bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor microenvironment evaluation to predict anti–PD-1 response of advanced gastric cancer: Results from a multicenter prospective clinical trial.
Authors: Liao Wangjun , Shi Min , Zeng Dongqiang , Luo Huiyan , Xiao Jian , Ye Feng , Xiong Hailin , Yuan Xia , Huang Yisheng , Li Yongqiang , Huang Na , Wu Jianhua , Li Shaowei , Zheng Siting , Wu Jiani , Sun Li , Rong Xiaoxiang , Wang Chunlin , Guo Jian , Deng Qiong 
Published: February 2023

415 Background: Clinical trials support the efficacy of immune checkpoint blockades (ICBs) plus chemotherapy in a subset of patients with metastatic gastric cancer (mGC). With the aim of identifying determinants of response, we developed a TMEscore assay (PCR assay with 30 genes) to assess tumor microenvironment, which was previously proved to be a robust predictive biomarker for patients treated with ICBs. Methods: Advanced GC patients treated with ICB combined with chemotherapy as first-line regimen were included in this multi-center prospective clinical trial (NCT#04850716). 65 tumor specimens obtained from 8 medical centers before treatment were applied to estimate TMEscore, PD-L1(CPS) and mismatch repair deficiency (MMR). Of 65 patients, 43 patients with treatment response and 34 patients with progression-free survival (PFS) were used to compare the predictiveness of biomarkers. Results: Theoverall response rate (ORR) and median PFS of this cohort were 39.9% and 4.67 months.Enhanced ORR was observed in TMEscore-high mGC patients (ORR = 61%), but only 16.7% in the low group. Regressive tumors (partial response, PR) had markedly higher TMEscore than stable and progressive tumors (stable disease, SD; progressive disease, PD, P = 0.001). By applying ROC curve analysis, the TMEscore was found to be an encouraging predictive biomarker that surpassed MMR and CPS statistically (AUC = 0.863, 0.525, and 0.519, respectively; Delong test, P = 0.003). Importantly, the Kaplan-Meier survival analysis demonstrated that a high TMEscore was significantly related to a more favorable PFS ( P = 0.0026, HR=0.18, 95%CI 0.06-0.55). Compared to TMEscoreA (immune score), TMEscoreB (stromal score) presented a dramatically higher hazard ratio for PFS (HR = 12.25, P = 0.0001), implicating stromal activation as a critical mechanism of intrinsic resistance to ICB plus chemotherapy. Meanwhile, PD-L1 (CPS) was not statistically associated with PFS, whether 1 or 5 were used as a cutoff to divide patients ( P = 1 and 0.22). Conclusions: This prospective clinical study indicated that the TMEscore assay is a robust biomarker for screening mGC patients who may derive survival benefit from ICB plus chemotherapy. Our data also suggest that TMEscore may be a more accurate predictive biomarker than MSI and CPS (PD-L1) for mGC patients, which warrants additional investigations in larger cohorts. Clinical trial information: NCT#04850716 .
Primary Retroperitoneal Lymph Node Dissection for Stage II Seminoma: Is Surgery the New Path Forward?
Authors: Tachibana Isamu , Alabd Andre , Tong Yan , Piroozi Alex , Mahmoud Mohammad , Kern Sean Q. , Masterson Timothy A. , Adra Nabil , Foster Richard S. , Hanna Nasser H. , Einhorn Lawrence H. , Cary Clint 
Published: February 2023

PURPOSE On the basis of National Comprehensive Cancer Network guidelines, clinical stage (CS) II seminoma is treated with radiotherapy or chemotherapy. Primary retroperitoneal lymph node dissection (RPLND) demonstrated recent success as first-line therapy for RP-only disease. Our aim was to confirm surgical efficacy and evaluate recurrences after primary RPLND for CS IIA/IIB seminoma to determine if various clinical factors could predict recurrences. PATIENTS AND METHODS Patients who underwent primary RPLND for seminoma from 2014 to 2021 were identified. All patients had at least 6 months of follow-up. Nineteen patients were part of a clinical trial. Patients receiving adjuvant chemotherapy were excluded from Kaplan-Meier recurrence-free survival (RFS) analysis. RESULTS We identified 67 patients who underwent RPLND for RP-only seminoma. One patient had pN0 disease. Median follow-up time after RPLND was 22.4 months (interquartile range, 12.3-36.1 months) and 11 patients were found to have a recurrence. The 2-year RFS for RPLND-only patients without adjuvant chemotherapy was 80.2%. Patients who developed RP disease for a period > 12 months had the lowest chance of recurrence, with a 2-year RFS of 92.2%. Seven initial CS II patients were on surveillance for 3-12 months before surgery and no patients experienced recurrence. Pathologic nodal stage and high-risk factors such as tumor size > 4 cm or rete testis invasion of the orchiectomy specimen did not affect recurrence. CONCLUSION CS II seminoma can be treated with surgery to avoid rigors of chemotherapy or radiotherapy. Patients with delayed development of CS II disease (> 12 months) had the best surgical results. Patients may present with borderline CS II disease, and careful surveillance may avoid overtreatment. Further study on patient selection and extent of dissection remains uncertain and warrants further investigation.
Deep Brain Stimulation for Advanced Parkinson Disease in Developing Countries: A Cost-Effectiveness Study From China
Authors: Guo Xinxia , Feng Chen , Pu Jiali , Jiang Hongjie , Zhu Zhoule , Zheng Zhe , Zhang Jianmin , Chen Gao , Zhu Junming , Wu Hemmings 
Published: February 2023

BACKGROUND:
The cost-effectiveness of deep brain stimulation (DBS) is more favorable than best medical treatment (BMT) for advanced Parkinson disease (PD) in developed countries. However, it remains unclear in developing countries, where the cost of DBS may not be reimbursed by health care system.

OBJECTIVE:
To model and evaluate the long-term cost-effectiveness of DBS for advanced PD in China from a patient payer perspective.

METHODS:
We developed a Markov model representing the clinical progress of PD to predict the disease progression and related medical costs in a 15-year time horizon. The incremental cost-effectiveness ratio (ICER) and net benefit were used to evaluate the cost-effectiveness of DBS vs BMT.

RESULTS:
DBS treatment led to discounted total costs of ¥370 768 ($56 515.20) (95% CI, ¥369 621.53-371 914.88), compared with ¥48 808 ($7439.68) (95% CI, ¥48 502.63-49 114.21) for BMT, with an additional 1.51 quality-adjusted life years gained, resulting in an ICER of ¥213 544 ($32 549.96)/quality-adjusted life years (95% CI, ¥208 177.35-218 910.10). Sensitivity analysis showed that DBS-related cost has the most substantial impact on ICER. Nation-wide net benefit of BMT and DBS were ¥33 819 ($5154.94) (95% CI, ¥30 211.24-37 426) and ¥30 361 ($4627.85) (95% CI, ¥25 587.03-39 433.66), respectively. Patient demographic analysis showed that more favorable DBS cost-effectiveness was associated with younger age and less severe disease stage.

CONCLUSION:
DBS is cost-effective for patients with advanced PD over a 15-year time horizon in China. However, compared with developed countries, DBS remains a substantial economic burden for patients when no reimbursement is provided. Our findings may help inform cost-effectiveness–based decision making for clinical care of PD in developing countries.
On-Call Junior Neurosurgery Residents Spend 9 hours of Their On-Call Shift Actively Using the Electronic Health Record
Authors: Patel Arati , Mummaneni Praveen V. , Zheng Jeff , Rosner Benjamin I. , Thombley Robert , Sorour Omar , Theodosopoulos Philip V. , Aghi Manish K. , Berger Mitchel S. , Chang Edward F. , Chou Dean , Manley Geoffrey T. , DiGiorgio Anthony M. 
Published: February 2023

BACKGROUND:
The electronic health record (EHR) is central to clinical workflow, yet few studies to date have explored EHR usage patterns among neurosurgery trainees.

OBJECTIVE:
To describe the amount of EHR time spent by postgraduate year (PGY)-2 and PGY-3 neurosurgery residents during on-call days and the distribution of EHR activities in which they engage.

METHODS:
This cohort study used the EHR audit logs, time-stamped records of user activities, to review EHR usage of PGY-2 and PGY-3 neurosurgery residents scheduled for 1 or more on-call days across 2 calendar years at the University of California San Francisco. We focused on the PGY-2 and PGY-3, which, in our training program, represent the primary participants in the in-house on-call pool.

RESULTS:
Over 723 call days, 12 different residents took at least one on-call shift. The median (IQR) number of minutes that residents spent per on-call shift actively using the EHR was 536.8 (203.5), while interacting with an average (SD) of 68.1 (14.7) patient charts. There was no significant difference between Active EHR Time between residents as PGY-2 and PGY-3 on paired t-tests. Residents spent the most time on the following EHR activities: patient reports, notes, order management, patient list, and chart review.

CONCLUSION:
Residents spent, on average, 9 hours of their on-call shift actively using the EHR, and there was no improved efficiency as residents gained experience. We noted several areas of administrative EHR burden, which could be reduced.
The Relevance of Biologically Effective Dose for Hearing Preservation After Stereotactic Radiosurgery for Vestibular Schwannomas: A Retrospective Longitudinal Study
Authors: Tuleasca Constantin , Toma-Dasu Iuliana , Duroux Sebastien , Starnoni Daniele , George Mercy , Maire Raphael , Daniel Roy Thomas , Patin David , Schiappacasse Luis , Dasu Alexandru , Faouzi Mohamed , Levivier Marc 
Published: February 2023

BACKGROUND:Stereotactic radiosurgery has become a common treatment approach for small-to-medium size vestibular schwannomas.OBJECTIVE:To evaluate relationship between time (beam-on and treatment) and risk of hearing decline after stereotactic radiosurgery for vestibular schwannomas in patients with Gardner–Robertson (GR) baseline classes I and II.METHODS:This retrospective longitudinal single-center study included 213 patients with GR I and II treated between June 2010 and December 2019. Risk of passing from GR classes I and II (coded 0) to other classes III, IV, and V (coded 1) and the increase in pure tone average (continuous outcome) were evaluated using a mixed-effect regression model. Biologically effective dose (BED) was further assessed for an alpha/beta ratio of 2.47 (Gy2.47).RESULTS:Binary outcome analysis revealed sex, dose rate, integral dose, time [beam-on time odds ratio 1.03,P= .03, 95% CI 1.00-1.06; treatment time (P= .02) and BED (P= .001) as relevant. Fitted multivariable model included the sex, dose rate, and BED. Pure tone average analysis revealed age, integral dose received by tumor, isocenter number, time (beam-on time odds ratio 0.20,P= .001, 95% CI 0.083-0.33) and BED (P= .005) as relevant.CONCLUSION:Our analysis showed that risk of hearing decline was associated with male sex, higher radiation dose rate (cutoff 2.5 Gy/minute), higher integral dose received by the tumor, higher beam-on time ≥20 minutes, and lower BED. A BED between 55 and 61 was considered as optimal for hearing preservation.
HER2 expression defines unique requirements for flotillin and c-Src in EGFR signaling
Authors: Abousawan John , Orofiamma Laura A. , Fairn Gregory D. , Antonescu Costin N. 
Published: February 2023

ABSTRACT
The epidermal growth factor receptor (EGFR) controls many cellular functions. Upon binding its ligand, the receptor undergoes dimerization, phosphorylation and activation of signals including the phosphoinositide-3-kinase (PI3K)–Akt pathway. Although some studies have indicated that EGFR signaling may be controlled by signal enrichment within various membrane rafts, such as flotillin nanodomains, others have found a limited effect of disruption of these nanodomains on EGFR signaling, suggesting that specific factors may define context-specific control of EGFR signaling. Ligand-bound EGFR can homodimerize or instead undergo heterodimerization with the related receptor HER2 (also known as ERBB2) when the latter is expressed. We examined how EGFR signaling in the presence of HER2 distinctly requires flotillin nanodomains. Induction of HER2 expression altered EGFR signaling duration, which is consistent with EGFR–HER2 heterodimer formation. EGFR and c-Src (also known as SRC) localized within plasma membrane structures demarked by flotillin-1 more prominently in HER2-expressing cells. Consistently, HER2-expressing cells, but not cells lacking HER2, were dependent on flotillin-1 and c-Src for EGFR signaling leading to Akt activation and cell proliferation. Hence, HER2 expression establishes a requirement for flotillin membrane rafts and c-Src in EGFR signaling.
Re-organization of nucleolar architecture in myogenic differentiation
Authors: Miyake Tetsuaki , McDermott John C. 
Published: February 2023

ABSTRACT
Myogenesis, the process of muscle differentiation, requires an extensive remodeling of the cellular transcriptome and proteome. Whereas the transcriptional program underpinning myogenesis is well characterized, the required adaptation in protein synthesis is incompletely understood. Enhanced protein synthesis necessitates ribosome biogenesis at the nucleolus. Nucleolar size and activity are inextricably linked with altered gene expression. Here, we report changes in nucleolar morphology and function during myogenic differentiation. Immunofluorescence analysis revealed alterations in nucleolar morphology that were dependent on the cellular state – proliferative or quiescent myogenic progenitors (myoblasts or reserve cells) contained multiple small nucleoli with a characteristic spherical shape, whereas multinucleated myotubes typically contained one large, often irregularly shaped nucleolus. These morphological alterations are consistent with changes to nucleolar phase separation properties. Re-organization of the nucleolar structure was correlated with enhanced rRNA production and protein translation. Inhibition of mTOR signaling with rapamycin perturbed nucleolar re-organization. Conversely, hyperactivated mTOR enhanced alterations in nucleolar morphology. These findings support the idea that there is an mTOR dependent re-organization of nucleolar structure during myogenesis, enhancing our understanding of myogenesis and possibly facilitating new approaches to therapeutic interventions in muscle pathologies.
Structure and function of distal and subdistal appendages of the mother centriole
Authors: Ma Dandan , Wang Fulin , Teng Junlin , Huang Ning , Chen Jianguo 
Published: February 2023

ABSTRACT
Centrosomes are composed of centrioles surrounded by pericentriolar material. The two centrioles in G1 phase are distinguished by the localization of their appendages in the distal and subdistal regions; the centriole possessing both types of appendage is older and referred to as the mother centriole, whereas the other centriole lacking appendages is the daughter centriole. Both distal and subdistal appendages in vertebrate cells consist of multiple proteins assembled in a hierarchical manner. Distal appendages function mainly in the initial process of ciliogenesis, and subdistal appendages are involved in microtubule anchoring, mitotic spindle regulation and maintenance of ciliary signaling. Mutations in genes encoding components of both appendage types are implicated in ciliopathies and developmental defects. In this Review, we discuss recent advances in knowledge regarding the composition and assembly of centriolar appendages, as well as their roles in development and disease.
Implementation of automated personalised breast radiotherapy planning techniques with scripting in Raystation
Authors: Gleeson Ian , Bolger Niall , Chun Harmony , Hutchinson Katie , Klodowska Magdalena , Mehrer Jennifer , Toomey Marian 
Published: February 2023

Objective: Implement scripted automatic breast planning (AP) for breast techniques within Raystation. Methods: Manual plans (MPs) were re-planned and compared with AP plans for whole breast (WB), partial breast (PB), hybrid volumetric modulated arc therapy simultaneous integrated boost (VMAT SIB) and VMAT nodal plans. Results: WB AP plans took 7 min comparing well to MP. One WB AP failed a mandatory dose constraint. Small statistically significant differences showed improved coverage for AP at expense of slightly hotter plans, however absolute differences were small (mean differences < 1% or D 0.5cc<0.2 Gy). PB AP plans took 9 min, showing improved coverage (V 24.7Gy97.6 vs 96.4 %). One PB AP case failed a mandatory constraint. Other dosimetric differences were non-significant. SIB AP plans took 14 min with one case failing a mandatory constraint with minor differences compared with MP except larger V 42.8Gy (3 vs 1.5 %) and more MU. VMAT AP plans took 12 min and were hotter for PTVp_4000 but had higher nodal coverage. Contra_Lung V 2.5Gy was higher (8.8 %) than MP plans (6.5 %). Conclusion: Automatic planning of modern breast techniques has been successfully introduced using a commercial planning system. AP plans are very similar to MP, requiring little manual interaction for most cases with significant timesaving potential. Advances in knowledge: Scripted breast plans produced within minutes for WB, PB, SIB and VMAT. Successfully introduced into large busy department. Plans similar to manual plans, requiring little manual interaction.
Interventions to support adolescents and young adults with the healthcare transition from paediatric to adult nephrology health services: A scoping review protocol
Authors: Kinch Melissa , Kroll Thilo , Stokes Diarmuid , Somanadhan Suja 
Published: February 2023

Background: Due to technological advancements and improved medical management of adolescents and young adults (AYAs) living with renal disease, there has been an exponential increase noted in the number of patients advancing from the paediatric to adult nephrology healthcare setting. Subsequently, more AYAs are required to undergo the process of healthcare transition from paediatric to adult healthcare services. This process is often a challenging period for young people and families and is often associated with a decline in physical and psychosocial health outcomes of AYAs with renal disorders. To ensure a successful transition, AYAs must develop the ability to manage their renal condition, including the medical and psychosocial aspects of their condition, independently. Despite significant research into the transition from paediatric to adult healthcare for this unique patient cohort, the transition period remains a challenge. The scoping review will aim to map, explore, and understand the interventions that are currently available to offer positive perceptions and experiences of transition for both AYAs living with renal disorders and their families. Methods: A systematic literature search will be conducted of PubMed, PsycInfo, CINAHL, ASSIA, EMBASE and Web of Science databases from the year 2000 to present. Two independent reviewers will screen the title and abstracts of peer-reviewed literature obtained and assess them against the inclusion criteria to determine their inclusion eligibility. Data will be extracted and synthesised using a template refined by the authors. The scoping review will be undertaken in accordance with PRISMA-ScR guidelines. Data will undergo a formal critical appraisal using recognised appraisal tools. Conclusions: Through mapping this knowledge, the scoping review will aim to identify interventions that are currently available and identify gaps within the literature. This evidence may support the development of transitional care interventions in the future, promote patient satisfaction, and improve patient outcome measures and experiences.
Influence of physical activity on cognitive functions - Potential mechanisms and benefits
Authors: Dwojaczny Blanka , Bejtka Monika 
Published: February 2023

Background and Study Aim. The results of many research indicate that systematic physical activity has also positive effect on functions of the central nervous system. For example, improvement of the cognitive functions level, such as memory and learning, under the influence of systematic physical training has been demonstrated. The positive effect of physical activity on the central nervous system is especially visible and widely described with regard to elderly people, who develop many adverse remodeling changes in the structure of the brain. However, particularly interesting are the studies which show that also among young people a positive effect of physical activity on cognitive processes is observed. Currently, several hypotheses are proposed, presenting potential mechanisms underlying the beneficial effects of physical activity on the central nervous system. The first hypothesis assumes the beneficial effect of physical activity on the expression of hippocampal genes related to synaptic plasticity. The second hypothesis assumes that physical effort per se is an inducer of the secretion of the growth factors (e.g., BDNF, IGF-1), which have a trophic effect on the nervous system. In addition, the results of the latest scientific studies indicate that the positive effect of physical activity on the central nervous system may be due to the action of phospholipase (Gpld-1), released to the bloodstream from the liver under the influence of physical exercise. This work indicates that due to the influence on cognitive functions, physical activity is absolutely essential to both elderly and young people population.
Conclusions. It seems necessary to educate both young and elderly people that the proper level of physical activity is a key factor allowing to maintain both physical and mental health at an appropriate, desirable level.
Prawda osoby – trzy wymiary. Reinterpretacja klasycznej formuły prawdy
Authors: Starnawski Witold 
Published: February 2023

Podjęty temat nawiązuje do teorii osoby Jana Pawła II. Głównym problemem jest relacja dwu pojęć: „osobowy wymiar prawdy” i „klasyczna formuła prawdy”. Osobowy wymiar prawdy wskazuje na podmiotowy aspekt poznania (poznanie dokonuje się w osobie) i nie jest sprzeczny z transcendencją i obiektywnością rezultatów poznania. „Zapodmiotowanie” prawdy w osobie oznacza zobowiązanie osoby: bycie wiernym prawdzie i własnemu poznaniu. Podstawą tego „zaangażowania” jest bezinteresowność poznania. Prawda osoby przejawia się w trzech wymiarach: (1) poznawczym – intelekt potwierdza prawdę rzeczywistości; (2) wewnętrznym – osoba upodmiotawia prawdę, przyjmuje ją za „swoją”; (3) moralnym – prawda staje się racją czynu i czynnikiem doskonalenia osoby. Potwierdzanie prawdy postawą i czynami jest najbardziej swoistym, unikalnym aktem osoby. Bycie sobą oznacza stałe przekraczanie i doskonalenie siebie. Pełna miara prawdy osoby tkwi w Stwórcy, Źródle jej istnienia i darów wyznaczających sens i cel osobowego życia. Ten, kto żyje prawdą i jest gotów jej służyć, staje się jej świadkiem.