Surface dose measurement by optically stimulated luminescent dosimeter: A phantom study.

INTRODUCTION: Radiotherapy is the standard treatment for breast cancer patients after surgery. However, radiotherapy can cause side effects such as dry and moist desquamation of the patient's skin. The dose calculation from a treatment planning system (TPS) might also be inaccurate. The purpose of this study is to measure the surface dose on the CIRS thorax phantom by an optically stimulated luminescent dosimeter (OSLD). METHODS: The characteristics of OSLD were studied in terms of dose linearity, reproducibility, and angulation dependence on the solid water phantom. To determine the surface dose, OSLD (Landauer lnc., USA) was placed on 5 positions at the CIRS phantom (Tissue Simulation and Phantom Technology, USA). The five positions were at the tip, medial, lateral, tip-medial, and tip-lateral. Then, the doses from OSLD and TPS were compared. RESULTS: The dosimeter's characteristic test was good. The maximum dose at a depth of 15 mm was 514.46 cGy, which was at 100%. The minimum dose at the surface was 174.91 cGy, which was at 34%. The results revealed that the surface dose from TPS was less than the measurement. The percent dose difference was -2.17 ± 6.34, -12.08 ± 3.85, and -48.71 ± 1.29 at the tip, medial, and lateral positions, respectively. The surface dose from TPS at tip-medial and tip-lateral was higher than the measurement, which was 12.56 ± 5.55 and 10.45 ± 1.76 percent dose different, respectively. CONCLUSION: The percent dose difference is within the acceptable limit, except for the lateral position because of the body curvature. However, OSLD is convenient to assess the radiation dose, and further study is to measure in vivo. IMPLICATION FOR PRACTICE: The OSL NanoDot dosimeter can be used for dose validation with a constant setup location. The measurement dose is higher than the dose from TPS, except for some tilt angles.

Assessment of four dose calculation algorithms using IAEA-TECDOC-1583 with medium dependency correction factor (Kmed) application.

PURPOSE: This study discusses the measurement of dose in clinical commissioning tests described in IAEA-TECDOC-1583. It explores the application of Monte Carlo (MC) modelled medium dependency correction factors (Kmed) for accurate dose measurement in bone and lung materials using the CIRS phantom. METHODS: BEAMnrc codes simulate radiation sources and model radiation transport for 6 MV and 15 MV photon beams. CT images of the CIRS phantom are converted to an MC compatible phantom. The PTW 30013 farmer chamber measures doses within modeled CIRS phantom. Kmed are determined by averaging values from four central voxels within the sensitive volume of the farmer chamber. Kmed is calculated for Dm.m and Dw.w algorithm types in bone and lung media for both photon beams. RESULTS: Average modelled correction factors for Dm.m calculations using the farmer chamber are 0.976 (±0.1 %) for 6 MV and 0.979 (±0.1 %) for 15 MV in bone media. Correspondingly, correction factors for Dw.w calculations are 0.99 (±0.3 %) and 0.992 (±0.4 %), respectively. For lung media, average correction factors for Dm.m calculations are 1.02 (±0.3 %) for 6 MV and 1.022 (±0.4 %) for 15 MV. Correspondingly, correction factors for Dw.w calculations are 1.01 (±0.3 %) and 1.012 (±0.2 %), respectively. CONCLUSIONS: This study highlights the significant impact of applying Kmed on dose differences between measurement and calculation during the dose audit process.

Age and Sex Differences in the Genetic Architecture of Measures of Subjective Health: Relationships With Physical Health, Depressive Symptoms, and Episodic Memory.

OBJECTIVES: Subjective health (SH) is not just an indicator of physical health, but also reflects active cognitive processing of information about one's own health and has been associated with emotional health measures, such as neuroticism and depression. Behavior genetic approaches investigate the genetic architecture of SH, that is, genetic and environmental influences on individual differences in SH and associations with potential components such as physical, cognitive, and emotional health. Previous twin analyses have been limited by sex, sample size, age range, and focus on single covariates. METHODS: The current analysis used data from 24,173 adults ranging in age from 40 to 90 years from the international Interplay of Genes and Environment across Multiple Studies consortium to investigate the genetic architecture of 3 measures of SH: self-rated health, health compared to others, and impact of health on activities. Independent pathways model of SH included physical health, depressive symptoms, and episodic memory, with age, sex, and country included as covariates. RESULTS: Most or all of the genetic variance for SH measures were shared with physical health, depressive symptoms, and episodic memory. Genetic architecture of SH differed across measures, age groups (40-65, 66-90), and sexes. Age comparisons indicated stronger correlations with all 3 covariates in older adults, often resulting from greater shared genetic variance. DISCUSSION: The predictive value of SH has been amply demonstrated. The higher genetic contributions to associations between SH and its components in older adults support the increasing conceptualization with age of SH as an intuitive summation of one's vital reserve.

Immune-Inflammatory Response And Compensatory Immune-Regulatory Reflex Systems And White Matter Integrity in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Low-grade neural and peripheral inflammation are among the proposed pathophysiological mechanisms of schizophrenia. White matter impairment is one of the more consistent findings in schizophrenia but the underlying mechanism remains obscure. Many cerebral white matter components are sensitive to neuroinflammatory conditions that can result in demyelination, altered oligodendrocyte differentiation, and other changes. We tested the hypothesis that altered immune-inflammatory response system (IRS) and compensatory immune-regulatory reflex system (IRS/CIRS) dynamics are associated with reduced white matter integrity in patients with schizophrenia. STUDY DESIGN: Patients with schizophrenia (SCZ, 70M/50F, age = 40.76 ±â€…13.10) and healthy controls (HCs, 38M/27F, age = 37.48 ±â€…12.31) underwent neuroimaging and plasma collection. A panel of cytokines were assessed using enzyme-linked immunosorbent assay. White matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging using a 3-T Prisma MRI scanner. The cytokines were used to generate 3 composite scores: IRS, CIRS, and IRS/CIRS ratio. STUDY RESULTS: The IRS/CIRS ratio in SCZ was significantly higher than that in HCs (P = .009). SCZ had a significantly lower whole-brain white matter average FA (P < .001), and genu of corpus callosum (GCC) was the most affected white matter tract and its FA was significantly associated with IRS/CIRS (r = 0.29, P = .002). FA of GCC was negatively associated with negative symptom scores in SCZ (r = -0.23, P = .016). There was no mediation effect taking FA of GCC as mediator, for that IRS/CIRS was not associated with negative symptom score significantly (P = .217) in SCZ. CONCLUSIONS: Elevated IRS/CIRS might partly account for the severity of negative symptoms through targeting the integrity of GCC.

CiRS-7 Enhances the Liquid-liquid Phase Separation of miRISC and Promotes DNA Damage Repair.

Noncoding RNAs have been found to play important roles in DNA damage repair, whereas the participation of circRNA remains undisclosed. Here, we characterized ciRS-7, a circRNA containing over 70 putative miR-7-binding sites, as an enhancer of miRISC condensation and DNA repair. Both in vivo and in vitro experiments confirmed the condensation of TNRC6B and AGO2, two core protein components of human miRISC. Moreover, overexpressing ciRS-7 largely increased the condensate number of TNRC6B and AGO2 in cells, while silencing ciRS-7 reduced it. Additionally, miR-7 overexpression also promoted miRISC condensation. Consistent with the previous report that AGO2 participated in RAD51-mediated DNA damage repair, the overexpression of ciRS-7 significantly promoted irradiation-induced DNA damage repair by enhancing RAD51 recruitment. Our results uncover a new role of circRNA in liquid-liquid phase separation and provide new insight into the regulatory mechanism of ciRS-7 on miRISC function and DNA repair.

Correlation of Immune-Inflammatory Response System (IRS)/Compensatory Immune-Regulatory Reflex System (CIRS) with White Matter Integrity in First-Episode Patients with Schizophrenia.

Several studies have reported compromised white matter integrity, and that some inflammatory mediators may underlie this functional dysconnectivity in the brain of patients with schizophrenia. The immune-inflammatory response system and compensatory immune-regulatory reflex system (IRS/CIRS) are novel biomarkers for exploring the role of immune imbalance in the pathophysiological mechanism of schizophrenia. This study aimed to explore the little-known area regarding the composite score of peripheral cytokines, the IRS/CIRS, and its correlation with white matter integrity and the specific microstructures most affected in schizophrenia. First-episode patients with schizophrenia (FEPS, n = 94) and age- and sex-matched healthy controls (HCs, n = 50) were enrolled in this study. Plasma cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA), and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). The whole brain white matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging (DTI) using a 3-T Prisma MRI scanner. The IRS/CIRS in FEPS was significantly higher than that in HCs (p = 1.5 × 10-5) and Cohen's d effect size was d = 0.74. FEPS had a significantly lower whole-brain white matter average FA (p = 0.032), which was negatively associated with IRS/CIRS (p = 0.029, adjusting for age, sex, years of education, BMI, and total intracranial volume), but not in the HCs (p > 0.05). Among the white matter microstructures, only the cortico-spinal tract was significantly correlated with IRS/CIRS in FEPS (r = - 0.543, p = 0.0009). Therefore, elevated IRS/CIRS may affect the white matter in FEPS.

Prognostic value of comorbidities in older patients with cancer: the ELCAPA cohort study.

BACKGROUND: In older patients, comorbidities competed with cancer for mortality risk. We assessed the prognostic value of comorbidities in older patients with cancer. PATIENTS AND METHODS: We analysed all patients >70 years of age with colorectal, breast, prostate, or lung cancer included in the prospective ELCAPA cohort. The Cumulative Illness Rating Scale-Geriatrics (CIRS-G) score was used to assess comorbidities. The primary endpoint was overall survival (OS) at 3, 12, and 36 months. The adjusted difference in the restricted mean survival time (RMST) was used to assess the strength of the relationship between comorbidities and survival. RESULTS: Of the 1551 patients included (median age 82 years; interquartile range 78-86 years), 502 (32%), 575 (38%), 283 (18%), and 191 (12%) had colorectal, breast, prostate, and lung cancer, respectively, and 50% had metastatic disease. Hypertension, kidney failure, and cognitive impairment were the most common comorbidities (67%, 38%, and 29% of the patients, respectively). A CIRS-G score >17, two or more severe comorbidities, more than seven comorbidities, heart failure, and cognitive impairment were independently associated with shorter OS. The greatest effect size was observed for CIRS-G >17 (versus CIRS-G <11): at 36 months, the adjusted differences in the RMST (95% confidence interval) were -6.0 months (-9.3 to -2.6 months) for colorectal cancer, -9.1 months (-13.2 to -4.9 months) for breast cancer, -8.3 months (-12.8 to -3.9 months) for prostate cancer, and -5.5 months (-9.9 to -1.1 months) for lung cancer (P < 0.05 for all). CONCLUSIONS: Comorbidities' type, number, and severity were independently associated with shorter OS. A 17-point cut-off over 56 for the total CIRS-G score could be considered in clinical practice.

The role of CDR1as/ciRS-7 in cardio-cerebrovascular diseases.

Cerebellar degeneration-related protein 1 antisense RNA (CDR1as), also known as ciRS-7, is a circular natural antisense transcript of CDR1. It is a widely studied and powerful representative of circular RNAs. Based on its widely reported role in cancer, CDR1as is considered one of the most promising biomarkers for diagnosing and treating tumours. However, some recent studies have extensively focused on its regulatory role in cardio-cerebrovascular diseases instead of in tumours. Studies have shown that CDR1as plays a unique role in the occurrence of cardio-cerebrovascular diseases; thus, it may be a potential target for preventing and treating cardio-cerebrovascular diseases. Furthermore, CDR1as has also been found to be related to signal transduction pathways related to inflammatory response, oxidative stress, etc., which may reveal its potential mechanism in cardio-cerebrovascular diseases. However, there is no literature to summarize the role and possible mechanism of CDR1as in cardio-cerebrovascular diseases. Therefore, in the present review, we have comprehensively summarised the latest progress in the biological characteristics, development processes, regulatory mechanisms, and roles of CDR1as in cardio-cerebrovascular diseases, aiming to provide a reference and guidance for future studies.

Evaluating Interoperability in German Critical Incident Reporting Systems.

INTRODUCTION: In industrialised countries, one in ten patients suffers harm during hospitalization. Critical Incident Reporting Systems (CIRS) aim to minimize this by learning from errors and identifying potential risks. However, a lack of interoperability among the 16 CIRS in Germany hampers their effectiveness. METHODS: This study investigates reports' syntactic and semantic interoperability across seven different reporting systems. Syntactic interoperability was examined using WHO's Minimal Information Models (MIM), while semantic interoperability was evaluated with SNOMED concepts. RESULTS: The findings reveal a low structural overlap, with only two terms correctly represented in the SNOMED CT terminology. In addition, most systems showed no syntactic interoperability. CONCLUSION: Improving interoperability is essential for increasing the effectiveness and usability of CIRS. The study suggests a unified data model such as MIM or using Health Level 7 Fast Healthcare Interoperability Resources (HL7 FHIR) resources and expanding SNOMED CT with patient safety-relevant terms for semantic interoperability. Given the current lack of both syntactic and semantic interoperability in CIRS, developing a patient safety ontology is recommended for efficient critical incident analysis too.

Circular RNA ciRS-7 signature as a potential biomarker for the early detection of diabetes with Alzheimer's disease: a hypothesis.

In the 1970s, Circular RNAs (CircRNAs) were first discovered in RNA viruses as viroids and were initially assumed to be RNA splicing defects. The roles and topologies of these circular RNA loops were later revealed using computer analysis and RNA-sequencing. They were found to demonstrate various functions, including protein scaffolding, parental gene regulation, microRNA sponges, and RNA-protein interactions. CircRNAs play a crucial role in controlling gene expression and are essential for biological development and illness detection, as demonstrated by their roles as miRNA sponges, endogenous RNAs, and potential biomarkers. Insulin resistance is caused by damage to ß-cells in the pancreatic islets, which reduces the body's response to the hormone insulin. This reduction in insulin response hinders glucose from entering cells and providing energy for critical processes. As a result, insulin-resistant cells elevate blood sugar levels, leading to diabetes. Diabetes, in turn, increases the risk of heart disease and stroke, which can damage the heart and arteries. Additionally, an excess of insulin can impact the brain's chemical balance, contributing to the development of Alzheimer's disease. Furthermore, oxidative stress created by damaged pancreatic cells during high blood sugar conditions may lead to the destruction of brain cells and the onset of Alzheimer's disease. The hypothesis of this review is to provide an overview of the most dominant ciRS-7 circRNA identified in pancreatic islet cell dysfunction and neurologic disorders, such as Alzheimer's disease. By considering ciRS-7 circRNA as a potential biomarker for diabetes, early detection and treatment of diabetes may be facilitated, potentially reducing the risk of Alzheimer's disease onset in the future.

Performance evaluation of Monaco radiotherapy treatment planning system using CIRS Thorax Phantom: Dosimetric assessment of flattened and non-flattened photon beams.

Aim: The present study was undertaken to evaluate the performance of different algorithms for flattening filter-free (FFF) and flattened (FF) photon beams in three different in-homogeneities. Materials and Method: Computed tomography (CT) image sets of the CIRS phantom maintained in the SAD setup by placing the ionization chamber in the lung, bone, and tissue regions, respectively, were acquired. The treatment planning system (TPS) calculated and the ionization chamber measured the doses at the center of the chamber (in the three mediums) were recorded for the flattened and non-flattened photon beams. Results: The results were reported for photon energies of 6 MV, 10 MV, 15 MV, 6 FFF, and 10 FFF of field sizes 5 × 5 cm2, 10 × 10 cm2, and 15 × 15 cm2. In the bone inhomogeneity, the pencil beam algorithm predicted that the maximum dose variation was 4.88% of measured chamber dose in 10-MV photon energy for the field size 10 × 10 cm2. In water inhomogeneity, both the collapsed cone and Monte Carlo algorithm predicted that the maximum dose variation was ± 3% of measured chamber dose in 10-MV photon energy for the field size 10 × 10 cm2 and in 10-MV FFF photon energy for the field size 5 × 5 cm2, whereas in lung inhomogeneity, the pencil beam algorithm predicted that the highest dose variation was - 6.9% of measured chamber dose in 10-MV FFF photon energy for the field size 5 × 5 cm2. Conclusion: FF and FFF beams performed differently in lung, water, and bone mediums. The assessment of algorithms was conducted using the anthropomorphic phantom; therefore, these findings may help in the selection of appropriate algorithms for particular clinical settings in radiation delivery.

Pulmonary Rehabilitation Outcomes of Post-Acute COVID-19 Patients during Different Waves of the Pandemic.

(1) Background: Between the beginning of the coronavirus pandemic and summer 2022, we distinguished four pandemic waves, with different characteristics of the affected patients. This study investigated the impact of patient characteristics on the outcome of inpatient pulmonary rehabilitation (PR). (2) Methods: Using a prospective approach, the characteristics of post-acute COVID-19 patients of the different waves who participated in inpatient PR were compared based on their assessments and results collected as part of PR (Cumulative Illness Rating Scale (CIRS), six-minute walk test (6-MWT), Pulmonary Function Testing (PFT), and Functional Independent Measurement (FIM). (3) Results: A total of 483 patients were included in the analysis (Wave 1 n = 51, Wave 2 n = 202, Wave 3 n = 84, Wave 4 n = 146). Compared to Wave 3 + 4, patients of Wave 1 + 2 were older (69 vs. 63 years; p < 0.001), had a significantly lower CIRS (13.0 vs. 14.7 points; p = 0.004), had significant better PFT (FVC: 73 vs. 68%pred; p = 0.009; DLCOSB: 58 ± 18 vs. 50 ± 17%pred; p = 0.001), and showed significantly more comorbidities (2.0 vs. 1.6 n/pers.; p = 0.009). Wave 3 + 4 showed significantly greater improvements according to the 6-MWT (147 vs. 188 m; p < 0.001) and the FIM (5.6 vs. 21.1 points; p < 0.001). (4) Conclusions: Patients of the COVID-19 infection waves differed significantly according to their anthropometric data, incidence of comorbidities, and impact of the infection. All cohorts achieved clinically relevant and significant functional improvements during PR, with significant higher improvements in Wave 3 + 4.

Circular RNA ciRS-7 affects the propagation of Cryptosporidium parvum in HCT-8 cells via regulating miR-135a-5p/stat1 axis.

Cryptosporidium spp. are protozoan parasites that mainly inhabit intestinal epithelial cells, causing diarrheal diseases in humans and a great number of animals. Cryptosporidium parvum is the most common zoonotic species, responsible for nearly 45% of human cryptosporidiosis worldwide. Understanding the interaction mechanisms between C. parvum and host gastrointestinal epithelial cells has significant implications to control cryptosporidiosis. One up-regulated circRNA ciRS-7 was found previously by our group to promote in vitro propagation of C. parvum in HCT-8 cells. In the present study, miR-135a-5p, was found to be a miRNA target of ciRS-7. Cryptosporidium parvum infection induced significantly down-regulation of miR-135a-5p and dramatic up-regulation of its potential target stat1 gene at mRNA and protein levels. Dual luciferase reporter assays validated the physical interactions between miR-135a-5p and stat1, and between ciRS-7 and miR-135a-5p. Further study revealed that ciRS-7 could sponge miR-135a-5p to positively regulate the protein levels of STAT1 and phosphorylated STAT1 (p-STAT1) and thus promote C. parvum propagation in HCT-8 cells. Our findings further reveal the mystery of regulatory roles of host circRNAs during Cryptosporidium infection, and provide a novel insight to develop strategies to control cryptosporidiosis.

Breviscapine Combined with BMSCs Reduces Aß Deposition in Rat with Alzheimer's Disease by Regulating Circular RNA ciRS-7.

AIMS: This study aimed to clarify that breviscapine combined with bone marrow mesenchymal stem cells (BMSCs) treatment can reduce Aß deposition in Alzheimer's disease (AD) patients. BACKGROUND: AD is a common degenerative disease of the central nervous system. Aß protein deposition in the cerebral cortex and hippocampus causes neuronal peroxidation damage, synaptic dysfunction, neuroinflammation, and nerve cell apoptosis, and ultimately leads to AD. OBJECTIVE: To investigate whether breviscapine combined with BMSCs treatment can reduce Aß deposition in AD. METHODS: The AD rat model was successfully induced by Aß1-42. The expression of protein and mRNA was detected by western blot and reverse transcription-quantitative PCR (RT-qPCR), respectively. RESULTS: In AD rat brain tissue, the expression of circular RNA ciRS-7 (ciRS-7), ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), and NF-kappaB p65 was significantly downregulated, and the expression of ß-amyloid precursor protein (APP), ß-site APPcleaving enzyme 1 (BAEC1), and Aß was upregulated. The expression of ciRS-7, UCHL1, and p65 was significantly upregulated after breviscapine or BMSCs treatment, and there was increased APP and BAEC1 degradation. Notably, breviscapine combined with BMSCs treatment was more effective than either treatment alone. In SH-SY5Y cells, overexpression of ciRS-7 reduced Aß deposition by upregulating UCHL1 to degrade APP and BAEC1, but these effects were reversed with inhibition of NF-kB signaling. Finally, knockdown of ciRS-7 elevated Aß, APP, and BAEC1 expression in each group of rats compared with the control. CONCLUSION: Breviscapine combined with BMSCs treatment can reduce Aß deposition in AD rats and promote the degradation of APP and BAEC1 by activating NF-kB to promote UCHL1 expression.

Circular RNA ciRS-7 promotes laryngeal squamous cell carcinoma development by inducing TGM3 hypermethylation via miR-432-5p/DNMT3B axis.

OBJECTIVE: This work is to explore the mechanism by which circular RNA ciRS-7 affects laryngeal squamous cell carcinoma (LSCC). METHODS: ciRS-7 expression in LSCC tissues was detected by qRT-PCR, and the association between ciRS-7 with clinicopathological features of LSCC patients was evaluated. HN-4 and UM-SCC-10A cells were transfected or cotransfected with si-ciRS-7, miR-432-5p inhibitor, LV-DNMT3B or si-TGM3. Then, the viability and aggressive nature of the cells were tested. The binding site between ciRS-7 and miR-432-5p or between miR-432-5p and DNMT3B was predicted and the targeting relationship was identified. The specific binding between ciRS-7 and miR-432-5p was further verified by AGO2 RIP assay. HN-4 cells transfected with si-ciRS-7 was injected into nude mice to induce xenograft tumors. RESULTS: Higher ciRS-7 expression in LSCC tissues was closely associated with higher clinical stage, and exacerbated infiltration and lymph node metastasis in LSCC patients. Silencing ciRS-7 inhibited LSCC cell viability, epithelial-mesenchymal transition (EMT), and promoted the apoptosis. When miR-432-5p was inhibited or DNMT3B was overexpressed, the growth and EMT of LSCC cells were stimulated despite ciRS-7 silencing. Downregulation of ciRS-7 restrained the growth of xenograft tumors in vivo. CONCLUSION: ciRS-7 promotes the progression of LSCC through increasing TGM3 methylation via miR-432-5p/DNMT3B axis.

Coexisting conditions and concomitant medications do not affect venetoclax management and survival in chronic lymphocytic leukemia.

Background: The question of which parameters may be informative on venetoclax outcome in chronic lymphocytic leukemia (CLL) is still unclear. Furthermore, the choice to treat with venetoclax can be challenging in patients with baseline characteristics or comorbidities that may potentially favor some specific adverse events. Objectives: This study was aimed to evaluate whether age, fitness status, patients'/disease characteristics, or concomitant medications may predict outcomes in CLL patients receiving venetoclax. Design: Retrospective observational study. Methods: Impact of age, presence of Cumulative Illness Rating Scale (CIRS) >6 or severe organ impairment (CIRS3+), Eastern Cooperative Oncology Group-Performance Status (ECOG-PS), renal function, and concomitant medications were retrospectively analyzed on treatment management (definitive discontinuation due to toxicity, discontinuation due to toxicity, Tox-DTD; permanent dose reduction, PDR) and survival [progression free survival (PFS), event free survival (EFS), overall survival (OS)] in unselected patients receiving venetoclax monotherapy in common practice. Results: A total of 221 relapsed/refractory patients were included. Tox-DTD and PDR were reported in 5.9% and 21.7%, respectively, and were not influenced by any fitness parameter, age, number or type of concomitant medication, baseline neutropenia, or impaired renal function. None of these factors were associated with tumor lysis syndrome (TLS) development. Age and coexisting conditions had no influence on PFS and EFS. At univariate analysis, OS was significantly shorter only in patients with ECOG-PS >1 (p < 0.0001) and elderly (⩾65 years) with CIRS >6 (p = 0.014) or CIRS3+ (p = 0.031). ECOG-PS >1 retained an independent role only for EFS and OS. While Tox-DTD affected all survival outcomes, no differences in PFS were reported among patients permanently reducing dose or interrupting venetoclax for > 7 days. Conclusion: Clinical outcome with venetoclax is not influenced by comorbidities, patients' clinical characteristics, or concomitant medications. Differently from other targeted therapies, this demonstrates that, except ECOG-PS, none of the parameters generally considered for treatment choice, including baseline neutropenia or impaired renal function, should rule the decision process with this agent. Anyway, if clinically needed, a correct drug management does not compromise treatment efficacy and may avoid toxicity-driven discontinuations. Plain Language Summary: Chapter 1: Why was this study done? Chapter 2: Which are the main findings of the study? Chapter 3: How these findings may impact on clinical practice? Coexisting conditions and concomitant medications do not affect venetoclax management and survival in chronic lymphocytic leukemia • The question of which parameters may be informative on venetoclax outcome in chronic lymphocytic leukemia is still unclear. Furthermore, the choice to treat with venetoclax can be challenging in patients with baseline characteristics or comorbidities that may potentially favor some specific adverse events (e.g. compromised renal function or baseline neutropenia).• In our large series of patients treated outside of clinical trials, we demonstrated that neither age, fitness, comorbidities nor concomitant medications impact on venetoclax management and survival. Importantly, patients presenting with baseline neutropenia or impaired renal function did not have a higher rate of dose reductions or toxicity-driven discontinuations, thus further underlining that venetoclax may be safely administered even in those categories with no preclusions.• Differently from other targeted agents, our data demonstrate that none of the baseline factors commonly considered in treatment decision process retains a role with venetoclax. Finally, permanent dose reductions and temporary interruptions did not adversely impact PFS suggesting that, if clinically needed, a correct drug management should be adopted with no risk of compromising venetoclax efficacy.

[Clinical significance of CIRS-G comorbid status assessment in patients with localized prostate cancer.]

Among the male population, one of the most common cancers is prostate cancer. The predominant number of patients suffering from this pathology are patients of the older age group. Today, modern medicine has a large number of methods of radical treatment of prostate cancer with good survival rates. However, elderly and senile patients are quite difficult to treat surgically due to the presence of comorbidity. Any concomitant pathology should be compensated in time in the preoperative period in order to achieve the maximum possible positive clinical results after surgery.

Circulating ciRS-7 as a potential non-invasive biomarker for epithelial ovarian cancer: An investigative study.

Background: Ovarian cancer (OC) is the most common malignant neoplasm of the female reproductive system in developed countries. Early detection, diagnosis and prognosis are particularly important to OC. The potential of circulating circular RNAs (circRNAs) as non-invasive biomarkers of various tumors has been especially described in recent years. The aim of this study was to explore the diagnostic and prognostic value of circulating cirRS-7 in patients with epithelial ovarian cancer (EOC). Methods: Pre- and postoperative plasma samples from 111 EOC patients (47 cases with FIGO stage IA-IIB and 64 cases with FIGO stage IIB-IV) and healthy female volunteers was collected. Circulating ciRS-7 and hsa-miR-7-5p was analyzed using reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of circulating cirRS-7 as biomarker was estimated by the Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) and Kaplan-Meier analysis. Results: The preoperative expression levels of circulating ciRS-7 were increased in plasma of EOC FIGO stage I-IV patients than in the healthy controls (p < 0.001). However, the expression levels of ciRS-7 in the postoperative period were significantly lower in EOC FIGO stage IIA-IIA patients than healthy controls and EOC FIGO stage IIB-IV patients (p < 0.05, p < 0.001). The AUC of ciRS-7 for diagnosing EOC FIGO stage I-IV patients in pre-and postoperative periods was 0.90, 0.92, 0.84, 0.88, 0.58 and 0.86, respectively. Higher circulating ciRS-7 expression is associated with lymph node invasion, FIGO stage, distant metastasis, and worse overall survival (OS) of patients. Moreover, multivariate Cox analysis showed that higher circulating ciRS-7 was an independent predictor of OS in EOC FIGO stage IIB-IV patients. In addition, in plasma of EOC patients, ciRS-7 negatively correlated with has-miR-7-5p in pre-and postoperative periods (p < 0.001). Conclusions: Circulating ciRS-7 levels in plasma can be considered a potential candidate biomarker for diagnosing EOC patients. Dysregulation of ciRS-7 may participate in the molecular mechanism of EOC through hsa-miR-7-5p sponging.

Domestication and improvement genes reveal the differences of seed size- and oil-related traits in soybean domestication and improvement.

To address domestication and improvement studies of soybean seed size- and oil-related traits, a series of domesticated and improved regions, loci, and candidate genes were identified in 286 soybean accessions using domestication and improvement analyses, genome-wide association studies, quantitative trait locus (QTL) mapping and bulked segregant analyses in this study. As a result, 534 candidate domestication regions (CDRs) and 458 candidate improvement regions (CIRs) were identified in this study and integrated with those in five and three previous studies, respectively, to obtain 952 CDRs and 538 CIRs; 1469 loci for soybean seed size- and oil-related traits were identified in this study and integrated with those in Soybase to obtain 433 QTL clusters. The two results were intersected to obtain 245 domestication and 221 improvement loci for the above traits. Around these trait-related domestication and improvement loci, 7 domestication and 7 improvement genes were found to be truly associated with these traits, and 372 candidate domestication and 87 candidate improvement genes were identified using gene expression, SNP variants in genome, miRNA binding, KEGG pathway, DNA methylation, and haplotype analysis. These genes were used to explain the trait changes in domestication and improvement. As a result, the trait changes can be explained by their frequencies of elite haplotypes, base mutations in coding region, and three factors affecting their expression levels. In addition, 56 domestication and 15 improvement genes may be valuable for future soybean breeding. This study can provide useful gene resources for future soybean breeding and molecular biology research.

How to Improve the Drafting of Health Profiles.

Delineating patients' health profiles is essential to allow for a proper comparison between medical care and its results in patients with comorbidities. The aim of this work was to evaluate the concordance of health profiles outlined by ward doctors and by epidemiologists and the effectiveness of training interventions in improving the concordance. Between 2018 and 2021, we analyzed the concordance between the health profiles outlined by ward doctors in a private hospital and those outlined by epidemiologists on the same patients' medical records. The checks were repeated after training interventions. The agreement test (Cohen's kappa) was used for comparisons through STATA. The initial concordance was poor for most categories. After our project, the concordance improved for all categories of CIRS. Subsequently, we noted a decline in concordance between ward doctors and epidemiologists for CIRS, so a new training intervention was needed to improve the CIRS profile again. Initially, we found a low concordance, which increased significantly after the training interventions, proving its effectiveness.