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Purpose: This German S3 clinical practice guideline offers evidence-based recommendations for the use of composite materials in direct restorations of permanent teeth. Outcomes considered were the survival rates and restoration quality and process quality of the manufacturing process. Part 1 of this two-part presentation deals with the indication classes. Materials and Methods: A systematic literature search was conducted by two methodologists using MEDLINE and the Cochrane Library via the OVID platform, including studies up to December 2021. Six PICO questions were developed to guide the search. Recommendations were formulated by a panel of dental professionals from 20 national societies and organizations based on the collected evidence. Results: Composite materials are a viable option for the direct restoration of cavity Classes I-V and may also be used for restorations with cusp replacement, and tooth shape corrections. In the posterior region, direct composite restorations should be preferred over indirect composite inlays. For Class V restorations, composite materials can be used if adequate contamination control and adhesive technique are ensured. Conclusion: The guideline is the first to provide comprehensive evidence on the use of direct composite materials. However, further long-term clinical studies with comparators such as (modified) glass-ionomer cements are necessary. Regular updates will detail the future scope and limitations of direct composite restorations. [ABSTRACT FROM AUTHOR]

Purpose: Part 2 of this German S3 clinical practice guideline provides recommendations for the process of manufacturing composite restorations. It covers key aspects like caries removal, field isolation, matrix and adhesive techniques, as well as light curing and polishing. The outcomes of interest include survival rates and restoration quality. Materials and Methods: A systematic literature search was conducted by two methodologists using MEDLINE and the Cochrane Library via the OVID platform, including studies up to December 2021. Additionally, the reference lists of relevant manuscripts were manually reviewed. Six PICO questions were developed to guide the search. Consensus-based recommendations were formulated by a panel of dental professionals from 20 national societies and organizations based on the collected evidence and expert opinion. Results: The guideline advocates for one-stage selective caries removal near the pulp and underscores the effectiveness of various isolation techniques, adhesive systems, and the crucial role of light polymerization. The use of anatomically preformed sectional matrices and phosphoric acid etching is recommended to enhance restoration quality. Additionally, polishing composite restorations is advised to improve surface finish. Conclusion: This guideline provides comprehensive recommendations that inform clinicians on optimizing the composite restoration manufacturing processes. The adoption of these best practices can improve the quality and longevity of dental restorations. [ABSTRACT FROM AUTHOR]

Disruption of host-associated microbial communities can have detrimental impacts on host health. However, the capacity of individual host-associated microbial communities to resist disturbance has not been well defined. Using a novel fecal sampling method for honey bees (Apis mellifera), we examined the resistance of the honey bee gut microbiome to disruption from a low dose of the antibiotic, tetracycline (4.5 μg). Prior to the experiment, bacterial communities from fecal samples were compared to communities from dissected whole guts of the same individuals to ensure fecal samples accurately represented the gut microbiome. Fecal samples were collected from lab-caged honey bees prior to, and five days after, tetracycline exposure to assess how antibiotic disturbance affected the communities of individuals. We used metrics of alpha and beta diversity calculated from 16S rRNA gene amplicon sequences to compare gut community structure. Low dose tetracycline exposure did not consistently change honey bee gut microbiome structure, but there was individual variation in response to exposure and specific taxa (one ASV assigned to Lactobacillus kunkeei and one ASV in the genus Bombella) were differentially abundant following tetracycline treatment. To assess whether individual variation could be influenced by the presence of tetracycline resistance genes, we quantified the abundance of tet(B) and tet(M) with qPCR. The abundance of tet(M) prior to tetracycline treatment was negatively correlated with change in community membership, assessed by difference in Jaccard dissimilarity over the five-day experiment. Our results suggest that the honey bee gut microbiome has some ability to resist or recover from antibiotic-induced change, specific taxa may vary in their susceptibility to tetracycline exposure, and antibiotic resistance genes may contribute to gut microbiome resistance. [ABSTRACT FROM AUTHOR]

Background and importance: The emergency department (ED) is a hectic place, where many critically ill patients are treated. For residents working in the ED, this environment may be demanding. Objectives: The aim of this study was to investigate the [1] cognitive load experienced by residents working in the ED, and [2] differences in cognitive load during the day. Methods: In this multicentre, prospective study in three EDs in the Netherlands, the experienced cognitive load was graded by residents on three scales, agreed upon during Delphi meetings: the complexity (low-high: 1–3), mental effort (low-high: 1–9) and comfortability scale (low-high: 0–100%). We applied the scores per decision, 1-hour and 2-hour intervals, patient and shift. Main results: We observed 14 residents and analysed 74 1-hour and 45 2-hour intervals, 79 patients, 24 shifts and 592 separate decisions. The experienced cognitive load per decision was low. In contrast, the cognitive load was higher per 2-hour interval (mental effort: median 4.0 (IQR 4.0) and comfortability 80% (IQR 20)) and per shift (mental effort: median 5.5 (IQR 4.0) and comfortability 80% (IQR 20). Complexity was low for all measurements. Mental effort rose from 17h onwards higher values, whereas a decrease in comfortability was seen from 21h onwards. Conclusion: From 17h onwards, residents working in the ED experienced rather high mental effort and reported feeling not optimally comfortable when making decisions. The mental effort was highest between 21-23h. This was found when cognitive load was measured per 2-hour interval and per shift, but not per decision. This study may provide an insights to optimise cognitive load by reorganisation of the ED. [ABSTRACT FROM AUTHOR]

Background: Prenatal development of autonomic innervation of sinus venosus-related structures might be related to atrial arrhythmias later in life. Most of the pioneering studies providing embryological background are conducted in animal models. To date, a detailed comparison with the human cardiac autonomic nervous system (cANS) is lacking. The aim of this study was to compare the morphological and functional development of the cANS between mouse and human, specifically aimed at the venous pole. Methods: Wildtype mouse embryos (E9.5–E18.5) and healthy human fetuses (6–38 weeks gestational age (WGA)) were studied at sequential stages to obtain a comparative developmental series. Cardiac autonomic function was assessed through heart rate variability (HRV) analysis using ultrasound. Morphological assessment of the venous pole was performed using immunohistochemical stainings for neural crest cells and autonomic nerve markers. Results: Murine cANS function did not definitively establish in utero as HRV parameters depicted no trend prior to birth. In contrast, human HRV parameters greatly increased from 20 to 30 WGA, indicating that human cANS function is established prenatally around 20 WGA and matures thereafter. Morphologically, cANS development followed a similar sequence with neural crest-derived nerves entering the venous pole in proximity to the developing pulmonary vein in both species. However, the timing of differentiation into sympathetic or parasympathetic phenotype was markedly distinct, as human autonomic markers emerged relatively later when related to major cardiogenesis. Structures related to arrhythmogenicity in humans, such as the ligament/vein of Marshall and the myocardium surrounding the pulmonary veins, become highly innervated during embryonic development in both mice and humans. Conclusion: Although early morphological cANS development at sinus venosus-related structures follows a similar sequence in mice and humans, there are substantial differences in the timing of functional establishment and differentiation in sympathetic and parasympathetic phenotypes, which should be taken into account when extrapolating mouse studies of the cANS to humans. The abundant innervation of sinus venosus-related structures may play a modulatory role in arrhythmogenesis under pathological conditions. [ABSTRACT FROM AUTHOR]

The urgent need for effective treatments for acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. The 2023 American Thoracic Society Workshop on Precision-Cut Lung Slices (PCLSs) brought together 35 experts to discuss and address the role of human tissue–derived PCLSs as a unique tool for target and drug discovery and validation in pulmonary medicine. With increasing interest and usage, together with advancements in methods and technology, there is a growing need for consensus on PCLS methodology and readouts. The current document recommends standard reporting criteria and emphasizes the requirement for careful collection and integration of clinical metadata. We further discuss current clinically relevant readouts that can be applied to PCLSs and highlight recent developments and future steps for implementing novel technologies for PCLS modeling and analysis. The collection and correlation of clinical metadata and multiomic analysis will further advance the integration of this preclinical platform into patient endotyping and the development of tailored therapies for patients with lung disease. [ABSTRACT FROM AUTHOR]

Aim: To analyse the potential drivers (glucose level, complications, diabetes type, gender, age and mental health) of diabetes symptoms using continuous glucose monitoring (CGM) and ecological momentary assessment. Materials and Methods: Participants used a smartphone application to rate 25 diabetes symptoms in their daily lives over 8 days. These symptoms were grouped into four blocks so that each symptom was rated six times on 2 days (noon, afternoon and evening). The symptom ratings were associated with the glucose levels for the previous 2 hours, measured with CGM. Linear mixed‐effects models were used, allowing for nested random effects and the conduct of N = 1 analysis of individual associations. Results: In total, 192 individuals with type 1 diabetes and 179 with type 2 diabetes completed 6380 app check‐ins. Four symptoms showed a significant negative association with glucose values, indicating higher ratings at lower glucose (speech difficulties, P =.003; coordination problems, P =.00005; confusion, P =.049; and food cravings, P =.0003). Four symptoms showed a significant positive association with glucose values, indicating higher scores at higher glucose (thirst, P =.0001; urination, P =.0003; taste disturbances, P =.021; and itching, P =.0120). There were also significant positive associations between microangiopathy and eight symptoms. Elevated depression and diabetes distress were associated with higher symptom scores. N = 1 analysis showed highly idiosyncratic associations between symptom reports and glucose levels. Conclusions: The N = 1 analysis facilitated the creation of personalized symptom profiles related to glucose levels with consideration of factors such as complications, gender, body mass index, depression and diabetes distress. This approach can enhance precision monitoring for diabetes symptoms in precision medicine. [ABSTRACT FROM AUTHOR]

Background: Aim of this questionnaire-based cross-sectional study was to compare self-efficacy, social support, oral hygiene-related self-efficacy (OHRSE) and oral health-related quality of life (OHRQoL) between patients under chronic hemodialysis (HD) and patients after kidney transplantation (KTx) as well as a healthy comparison group (HC). Methods: Patients under HD were recruited during their routine outpatient dialysis therapy, KTx patients during their maintenance appointment and HC patients during their regular dental check-up in the dental clinic. General self-efficacy, the OHRSE, social support (F-SozU-K14) and the OHRQoL (OHIP-G5) were assessed by specific validated questionnaires. The survey was performed by one experienced dentist. Results: 44 HD, 40 KTx and 45 HC patients were included, between which the age and gender distribution was comparable (p > 0.05). With a median of 1.5 [IQR: 0–3], HD patients showed higher OHIP-G5 than the participants in KTx group (p < 0.01). Similarly, a significant difference was found between KTx (0, [0–0.5]) and HC (0, [0–3]; p < 0.01). HD patients showed a lower sum score of OHRSE, tooth-brushing, interdental-cleaning and dental-visit self-efficacy than the HC (p < 0.01). Similarly, HD patients had a lower sum score of OHRSE, tooth-brushing and dental-visit self-efficacy than the KTx group (p < 0.01). Moreover, the KTx group had a lower interdental-cleaning self-efficacy (p < 0.01) and sum score (p = 0.02) than the HC. The sum score of the general self-efficacy was comparable between the three groups (p = 0.19). The F-SozU-K14 revealed higher values in KTx (65.40 ± 5.33) compared with HD (60.95 ± 9.28) and HC group (61.71 ± 9.24; p = 0.03). Only in the KTx group, a significant association between F-SozU-K14 and OHIP-G5 was revealed (p = 0.05). Conclusions: Patients under HD show a reduced OHRSE compared to KTx and HC and a slightly reduced OHRQoL compared to KTx patients. While general self-efficacy was comparable between groups, social support of HD patients was lower than of KTx patients. The OHRSE and OHRQoL might receive increased attention in dental care of HD patients. [ABSTRACT FROM AUTHOR]

Genetic aberrations and immune escape are fundamental in MDS and CMML initiation and progression to sAML. Therefore, quantitative and spatial immune cell organization, expression of immune checkpoints (ICP), classical human leukocyte antigen class I (HLA-I) and the non-classical HLA-Ib antigens were analyzed in 274 neoplastic and 50 non-neoplastic bone marrow (BM) biopsies using conventional and multiplex immunohistochemistry and correlated to publicly available dataset. Higher numbers of tissue infiltrating lymphocytes (TILs) were found in MDS/CMML (8.8%) compared to sAML (7.5%) and non-neoplastic BM (5.3%). Higher T cell abundance, including the CD8+ T cell subset, inversely correlated with the number of pathogenic mutations and was associated with blast BM counts, ICP expression, spatial T cell distribution and improved patients' survival in MDS and CMML. In MDS/CMML, higher PD-1/PD-L1/PD-L2 and HLA-I, but lower HLA-G expression correlated with a significantly better patients' outcome. Moreover, a closer spatial proximity of T cell subpopulations and their proximity to myeloid blasts showed a stronger prognostic impact when compared to TIL numbers. In sAML – the continuum of MDS and CMML – the number of TILs had no impact on prognosis, but higher CD28 and HLA-I expression correlated with a better outcome of sAML patients. This study underlines the independent prognostic value of the tumor microenvironment in MDS/CMML progression to sAML, which shows the most pronounced immune escape. Moreover, new prognostic markers, like HLA-G expression and spatial T cell distribution, were described for the first time, which might also serve as therapeutic targets. [ABSTRACT FROM AUTHOR]

Purpose: The management of inferior vena cava (IVC) tumor thrombus in patients with renal cell carcinoma (RCC) is among the most challenging surgical procedures. We aimed to define a minimum annual caseload for sufficient expertise. Methods: We identified all cases with RCC, nephrectomy, and IVC procedures in the Federal Statistical Office billing database (2006–2020). We defined annual hospital caseload categories as low (< 4 cases), medium (4–9 cases) and high (> 9 cases) volume. Logistic multivariate models identified mortality-related factors. In addition, we analyzed data on tumor stage distribution from German cancer registries. Results: We recorded 3,700 nephrectomies with IVC-tumor resection with stable annual case number of 247 mean. This correlated with a stable incidence of T3b/c RCC. Patient age was 66 ± 14 years. Of all cases, 56% occurred in low, 30% in medium, and 14% in high volume clinics without a significant trend towards centralization. The overall in-hospital mortality rate was 5.8% and the transfusion rate 72%. An annual caseload of 8 showed to be a significant cut-off for mortality with 6.2% at < 8 cases and 2.8% for > = 8 cases annually (p < 0.001). Multivariate analysis revealed patient age (OR 6.4 for octogenerians) ventilation time (OR 14.3 for > 24 h) and hospital caseload (OR 2.6) as the most important risk factors for in-hospital mortality. Conclusion: Our results show a negative correlation of annual caseload and mortality for this procedure. A minimum number of 8 procedures per year seems reasonable for the successful management of IVC tumor thrombus with significantly lower mortality. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Despite this, current diagnostic tools are still not satisfactory, lacking sensitivity for early-stage or single-cell diagnosis. This study describes the development of small-molecule tracers for the well-known tumor marker prostate-specific membrane antigen (PSMA). These tracers contain a urea motif for PSMA-targeting and iodinated aromatic moieties to allow detection via X-ray fluorescence imaging (XFI). Tracers with a triiodobenzoyl moiety allowed the specific targeting and successful imaging of PSMA+ cell lines with XFI. The XFI-measured uptake of 7.88 × 10−18 mol iodine (I) per cell is consistent with the uptake of known PSMA tracers measured by other techniques such as inductively coupled plasma mass spectrometry (ICP-MS). This is the first successful application of XFI to tumor cell targeting with a small-molecule tracer. In addition, iodinated tracers were used for the characterization of quantum dots (QDs) conjugated to PSMA-targeting urea motifs. The resulting targeted QD conjugates were shown to selectively bind PSMA+ cell lines via confocal microscopy. The immobilized iodinated targeting vectors allowed the determination of the tracer/QD ratio via XFI and ICP-MS. This ratio is a key property of targeted particles and difficult to measure by other techniques. [ABSTRACT FROM AUTHOR]

Background Melioidosis, attributable to the soil-dwelling bacterium Burkholderia pseudomallei , stands as a paramount global health challenge, necessitating extended courses of antibiotics. While murine studies identified the gut microbiota as a modulator of bacterial dissemination during melioidosis, the human intestinal microbiota during melioidosis remains uncharacterized. Here, we characterized gut microbiota composition and antimicrobial resistance (AMR) genes at diagnosis, during treatment, and postdischarge for melioidosis. We hypothesized that the gut microbiota of melioidosis patients would be extensively distorted. Methods In this prospective observational cohort, stool samples of patients with culture-confirmed melioidosis admitted to a tertiary care hospital in India were collected at diagnosis, 14 days after diagnosis, or discharge (whichever occurred first) and at 6 months postinfection. Family members or neighbors served as community controls. The gut microbiota and resistome were profiled by shotgun metagenomic sequencing. Results We longitudinally analyzed the gut microbiota of 70 fecal samples from 28 patients and 16 community controls. At diagnosis, the gut microbiota of patients differed from that of controls, characterized by high abundances of potentially pathogenic bacteria, a loss of butyrate-producing bacteria, and higher levels of AMR genes. Microbiota composition and resistome remained different from community controls at 6 months, driven by total antibiotic exposure. During hospitalization, gut microbiota profiles were associated with secondary Klebsiella pneumoniae infections. Conclusions This first study on gut microbiota composition and resistome in human melioidosis showed extensive disruptions during hospitalization, with limited signs of restoration 6 months postinfection. Given the adverse outcomes linked with microbiome perturbations, limiting microbiota disruptions or using microbiota-restorative therapies (eg, butyrate-producing probiotics) may be beneficial. [ABSTRACT FROM AUTHOR]

A diaminocyclopentadienone ruthenium complex allows control of regioselectivity in the ruthenium-catalyzed isomerization of propargyl alcohols through the choice of additive. Thereby, both products of the Meyer–Schuster rearrangement and redox isomerization products are selectively accessible. In the presence of hydroxylamine- O -sulfonic acid, unsaturated nitriles are formed instead. The ruthenium catalyst is readily available and stable to moisture, air, and acidic conditions. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Diabetes distress is one of the most frequent mental health issues identified in people with type 1 and type 2 diabetes. Little is known about the role of glucose control as a potential contributor to diabetes distress and whether the subjective perception of glucose control or the objective glycaemic parameters are more important for the experience. With the emergence of continuous glucose monitoring (CGM), this is a relevant question as glucose values are now visible in real-time. We employed a precision monitoring approach to analyse the independent associations of perceived and measured glucose control with diabetes distress on a daily basis. By using n-of-1 analyses, we aimed to identify individual contributors to diabetes distress per person and analyse the associations of these individual contributors with mental health at a 3 month follow-up. Methods: In this prospective, observational study, perceived (hypoglycaemia/hyperglycaemia/glucose variability burden) and measured glucose control (time in hypoglycaemia and hyperglycaemia, CV) were assessed daily for 17 days using an ecological momentary assessment (EMA) approach with a special EMA app and CGM, respectively. Mixed-effect regression analysis was performed, with daily diabetes distress as the dependent variable and daily perceived and CGM-measured metrics of glucose control as random factors. Individual regression coefficients of daily distress with perceived and CGM-measured metrics were correlated with levels of psychosocial well-being at a 3 month follow-up. Results: Data from 379 participants were analysed (50.9% type 1 diabetes; 49.6% female). Perceived glucose variability (t=14.360; p<0.0001) and perceived hyperglycaemia (t=13.637; p<0.0001) were the strongest predictors of daily diabetes distress, while CGM-based glucose variability was not significantly associated (t=1.070; p=0.285). There was great heterogeneity between individuals in the associations of perceived and measured glucose parameters with diabetes distress. Individuals with a stronger association between perceived glucose control and daily distress had more depressive symptoms (β=0.32), diabetes distress (β=0.39) and hypoglycaemia fear (β=0.34) at follow-up (all p<0.001). Individuals with a stronger association between CGM-measured glucose control and daily distress had higher levels of psychosocial well-being at follow-up (depressive symptoms: β=−0.31; diabetes distress: β=−0.33; hypoglycaemia fear: β=−0.27; all p<0.001) but also higher HbA1c (β=0.12; p<0.05). Conclusions/interpretation: Overall, subjective perceptions of glucose seem to be more influential on diabetes distress than objective CGM parameters of glycaemic control. N-of-1 analyses showed that CGM-measured and perceived glucose control had differential associations with diabetes distress and psychosocial well-being 3 months later. The results highlight the need to understand the individual drivers of diabetes distress to develop personalised interventions within a precision mental health approach. [ABSTRACT FROM AUTHOR]

Objectives: To assess maternal complications after fetoscopic laser surgery (FLS) for the twin‐to‐twin transfusion syndrome (TTTS). Methods: All consecutive cases treated with FLS for TTTS between 2008 and 2021 at the Leiden University Medical Center (LUMC) were included. We allocated complications in three timeframes: "Admission for laser surgery," "pregnancy after laser," and "delivery and third stage of labor." Maternal complications were graded according to the Maternal and Fetal Adverse Event Terminology (MFAET) and for intra‐abdominal hemorrhage, the Common Terminology Criteria for Adverse Events (CTCAE). Results: In the study period, 637 mothers were treated for TTTS with FLS. There were 1559 occurrences of maternal complications. The rate of severe maternal complications (grade 3 or 4) was 8.0%. Severe complications consisted of six cases of severe intra‐abdominal hemorrhage, nine cases of severe hemorrhage in pregnancy, one with severe chorioamnionitis, 10 with severe preeclampsia/HELLP syndrome, and 25 with a severe postpartum hemorrhage. Conclusions: Even though it is the gold standard for treating TTTS, FLS comes at a risk to the mother which should not be neglected. And even though not all complications have serious consequences to the mother, the severe maternal complication rate of 8.0% should be added to the inherent risks for the fetus, and should be discussed with patients eligible for surgery in order to make an informed decision on treatment options. [ABSTRACT FROM AUTHOR]

Existing research on parental information literacy focuses on parents' ability to evaluate information. This approach does not account for conflicting or unwanted information and obscures the emotional impact of unsought information. We aimed to (1) document the sources women use most frequently for accessing breastfeeding information, (2) explore the reasons women choose some sources over others, (3) test the relationship between source characteristics and breastfeeding self-efficacy, and (4) determine the extent to which four source characteristics – competence, trustworthiness, goodwill, and social support – predict breastfeeding self-efficacy. This study was conducted in two phases. The first phase consisted of interviews and focus groups, which we analyzed inductively using a grounded theory approach. In phase two, we conducted a cross-sectional survey of women who were currently breastfeeding, collecting data on the source credibility and social support associated with the source they use most frequently and the participants' breastfeeding self-efficacy. We used multiple regression to analyze our survey data. The frequency with which our participants encountered conflicting and unsought prompted them to view sources that combine expertise and social support as ideal. However, these sources are often difficult to access, leading to a reliance on online sources. This compromise has implications for breastfeeding tenure, as both competence and social support predicted breastfeeding self-efficacy. This study demonstrates how emotional aspects of information seeking shape women's preferred sources, how accessibility limits the use of preferred sources, and how source competence and social support influence breastfeeding self-efficacy. [ABSTRACT FROM AUTHOR]

We demonstrate liquid-jet photoelectron spectroscopy from a flatjet formed by the impingement of two micron-sized cylindrical jets of different aqueous solutions. Flatjets provide flexible experimental templates enabling unique liquid-phase experiments that would not be possible using single cylindrical liquid jets. One such possibility is to generate two co-flowing liquid-jet sheets with a common interface in vacuum, with each surface facing the vacuum being representative of one of the solutions, allowing face-sensitive detection by photoelectron spectroscopy. The impingement of two cylindrical jets also enables the application of different bias potentials to each jet with the principal possibility to generate a potential gradient between the two solution phases. This is shown for the case of a flatjet composed of a sodium iodide aqueous solution and neat liquid water. The implications of asymmetric biasing for flatjet photoelectron spectroscopy are discussed. The first photoemission spectra for a sandwich-type flatjet comprised of a water layer encapsulated by two outer layers of an organic solvent (toluene) are also shown. [ABSTRACT FROM AUTHOR]

Background: Older adults account for a large proportion of hospital admissions. In this study we aim to bridge a gap between medical and psychosocial factors in predicting hospitalisation. Methods: Demographic and social characteristics of community-dwelling pre-frail and frail older people were collected by questionnaires every six months during a two year follow-up. Hospital admission within this period was dichotomised as yes/no. To define pre-frailty and frailty the Fried frailty criteria were used. Analysis of risk factors for hospitalisation was performed using multivariable logistic regression. Results: Hospitalised participants (n = 1803) were more often male and frail in comparison to not-hospitalised participants. They also experienced more chronic diseases (54.5% ≥ 4 chronic diseases), poorer self-perceived health (SPH) (76.4% fair to very poor) and lack of informal care (20.1%). In multivariable logistic regression male gender (Odds ratio (OR) 1.65, p < 0.001), frailty (vs. pre-frailty) (OR 1.66, p = 0.002), reporting lower SPH (OR 3.12, p < 0.001) and lacking informal care (OR 1.69, p < 0.001) showed significant associations with hospital admission. Subgroup analysis of pre-frail and frail participants, showed consistent associations between male gender (respectively OR 1.61, p < 0.001 ; OR 1.72, p = 0.085), lower SPH (OR 2.23, p = 0.001; OR 31.16, p < 0.001), lack of informal care (OR 1.64, p = 0.005; OR 2.63, p = 0.012) and hospitalisation. Conclusion: Frailty, male gender, lower SPH and lack of informal care are risk factors for hospitalisation within community-dwelling older people, showing the need of a holistic approach to possibly prevent hospitalisation. Further research should focus on evaluating individual factors for hospitalisation, particularly targeting pre-frail individuals. Key points: - Frail older adults are at higher risk for hospitalisation compared to pre-frail. - Associations with hospitalisation: male gender, frailty, lower SPH, no informal care. - Psychosocial factors emerge as important determinants for hospitalisation. - Understanding medical and psychosocial factors of frailty is key for effective care planning. [ABSTRACT FROM AUTHOR]

Background: Despite its low incidence rate, small-cell lung cancer (SCLC), which accounts for approximately 10%–15% of all lung cancers, is concerningly characterized by its rapid progression, strong metastatic potential, and high fatality rate. Therefore, an effective predictive model for SCLC treatment is imperative for early intervention. Objective: In this study, we aimed to enhance the cancer stem cell (CSC) capabilities of SCLC through a three-dimensional (3D) culturing approach and to evaluate its potential as a predictive model for therapeutic response in SCLC by transplanting the spheroids into mice. Results: To achieve uniform and scalable production of 3D SCLC spheroids, the SpheroFILM culture platform was employed and the expression of CSC markers was verified at the gene and protein levels within the spheroids cultured onboard. Moreover, spheroids were transplanted into mice to confirm gene and protein expression of CSC markers, tumor-formation capacity, proliferation ability, and invasion potential through histological staining. Conclusion: Based on our results, the transplantation of enhanced CSC-functioning 3D SCLC cell lines into mice led to a significant increase in tumor-formation capacity along with elevated expression of CSC markers. Thus, the results collectively suggest that the augmentation of CSC properties in 3D cultured cell lines, when transplanted into animal models, reduces necrosis and enhances tumor formation, proliferation, and invasion. [ABSTRACT FROM AUTHOR]

Titanium dioxide (TiO2) and biochar have been used as amendments to adsorb vanadium (V) in aqueous solutions; however, their simultaneous application in the remediation of V‐contaminated neutral‐alkaline soils is rare. TiO2 nanoparticles, biochar, and a blend of biochar+TiO2 were investigated as amendments for an alkaline V‐contaminated soil. Treatments involved mixing (weight basis) 1% TiO2 (T1), 5% biochar (T2), 1% TiO2 + 5% biochar (T3) with soil, and an unamended soil (T4). An adsorption edge study was performed from pH 4 to 10 at the V concentration of 200 mg L−1. A standard vanadium (V) solution was prepared using NaVO3. An incubation study was conducted over 3 months with V‐contaminated soil at a rate of 200 mg kg−1, at 80% field capacity. At the end of the incubation period, the treated soils were subjected to V fractionation. X‐ray diffraction (XRD) patterns and FTIR spectra of TiO2 nanoparticles, biochar, uncontaminated soil, and four treated soils were obtained. The adsorption edge of V was below pH 4.6, suggesting reduced retention of V in alkaline soils. In the combined treatment, the adsorption edge was elevated by one unit compared to the control. V adsorption increased in TiO2, biochar, and combined TiO2+biochar treatments at 7%, 4%, and 20%, respectively, compared with the unamended soil (control) at a pH of ~7.6. Functional groups revealed the possibility of inner‐sphere and outer‐sphere adsorption mechanisms between vanadate and the mix amendment of TiO2+biochar. The labile V fraction decreased, and the nonlabile V fraction increased, significantly in the TiO2+biochar amended soil compared to the unamended soil. Applying a blend of biochar+TiO2 reduced the mobility of V in a neutral‐alkaline soil, thereby preventing it from contaminating the nearby soil and water bodies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potency and efficacy of a library of dopamine receptor D2 (D2R) antagonists in the mitigation of fibrotic activation in retinal pigment epithelial (RPE) cells. Methods: ARPE-19 cells were cultured and treated with methotrexate or 27 district D2R antagonists using a fibronectin deposition assay. The most potent compounds were then further assessed in assays measuring cellular proliferation, cellular migration, and profibrotic gene expression. Results: The previously established antifibrotic D2R antagonist loxapine exerted a robust and dose-dependent inhibition of fibronectin deposition, whereas methotrexate exerted minimal inhibition. The most potent D2R antagonist identified, fluphenazine, effectively blocked in vitro models of fibrosis at 300–1,000 nM concentrations. Conclusions: Here we found multiple FDA-approved D2R antagonists that potently block RPE cell fibrogenesis. These findings further support the potential of D2R antagonism as a potential therapeutic for retinal fibrotic disease. [ABSTRACT FROM AUTHOR]

Objective: To determine patients' perspectives on home monitoring at emergency department (ED) presentation and shortly after admission and compare these with their physicians' perspectives. Methods: Forty Dutch hospitals participated in this prospective flash mob study. Adult patients with acute medical conditions, treated by internal medicine specialties, presenting at the ED or admitted at the admission ward within the previous 24 h were included. The primary outcome was the proportion of patients who were able and willing to undergo home monitoring. Secondary outcomes included identifying barriers to home monitoring, patient's prerequisites, and assessing the agreement between the perspectives of patients and treating physicians. Results: On February 2, 2023, in total 665 patients [median age 69 (interquartile range: 55–78) years; 95.5% community dwelling; 29.3% Modified Early Warning Score ≥3; 29.5% clinical frailty score ≥5] were included. In total, 19.6% of ED patients were admitted and 26% of ward patients preferred home monitoring as continuation of care. Guaranteed readmission (87.8%), ability to contact the hospital 24/7 (77.3%), and a family caregiver at home (55.7%) were the most often reported prerequisites. Barriers for home monitoring were feeling too severely ill (78.8%) and inability to receive the required treatment at home (64.4%). The agreement between patients and physicians was fair (Cohens kappa coefficient 0.26). Conclusions: A substantial proportion of acutely ill patients stated that they were willing and able to be monitored at home. Guaranteed readmission, availability of a treatment team (24/7), and a home support system are needed for successful implementation of home monitoring in acute care. [ABSTRACT FROM AUTHOR]

Background: Many patients with lung cancer have underlying chronic lung diseases. We assume that baseline lung functions might also affect the prognosis of non-small cell lung cancer (NSCLC) patients receiving immunotherapy. Objectives: We aimed to assess the impact of pretreatment clinical parameters, including lung function measures such as forced vital capacity (FVC), on the prognosis of patients with NSCLC following immune checkpoint inhibitors (ICIs) therapy. Design: Retrospective multicenter study. Methods: Study subjects were consecutively selected from a multicenter cohort of patients with NSCLC who were undergoing immunotherapy. Patients were selected regardless of their initial cancer stage and prior treatment. The primary outcome was immunotherapy-related overall survival (iOS), defined as the duration from the initiation of immunotherapy to the time patients were censored. Spirometry values were acquired before bronchodilator application and were performed within the year before the first ICI treatment Results: We selected 289 patients for evaluation. The median iOS was 10.9 months (95% confidence interval (CI), 7.5–14.3). Programmed death-ligand 1 (PD-L1) expression, tested by SP263, was <1% in 20.9%, 1%–49% in 44.3%, and ⩾50% in 32.6% of the patients. ICI was used most often as second-line treatment (70.2%), followed by first line (13.1%), and third line (11.4%). In the Kaplan–Meier analysis, the median iOS of the low FVC group was significantly shorter than that in the preserved FVC group (6.10 (95% CI, 4.45–7.76) months vs 14.40 (95% CI, 10.61–18.34) months, p < 0.001)). A Cox regression analysis for iOS showed that age, poor performance status, PD-L1 expression measured by SP263, stage at diagnosis, and FVC (% predicted) were independent predictive factors. When we replaced FVC (%) in the multivariable analysis with forced expiratory volume in 1 s (%), diffusing lung capacity for carbon monoxide (DLco; %), or DLco (absolute), each of the pulmonary function factors showed a significant association with iOS. Conclusion: Pre-immunotherapy FVC (%) predicted immunotherapy-related outcomes in NSCLC patients, regardless of initial stage at diagnosis and prior treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Pyrazinamide (PZA) usage has been associated with adverse drug reactions, prompting its avoidance in treating elderly tuberculosis (TB) patients. This study aims to examine whether the administration of PZA is associated with poor outcomes during TB treatment among elderly individuals. Methods: A retrospective analysis was undertaken on data collected from a prospective cohort conducted between July 2019 and June 2023, which involved tuberculosis patients from 18 institutions across the Republic of Korea. The study aimed to assess the impact of PZA on the incidence of serious adverse events (SAEs), medication interruptions, and becoming loss to follow-up (LTFU) during standard short courses of TB treatment in elderly (≥65 years old) patients. Results: PZA was administered to 356 of 390 elderly patients (91.3%), and 98 of the 390 (25.1%) experienced SAEs. Treatment success was significantly lower in patients not treated with PZA compared to those who received PZA (64.7% vs 89.9%, p < 0.001). The incidence of SAEs, medication interruption, or LTFU was higher in patients not given PZA compared those who received PZA (52.9% vs. 27.2%, p = 0.002). A multivariate logistic regression analysis, factoring in covariates such as age, comorbidities, and baseline laboratory data, revealed that PZA was not a risk factor for SAEs, medication interruption, or LTFU in TB treatment (odds ratio [OR] 0.457, 95% confidence interval [CI] 0.201–1.041). Conclusion: Treating elderly TB patients with PZA did not increase the incidence of SAEs, medication interruptions, or LTFU during the standard short course of TB treatment. Therefore, considering its potential advantages, incorporating PZA into the treatment regimen for elderly TB patients may be advisable. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the diagnostic value of pre-existing computed tomography (CT) examinations for the detection of dental pathologies compared with clinical dental examination in patients with end-stage heart failure. Methods: For this purpose, 59 patients with end-stage heart failure and pre-existing non-dental CT images of the craniofacial region were included. Virtual orthopantomograms (vOPG) were reconstructed. Dental pathologies were analyzed in vOPG and source-CT images. Imaging and clinical findings less than 6 months apart were compared (n = 24). Results: The subjective image quality of vOPG was more often rated as insufficient than CT (66%; 20%; p < 0.01). Depending on examination (CT, vOPG or clinic), between 33% and 92% of the patients could require dental intervention such as treatment of caries and periodontitis or tooth extraction. vOPG led to a higher (80%) prevalence of teeth requiring treatment than CT (39%; p < 0.01). The prevalence of teeth requiring treatment was similar in CT (29%) and clinic (29%; p = 1.00) but higher in vOPG (63%; p < 0.01). CT (stage 3 or 4: 42%) and vOPG (38%) underestimated the stage of periodontitis (clinic: 75%; p < 0.01). Conclusions: In conclusion, available CT images including the craniofacial region from patients with end-stage heart failure may contain valuable information regarding oral health status. The assessability of vOPGs might be insufficient and must be interpreted with caution. [ABSTRACT FROM AUTHOR]

This study describes the external quality assessment (EQA) scheme for molecular testing of RET alterations in non-small cell lung cancer (NSCLC), medullary thyroid carcinomas (MTC), and non-MTC. The lead panel institute and Quality Assurance Initiative in Pathology (Qualitätssicherungs-Initiative Pathologie [QuIP] GmbH) selected formalin-fixed paraffin-embedded (FFPE) tissue from MTC for RET mutation testing by next-generation sequencing (NGS) methods and FFPE tissue from NSCLC and non-MTC for RET gene fusion testing using either in situ hybridisation (ISH) or NGS methods, forming 3 sub-schemes of the EQA scheme. Tissue material underwent an internal validation phase followed by an external testing phase. The internal validation phase served as a cross-validation step conducted by panel institutes. In the external testing phase, the number of participating institutes in the RET point mutation sub-scheme, RET fusion (ISH) sub-scheme, and RET fusion (NGS) sub-scheme was 32, 24, and 38, respectively. The reported success rates for external testing were 96.0%, 89.5%, and 93.5% for the RET point mutation, the ISH RET fusion, and the NGS RET fusion EQA sub-schemes, respectively. These findings confirm the reliability of the NGS method in detecting RET alterations and align with current screening recommendations. Overall, 31 institutes were certified for RET point mutation testing by NGS methods, 22 institutes were certified for RET fusion testing by ISH, and 36 institutes were certified for RET fusion testing by NGS methods. Results can be employed to inform real-world diagnostic decisions in Germany, Austria, and Switzerland. [ABSTRACT FROM AUTHOR]

Introduction: Visual imaging of subsurface caries lesions is of vital interest in dentistry, which can be obtained by invasive radiography technique as well as by available non-destructive imaging approaches. Thus, as a first step toward the development of a new innovative approach, Spectral-domain optical coherence tomography (SD-OCT) was applied to detect the lesion depth in comparison to the established reference technique (transverse microradiography [TMR]). Methods: Bovine enamel specimens were demineralized for 5 days, following previous studies. For OCT, the resulting artificial lesions were scanned three-dimensionally (SD-OCT) and semi-automated measured (CarLQuant). For TMR, specimens were sectioned and the lesion depth was manually determined (Inspektor Research System). Results: The range of lesion depth detected with OCT was 24.0–174.0 μm (mouth rinse study), 18.0–178.0 μm (toothpastes study) and with TMR 59.2–198.0 μm (mouth rinse study), 33.2–133.4 μm (toothpastes study). We found a strong correlation between both methods in terms of lesion depth (Spearman rankwith outlierp < 0.001, Rho = 0.75, Spearman rankwithout outlierp = 0.001, Rho = 0.79). The two methods produce similar results (Passing-Bablok regression, 1.16). As deeper is the lesion, the smallest is the difference between both methods as indicated by Bland-Altman-plots. Conclusion: Especially in the case of deep lesions, the values obtained by both methods are in agreement, and OCT can potentially substitute TMR to detect and assess lesion depth with the benefit of being non-destructive. [ABSTRACT FROM AUTHOR]

Let f = f (z , t) be a function holomorphic in z ∈ O ⊆ C d for fixed t ∈ Ω and measurable in t for fixed z and such that z ↦ f (z , ·) is bounded with values in E : = L p (Ω) , 1 ≤ p ≤ ∞ . It is proved (among other things) that ⟨ t ↦ φ (f (· , t)) , μ ⟩ = φ (z ↦ ⟨ f (z , ·) , μ ⟩) whenever μ ∈ E ′ and φ is a bp-continuous linear functional on H ∞ (O) . [ABSTRACT FROM AUTHOR]

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This article discusses a study conducted in Germany that examines the relationship between regional socioeconomic factors and the use of certain medications for adults with type 2 diabetes. The study finds that individuals in socioeconomically disadvantaged areas have lower access to newer glucose-lowering medications, such as SGLT2 inhibitors and GLP-1RAs. This disparity in access may contribute to socioeconomic disparities in cardiovascular health outcomes. The study suggests that further investigation into structural factors is needed to address these disparities. The study also highlights the importance of raising awareness among healthcare providers and overcoming barriers to access for newer treatment options in order to reduce inequalities. [Extracted from the article]

SUMMARY: Weeds in agricultural settings continually adapt to stresses from ecological and anthropogenic sources, in some cases leading to resistant populations. However, consequences of repeated sub‐lethal exposure of these stressors on fitness and stress "memory" over generations remain poorly understood. We measured plant performance over a transgenerational experiment with Arabidopsis thaliana where plants were exposed to sub‐lethal stress induced by the herbicides glyphosate or trifloxysulfuron, stresses from clipping or shading in either one (G1) or four successive generations (G1–G4), and control plants that never received stress. We found that fourth‐generation (G4) plants that had been subjected to three generations of glyphosate or trifloxysulfuron stress produced higher post‐stress biomass, seed weight, and rosette area as compared to that produced by plants that experienced stress only in the first generation (G1). By the same measure, clipping and shade were more influential on floral development time (shade) and seed weight (clipping) but did not show responsive phenotypes for vegetative metrics after multiple generations. Overall, we found that plants exhibited more rapid transgenerational vegetative "stress memory" to herbicides while reproductive plasticity was stressor dependent and similar between clipping/shade and anthropogenic stressors. Our study suggests that maternal plant stress memory aids next‐generation plants to respond and survive better under the same stressors. Significance Statement: We show differential transgenerational phenotypes to different stressors over four generations in Arabidopsis. [ABSTRACT FROM AUTHOR]

The direct electrochemical reduction of nicotinamide adenine dinucleotide (NAD+) results in various products, complicating the regeneration of the crucial 1,4‐NADH cofactor for enzymatic reactions. Previous research primarily focused on steady–state polarization to examine potential impacts on product selectivity. However, this study explores the influence of dynamic conditions on the selectivity of NAD+ reduction products by comparing two dynamic profiles with steady‐state conditions. Our findings reveal that the main products, including 1,4‐NADH, several dimers, and ADP‐ribose, remained consistent across all conditions. A minor by–product, 1,6‐NADH, was also identified. The product distribution varied depending on the experimental conditions (steady state vs. dynamic) and the concentration of NAD+, with higher concentrations and overpotentials promoting dimerization. The optimal yield of 1,4‐NADH was achieved under steady–state conditions with low overpotential and NAD+ concentrations. While dynamic conditions enhanced the 1,4‐NADH yield at shorter reaction times, they also resulted in a significant amount of unidentified products. Furthermore, this study assessed the potential of using pulsed electrochemical regeneration of 1,4‐NADH with enoate reductase (XenB) for cyclohexenone reduction. [ABSTRACT FROM AUTHOR]

Background: Lazertinib is an oral, third‐generation EGFR‐TKI, which specifically targets the EGFR T790M mutation along with activating mutations Ex19del and L858R. More real‐world data are needed to evaluate its efficacy and safety in treating locally advanced and metastatic non‐small cell lung cancer (NSCLC) following prior EGFR TKI treatment. Methods: This multicenter retrospective study was conducted at seven university hospitals affiliated to the Catholic Medical Center (CMC) in Korea. A clinical data warehouse (CDW) platform was used to access and extract information. Results: A total of 48 patients were assessed. The majority were female (75%) and diagnosed with adenocarcinoma (95.8%). All patients had the EGFR mutation at diagnosis, 27 (56.3%) had the exon 19 deletion, 20 (41.7%) had the L858R mutation, and one (2.0%) had the exon 18 mutation. The median progression‐free survival (PFS) was 15.4 months. At 6, 12, and 18 months, PFS rates were 79.1%, 53.6%, and 27.3%, respectively. When PFS was analyzed by prior TKI duration (<18 months vs. >18 months), significant differences were noted at the 6 and 9‐month mark (p = 0.013 and p = 0.010, respectively). In multivariate analysis for PFS, only prior TKI duration and ECOG score showed statistical significance (p = 0.026 and p = 0.049, respectively). In the multivariate analysis for OS, ECOG score showed statistical significance (p = 0.006). Among 48 patients, 34 (70.8%) experienced adverse events (AEs) related to lazertinib. The most frequent AEs were skin reaction (29.8%), diarrhea (21.3%), and peripheral neuropathy (20.8%). Conclusions: The results suggest that lazertinib is effective in second or more line settings, with tolerable safety profile. More patient data are necessary to find possible prognostic markers associated with patient outcome. [ABSTRACT FROM AUTHOR]

Background: The rise in asthma has been linked to different environmental and lifestyle factors including dietary habits. Whether dietary salt contributes to asthma incidence, remains controversial. We aimed to investigate the impact of higher salt intake on asthma incidence in humans and to evaluate underlying mechanisms using mouse models. Methods: Epidemiological research was conducted using the UK Biobank Resource. Data were obtained from 42,976 participants with a history of allergies. 24‐h sodium excretion was estimated from spot urine, and its association with asthma incidence was assessed by Cox regression, adjusting for relevant covariates. For mechanistic studies, a mouse model of mite‐induced allergic airway inflammation (AAI) fed with high‐salt diet (HSD) or normal‐salt chow was used to characterize disease development. The microbiome of lung and feces (as proxy for gut) was analyzed via 16S rRNA gene based metabarcoding approach. Results: In humans, urinary sodium excretion was directly associated with asthma incidence among females but not among males. HSD‐fed female mice displayed an aggravated AAI characterized by increased levels of total IgE, a TH2‐TH17‐biased inflammatory cell infiltration accompanied by upregulation of osmosensitive stress genes. HSD induced distinct changes in serum short chain fatty acids and in both gut and lung microbiome, with a lower Bacteroidetes to Firmicutes ratio and decreased Lactobacillus relative abundance in the gut, and enriched members of Gammaproteobacteria in the lung. Conclusions: High dietary salt consumption correlates with asthma incidence in female adults with a history of allergies. Female mice revealed HSD‐induced T‐cell lung profiles accompanied by alterations of gut and lung microbiome. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis is an interstitial scarring disease of the lung characterized by poor prognosis and limited treatment options. Tissue transglutaminase 2 (TG2) is believed to promote lung fibrosis by crosslinking extracellular matrix components and activating latent TGFβ. This study assessed physiologic pulmonary function and metabolic alterations in the mouse bleomycin model with TG2 genetic deletion. TG2‐deficient mice demonstrated attenuated the fibrosis and preservation of lung function, with significant reduction in elastance and increases in compliance and inspiratory capacity compared to control mice treated with bleomycin. Bleomycin induced metabolic changes in the mouse lung that were consistent with increased aerobic glycolysis, including increased expression of lactate dehydrogenase A and increased production of lactate, as well as increased glutamine, glutamate, and aspartate. TG2‐deficient mice treated with bleomycin exhibited similar metabolic changes but with reduced magnitude. Our results demonstrate that TG2 is required for a typical fibrosis response to injury. In the absence of TG2, the fibrotic response is biochemically similar to wild‐type, but lesions are smaller and lung function is preserved. We also show for the first time that profibrotic pathways of tissue stiffening and metabolic reprogramming are interconnected, and that metabolic disruptions in fibrosis go beyond glycolysis. [ABSTRACT FROM AUTHOR]

The Eurasian Bronze Age (BA) has been described as a period of substantial human migrations, the emergence of pastoralism, horse domestication, and development of metallurgy. This study focuses on two north Eurasian sites sharing Siberian genetic ancestry. One of the sites, Rostovka, is associated with the Seima-Turbino (ST) phenomenon (~2200-1900 BCE) that is characterized by elaborate metallurgical objects found throughout Northern Eurasia. The genetic profiles of Rostovka individuals vary widely along the forest-tundra Siberian genetic cline represented by many modern Uralic-speaking populations, and the genetic heterogeneity observed is consistent with the current understanding of the ST being a transcultural phenomenon. Individuals from the second site, Bolshoy Oleni Ostrov in Kola, in comparison form a tighter cluster on the Siberian ancestry cline. We further explore this Siberian ancestry profile and assess the role of the ST phenomenon and other contemporaneous BA cultures in the spread of Uralic languages and Siberian ancestry. This study highlights Bronze Age northern Eurasia as a region of interaction between various groups sharing a Siberian ancestry component and the spread of languages and cultures. [ABSTRACT FROM AUTHOR]

Peanut (Arachis hypogaea L.) is a rainfed crop grown in both tropical and subtropical agro-climatic regions of the world where drought causes around 20% yield losses per year. In the United States, annual losses caused by drought are around $50 million. The objective of this research was to (1) identify genetic variation for the normalized difference vegetation index (NDVI), canopy temperature depression (CTD), relative chlorophyll content by SPAD reading (SCMR), CO2 assimilation rate, and wilting among recombinant inbred lines (RILs) derived from two diverse parents N08086olJCT and ICGV 86015, to (2) determine if the physiological traits can be used for expediting selection for drought tolerance, and (3) experimental validation to identify lines with improved yield under water-limited conditions. Initially, 337 lines were phenotyped under rainfed production and a selected subset of 52 RILs were tested under rainout shelters, where drought was imposed for eight weeks during the midseason (July and August). We found that under induced drought, pod yield was negatively correlated with wilting and CTD, i.e., cooler canopy and high yield correlated positively with the NDVI and SPAD. These traits could be used to select genotypes with high yields under drought stress. RILs #73, #56, #60, and #31 performed better in terms of yield under both irrigated and drought conditions compared to check varieties Bailey, a popular high-yielding commercial cultivar, and GP-NC WS 17, a drought-tolerant germplasm. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review explores cardiac adaptation in monochorionic (MC) twins with twin–twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) and assesses the risk of congenital heart defects (CHDs). Methods: Adhering to PRISMA guidelines, 63 studies were reviewed (49 on cardiac adaptation, 13 on CHD, one on both). A narrative synthesis of cardiac adaptation patterns was performed. Additionally, a meta‐analysis compared the livebirth prevalence of CHD in TTTS and sFGR against uncomplicated MC twins. Results: In TTTS recipients, cardiac function may be impaired for diastolic, systolic, as well as global functions, while in donors, cardiac function is generally preserved. In sFGR, large twins may show hypertrophic cardiomyopathy, and small twins may show impaired systolic function. Co‐occurrence of TTTS and sFGR magnifies cardiac impact but is often underreported. Meta‐analysis for CHD prevalence revealed a relative risk ratio of 3.5 (95% CI: 2.5–4.9) for TTTS and 2.2 (95%CI: 1.3–3.5) for sFGR compared with uncomplicated MC twins. Conclusions: This study highlights the well‐documented cardiac adaptation in TTTS, contrasting with limited understanding in sFGR. Elevated CHD risks were observed in both conditions. Enhanced cardiovascular surveillance is warranted in complicated MC twin pregnancies. Future research should explore cardiac adaptation in sFGR and its long‐term consequences. Key points: What is already known about this topic? Existing literature extensively documents that the hemodynamic imbalance in twin–twin transfusion syndrome (TTTS) induces distinct cardiac adaptation in both the recipient and the donor.TTTS twins are more prone to congenital heart disease (CHD) than singletons and uncomplicated monochorionic (MC) twins. What does this review add? Cardiac adaptation also applies to selective fetal growth restricted (sFGR) twins, affecting both the larger and smaller twins, highlighting a crucial, yet underexplored aspect for future studies.TTTS twins are 3.5 times and sFGR twins are 2.2 times more likely to develop structural heart defects than uncomplicated MC twins. [ABSTRACT FROM AUTHOR]

Background/Objectives: International guidelines recommend transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC). However, it is used outside these recommendations and has proven beneficial in prolonging survival. Since the role of TACE outside BCLC stage B is unclear, the present study analyzed the results of TACE performed at a tertiary center in Switzerland for different treatment groups, and aims to highlight the treatment outcomes for these groups. Methods: This retrospective cohort study includes 101 HCC patients undergoing TACE at our center. Patients were further subdivided into groups according to therapy combinations (therapies applied before and after index TACE). Kaplan–Meier survival curves were calculated for the Barcelona Center for Liver Cancer (BCLC) subgroups. Results: After TACE, the median survival was 28.1 months for BCLC 0, 31.5 months for BCLC A, 20.5 months for BCLC B, 10.8 for BCLC C, and 7.5 months for BCLC D. A lesion size larger than 55 mm was negatively associated with survival (HR 2.8, 95% CI 1.15–6.78). Complications occurred after TACE procedures: Clavien–Dindo I + II = 30, Clavien–Dindo > 3 = 2. Conclusions: TACE was performed in a substantial part of our cohort outside of routinely used treatment guidelines. The combination of the survival data and complication rate in these patients suggests it was a safe and beneficial strategy. Furthermore, our data show that in our cohort, the survival benefit associated with TACE was restricted to patients with a lesion size smaller than 55 mm. [ABSTRACT FROM AUTHOR]

Fetal hydrops as detected by prenatal ultrasound usually carries a poor prognosis depending on the underlying aetiology. We describe the prenatal and postnatal clinical course of two unrelated female probands in whom de novo heterozygous missense variants in the planar cell polarity gene CELSR1 were detected using exome sequencing. Using several in vitro assays, we show that the CELSR1 p.(Cys1318Tyr) variant disrupted the subcellular localisation, affected cell-cell junction, impaired planar cell polarity signalling and lowered proliferation rate. These observations suggest that deleterious rare CELSR1 variants could be a possible cause of fetal hydrops. [ABSTRACT FROM AUTHOR]