bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune microenvironment dynamics in breast cancer during pregnancy: impact of gestational age on tumor-infiltrating lymphocytes and prognosis
Authors: Sajjadi Elham , Venetis Konstantinos , Ivanova Mariia , Noale Marianna , Blundo Concetta , Di Loreto Eugenia , Scarfone Giovanna , Ferrero Stefano , Maggi Stefania , Veronesi Paolo , Galimberti Viviana E. , Viale Giuseppe , Peccatori Fedro A. , Fusco Nicola , Guerini-Rocco Elena 
Published: August 2023

BackgroundBreast cancer during pregnancy (PrBC) is a rare condition known for its aggressive clinical behavior. The presence of tumor-infiltrating lymphocytes (TILs) has been shown to have a significant impact on the prognosis of these patients. Despite some biological characteristics of the tumor that may differ depending on the gestational age, little is known about the dynamics of the immune landscape within the tumor microenvironment (TME) in PrBC. Therefore, in this study, our objective was to gain comprehensive insights into the relationship between gestational age at breast cancer diagnosis and the composition of the TME.Methodsn = 108 PrBC were selected from our institutional registry and categorized based on the gestational age by trimester. For all cases, TILs were profiled according to the International TILs Working Group recommendations, and subtyped by CD4, CD8, and forkhead box P3 (FOXP3) immunohistochemistry. PD-L1 was tested according to the combined positive score (CPS) using the IHC 22C3 pharmDx assay, with a cutoff value of ≥10 for positivity. The statistical approach encompassed Fisher’s and Chi-squared tests, with appropriate adjustments for multiple comparisons, logistic regression models, and survival analyses based on the Kaplan–Meier method.ResultsThe proportion of patients with poorly differentiated (G3) neoplasms increased as the gestational age advanced (first trimester, n = 25, 56.8%; second trimester, n = 27, 69.2%; third trimester, n = 21, 87.5%; p = 0.03). The histologic subtypes as well as the hormone receptor (HR) and HER2 status did not show significant changes across different pregnancy trimesters. In the HR+/HER2– subtype, there was a higher proportion of tumors with high/moderate TILs in the early phases of pregnancy, similar to FOXP3 expression (TILs: first trimester, n = 10, 35.7%; second trimester, n = 2, 10.5%; third trimester, n = 0; p = 0.02; FOXP3: first trimester, n = 10, 40%; second trimester, n = 3, 15.8%; third trimester, n = 0; p = 0.03). The median follow-up for our cohort was 81 months. Patients who relapsed after a breast cancer diagnosis during the first trimester were more frequently PD-L1-negative, unlike those with no disease recurrence (n = 9, 100% vs. n = 9, 56.3%; p = 0.03; hormone therapy and n = 9, 100% vs. n = 7, 53.9%; p = 0.02; chemotherapy). No statistically significant differences were seen among the three trimesters in terms of survival outcome.ConclusionThe TME dynamics of HR+/HER2− PrBC vary based on gestational age, suggesting that immune tolerance expression during later gestational age could explain the increased aggressiveness of tumors diagnosed at that stage.
A proposed methodology for detecting the malignant potential of pulmonary nodules in sarcoma using computed tomographic imaging and artificial intelligence-based models
Authors: Baidya Kayal Esha , Ganguly Shuvadeep , Sasi Archana , Sharma Swetambri , DS Dheeksha , Saini Manish , Rangarajan Krithika , Kandasamy Devasenathipathy , Bakhshi Sameer , Mehndiratta Amit 
Published: August 2023

The presence of lung metastases in patients with primary malignancies is an important criterion for treatment management and prognostication. Computed tomography (CT) of the chest is the preferred method to detect lung metastasis. However, CT has limited efficacy in differentiating metastatic nodules from benign nodules (e.g., granulomas due to tuberculosis) especially at early stages (&lt;5 mm). There is also a significant subjectivity associated in making this distinction, leading to frequent CT follow-ups and additional radiation exposure along with financial and emotional burden to the patients and family. Even 18F-fluoro-deoxyglucose positron emission technology-computed tomography (18F-FDG PET-CT) is not always confirmatory for this clinical problem. While pathological biopsy is the gold standard to demonstrate malignancy, invasive sampling of small lung nodules is often not clinically feasible. Currently, there is no non-invasive imaging technique that can reliably characterize lung metastases. The lung is one of the favored sites of metastasis in sarcomas. Hence, patients with sarcomas, especially from tuberculosis prevalent developing countries, can provide an ideal platform to develop a model to differentiate lung metastases from benign nodules. To overcome the lack of optimal specificity of CT scan in detecting pulmonary metastasis, a novel artificial intelligence (AI)-based protocol is proposed utilizing a combination of radiological and clinical biomarkers to identify lung nodules and characterize it as benign or metastasis. This protocol includes a retrospective cohort of nearly 2,000–2,250 sample nodules (from at least 450 patients) for training and testing and an ambispective cohort of nearly 500 nodules (from 100 patients; 50 patients each from the retrospective and prospective cohort) for validation. Ground-truth annotation of lung nodules will be performed using an in-house-built segmentation tool. Ground-truth labeling of lung nodules (metastatic/benign) will be performed based on histopathological results or baseline and/or follow-up radiological findings along with clinical outcome of the patient. Optimal methods for data handling and statistical analysis are included to develop a robust protocol for early detection and classification of pulmonary metastasis at baseline and at follow-up and identification of associated potential clinical and radiological markers.
At-home use of parasacral transcutaneous electrical nerve stimulation for pediatric voiding dysfunction: a randomized controlled trial to assess its safety and feasibility
Authors: Malhotra Neha R. , Siegal Alexandra R. , Lange Suzanne M. , Cervantez DeeAnn , White Heidi K. , Hannon AnnMarie , Schaeffer Anthony J. , Lau Glen A. 
Published: August 2023

IntroductionTreating pediatric voiding dysfunction involves behavioral changes that require significant time or medications that are often avoided or discontinued due to side effects. Using parasacral transcutaneous electrical nerve stimulation (PTENS) has shown to have reasonable efficacy, but the safety and feasibility of its off-label use for pediatric voiding dysfunction are not well-established. Concerns have also been raised over treatment adherence. In-home therapy might improve adherence compared with office-based therapy; however, no studies have evaluated in-home feasibility to date. This study aims to assess the safety and feasibility of off-label use of PTENS for pediatric voiding dysfunction.Materials and methodsA single-institution prospective, randomized controlled study was conducted from March 2019 to March 2020. Participants aged 6–18 years diagnosed with voiding dysfunction, overactive bladder, or urinary incontinence were eligible for the study. Those with known neurologic disorders, implanted electrical devices, anatomic lower urinary tract abnormality, and recurrent urinary tract infections and those taking bladder medications were excluded. Children with primary monosymptomatic nocturnal enuresis were also excluded due to previous work suggesting a lack of efficacy. Participants were randomly assigned to receive 12 weeks of urotherapy alone (control) or urotherapy plus at-home PTENS treatment. Families were contacted weekly to assess for adverse events (AEs) and treatment adherence. The primary and secondary outcomes were safety, defined as the absence of AEs and treatment adherence, respectively.ResultsA total of 30 eligible participants were divided into two groups, with 15 participants in each arm. The median age was 9.4 years (interquartile range: 7.7–10.6). In total, 60% were male. Baseline demographics and urotherapy compliance were similar between the two groups. With PTENS use, two AEs were reported, including mild pruritus at the pad site and discomfort when removing pads, while no AEs were noted in the control group. In total, 60% of patients completed three 30-min sessions per week, and all participants were able to complete treatment sessions for at least 10 weeks, involving 30 min of PTENS treatment each time.ConclusionThis randomized controlled study confirms that at-home use of PTENS is feasible with reasonable treatment adherence and minimal AEs. Future collaborative, multi-institutional studies may better determine the efficacy of this treatment modality.
Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level
Authors: Jiang Zhi , Zou Qiuping , Chen Qicheng , Zhang Junhong , Tang Hailin , Chen Jingbao , Qin You , Yang Liming , Chen Zhiqiang , Cao Lixing 
Published: August 2023

Introduction: Previous studies indicated that Wuda Granule (WDG) has been applied in the treatment of gastrointestinal motility disorder (GMD), but the effect and underlying mechanisms is yet to be elucidated. This study aimed to explore the mechanism and pharmacological effect of WDG for GMD via network analysis, verification of animal experiments and clinical experiments.Methods: The chemical components of WDG were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, http://lsp.nwu.edu.cn/index.php), and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/Index/) according to oral bioavailability (OB) ≥ 20% and drug-likeness (DL) ≥ 0.10. The targets of WDG compounds were retrieved from the Swiss Target Prediction database (http://www.swisstargetprediction.ch/) and targets related to GMD were retrieved from GeneCards database (https://www.genecards.org/). Network analysis were performed to screen the key active compounds of WDG and its hub targets. Then the pharmacological effect of WDG were verified via vivo experiments in rats and clinical experiments.Results: The results showed that 117 effective active compounds of WDG were screened and 494 targets of WDG compounds targeting GMD were selected. These targets were involved in the biological process of inflammatory regulation and the regulation of gastrointestinal motility. The mechanism was mainly involved in the regulation of PI3K-Akt signaling pathway and Rap1 signaling pathway. In addition, molecular docking analysis suggested that eight key active compounds of WDG may be mainly responsible for the effect of WDG on GMD by targeting HARS, AKT, and PIK3CA, respectively. Animal experiments and clinical trials both suggested that WDG could exert therapeutical effect on GMD via inhibiting inflammation and promoting gastrointestinal motility, it could also improve digestive function of patients with laparoscopic colorectal cancer after surgery.Conclusion: This study was the first to demonstrate that WDG improved GMD mainly via inhibiting inflammatory level and promoting gastrointestinal motility, providing new insights for the understanding of WDG for GMD, inspiration for future research and reference for clinical strategy in terms of the treatment of GMD.
Modeling of the control logic of a UASS based on coefficient of variation spraying distribution analysis in an indoor flight simulator
Authors: Hanif Adhitya Saiful , Han Xiongzhe , Yu Seung-Hwa , Han Cheolwoo , Baek Sun Wook , Lee Chun-Gu , Lee Dae-Hyun , Kang Yeong Ho 
Published: August 2023

IntroductionIn the past decade, unmanned aerial spraying systems (UASS) have emerged as an effective crop treatment platform option, competing with other ground vehicle treatments. The development of this platform has provided an effective spraying system that can be used on all crop types and in all weather conditions. However, related research has not been able to develop a UASS that can be operated in windy conditions with a low drift percentage.MethodsIn this research, spraying was simulated in an indoor flight simulator by considering flight speed, altitude, wind speed, wind direction, rotor rotation, interval, spraying pattern, and nozzle type, which were used as the parameters affecting the output value of the coefficient of variation (CV) of spraying. These parameters were referenced as properties that occur in the field, and using machine learning methods, the CV value was used as a dataset to develop a model that can execute pump opening by controlling the flow rate. There are four machine learning methods used, i.e. random forest regression, gradient boosting, ada boost, and automatic relevance determination regression which are compared with simple linear regression and ridge regression as linear regression.ResultsThe results revealed that the random forest regression model was the most accurate, with R2 of 0.96 and root mean square error (RMSE) of 0.04%. The developed model was used to simulate spraying with pump opening A, which connects two nozzles in front, and pump opening AB, which connects all four nozzles.DiscussionUsing the logic based on CV value and pesticide quantity, the model can execute the pump opening against the environment and UASS operation.
Nitrogen acquisition strategy and its effects on invasiveness of a subtropical invasive plant
Authors: Guan Ming , Pan Xiao-Cui , Sun Jian-Kun , Chen Ji-Xin , Kong De-Liang , Feng Yu-Long 
Published: August 2023

IntroductionPreference and plasticity in nitrogen (N) form uptake are the main strategies with which plants absorb soil N. However, little effort has been made to explore effects of N form acquisition strategies, especially the plasticity, on invasiveness of exotic plants, although many studies have determined the effects of N levels (e.g. N deposition).MethodsTo address this problem, we studied the differences in N form acquisition strategies between the invasive plant Solidago canadensis and its co-occurring native plant Artemisia lavandulaefolia, effects of soil N environments, and the relationship between N form acquisition strategy of S. canadensis and its invasiveness using a 15N-labeling technique in three habitats at four field sites.ResultsTotal biomass, root biomass, and the uptakes of soil dissolved inorganic N (DIN) per quadrat were higher for the invasive relative to the native species in all three habitats. The invader always preferred dominant soil N forms: NH4+ in habitats with NH4+ as the dominant DIN and NO3- in habitats with NO3- as the dominant DIN, while A. lavandulaefolia consistently preferred NO3- in all habitats. Plasticity in N form uptake was higher in the invasive relative to the native species, especially in the farmland. Plant N form acquisition strategy was influenced by both DIN levels and the proportions of different N forms (NO3-/NH4+) as judged by their negative effects on the proportional contributions of NH4+ to plant N (fNH4+) and the preference for NH4+ (βNH4+). In addition, total biomass was positively associated with fNH4+ or βNH4+ for S. canadensis, while negatively for A. lavandulaefolia. Interestingly, the species may prefer to absorb NH4+ when soil DIN and/or NO3-/NH4+ ratio were low, and root to shoot ratio may be affected by plant nutrient status per se, rather than by soil nutrient availability.DiscussionOur results indicate that the superior N form acquisition strategy of the invader contributes to its higher N uptake, and therefore to its invasiveness in different habitats, improving our understanding of invasiveness of exotic plants in diverse habitats in terms of utilization of different N forms.
Gold complex compounds that inhibit drug-resistant Staphylococcus aureus by targeting thioredoxin reductase
Authors: Tharmalingam Nagendran , Xu Shi , Felix Lewis Oscar , Roy Biswajit , Xian Ming , Mylonakis Eleftherios , Fuchs Beth Burgwyn 
Published: August 2023

IntroductionThere is a significant need for new antimicrobial compounds that are effective against drug-resistant microbes. Thioredoxin reductase (TrxR) is critical in redox homeostasis and was identified as a potential drug target and confirmed through inhibition by compounds auranofin and Bay11-7085.MethodsAdditional TrxR inhibitors were designed and found to exhibit antimicrobial activity against Gram-positive (Enterococcus faecium and Staphylococcus aureus) and glutathione-deficient bacteria (Helicobacter pylori). Investigational compounds were tested for antimicrobial activity, anti-biofilm efficacy, target impact, and cytotoxicity.ResultsThe first-generation molecules AU1 and AU5 inhibited TrxR activity and inhibited methicillin-resistant S. aureus strain MW2 with minimal inhibitory concentrations (MIC) of 0.125 and 0.5 μg/mL, respectively. In an S. aureus enzymatic assay, AU1 inhibited TrxR enzymatic activity in a dose-dependent manner causing a decrease in intracellular free thiols. In addition, biofilm studies demonstrated that AU1 and AU5 reduced biofilm formation at 1X MIC and disrupted mature biofilms at 4X MIC. Cytotoxicity profiles were created using human cell lines and primary cells with LD50 exceeding MICs by at least 12X.DiscussionThus, AU1 and AU5 were TrxR inhibitors that yielded low-concentration antimicrobial activity impacting S. aureus in planktonic and biofilm forms with limited toxic liability.
Improving data use in decision-making and utilization of maternal healthcare services through a data-informed platform for health approaches in districts of the Gedeo Zone, southern Ethiopia, 2023: a cluster-randomized control trial
Authors: Zenebe Getachew Assefa , Alemu Wagaye , Yehualashet Daniel , Nakachew Mequanint 
Published: August 2023

BackgroundIn low-resource countries such as Ethiopia, the utilization of local data for planning and decision-making health systems was frequently constrained. In addition, despite several government initiatives, maternal health services were not completely utilized. On the other hand, efforts to effectively utilize the local data available to improve the utilization level of maternal healthcare services were insufficient, necessitating the need for a different approach.ObjectiveThis implementation study aims to test and validate the effectiveness of a data-informed platform for health (DIPH) strategies on data use for decision-making and utilization of maternal health services in districts of the Gedeo Zone, southern Ethiopia.MethodsA two-arm parallel group, type II hybrid, cluster-randomized control trial design has been implemented to conduct the study between 1 September 2022 and 29 February 2024. Six woredas/districts have been assigned to the intervention arm and the other six to the control arm. Baseline and end-line data have been collected from 120 eligible health management staff (from both intervention arm and control arm). In the intervention arm, district health management staff have been given specialized training and continuous technical assistance as a package called the DIPH strategy by embedding it with the district's current decision-making platform such as Performance Review Team meetings. The DIPH strategy has mainly focused on five-step approaches such as situational assessment, stakeholder engagement, defining/setting priorities, planning, and follow-up. Health management staff in the control arm have performed their regular daily activities. The χ2 and t-tests have been used to check the effect of the intervention. In addition, difference-in-differences estimates have been calculated because the change may inherently occur over time. A P-value of &lt;0.05 and a 95% confidence interval have been used to declare the significance of the intervention.DiscussionThe findings of this study were supposed to give insights into implementation strategies that improve data use in decision-making and utilization of maternal healthcare services at the woreda level and uncover contextual factors that boost the response of these strategies.
Development of in vitro methods to model the impact of vaginal lactobacilli on Staphylococcus aureus biofilm formation on menstrual cups as well as validation of recommended cleaning directions
Authors: Friberg Maria , Woeller Kara , Iberi Vighter , Mancheno Paolo Palacio , Riedeman James , Bohman Lisa , Davis Catherine C. 
Published: August 2023

IntroductionMenstrual cups (MC) are a reusable feminine hygiene product. A recent publication suggested that Staphylococcus aureus (S. aureus) biofilms can form on MCs which may lead to increased risk of menstrual Toxic Shock Syndrome (mTSS). Additionally, there is concern that buildup of residual menses may contribute to microbial growth and biofilm formation further increasing mTSS risk. Quantitative and qualitative analysis of in vitro tests were utilized to determine if S. aureus biofilm could form on MC in the presence of the keystone species Lactobacillus after 12 h of incubation. The methodology was based on a modification of an anaerobic in vitro method that harnesses the keystone species hypothesis by including a representative of vaginal lactic acid bacteria.MethodsMCs were incubated anaerobically for 12 h in Vaginal Defined Media (VDM) with the two morphologically distinct bacteria, Lactobacillus gasseri (L. gasseri) and S. aureus. Colony Forming Units (CFU) for each organism from the VDM broth and sonicated MC were estimated. In addition, a separate experiment was conducted where S. aureus was grown for 12 h in the absence of L. gasseri. Qualitative analysis for biofilm formation utilized micro-CT (µ-CT) and cryogenic scanning electron microscopy (Cryo-SEM).ResultsSamples collected from the media control had expected growth of both organisms after 12 h of incubation. Samples collected from VDM broth were similar to media control at the end of the 12-h study. Total S. aureus cell density on MC following sonication/rinsing was minimal. Results when using a monoculture of S. aureus demonstrated that there was a significant growth of the organism in the media control and broth as well as the sonicated cups indicating that the presence of L. gasseri was important for controlling growth and adherence of S. aureus. Few rod-shaped bacteria (L. gasseri) and cocci (S. aureus) could be identified on the MCs when grown in a dual species culture inoculum and no biofilm was noted via µ-CT and cryo-SEM. Additionally, efforts to model and understand the validity of the current labeled recommendations for MC cleaning in-between uses are supported.DiscussionThe data support continued safe use of the Tampax® cup when used and maintained as recommended.