bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancing diagnostics: integrating microRNA profiling and protein markers in ectopic pregnancy detection
Authors: Selvarajan Sathya , Ramalingam Jothi Malar , Senthil Kumar Dhivya 
Published: October 2024

IntroductionEctopic pregnancy (EP) poses significant health risks, particularly in developing nations, necessitating improved diagnostic methods. This study aimed to explore potential biomarkers for EP diagnosis.MethodsA case–control study was conducted at the Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu. It included 140 EP cases and 140 pregnant controls, aged 19–38 years, attending routine visits. Serum samples were analysed for beta-human chorionic gonadotropin (β-hCG), progesterone, soluble fms-like tyrosine kinase-1 (sFLT-1) and eight microRNAs (miRs).ResultsDifferential expression of biomarkers was observed in EP cases. Four miRs (hsa-miR-141, hsa-miR-218, hsa-miR-519d and hsa-miR-873) were downregulated, and four miRs (hsa-miR-223, hsa-miR-517a, hsa-miR-523 and hsa-miR-323-3p) were upregulated. Statistically significant expression fold changes were noted (p<0.05), except for hsa-miR-141 and hsa-miR-218. miR-519d exhibited promising diagnostic potential with the highest specificity (97.1%) and a sensitivity of 47.1%. sFLT-1, as an individual marker, demonstrated a sensitivity of 98.6% and a specificity of 90%. The combination of sFLT-1 and miR-519d significantly enhanced the sensitivity to 100% with a specificity of 87.1%.ConclusionsThe combination of miR-519d and sFLT-1 emerges as a promising diagnostic tool for EP, offering a sensitivity of 100% and a specificity of 87.1%. These findings underscore the potential of biomarker-based approaches in improving EP diagnosis, especially in resource-limited settings. Further validation and clinical implementation studies are warranted to corroborate these findings and enhance EP management strategies.
Depressive symptomatology, NT-proBNP levels and health status in patients with heart failure: a prospective observational study
Authors: Balata Mahmoud , Becher Marc Ulrich , Conrad Rupert 
Published: October 2024

BackgroundDepressive symptoms frequently occur in patients with heart failure (HF). However, research on the relationship between these symptoms and N-terminal pro-brain natriuretic peptide (NT-proBNP), a key biomarker for HF severity and treatment, is scarce and yields inconsistent results.AimsThis study investigates the relationship among depressive symptomatology, NT-proBNP and health status in a cohort of patients with HF. Additionally, it assesses the impact of depressive symptoms on their clinical outcomes.MethodsA cohort of 151 patients with HF was followed for 1 year. The Hospital Anxiety and Depression Scale—Depression (HADS-D) Score was used to assess anxiety and depressive symptoms, and NT-proBNP levels were measured. Health status was evaluated using the Kansas City Cardiomyopathy Questionnaire (KCCQ).ResultsPatients with HADS-D scores>5 points showed significantly higher NT-proBNP levels and lower KCCQ scores at baseline. Over the year, changes in HADS-D scores correlated positively with changes in NT-proBNP levels and negatively with changes in KCCQ scores. A baseline HADS-D score>5 points was significantly associated with an increased risk of the composite outcome of all-cause mortality and HF hospitalisation, even after adjusting for baseline characteristics (adjusted hazard ratio (HR): 2.17; 95% CI 1.05 to 4.48; p=0.036).ConclusionsHADS-D scores are significantly correlated with NT-proBNP levels and health status in patients with HF. A baseline HADS-D score>5 points is significantly associated with an elevated risk for the composite outcome of all-cause mortality and hospitalisation due to HF.
Intratumoral STING agonist reverses immune evasion in PD-(L)1-refractory Merkel cell carcinoma: mechanistic insights from detailed biomarker analyses
Authors: Pulliam Thomas , Jani Saumya , Goff Peter H , Bhakuni Rashmi , Tabachnick-Cherny Shira , Smythe Kimberly , Seaton Brandon W , Tachiki Lisa , Kulikauskas Rima , Church Candice , Koelle David M , Nghiem Paul , Bhatia Shailender 
Published: October 2024

BackgroundAntibodies blocking programmed death (PD)-1 or its ligand (PD-L1) have revolutionized cancer care, but many patients do not experience durable benefits. Novel treatments to stimulate antitumor immunity are needed in the PD-(L)1 refractory setting. The stimulator of interferon genes (STING) protein, an innate sensor of cytoplasmic DNA, is a promising target with several agonists in development. However, response rates in most recent clinical trials have been low and mechanisms of response remain unclear. We report detailed biomarker analyses in a patient with anti-PD-L1 refractory, Merkel cell polyomavirus (MCPyV)-positive, metastatic Merkel cell carcinoma (MCC) who was treated with an intratumoral (IT) STING agonist (ADU-S100) plus intravenous anti-PD-1 antibody (spartalizumab) and experienced a durable objective response with regression of both injected and non-injected lesions.MethodsWe analyzed pretreatment and post-treatment tumor and peripheral blood samples from our patient with single-cell RNA sequencing, 30-parameter flow cytometry, T cell receptor sequencing, and multiplexed immunohistochemistry. We analyzed cancer-specific CD8 T cells using human leukocyte antigen (HLA)-I tetramers loaded with MCPyV peptides. We also analyzed STING expression and signaling in the tumor microenvironment (TME) of 88 additional MCC tumor specimens and in MCC cell lines.ResultsWe observed high levels of MCPyV-specific T cells (12% of T cells) in our patient’s tumor at baseline. These cancer-specific CD8 T cells exhibited characteristics of exhaustion including high TOX and low TCF1 proteins. Following treatment with STING-agonist plus anti-PD-1, IT CD8 T cells expanded threefold. We also observed evidence of likely improved antigen presentation in the MCC TME (greater than fourfold increase of HLA-I-positive cancer cells). STING expression was not detected in any cancer cells within our patient’s tumor or in 88 other MCC tumors, however high STING expression was observed in immune and stromal cells within all 89 MCC tumors.ConclusionsOur results suggest that STING agonists may be able to work indirectly in MCC via signaling through immune and stromal cells in the TME, and may not necessarily need STING expression in the cancer cells. This approach may be particularly effective in tumors that are already infiltrated by inflammatory cells in the TME but are evading immune detection via HLA-I downregulation.
Numerical modeling assisting in surgical treatment of total anomalous pulmonary venous connection in children
Authors: Jin Jie , Gu Kaiyun , Liang Jiawei , Yu Jing , Fan Xiangming 
Published: October 2024

ObjectiveTo develop a model using patient-specific computational fluid dynamics (CFD) to predict the required anastomotic size for total anomalous pulmonary venous connection (TAPVC) surgery and to forecast surgical outcomes.MethodsBased on clinical data from patients, a CFD model was used to simulate the anastomosis between pulmonary venous confluence and the left atrium. Blood flow velocity, wall shear stress, power loss, and pressure were calculated using numerical algorithms within the model. Various sizes of anastomosis were applied during the simulation. The energy dissipation at the anastomosis was computed from the results and compared with real-world data.ResultsAs the simulated anastomotic size increased, blood flow velocity, pulmonary venous pressure, and energy loss decreased. However, when the anastomotic size exceeded 18 mm, the efficiency of energy conversion no longer improved. The realistic and simulated velocities matched well for anastomosis sizes ranging from 15 to 20 mm.ConclusionThe model can assist surgeons in preoperative planning for determining the anastomotic size in TAPVC surgical treatment.
An interpretation of scalars in SO(32)
Authors: Rivero Alejandro 
Published: October 2024

AbstractWe propose an interpretation for the adjoint representation of the SO(32) group to classify the scalars of a generic Supersymmetric Standard Model having just three generations of particles, via a flavour group SU(5). We show that this same interpretation arises from a simple postulate of self-consistence of composites for these scalars. The model looks only for colour and electric charge, and it pays the cost of an additional chiral $$+4/3$$

+
4
/
3

quark per generation.
Kepler’s problem of a two-body system perturbed by a third body
Authors: Abdel-Rahman A. S. , Sabry Youssef A. , Ahmed E. M. 
Published: October 2024

AbstractOne of the most important problems in basic physics and astronomy is studying the motion of planets, satellites, and other celestial bodies. The solution to the two-body problem enables astronomers to predict the orbits of the Moon, satellites, and spaceships around the Earth. The general analytic solution for the three-body problem stands unsolved except in some special cases. This reduces the problem to a two-body problem. In this work, the authors present a closed-form approach to the three-body problem theoretically and numerically based on particle–particle vector analysis. The theoretical approach, which is based on the real Moon–Sun–Earth problem information, illustrates the perturbation of the Moon in the Sun–Earth problem and shows an expected orbital motion with a perturbation in the Sun–Earth orbit due to the revolution of the Moon. The numerical investigation uses the same information to study the same problem and calculate the angular momentums of each pair of objects. The two solutions show good agreement with the well-known Earth-Moon and Sun–Earth momentums. The Moon–Sun orbit is close to an elliptic shape with angular momentum of about 3.27 × 1038 J.s. This approach is the key to future studies for n-body problem solutions.
Towards a theory of steady-state solidification process with a quasi-equilibrium two-phase region
Authors: Makoveeva Eugenya V. , Koroznikova Irina E. , Glebova Alexandra E. , Ivanov Alexander A. , Alexandrova Irina V. , Bulycheva Svetlana V. , Alexandrov Dmitri V. , Toropova Liubov V. 
Published: October 2024

AbstractThe process of directional crystallization in the presence of a quasi-equilibrium two-phase region located between the solid material and the liquid phase is studied theoretically. The mathematical model of the process is based on heat and mass transfer equations in the solid, liquid and two-phase regions, as well as boundary conditions at the phase interfaces “solid phase” – “two-phase region” and “two-phase region” – “liquid phase”, which are moving with a constant velocity. The process of directional crystallization is given by fixed temperature gradients in the solid and liquid phases, which determine a constant velocity of melt solidification. An exact analytical solution of the nonlinear problem with two moving boundaries of phase transformation is obtained, which is based on the transition to a new independent variable, the solid phase fraction, when integrating the nonlinear heat and mass transfer equations in the two-phase region. As a result of solving the problem, the distributions of temperature and concentration of dissolved impurity, the solid phase fraction in a two-phase region, the laws and velocities of motion of its interphase boundaries are determined. It is analytically shown that the impurity concentration and temperature in the two-phase region are only the functions of solid phase fraction, which, in turn, depends on the spatial coordinate. Analysis of the obtained solutions shows that the solid phase fraction in a two-phase region can be both a decreasing and increasing function of the spatial coordinate, which is directed from the solid material to the melt. This determines the internal structure of two-phase region, its permeability, average interdendritic spacing, distribution of dissolved impurity, crystallization velocity and laws of two-phase region boundaries.
A 7-Year Retrospective Review of Flexor Sheath Infections
Authors: RIYAT Harjoat , MORRIS Holly , CHEADLE Caroline , LEATHERBARROW Amanda , RAE Dupinderjit Singh , JOHNSON Nick 
Published: October 2024

Background: Flexor sheath infections require prompt diagnosis, and management with intravenous antibiotics and/or surgical washout followed by hand therapy. Complication rates as high as 38% have been reported. Our unit takes a relatively conservative approach to the management of flexor sheath infections and select patients are managed non-surgically via our outpatient antibiotic service where they are clinically reviewed and receive a once daily dose of intravenous antibiotics. The aim of this study is to determine if outpatient management of flexor sheath infections was associated with an increased risk of complications compared to those admitted as an inpatient. Methods: A retrospective review was carried out with all patients clinically diagnosed with flexor sheath infection who were seen at our unit between January 2014 and December 2020. Age, gender, co-morbidities, cause of infection, management and subsequent complications were recorded. Results: A total of 128 patients with flexor sheath infections were treated. And 68% were male. Mean age was 50.4 years. A trend towards fewer presentations each year with animal bites, foreign bodies and penetrating trauma as the main cause of infection was noted. And 89% (n = 114) required admission with the other 11% (n = 14) treated as an outpatient. And 77% (n = 98) underwent surgical washout. And 6% (n = 8) suffered a complication. Conclusions: While flexor sheath washout continues to be standard practice, 23% of patients were safely managed with intravenous antibiotics and 11% purely via an outpatient service. Level of Evidence: Level IV (Therapeutic)
Diagnostic Potential of Salivary Interleukin‐1β and IL‐10 for Distinguishing Periodontal Health From Periodontitis and Stable From Unstable Periodontitis: A Case–Control Study
Authors: Raheem Zainab J. , Abdulbaqi Hayder Raad 
Published: October 2024

Objective: This case–control study aimed to investigate the diagnostic accuracy of salivary interleukin (IL)‐1β, IL‐10, and IL‐1β/IL‐10 ratio to discriminate periodontitis from periodontal health and stable from unstable periodontitis.Methods: Saliva samples were collected from 135 (healthy on an intact periodontium = 45 [as healthy control], stable periodontitis = 39, and unstable periodontitis = 51) participants, and then clinical periodontal parameters were recorded. An enzyme‐linked immunosorbent assay was used to determine salivary levels of IL‐1β and IL‐10. Area under the curves (AUCs), sensitivity, and specificity of IL‐1β, IL‐10, and IL‐1β/IL‐10 were estimated to discriminate between groups.Result: The level of salivary IL‐1β was significantly higher in unstable periodontitis than in stable periodontitis and healthy control groups (426 ± 59, 247 ± 55, and 204 ± 36 pg/ml [picograms per milliliter], respectively). While the level of salivary IL‐10 was significantly higher in the control group (360.7 ± 80.5 pg/ml) than unstable periodontitis group (146.92 ± 1.8 pg/ml), no significant difference was found between the control and stable periodontitis (317.04 ± 59.8 pg/ml) groups. IL‐1β, IL‐10, and IL‐1β/IL‐10 had significant diagnostic accuracy for differentiating healthy control from unstable periodontitis (AUCs = 0.99, 0.96, and 1; sensitivity = 0.98,1, and 1; specificity = 0.95, 0.95, and 1, respectively). Similarly, they showed significant diagnostic accuracy in distinguishing unstable from stable periodontitis (AUCs = 0.98, 0.99, and 1; sensitivity = 0.94, 1, and 1; specificity = 0.94, 0.97, and 1, respectively).Conclusion: Salivary IL‐1β, IL‐10, and IL‐1β/IL‐10 have a high potential to discriminate healthy control from periodontitis and stable from unstable periodontitis.Trial Registration: ClinicalTrials.gov identifier: NCT05722613
Changes in Breast Cancer Screening Prevalence in the United States during the COVID-19 Pandemic, 2018 to 2022
Authors: Ashad-Bishop Kilan C. , Star Jessica , Giaquinto Angela N. , Smith Robert A. , Jemal Ahmedin , Bandi Priti 
Published: October 2024

Abstract

Background:
Annual mammography screening declined year-on-year during the COVID-19 pandemic through 2021. This study examined changes in 2022 compared with 2018 in the national prevalence of self-reported up-to-date mammography.

Methods:
Using 2018 to 2022 data from the Center for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System, we assess relative changes defined as annual prevalence ratios (aPR) in the SR receipt of past-year and up-to-date (UTD) breast cancer screening (biannual mammography in women of ages 50–74 years) during the third year of the COVID-19 pandemic overall and by sociodemographic characteristics.

Results:
UTD breast cancer screening declined for the first time since 2018 [2018 compared with 2022, from 78.7%–76.6%; aPR, 0.97; 95% confidence interval (CI), 0.96–0.98] despite a small increase in past-year breast cancer screening from 2020 to 2022 (57.9%–59.6%; aPR, 1.03; 95% CI, 1.01–1.05). This translated to 747,791 fewer women reporting UTD with recommended breast cancer screening in 2022 versus 2018. UTD breast cancer screening declines between 2018 and 2022 were largest for American Indian/Alaska Native women (74.8%–62.2%; aPR, 0.83; 95% CI, 0.74–0.93), women with less formal educational attainment (&lt; high school: 73.1%–65.5%; aPR, 0.9; 95% CI, 0.85–0.95), and women without a usual source of care (48%–42.9%; aPR, 0.85; 95% CI, 0.78–0.92).

Conclusions:
Previously noted pandemic-related declines in past-year breast cancer screening now reflect in women reporting being UTD, with the largest declines in American Indian/Alaska Native women and those with lower socioeconomic status.

Impact:
Future studies should monitor screening prevalence in relation to breast cancer diagnostic stage overall and by sociodemographic groups.
Trastuzumab Deruxtecan with Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study
Authors: Hamilton Erika , Galsky Matthew D. , Ochsenreither Sebastian , Del Conte Gianluca , Martín Miguel , De Miguel Maria José , Yu Evan Y. , Williams Anja , Gion Maria , Tan Antoinette R. , Agrawal Laila , Rutten Annemie , Machiels Jean-Pascal , Cresta Sara , Debruyne Philip R. , Hennequin Audrey , Moreno Victor , Minchom Anna , Valdes-Albini Frances , Petrylak Daniel , Li Li , Tsuchihashi Zenta , Suto Fumitaka , Cheng Fu-Chih , Kandil Maha , Barrios Daniel , Hurvitz Sara 
Published: October 2024

Abstract

Purpose:
This multicenter phase Ib study investigated trastuzumab deruxtecan (T-DXd) plus nivolumab in patients with HER2-expressing metastatic breast cancer (mBC) and metastatic urothelial cancer (mUC).

Patients and Methods:
Part 1 determined the recommended dose for expansion of T-DXd plus nivolumab. Part 2 evaluated efficacy and safety; the primary endpoint was confirmed objective response rate by independent central review.

Results:
In part 1, seven patients with mBC were enrolled and received T-DXd 3.2 mg/kg (four patients) or 5.4 mg/kg (three patients) plus nivolumab. The recommended dose for expansion for T-DXd was 5.4 mg/kg plus nivolumab 360 mg intravenously every 3 weeks. In part 2, 32 patients with HER2-positive mBC (cohort 1; inclusive of three administered 5.4 mg/kg in part 1), 16 with HER2-low mBC (cohort 2), 30 with HER2-high mUC (cohort 3), and four with HER2-low mUC (cohort 4) were enrolled. At data cutoff (July 22, 2021), the confirmed objective response rates (95% confidence interval) for cohorts 1 to 4 were 65.6% (46.8%−81.4%), 50.0% (24.7%−75.3%), 36.7% (19.9%−56.1%), and not assessed due to small sample size, respectively. The median treatment duration (range) with T-DXd in cohorts 1 to 4 was 8.9 (1–23) months, 6.9 (1–21) months, 3.9 (1–21) months, and not assessed, respectively; the most common treatment-emergent adverse event was nausea (55.2%, 62.5%, 73.3%, and 75.0%, respectively). Adjudicated drug-related interstitial lung disease/pneumonitis rates (cohorts 1–3) were 20.7%, 0%, and 20.0%, respectively (one grade 5 each, cohorts 1 and 3).

Conclusions:
T-DXd plus nivolumab demonstrated promising antitumor activity in HER2-expressing mBC or mUC and safety consistent with the known profile of T-DXd. Interstitial lung disease/pneumonitis is an important risk and requires careful monitoring and prompt intervention.
FDA Approval Summary: Polatuzumab Vedotin in the First-Line Treatment of Select Large B-Cell Lymphomas
Authors: Sarraf Yazdy Maryam , Kasamon Yvette L. , Gu Wenjuan , Rodriguez Lisa R. , Jin Susan , Bhatnagar Vishal , Richardson Nicholas C. , Theoret Marc R. , Pazdur Richard , Gormley Nicole J. 
Published: October 2024

Abstract
In April 2023, the U.S. FDA granted regular approval to polatuzumab vedotin-piiq in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (pola+R-CHP) for adult patients who have previously untreated diffuse large B-cell lymphoma, not otherwise specified, or high-grade B-cell lymphoma and who have an International Prognostic Index score of 2 or greater. Approval was based on POLARIX, a randomized, double-blinded, placebo-controlled trial evaluating the superiority of substituting vincristine with polatuzumab vedotin in the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone regimen as first-line therapy for patients with large B-cell lymphoma. Efficacy was based on investigator-assessed progression-free survival (PFS) in 879 patients who were randomized to receive pola+R-CHP or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, followed by two cycles of rituximab alone. PFS was statistically significantly longer with pola+R-CHP, with an HR of 0.73 (95% confidence interval, 0.57–0.95) and log-rank P value of 0.0177 (two-sided α = 0.05). There was no improvement demonstrated in the key secondary endpoints of the complete response rate at the end of therapy or overall survival (OS). Several issues raised uncertainty about the benefit–risk profile of polatuzumab vedotin in this curative-intent setting, including the modest PFS benefit of pola+R-CHP and lack of OS benefit. The application was therefore presented at an Oncology Drugs Advisory Committee. This article summarizes key aspects of the regulatory review, including perspectives on PFS and OS results and other endpoints.
Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia
Authors: Chen Yu , Yin Zhenghao , Westover Kenneth D. , Zhou Zhiwei , Shu Liping 
Published: October 2024

Abstract
RAS mutations are prevalent in leukemia, including mutations at G12, G13, T58, Q61, K117, and A146. These mutations are often crucial for tumor initiation, maintenance, and recurrence. Although much is known about RAS function in the last 40 years, a substantial knowledge gap remains in understanding the mutation-specific biological activities of RAS in cancer and the approaches needed to target specific RAS mutants effectively. The recent approval of KRASG12C inhibitors, adagrasib and sotorasib, has validated KRAS as a direct therapeutic target and demonstrated the feasibility of selectively targeting specific RAS mutants. Nevertheless, KRASG12C remains the only RAS mutant successfully targeted with FDA-approved inhibitors for cancer treatment in patients, limiting its applicability for other oncogenic RAS mutants, such as G12D, in leukemia. Despite these challenges, new approaches have generated optimism about targeting specific RAS mutations in an allele-dependent manner for cancer therapy, supported by compelling biochemical and structural evidence, which inspires further exploration of RAS allele-specific vulnerabilities. This review will discuss the recent advances and challenges in the development of therapies targeting RAS signaling, highlight emerging therapeutic strategies, and emphasize the importance of allele-specific approaches for leukemia treatment.