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IntroductionThis study aims to quantify the shear wave speed (SWS) and stiffness of the uterine cervix (close to the internal cervical ostium (IOC) which is the cranial portion of cervix and close to the external cervical ostium (EOC) which is the caudal portion of cervix), caruncular areas, and vulvar labia during the postpartum period in healthy Kivircik ewes by using shear-wave elastography. Power Doppler ultrasonography was performed to evaluate the color pixel percentage (CPP) of the caruncles.MethodsThe study included 13 healthy pregnant Kivircik ewes, which were randomly selected. A total of 12 measurements were taken from the uterine cervix and vulva from the postpartum first day to PP42 (daily for the first week and weekly from PP14 to PP42). However, only eight measurements were obtained from the caruncles because they could not be visible after day 14.ResultsThe time-dependent differences in the widest cross-sectional diameter of the caruncles were statistically significant (p < 0.001) both in ewes giving birth to singletons and twins. As a result of power Doppler ultrasonography examination, the time-dependent differences in the CPP of the caruncles were statistically significant (p < 0.01) in ewes giving birth to both singletons and twins. The diameter of the cervix at PP3 was significantly higher than the ones at PP14, PP21, PP28 (p < 0.05). The SWS and stiffness in the IOC for all ewes at PP35 were significantly higher than the ones at PP1, PP4, PP7, and PP14 (p < 0.05 and p < 0.01; respectively). However, the time-dependent differences in SWS and stiffness in the EOC were not statistically significant (p > 0.05). The time-dependent differences in the SWS and stiffness in the vulva were statistically significant (p < 0.001) in ewes giving birth to both singletons and twins.DiscussionIn conclusion, it is possible to describe the changes throughout the postpartum period and evaluate the involution of the uterine cervix, caruncles, and vulvar labia and tissue stiffness with significant results by B mode ultrasonography, power Doppler and shear wave elastography. We provided valuable information to elucidate the differences in the involution process of the uterine cervix, caruncles, and vulva concerning the number of offspring during the postpartum period in Kivircik ewes.

Life course immunisation looks at the broad value of vaccination across multiple generations, calling for more data power, collaboration, and multi-disciplinary work. Rapid strides in artificial intelligence, such as machine learning and natural language processing, can enhance data analysis, conceptual modelling, and real-time surveillance. The GRADE process is a valuable tool in informing public health decisions. It must be enhanced by real-world data which can span and capture immediate needs in diverse populations and vaccination administration scenarios. Analysis of data from multiple study designs is required to understand the nuances of health behaviors and interventions, address gaps, and mitigate the risk of bias or confounding presented by any single data collection methodology. Secure and responsible health data sharing across European countries can contribute to a deeper understanding of vaccines.

MXenes, as two-dimensional (2D) materials, offer significant potential for various nanoscience applications due to their diverse chemistry, high conductivity, and large surface area. However, their use in creating unique microstructures with binary carbide/nitride MX phases has been minimally explored. This study investigates the use of multilayered Ti3C2Tz MXene as a precursor for forming bulk TiCx/Al2O3 composites with highly oriented carbide reinforcement. To evaluate this prospect, we conducted a side-by-side comparison of the processing, microstructure, and properties of MXene-derived TiC0.67/Al2O3 and conventional TiC/Al2O3 composites. The MXene-derived TiC0.67/Al2O3 exhibited inferior mechanical properties due to the formation of AlF3 or Ti2.25Al0.75O5 phases alongside the TiC0.67 particles. Not only did the fluorine present in the precursor MXene cause formation of these undesirable phases, but it also weakened the alumina matrix, leading to significant grain growth and compromised mechanical integrity. Despite these challenges, the proposed approach shows promise. As the desired preferred orientation was achieved, with particles elongated perpendicular to the applied pressure during sintering. This new morphology reached the percolation threshold and demonstrated high electrical conductivity with roughly a third of the TiC content required in conventional composites. The findings underscore the need for optimizing precursor MXene preparation and controlling surface terminations to maximize the benefits of MXene-derived reinforcements in ceramic composites.

BackgroundPain assessment in the infant population is challenging owing to their inability to verbalize and hence self-report pain. Currently, there is a paucity of data on how parents identify and manage this pain at home using standardized pain assessment tools. ObjectiveThis study aimed to explore parents’ assessment and intervention of pain in their infants at home following same-day surgery, using standardized pain assessment tools. MethodsThis prospective study initially recruited 109 infant boys undergoing circumcision (same-day surgery). To assess pain at home over 3 days after surgery, parents using iOS devices were assigned to use the PainChek Infant tool, which is a point-of-care artificial intelligence–enabled tool, while parents using Android devices were assigned to use the Observer-Administered Visual Analog Scale (ObsVAS) tool. Chi-square analysis compared the intervention undertaken and pain presence. Generalized estimating equations were used to evaluate outcomes related to construct validity and clinical utility. Receiver operating characteristic analysis assessed pain score cutoffs in relation to the intervention used. ResultsA total of 69 parents completed postsurgery pain assessments at home and returned their pain diaries. Of these 69 parents, 24 used ObsVAS and 45 used PainChek Infant. Feeding alone and feeding with medication were the most common pain interventions. Pain presence over time reduced. In the presence of pain, an intervention was likely to be administered (χ22=21.4; P

Amid mushrooming net-zero commitments and pledges made by states and non-state entities, a gap remains between those pledges, and the action needed in order to stay within the temperature goals of the Paris Agreement. In response, scholars and policymakers have started to examine physical, technological, economic, and policy pathways to net‐zero emissions across different sectors. This article examines the existing legislation and litigation for a net-zero world in four jurisdictions: Germany, the United States, Brazil, and China. We propose a taxonomy for identifying and comparing existing legal mechanisms to reach net-zero across these jurisdictions. We identify and analyze different legislative and regulatory mechanisms that incorporate net-zero mandates and three net-zero litigation strategies in these countries. These jurisdictions provide a useful snapshot of the variety of legal mechanisms currently being used by, or imposed on, large emitting jurisdictions and entities. We then consider the critical ways in which climate law can contribute to, or hinder, emissions reductions in line with net-zero targets.

ABSTRACTChronic digestive disorders are of increasing incidence worldwide with expensive treatments and no available cure. Available therapeutic schemes mainly rely on symptom relief, with large degrees of variability in patients’ response to such treatments, underlining the need for new therapeutic strategies. There are strong indications that the gut microbiota’s contribution seems to be a key modulator of disease activity and patients’ treatment responses. Hence, efforts have been devoted to understanding host–microbe interactions and the mechanisms underpinning such variability. Animal models, being the gold standard, provide valuable mechanistic insights into host–microbe interactions. However, they are not exempt from limitations prompting the development of alternative methods. Emerging microfluidic technologies and gut-on-chip models were shown to mirror the main features of gut physiology and disease state, reflect microbiota modification, and include functional readouts for studying host responses. In this commentary, we discuss the relevance of animal models in understanding host–microbe interactions and how gut-on-chip technology holds promises for addressing patient variability in responses to chronic digestive disease treatment.

Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of Faecalibacterium prausnitzii have been associated with a positive response to ICI in multiple cancer types. Here, based on fecal shotgun metagenomics data, we show in two independent cohorts of patients with non-small cell lung cancer and advanced melanoma that a high level of F. prausnitzii at baseline is positively associated with a better clinical response to ICI. In MCA205 tumor-bearing mice, administration of F. prausnitzii strain EXL01, already in clinical development for Inflammatory Bowel Disease, restores the anti-tumor response to ICI in the context of antibiotic-induced microbiota perturbation at clinical and tumor transcriptomics level. In vitro, EXL01 strain enhances T cell activation in the presence of ICI. Interestingly, oral administration of EXL01 strain did not induce any change in fecal microbiota diversity or composition, suggesting a direct effect on immune cells in the small intestine. F. prausnitzii strain EXL01 will be evaluated as an adjuvant to ICI in multiple cancers in the near future.

The intestinal microbiota is increasingly recognized as a crucial player in the development and maintenance of various chronic conditions, including obesity and associated metabolic diseases. While most research focuses on the fecal microbiota due to its easier accessibility, the small intestine, as a major site for nutrient sensing and absorption, warrants further investigation to determine its microbiota composition and functions. Here, we conducted a clinical research project in 30 age- and sex-matched participants with (n = 15) and without (n = 15) obesity. Duodenojejunal fluid was obtained by aspiration during endoscopy. Phenotyping included clinical variables related to metabolic status, lifestyle, and psychosocial factors using validated questionnaires. We performed metagenomic analyses of the oral, duodenojejunal, and fecal microbiome, alongside metabolomic data from duodenojejunal fluid and feces, integrating these data with clinical and lifestyle information. Our results highlight significant associations between duodenojejunal microbiota composition and usual dietary intake, as well as clinical phenotypes, with larger effect sizes than the associations between these variables and fecal microbiota. Notably, we found that the duodenojejunal microbiota of patients with obesity exhibited higher diversity and showed distinct differences in the abundance of several duodenojejunal microbiota species compared with individuals without obesity. Our findings support the relevance of studying the role of the small intestinal microbiota in the pathogenesis of nutrition-related diseases.

Background: Response to induction chemotherapy has been shown to predict outcome in patients with high-risk neuroblastoma (HR-NB), with those achieving a complete response (CR) having superior outcomes. Methods: We evaluated whether conventional prognostic factors remain prognostic in subsets of patients defined by response to induction. 1244 Patients from four COG high-risk trials were included. End-induction response was coded as CR, partial response (PR) or better, less than PR without progressive disease (PD), and PD. Cox regression models were performed to calculate event-free and overall survival (EFS, OS) hazard ratios, including interaction terms between induction response and prognostic factors including sex, age, stage, primary tumor location, LDH, ferritin, ploidy, MYCN status, ALK status, histology, MKI, grade, and study era. Results: Among patients who achieved a CR after induction, INSS stage 4 disease and trial era were the only factors that remained significantly associated with inferior OS. For those who achieved less than a PR, adrenal primary site, MYCN amplification, and 1p LOH were associated with inferior outcomes. Multivariable models showed that end-induction response remained prognostic of EFS and OS even after controlling for other factors. Multiple significant statistical interactions were observed between end-induction response and other prognostic factors. Conclusion: The impact of conventional prognostic factors is not static in patients with HR-NB. Instead, response to induction chemotherapy modifies the effect of conventional prognostic factors. These data can help to further refine prognosis for patients with variable responses to induction and help to identify candidates who might benefit from treatment other than standard post-induction therapy.

Стаття присвячена актуальним питанням правової регламентації відносин щодо набуття на умовах постійного користування земельних ділянок відповідного цільового призначення. Проводиться історичний аналіз безстрокового користування починаючи із 1918 року при передачі селянам поміщицьких земель без викупу. Значна увага присвячена характеристиці Земельного кодексу 1990 року, із висвітленням переліку фізичних та юридичних осіб, яким земельні ділянки надавалися на праві постійного користування. Детально досліджено судову практику щодо переходу права постійного користування, набутого у встановленому порядку, до 1 січня 2002 року фізичною особою для ведення селянського (фермерського) господарства до фермерського господарства зі статусом юридичної особи, а також перехід такого титульного права до правонаступників в результаті реорганізації не залежно від організаційно-правової форми та виду діяльності. Висвітлено перелік чітких кроків щодо можливості перереєстрації права постійного користування чи оренди із засновника (члена) фізичної особи на фермерське господарство як юридичну особу. Охарактеризовано види діяльності, які можуть здійснювати постійні землекористувачі на земельних ділянках сільськогосподарського призначення. За результатами проведеного аналізу нормативно-правової бази та судової практики сформульовано перелік суб’єктів, які на сьогодні можуть мати на праві постійного користування земельні ділянки. Серед них: 1) суб’єкти, які можуть набувати земельні ділянки згідно ч. 2 ст. 92 ЗК України; 2) фізичні особи, які мають земельні ділянки для ведення особистого (підсобного) господарства; 3) фізичні особи, які мають земельні ділянки для ведення селянського (фермерського) господарства; 4) фермерські господарства, які мають земельні ділянки для ведення селянського (фермерського) господарства; 5) юридичні особи, перелік яких визначено ст. 7 ЗУ УРСР, якщо вони діють до сьогодні або у випадку реорганізації їх правонаступники, не залежно від організаційно-правової форми та виду діяльності.

Стаття присвячена кримінально-правовій ха­рактеристиці незаконної порубки лісу або не­законного перевезення, зберігання, збуту лісу. Виокремлено чіткі риси предмета злочину, такі як: цілісність дерев та чагарників, їх сироростучість, відсутність критеріїв вікового обме­ження зрубаних дерев та чагарників. Сформу­льовані критерії віднесення окремих територій до місця вчинення злочину. Звернено увагу на те, що розуміння порубки лісу лише як відділення дерева від кореня обу­мовлює звуження кола кримінально-правової заборони, адже такі дії як пошкодження, викор­човування, заподіюючи істотну шкоду довкіллю, залишаються поза межами кримінальної відпові­дальності. Пропонується дати чітке роз’яснення щодо змісту поняття “порубка лісу” у примітці до ст. 246 КК України. Акцентується увага на критичних зауважен­нях щодо розширення законодавцем меж об’єк­тивної сторони, а саме включенню у диспозицію ч. 1 ст. 246 КК України, окрім порубки лісу, таких дій як перевезення, зберігання, збут незаконно зрубаних дерев або чагарників, що заподіяли істотну шкоду. Встановлено, що законодавчий підхід щодо формулювання матеріального скла­ду злочину, ознакою якого є вказані дії, створює низку проблем у процесі кваліфікації діяння. Наведено аргументи щодо недоцільності декриміналізації перевезення, зберігання, збуту незаконно зрубаних дерев або чагарників, що заподіяли істотну шкоду, оскільки такі дії не втрачають своєї суспільної небезпеки, особли­во в умовах ускладненої війною, екологічної ситуації. Водночас, не підтримується думка про доцільність встановлення адміністративної від­повідальності за перевезення та зберігання не­законно зрубаних дерев та чагарників. Запро­поновано диференціювати кримінальну відпові­дальність у цій частині. Перевезення, зберіган­ня, збут незаконно зрубаних дерев або чагарни­ків передбачити як кримінальний проступок із формальним складом (ч. 1 ст. 246 КК України), вилучивши при цьому перевезення та зберіган­ня незаконно зрубаних дерев або чагарників із диспозиції ч. 1 ст. 65 КУпАП, як адміністративно карані дії. Відповідальність за незаконну поруб­ку дерев або чагарників у лісах, захисних та ін­шихлісових насадженнях, що заподіяла істотну шкоду передбачити у ч. 2 ст. 246 КК України (як злочин з матеріальним складом). З’ясовано, що найбільш поширеними мотивами цього злочину є корисливі мотиви.

PurposeAlpelisib is a PI3K alpha (PI3Kα)-selective inhibitor approved for the treatment of hormone receptor-positive/HER2-negative (HR+/HER2-) PIK3CA-mutated advanced breast cancer (ABC) based on the SOLAR-1 trial, which defined 11 substitutions in exons 7, 9, and 20 in PIK3CA (SOLAR1m). We report alpelisib effectiveness for ABC harboring SOLAR1m, as well as other pathogenic PIK3CA mutations (OTHERm) using comprehensive genomic profiling (CGP).Experimental designA total of 33,977 tissue and 1,587 liquid biopsies were analyzed using hybrid capture-based CGP covering the entire coding sequence of PIK3CA. Clinical characteristics and treatment history were available for 10,750 patients with ABC in the deidentified Flatiron Health-Foundation Medicine clinico-genomic database (FH-FMI CGDB).ResultsPIK3CAm were detected in 11,767/33,977 (35%) of tissue biopsies, including 2,300 (7%) samples with OTHERm and no SOLAR1m. Liquid biopsy had 77% sensitivity detecting PIK3CAm, increasing to 95% with circulating tumor DNA fraction ≥2%. In patients with HR+/HER2- ABC and PIK3CAm receiving alpelisib/fulvestrant (ALP+FUL; n = 182) or fulvestrant alone (FUL; n = 119), median real-world progression-free survival (rwPFS) was 5.9 months on ALP+FUL [95% confidence interval (CI): 5.1-7.4] versus 3.1 months on FUL (95% CI: 2.7-3.7; P < 0.0001). In patients with OTHERm, median rwPFS was 4.0 months on ALP+FUL (95% CI: 2.8-10.1) versus 2.5 months on FUL (95% CI: 2.2-3.7; P = 0.0054).ConclusionsCGP detects diverse PIK3CAm in a greater number of patients with ABC than PCR hotspot testing; 20% of patients with PIK3CAm do not have SOLAR1m. These patients may derive benefit from alpelisib. See related commentary by Tau and Miller, p. 989.

BackgroundExtremely preterm (EPT) birth has been related to dysregulation of stress responses and behavioral/learning problems at school age. Early adverse experiences can blunt HPA axis reactivity. We hypothesized that an attenuated cortisol awakening response would be associated with developmental and behavioral problems at school age in EPT children.MethodsThis secondary analysis of a sub-cohort of the SUPPORT study included children born between 24 and 27 weeks, evaluated at 6-7 years with a neurodevelopmental battery and cortisol measures. Differences were tested between EPT and a term-born group. Relationships of cortisol awakening response to test scores were analyzed.ResultsCortisol was measured in 110 EPT and 29 term-born 6-7 year olds. Unadjusted WISC-IV and NEPSY-II scores were significantly worse among EPT children only. Conners Parent Rating Scale behavior scores were significantly worse among EPT children. After adjusting for covariates, blunted cortisol awakening responses were found to be associated with poorer scores on memory tests and greater problems with inattention for the EPT group (p

Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.

Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) diversity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use-inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant diversity and inclusive research practices; and increased and improved data flow, access, and skill-building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science.

Effective feedback is an art that every leading teacher must improve. The student, who receives excellent feedback during the lesson, walks out of the door feeling confident and motivated for further improving. A student who receives poor feedback will feel the opposite. The feedback should be defined like "great work" with the meaning not only about how to correct the mistakes of students so that they can study in the future without undermining their confidence but also about the modern teacher's role in educational process. The article has been raised the issue of the specific features of the teaching activities, the essence of the concept of "syncretic activity of the teacher "is reveald, in particular the concept of "role functions" is clarified, approaches to interpreting the features of the role functions of a teacher are considered. The main instructions of the teacher which provide the identification of teacher's new qualities in the conditions of modern higher school have been highlighted. The teacher is entrusted with such functions as coordination of educational activities, adjustment of the content of education, counseling, etc. The solution of this problem in terms of personal and professional growth of the teacher has been proposed, which allows to improve the teaching process in higher education. The author's understanding of the main roles of the teacher in higher school has been outlined, the attention on urgent tasks, the features of the role functions of a teacher as syncretic multifunctional interaction between the teacher and the student on preparation of experts for information society has been emphasized. The sequence and priority of the teacher's roles in the syncretic activity in the teaching process have been revealed. The psychological structure of the teacher's syncretic activity has been clarified from the point of view of the requirements for teacher's personality with an explanation of the set of skills that the teacher of a higher education institution should have. The professional skills of the teacher in relation to the peculiarities of his or her activity, which are shown in various types of the teacher's role functions in accordance with the situation and professional tasks of teaching have been analyzed. It has been shown that the transformation of educational activities and role functions of a modern teacher of higher education testifies to constant changes in his personal and professional growth, which also affects the development of the personality of a student - a future professional - in the process of his training.

Cultural, racial, social, religious, ethnic heterogeneity of educational groups is a problem of modern education in the context of integration and globalization. This often becomes a reason for misunderstandings, sometimes aggression in the interaction of representatives of opposing worldviews, preferences or traditions. Tolerance in the communicative culture of the educational manager, activated at the level of management structures and broadcast vertically and horizontally through the education system through pedagogical teams to all categories of consumers of educational services, will be able to prevent this. The aim of the article is to outline the role of tolerance in the communicative culture of the modern education manager. According to the purpose the following tasks of research have been defined: - to analyze sources of various branches of science and to find out meanings of basic concepts; - to outline the features of management in education in communication area; - to define its structure, establish relationships between components and develop a structural and semantic model of tolerance in the communicative culture of the education manager. The following research methods have been used to study the backgrounds of the problem: information, terminology, analysis, synthesis, methods of scientific research. The comparativetypological method has been used to compare, identify signs of similarities and differences between phenomena and facts Methods of forecasting and theoretical modeling have been used in the development of structural and semantic model. Systematization, classification and use of structuralfunctional analysis have been contributed to the generalization of the research results. Interdisciplinary approaches (sociocultural and multicultural) to the study of management, along with axiological, holistic, systemic, activity and synergetic are the methodological basis of the study. Methodological principles (synergetic, complementarity, activity (action and creative), interaction between the subjects of the educational process, convergence from the abstract to the concrete) have been applied. The scientific novelty of the research: - for the first time the meaning and valuesemantic nature of tolerance in the communicative culture of an educational manager have been determined; - the determinants of educational management in the projection on communication have been clarified; - the interrelations between the components have been established and the possibilities for realization of tolerance in different directions of communicative culture have been revealed; - a structural and semantic model of tolerance in the communicative culture of the education manager has been developed. The main results of the study are the analysis of the source base from the standpoint of scientific approaches to various fields of knowledge (economics, sociology, psychology, pedagogy, management, culturology, etc.), which made it possible to identify a modern interpretation of "education management". The determinants of educational management as a component of social in the context of intangible, spiritual resource of education have been revealed. The similar and different characteristics of the managerial activity of the education manager and the pedagogical worker have been outlined. The essence, origin, structure, types and directions of functioning of communicative culture of the manager of education have been determined.