Arquivar atividades em termos de autenticidade de documentos eletrônicos e variação do número de cópias

The article is devoted to the problems of archive activity during the digital era, which are conditioned from the authors' point of view by the introduction of electronic documents that have changed the content of paperwork and archiving key categories - authenticity and copy number variation, as well as related originality and authenticity. The technologies of work in the archive, always considered as a unique system of originals are based on the traditional understanding of these categories. Using the method of expert assessments during the determination of key category content, the authors conclude that the current activity of the archives is aimed at copy production activity increase, their management and the provision of authenticity, reliability, integrity and suitability for use. Nowadays the issue of document archiving requires the consolidation of state and non-state structure efforts to develop a new attitude to the authenticity of electronic documents, to change the usual nature of archival institution interaction with users and interested citizens, state authorities and administration, law enforcement and judicial system.El artículo está dedicado a los problemas de la actividad de archivo durante la era digital, que están condicionados desde el punto de vista de los autores por la introducción de documentos electrónicos que han cambiado el contenido del papeleo y las categorías clave de archivo: autenticidad y variación del número de copias, como así como la originalidad y autenticidad relacionadas. Las tecnologías de trabajo en el archivo, siempre consideradas como un sistema único de originales, se basan en el entendimiento tradicional de estas categorías. Usando el método de evaluaciones de expertos durante la determinación del contenido de la categoría clave, los autores concluyen que la actividad actual de los archivos está dirigida a aumentar la actividad de producción de copias, su gestión y la provisión de autenticidad, confiabilidad, integridad y adecuación para su uso. Hoy en día, el tema del archivo de documentos requiere la consolidación de los esfuerzos de la estructura estatal y no estatal para desarrollar una nueva actitud hacia la autenticidad de los documentos electrónicos, para cambiar la naturaleza habitual de la interacción de la institución archivística con los usuarios y ciudadanos interesados, las autoridades estatales, la administración y la ley.O artigo é dedicado aos problemas da atividade de arquivo durante a era digital, eles são condicionados a partir do ponto de vista dos autores para a introdução de documentos eletrônicos que mudaram o conteúdo de documentos e categorias de arquivos-chave: autenticidade e variação do número de cópias, bem como a originalidade e autenticidade relacionadas. Tecnologias de trabalho no arquivo, sempre considerado como um único sistema original, com base no entendimento tradicional destas categorias. Usando o método de avaliações de peritos para a determinação da categoria-chave, os autores concluem que a atividade de arquivos atual visa aumentar cópias atividade de produção, gestão e prestação de autenticidade, confiabilidade, integridade e adequação para uso. Hoje, a questão do arquivamento de documentos requer a consolidação dos esforços de estruturas estatais e não-estatais para desenvolver uma nova atitude em relação à autenticidade dos documentos eletrônicos, para mudar a natureza habitual da interação da instituição de arquivo utilizadores e cidadãos interessados, autoridades estatais, administração e direito

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Neuronal Hyperactivation in EEG Data during Cognitive Tasks Is Related to the Apolipoprotein J/Clusterin Genotype in Nondemented Adults

The clusterin (CLU) rs11136000 CC genotype is a probable risk factor for Alzheimer’s disease (AD). CLU, also known as the apolipoprotein J gene, shares certain properties with the apolipoprotein E (APOE) gene with a well-established relationship with AD. This study aimed to determine whether the electrophysiological patterns of brain activation during the letter fluency task (LFT) depend on CLU genotypes in adults without dementia. Previous studies have shown that LFT performance involves activation of the frontal cortex. We examined EEG alpha1 and alpha2 band desynchronization in the frontal regions during the LFT in 94 nondemented individuals stratified by CLU (rs11136000) genotype. Starting at 30 years of age, CLU CC carriers exhibited more pronounced task-related alpha2 desynchronization than CLU CT&TT carriers in the absence of any differences in LFT performance. In CLU CC carriers, alpha2 desynchronization was significantly correlated with age. Increased task-related activation in individuals at genetic risk for AD may reflect greater “effort” to perform the task and/or neuronal hyperexcitability. The results show that the CLU genotype is associated with neuronal hyperactivation in the frontal cortex during cognitive tasks performances in nondemented individuals, suggesting systematic vulnerability of LFT related cognitive networks in people carrying unfavorable CLU alleles

Safety of Pembroria® during non-medical switching from Keytruda® in patients with advanced malignant neoplasms of various localizations: the REFLECTION real-world study

Background. Post-registration observational studies with switching therapy from the original drug to a biosimilar for non-medical indications allow us to assess the safety and effectiveness of this type of switching in real clinical practice. Aim. Evaluation of the safety and effectiveness of non-medical switching from the original drug Keytruda® to the biosimilar drug Pembroria® in patients with various oncological pathologies in real clinical practice (REFLECTION). Materials and methods. A retrospective analysis of data from electronic medical records from 21 medical institutions of the Russian Federation for the period 2020–2023 was carried out. Data were included from patients with cancer of various locations who received at least 2 injections of Keytruda® followed by switching to Pembroria® for non-medical indications (at least 2 injections). Primary criteria: incidence of immune-mediated adverse reactions (ImARs) of any severity. Secondary indicators: incidence of ImARs of various degrees of severity and infusion reactions, frequency of objective response rate (according to RECIST 1.1 criteria). Results. The analysis included data from 382 patients (male/female 200/182, median age 62 years) with NSCLC (24.1%), RCC (23.3%), melanoma (20.4%) and cancer of other localization. Patients received Keytruda® on 1st and 2nd lines (54.2 and 25.4% of patients, respectively), on 3 or 4 lines (14.1%), or as part of adjuvant therapy (6.3%). 50.5% of patients received pembrolizumab as monotherapy. The median number of administrations was 7.0 and 5.0 for Keytruda® and Pembroria®, respectively. ImARs were registered in 44 (11.5%) patients (60 ImARs), including 40 ImARs in 35 (9.2%) patients while using Keytruda® and 20 ImARs in 17 (2.4%) patients with Pembroria®. The most common ImARs were hypothyroidism, hyperthyroidism, and hepatitis; the frequency of these ImARs was higher with Keytruda® (EAER for hypothyroidism 0.00422 and 0.00144, for hepatitis – 0.00124 and 0.00096, respectively). All 5 reported cases of hyperthyroidism in patients on Keytruda® (EAER 0.00124), were resolved before switching to Pembroria®. No infusion-related reactions or deaths due to ImARs have been reported. The objective response rate was comparable – 104 (32.6%) and 90 (29.2%) patients оn Keytruda® and Pembroria® therapy, respectively. Most patients maintained disease control after switching to Pembroria® [progression was recorded in 29 (9.4%) patients after switching to a biosimilar]. Conclusion. The safety profiles of Keytruda® and Pembroria® were satisfactory and comparable in this study. Switching from therapy with Keytruda® to Pembroria® is not accompanied by an increase in the frequency or severity of ImARs. Switching from Keytruda® to Pembroria® maintains disease control in most patients

β-Hydroxybutyrate suppresses colorectal cancer.

Colorectal cancer (CRC) is among the most frequent forms of cancer, and new strategies for its prevention and therapy are urgently needed1. Here we identify a metabolite signalling pathway that provides actionable insights towards this goal. We perform a dietary screen in autochthonous animal models of CRC and find that ketogenic diets exhibit a strong tumour-inhibitory effect. These properties of ketogenic diets are recapitulated by the ketone body β-hydroxybutyrate (BHB), which reduces the proliferation of colonic crypt cells and potently suppresses intestinal tumour growth. We find that BHB acts through the surface receptor Hcar2 and induces the transcriptional regulator Hopx, thereby altering gene expression and inhibiting cell proliferation. Cancer organoid assays and single-cell RNA sequencing of biopsies from patients with CRC provide evidence that elevated BHB levels and active HOPX are associated with reduced intestinal epithelial proliferation in humans. This study thus identifies a BHB-triggered pathway regulating intestinal tumorigenesis and indicates that oral or systemic interventions with a single metabolite may complement current prevention and treatment strategies for CRC

Prevalence and Risk Factors of Post-COVID-19 Condition in Adults and Children at 6 and 12 Months After Hospital Discharge: A Prospective, Cohort Study in Moscow (Stop COVID)

Background: Previous studies assessing the prevalence of COVID-19 sequelae in adults and children were performed in the absence of an agreed definition. We investigated prevalence of post-COVID-19 condition (PCC) (WHO definition), at 6- and 12-months follow-up, amongst previously hospitalised adults and children and assessed risk factors. Methods: Prospective cohort study of children and adults with confirmed COVID-19 in Moscow, hospitalised between April and August, 2020. Two follow-up telephone interviews, using the International Severe Acute Respiratory and Emerging Infection Consortium survey, were performed at 6 and 12 months after discharge. Results: One thousand thirteen of 2509 (40%) of adults and 360 of 849 (42%) of children discharged participated in both the 6- and 12-month follow-ups. PCC prevalence was 50% (95% CI 47–53) in adults and 20% (95% CI 16–24) in children at 6 months, with decline to 34% (95% CI 31–37) and 11% (95% CI 8–14), respectively, at 12 months. In adults, female sex was associated with PCC at 6- and 12-month follow-up (OR 2.04, 95% CI 1.57 to 2.65) and (OR 2.04, 1.54 to 2.69), respectively. Pre-existing hypertension (OR 1.42, 1.04 to 1.94) was associated with post-COVID-19 condition at 12 months. In children, neurological comorbidities were associated with PCC both at 6 months (OR 4.38, 1.36 to 15.67) and 12 months (OR 8.96, 2.55 to 34.82) while allergic respiratory diseases were associated at 12 months (OR 2.66, 1.04 to 6.47). Conclusions: Although prevalence of PCC declined one year after discharge, one in three adults and one in ten children experienced ongoing sequelae. In adults, females and persons with pre-existing hypertension, and in children, persons with neurological comorbidities or allergic respiratory diseases are at higher risk of PCC