into the affective component of pain. Further testing of this methodology is warranted by performing a clinical study that evaluates drug effects on the affective component of pain.
Case Report: Coexistence of Rosai-Dorfman disease and B-cell acute lymphoblastic leukemia in an adolescent
Authors: Jenabzadeh Alireza , Binesh Fariba , Shahbaz Amir Pasha Amel , Alavi Samin
Published: February 2025

Rosai–Dorfman disease (RDD) is an unusual, non-malignant proliferative disorder involving non-Langerhans cell histiocytes, characterized by a wide range of clinical presentations and distinctive atypical morphological patterns. The concurrent manifestation of acute lymphoblastic leukemia (ALL) alongside RDD is exceptionally rare. Here, we present the case of a 14-year-old male patient diagnosed with ALL who, during the consolidation phase of chemotherapy, developed multifocal bone, dural, and liver lesions, as confirmed through CT and MRI imaging. Histopathological evaluations of the bone and liver lesions identified features consistent with Rosai–Dorfman disease. To the best of our knowledge, this case represents the first reported instance of RDD co-occurring with high-risk pre-B-cell ALL in an adolescent undergoing chemotherapy. Unfortunately, the patient experienced a relapse of ALL and died due to a fungal infection. In this report, we analyze the distinct clinical features and disease progression of both conditions and offer an extensive review of relevant literature.
MONSTROUS: a web-based chemical-transporter interaction profiler
Authors: AbdulHameed Mohamed Diwan M. , Dey Souvik , Xu Zhen , Clancy Ben , Desai Valmik , Wallqvist Anders
Published: February 2025

Transporters are membrane proteins that are critical for normal cellular function and mediate the transport of endogenous and exogenous chemicals. Chemical interactions with these transporters have the potential to affect the pharmacokinetic properties of drugs. Inhibition of transporters can cause adverse drug-drug interactions and toxicity, whereas if a drug is a substrate of a transporter, it could lead to reduced therapeutic effects. The importance of transporters in drug efficacy and toxicity has led regulatory agencies, such as the U.S. Food and Drug Administration and the European Medicines Agency, to recommend screening of new molecular entities for potential transporter interactions. To aid in the rapid screening and prioritization of drug candidates without transporter liability, we developed a publicly available, web-based transporter profiler, MOlecular traNSporT inhibitoR and substrate predictOr Utility Server (MONSTROUS), that predicts the potential of a chemical to interact with transporters recommended for testing by regulatory agencies. We utilized publicly available data and developed machine learning or similarity-based classification models to predict inhibitors and substrates for 12 transporters. We used graph convolutional neural networks (GCNNs) to develop predictive models for transporters with sufficient bioactivity data, and we implemented two-dimensional similarity-based approach for those without sufficient data. The GCNN inhibitor models have an average five-fold cross-validated receiver operating characteristic area under the curve (ROC-AUC) of 0.85 ± 0.07, and the GCNN substrate models have an average ROC-AUC of 0.79 ± 0.08. We implemented the models along with applicability domain calculations in an easy-to-use web interface and made it publicly available at https://monstrous.bhsai.org/.
Economic impact of individualized antimicrobial dose optimization in the critically ill patient in Spain
Authors: Grau Santiago , Luque Sonia , Ferrandez Olivia , Benitez Cano Adela , Rubio-Rodríguez Darío , Rubio-Terrés Carlos
Published: February 2025

Objective

To estimate the economic impact of individualized dose optimization guided by antimicrobial therapeutic drug monitoring (TDM) in Spain, compared to no monitoring.

Methods

A cost analysis of antibiotic treatment of critically ill patients, with and without TDM, was performed using a probabilistic Markov model (with second-order Monte Carlo simulations). Three scenarios were analyzed based on three published meta-analyses (Analysis 1: Pai Mangalore, 2022; Analysis 2: Sanz-Codina, 2023; Analysis 3: Takahashi, 2023).

Results

TDM, compared to the no-TDM option, generated according to the meta-analysis, a per patient expenditure of €195 (95%CI €194; €197) in analysis 1 or savings of -€301 (95%CI -€300; -€304) and -€685 (95%CI -€685; -€684) in analyses 2 and 3. The probability of TDM (vs. no-TDM) generating savings would be 39.4%, 63.5% and 79.7% in analyses 1, 2 and 3, respectively. This discrepancy in the results is due to methodological differences, in particular in the cure rate with TDM (vs. no-TDM) obtained in the meta-analyses: 12.2%, 16.6% and 16.0% more in analyses 1, 2 and 3, respectively.

Conclusion

In critically ill patients undergoing antimicrobial therapy TDM, there is an increased likelihood of cure. However, the currently available data are not conclusive on the economic impact of such a therapeutic effect.
Pharmacokinetic effect of disease severity and use of extracorporeal membrane oxygenation in critically ill Asian patients receiving vancomycin
Authors: Avachat Charul , Hung Pi-lien , Birnbaum Angela K. , Healy Daniel P. , Sherwin Catherine M. , Lin Alex C.
Published: February 2025

Purpose

Vancomycin is an essential antibiotic for the treatment of severe gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA). In critically ill patients, particularly children, attaining the appropriate dosage is crucial to avert drug resistance and ensure therapeutic efficacy. This study sought to investigate the pharmacokinetics of vancomycin in critically ill Asian pediatric patients and evaluate the influence of extracorporeal membrane oxygenation (ECMO) and disease severity on vancomycin clearance.

Methods

This retrospective analysis examined data from 90 critically ill Asian patients residing in Kaohsiung, Taiwan, encompassing 263 data points gathered over 2 years. A one-compartment pharmacokinetic model with first-order elimination was constructed using nonlinear mixed-effects modeling to assess the impact of ECMO and infection severity on vancomycin clearance.

Results

The pharmacokinetics of vancomycin were markedly affected by ECMO and the severity of the illness. Patients using ECMO demonstrated a 56% decrease in vancomycin clearance relative to non-ECMO patients. Furthermore, patients with milder infections (e.g., cellulitis, surgical prophylaxis, neutropenic fever) had a 39% decrease in vancomycin clearance relative to those with more severe infections (e.g., pneumonia, bacteremia, osteomyelitis, meningitis, deep tissue infection).

Conclusion

The study demonstrates that ECMO and infection severity are major factors influencing vancomycin clearance in critically unwell pediatric patients. The significant decrease in clearance linked to ECMO and reduced infection severity underscores the necessity for meticulous therapeutic drug monitoring and tailored dosing strategies to enhance vancomycin treatment in this at-risk population. The findings highlight the significant interindividual diversity in vancomycin pharmacokinetics in critically unwell pediatric patients.
Muscle loss in cancer cachexia: what is the basis for nutritional support?
Authors: Faiad Jaline , Andrade Márcia Fábia , de Castro Gabriela , de Resende Joyce , Coêlho Marina , Aquino Giovana , Seelaender Marilia
Published: February 2025

Cancer cachexia (CC) is characterized by significant skeletal muscle wasting, and contributes to diminished quality of life, while being associated with poorer response to treatment and with reduced survival. Chronic inflammation plays a central role in driving CC progression, within a complex interplay favoring catabolism. Although cachexia cannot be fully reversed by conventional nutritional support, nutritional intervention shows promise for the prevention and treatment of the syndrome. Of special interest are nutrients with antioxidant and anti-inflammatory potential and those that activate pathways involved in muscle mass synthesis and/or in the inhibition of muscle wasting. Extensive research has been carried out on novel nutritional supplements’ power to mitigate CC impact, while the mechanisms through which some nutrients or bioactive compounds exert beneficial effects on muscle mass are still not totally clear. Here, we discuss the most studied supplements and nutritional strategies for dealing with muscle loss in CC.
High-performance PBPK model for predicting CYP3A4 induction-mediated drug interactions: a refined and validated approach
Authors: Yang Cheng-Guang , Chen Tao , Si Wen-Teng , Wang An-Hai , Ren Hong-Can , Wang Li
Published: February 2025

Introduction

The cytochrome P450 enzyme 3A4 (CYP3A4) mediates numerous drug-drug interactions (DDIs) by inducing the metabolism of co-administered drugs, which can result in reduced therapeutic efficacy or increased toxicity. This study developed and validated a Physiologically Based Pharmacokinetic (PBPK) model to predict CYP3A4 induction-mediated DDIs, focusing on the early stages of clinical drug development.

Methods

The PBPK model for rifampicin, a potent CYP3A4 inducer, was developed and validated using human pharmacokinetic data. Subsequently, PBPK models for ‘victim’ drugs were constructed and validated. The PBPK-DDI model’s predictive performance was assessed by comparing predicted area under the curve (AUC) and maximum concentration (Cmax) ratioswith empirical data, using both the 0.5 to 2-fold criterion and theGuest criteria.

Results

The rifampicin PBPK model accurately simulated human pharmacokinetic profiles. The PBPK-DDI model demonstrated high predictive accuracy for AUC ratios, with 89% of predictions within the 0.5 to 2-fold criterion and 79% meeting the Guest criteria. For Cmax ratios, an impressive 93% of predictions were within the acceptable range. The model significantly outperformed the static model, particularly in estimating DDI risks associated with CYP3A4 induction.

Discussion

The PBPK-DDI model is a reliable tool for predicting CYP3A4 induction-mediated DDIs. Its high predictive accuracy, confirmed by adherence to evaluation standards, affirms its reliability for drug development and clinical pharmacology. Future refinements may further enhance its predictive value.
Research on relaxation characteristics of columnar jointed basalts of deep foundation in hydropower station
Authors: Gu Jinjian , Wang Jianxin , He Mingjie , Yang Shu , Li Shuaikang
Published: February 2025

The columnar basalt is a widely distributed in Southwestern China with different types. The first type of columnar jointed basalt is distributed below the elevation of 665 m on the left bank and 590 m on the right bank of the arch dam foundation. Micro-fissures are prevalent within the columns, with gently dipping structural surfaces and an intermittent mosaic structure despite poor overall integrity. The structure is easy to relax after unloading, and the acoustic wave of rock mass is obviously reduced. The control of relaxation deformation of columnar joint basalt is a key problem of hydropower exploration. Based on the structural of columnar jointed basalt, this paper analyzed the relaxation characteristics of columnar jointed basalt.