Search

Diminished ovarian reserve (DOR) is associated with reduced fertility and poor reproductive outcomes. The association between dietary patterns and DOR was not well studied. The purpose of this study was to evaluate the relationship between adhering to the healthy eating index (HEI-2015) and the risk of DOR. In this case–control study, 370 Iranian women (120 with DOR and 250 age- and BMI-matched controls) were examined. A reliable semi-quantitative food frequency questionnaire was used to collect diet-related data. We analyzed the HEI-2015 and their dietary intake data to determine major dietary patterns. The multivariable logistic regression was used in order to analyze the association between HEI-2015 and risk of DOR. We found no significant association between HEI-2015 score and risk of DOR in the unadjusted model (OR 0.78; 95%CI 0.59, 1.03). After controlling for physical activity and energy intake, we observed that women in the highest quartile of the HEI-2015 score had 31% decreased odds of DOR (OR 0.69; 95%CI 0.46, 0.93). This association remained significant even after adjusting for all potential confounders. Overall, increased adherence to HEI may lead to a significant reduction in the odds ratio of DOR. Clinical trials and prospective studies are needed to confirm this association. [ABSTRACT FROM AUTHOR]

Tryptophan (TRP) and its indole metabolites exhibit numerous biological effects, especially their antioxidant properties. This study used untargeted metabolomics in conjunction with targeted metabolomics to investigate the differential expression of tryptophan and its indole metabolites in follicular fluid (FF) of diminished ovarian reserve (DOR) and normal ovarian reserve (NOR) populations. This study included patients with DOR (n = 50) and females with NOR (n = 35) who received in vitro fertilization and embryo transfer. Untargeted metabolomics suggests that diminished ovarian reserve affects the metabolic profile of FF, TRP and indole metabolites were significantly down-regulated in the DOR group. Targeted metabolomics quantification revealed that the levels of TRP, IPA and IAA in the FF of the DOR group were significantly lower than those of the NOR group (P < 0.01). The concentration of TRP in FF is positively correlated with the available embryo rate in NOR females. These results provide data support to explore the pathogenesis of DOR and to look for new biomarkers and ovarian protectors. Additionally, alterations in TRP and its indole metabolites in FF may indirectly reflect the interaction between intestinal flora and the follicular microenvironment. [ABSTRACT FROM AUTHOR]

Oxygenation is a crucial indicator of tissue viability and function. Oxygen tension ( pO 2 ), i.e. the amount of molecular oxygen present in the tissue is a direct result of supply (perfusion) and consumption. Thus, measurement of pO 2 is an effective method to monitor tissue viability. However, tissue oximetry sensors commonly used in clinical practice instead rely on measuring oxygen saturation ( StO 2 ), largely due to the lack of reliable, affordable pO 2 sensing solutions. To address this issue we present a proof-of-concept design and validation of a low-cost, lifetime-based oxygen sensing fiber. The sensor consists of readily-available off-the shelf components such as a microcontroller, a light-emitting diode (LED), an avalanche photodiode (APD), a temperature sensor, as well as a bright in-house developed porphyrin molecule. The device was calibrated using a benchtop setup and evaluated in three in vivo animal models. Our findings show that the new device design in combination with the bright porphyrin has the potential to be a useful and accurate tool for measuring pO 2 in tissue, while also highlighting some of the limitations and challenges of oxygen measurements in this context. [ABSTRACT FROM AUTHOR]

Biochar made-up of dry olive residue (DOR), a biomass resulting from the olive oil extraction industry, has been proposed to be used as a reclamation agent for the recovery of metal contaminated soils. The aim of the present study was to investigate whether the soil application of DOR-based biochar alone or in combination with arbuscular mycorrhizal fungi (AMF) leads to an enhancement in the functionality and abundance of microbial communities inhabiting metal contaminated soils. To study that, a greenhouse microcosm experiment was carried out, where the effect of the factors (i) soil application of DOR-based biochar, (ii) biochar pyrolysis temperature (considering the variants 350 and 500 °C), (iii) soil application dose of biochar (2 and 5%), (iv) soil contamination level (slightly, moderately and highly polluted), (v) soil treatment time (30, 60 and 90 days) and (vi) soil inoculation with Funneliformis mosseae (AM fungus) on β-glucosidase and dehydrogenase activities, FA (fatty acid)-based abundance of soil microbial communities, soil glomalin content and AMF root colonization rates of the wheat plants growing in each microcosm were evaluated. Biochar soil amendment did not stimulate enzyme activities but increased microbial abundances. Dehydrogenase activity and microbial abundances were found to be higher in less contaminated soils and at shorter treatment times. Biochar pyrolysis temperature and application dose differently affected enzyme activities, but while the first factor did not have a significant effect on glucosidase and dehydrogenase, a higher biochar dose resulted in boosted microbial abundances. Soil inoculation with F. mosseae favored the proliferation of soil AMF community and increased soil glomalin content as well as rates of AMF root colonization. This factor also interacted with many of the others evaluated to significantly affect soil enzyme activities, microbial abundances and AMF community. Our results indicate that the application of DOR-based biochar along with AMF fungi is an appropriate approach to improve the status of microbial communities in soils with a moderate metal contamination at short-term. [ABSTRACT FROM AUTHOR]

Delta opioid receptor (DOR) agonists have been identified as a promising novel therapy for headache disorders. DORs are broadly expressed in several peripheral and central regions important for pain processing and mood regulation; and it is unclear which receptors regulate headache associated symptoms. In a model of chronic migraine-associated pain using the human migraine trigger, nitroglycerin, we observed increased expression of DOR in cortex, hippocampus, and striatum; suggesting a role for these forebrain regions in the regulation of migraine. To test this hypothesis, we used conditional knockout mice with DORs deleted from forebrain GABAergic neurons (Dlx-DOR), and investigated the outcome of this knockout on the effectiveness of the DOR agonist SNC80 in multiple headache models. In DOR loxP controls SNC80 blocked the development of acute and chronic cephalic allodynia in the chronic nitroglycerin model, an effect that was lost in Dlx-DOR mice. In addition, the anti-allodynic effects of SNC80 were lost in a model of opioid induced hyperalgesia/medication overuse headache in Dlx-DOR conditional knockouts. In a model reflecting negative affect associated with migraine, SNC80 was only effective in loxP controls and not Dlx-DOR mice. Similarly, SNC80 was ineffective in the cortical spreading depression model of migraine aura in conditional knockout mice. Taken together, these data indicate that forebrain DORs are necessary for the action of DOR agonists in relieving headache-related symptoms and suggest that forebrain regions may play an important role in migraine modulation. [ABSTRACT FROM AUTHOR]

The diagnostic value of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules is still controversial, so we used meta-analysis to seek controversial answers. The PubMed, OVID, and CNKI databases were searched according to the inclusion and exclusion criteria. The literature was selected from the establishment of each database to February 2024. The QUADAS-2 tool assessed diagnostic test accuracy. SROC curves and Spearman's correlation coefficient were made by Review Manager 5.4 software to assess the presence of threshold effects in the literature. Meta-Disc1.4 software was used for Cochrane-Q and χ2 tests, which be used to evaluate heterogeneity, with P-values and I2 indicating heterogeneity levels. The appropriate effect model was selected based on the results of the heterogeneity test. Stata18.0 software was used to evaluate publication bias. The diagnostic accuracy of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules was evaluated by calculating the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, DOR, and area under the SROC curve. A total of 31 studies included 3811 patients with 4718 nodules were analyzed. There is no heterogeneity caused by the threshold effect, but there is significant non-threshold heterogeneity. Combined diagnostic metrics were: sensitivity = 0.93, specificity = 0.91, DOR = 168.41, positive likelihood ratio = 10.60, and negative likelihood ratio = 0.07. The SROC curve area was 0.97. Contrast-enhanced ultrasound and elastography show high diagnostic accuracy for thyroid nodules, offering a solid foundation for early diagnosis and treatment. Trial registration. CRD42024509462. [ABSTRACT FROM AUTHOR]

Opiate alkaloids and their synthetic derivatives are still widely used in pain management, drug addiction, and abuse. To avoid serious side effects, compounds with properly designed pharmacological profiles at the opioid receptor subtypes are long needed. Here a series of 17-N-substituted derivatives of normorphine and noroxymorphone analogues with five- and six-membered ring substituents have been synthesized for structure–activity study. Some compounds showed nanomolar affinity to MOR, DOR and KOR in in vitro competition binding experiments with selective agonists [3H]DAMGO, [3H]Ile5,6-deltorphin II and [3H]HS665, respectively. Pharmacological characterization of the compounds in G-protein signaling was determined by [35S]GTPγS binding assays. The normorphine analogues showed higher affinity to KOR compared to MOR and DOR, while most of the noroxymorphone derivatives did not bind to KOR. The presence of 14-OH substituent resulted in a shift in the pharmacological profiles in the agonist > partial agonist > antagonist direction compared to the parent compounds. A molecular docking-based in silico method was also applied to estimate the pharmacological profile of the compounds. Docking energies and the patterns of the interacting receptor atoms, obtained with experimentally determined active and inactive states of MOR, were used to explain the observed pharmacological features of the compounds. [ABSTRACT FROM AUTHOR]

Describing animal space use is essential for understanding their ecological needs and for planning effective conservation schemes. Notably, certain biomes and life histories are understudied due to methodological challenges in tracking animals in their natural habitats. Specifically, both arid environments and nocturnal species are not sufficiently researched compared to diurnal species and to other biomes. This knowledge gap hinders our ability to properly prioritize habitats for species protection in areas undergoing human-related development. Here, we investigate the movement ecology of the Egyptian Nightjar (Caprimulgus aegyptius) in the arid Dead-sea region of Israel, the Palestinian Authority (the West Bank) and Jordan. This nocturnal insectivore is a cryptic desert-dweller and was considered locally extinct until it was rediscovered in 2016. For this work we tracked twelve individuals using GPS tags to determine how this resource-poor environment affects their home range, (predicting large areas), habitat use, and day-roost ecology. We found that the tracked Egyptian Nightjars had a much larger home range area than other Nightjar species, commuting nightly between foraging grounds and day-roosts. We found, as expected, intensive foraging activity at agricultural fields, where artificial irrigation likely supports higher resource (insect) density. Additionally, we found that individuals showed very high roosting site fidelity, often returning to the same specific site, located in extremely dry and exposed habitats, presumably for predator avoidance. This finding highlights the ecological value of these barren habitats that are often considered "lifeless" and therefore of lower priority for conservation. Consequently, our research demonstrates the importance of describing the space-use of nocturnal animals in arid habitats for conservation efforts. [ABSTRACT FROM AUTHOR]

In the sterile insect technique, it is important to measure the impact of mass-rearing and handling of sterile males to allow a successful control of the target wild population. This study evaluates the effect of pre-release chilling on the survival, escape ability, and sexual competitiveness of male Aedes aegypti. To determine survival and escape ability, mosquitoes were chilled at 4 °C using four different treatments of either one exposure (25 min) or two consecutive exposures (25 + 25 min, 25 + 50 min, 25 + 100 min). For sexual competitiveness, two different treatments were evaluated, chilling for 25 min once and twice. Results showed that the longest exposure to chilling caused a significant reduction of survival time, from 67 to 54 days. Escape ability was reduced by the first chilling from 25 to 7% and with the second chilling, it was reduced from 30 to 24% in the control to 4.9, 2.0 and 0.5% for 25, 50 and 100 min, respectively. Sexual competitiveness index was reduced from 1.16 in the control, to 0.32 and − 0.11 for treatments involving one and two chilling periods, respectively. It is recommended to increase the chilling temperature and reduce the exposure time to reduce the harmful effects on sterile males. [ABSTRACT FROM AUTHOR]

Human migration facilitates the spread of infectious disease. However, little is known about the contribution of migration to the spread of tuberculosis in South Africa. We analyzed longitudinal data on all tuberculosis test results recorded by South Africa's National Health Laboratory Service (NHLS), January 2011–July 2017, alongside municipality-level migration flows estimated from the 2016 South African Community Survey. We first assessed migration patterns in people with laboratory-diagnosed tuberculosis and analyzed demographic predictors. We then quantified the impact of cross-municipality migration on tuberculosis incidence in municipality-level regression models. The NHLS database included 921,888 patients with multiple clinic visits with TB tests. Of these, 147,513 (16%) had tests in different municipalities. The median (IQR) distance travelled was 304 (163 to 536) km. Migration was most common at ages 20–39 years and rates were similar for men and women. In municipality-level regression models, each 1% increase in migration-adjusted tuberculosis prevalence was associated with a 0.47% (95% CI: 0.03% to 0.90%) increase in the incidence of drug-susceptible tuberculosis two years later, even after controlling for baseline prevalence. Similar results were found for rifampicin-resistant tuberculosis. Accounting for migration improved our ability to predict future incidence of tuberculosis. [ABSTRACT FROM AUTHOR]

In-depth understanding of the reorganization of the hydrological cycle in response to global climate change is crucial in highly sensitive regions like the eastern Mediterranean, where water availability is a major factor for socioeconomic and political development. The sediments of Lake Lisan provide a unique record of hydroclimatic change during the last glacial to Holocene transition (ca. 24–11 ka) with its tremendous water level drop of ~ 240 m that finally led to its transition into the present hypersaline water body—the Dead Sea. Here we utilize high-resolution sedimentological analyses from the marginal terraces and deep lake to reconstruct an unprecedented seasonal record of the last millennia of Lake Lisan. Aragonite varve formation in intercalated intervals of our record demonstrates that a stepwise long-term lake level decline was interrupted by almost one millennium of rising or stable water level. Even periods of pronounced water level drops indicated by gypsum deposition were interrupted by decades of positive water budgets. Our results thus highlight that even during major climate change at the end of the last glacial, decadal to millennial periods of relatively stable or positive moisture supply occurred which could have been an important premise for human sedentism. [ABSTRACT FROM AUTHOR]

Chimerism is a coalescence of conspecific genotypes. Although common in nature, fundamental knowledge, such as the spatial distribution of the genotypes within chimeras, is lacking. Hence, we investigated the spatial distribution of conspecific genotypes within the brooding coral Stylophora pistillata, a common species throughout the Indo-Pacific and Red Sea. From eight gravid colonies, we collected planula larvae that settled in aggregates, forming 2–3 partner chimeras. Coral chimeras grew in situ for up to 25 months. Nine chimeras (8 kin, 1 non-related genotypes) were sectioned into 7–17 fragments (6–26 polyps/fragment), and genotyped using eight microsatellite loci. The discrimination power of each microsatellite-locus was evaluated with 330 'artificial chimeras,' made by mixing DNA from three different S. pistillata genotypes in pairwise combinations. In 68% of 'artificial chimeras,' the second genotype was detected if it constituted 5–30% of the chimera. Analyses of S. pistillata chimeras revealed that: (a) chimerism is a long-term state; (b) conspecifics were intermixed (not separate from one another); (c) disproportionate distribution of the conspecifics occurred; (d) cryptic chimerism (chimerism not detected via a given microsatellite) existed, alluding to the underestimation of chimerism in nature. Mixed chimerism may affect ecological/physiological outcomes for a chimera, especially in clonal organisms, and challenges the concept of individuality, affecting our understanding of the unit of selection. [ABSTRACT FROM AUTHOR]

Emiliania huxleyi is a cosmopolitan coccolithophore widespread in temperate oceans. This unicellular photoautotroph forms massive recurring blooms that play an important role in large biogeochemical cycles of carbon and sulfur, which play a role in climate change. The mechanism of bloom formation and demise, controlled by giant viruses that routinely infect these blooms, is poorly understood. We generated a pan-transcriptome of E. huxleyi, derived from three strains with different susceptibility to viral infection. Expression profiling of E. huxleyi sensitive and resistant strains showed major basal differences, including many genes that are induced upon viral infection. This suggests that basal gene expression can affect the host metabolic state and the susceptibility of E. huxleyi to viruses. Due to its ecological importance, the pan-transcriptome and its protein translation, applicable to many E. huxleyi strains, is a powerful resource for investigation of eukaryotic microbial communities. [ABSTRACT FROM AUTHOR]

A nomogram for assessing the risk of IgA vasculitis nephritis (originally termed Henoch–Schönlein purpura nephritis, HSPN) in IgA vasculitis (originally termed Henoch–Schönlein purpura, HSP) pediatric patients can effectively improve early diagnosis and prognosis of IgA vasculitis nephritis. However, currently, no nomogram is available. 246 IgA vasculitis and 142 IgA vasculitis nephritis Asian pediatric patients confirmed by renal biopsy were enrolled. Univariate and multivariate logistic regressions were performed to identify the independent risk factors and construct a series of predictive models. The receiver operating characteristic curve, calibration plot, decision curve analysis, net reclassification index and integrated discrimination index were used to screen the best model. Stratification analysis was applied to optimize model's clinical utility. An external validation set was introduced to verify the predictive efficiency. The final predictive model was converted to nomogram for visual use. We identified age, duration of rash (Dor), D-dimer and IgG as independent risk factors and constructed four models as follows: AIDD (Age + IgG + Dor + D-dimer), AIDi (Age + IgG + D-dimer), AIDo (Age + IgG + Dor) and ADD (Age + Dor + D-dimer), which achieved the receiver operator characteristic curve (AUROC) of 0.931, 0.920, 0.856 and 0.907, respectively. Finally, AIDi model with an AUROC of 0.956 and 0.897 in internal and external validating sets was proposed as a novel predictive model. In stratification analysis by gender and histological grade, the AUROC of AIDi was 0.949 in female, 0.926 in male, 0.933 in mild histological grades and 0.939 in severe histological grades, respectively. AIDi nomogram is an effective and visual tool for assessing the risk of nephritis in IgA vasculitis Asian pediatric patients, regardless of IgA vasculitis nephritis histological grades and gender. [ABSTRACT FROM AUTHOR]

As the novel coronavirus (COVID-19) has spread globally, a significant portion of pregnant and delivering women were infected with COVID-19. While emerging studies examined birth outcomes in COVID-19 positive women, knowledge of the psychological experience of childbirth and maternal wellness remains lacking. This matched-control survey-based study included a sample of women recruited during the first wave of the pandemic in the US who gave birth in the previous six months. Women reporting confirmed/suspected COVID-19 (n = 68) during pregnancy or childbirth were matched on background factors with women reporting COVID-19 negativity (n = 2,276). We found nearly 50% of COVID positive women endorsed acute traumatic stress symptoms at a clinical level in response to childbirth. This group was more than twice as likely to endorse acute stress and to have no visitors during maternity hospitalization than COVID negative women; they were also less likely to room-in with newborns. The COVID positive group reported higher levels of pain in delivery, lower newborn weights, and more infant admission to neonatal intensive care units. Our findings suggest COVID-19 affected populations are at increased risk for traumatic childbirth and associated risk for psychiatric morbidity. Attention to delivering women's wellbeing is warranted during the pandemic. [ABSTRACT FROM AUTHOR]

Probe-based confocal laser endomicroscopy (pCLE), also known as optical biopsy, is a new endoscopic technique that provides real-time magnification of 1000 × microscopic tissue information to diagnose indeterminate biliary strictures. Tissue sampling by endoscopic retrograde cholangiopancreatography (ERCP) is routinely performed to evaluate indeterminate biliary strictures. To evaluate the accuracy of pCLE and tissue sampling by ERCP in the diagnosis of indeterminate biliary strictures, 18 articles were included from 2008 to 2021 through Embase, PubMed, Web of Science, and Cochrane library databases. The summary estimates for the pCLE diagnosis of indeterminate biliary strictures were: sensitivity 0.88 (95% confidence interval (CI), 0.84–0.91); specificity 0.79 (95% CI 0.74–0.83); and Diagnostic Odds Ratio (DOR) 24.63 (95% CI 15.76–38.48). The summary estimates for tissue sampling by ERCP diagnosis for indeterminate biliary strictures were: sensitivity 0.54 (95% CI 0.49–0.59); specificity 0.96 (95% CI 0.94–0.98); and DOR 11.31 (95% CI 3.90–32.82). The area under the sROC curve of pCLE diagnosis of indeterminate biliary strictures is 0.90 higher than 0.65 of tissue sampling by ERCP. The pCLE is a better approach than tissue sampling by ERCP for the diagnosis of indeterminate biliary strictures by providing real-time microscopic images of the bile ducts. [ABSTRACT FROM AUTHOR]

Anti-Mullerian hormone (AMH) and testosterone (T) both play distinct roles in the early stages of folliculogenesis. However, the relationship between serum T and AMH levels is poorly understood. This study aimed to investigate the association between serum T and AMH levels in infertile women. A total of 1935 infertile women aged 20–46 years were included in the cross-sectional study and divided into four quartile groups (Q1 to Q4) based on serum T levels. Compared to the subjects in the highest T quartile (Q4), those in the lowest T quartile (Q1) showed significantly lower AMH levels. After adjustment for age, body weight, body mass index and FSH, increasing T quartile categories were associated with higher AMH levels. Binary logistic regression analyses revealed that the odds for the risk of diminished ovarian reserve (DOR) were 11.44-fold higher in Q1 than in Q4 and the odds for the risk of excess ovarian reserve (EOR) were 10.41-fold higher in Q4 than in Q1. Our data show that serum T levels are positively associated with serum AMH levels and suggest that androgen insufficiency may be a potential risk factor for DOR; androgen excess may lead to EOR in infertile women. [ABSTRACT FROM AUTHOR]

Recent health reforms have created incentives for cardiologists and accountable care organizations to participate in value-based care models for heart failure (HF). Accurate risk stratification of HF patients is critical to efficiently deploy interventions aimed at reducing preventable utilization. The goal of this paper was to compare deep learning approaches with traditional logistic regression (LR) to predict preventable utilization among HF patients. We conducted a prognostic study using data on 93,260 HF patients continuously enrolled for 2-years in a large U.S. commercial insurer to develop and validate prediction models for three outcomes of interest: preventable hospitalizations, preventable emergency department (ED) visits, and preventable costs. Patients were split into training, validation, and testing samples. Outcomes were modeled using traditional and enhanced LR and compared to gradient boosting model and deep learning models using sequential and non-sequential inputs. Evaluation metrics included precision (positive predictive value) at k, cost capture, and Area Under the Receiver operating characteristic (AUROC). Deep learning models consistently outperformed LR for all three outcomes with respect to the chosen evaluation metrics. Precision at 1% for preventable hospitalizations was 43% for deep learning compared to 30% for enhanced LR. Precision at 1% for preventable ED visits was 39% for deep learning compared to 33% for enhanced LR. For preventable cost, cost capture at 1% was 30% for sequential deep learning, compared to 18% for enhanced LR. The highest AUROCs for deep learning were 0.778, 0.681 and 0.727, respectively. These results offer a promising approach to identify patients for targeted interventions. [ABSTRACT FROM AUTHOR]

This study aims to systematically review the diagnostic accuracy of a digital blood pressure measurement device compared to the gold standard mercury sphygmomanometer in published studies. Searches were conducted in PubMed, Cochrane, EBSCO, EMBASE and Google Scholar host databases using the specific search strategy and filters from 1st January 2000 to 3rd April 2021. We included studies reporting data on the sensitivity or specificity of blood pressure measured by digital devices and mercury sphygmomanometer used as the reference standard. Studies conducted among children, special populations, and specific disease groups were excluded. We considered published manuscripts in the English language only. The risk of bias and applicability concerns were assessed based on the author's judgment using the QUADAS2 manual measurement evaluation tool. Based on the screening, four studies were included in the final analysis. Sensitivity, specificity, diagnostic odds ratio (DOR), and 95% confidence interval were estimated. The digital blood pressure monitoring has a moderate level of accuracy and the device can correctly distinguish hypertension with a pooled estimate sensitivity of 65.7% and specificity of 95.9%. After removing one study, which had very low sensitivity and very high specificity, the pooled sensitivity estimate was 79%, and the specificity was 91%. The meta-analysis of DOR suggests that the digital blood pressure monitor had moderate accuracy with a mercury sphygmomanometer. This will provide the clinician and patients with accurate information on blood pressure with which diagnostic and treatment decisions could be made. [ABSTRACT FROM AUTHOR]

Clinical trials revealed significant antitumor activity for immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (mUC). Due to their strict eligibility criteria, clinical trials include selected patient cohorts, and thus do not necessarily represent real-world population outcomes. In this multicentric, retrospective study, we investigated real-world data to assess the effectiveness of pembrolizumab and atezolizumab and to evaluate the prognostic value of routinely available clinicopathological and laboratory parameters. Clinical and follow-up data from mUC patients who received ICIs (01/2017-12/2021) were evaluated. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and duration of response (DOR) were used as endpoints. Patients' (n = 210, n = 76 atezolizumab and 134 pembrolizumab) median OS and PFS were 13.6 and 5.9 months, respectively. Impaired ECOG-PS, the presence of visceral, liver or bone metastases, and hemoglobin levels were independently associated with poor OS and DCR. Furthermore, Bellmunt risk factors and the enhanced Bellmunt-CRP score were shown to be prognostic for OS, PFS and DCR. In conclusion, ICIs are effective treatments for a broad range of mUC patients. Our results confirmed the prognostic value of numerous risk factors and showed that Bellmunt risk scores can further be improved when adding CRP to the model. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs) are important modulators of many physiological functions and excellent drug targets for many diseases. However, to study the functions of endogenous GPCRs is still a challenging task, partially due to the low expression level of GPCRs and the lack of highly potent and selective GPCR antibodies. Overexpression or knock-in of tagged GPCRs, or knockout of specific GPCRs in mice, are common strategies used to study the in vivo functions of these receptors. However, generating separate mice carrying tagged GPCRs or conditional alleles for GPCRs is labor intensive, and requires additional breeding costs. Here we report the generation of mice carrying an HA-tagged DOR (delta opioid receptor) flanked by LoxP sequences at the endogenous DOR locus using a single recombination step, aided by the TALEN system. These animals can be used directly to study the expression, localization, protein-protein interaction and signal transduction of endogenous DOR using anti-HA antibodies. By crossing with mice expressing tissue-specific Cre, these mice can also generate offspring with DOR knockout within specific tissues. These mice are powerful tools to study the in vivo functions of DOR. Furthermore, the gene modification strategy could also be used to study the functions of many other GPCRs. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer has become the most frequent cause of deaths among gynecologic malignancies. Our study elucidates the diagnostic performance of Risk of Ovarian Malignancy Algorithm (ROMA), Human epididymis secretory protein 4 (HE4) and cancer antigen (CA125). To compare the diagnostic accuracy of ROMA, HE-4 and CA125 in the early diagnosis and screening of Epithelial Ovarian Cancer. Literature search in electronic databases such as Medicine: MEDLINE (through PUBMED interface), EMBASE, Google Scholar, Science Direct and Cochrane library from January 2011 to August 2020. Studies that evaluated the diagnostic measures of ROMA, HE4 and CA125 by using Chemilumincence immunoassay or electrochemiluminescence immunoassay (CLIA or ECLIA) as index tests. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We included 32 studies in our meta-analysis. We calculated AUC by SROC, pooled estimated like sensitivity, specificity, likelihood ratio, diagnostic odds ratio (DOR), Tau square, Cochran Q through random effect analysis and meta-regression. Data was retrieved from 32 studies. The number of studies included for HE4, CA125 and ROMA tests was 25, 26 and 22 respectively. The patients with EOC were taken as cases, and women with benign ovarian mass were taken as control, which was 2233/5682, 2315/5875 and 2281/5068 respectively for the markers or algorithm. The pooled estimates of the markers or algorithm were sensitivity: ROMA (postmenopausal) (0.88, 95% CI 0.86–0.89) > ROMA (premenopausal) 0.80, 95% CI 0.78–0.83 > CA-125(0.84, 95% CI 0.82–0.85) > HE4 (0.73, 95% CI 0.71–0.75) specificity: HE4 (0.90, 95% CI 0.89–0.91) > ROMA (postmenopausal) (0.83, 95% CI 0.81–0.84) > ROMA (premenopausal) (0.80, 95% CI 0.79–0.82) > CA125 (0.73, 95%CI 0.72–0.74), Diagnostic odd's ratio ROMA (postmenopausal) 44.04, 95% CI 31.27–62.03, ROMA (premenopausal)-18.93, 95% CI 13.04–27.48, CA-125-13.44, 95% CI 9.97–18.13, HE4-41.03, 95% CI 27.96–60.21 AUC(SE): ROMA (postmenopausal) 0.94(0.01), ROMA (premenopausal)-0.88(0.01), HE4 0.91(0.01), CA125-0.86(0.02) through bivariate random effects model considering the heterogeneity. Our study found ROMA as the best marker to differentiate EOC from benign ovarian masses with greater diagnostic accuracy as compared to HE4 and CA125 in postmenopausal women. In premenopausal women, HE4 is a promising predictor of Epithelial ovarian cancer; however, its utilisation requires further exploration. Our study elucidates the diagnostic performance of ROMA, HE4 and CA125 in EOC. ROMA is a promising diagnostic marker of Epithelial ovarian cancers in postmenopausal women, while HE4 is the best diagnostic predictor of EOC in the premenopausal group. Our study had only EOC patients as cases and those with benign ovarian masses as controls. Further, we considered the studies estimated using the markers by the same index test: CLIA or ECLIA. The good number of studies with strict inclusion criteria reduced bias because of the pooling of studies with different analytical methods, especially for HE4. We did not consider the studies published in foreign languages. Since a few studies were available for HE4 and CA125 in the premenopausal and postmenopausal group separately, data were inadequate for sub-group analysis. Further, we did not assess these markers' diagnostic efficiency stratified by the stage and type of tumour due to insufficient studies. [ABSTRACT FROM AUTHOR]

Biosurfactant-based dispersants were formulated by mixing glycolipids from Weissella cibaria PN3 and lipopeptides from Bacillus subtilis GY19 to enhance the synergistic effect and thereby achieve hydrophilic-lipophilic balance. The proportions of each biosurfactant and dispersant-to-oil ratios (DORs) were varied to obtain the appropriated formulations. The most efficient glycolipid:lipopeptide mixtures (F1 and F2) had oil displacement activities of 81–88% for fuel and crude oils. The baffled flask test of these formulations showed 77–79% dispersion effectiveness at a DOR of 1:25. To reduce the cost of the dispersant, this study optimized the glycolipid production process by using immobilized cells in a stirred tank fermenter. Semicontinuous glycolipid production was carried out conveniently for 3 cycles. Moreover, food wastes, including waste coconut water and waste frying oil, were found to promote glycolipid production. Glycolipids from the optimized process and substrates had similar characteristics but 20–50% lower cost than those produced from basal medium with soybean oil in shaking flasks. The lowest cost dispersant formulation (F2*) contained 10 g/L waste-derived cell-bound glycolipid and 10 g/L lipopeptide and showed high dispersion efficiency with various oils. Therefore, this biosurfactant-based dispersant could be produced on a larger scale for further application. [ABSTRACT FROM AUTHOR]

Clinical trials revealed significant antitumor activity for immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (mUC). Due to their strict eligibility criteria, clinical trials include selected patient cohorts, and thus do not necessarily represent real-world population outcomes. In this multicentric, retrospective study, we investigated real-world data to assess the effectiveness of pembrolizumab and atezolizumab and to evaluate the prognostic value of routinely available clinicopathological and laboratory parameters. Clinical and follow-up data from mUC patients who received ICIs (01/2017-12/2021) were evaluated. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and duration of response (DOR) were used as endpoints. Patients' (n = 210, n = 76 atezolizumab and 134 pembrolizumab) median OS and PFS were 13.6 and 5.9 months, respectively. Impaired ECOG-PS, the presence of visceral, liver or bone metastases, and hemoglobin levels were independently associated with poor OS and DCR. Furthermore, Bellmunt risk factors and the enhanced Bellmunt-CRP score were shown to be prognostic for OS, PFS and DCR. In conclusion, ICIs are effective treatments for a broad range of mUC patients. Our results confirmed the prognostic value of numerous risk factors and showed that Bellmunt risk scores can further be improved when adding CRP to the model. [ABSTRACT FROM AUTHOR]

The cell cycle arrest markers tissue inhibitor metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as potential biomarkers of acute kidney injury (AKI) in critically ill adults in intensive care units and cardiac surgery-associated AKI (CSA-AKI). However, the clinical impact on all-cause AKI remains unclear. Here, we report a meta-analysis performed to evaluate the predictive value of this biomarker for all-cause AKI. The PubMed, Cochrane, and EMBASE databases were systematically searched up to April 1, 2022. We used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We extracted useful information from these studies and calculated the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Twenty studies with 3625 patients were included in the meta-analysis. The estimated sensitivity of urinary [TIMP-2] × [IGFBP7] in the diagnosis of all-cause AKI was 0.79 (95% CI 0.72, 0.84), and the specificity was 0.70 (95% CI 0.62, 0.76). The value of urine [TIMP-2] × [IGFBP7] in the early diagnosis of AKI was assessed using a random effects model. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 2.6 (95% CI 2.1, 3.3), 0.31 (95% CI 0.23, 0.40), and 8 (95% CI 6, 13), respectively. The AUROC was 0.81 (95% CI 0.78–0.84). No significant publication bias was observed in eligible studies. Subgroup analysis indicated that the diagnostic value was related to the severity of AKI, time measurement, and clinical setting. This study shows that urinary [TIMP-2] × [IGFBP7] is a reliable effective predictive test for all cause-AKI. However, whether and how urinary [TIMP-2] × [IGFBP7] can be used in clinical diagnosis still requires further research and clinical trials. [ABSTRACT FROM AUTHOR]

Advanced triple negative breast cancer (TNBC) is an aggressive, but initially chemo-sensitive disease. The prognosis is poor and more than three quarters of patients experience progression 12 months after the initiation of conventional first-line chemotherapy. Approximately two thirds of TNBC express epidermal growth factor receptor 1 (EGFR). We have developed an anti-EGFR targeted nanocontainer drug by inserting anti-EGFR antibody fragments into the membrane of pegylated liposomes (anti-EGFR-ILs-dox). The payload consists of doxorubicin, a standard drug for TNBC. In a first-in-human phase I trial in 26 patients with various advanced solid malignancies, anti-EGFR-ILs-dox has shown little toxicity and encouraging efficacy. In this single-arm phase II trial, we assessed the efficacy of anti-EGFR-ILs-dox as first-line therapy in patients with advanced, EGFR + TNBC. The primary endpoint was progression-free survival at 12 months (PFS12m). Secondary endpoints included overall response rate (ORR), duration of response (DOR), time to progression (TTP), overall survival (OS) and adverse events (AEs). 48 patients received anti-EGFR-ILs-dox 50 mg/m2 iv, on day one of a 28 days-cycle until progression. The Kaplan–Meier estimate for PFS12m was 13% (one-sided 90% CI 7%, 95% CI [5%, 25%]), median PFS was 3.5 months (95% CI 1.9, 5.4). The trial has not reached its primary endpoint. There were no new toxicity signals. Based on these results, anti-EGFR-ILs-dox should not be further developed for TNBC. It remains an open question whether anti-EGFR-ILs-dox would offer more opportunities in other EGFR-expressing malignancies, where targeting this receptor has already shown anticancer effects. Trial registration: This trial was registered at clinicaltrials.gov: NCT02833766. Registered 14/07/2016. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1038/s41598-021-00981-5. Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-00981-5, published online 19 November 2021 The original version of this Article contained an error in the Received date which was incorrectly given as 17 March 2021. [Extracted from the article]

Many recent studies reported coronavirus point-of-care tests (POCTs) based on isothermal amplification. However, the performances of these tests have not been systematically evaluated. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy was used as a guideline for conducting this systematic review. We searched peer-reviewed and preprint articles in PubMed, BioRxiv and MedRxiv up to 28 September 2020 to identify studies that provide data to calculate sensitivity, specificity and diagnostic odds ratio (DOR). Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was applied for assessing quality of included studies and Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) was followed for reporting. We included 81 studies from 65 research articles on POCTs of SARS, MERS and COVID-19. Most studies had high risk of patient selection and index test bias but low risk in other domains. Diagnostic specificities were high (> 0.95) for included studies while sensitivities varied depending on type of assays and sample used. Most studies (n = 51) used reverse transcription loop-mediated isothermal amplification (RT-LAMP) to diagnose coronaviruses. RT-LAMP of RNA purified from COVID-19 patient samples had pooled sensitivity at 0.94 (95% CI: 0.90–0.96). RT-LAMP of crude samples had substantially lower sensitivity at 0.78 (95% CI: 0.65–0.87). Abbott ID Now performance was similar to RT-LAMP of crude samples. Diagnostic performances by CRISPR and RT-LAMP on purified RNA were similar. Other diagnostic platforms including RT- recombinase assisted amplification (RT-RAA) and SAMBA-II also offered high sensitivity (> 0.95). Future studies should focus on the use of un-bias patient cohorts, double-blinded index test and detection assays that do not require RNA extraction. [ABSTRACT FROM AUTHOR]

Radioactive iodine (RAI) is safe and effective in most patients with hyperthyroidism but not all individuals are cured by the first dose, and most develop post-RAI hypothyroidism. Postoperative RAI therapy for remnant ablation is successful in 80–90% of thyroid cancer patients and sometimes induces remission of nonresectable cervical and/or distant metastatic disease but the effective tumor dose is usually not precisely known and must be moderated to avoid short- and long-term adverse effects on other tissues. The Collar Therapy Indicator (COTI) is a radiation detection device embedded in a cloth collar secured around the patient's neck and connected to a recording and data transmission box. In previously published experience, the data can be collected at multiple time points, reflecting local cervical RAI exposure and correlating well with conventional methods. We evaluated the real-time uptake of RAI in patients with hyperthyroid Graves' disease and thyroid cancer. We performed a pilot feasibility prospective study. Data were analyzed using R© (version 4.0.3, The R Foundation for Statistical Computing, 2020), and Python (version 3.6, Matplotlib version 3.0.3). The COTI was able to provide a quantitative temporal pattern of uptake within the thyroid in persons with Graves' disease and lateralized the remnant tissue in persons with thyroid cancer. The study has demonstrated that the portable collar radiation detection device outside of a healthcare facility is accurate and feasible for use after administration of RAI for diagnostic studies and therapy to provide a complete collection of fractional target radioactivity data compared to that traditionally acquired with clinic-based measurements at one or two time-points. Clinical Trials Registration NCT03517579, DOR 5/7/2018. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) mutation is a reliable and sensitive biomarker for EGFR-TKI therapy in non-small-cell lung cancer (NSCLC). However, detection of EGFR mutation in tissues has obvious limitations. Circulating free DNA (cfDNA) has been reported as an alternative approach for the detection of EGFR mutations. This systematic review and meta-analysis was designed to assess the diagnostic performance of cfDNA, compared with tissues. True-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values were extracted or calculated for each study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall diagnostic performance. 20 eligible studies involving 2012 cases were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.674 (95%CI: 0.517-0.800), 0.935 (95%CI: 0.888-0.963), 10.307 (95%CI: 6.167-17.227), 0.348 (95%CI: 0.226-0.537), and 29.582 (95%CI: 4.582-60.012), respectively. The AUC was 0.93 (95% CI: 0.90-0.95). The meta-analysis suggests that detection of EGFR mutation by cfDNA is of adequate diagnostic accuracy and cfDNA analysis could be a promising screening test for NSCLC. [ABSTRACT FROM AUTHOR]

The diagnosis of tuberculous pericarditis (TBP) remains challenging. This prospective study evaluated the diagnostic value of Xpert MTB/RIF (Xpert) and T-SPOT.TB and adenosine deaminase (ADA) for TBP in a high burden setting. A total of 123 HIV-negative patients with suspected TBP were enrolled at a tertiary referral hospital in China. Pericardial fluids were collected and subjected to the three rapid tests, and the results were compared with the final confirmed diagnosis. Of 105 patients in the final analysis, 39 (37.1%) were microbiologically, histopathologically or clinically diagnosed with TBP. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) for Xpert were 66.7%, 98.5%, 96.3%, 83.3%, 44.0, 0.338, and 130.0, respectively, compared to 92.3%, 87.9%, 81.8%, 95.1%, 7.6, 0.088, and 87.0, respectively, for T-SPOT.TB, and 82.1%, 92.4%, 86.5%, 89.7%, 10.8, 0.194, and 55.8, respectively, for ADA (≥ 40 U/L). ROC curve analysis revealed a cut-off point of 48.5 spot-forming cells per million pericardial effusion mononuclear cells for T-SPOT.TB, which had a DOR value of 183.8, while a cut-off point of 41.5 U/L for ADA had a DOR value of 70.9. Xpert (Step 1: rule-in) followed by T-SPOT.TB [cut-off point] (Step 2: rule-out) showed the highest DOR value of 252.0, with only 5.7% (6/105) of patients misdiagnosed. The two-step algorithm consisting of Xpert and T-SPOT.TB could offer rapid and accurate diagnosis of TBP. [ABSTRACT FROM AUTHOR]

Estimating the potential distribution of invasive species has been primarily achieved by employing species distribution models (SDM). Recently introduced joint species distribution models (JSDM) that include species interactions are expected to improve model output. Here we compare the predictive ability of SDM and JSDM by modelling the distribution of one of the most prolific avian invaders in the world, the common myna (Acridotheres tristis), in a recent introduction in Israel. Our results indicate that including information on the local species composition did not improve model accuracy, possibly because of the unique characteristics of this species that include broad environmental tolerance and behavior flexibility. However, the JSDM provided insights into co-occurrence patterns of common mynas and their local heterospecifics, suggesting that at this time point, there is no evidence of species exclusion by common mynas. Our findings suggest that the invasion potential of common mynas depends greatly on urbanization and less so on the local species composition and reflect the major role of anthropogenic impact in increasing the distribution of avian invaders. [ABSTRACT FROM AUTHOR]

Many patients with hiatal hernias (HH) are asymptomatic; however, symptoms may include heartburn, regurgitation, dysphagia, nausea, or vague epigastric pain depending on the hernia type and severity. The ideal technique and timing of repair remains controversial. This report describes short-term outcomes and readmissions of patients undergoing HH repair at our institution. All patients who underwent HH repair from January 2012 through April 2017 were reviewed. Patients undergoing concomitant bariatric surgery were excluded. 239 patients were identified and 128 were included. Eighty-eight were female (69%) and 40 were male (31%) with a mean age of 59 years (range 20–91 years) and a mean BMI of 29.2 kg/m2 (17–42). Worsening GERD was the most common presenting symptom in 79 (61.7%) patients. Eighty-four laparoscopic cases (65.6%) and 44 robotic assisted (34.4%) procedures were performed. Mesh was used in 59 operations (3 polytetrafluoroethylene; 56 biologic). All hiatal hernia types (I-IV) were collected. Majority were initial operations (89%). Techniques included: Toupet fundoplication in 68 cases (63.0%), Nissen fundoplication in 36 (33.3%), Dor fundoplication in 4 (3.7%), concomitant Collis gastroplasty in 4 (3.1%), and primary suture repair in 20 (15.6%). Outcomes between robotic and laparoscopic procedures were compared. Length of stay was reported as median and interquartile range for laparoscopic and robotic: 1.0 day (1.0–3.0) and 2.0 days (1.0–2.5); p = 0.483. Thirty-day readmission occurred in 9 patients, 7 (8.3%) laparoscopic and 2 (4.6%) robotic; p = 0.718. Two 30-day reoperations occurred, both laparoscopic; p = 0.545. Total of 16 complications occurred; 18.6% had a complication with the use of mesh compared to 8.7% without the use of mesh, p = 0.063. There were no conversion to open modality and no mortalities were reported. Hiatal hernia repair can be performed safely with a low incidence of complications. [ABSTRACT FROM AUTHOR]

Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is currently the most common acquired heart disease in children in many countries. Nevertheless, there is no single useful marker existing for predicting CAL of KD. Recently, many reports have noted that N-terminal pro-brain natriuretic peptide (NT-proBNP) can be utilized as a biomarker to predict CAL. Thus, we perform a meta-analysis to ascertain the diagnostic value of NT-proBNP in detecting CAL of KD in the acute phase. PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and China National Knowledge Infrastructure were searched to detect relevant publications. Finally, eight eligible studies were included. The overall diagnostic sensitivity and specificity were 0.84 (95% confidence interval [CI]: 0.78–0.89) and 0.71 (95% CI: 0.68–0.75), respectively. The area under the summary receiver operating characteristic curves value (SROC) curve was 0.8582 ± 0.0531. Moreover, the overall sensitivity and specificity across five studies adopted the threshold of approximately 900 ng/L were 0.82 (95% CI: 0.73–0.89) and 0.72 (95% CI: 0.68–0.76), respectively. SROC was 0.8868 ± 0.0486. This meta-analysis would be the first one to describe the role of NT-proBNP in detecting CAL of KD. We register this study with PROSPERO (CRD42019130083). [ABSTRACT FROM AUTHOR]

DNA methylation plays a significant role in regulating transcription and exhibits a systematic change with age. These changes can be used to predict an individual's age. First, to identify methylation sites associated with biological age; second, to construct a biological age prediction model and preliminarily explore the biological significance of methylation-associated genes using machine learning. A biological age prediction model was constructed using human methylation data through data preprocessing, feature selection procedures, statistical analysis, and machine learning techniques. Subsequently, 15 methylation data sets were subjected to in-depth analysis using SHAP, GO enrichment, and KEGG analysis. XGBoost, LightGBM, and CatBoost identified 15 groups of methylation sites associated with biological age. The cg23995914 locus was identified as the most significant contributor to predicting biological age by calculating SHAP values. Furthermore, GO enrichment and KEGG analyses were employed to initially explore the methylated loci's biological significance. [ABSTRACT FROM AUTHOR]

This research was intended to compare the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) in conjunction with lenvatinib and PD1 inhibitors to first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma(ICC). The research enrolled advanced ICC patients who underwent HAIC plus lenvatinib and PD1 inhibitor(n = 51) or first-line systemic chemotherapy(cisplatin + gemcitabine, n = 39) between July 2020 to January 2023 in Zhongshan People's Hospital.Their clinical outcomes were assessed through measurement of parameters encompassing objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). In accordance with the RECIST1.1, the ORR in the HAIC + L + P and SC groups was 43.1% and 20.5%, while the DCR was 90.2% and 69.2%, respectively (P = 0.04 and = 0.02, respectively). The change in the maximum diameter of intrahepatic target lesions in patients before and after treatment and the diameter of intrahepatic tumors in the HAIC + L + P group were sharply smaller versus the SC group (P < 0.001). The HAIC + L + P group had prolonged mOS (16.8 months vs. 11.0 months, P = 0.01) and mPFS (12.0 months vs. 6.9 months, P < 0.01) in comparison with the SC group. Compared to first-line systemic chemotherapy(cisplatin + gemcitabine), HAIC plus lenvatinib and PD-1 inhibitors contributes to improvement of tumor response and prolongation of OS and PFS in advanced ICC patients. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic bacterium that is widely distributed in aquatic environments and causes major economic losses in fish and public health hazards.This study aimed to identify the occurrence of P. aeruginosa in samples collected from fish and fish handlers, and to investigate the antimicrobial susceptibility, virulence determinants, and biofilm genes of P. aeruginosa isolates. A total of 276 samples were cross-sectionally collected from Nile tilapia (53), Golden grey mullet (52), Mediterranean horse mackerel (50), Striped red mullet (71), and fish handlers (50) at five different retail fish markets in Damietta Governorate, Egypt. Pseudomonas species (spp.) were biochemically identified in 57.9% of the total examined samples. Peudomonas aeruginosa were the most prevalent species isolated from the fish and human samples via PCR technique. Peudomonas aeruginosa isolates exhibited full resistance (100%) to tobramycin (TOB), gentamicin (CN), and colistin (CL), with a high level of susceptibility (88.5%) to imipenem (IPM) using the disk diffusion method. Most P. aeruginosa isolates (84.6%) exhibited drug resistance, with 61.5% were multidrug resistance (MDR) and 23.1% were extensive drug resistance (XDR). Most isolates had at least four virulence-associated genes (lasB, toxA, exoU, and oprL) and three biofilm genes (psIA, peIA, and lasR) by using uniplex PCR. The lasI, and rhlR Quorum Sensing (QS) genes were identified in 84.6% and 61.5% in the examined P. aeruginosa isolates, respectively. The highest mortality rate in Nile tilapia experimentally infected with P. aeruginosa isolate encoding most of virulent genes. Multivariate analyses revealed high heterogeneity among the examined isolates. This study revealed the emergence of virulent and drug resistant P. aeruginosa isolates in fish, poses high risks to consumers and food. Thus, strict hygienic measures should be considered when catching, handling, and storing fish, in addition to the routine application of antimicrobial susceptibility testing. [ABSTRACT FROM AUTHOR]

DNA methylation plays a significant role in regulating transcription and exhibits a systematic change with age. These changes can be used to predict an individual’s age. First, to identify methylation sites associated with biological age; second, to construct a biological age prediction model and preliminarily explore the biological significance of methylation-associated genes using machine learning. A biological age prediction model was constructed using human methylation data through data preprocessing, feature selection procedures, statistical analysis, and machine learning techniques. Subsequently, 15 methylation data sets were subjected to in-depth analysis using SHAP, GO enrichment, and KEGG analysis. XGBoost, LightGBM, and CatBoost identified 15 groups of methylation sites associated with biological age. The cg23995914 locus was identified as the most significant contributor to predicting biological age by calculating SHAP values. Furthermore, GO enrichment and KEGG analyses were employed to initially explore the methylated loci’s biological significance. [ABSTRACT FROM AUTHOR]

This research was intended to compare the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) in conjunction with lenvatinib and PD1 inhibitors to first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma(ICC). The research enrolled advanced ICC patients who underwent HAIC plus lenvatinib and PD1 inhibitor(n = 51) or first-line systemic chemotherapy(cisplatin + gemcitabine, n = 39) between July 2020 to January 2023 in Zhongshan People's Hospital.Their clinical outcomes were assessed through measurement of parameters encompassing objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). In accordance with the RECIST1.1, the ORR in the HAIC + L + P and SC groups was 43.1% and 20.5%, while the DCR was 90.2% and 69.2%, respectively (P = 0.04 and = 0.02, respectively). The change in the maximum diameter of intrahepatic target lesions in patients before and after treatment and the diameter of intrahepatic tumors in the HAIC + L + P group were sharply smaller versus the SC group (P < 0.001). The HAIC + L + P group had prolonged mOS (16.8 months vs. 11.0 months, P = 0.01) and mPFS (12.0 months vs. 6.9 months, P < 0.01) in comparison with the SC group. Compared to first-line systemic chemotherapy(cisplatin + gemcitabine), HAIC plus lenvatinib and PD-1 inhibitors contributes to improvement of tumor response and prolongation of OS and PFS in advanced ICC patients. [ABSTRACT FROM AUTHOR]

Plasma epidermal growth factor receptor mutation (EGFRm) circulating tumor DNA (ctDNA) dynamics exhibit promise in predicting outcomes in patients with EGFRm-advanced non-small cell lung cancer (NSCLC). However, there remains limited trial-level data on integrating ctDNA monitoring into clinical practice. We performed a prospective, multicenter trial to investigate the relationship between EGFRm ctDNA dynamic changes and clinical outcomes in NSCLC patients with EGFRm. Ninety-eight treatment-naive EGFRm-advanced NSCLC patients were recruited and administered icotinib until disease progression. Plasma samples were collected at baseline and four weeks after icotinib administration. ctDNA was analyzed using a droplet-digital polymerase chain reaction. At baseline, 71.4% of patients had detectable EGFRm ctDNA. Among them, 45.9% of patients' ctDNA became undetectable within four weeks of treatment. These patients demonstrated significantly longer progression-free survival (PFS) and overall survival (OS) than those with detectable ctDNA after treatment (P = 0.004 and < 0.001, respectively) and were comparable to those with undetectable ctDNA at both baseline and four weeks. ctDNA detectable at four weeks emerged as a poor independent risk factor for PFS and OS. Patients whose ctDNA became undetectable after treatment had outcomes similar to those with initially undetectable ctDNA, underscoring the predictive value of ctDNA dynamics in treatment efficacy. Registry and the Registration No. of the study/trial: ChiCTR-DDD-17013131. Date of registration: 2017-10-27. [ABSTRACT FROM AUTHOR]

Commonly comprised of cyanobacteria, algae, bacteria and fungi, hypolithic communities inhabit the underside of cobblestones and pebbles in diverse desert biomes. Notwithstanding their abundance and widespread geographic distribution and their growth in the driest regions on Earth, the source of water supporting these communities remains puzzling. Adding to the puzzle is the presence of cyanobacteria that require liquid water for net photosynthesis. Here we report results from six-year monitoring in the Negev Desert (with average annual precipitation of ~ 90 mm) during which periodical measurements of the water content of cobblestone undersides were carried out. We show that while no effective wetting took place following direct rain, dew or fog, high vapor flux, induced by a sharp temperature gradient, took place from the wet subsurface soil after rain, resulting in wet-dry cycles and wetting of the cobblestone undersides. Up to 12 wet-dry cycles were recorded following a single rain event, which resulted in vapor condensation on the undersides of the cobblestones, with the daily wet phase lasting for several hours during daylight. This 'concealed mechanism' expands the distribution of photoautotrophic organisms into hostile regions where the abiotic conditions limit their growth, and provides the driving force for important evolutionary processes not yet fully explored. [ABSTRACT FROM AUTHOR]

Caregiving plays a critical role in children’s cognitive, emotional, and psychological well-being. In the current longitudinal study, we investigated the enduring effects of early maternal behavior on processes of interbrain synchrony in adolescence. Mother-infant naturalistic interactions were filmed when infants were 3–4 months old and interactions were coded for maternal sensitivity and intrusiveness with the Coding Interactive Behavior Manual. In early adolescence (Mean = 12.30, SD = 1.25), mother-adolescent interbrain synchrony was measured using hyperscanning EEG during a naturalistic interaction of positive valence. Guided by previous hyperscanning studies, we focused on interbrain connections within the right frontotemporal interbrain network. Results indicate that maternal sensitivity in early infancy was longitudinally associated with neural synchrony in the right interbrain frontotemporal network. Post-hoc comparisons highlighted enhancement of mother-adolescent frontal-frontal connectivity, a connection that has been implicated in parent-child social communication. In contrast, maternal intrusiveness in infancy was linked with attenuation of interbrain synchrony in the right interbrain frontotemporal network. Sensitivity and intrusiveness are key maternal social orientations that have shown to be individually stable in the mother-child relationship from infancy to adulthood and foreshadow children’s positive and negative social-emotional outcomes, respectively. Our findings are the first to demonstrate that these two maternal orientations play a role in enhancing or attenuating the child’s interbrain frontotemporal network, which sustains social communication and affiliation. Results suggest that the reported long-term impact of maternal sensitivity and intrusiveness may relate, in part, to its effects on tuning the child’s brain to sociality. [ABSTRACT FROM AUTHOR]

Animals’ ability to orient and navigate relies on selecting an appropriate motor response based on the perception and integration of the environmental information. This is the case, for instance, of the optokinetic response (OKR) in Drosophila melanogaster, where optic flow visual stimulation modulates head movements. Despite a large body of literature on the OKR, there is still a limited understanding, in flies, of the impact on OKR of concomitant, and potentially conflicting, inputs. To evaluate the impact of this multimodal integration, we combined in D. melanogaster, while flying in a tethered condition, the optic flow stimulation leading to OKR with the simultaneous presentation of olfactory cues, based on repellent or masking compounds typically used against noxious insect species. First, this approach allowed us to directly quantify the effect of several substances and of their concentration on the dynamics of the flies’ OKR in response to moving gratings by evaluating the number of saccades and the velocity of the slow phase. Subsequently, this analysis was capable of easily revealing the actual effect, i.e. masking vs. repellent, of the compound tested. In conclusion, we show that D. melanogaster, a cost-affordable species, represents a viable option for studying the effects of several compounds on the navigational abilities of insects. [ABSTRACT FROM AUTHOR]

At present, the availability of nonrenewable sources and their usage for electric vehicle technology is reducing gradually because of their disadvantages are more environmental pollution, direct effect on human health, less reliability, and taking more time to start functioning. So, in this article, the proton exchange membrane fuel cell (PEMFC) is considered for the automotive application because of its advantages quick startup, more power density, more safety to handle, high efficiency, and capability of operating at very low operational temperature conditions. However, the drawback of PEMFC is very difficult to identify the accurate MPP position of the fuel system. Here, the improved variable step genetic algorithm is added with the adaptive neuro-fuzzy inference system for tracking the operational point of the proposed system with high efficiency. These hybrid MPPT controller features are easy to understand, more accurate, have a better dynamic response, and have low design complexity. The evaluated proposed MPPT controller operational efficiency, and settling time of the converter voltage at different fuel stack temperature conditions are 98.7402%, and 0.01607 s respectively. Finally, the boost converter is used in this work to enhance the voltage supply capability of the entire system. The proposed system is investigated by applying the MATLAB tool. [ABSTRACT FROM AUTHOR]

Data storage in DNA has recently emerged as a promising archival solution, offering space-efficient and long-lasting digital storage solutions. Recent studies suggest leveraging the inherent redundancy of synthesis and sequencing technologies by using composite DNA alphabets. A major challenge of this approach involves the noisy inference process, obstructing large composite alphabets. This paper introduces a novel approach for DNA-based data storage, offering, in some implementations, a 6.5-fold increase in logical density over standard DNA-based storage systems, with near-zero reconstruction error. Combinatorial DNA encoding uses a set of clearly distinguishable DNA shortmers to construct large combinatorial alphabets, where each letter consists of a subset of shortmers. We formally define various combinatorial encoding schemes and investigate their theoretical properties. These include information density and reconstruction probabilities, as well as required synthesis and sequencing multiplicities. We then propose an end-to-end design for a combinatorial DNA-based data storage system, including encoding schemes, two-dimensional (2D) error correction codes, and reconstruction algorithms, under different error regimes. We performed simulations and show, for example, that the use of 2D Reed-Solomon error correction has significantly improved reconstruction rates. We validated our approach by constructing two combinatorial sequences using Gibson assembly, imitating a 4-cycle combinatorial synthesis process. We confirmed the successful reconstruction, and established the robustness of our approach for different error types. Subsampling experiments supported the important role of sampling rate and its effect on the overall performance. Our work demonstrates the potential of combinatorial shortmer encoding for DNA-based data storage and describes some theoretical research questions and technical challenges. Combining combinatorial principles with error-correcting strategies, and investing in the development of DNA synthesis technologies that efficiently support combinatorial synthesis, can pave the way to efficient, error-resilient DNA-based storage solutions. [ABSTRACT FROM AUTHOR]

The significant advances in the differentiation of human pluripotent stem (hPS) cells into pancreatic endocrine cells, including functional β-cells, have been based on a detailed understanding of the underlying developmental mechanisms. However, the final differentiation steps, leading from endocrine progenitors to mono-hormonal and mature pancreatic endocrine cells, remain to be fully understood and this is reflected in the remaining shortcomings of the hPS cell-derived islet cells (SC-islet cells), which include a lack of β-cell maturation and variability among different cell lines. Additional signals and modifications of the final differentiation steps will have to be assessed in a combinatorial manner to address the remaining issues and appropriate reporter lines would be useful in this undertaking. Here we report the generation and functional validation of hPS cell reporter lines that can monitor the generation of INS+ and GCG+ cells and their resolution into mono-hormonal cells (INSeGFP, INSeGFP/GCGmCHERRY) as well as β-cell maturation (INSeGFP/MAFAmCHERRY) and function (INSGCaMP6). The reporter hPS cell lines maintained strong and widespread expression of pluripotency markers and differentiated efficiently into definitive endoderm and pancreatic progenitor (PP) cells. PP cells from all lines differentiated efficiently into islet cell clusters that robustly expressed the corresponding reporters and contained glucose-responsive, insulin-producing cells. To demonstrate the applicability of these hPS cell reporter lines in a high-content live imaging approach for the identification of optimal differentiation conditions, we adapted our differentiation procedure to generate SC-islet clusters in microwells. This allowed the live confocal imaging of multiple SC-islets for a single condition and, using this approach, we found that the use of the N21 supplement in the last stage of the differentiation increased the number of monohormonal β-cells without affecting the number of α-cells in the SC-islets. The hPS cell reporter lines and the high-content live imaging approach described here will enable the efficient assessment of multiple conditions for the optimal differentiation and maturation of SC-islets. [ABSTRACT FROM AUTHOR]

The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival. [ABSTRACT FROM AUTHOR]

Mangrove trees occur in a variety of geomorphic and sedimentary settings. Yet, studies investigating their role as habitat providers often focus on the most common biophysical types, such as deltaic, estuarine, open coast or lagoonal mangroves on soft sediments, disregarding less typical environments. Here, we investigated the influence of individual mangrove trees growing on a consolidated backreef system (Laucala Bay, Fiji) on habitat use by reef fishes. Combining field surveys and an experiment, we quantified the extent to which reef mangrove trees serve as habitat for solitary or shoaling reef fishes. Using mangrove tree mimics, we disentangled effects attributable to the physical structure of trees from those related to their bio-chemical properties. We found that fish numbers were 3.7 times higher within close proximity to the mangrove trees than at control sites and correlated significantly with root system perimeter. The roots of larger trees sheltered aggregations of juveniles and adults at incoming and high tides. Mangrove trees and mimics attracted fishes alike. We show that mangrove trees on backreefs provide habitat for shoaling and adult reef fishes in addition to serving as nursery areas, an ecosystem service otherwise lacking on backreef areas with low structural complexity. [ABSTRACT FROM AUTHOR]

SLAMF9, a member of the conserved lymphocyte activation molecules family (SLAMF), has been less investigated compared to other SLAMs, especially concerning its implications across various cancer types. In our systematic pan-cancer investigation, we observed elevated SLAMF9 expression in various tumor tissues, which was correlated with reduced patient survival across most malignancies. Correlation analyses further revealed significant associations between SLAMF9 expression and immune cell infiltrates, immune checkpoint inhibitors, tumor mutation load, microsatellite instability, and epithelial–mesenchymal transition (EMT) scores. Cell-based assays demonstrated that SLAMF9 knockdown attenuated the proliferative, motile, and invasive capacities of colorectal cancer (CRC) cells. In a nude mouse xenograft model, suppression of SLAMF9 expression substantially inhibited tumor growth. These findings highlight the potential of SLAMF9 as a prognostic and therapeutic biomarker across tumors, with notable implications for CRC cell proliferation and migration. [ABSTRACT FROM AUTHOR]

Tissue-resident memory T (TRM) cells are characterized by their surface expression of CD69 and can be subdivided in CD103+ and CD103− TRM cells. The origin and functional characteristics of TRM cells in the renal allograft are largely unknown. To determine these features we studied TRM cells in transplant nephrectomies. TRM cells with a CD103+ and CD103− phenotype were present in all samples (n = 13) and were mainly CD8+ T cells. Of note, donor-derived TRM cells were only detectable in renal allografts that failed in the first month after transplantation. Grafts, which failed later, mainly contained recipient derived TRM cells. The gene expression profiles of the recipient derived CD8+ TRM cells were studied in more detail and showed a previously described signature of tissue residence within both CD103+ and CD103− TRM cells. All CD8+ TRM cells had strong effector abilities through the production of IFNγ and TNFα, and harboured high levels of intracellular granzyme B and low levels of perforin. In conclusion, our results demonstrate that donor and recipient TRM cells reside in the rejected renal allograft. Over time, the donor-derived TRM cells are replaced by recipient TRM cells which have features that enables these cells to aggressively respond to the allograft. [ABSTRACT FROM AUTHOR]