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InP-based quantum dots (QDs) have Stokes shifts and photoluminescence (PL) line widths that are larger than in II–VI semiconductor QDs with comparable exciton energies. The mechanisms responsible for these spectral characteristics are investigated in this paper. Upon comparing different semiconductors, we find the Stokes shift decreases in the following order: InP > CdTe > CdSe. We also find that the Stokes shift decreases with core size and decreases upon deposition of a ZnSe shell. We suggest that the Stokes shift is largely due to different absorption and luminescent states in the angular momentum fine structure. The energy difference between the fine structure levels, and hence the Stokes shifts, are controlled by the electron–hole exchange interaction. Luminescence polarization results are reported and are consistent with this assignment. Spectral widths are controlled by the extent of homogeneous and inhomogeneous broadening. We report PL and PL excitation (PLE) spectra that facilitate assessing the roles of homogeneous and different inhomogeneous broadening mechanisms in the spectra of zinc-treated InP and InP/ZnSe/ZnS particles. There are two distinct types of inhomogeneous broadening: size inhomogeneity and core–shell interface inhomogeneity. The latter results in a distribution of core–shell band offsets and is caused by interfacial dipoles associated with In–Se or P–Zn bonding. Quantitative modeling of the spectra shows that the offset inhomogeneity is comparable to but somewhat smaller than the size inhomogeneity. The combination of these two types of inhomogeneity also explains several aspects of reversible hole trapping dynamics involving localized In3+/VZn2− impurity states in the ZnSe shells. [ABSTRACT FROM AUTHOR]

The ocean response to Antarctic Ice Sheet (AIS) mass loss has been extensively studied using numerical models, but less attention has been given to the atmosphere. We examine the global atmospheric response to AIS meltwater in an ensemble of experiments performed using two fully coupled climate models under a pre‐industrial climate. In response to AIS meltwater, the experiments yield cooling from the surface to the tropopause over the subpolar Southern Ocean, warming in the Southern Hemisphere polar stratosphere, and cooling in the upper tropical troposphere. Positive feedbacks, initiated by disrupted ocean‐atmosphere heat exchange, result in a change in the top‐of‐atmosphere radiative balance caused primarily through surface and near‐surface albedo changes. Changes in the atmospheric thermal structure alter the jet streams aloft. The results highlight the global influence of AIS melting on the climate system and the potential for impacts on mid‐latitude climate patterns and delayed regional warming signals. Plain Language Summary: The Antarctic Ice Sheet is expected to melt as the climate warms and many studies have focused on understanding how the ocean state might respond. How the structure of the global atmosphere, including temperature and global wind patterns, will respond to this added meltwater and associated ocean state changes remains unclear. We investigate changes in atmospheric properties including temperature, clouds, radiation, water vapor, and global wind patterns that occur when meltwater is added to the Antarctic coast in two climate models. We find temperatures within the troposphere to generally decrease, whereas temperatures in the stratosphere increase over the Southern Hemisphere polar region. Temperatures also decrease in the high‐altitude troposphere near the equator. Changes throughout the atmosphere, including clouds and water vapor, in combination with changes in atmosphere‐ocean heat exchange, impact the amount of energy within the climate system. Changes in the temperature structure of the atmosphere have far‐reaching effects on global wind patterns. The response to isolated Antarctic Ice Sheet melting, which we present, generally opposes that found for typical global warming scenarios lacking the ice sheet response. All of this highlights the remote consequences of Antarctic Ice Sheet melting. Key Points: Freshwater is added along the coast of Antarctica in two climate models and changes in the full‐column global atmosphere are investigatedTemperature changes extend from the surface to the stratosphere and from the Southern Ocean to the upper tropical troposphereMeltwater‐induced changes in the atmosphere's thermal structure result in altered large‐scale wind patterns [ABSTRACT FROM AUTHOR]

PEGylation (the covalent attachment of one or more poly(ethylene glycol) (PEG) units to a therapeutic) is a well-established technique in the pharmaceutical industry to increase blood-residence time and decrease immunogenicity. A challenging aspect of PEGylation is the dispersity of PEGylation agents, which results in batch-to-batch variations and analytical limitations. Herein, we present an approach to overcome these limitations by manufacturing a defined molecular weight (dispersity-free) PEGylation agent. We synthesise a defined molecular weight (Mw), linear 5 kDa methoxy-PEG (mPEG) active ester in an efficient and scalable manner using an iterative liquid-phase approach based on Nanostar Sieving. We then perform a comparative study on the random PEGylation and subsequent characterisation of the protein bovine serum albumin (BSA), using both the defined Mw, dispersity-free mPEG active ester, and a commercially available disperse 5 kDa mPEG active ester. We demonstrate that the defined Mw PEG both allows for facile monitoring of chemical modification reactions during the synthesis of the PEGylation agents, and facilitates straightforward identification of the PEGylated fragments within a PEGylated protein via a simple peptide mapping approach using UPLC-MS. PEGylation, the covalent attachment of one or more poly(ethylene glycol) (PEG) units to a therapeutic, is commonly used in the pharmaceutical industry, but the dispersity of PEGylation agents results in batch-to-batch variations and analytical limitations. Here, the authors present an approach to overcome these limitations by manufacturing a defined molecular weight, dispersity-free, 5 kDa methoxy PEG-succinimidyl propionate (mPEG-SP5135) using Nanostar Sieving. [ABSTRACT FROM AUTHOR]

The wind energy requirements for high temporal and spatial observations, unavailable in many countries, are met by reanalysed wind data, which are increasingly used in wind power assessments. However, these data also include unrealistic features, making their validation compulsory. The validation analysis of ERA5 and MERRA-2 wind data, two of the most successful wind reanalyses, with observations near Morocco's coast, highlighted the existence of bias in both datasets, and other shortcomings. The study was conducted at eight selected sites in the period 2011-2020 using linear and probability density function based statistical tests. The local ERA5-BA and MERRA-2 BA velocity fields were created using Bias Adjustment (BA) Techniques. Only part of the observed and modelled datasets (training period) were used to identify the transfer function. The BA fields were verified against observations during the remaining period (verification period). They outperformed their respective non-adjusted fields and also the WFDE5 (the global bias-corrected ERA5 wind field) in the wind potential assessments, represented by capacity factor and low-wind day. At every location, the relative errors in the latter's estimates using ERA5-BA were lowered to less than 10 %, and the same was true for MERRA-2-BA. Thus, an observational dataset of reduced length can help overcome some reanalysed wind data limitations for wind power estimations. Additionally, this methodology can be applied to the correction of each reanalysis update. [ABSTRACT FROM AUTHOR]

Humans have used medicinal plants to treat various diseases for thousands of years. Cistus species are also widely used in traditional medicine and have various medicinal applications; therefore, they deserve more in-depth research. The present study evaluated the chemical profile, antioxidant, enzyme inhibition, and cytotoxic properties of the twigs and leaves of C. creticus L., C. laurifolius L., and C. salviifolius L. grown in Türkiye. The methanolic extracts of the three species were rich in phenolics, mainly flavonoids. Exerted potent antioxidant activity with a methanolic extract from the leaves of C. salviifolius displayed the highest total phenolic (97.08-mg gallic acid equivalent/g) and flavonoid (49.60-mg rutin equivalent/g) contents, as well as antiradical (2,2-diphenyl-1-picrylhydrazyl) assay = 612.11 mg TE (trolox equivalent)/g; (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) = 804.66 mg TE/g), reducing ions (cupric reducing antioxidant capacity) = 690.54 mg TE/g; ferric reducing antioxidant power = 459.34 mg TE/g), and chelating (15.58 mg EDTAE/g) properties. It also revealed the best amylase and glucosidase inhibitory activity. Extracts from the twigs of the three Cistus species, except the leaves of C. salviifolius and C. laurifolius, displayed comparable acetylcholinesterase inhibitory activity (2.48-2.57 mg galanthamine equivalent (GALAE)/g). The twig of C. laurifolius also exerted the best antibutyrylcholinesterase (10.50 mg GALAE/g) and antityrosinase (73.15 mg kojic acid equivalent/g) activities. C. creticus leaves revealed toxicity toward the RAW cell line (cell viability reduced to 68.8%) and were not toxic to normal cells (S17). In conclusion, these three Cistus species were shown to be a rich source of bioactive compounds with the potential for future applications in the food, pharmaceutical, and cosmetic industries. [ABSTRACT FROM AUTHOR]

This paper explores the relationship between family ownership and a firm's leverage from the socioemotional wealth (SEW) theory. We propose that SEW objectives (i.e., family control, long-term horizon, and family firm reputation) might have a mediating effect on the family ownership-leverage link. In addition, we argue that an internal contingency—such as below aspiration performance—may moderate SEW's influence on the family ownership-leverage relationship as a result of a shift in focus from non-economic to economic goals. Using a sample of European listed firms from 2011 to 2018, we find that the negative impact of family ownership on a firm's leverage is mediated through SEW objectives. Moreover, our evidence suggests that a negative performance-aspiration gap weakens the mediating influence of these SEW objectives on leverage. Over all, our study reveals that SEW is a key channel which drives family firms' reluctance to leverage. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the impact of the COVID-19 pandemic and associated stay-at-home orders on the breastfeeding experiences of U.S. people a identify facilitators and barriers to breastfeeding during this period, and to assess the effects of maternal stress and misinformation on breastfeeding practices. Methods: U.S. women with infants were selected through purposive and convenience sampling. An online survey, distributed during summer 2020, measured changes in infant feeding practices, maternal stress levels, use of lactation support resources, and the influence of misinformation on feeding decisions. Quantitative data were analyzed using descriptive statistics, and qualitative responses underwent thematic analysis. Results: Our sample (n = 1,861) revealed that 34% of U.S. women realized the pandemic affected their feeding practices, 544 women provided qualitative data. Major themes from qualitative analysis included ease of breastfeeding at home, bonding, increased breastfeeding duration, and challenges like limited access to lactation support. Logistic regressions highlighted demographic influences on breastfeeding practices, with no significant effects found related to the child's age or women's income on changes in feeding practices. Conclusions for Practice: The COVID-19 pandemic substantially impacted breastfeeding experiences of U.S. women, yielding insights for future policy and healthcare practices. The findings underscore the potential benefits of telehealth lactation support services and flexible remote work environments for breastfeeding people. Clear and scientifically-grounded communication regarding breastfeeding, mental health support, and policy development, are essential to promote equitable and flexible work and maternity leave options for breastfeeding people especially during global health crises. Significance: This study provides new insights into how the COVID-19 pandemic's stay-at-home orders uniquely impacted breastfeeding practices among a large and diverse sample of U.S. women across various regions, income levels, and racial/ethnic backgrounds. By capturing a wide range of experiences, we address a critical gap in understanding the effects of sudden societal changes on breastfeeding across different demographics. Our findings highlight both facilitators—such as increased time at home leading to easier breastfeeding, stronger mother-infant bonding, and extended breastfeeding duration—and barriers—including limited access to lactation support and heightened maternal stress. The diversity of our sample enhances the applicability of our results to inform maternal and child health policies and practices. We underscore the potential benefits of telehealth lactation services and flexible remote work policies in enhancing breastfeeding outcomes and reducing health inequities, emphasizing the need for supportive measures that promote breastfeeding, especially during global health crises. [ABSTRACT FROM AUTHOR]

Rationale: Knowledge regarding the prevalence and shared and unique characteristics of the restrictive spirometric pattern (RSP) and preserved ratio impaired spirometry (PRISm) is lacking for a general population investigated with post-bronchodilator spirometry and computed tomography of the lungs. Objectives: To investigate shared and unique features for RSP and PRISm. Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), a general population sample of 28,555 people aged 50–64 years (including 14,558 never-smokers) was assessed. The participants answered a questionnaire and underwent computed tomography of the lungs, post-bronchodilator spirometry, and coronary artery calcification score. Odds ratios with 95% confidence intervals (CIs) were calculated using adjusted logistic regression. RSP was defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ≥0.70 and FVC <80%. PRISm was defined as FEV1/FVC ≥0.70 and FEV1 <80%. A local reference equation was applied. Results: The prevalence of RSP and PRISm were 5.1% (95% CI, 4.9–5.4) and 5.1% (95% CI, 4.8–5.3), respectively, with similar values seen in never-smokers. For RSP and PRISm, shared features were current smoking, dyspnea, chronic bronchitis, rheumatic disease, diabetes, ischemic heart disease, bronchial wall thickening, interstitial lung abnormalities, and bronchiectasis. Emphysema was uniquely linked to PRISm (odds ratio, 1.69; 95% CI, 1.36–2.10) versus 1.10 (95% CI, 0.84–1.43) for RSP. Coronary artery calcification score ≥300 was related to PRISm, but not among never-smokers. Conclusions: PRISm and RSP have respiratory, cardiovascular, and metabolic conditions as shared features. Emphysema is only associated with PRISm. Coronary atherosclerosis may be associated with PRISm. Our results indicate that RSP and PRISm may share more features than not. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Although statistical models for predicting type 1 diabetes risk have been developed, approaches that reveal the heterogeneity of the at-risk population by identifying clinically meaningful clusters are lacking. We aimed to identify and characterise clusters of islet autoantibody-positive individuals who share similar characteristics and type 1 diabetes risk. Methods: We tested a novel outcome-guided clustering method in initially non-diabetic autoantibody-positive relatives of individuals with type 1 diabetes, using the TrialNet Pathway to Prevention study data (n=1123). The outcome of the analysis was the time to development of type 1 diabetes, and variables in the model included demographic characteristics, genetics, metabolic factors and islet autoantibodies. An independent dataset (the Diabetes Prevention Trial of Type 1 Diabetes Study) (n=706) was used for validation. Results: The analysis revealed six clusters with varying type 1 diabetes risks, categorised into three groups based on the hierarchy of clusters. Group A comprised one cluster with high glucose levels (median for glucose mean AUC 9.48 mmol/l; IQR 9.16–10.02) and high risk (2-year diabetes-free survival probability 0.42; 95% CI 0.34, 0.51). Group B comprised one cluster with high IA-2A titres (median 287 DK units/ml; IQR 250–319) and elevated autoantibody titres (2-year diabetes-free survival probability 0.73; 95% CI 0.67, 0.80). Group C comprised four lower-risk clusters with lower autoantibody titres and glucose levels (with 2-year diabetes-free survival probability ranging from 0.84–0.99 in the four clusters). Within group C, the clusters exhibit variations in characteristics such as glucose levels, C-peptide levels and age. A decision rule for assigning individuals to clusters was developed. Use of the validation dataset confirmed that the clusters can identify individuals with similar characteristics. Conclusions/interpretation: Demographic, metabolic, immunological and genetic markers may be used to identify clusters of distinctive characteristics and different risks of progression to type 1 diabetes among autoantibody-positive individuals with a family history of type 1 diabetes. The results also revealed the heterogeneity in the population and complex interactions between variables. [ABSTRACT FROM AUTHOR]

Environmental conditions (i.e., climatic variation) can strongly influence the cost and benefits of reproductive traits. Yet there is still no consensus on whether changing environmental conditions strengthen or relax sexual selection. Evidence from the literature suggests that highly variable environments can limit mate choice and investment in sexual traits, hence relaxing sexual selection pressures. Here, we tested this hypothesis using the nuptial gift-giving spider Paratrechalea ornata , in which males can either wrap nutritive (fresh prey) or worthless (prey leftovers) items in silk. We examined changes in males' sexual trait and female choice among six populations living under different climatic conditions. We found that large variation in precipitation limits female choice, potentially favoring the spread of deceptive worthless gifts. In populations under highly variable conditions and with the highest frequencies of worthless gifts (70%), males offering such gifts acquire longer mating durations than those offering nutritive gifts. In contrast, in populations with less variable conditions and the lowest frequencies of worthless gift (36%), females shortened mating duration to males offering worthless gifts. Our findings are consistent with the prediction that highly variable environmental conditions relax sexual selection. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) represents cardiometabolic dysregulation, defined by hypertension, obesity, diabetes, and dyslipidemia. There remains a significant gap in our understanding of whether MetS impacts outcomes of abdominal body contouring procedures. We aimed to assess the influence of MetS on postoperative outcomes of abdominal body contouring by concurrent abdominoplasty and panniculectomy. Methods: The ACS-NSQIP database was utilized to identify patients who underwent concurrent abdominoplasty and panniculectomy procedures from 2012 to 2022. Through propensity score matching, distinct cohorts were established based on the presence of MetS, characterized by patients receiving medical interventions for diabetes mellitus and hypertension, with a body mass index exceeding 30 kg/m2. Univariate and multivariate analyses were conducted to evaluate differences between groups. Results: A total of 14,642 patients underwent abdominal body contouring from 2012 to 2022. Following propensity score matching, 730 patients were included in the analysis, with 365 in each group (MetS vs. non-MetS). Bivariate analysis revealed a longer hospital length of stay (2.3 vs. 1.6 days; p = 0.007) in the MetS cohort compared to the non-MetS cohort. Patients diagnosed with MetS had an average length of stay of 0.6 days longer than non-MetS patients (95% CI [0.17, 1.01]; p = 0.007). No noteworthy disparities were observed in the rates of 30-day wound complications, mild systemic, and severe systemic complications, and readmission rates between the groups. Conclusions: Our findings suggest that abdominal body contouring remains a secure option for patients with MetS. Nonetheless, the longer hospital length stays observed in patients with MetS may translate to increased overall costs to the healthcare system. Continued research is warranted to comprehensively assess the economic implications of MetS in the context of abdominal body contouring. Level of Evidence III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

The human Golgi α-mannosidase, hGMII, removes two mannose residues from GlcNAc-Man5GlcNAc2 to produce GlcNAcMan3GlcNAc2, the precursor of all complex N-glycans including tumour-associated ones. The natural product GMII inhibitor, swainsonine, blocks processing of cancer-associated N-glycans, but also inhibits the four other human α-mannosidases, rendering it unsuitable for clinical use. Our previous structure-guided screening of iminosugar pyrrolidine and piperidine fragments identified two micromolar hGMII inhibitors occupying the enzyme active pockets in adjacent, partially overlapping sites. Here we demonstrate that fusing these fragments yields swainsonine-configured indolizidines featuring a C3-substituent that act as selective hGMII inhibitors. Our structure-guided GMII-selective inhibitor design complements a recent combinatorial approach that yielded similarly configured and substituted indolizidine GMII inhibitors, and holds promise for the potential future development of anti-cancer agents targeting Golgi N-glycan processing. [ABSTRACT FROM AUTHOR]

In seasonal environments, organisms with complex life cycles not only contend with seasonal time constraints (TC) but also increasingly face global change stressors that may interfere with responses to TC. Here, we tested how warming and predator stress imposed during the egg and larval stages shaped life history and behavioural responses to TC in the temperate damselfly Ischnura elegans. Eggs from early and late clutches in the season were subjected to ambient and 4 °C warming temperature and the presence or absence of predator cues from perch and signal crayfish. After hatching, larvae were retained at the same thermal regime, and the predator treatment was continued or not up to emergence. The late eggs decreased their development time, especially under warming and when not exposed to predator cues. However, the late eggs increased their development time when exposed to predator cues, especially to crayfish cues. The TC decreased survival of late larvae that were as eggs exposed to crayfish cues, indicating a carry-over effect. The TC and warming additively reduced late larvae development time to emergence. Independent of the TC, predator cue effects on development time were stronger during the egg than during the larval stage. The late individuals expressed lower mass at emergence, which mirrored the size difference between field-collected mothers. Warming caused a higher mass at emergence. The late individuals increased their boldness and showed a higher number of moves, whereas warming caused a decreased boldness. There was no predator cue effect on larval behaviour. The results indicate that late individuals compensate for late season egg laying, which is facilitated under warming but counteracted under predation risk, especially when imposed by the crayfish. [ABSTRACT FROM AUTHOR]

Background: The popularity of cosmetic tourism may increase unnecessary risks for patients as postoperative care is variable. However, little is known about the current trends and public perception of this growing phenomenon. This study compares interest in cosmetic tourism in popular medical tourism destinations relative to the US. Methods: Google Trends was queried from October 2017 to September 2023, examining trends over the full period and dissecting changes between 2017–2020 and 2020–2023. Search volume data were retrieved for the top international countries and the US for each of the top five cosmetic procedures, according to the ISAPS 2022 Global Survey. A p value < 0.05 was used for statistical significance. Results: Searches for liposuction, blepharoplasty, breast augmentation, mastopexy, and abdominoplasty were compared between the US, Mexico, Turkey, Thailand, and Colombia. Google Trends data mirrored the prevalence of the two most common procedures, liposuction, and breast augmentation. Differences in interest regarding liposuction were greatest in Mexico, Thailand, and Turkey compared to the US (p < 0.05). Medical tourism for blepharoplasty had the highest search interest scores for Turkey and Thailand from 2017 to 2023 (p < 0.05). Significant differences were also consistent across all time intervals for breast augmentation, mastopexy, and abdominoplasty, with higher interest in Mexico and Turkey (p < 0.05). Conclusions: Google Trends analysis serves as an insightful tool for understanding cosmetic tourism. Changing trends bring the potential to assess worldwide versus country-specific procedure interest. These observed trends may foreshadow future international aesthetic procedure trends. No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 [ABSTRACT FROM AUTHOR]

With advances in technology, the generation of electrical energy through the harvesting of energies dissipated in the form of mechanical vibration, known as power harvesting, has received increasing attention in recent decades. It is undoubtedly an interesting means to power systems with low energy consumption. This research aims to evaluate an energy generation system based on the piezoelectric effect activated by mechanical excitation and develop a system capable of powering devices and sensors for temperature monitoring in a practical situation, such as in an engine room, aiming to ensure its safe operation. Two transducers subjected to vibrational excitation were evaluated, and then an energy generation system using a buck DC-DC converter circuit was assessed. The transducer was connected to the input of the board, the microcontroller to the output, and the LM35 temperature sensor along with the battery was used to ensure the circuit's autonomy. Additionally, the Attiny85 microcontroller was programmed to perform temperature monitoring tasks in a continuous low-energy-consumption mode. The obtained spectral analysis results showed a maximum generation power of 8.88 mW for the PZT-5H transducer and 3.3 mW for the P5-13B transducer. The use of LTC3588-1 increased the autonomy of the monitoring system by 64.3% and reduced the system's usage time in cases of temperature anomalies by 50%. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatohepatitis (MASH) represents a global health threat. MASH pathophysiology involves hepatic lipid accumulation and progression to severe conditions like cirrhosis and, eventually, hepatocellular carcinoma. Fibroblast growth factor (FGF)-19 has emerged as a key regulator of metabolism, offering potential therapeutic avenues for MASH and associated disorders. We evaluated the therapeutic potential of non-mitogenic (NM)-FGF19 mRNA formulated in liver-targeted lipid nanoparticles (NM-FGF19-mRNAs-LNPs) in C57BL/6NTac male mice with diet-induced obesity and MASH (DIO-MASH: 40% kcal fat, 20% kcal fructose, 2% cholesterol). After feeding this diet for 21 weeks, NM-FGF19-mRNAs-LNPs or control (C-mRNA-LNPs) were administered (0.5 mg/kg, i.v.) weekly for another six weeks, in which diet feeding continued. NM-FGF19-mRNAs-LNPs treatment in DIO-MASH mice resulted in reduced body weight, adipose tissue depots, and serum transaminases, along with improved insulin sensitivity. Histological analyses confirmed the reversal of MASH features, including steatosis reduction without worsening fibrosis. NM-FGF19-mRNAs-LNPs reduced total hepatic bile acids (BAs) and changed liver BA composition, markedly influencing cholesterol homeostasis and metabolic pathways as observed in transcriptomic analyses. Extrahepatic effects included the down-regulation of metabolic dysfunction-associated genes in adipose tissue. This study highlights the potential of NM-FGF19-mRNA-LNPs therapy for MASH, addressing both hepatic and systemic metabolic dysregulation. NM-FGF19-mRNA demonstrates efficacy in reducing liver steatosis, improving metabolic parameters, and modulating BA levels and composition. Given the central role played by BA in dietary fat absorption, this effect of NM-FGF19-mRNA may be mechanistically relevant. Our study underscores the high translational potential of mRNA-based therapies in addressing the multifaceted landscape of MASH and associated metabolic perturbations. [ABSTRACT FROM AUTHOR]

Background/Objectives: Currently, the prediction of disease recurrence after radical prostatectomy (RP) in localized prostate cancer (PCa) relies on clinicopathological parameters, which lack accuracy in predicting clinical outcomes. This study focused on evaluating the utility of cfDNA levels and fragmentation patterns as prognostic biomarkers in progressive prostate-specific antigen (PSA) patients, including those with persistent PSA and biochemical recurrence (BR), after primary treatment in localized PCa patients. Methods: Twenty-nine high-risk localized PCa patients were enrolled in the study between February 2022 and May 2023. Blood samples were obtained before robotic RP. cfDNA concentration and fragment size were quantified using the Quant-it PicoGreen dsDNA Assay kit and Agilent 2200 TapeStation System, respectively. Results: The mean PSA value at diagnosis was 9.4 ng/mL. Seven patients (24.1%) had stage pT2 and 22 (75.9%) pT3. Nine patients (31%) had detectable PSA at the first PSA control six weeks after surgery, and four patients (20%) had BR during a mean follow-up of 18.4 months. No associations were found between cfDNA levels or fragmentation patterns and clinicopathological data. Although not statistically significant, patients with detectable PSA levels post-surgery exhibited higher cfDNA levels and shorter fragments compared with those with undetectable PSA. Conclusions: Our study indicated a tendency toward more fragmented cfDNA levels in PCa patients with persistent PSA. Strikingly, biochemical recurrent PCa patients exhibited similar cfDNA levels and fragmentation patterns compared to non-recurrent patients. Further studies exploring liquid biopsy-derived biomarkers in localized PCa patients are needed to elucidate their clinical utility in predicting PSA persistence. [ABSTRACT FROM AUTHOR]

Background: Nelore cattle play a key role in tropical production systems due to their resilience to harsh conditions, such as heat stress and seasonally poor nutrition. Monitoring their genetic diversity is essential to manage the negative impacts of inbreeding. Traditionally, inbreeding and inbreeding depression are assessed by pedigree-based coefficients (F), but recently, genetic markers have been preferred for their precision in capturing the inbreeding level and identifying animals at risk of reduced productive and reproductive performance. Hence, we compared the inbreeding and inbreeding depression for productive and reproductive performance traits in Nelore cattle using different inbreeding coefficient estimation methods from pedigree information (FPed), the genomic relationship matrix (FGRM), runs of homozygosity (FROH) of different lengths (> 1 Mb (genome), between 1 and 2 Mb - FROH 1−2; 2–4 Mb FROH 2−4 or > 8 Mb FROH >8) and excess homozygosity (FSNP). Results: The correlation between FPed and FROH was lower when the latter was based on shorter segments (r = 0.15 with FROH 1−2, r = 0.20 with FROH 2−4 and r = 0.28 with FROH 4−8). Meanwhile, the FPed had a moderate correlation with FSNP (r = 0.47) and high correlation with FROH >8 (r = 0.58) and FROH−genome (r = 0.60). The FROH−genome was highly correlated with inbreeding based on FROH>8 (r = 0.93) and FSNP (r = 0.88). The FGRM exhibited a high correlation with FROH−genome (r = 0.55) and FROH >8 (r = 0.51) and a lower correlation with other inbreeding estimators varying from 0.30 for FROH 2−4 to 0.37 for FROH 1−2. Increased levels of inbreeding had a negative impact on the productive and reproductive performance of Nelore cattle. The unfavorable inbreeding effect on productive and reproductive traits ranged from 0.12 to 0.51 for FPed, 0.19–0.59 for FGRM, 0.21–0.58 for FROH−genome, and 0.19–0.54 for FSNP per 1% of inbreeding scaled on the percentage of the mean. When scaling the linear regression coefficients on the standard deviation, the unfavorable inbreeding effect varied from 0.43 to 1.56% for FPed, 0.49–1.97% for FGRM, 0.34–2.2% for FROH−genome, and 0.50–1.62% for FSNP per 1% of inbreeding. The impact of the homozygous segments on reproductive and performance traits varied based on the chromosomes. This shows that specific homozygous chromosome segments can be signs of positive selection due to their beneficial effects on the traits. Conclusions: The low correlation observed between FPed and genomic-based inbreeding estimates suggests that the presence of animals with one unknown parent (sire or dam) in the pedigree does not account for ancient inbreeding. The ROH hotspots surround genes related to reproduction, growth, meat quality, and adaptation to environmental stress. Inbreeding depression has adverse effects on productive and reproductive traits in Nelore cattle, particularly on age at puberty in young bulls and heifer calving at 30 months, as well as on scrotal circumference and body weight when scaled on the standard deviation of the trait. [ABSTRACT FROM AUTHOR]

Aims: The prevalence of iron deficiency (ID) in newly diagnosed heart failure (HF) and the progression of ID in patients after initiation of HF therapy are unknown. We aimed to describe the natural trajectory of ID in patients with new onset HF during the first year after HF diagnosis, assessing associations between ID, clinical factors, and quality of life (QoL). Methods and results: A prospective cohort of patients with new onset HF in hospitals or outpatient clinics at five major hospitals in Stockholm, Sweden, during 2015–2018 were analysed with clinical assessment, electrocardiogram, blood samples including iron levels, Minnesota living with heart failure questionnaire (MLHFQ), and echocardiogram at baseline and after 12 months. Of 547 patients with new‐onset HF, 482 (88%) had complete iron data at baseline. Median age was 70 years (interquartile range 61–77) and 311 (65%) were men; 55% of patients had ejection fraction (EF) ≤ 40%, 19% had EF 41–49%, and 26% had HF with preserved EF (HFpEF) [Correction added on 26 June 2024, after first online publication: The 'Mean age was 70 years' has been corrected to 'Median age was 70 years' in this version.]. At baseline, 163 patients (34%) had ID defined as ferritin <100 μg/L or ferritin 100–299 μg/L and transferrin saturation <20%. After 12 months of follow‐up, 119 (32%) had ID of the 368 patients who had complete iron data both at baseline and after 12 months and did not receive intravenous (i.v.) iron during follow‐up. During the first year after HF diagnosis, 19% had persistent ID, 13% developed ID, 11% resolved ID, and 57% never had ID, consequently 24% changed their classification. Anaemia at baseline was the strongest independent predictor of ID 1 year after diagnosis [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.88–8.13, P < 0.001], followed by HF hospitalization (OR 2.21, 95% CI 1.24–3.95, P < 0.01), female sex (OR 2.04, 95% CI 1.25–3.32, P < 0.01), HFpEF (OR 1.96, 95% CI 1.13–3.39, P < 0.05), and diabetes mellitus (OR 1.92, 95% CI 1.06–3.48, P < 0.05). ID was associated with low QoL at baseline (MLHFQ score mean difference 7.4 points, 95% CI 3.1–11.7, P < 0.001), but not at follow‐up. Conclusions: About one third of patients with new onset HF had ID both at the time of HF diagnosis and after 1 year, though a quarter of the patients changed their ID status. Patients with anaemia, HF hospitalization, female gender, HFpEF, or diabetes mellitus at baseline were more likely to have ID after 1 year implying that these should be carefully screened for ID to find those in need of i.v. iron treatment. [ABSTRACT FROM AUTHOR]

Disruptions in circadian rhythms are associated with an increased risk of developing metabolic diseases. General control nonderepressible 2 (GCN2), a primary sensor of amino acid insufficiency and activator of the integrated stress response (ISR), has emerged as a conserved regulator of the circadian clock in multiple organisms. The objective of this study was to examine diurnal patterns in hepatic ISR activation in the liver and whole body rhythms in metabolism. We hypothesized that GCN2 activation cues hepatic ISR signaling over a natural 24-h feeding-fasting cycle. To address our objective, wild-type (WT) and whole body Gcn2 knockout (GCN2 KO) mice were housed in metabolic cages and provided free access to either a control or leucine-devoid diet (LeuD) for 8 days in total darkness. On the last day, blood and livers were collected at CT3 (CT = circadian time) and CT15. In livers of WT mice, GCN2 phosphorylation followed a diurnal pattern that was guided by intracellular branched-chain amino acid concentrations (r2 = 0.93). Feeding LeuD to WT mice increased hepatic ISR activation at CT15 only. Diurnal oscillations in hepatic ISR signaling, the hepatic transcriptome including lipid metabolic genes, and triglyceride concentrations were substantially reduced or absent in GCN2 KO mice. Furthermore, mice lacking GCN2 were unable to maintain circadian rhythms in whole body energy expenditure, respiratory exchange ratio, and physical activity when fed LeuD. In conclusion, GCN2 activation functions to maintain diurnal ISR activation in the liver and has a vital role in the mechanisms by which nutrient stress affects whole body metabolism. NEW & NOTEWORTHY: This work reveals that the eIF2 kinase GCN2 functions to support diurnal patterns in the hepatic integrated stress response during natural feeding and is necessary to maintain circadian rhythms in energy expenditure, respiratory exchange ratio, and physical activity during amino acid stress. [ABSTRACT FROM AUTHOR]

Background: Radiographs are useful for the initial evaluation of the hip joints. The information can be utilized for the betterment of animal health or other goals such as anatomic studies and gait analysis, among others. Therefore, this study aimed to evaluate radiographic measurements of the hip joint in capuchin monkeys, kept under human care at a reference center for wildlife. Methods: Twelve capuchin monkeys (Sapajus spp.) (three adult males, seven adult females, and two sub‐adult females) were evaluated. Ventrodorsal radiographic views were taken under chemical restraint. All measurements on the digital images were performed in triplicate by one examiner. Results and Conclusions: None of the measurements evaluated were statistically different between males and females. No statistical differences were found between hind limbs. The mean (±SD) Norberg angle was 104.92° (±2.82°) and the Wiberg angle was 15.26° (±1.86°). The percentage of the femoral head covered by the acetabulum was 68.57% (±3.65%) and the acetabular index depth to width ratio was 54.66% (±3.85%). In conclusion, the radiographic measurements showed certain morphological features of the hip joint in Sapajus spp. that contribute to improving species knowledge. [ABSTRACT FROM AUTHOR]

Given the failure of high-density lipoprotein (HDL) raising therapies to reduce cardiovascular disease risk, attention has turned towards HDL composition and vascular protective functions. In individuals with insulin resistance, exercise interventions recover HDL function. However, the effect of exercise on HDL in otherwise healthy individuals is unknown. This cross-sectional study aimed to measure HDL composition and antioxidant/endothelial anti-inflammatory function in insulin sensitive endurance athlete and healthy control men. HDL was isolated using density gradient ultracentrifugation. HDL composition was measured using microplate assays for apolipoprotein A-I, total cholesterol content and apolipoprotein M. HDL protein composition was measured using nano-liquid chromatography tandem mass spectrometry. HDL subclass distribution was measured by native gel electrophoresis. HDL in vitro antioxidant function was measured by paraoxonase-1 activity assay and anti-inflammatory function assessed in endothelial cells. Compared with controls, endurance athlete HDL had higher apolipoprotein A-1 (1.65 + 0.62 mg/ml vs 1.21 - 0.34 mg/ml, P=0.028) and higher total cholesterol content (2.09 - 0.44 mmol/L vs 1.54 + 0.33 mmol/L, P<0.001). Proteomics revealed higher apolipoprotein A-II, A-IV and D and transthyretin in endurance athlete HDL versus controls. There was no difference observed in in vitro HDL antioxidant or anti-inflammatory functions between controls and endurance athletes. Despite a more favourable composition, endurance athlete HDL did not have higher in vitro antioxidant or anti-inflammatory function. It is possible that HDL has a ceiling of function, i.e. that healthy HDL function cannot be enhanced by endurance exercise. [ABSTRACT FROM AUTHOR]

This microreview, conducted by interdisciplinary teams, examines complex heritage material systems, such as medieval colors and modern and contemporary artworks. Our multi-analytical approach, a significant aspect of our research, is a means to this end. The conservation of works of art is our shared goal, as it ensures their accessibility and the transfer of cultural heritage to future generations. We seek to interpret the damage, usefulness, and innovation of the experimental design in this context. As Jan Wouters rightly points out, "The terminology used nowadays to describe the potential damage to objects caused by analysis should be refined beyond the destructiveness/non-invasiveness polarization. A terminology should include at least degree level intervention (low, medium, high), usefulness, and innovation". Complementing micro- or sub-micro-sampling with the appropriate analytical methods is crucial, as exemplified in medieval, modern, and contemporary collections studies. Finally, a novel perspective for exploring the information contained in the multiscale heterogeneity of organic historical materials is envisaged, and it includes UV/Visible photoluminescence spectral imaging using a low-intensity ultraviolet synchrotron beam. [ABSTRACT FROM AUTHOR]

Navigating social‐ecological systems toward sustainable trajectories is an important challenge of the Anthropocene. Models of social‐ecological systems can increase our understanding of how social and ecological subsystems interact, their response to environmental changes, and how their dynamics may be altered by management interventions. However, the level of representational detail required for models to describe a particular social‐ecological system with high fidelity (i.e., accurately quantifying system dynamics) may hamper both the interpretability of model results and our ability to identify key processes and feedbacks within the system. In contrast, stylized models describe simplified interactions between a small subset of social‐ecological system elements. Stylized models are a useful tool to identify potential consequences of specific key processes and feedbacks on system functioning. However, the relatively low level of representational detail in these models limits their ability to deliver concrete management options for a particular social‐ecological system. Here, we describe how an exploratory modeling approach can utilize the strengths of stylized models before the construction of social‐ecological system models with high fidelity and representational detail. This exploratory modeling approach is an iterative strategy, with the initial steps comprising the development of stylized models informed by empirical observations. We illustrate this with two examples of stylized modeling of isolated and connected social‐ecological systems. Through repeated confrontation of alternative models with empirical data, exploratory modeling provides useful stepping stones toward the development of models that describe social‐ecological systems in increasingly specific settings with increasing levels of representational detail. When these latter types of models reach a high level of fidelity, they could be used for scenario‐based analyses and participatory decision‐making processes. At this stage, the conceptual insights previously obtained during the exploratory modeling phase may aid in the interpretation and communication of the outcomes of scenario‐based analyses. Hence, exploratory modeling aims to create a synergy between the insights obtained from stylized models and system‐specific, high‐fidelity models in order to generate a deep understanding of the drivers of social‐ecological system dynamics, and how to leverage these drivers to initiate desired changes. [ABSTRACT FROM AUTHOR]

Hydrogel materials are continually developing in biomedical engineering and recently a lot of effort has gone into their engineered performance in physiological applications. Porosity is an important characteristic for tissue engineering scaffolds to allow enhanced biocompatibility and the pore size needed is dependent on the application and type of tissue for which the hydrogel is being used to regenerate. Regarding biomedical applications, the use of conducting polymers is gaining in popularity due to their promising biocompatibility and potential to stimulate cell growth and proliferation through electrical stimulation. Building on previous hydrogel development by the authors, this study focuses on developing a biocompatible hydrogel scaffold with adjustable porosity and swelling capabilities, robust mechanical properties, electrical conductivity, and high thermal stability. The objective of this work is to examine the effect of freezing temperature, cross‐linker and porosity on the final characteristics of the scaffold and to then determine possible applications. The porosity, swelling degree, compression strength, biocompatibility, electrical conductivity, and thermal characteristics of the final material were analyzed and were found to be affected by the varied synthesis methods used. Overall, the synthesized scaffolds exhibit good biocompatibility with increased fluorescence over 3 days and over 70% cell viability, thermal stability up to 200°C and a range of swelling of 1725% to 8472%. They also portray robust mechanical properties with a Young's Moduli range of 11 kPa to 4.54 MPa and a porosity range of 0.78–71.98 μm depending on the synthesis methods used. Through variations in synthesis methods, highly porous, absorbent, and stable scaffolds have been synthesized. Notably, this single recipe is highly tailorable for use in a range of biomedical applications from tissue engineering to drug delivery and wound repair. [ABSTRACT FROM AUTHOR]

Simple Summary: The sweet potato is an important food crop grown and traded in many regions of the world, especially in tropical, subtropical, and temperate regions. Several insect pests feed on sweet potatoes in open fields and storage. As a result, the yield and quality are generally impacted. In addition, some of the insect pests are of regulatory importance. Indeed, the United States and Brazil are subject to stringent pest and quarantine regulations concerning sweet potatoes, encompassing the plant's roots and aerial parts. This review describes the current status of sweet potato regulations and management options in the United States and Brazil. We also describe research on sweet potato production, monitoring, biological control, and regulatory pest management information that may relieve these problems. This can help small and large farmers produce sweet potatoes in the United States and Brazil. The sweet potato [Ipomoea batatas (L.) Lam] is considered one of the most important crops in the world as food, fodder, and raw material for starch and alcohol production. Sweet potato consumption and demand for its value-added products have increased significantly over the past two decades, leading to new cultivars, expansion in acreage, and increased demand in the United States and its export markets. Due to its health benefits, sweet potato production has multiplied over the past decade in Brazil, promoting food security and economic development in rural areas. Their adaptability and nutritional value make them a food of great importance for Brazil. As pest attacks and disease infection are the main limiting aspects that often cause yield loss and quality degradation in sweet potatoes, there is a great demand to develop effective defense strategies to maintain productivity. There is a critical need for research into non-pesticide control approaches that can provide safe, cost-effective, sustainable, and environmentally friendly pest and disease management techniques. Pests which feed on roots have trade implications worldwide. For example, sweet potato tuber shipments infested with the sweet potato weevil are generally not allowed for trade in North and South America. [ABSTRACT FROM AUTHOR]

Daily oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, though efficacy depends on adherence. Digital pill systems (DPS) can enable direct, real-time adherence measurement. HIV-negative men who have sex with men (MSM) with substance use (excluding alcohol) utilized a DPS over 90 days and completed weekly surveys reporting sexual activity, condom use, and substance use. Responses indicating (1) any sexual activity and substance use or (2) condomless anal intercourse (CAI) in the prior week were categorized as high risk for HIV acquisition. PrEP adherence data for the 7-day period preceding each response was dichotomized as ≤ 3 and ≥ 4 doses/week, indicating prevention-effective adherence, and compared by HIV risk level. Thirteen MSM were analyzed (median age: 32). Of 113 surveys, 48.7% indicated high HIV risk, with 12.4% reporting CAI alone, 16.8% any sexual activity and substance use, and 19.5% both CAI and substance use. Weekly mean PrEP adherence was 90.3% (6.3 of 7 doses/week), with ≥ 4 doses/week recorded during 92.0% of weeks. The proportion of participants with ≥ 4 recorded doses/week was 88.9% during weeks with CAI alone, 89.5% during weeks with any sexual activity and substance use, 92.0% during weeks with both CAI and substance use, and 92.8% during lower risk weeks. Participants ingested ≥ 4 doses/week during 89.1% of all high-risk weeks and 94.8% of low-risk weeks. Overall, participants maintained high levels of PrEP adherence while engaging in HIV risk behaviors. DPS can be deployed concurrently with data collection tools to assess ingestion patterns during periods of elevated risk. [ABSTRACT FROM AUTHOR]

Background The impact of migration on HIV risk among non-migrating household members is poorly understood. We measured HIV incidence among non-migrants living in households with and without migrants in Uganda. Methods We used four survey rounds of data collected from July 2011 to May 2018 from non-migrant participants aged 15–49 years in the Rakai Community Cohort Study. Non-migrants were individuals with no-migration between surveys or at the prior survey. Household migration was defined as ≥1 household member migrating into or out of the house from another community between surveys (∼18 months). Incident HIV was defined as testing HIV seropositive following a negative result. Incidence rate ratios (IRRs) were estimated using Poisson regression with generalized estimating equations. Analyses were stratified by gender, migration into or out of the household and the relationship between non-migrants and migrants (e.g. spouse, child). Results About 11 318 non-migrants (5674 women) were followed for 37 320 person-years. Twenty-eight percent (6059/21 370) of non-migrant person-visits had recent migration into or out of the household, and 240 HIV incident cases were identified. Overall, non-migrants in migrant households were not at greater risk of acquiring HIV than non-migrants in households without any migration. However, men were significantly more likely to acquire HIV if their spouse had recently migrated in [adjusted IRR: 2.12; 95% confidence interval (CI): 1.05–4.27] or out (adjusted IRR: 4.01; 95% CI, 2.16–7.44) compared with men with no spousal migration. Conclusions HIV incidence is higher among non-migrant men with migrant spouses. Targeted HIV testing and prevention interventions like pre-exposure prophylaxis could be considered for men with migrant spouses. [ABSTRACT FROM AUTHOR]

Objective: The objective was to study metabolic characteristics and transcriptome of renal sinus adipose tissue (RSAT) located around renal arteries and veins. Methods: Adipose tissue biopsies from RSAT, omental (OAT), and subcutaneous (SAT) depots were obtained from healthy kidney donors (20 female, 20 male). Adipocyte glucose uptake rate and cell size were measured, and gene expression analyses using transcriptomics were performed. Results: RSAT adipocytes were significantly smaller, with a higher basal glucose uptake rate, than adipocytes from SAT and OAT. Transcriptomic analyses revealed 29 differentially expressed genes between RSAT and OAT (RSAT: 23 lower, 6 higher) and 1214 differentially expressed genes between RSAT and SAT (RSAT: 859 lower, 355 higher). RSAT demonstrated molecular resemblance to OAT, both exhibiting lower metabolic gene expression and higher expression of immune‐related pathways, including IL‐17, TNFα, and NF‐κB signaling than SAT. Weighted gene coexpression network analysis associated RSAT with immune response and nucleic acid transport processes. Despite its location near the renal hilum, RSAT closely resembled OAT and there was a lack of expression in the classical brown adipose tissue genes. Gene enrichment analyses suggest an inflammatory environment in RSAT compared with SAT and, to some extent, OAT. Conclusions: The findings suggest specific RSAT functions that could impact renal function and, possibly, the development of renal and cardiometabolic disorders. [ABSTRACT FROM AUTHOR]

This retrospective cohort study aimed to assess whether basal septal wall thickness (BSWT), anterior (AML) and posterior (PML) mitral leaflet length, or sex were associated with remaining left ventricular outflow tract obstruction (LVOTO) in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA). One hundred fifty-four patients who underwent ASA at the Karolinska University Hospital in Stockholm, Sweden, between 2009 and 2021, were included retrospectively. Anatomical and hemodynamic parameters were collected from invasive catheterization before and during ASA, and from echocardiography (ECHO) examinations before, during, and at 1-year follow-up after ASA. Linear and logistic regression models were used to assess the association between sex, BSWT, AML, PML, and outcome, which was defined as the remaining LVOTO (≥ 30 mmHg) after ASA. The median follow-up was 364 days (interquartile range 334–385 days). BSWT ≥ 23 mm (n = 13, 12%) was associated with remaining LVOTO at follow-up (p = 0.004). Elongated mitral valve leaflet length (either AML or PML) was present in 125 (90%) patients. Elongated AML (> 24 mm) was present in 67 (44%) patients, although AML length was not associated with remaining LVOTO at follow-up. Elongated PML (> 14 mm) was present in 114 (74%) patients and was not associated with remaining LVOTO at follow-up. No significant sex differences were observed regarding the remaining LVOTO. ECHO measurement of BSWT can be effectively used to select patients for successful ASA and identify those patients with a risk of incomplete resolution of LVOTO after ASA. [ABSTRACT FROM AUTHOR]

The effects of three medicinal plants in the feeds of juvenile Nile tilapia (Oreochromis niloticus) were investigated on growth, survival, immunity, and digestive histology at various inclusion levels: (A) Guiera senegalensis at 0, 1, 2, 4, and 8%; (B) Pluchea odorata at 0, 0.5, 1, 2, and 4%; (C) Piliostigma reticulatum at 0, 1, and 2%; and (D) a mixture of the three at 0, 1, and 2%. After 28 days of feeding, fish were infected with Aeromonas hydrophila for 12 days. The results showed that, except for G. senegalensis, the inclusion of the medicinal plants, alone or combined, enhanced the immune response. The diet with 4% P. odorata significantly increased plasma lysozyme and bactericidal activities without affecting feed conversion efficiency or growth. Despite improved immunity, none of the treatments enhanced post-infection survival rates. However, fish fed the 1% mixture showed healthier livers and intestines, with reduced cell swelling and normal lipid deposits, followed by the 2% mixture and the control. These results highlight the potential benefits of incorporating P. odorata and the plant mixture into the diets of Nile tilapia juveniles for enhancing their immune response against A. hydrophila. [ABSTRACT FROM AUTHOR]

Background: The TrialNet Oral Insulin (OI) prevention trial showed no overall treatment effect, using the diagnosis of type 1 diabetes as an endpoint. A significant delay in onset was only found in a high‐risk stratum (termed secondary stratum 1) of participants with low first‐phase insulin release (FPIR). Methods: Since trials with an endpoint of type 1 diabetes take years to complete, in this post hoc analysis, we assessed whether a novel combination of glucose and C‐peptide markers could identify a therapeutic benefit after 1 year of follow‐up (trial participants followed for a median 2.7 years). Results: Participants were relatives with multiple islet autoantibodies and low FPIR (n = 40). Glucose rose, and C‐peptide declined in the placebo group, whereas glucose rose minimally, and C‐peptide increased in the OI group. When glucose and C‐peptide were plotted on two‐dimensional grids using 30–120‐min oral glucose tolerance test (OGTT) time points, changes in ratios of their central points (centroid ratio) differed between groups (p = 0.037 adjusted for age, BMI, and baseline C‐peptide and glucose). Conclusions: These findings support a favorable early effect of OI on combined glucose and C‐peptide endpoints in high‐risk individuals, indicating metabolic benefit. With further study, these measures may allow for shorter trials compared to the standard endpoint of type 1 diabetes diagnosis. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic affected countries across the globe, demanding drastic public health policies to mitigate the spread of infection, which led to economic crises as a collateral damage. In this work, we investigate the impact of human mobility, described via international commercial flights, on COVID-19 infection dynamics on a global scale. We developed a graph neural network (GNN)-based framework called Dynamic Weighted GraphSAGE (DWSAGE), which operates over spatiotemporal graphs and is well-suited for dynamically changing flight information updated daily. This architecture is designed to be structurally sensitive, capable of learning the relationships between edge features and node features. To gain insights into the influence of air traffic on infection spread, we conducted local sensitivity analysis on our model through perturbation experiments. Our analyses identified Western Europe, the Middle East, and North America as leading regions in fueling the pandemic due to the high volume of air traffic originating or transiting through these areas. We used these observations to propose air traffic reduction strategies that can significantly impact controlling the pandemic with minimal disruption to human mobility. Our work provides a robust deep learning-based tool to study global pandemics and is of key relevance to policymakers for making informed decisions regarding air traffic restrictions during future outbreaks. [ABSTRACT FROM AUTHOR]

PURA is mapped to chromosome 5q31 and plays a vital role in neuronal development and synapse formation. Here, we aim to explore PURA's impact on cognitive development and epilepsy phenotype by comparing patients with single nucleotide variants (SNPs) in the PURA gene (PURA‐SNP patients) to those with 5q31 microdeletions including PURA (5q31del + PURA) and those with 5q31 microdeletions not including the PURA gene (5q31del‐PURA). A systematic literature search was conducted in PubMed. Two separate searches were performed in order to find patients with PURA SNPs and 5q31 microdeletions. This review includes data from 191 patients collected from a total of 18 articles; 174 of the patients had PURA SNPs, 13 had 5q31 microdeletions involving the PURA gene, and 4 had 5q31 microdeletions without PURA gene implication. All patients exhibited hypotonia, feeding difficulties and dysmorphic features, however epilepsy was primarily present in patients with PURA syndrome, that is, groups PURA‐SNP and 5q31del + PURA. Regarding the developmental milestones the 5q31del + PURA group stood out as being the most severe, while the 5q31del‐PURA group showed a relatively mild phenotype. Our findings support the hypothesis of PURA being the key contributor of developmental delay and epilepsy among patients with PURA syndrome. [ABSTRACT FROM AUTHOR]

Objective: The quality of the relationship between persons with dementia and family carers influences health and quality-of-life outcomes. Little is known regarding those at higher risk of experiencing a decline in relationship quality, who could potentially benefit the most from interventions. We aimed to identify these risk profiles and explore the underlying factors. Methods: We applied a latent profile analysis to relationship quality data from a 1-year follow-up of 350 dyads of persons with dementia and their informal carers from the Actifcare cohort in eight European countries. Assessments included sociodemographic, clinical, functional, psychosocial and quality-of-life measures. Relationship quality was assessed with the Positive Affect Index. A discriminant analysis explored factors influencing the risk profiles. Results: There were two relationship quality profiles among persons with dementia (gradually decreasing, 74.0%; low but improving, 26%) and two among carers (steadily poor, 57.7%; consistently positive, 42.3%). The 'gradually decreasing' profile (persons with dementia) was related to their levels of dependence and unmet needs, along with carers' social distress and negative feelings, lower baseline RQ and sense of coherence. The 'steadily poor' profile (carers) was influenced by their social distress and negative feelings, lower sense of coherence and perceived social support. These two predominant profiles showed significant decreases in quality-of-life over one year. Conclusions: Specific profiles of persons with dementia and their carers are at risk of worse relationship quality trajectories. By considering modifiable related factors (e.g., carers' stress), our findings can help develop tailored, effective interventions. [ABSTRACT FROM AUTHOR]

Circadian rhythms in conditioned threat extinction emerge from a tissue-level circadian timekeeper, or local clock, in the ventromedial prefrontal cortex (vmPFC). Yet it remains unclear how this local clock contributes to extinction-dependent adaptations. Here we used single-unit and local field potential analyses to interrogate neural activity in the male rat vmPFC during repeated extinction sessions at different times of day. In association with superior recall of a remote extinction memory during the circadian active phase, vmPFC putative principal neurons exhibited phasic firing that was amplified for cue presentations and diminished at transitions in freezing behavior. Coupling of vmPFC gamma amplitude to the phase of low-frequency oscillations was greater during freezing than mobility, and this difference was augmented during the active phase, highlighting a time-of-day dependence in the organization of freezing- versus mobility-associated cell assemblies. Additionally, a greater proportion of vmPFC neurons were phase-locked to low-frequency oscillations during the active phase, consistent with heightened neural excitability at this time of day. Our results suggest that daily fluctuations in vmPFC excitability precipitate enhanced neural recruitment into extinction-based cell assemblies during the active phase, providing a potential mechanism by which the vmPFC local clock modulates circuit and behavioral plasticity during conditioned threat extinction. [ABSTRACT FROM AUTHOR]

Piceatannol is a naturally occurring hydroxylated analogue of the stilbene phytoalexin resveratrol that can be found in grape fruit and derived products. Piceatannol has aroused great interest as it has been shown to surpass some human health-beneficial properties of resveratrol including antioxidant activity, several pharmacological activities and also bioavailability. The plant biosynthetic pathway of piceatannol is still poorly understood, which is a bottleneck for the development of both plant defence and bioproduction strategies. Cell cultures of Vitis vinifera cv. Gamay, when elicited with dimethyl-β-cyclodextrin (MBCD) and methyl jasmonate (MeJA), lead to large increases in the accumulation of resveratrol, and after 120 h of elicitation, piceatannol is also detected due to the regiospecific hydroxylation of resveratrol. Therefore, an ortho-hydroxylase must participate in the biosynthesis of piceatannol. Herein, three possible types of resveratrol hydroxylation enzymatic reactions have been tested, specifically, a reaction catalyzed by an NADPH-dependent cytochrome, P450 hydroxylase, a 2-oxoglutarate-dependent dioxygenase and ortho-hydroxylation, similar to polyphenol oxidase (PPO) cresolase activity. Compared with P450 hydoxylase and the dioxygenase activities, PPO displayed the highest specific activity detected either in the crude extract, the particulate or the soluble fraction obtained from cell cultures elicited with MBCD and MeJA for 120 h. The overall yield of PPO activity present in the crude extract (107.42 EU) was distributed mostly in the soluble fraction (66.15 EU) rather than in the particulate fraction (3.71 EU). Thus, partial purification of the soluble fraction by precipitation with ammonium sulphate, dialysis and ion exchange chromatography was carried out. The soluble fraction precipitated with 80% ammonium sulphate and the chromatographic fractions also showed high levels of PPO activity, and the presence of the PPO protein was confirmed by Western blot and LC-MS/MS. In addition, a kinetic characterization of the cresolase activity of partially purified PPO was carried out for the resveratrol substrate, including Vmax and Km parameters. The Km value was 118.35 ± 49.84 µM, and the Vmax value was 2.18 ± 0.46 µmol min−1 mg−1. [ABSTRACT FROM AUTHOR]

Featured Application: During the desalting process of salted cod, important biochemical changes occur, which will reflect on the organoleptic properties of the final product (desalted cod). Subsequent high-pressure processing with low temperature (4 °C) desalting processes can improve the physicochemical and microbial quality of desalted cod. During the desalting of salted cod, significant textural, histological, and biochemical changes occur. Understanding these changes is crucial for enhancing the preservation and extending the shelf life of desalted cod. This study aimed to investigate the physicochemical quality parameters and enzymatic activities during the desalting process of cod (16 h at 4 and 20 °C) and to extend the shelf life of desalted cod through high-pressure processing (HPP) at 400 and 550 MPa for 5 min. During desalting, a correlation was noted between the pH and trimethylamine content in samples desalted at 20 °C, with both parameters increasing in the initial 4 h and stabilizing thereafter. The soluble protein in cod muscle decreased over desalting time, as it dissolved into the desalting water. Enzymatic activity showed a decline in cathepsins (B and D) and acid phosphatase throughout desalting, whereas lipase activity increased, particularly at 20 °C. HPP effectively extended the shelf life of desalted cod by controlling endogenous microbial growth, enabling an extension to 14–21 days compared to the 7 days observed in untreated control samples. This study highlights quality changes during desalting, with lesser effects at lower temperatures. Subsequent HPP improved the microbiological quality of desalted cod during refrigerated storage. [ABSTRACT FROM AUTHOR]

In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. Although this process is critical to the metabolic supply of healthy brain tissue, it may also be a point of vulnerability in disease. Deterioration of capillary networks is a feature of many neurological disorders and injuries and how this web is engaged during vascular damage remains unknown. We performed in vivo two-photon microscopy on young adult mural cell reporter mice and induced focal capillary injuries using precise two-photon laser irradiation of single capillaries. We found that ~59% of the injuries resulted in regression of the capillary segment 7 to 14 d following injury, and the remaining repaired to reestablish blood flow within 7 d. Injuries that resulted in capillary regression induced sustained vasoconstriction in the upstream arteriole-capillary transition (ACT) zone at least 21 days postinjury in both awake and anesthetized mice. The degree of vasomotor dynamics was chronically attenuated in the ACT zone consequently reducing blood flow in the ACT zone and in secondary, uninjured downstream capillaries. These findings demonstrate how focal capillary injury and regression can impair the microvascular sensory web and contribute to cerebral hypoperfusion. [ABSTRACT FROM AUTHOR]

Regulation of neutrophil activation is critical for disease control. Neutrophil extracellular traps (NETs), which are web-like structures composed of DNA and neutrophil-derived proteins, are formed following pro-inflammatory signals; however, if this process is uncontrolled, NETs contribute to disease pathogenesis, exacerbating inflammation and host tissue damage1,2. Here we show that myeloid inhibitory C-type lectin-like (MICL), an inhibitory C-type lectin receptor, directly recognizes DNA in NETs; this interaction is vital to regulate neutrophil activation. Loss or inhibition of MICL functionality leads to uncontrolled NET formation through the ROS–PAD4 pathway and the development of an auto-inflammatory feedback loop. We show that in the context of rheumatoid arthritis, such dysregulation leads to exacerbated pathology in both mouse models and in human patients, where autoantibodies to MICL inhibit key functions of this receptor. Of note, we also detect similarly inhibitory anti-MICL autoantibodies in patients with other diseases linked to aberrant NET formation, including lupus and severe COVID-19. By contrast, dysregulation of NET release is protective during systemic infection with the fungal pathogen Aspergillus fumigatus. Together, we show that the recognition of NETs by MICL represents a fundamental autoregulatory pathway that controls neutrophil activity and NET formation.How MICL recognizes and autoregulates the formation of neutrophil extracellular traps is explored in mouse models and human patients where disease severity is associated with aberrant neutrophil extracellular trap formation. [ABSTRACT FROM AUTHOR]

Purpose: To describe the prevalence of nocturia and obstructive sleep apnea (OSA) in a cohort of spinal cord injury (SCI) patients and to describe their association. Additionally, to assess clinical and urodynamic data explaining nocturia and to evaluate the effect of OSA management with continuous positive airway pressure (CPAP). Method: Retrospective analysis of data from patients with SCI followed in a tertiary care rehabilitation center with a specialized sleep and neuro-urology units. All adult SCI patients who underwent urodynamic assessment before polysomnography (PSG) between 2015 and 2023 were eligible. Subjective (nocturia) and objective data (urodynamic data, polysomnography, CPAP built-in software) were collated from the Handisom database (database register no. 20200224113128) and the medical records of SCI patients. Statistical testing used Mann-Whitney test for non-parametric variables, Fisher's exact test for contingency analysis and the Spearman correlation test to assess correlations. A p-value < 0.05 was considered significant. Statistical analyses were performed using GraphPad Prism v9. Results: 173 patients (131 males, 42 females) were included. The majority of patients were paraplegic (n = 111 (64,2%)) and had complete lesions (n = 75 (43,4%)). A total of 100 patients had nocturia (57,5%). The prevalence of OSA (Apnea Hypopnea Index (AHI) ≥ 15/h) in the studied population was 61,9%. No correlation was found between nocturia and OSA. A significant difference was observed between patients with and without nocturia in terms of the presence of neurogenic detrusor overactivity (p = 0,049), volume at the first detrusor contraction (p = 0,004) and the bladder functional capacity (p < 0,001). Conclusion: Nocturia and OSA are highly prevalent in patients with SCI, but no statistical association was found between these two disorders. A prospective study focusing on nocturnal polyuria will be needed to assess the impact of OSA on lower urinary tract symptoms in SCI patients. [ABSTRACT FROM AUTHOR]