Spatially preserved multi-region transcriptomic subtyping and biomarkers of chemoimmunotherapy outcome in extensive-stage small cell lung cancer.

BACKGROUND: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. PATIENTS AND METHODS: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm phase IIIb studies evaluating front-line chemoimmunotherapy in Spain: n=32 from the IMfirst trial, and n=26 from the CANTABRICO trial. We utilized the GeoMxTM DSP system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). RESULTS: Subtype distribution was similar between both cohorts, except for SCLC-P, not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple co-existing transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity were not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ³12 months) contained an IFNg-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. CONCLUSIONS: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Pre-existing IFNg-driven immunity and mitochondrial metabolism seem correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.

Spiritual well-being, faith, meaning in life, peace, and purpose in life for cancer-related fatigue: systematic review with meta-analysis and meta-regressions.

BACKGROUND: Cancer-related fatigue is associated with spiritual distress. Spiritual well-being, characterized by the presence of factors such as meaning in life or purpose in life, seems to play an important role in the management of symptoms of cancer. Currently, the number of studies evaluating the association between cancer-related fatigue and spiritual well-being is increasing and no systematic review has been conducted. AIM: To summarize the association between cancer-related fatigue and spiritual well-being, faith, meaning in life, peace, and purpose in life. DESIGN: A systematic review with meta-analysis. DATA SOURCES: The CINAHL, Embase, PsycINFO, and PubMed databases were searched from inception to 9 October 2023. We considered studies evaluating the cross-sectional or longitudinal association between cancer-related fatigue and the spiritual factors above mentioned. The Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies and the Quality in Prognosis Studies tool assessed the methodological quality of cross-sectional and longitudinal studies, respectively. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system rated the certainty of evidence. Meta-analyses, meta-regressions, subgroup meta-analyses, and sensitivity analyses were conducted. RESULTS: A total of 13 studies were included and no longitudinal findings were found. One meta-analysis showed that cancer-related fatigue may be negatively correlated with spiritual well-being (r = - 0.37 (95%CI - 0.44 to - 0.28) p < 0.01). In addition, another meta-analysis found the correlation between cancer-related fatigue and faith was not statistically significant (r = - 0.25 (95%CI - 0.66 to 0.28) p = 0.36). CONCLUSIONS: Cancer-related fatigue may be correlated with spiritual well-being. However, the certainty of evidence was very low across the meta-analyzed outcomes. IMPLICATIONS FOR CANCER SURVIVORS: A negative correlation was observed between spiritual well-being and cancer-related fatigue.

Shipwrecked on the Rock, or Not Quite: Gypsophytes and Edaphic Islands.

Species-area relationships (SAR) constitute a key aspect of ecological theory and are integral to other scientific disciplines, such as biogeography, which have played a crucial role in advancing biology. The theory of insular biogeography provides a clear example. This theory initially expanded from true islands to other types of systems characterized by their insularity. One such approach was linked to geoedaphic islands, as seen in gypsum outcrops. While these continental areas have been considered insular systems, only limited and mostly indirect evidence thereof has been provided. This study utilized SAR to advance the understanding of gypsum outcrops as insular continental territories. It is hereby hypothesized that gypsum outcrops are edaphic islands, although their insular nature depends on the different functional or ecological plant types, and this nature will be reflected in the potential Arrhenius model z values. The results obtained support both hypotheses and provide insight into the ecological factors that help interpret the insularity of these areas. This interpretation goes beyond their mere extent and the distance among outcrops, emphasizing the importance of environmental filters. Said filters vary in permeability depending on the degree of gypsophily, or preference for gypsum, exhibited by different species.

RhoA/rho kinase pathway activation in age-associated endothelial cell dysfunction and thrombosis.

The small GTPase RhoA and the downstream Rho kinase (ROCK) regulate several cell functions and pathological processes in the vascular system that contribute to the age-dependent risk of cardiovascular disease, including endothelial dysfunction, excessive permeability, inflammation, impaired angiogenesis, abnormal vasoconstriction, decreased nitric oxide production and apoptosis. Frailty is a loss of physiological reserve and adaptive capacity with advanced age and is accompanied by a pro-inflammatory and pro-oxidative state that promotes vascular dysfunction and thrombosis. This review summarises the role of the RhoA/Rho kinase signalling pathway in endothelial dysfunction, the acquisition of the pro-thrombotic state and vascular ageing. We also discuss the possible role of RhoA/Rho kinase signalling as a promising therapeutic target for the prevention and treatment of age-related cardiovascular disease.

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in cN0 Breast Cancer: Impact of HER2-Positive Status on Survival.

Objective: High rates of negative sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) breast cancer (BC) after neoadjuvant chemotherapy (NAC) have been described. These results are associated with triple-negative (TNBC) and human epidermal growth factor receptor 2 (HER2+) subtypes achieving pathologic complete response (pCR). This study evaluates predictive variables and survival in order to assess the possible omission of SLNB after NAC. Materials and Methods: Prospective study of women with cN0 BC treated with NAC and subsequent surgery, between April 2010 and May 2021. SLNB technique included, performing axillary lymphadenectomy in the absence of detection or SLNB-positivity. Multivariable logistic regression was used for analysis of NAC-response and SLNB-results in molecular subtypes: HR-/HER2+, TNBC, HR+/HER2- and HR+/HER2+. Kaplan-Meyer and log-rank were used for survival analysis. Results: A total of 179 patients (50.5±10.1 years) were included. Of these, 39.7% achieved pCR (ypT0/Tis). HR-negative subtypes had higher pCR rates (HR-/HER2+: 59.4%; TNBC: 53.4%), with no cases of SLNB-positive. With residual disease, HR-/HER2+ and TNBC showed low rates of SLNB-positivity (6.7% and 10.3%) versus HR+ (HR+/HER2+: 20%; HR+/HER2-: 44%; p<0.001). Multivariable analysis identified independent predictors of SLNB-negativity (p<0.0001) to be: HR- [odds ratio (OR)=0.15; 95% confidence interval (CI): 0.06-0.37; p = 0.0001], HER2+ (OR=0.34; 95% CI: 0.14-0.81; p = 0.015) and high-grade Nottingham (OR=0.42; 95% CI: 0.18-0.99; p = 0.048). Disease-free survival showed worse outcomes with SLNB-positivity (p<0.0001), HR+/HER2- (p = 0.0277), larger tumor size (p = 0.002) and residual disease after NAC (p<0.0001). Conclusion: Patient selection based on NAC response, molecular subtype, and survival outcomes is a priority for establishing individualized therapeutic strategies after NAC. Molecular subtypes with higher pCR rates and lower rates of SLNB-positivity could benefit from non-invasive strategies that include omission of SLNB.

Long-term effects of a 6-week power-based resistance training and fast walking interval training program on physical function, muscle power, disability and frailty in pre-frail and frail older adults.

INTRODUCTION: Concurrent training has been shown to be a beneficial approach to improve overall health status in older adults. However, little is known about the adaptations of this type of training in the long term (i.e., after cessation of exercise), even less in older people affected by frailty syndrome.Therefore, this study aimed i) to assess the effects of a 6-week concurrent training program composed of power-oriented resistance training (RT) and fast walking interval training (FWIT) on physical function, muscle power, disability in activities of daily living and frailty in pre-frail and frail older people, and ii) to assess the effects of a 6-month detraining period on these outcomes. METHODS: A total of 59 pre-frail and frail older adults (>75 years old; Frailty Phenotype >1) were allocated into intervention (INT; n=32; 81.8 years; 21 women) or control (CON; n=27; 82.5 years; 19 women) groups. Primary outcomes of this study were Short Physical Performance Battery (SPPB), relative sit-to-stand (STS) power, Barthel index, Lawton scale and Frailty Phenotype. Assessments were performed at baseline (PRE), after the concurrent training programme (POST) and after 6 months of follow-up (DET) in both groups. Mixed model repeated measures ANOVA with Bonferroni's post hoc tests was used. RESULTS: Immediately after the intervention (∆= POST-PRE), INT improved SPPB (∆=3.0 points; p<0.001), relative STS power (∆=0.87 W·kg-1; p<0.001) and reduced their frailty levels (∆=-1.42 criteria; p<0.001), while no changes were observed in CON. After 6 months of detraining (∆= DET-PRE), INT showed higher SPPB (∆=2.2 points; p<0.001), higher relative STS power (∆=0.73 W·kg-1; p<0.001) and lower frailty (∆=-1.24 criteria; p<0.001) values than those reported at baseline, which were significantly different than those reported by CON. Both, Barthel index and Lawton scale values were not modified during the study in either group. CONCLUSIONS: The 6-week concurrent training program improved physical function, muscle power and reduced frailty in pre-frail and frail older people and these improvements were maintained above baseline levels after 6 months of detraining. However, due to the individual variability found, future studies of long-term responders vs. non-responders in frail populations are required.

Vaccination in pregnancy. Consensus document of the CAV-AEP and the SEGO.

During pregnancy, physiological changes in the immune response make pregnant women more susceptible to serious infection, increasing the risk for the mother as well as the foetus, newborn and infant. All women should be correctly and fully vaccinated as they enter their reproductive years, especially against diseases such as tetanus, hepatitis B, measles, rubella and varicella. In addition to the recommended vaccines, in risk situations, inactivated vaccines could be administered to women who were not correctly vaccinated before, while attenuated vaccines are contraindicated. Despite the fact that vaccination during pregnancy is a very important preventive measure and the existing recommendations from public health authorities, scientific societies and health professionals, the vaccination coverage could clearly be improved, especially against influenza and SARS-CoV-2, so any health professional involved in the care of pregnant women should proactively recommend these vaccines. The Spanish Association of Pediatrics (AEP), through its Advisory Committee on Vaccines, and the Spanish Society of Gynaecology and Obstetrics (SEGO) recommend vaccination against the following diseases during pregnancy: against influenza and COVID-19, in any trimester of pregnancy and during the postpartum period (up to 6 months post birth) in women not vaccinated during pregnancy; against pertussis, with the Tdap vaccine, between weeks 27 and 36 of gestation (in the CAV-AEP recommendations, preferably between weeks 27 and 28); and against RSV, with RSVPreF, between weeks 24 and 36 of gestation, preferably between weeks 32 and 36.

A systematic review and a comprehensive approach to PhD students' wellbeing.

The pursuit of a doctoral degree is a challenging process that can have a negative impact on the wellbeing of PhD students. Therefore, the aim here is to offer a systematic review of the current state of the literature on wellbeing among PhD students and the variables it involves in order to build an integrative model that will enrich future research. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology for systematic reviews has been used to lay out the process in a flow diagram. We systematically review studies up to 2021 (N = 38) published on the Web of Science and SCOPUS databases. The results show the current state of the literature on wellbeing in PhD students, the characteristics of the studies (location, study design, and sample), how the literature defines the concept, the variables involved, the study limitations, and future perspectives to improve the quality of life of doctoral students. Finally, a comprehensive approach to the topic is presented in an integrative model that encompasses all variables identified in the literature and offers a guide for future research.

Frailty Influences the Relationship between the Soluble Receptor for Advanced Glycation-End Products and Mortality in Older Adults with Diabetes Mellitus.

INTRODUCTION: Frailty is prevalent among older adults with diabetes mellitus. Elevated serum levels of the soluble receptor for advanced glycation-end products (sRAGE) predict mortality in frail older adults. The evidence that sRAGE is also related to higher mortality in older adults with diabetes mellitus is inconsistent. Therefore, this study explored if frailty status influences the relationship between sRAGE and mortality in older adults with this condition. METHODS: We analysed data of 391 participants with diabetes mellitus (median age, 76 years) from four European cohorts enrolled in the FRAILOMIC project. Frailty was evaluated at baseline using Fried's criteria. Serum sRAGE was determined by ELISA. Participants were stratified by frailty status (n = 280 non-frail and 111 frail). Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between sRAGE and mortality. RESULTS: During 6 years of follow-up, 98 participants died (46 non-frail and 52 frail). Non-survivors had significantly higher baseline levels of sRAGE than survivors (median [IQR]: 1,392 [962-2,043] pg/mL vs. 1,212 [963-1,514], p = 0.008). High serum sRAGE (>1,617 pg/mL) was associated with increased mortality in the whole diabetes sample after adjustment for relevant confounders (HR 2.06, 95% CI: 1.36-3.11, p < 0.001), and there was an interaction between sRAGE and frailty (p = 0.006). Accordingly, the association between sRAGE and mortality was stronger in the frail group compared to the non-frail group (HR 2.52, 95% CI: 1.30-4.90, p = 0.006 vs. HR 1.71, 95% CI: 0.91-3.23, p = 0.099, respectively). Likewise, Kaplan-Meier curves showed a significant difference in survival rates between frail participants with high sRAGE and those with low sRAGE (p = 0.001), whereas no survival difference was seen in the non-frail group (p = 0.09). CONCLUSIONS: Frailty status influences the relationship between sRAGE and mortality in older adults with diabetes mellitus. Determination of sRAGE in this population could be a useful tool for risk stratification.

Effect of electric field on physicochemical properties and resistant starch formation in ohmic heating processed corn starch.

This research investigated the impact of ohmic heating (OH) on the physicochemical properties and resistant starch formation in native corn starch. Electric field strengths (EFS) of 50, 75, and 100 V/cm were applied to native starch, at a starch-water ratio of 1:1 w/v. The conductivity of the medium is a crucial factor in ohmic heating. In this study, the conductivity values at 120 °C were measured at 1.5 mS/m. The study revealed two distinct outcomes resulting from the application of different EFS. Firstly, a thermal effect induced gelatinization, resulting in a reduction in the enthalpy of corn starch, an increase in the water absorption index (WAI) and the water solubility index (WSI), and a decrease in peak viscosity. Secondly, a non-thermal effect of OH was observed, leading to the electrolysis of certain starch compounds and water. This electrolysis process generated radicals (-OH) that interacted with starch components, augmenting the percentage of resistant starch. This increase was associated with elevated levels of carbonyl and carboxyl groups at 75 and 100 V/cm.

Recomendaciones SER sobre el tratamiento del síndrome de Behçet refractario / SER recommendations on treatment of refractory Behçet's syndrome

Objetivo: Elaborar recomendaciones multidisciplinares, basadas en la evidencia disponible y el consenso de expertos, para el manejo terapéutico de los pacientes con síndrome de Behçet refractario (difícil de tratar, resistente grave, recidivante grave) al tratamiento convencional. Métodos: Un panel de expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO –paciente, intervención, comparación, outcome o desenlace–. A continuación, se realizaron revisiones sistemáticas; la evaluación de la calidad de la evidencia se realizó siguiendo la metodología del grupo internacional de trabajo Grading of Recommendations, Assessment, Development, and Evaluation. Tras esto, el panel multidisciplinar formuló las recomendaciones. Resultados: Se seleccionaron 4 preguntas PICO relativas a la eficacia y seguridad de los tratamientos farmacológicos sistémicos en los pacientes con síndrome de Behçet con manifestaciones clínicas refractarias a terapia convencional, relacionadas con los fenotipos mucocutáneo y/o articular, vascular, neurológico-parenquimatoso y gastrointestinal. Se formularon un total de 7 recomendaciones estructuradas por pregunta, con base en la evidencia encontrada y el consenso de expertos. Conclusiones: El tratamiento de las manifestaciones clínicas más graves del síndrome de Behçet carece de evidencia científica sólida y no existen documentos de recomendaciones específicas para los pacientes con enfermedad refractaria a la terapia convencional. Con el fin de aportar una respuesta a esta necesidad, se presenta el primer documento de recomendaciones de la Sociedad Española de Reumatología específicas para el abordaje terapéutico de estos pacientes, que servirá de ayuda en la toma de decisiones clínica y la reducción de la variabilidad en la atención.(AU)

Objective: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (difficult to treat, severe resistant, severe relapse) to conventional treatment. Methods: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format –patient, intervention, comparison and outcome–. Systematic reviews of the evidence were conducted; the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations, Assessment, Development, and Evaluation. After that, the multidisciplinary panel formulated the specific recommendations. Results: Four PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with Behçet's syndrome with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. Conclusions: The treatment of most severe clinical manifestations of Behçet's syndrome lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.(AU)

SER recommendations on treatment of refractory Behçet's syndrome.

OBJECTIVE: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (BS) (difficult to treat, severe resistant, severe relapse) to conventional treatment. METHODS: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format (patient, intervention, comparison and outcome). Systematic reviews of the evidence were conducted, the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations Assessment, Development, and Evaluation (GRADE). After that, the multidisciplinary panel formulated the specific recommendations. RESULTS: 4 PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with BS with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. CONCLUSIONS: The treatment of most severe clinical manifestations of BS lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official Recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.

Relationship of endogenous plasma concentrations of ß-hydroxy ß-methyl butyrate (HMB) with frailty in community dwelling older adults with type-2 diabetes mellitus.

BACKGROUND: Supplementation with ß-hydroxy ß-methyl butyrate (HMB) appears to be effective in preserving muscle in older adults. However, the association between endogenously produced HMB with frailty has not been studied in people with chronic disease. OBJECTIVES: The purpose of this study is to explore whether an association exists between endogenous HMB levels and frailty status in older adults with type-2 diabetes mellitus (T2DM). METHODS: Data were taken from the Toledo Study of Healthy Ageing, a community-dwelling aged (65 years+) cohort. Frailty was assessed at baseline and at 2.99 median years according to the Frailty Phenotype (FP) standardized to our population and the Frailty Trait Scale 12 (FTS12). The associations between HMB levels and frailty were assessed using three nested multivariate logistic regressions and segmented by sex. Glucose, HMB and glucose interaction, age and body composition were used as covariables. RESULTS: 255 participants (mean age 75.3 years, 52.94% men) were included. HMB levels showed an inverse cross-sectional association with frailty, which was modified when the interaction term HMB*glucose was included, remaining significant only for FTS12 [OR (95% CI): 0.436 (0.253, 0.751), p-value 0.003]. The association between HMB endogenous levels and FTS12 appears to be independent of sex, in which the association was maintained after adjusting for the covariates. However, there appears to be threshold points for glucose levels, above which the protective effect of HMB is lost: 145.4 mg/dl adjusted by gender for the whole sample and 149.6 mg/dl and 138.9 mg/dl for men and women, respectively. Endogenous HMB levels were not found to be associated with incident frailty. CONCLUSIONS: Cross-sectional analysis revealed that endogenous HMB levels were inversely associated with frailty as assessed by the FTS12 in older people with T2DM. This association was found to be dependent on circulating fasted glucose levels.

How can clinicians enhance self-efficacy beliefs in osteoarthritis? An overview of systematic reviews with meta-analysis.

This overview of reviews aimed to synthesize the effectiveness of non-pharmacological approaches to enhance self-efficacy in people with osteoarthritis. The CINAHL, Embase, PsycINFO, PubMed, SPORTDiscus, and the Cochrane Library databases were searched from inception to December 2023. We considered systematic reviews with meta-analysis of randomized clinical trials evaluating any non-pharmacological intervention. We used AMSTAR 2 to assess the methodological quality of reviews. The overlap between reviews was calculated. We included eight systematic reviews with meta-analysis evaluating 30 different clinical trials. Overall, mind-body exercises, psychological interventions, and self-management strategies may improve arthritis self-efficacy. Specifically, the meta-analyses showed tai chi exercises, coping skills training, and the arthritis self-management program are more effective than controls to enhance arthritis self-efficacy in people with hip and/or knee osteoarthritis. In addition, inconsistent results were detected across meta-analyses regarding the effectiveness of multidisciplinary interventions. Finally, the degree of overlap between all reviews was moderate (CCA = 6%) and many included reviews reported most of the items of AMSTAR 2. Tai chi exercises, coping skills training, and the arthritis self-management program may be beneficial for enhancing arthritis self-efficacy. Open Science Framework Registration: https://doi.org/10.17605/OSF.IO/VX2T6 .

Single-cell dissection of the human motor and prefrontal cortices in ALS and FTLD.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) share many clinical, pathological, and genetic features, but a detailed understanding of their associated transcriptional alterations across vulnerable cortical cell types is lacking. Here, we report a high-resolution, comparative single-cell molecular atlas of the human primary motor and dorsolateral prefrontal cortices and their transcriptional alterations in sporadic and familial ALS and FTLD. By integrating transcriptional and genetic information, we identify known and previously unidentified vulnerable populations in cortical layer 5 and show that ALS- and FTLD-implicated motor and spindle neurons possess a virtually indistinguishable molecular identity. We implicate potential disease mechanisms affecting these cell types as well as non-neuronal drivers of pathogenesis. Finally, we show that neuron loss in cortical layer 5 tracks more closely with transcriptional identity rather than cellular morphology and extends beyond previously reported vulnerable cell types.

Enduring Consensus Guidelines for Cervical Cancer Screening and Management: Introduction to the Scope and Process.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines (Enduring Guidelines) effort is a standing committee to continuously evaluate new technologies and approaches to cervical cancer screening, management, and surveillance. METHODS AND RESULTS: The Enduring Guidelines process will selectively incorporate new technologies and approaches with adequate supportive data to more effectively improve cancer prevention for high-risk individuals and decrease unnecessary procedures in low-risk individuals. This manuscript describes the structure, process, and methods of the Enduring Guidelines effort. Using systematic literature reviews and primary data sources, risk of precancer will be estimated and recommendations will be made based on risk estimates in the context of established risk-based clinical action thresholds. The Enduring Guidelines process will consider health equity and health disparities by assuring inclusion of diverse populations in the evidence review and risk assessment and by developing recommendations that provide a choice of well-validated strategies that can be adapted to different settings. CONCLUSIONS: The Enduring Guidelines process will allow updating existing cervical cancer screening and management guidelines rapidly when new technologies are approved or new scientific evidence becomes available.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. RESULTS: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. CONCLUSIONS: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

Confirmatory Factor Analysis and Gender Invariance of the Coping Strategies Inventory in Academic University Stress / [Análisis factorial confirmatorio e invarianza de género del Inventario de Estrategias de Afrontamiento (CSI) en estrés académico universitario]

Background: Though the Spanish version of the Coping Strategies Inventory (CSI) is frequently used, it has not been subjected to any significant re-evaluation from a psychometric perspective. Method: We analysed CSI data that was focused on an academic stress situation, using a university sample of 874 participants, 50% of each gender. We conducted reliability, confirmatory factor, and factorial invariance across gender analyses. Results: The first-order factorial structure was confirmed, showing an adequate fit for the eight-factor coping strategies model with good reliability indices. Neither the second-order (problem-centred vs. emotion-centred) nor third-order (engagement vs. disengagement) strategies showed an adequate fit. Factorial invariance for gender was confirmed. Conclusions: The theoretical and applied implications of the results are discussed.(AU)

Antecedentes: Aunque la versión española del del Inventario de Estrategias de Afrontamiento (CSI) se usa frecuentemente, no se ha sometido a reevaluación psicométrica. Método: Analizamos datos del CSI aplicados a situaciones de estrés académico utilizando una muestra universitaria de 874 participantes, 50% de cada género. Llevamos a cabo análisis de fiabilidad, confirmatorios y de invarianza factorial por género. Resultados: Se confirmó la estructura factorial de primer orden, mostrando un ajuste adecuado el modelo de 8 estrategias de afrontamiento, con buenos índices de fiabilidad. No mostraron un ajuste adecuado las factorizaciones de segundo orden (centrado en el problema o en la emoción) ni de tercer orden (compromiso o retirada). Se confirmó la invarianza factorial por género. Conclusiones: Se discuten las implicaciones teóricas y aplicadas de los resultados.(AU)

A fuzzy description logic based IoT framework: Formal verification and end user programming.

The Internet of Things (IoT) has become one of the most popular technologies in recent years. Advances in computing capabilities, hardware accessibility, and wireless connectivity make possible communication between people, processes, and devices for all kinds of applications and industries. However, the deployment of this technology is confined almost entirely to tech companies, leaving end users with only access to specific functionalities. This paper presents a framework that allows users with no technical knowledge to build their own IoT applications according to their needs. To this end, a framework consisting of two building blocks is presented. A friendly interface block lets users tell the system what to do using simple operating rules such as "if the temperature is cold, turn on the heater." On the other hand, a fuzzy logic reasoner block built by experts translates the ambiguity of human language to specific actions to the actuators, such as "call the police." The proposed system can also detect and inform the user if the inserted rules have inconsistencies in real time. Moreover, a formal model is introduced, based on fuzzy description logic, for the consistency of IoT systems. Finally, this paper presents various experiments using a fuzzy logic reasoner to show the viability of the proposed framework using a smart-home IoT security system as an example.

Early hospital discharge through prediction of post-thyroidectomy hypoparathyroidism.

INTRODUCTION: Hypoparathyroidism is the most common postsurgical complication of total thyroidectomy. Furthermore, it is the main cause of prolonged hospitalisation after this procedure. OBJECTIVE: To predict the probability of post-thyroidectomy hypocalcaemia according to the levels of intact parathyroid hormone (iPTH), as well as to determine the needs for treatment with exogenous calcium according to the levels of serum calcium (Ca). MATERIALS AND METHODS: Retrospective study was carried out on patients who underwent total thyroidectomy between January 2017 and January 2020 at Los Arcos del Mar Menor University Hospital (HULAMM). iPTH and Ca levels ​​were measured at 4, 24 and 48 h after the surgery. Follow-up was 6 months. RESULTS: Ninety-four patients were operated on. Temporary and permanent postoperative hypoparathyroidism percentages were, respectively, 51.06% and 6.38%. iPTH level 24 h after the procedure was the most reliable predictor of post-thyroidectomy temporary hypoparathyroidism (Area Under the ROC Curve (AUC) = 0.933, p < .001). iPTH levels ​​≥29 pg/mL predicted normal parathyroid metabolism. CONCLUSIONS: The combined values of iPTH and Ca levels 24 h after thyroidectomy seems to be a reliable, safe and efficient method to control the post-thyroidectomy hypoparathyroidism. Our protocol could reduce the hospital stay of patients at low risk of hypocalcaemia, allowing them to be discharged from the hospital on the first postoperative morning and identifying patients at high risk of hypocalcaemia early.