Search

Abstract The escalating scarcity of freshwater resources presents significant challenges to global sustainability, demanding innovative solutions by integrating cutting-edge materials and technologies. Here we introduce an autonomous artificial forest (3D AF) for continuous freshwater acquisition. This system features a three-dimensional (3D) architecture incorporating a carbon nanofiber (CNF) network and MXene@polypyrrole (Ti3C2@PPy), enhancing surface area, light absorption, heat distribution, and surface wettability to improve solar vapor generation and fog collection efficiency. The autonomous operation is facilitated by an integrated photothermal actuator that adjusts to the day and night conditions. During daylight, the 3D AF tilts downward to maximize solar exposure for water evaporation, while at night, it self-adjusts to optimize fog particle collection. Notably, our device demonstrates the ability to harvest over 5.5 L m−2 of freshwater daily outdoors. This study showcases the potential of integrating advanced materials and technologies to address pressing global freshwater challenges, paving the way for future innovations in water harvesting.

Abstract Soft robots have drawn a lot of interest in the field of human–robot interfaces because they can mimic the propulsion of soft bodies and archive complex tasks that cannot be made by rigid robots such as performing the complex motion, avoiding collisions by absorbing impacts, and shape adaptation by elastic deformation. Herein, drawing inspiration from creatures in the Cambrian period, such as Hallucigenia, we develop a centimeter‐sized soft robot with multiple magnetic legs (referred to as a soft centirobot). This robot is equipped with graphitic carbon nitride (g‐C3N4) nanosheets to kill biological threats by photogenerated reactive oxygen species under black light illumination. The motion of g‐C3N4 soft centirobot is controlled by magnetic actuation even in complex wastewater samples (with a relative speed of 0.12 body lengths per second). The magnetic multilegs work as a propeller to walk across and cover large regions, and water disinfection is more efficient than what could be achieved by nano/micrometer scale sheets of g‐C3N4. Finally, factors affecting the accelerated propulsion of g‐C3N4 soft centirobot such as design principle, structure geometry, body mass, driving mechanism, and magnetic sensitivity, have been investigated. We envision that such a photoactive 2D material‐based integrated centimeter‐sized robot shall find application in many areas where pathogen removal is required.

Abstract Background Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. Results In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e’), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF

Abstract Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8–10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [13C6]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.

In lichen research, metagenomes are increasingly being used for evaluating symbiont composition and metabolic potential, but the overall content and limitations of these metagenomes have not been assessed. We reassembled over 400 publicly available metagenomes, generated metagenome-assembled genomes (MAGs), constructed phylogenomic trees, and mapped MAG occurrence and frequency across the data set. Ninety-seven percent of the 1,000 recovered MAGs were bacterial or the fungal symbiont that provides most cellular mass. Our mapping of recovered MAGs provides the most detailed survey to date of bacteria in lichens and shows that 4 family-level lineages from 2 phyla accounted for as many bacterial occurrences in lichens as all other 71 families from 16 phyla combined. Annotation of highly complete bacterial, fungal, and algal MAGs reveals functional profiles that suggest interdigitated vitamin prototrophies and auxotrophies, with most lichen fungi auxotrophic for biotin, most bacteria auxotrophic for thiamine and the few annotated algae with partial or complete pathways for both, suggesting a novel dimension of microbial cross-feeding in lichen symbioses. Contrary to longstanding hypotheses, we found no annotations consistent with nitrogen fixation in bacteria other than known cyanobacterial symbionts. Core lichen symbionts such as algae were recovered as MAGs in only a fraction of the lichen symbioses in which they are known to occur. However, the presence of these and other microbes could be detected at high frequency using small subunit rRNA analysis, including in many lichens in which they are not otherwise recognized to occur. The rate of MAG recovery correlates with sequencing depth, but is almost certainly influenced by biological attributes of organisms that affect the likelihood of DNA extraction, sequencing and successful assembly, including cellular abundance, ploidy and strain co-occurrence. Our results suggest that, though metagenomes are a powerful tool for surveying microbial occurrence, they are of limited use in assessing absence, and their interpretation should be guided by an awareness of the interacting effects of microbial community complexity and sequencing depth.

Abstract Fetal growth restriction (FGR) is associated with aberrant placentation and accounts for a significant proportion of perinatal deaths. microRNAs have been shown to be dysregulated in FGR. The purpose of this study was to determine microRNA-regulated molecular pathways altered using a caloric restricted mouse model of FGR. Pregnant mice were subjected to a 50% caloric restricted diet beginning at E9. At E18.5, RNA sequencing of placental tissue was performed to identify differences in gene expression between caloric restricted and control placentas. Significant differences in gene expression between caloric restricted and control placentas were observed in 228 of the 1546 (14.7%) microRNAs. Functional analysis of microRNA–mRNA interactions demonstrated enrichment of several biological pathways with oxidative stress, apoptosis, and autophagy pathways upregulated and angiogenesis and signal transduction pathways downregulated. Ingenuity pathway analysis also suggested that ID1 signaling, a pathway integral for trophoblast differentiation, is also dysregulated in caloric restricted placentas. Thus, a maternal caloric restriction mouse model of FGR results in aberrant microRNA-regulated molecular pathways associated with angiogenesis, oxidative stress, signal transduction, apoptosis, and cell differentiation. As several of these pathways are dysregulated in human FGR, our findings suggest that this model may provide an excellent means to study placental microRNA derangements seen in FGR.

A remarkable variety of cheeses are made in the US and Mexico, each with distinct sensory characteristics. Therefore, the objective of this study was to identify the sensory perception of eighteen varieties of cheeses, comprising eight manufactured in the US and ten manufactured in Mexico. Additionally, we evaluated the influence of the cultural context of the judges on the sensory profiles of different cheeses. Twelve semi-trained judges, divided equally between the US and Mexico, participated in intensive training during an exchange program held in both countries. The judges utilized sensory evaluation questionnaires in English, which encompassed three components: (1) the Rate-All-That-Apply (RATA) method, which assessed eighteen specific attributes of each cheese on a numerical scale from 1 to 10; (2) preliminary acceptability tests conducted using a 9-point hedonic scale; and (3) preliminary tests of willingness to buy the products, evaluated by a yes/no question. This study reveals the perception of the most popular cheeses made in Mexico and the US, where the main differences were in three attributes—elasticity, saltiness, and acidity—explained by different cheese-making practices. In general, a few significant differences were observed in the sensory perception of cheese based on the judges’ origins. The most notable differences were found in the cheeses manufactured in the US, particularly in terms of texture and taste attributes. This preliminary study identifies possible significant sensory trends in California, USA, and Aguascalientes, Mexico.

Summary: Background: There is an elevated co-occurrence of autism in trans individuals, with recent meta-analyses suggesting that 11% of trans individuals are autistic. The presence of autism in trans young people can create clinical challenges by adding complexity to the presentation, assessment and management of those presenting to gender clinics. Although many trans young people display traits of autism, how these traits relate to the nature of their gender diversity is unclear. Methods: This study compared gender identity, gender expression and gender dysphoria (GD) in trans young people with and without autistic traits. Baseline data from a cohort study of trans children and adolescents who first attended the Royal Children's Hospital Gender Service (Victoria, Australia) between February 2017 and January 2020 were analysed cross-sectionally. Autistic traits were assessed via the Social Responsiveness Scale-2. Gender was assessed using tools that measure gender identity, social transition, GD, body dissatisfaction, voice dysphoria, and chest dysphoria. Findings: 522 participants were included, of whom 239 (45.8%) exhibited autistic traits (SRS total T-score ≥60). Those with and without autistic traits were similar in their age (mean (SD) age 14.0 (2.9) and 13.1 (3.6) years respectively) and gender identity: the majority (73.7% (n = 174) and 70.5% (n = 198) respectively) identified in a binary way. Higher rates of social transition (specifically, changing pronouns) were noted in those with autistic traits (Difference in proportion 11.7, 95% confidence interval [CI] 2.4–21.1, p = 0.014). GD was high in both groups with ∼95% displaying clinically relevant levels of GD. Chest dysphoria was similar between groups, while voice dysphoria was higher in those with autistic traits (standardised mean difference [SMD] = 0.3, 95% confidence interval [CI]: 0.1–0.5 p = 0.00087). Dissatisfaction with secondary gendered characteristics (SMD = 0.3, CI: 0.1–0.5 p = 0.0011) and hormonally unresponsive body characteristics (SMD = 0.2, CI: 0.1–0.4 p = 0.016) was higher in trans young people with autistic traits. Interpretation: The similarly high severity of GD in those with and without autistic traits reinforces the importance of trans young people with and without autistic traits being availed the same opportunities to access gender-affirming care. Subtle differences identified between the groups in other areas of gender diversity suggest trans young people with autistic traits may have distinct needs and that gender-affirming care may need to be tailored accordingly. Funding: The Royal Children's Hospital Foundation, Hugh D.T. Williamson Foundation; Australian National Health and Medical Research Council—Clinical Trials and Cohort Studies scheme (GNT 2006529).

Abstract Accurate intraoperative assessment of parathyroid blood flow is crucial to preserve function postoperatively. Indocyanine green (ICG) angiography has been successfully employed, however its conventional application has limitations. A label-free method overcomes these limitations, and laser speckle contrast imaging (LSCI) is one such method that can accurately detect and quantify differences in parathyroid perfusion. In this study, twenty-one patients undergoing thyroidectomy or parathyroidectomy were recruited to compare LSCI and ICG fluorescence intraoperatively. An experimental imaging device was used to image a total of 37 parathyroid glands. Scores of 0, 1 or 2 were assigned for ICG fluorescence by three observers based on perceived intensity: 0 for little to no fluorescence, 1 for moderate or patchy fluorescence, and 2 for strong fluorescence. Speckle contrast values were grouped according to these scores. Analyses of variance were performed to detect significant differences between groups. Lastly, ICG fluorescence intensity was calculated for each parathyroid gland and compared with speckle contrast in a linear regression. Results showed significant differences in speckle contrast between groups such that parathyroids with ICG score 0 had higher speckle contrast than those assigned ICG score 1, which in turn had higher speckle contrast than those assigned ICG score 2. This was further supported by a correlation coefficient of -0.81 between mean-normalized ICG fluorescence intensity and speckle contrast. This suggests that ICG angiography and LSCI detect similar differences in blood flow to parathyroid glands. Laser speckle contrast imaging shows promise as a label-free alternative that overcomes current limitations of ICG angiography for parathyroid assessment.

Abstract Isoetes candelariensis is a new species of Isoetaceae from Misiones, Argentina. This species is ephemeral, and grows on basaltic bedrock outcrop pools, in Urutau Reserve from Candelaria Department. This taxon differs from other aquatic Isoetes in this region by the unique combination of characters of its leaves, ligule, labium and megaspore ornamentation.

Abstract Wearable sensors have made significant progress in sensing physiological and biochemical markers for telehealth. By monitoring vital signs like body temperature, arterial oxygen saturation, and breath rate, wearable sensors provide enormous potential for the early detection of diseases. In recent years, significant advancements have been achieved in the development of wearable sensors based on two-dimensional (2D) materials with flexibility, excellent mechanical stability, high sensitivity, and accuracy introducing a new approach to remote and real-time health monitoring. In this review, we outline 2D materials-based wearable sensors and biosensors for a remote health monitoring system. The review focused on five types of wearable sensors, which were classified according to their sensing mechanism, such as pressure, strain, electrochemical, optoelectronic, and temperature sensors. 2D material capabilities and their impact on the performance and operation of the wearable sensor are outlined. The fundamental sensing principles and mechanism of wearable sensors, as well as their applications are explored. This review concludes by discussing the remaining obstacles and future opportunities for this emerging telehealth field. We hope that this report will be useful to individuals who want to design new wearable sensors based on 2D materials and it will generate new ideas.

Abstract Flexible aqueous zinc-ion batteries can store energy safely and at a low cost, which benefits wearable electronic gadgets; however, currently used cathodes restrict these devices with a low specific capacity and energy density. Herein, we developed a flexible zinc-sulfur (Zn–S) battery constructed by Ti3C2Tx decorated with sulfur (S@Ti3C2Tx) as a cathode and Zn metal anode with iodine-added amphiphilic gel electrolyte (AGE). Benefiting from the confinement synergy of S@Ti3C2Tx cathode, the Zn-S battery exhibited a high storage capacity of 772.7 mAh g−1 at 300 mA g−1, which is higher than a conventional S-decorated carbon cathode (491.7 mAh g−1). More specially, the flexible device offers good cycling stability (82.7%) and excellent mechanical stability with 91% capacity retention after 90° bending (500 cycles). To demonstrate real applications, the flexible Zn–S batteries were integrated in series to power electrical gadgets (e.g., digital clock, light-emitting diode, and robot). It exhibits exceptional flexibility to sustain different deformations and maintains a steady supply of power to run the wearable electronic gadget. These findings offer a fresh starting point for flexible energy storage technologies and show the promising potential of the Zn–S battery in real-world applications.

BackgroundDescribing correlates of physical activity (PA) and sedentary behavior (SB) among postmenopausal cancer survivors can help identify risk profiles and can be used to support development of targeted interventions to improve PA and reduce SB in this population.ObjectiveTo describe PA/SB and identify correlates of PA/SB among cancer and cancer-free post-menopausal women.MethodsWomen from the Women's Health Study (N = 16,629) and Women's Health Initiative/Objective Physical Activity and Cardiovascular Health Study (N = 6,079) were asked to wear an accelerometer on the hip for 7 days. Multiple mixed-effects linear regression models were used to identify sociodemographic-, health-, and chronic condition-related correlates (independent variables) associated with PA and SB (dependent variables) among women with (n = 2,554) and without (n = 20,154) a history of cancer. All correlates were mutually adjusted for each other.ResultsIn unadjusted analyses, women with a history of cancer took fewer mean daily steps (4,572 (standard deviation 2557) vs 5,029 (2679) steps/day) and had lower mean moderate-to-vigorous PA (74.9 (45.0) vs. 81.6 (46.7) minutes/day) than cancer-free women. In adjusted analyses, for cancer and cancer-free women, age, diabetes, overweight, and obesity were inversely associated with all metrics of PA (average vector magnitude, time in moderate-to-vigorous PA, step volume, time at ≥40 steps/minutes, and peak 30-minute step cadence). In unadjusted analyses, mean SB was similar for those with and without cancer (529.7 (98.1) vs. 521.7 (101.2) minutes/day). In adjusted analyses, for cancer and cancer-free women, age, diabetes, cardiovascular disease, current smoking, overweight, and obesity were positive correlates of SB, while Black or Hispanic race/ethnicity, weekly/daily alcohol intake, and excellent/very good/good self-rated health were inverse correlates of SB.ConclusionSeveral sociodemographic, health, and chronic conditions were correlates of PA/SB for postmenopausal women with and without cancer. Future studies should examine longitudinal relationships to gain insight into potential determinants of PA/SB.

Introduction Trans young people are at a higher risk of mental health difficulties such as depression, anxiety and suicidality than their cisgender peers, due in part to their experiences of minority stress. This protocol describes a feasibility trial and subsequent pilot randomised controlled trial (RCT) of a codesigned group cognitive–behavioural therapy intervention for trans young people, named Trans Adolescent Group ThErapy for Alleviating Minority stress (TAG TEAM).Methods and analysis To evaluate TAG TEAM, we will conduct a feasibility trial followed by a pilot RCT with trans young people aged 14–16 years who have been referred to the Royal Children’s Hospital Gender Service in Melbourne, Australia. In the feasibility trial, we aim to enrol 32 participants who will be randomised at a 1:1 ratio to either in-person or online intervention arms. Participants will be assessed at baseline and post-treatment, with a nested qualitative evaluation post-treatment. Primary outcomes are the feasibility and acceptability of the intervention and the study design and associated procedures, including comparison of the in-person and online delivery modes. In the subsequent pilot RCT, we aim to enrol 64 participants who will be randomised at a 1:1 ratio to an intervention or waitlist control arm, with delivery mode determined by the feasibility trial. Participants will complete assessments at baseline, post-treatment and 3-month follow-up. Primary outcomes are the feasibility and acceptability of the RCT study design. In both the feasibility trial and pilot RCT, participants will complete assessments related to mood, anxiety, suicidality, quality of life, minority stress, family support and social transition. Quantitative data will be analysed using descriptive statistics. Qualitative data will be analysed using thematic and interpretive analysis.Ethics and dissemination The Royal Children’s Hospital Human Research Ethics Committee has approved this study (#91162). Informed consent will be obtained in writing from all participants and a legal guardian. Findings will inform the development of a full-scale RCT to evaluate the efficacy of TAG TEAM and will be disseminated through conferences and peer-reviewed journals.Trial registration number ACTRN12623000302651, ACTRN12623000318684.

BackgroundAlthough DBT is the standard initial imaging modality for women with focal breast symptoms, the importance of ultrasound has grown rapidly in the past decades. Therefore, the Breast UltraSound Trial (BUST) focused on assessing the diagnostic value of ultrasound and digital breast tomosynthesis (DBT) for the evaluation of breast symptoms by reversing the order of breast imaging; first performing ultrasound followed by DBT. This side-study of the BUST evaluates patients' perceptions of ultrasound and DBT in a reversed setting.MethodsAfter imaging, 1181/1276 BUST participants completed a survey consisting of open and closed questions regarding both exams (mean age 47.2, ±11.74). Additionally, a different subset of BUST participants (n = 29) participated in six focus group interviews 18-24 months after imaging to analyze their imaging experiences in depth.ResultsA total of 55.3% of women reported reluctance to undergoing DBT, primarily due of pain, while the vast majority also find bilateral DBT reassuring (87.3%). Thematic analysis identified themes related to 1) imaging reluctance (pain/burden, result, and breast harm) and 2) ultrasound and DBT perceptions. Regarding the latter, the theme comfort underscores DBT as burdensome and painful, while ultrasound is largely perceived as non-burdensome. Ultrasound is also particularly valued for its interactive nature, as highlighted in the theme interaction. Perceived effectiveness reflects women's interest in bilateral breast evaluation with DBT and the visibility of lesions, while they express more uncertainty about the reliability of ultrasound. Emotional impact portrays DBT as reassuring for many women, whereas opinions on the reassurance provided by ultrasound are more diverse. Additional themes include costs, protocols and privacy.ConclusionsUltrasound is highly tolerated, and particularly valued is the interaction with the radiologist. Nearly half of women express reluctance towards DBT; nevertheless, a large portion report feeling more confident after undergoing bilateral DBT, reassuring them of the absence of abnormalities. Understanding patients' perceptions of breast imaging examinations is of great value when optimizing diagnostic pathways.

Abstract Iatrogenic nerve injuries contribute significantly to postoperative morbidity across various surgical disciplines and occur in approximately 500,000 cases annually in the US alone. Currently, there are no clinically adopted means to intraoperatively visualize nerves beyond the surgeon’s visual assessment. Here, we report a label-free method for nerve detection using diffuse reflectance spectroscopy (DRS). Starting with an in vivo rat model, fiber- and imaging-based DRS independently identified similar wavelengths that provided optimal contrast for nerve identification with an accuracy of 92%. Optical property measurements of rat and human cadaver tissues verify that the source of contrast between nerve and surrounding tissues is largely due to higher scattering in nerve and differences in oxygenated hemoglobin content. Clinical feasibility was demonstrated in patients undergoing thyroidectomies using both probe-based and imaging-based approaches where the nerve were identified with 91% accuracy. Based on our preliminary results, DRS has the potential to both provide surgeons with a label-free, intraoperative means of nerve visualization and reduce the incidence of iatrogenic nerve injuries along with its detrimental complications.

Most single-use face masks are made of synthetic plastics, thus their disposal poses a direct threat to wildlife as well as potential ecotoxicological effects in the form of microplastics. Here, the authors introduce a 1D magnetic photoactive microswarm capable of actively navigating, adhering to, and accelerating the degradation of the polypropylene microfiber of single-use face masks.

Tactile sensors in human-machine interaction systems can provide precise input signals and the necessary feedback between humans and machines. Here, the authors developed a black phosphorous-based tactile sensor array system that can provide touch into audio feedback.

The consumption of functional dairy products continues to rise due to consumer needs. This study aimed to develop a dairy guava functional symbiotic petit cheese product that included probiotics (Bifidobacterium animalis subsp. lactis BB-12, Chr. Hansen, Denmark) and prebiotics (inulin), which had adequate organoleptic characteristics. Moreover, adequate physicochemical, microbiological, and sensory characteristics during its shelf life were expected. A pasteurized skim milk curd flavored with a guava pulp was stabilized with gelatin to formulate this product. As sweeteners, iso maltol, erythritol, and Luo Han Guo extract from monk fruit (Siraitia Grosvenorii) were added. The prebiotic used was inulin, and the probiotic (Bifidobacterium animalis subsp. lactis BB-12, Chr. Hansen, Denmark). The product was kept refrigerated (4 °C) during the shelf life of 28 days. For the organoleptic analysis (100 consumers), the evaluations performed were: (1) overall liking (OL), (2) CATA (Check all that apply) testing 19 attributes, and (3) purchase intention was evaluated. Results were analyzed with FIZZ Software Biosystèmes. During shelf life, (1) physicochemical, microbiological, and sensory tests were performed. The product was evaluated as “liked much'' (7.16 out of 9); it was described as a creamy (71 %) natural product (73 %) with a fruity odor (57 %). It could be suitable for marketing because 82 % of the consumers would buy it. The product's probiotic character (over 1 × 106) was established through a microbiological count. On day one, the CFU was found to be 4.15 × 108, and after 28 days, 1.98 × 108 CFU of viable Bifidobacterium animalis subsp. lactis BB-12, leading us to establish its probiotic characteristics. The shelf life was estimated at 21 days.

Summary: Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors.

Somatic frameshift mutations in exon 9 of calreticulin (CALR) gene are recognized as disease drivers in primary myelofibrosis (PMF), one of the three classical Philadelphia-negative myeloproliferative neoplasms (MPNs). Type 1/type 1-like CALR mutations particularly confer a favorable prognostic and survival advantage in PMF patients. We report an unusual case of PMF incidentally diagnosed in a 68-year-old woman known with hepatitis C virus (HCV) cirrhosis who developed a progressive painful splenomegaly, without anomalies in blood cell counts. While harboring a type 1 CALR mutation, the patient underwent a leukemic transformation in less than 1 year from diagnosis, with a lethal outcome. Analysis of paired DNA samples from chronic and leukemic phases by a targeted next-generation sequencing (NGS) panel and single-nucleotide polymorphism (SNP) microarray revealed that the leukemic clone developed from the CALR-mutated clone through the acquisition of genetic events in the RAS signaling pathway: an increased variant allele frequency of the germline NRAS Y64D mutation present in the chronic phase (via an acquired uniparental disomy of chromosome 1) and gaining NRAS G12D in the blast phase. SNP microarray analysis showed five clinically significant copy number losses at regions 7q22.1, 8q11.1-q11.21, 10p12.1-p11.22, 11p14.1-p11.2, and Xp11.4, revealing a complex karyotype already in the chronic phase. We discuss how additional mutations, detected by NGS, as well as HCV infection and antiviral therapy, might have negatively impacted this type 1 CALR-mutated PMF. We suggest that larger studies are required to determine if more careful monitoring would be needed in MPN patients also carrying HCV and receiving anti-HCV treatment.

We investigated the extent, biologic characterization, phenotypic specificity, and possible regulation of a β1-adrenergic receptor–linked (β1-AR–linked) gene signaling network (β1-GSN) involved in left ventricular (LV) eccentric pathologic remodeling. A 430-member β1-GSN was identified by mRNA expression in transgenic mice overexpressing human β1-ARs or from literature curation, which exhibited opposite directional behavior in interventricular septum endomyocardial biopsies taken from patients with beta-blocker–treated, reverse remodeled dilated cardiomyopathies. With reverse remodeling, the major biologic categories and percentage of the dominant directional change were as follows: metabolic (19.3%, 81% upregulated); gene regulation (14.9%, 78% upregulated); extracellular matrix/fibrosis (9.1%, 92% downregulated); and cell homeostasis (13.3%, 60% upregulated). Regarding the comparison of β1-GSN categories with expression from 19,243 nonnetwork genes, phenotypic selection for major β1-GSN categories was exhibited for LV end systolic volume (contractility measure), ejection fraction (remodeling index), and pulmonary wedge pressure (wall tension surrogate), beginning at 3 months and persisting to study completion at 12 months. In addition, 121 lncRNAs were identified as possibly involved in cis-acting regulation of β1-GSN members. We conclude that an extensive 430-member gene network downstream from the β1-AR is involved in pathologic ventricular remodeling, with metabolic genes as the most prevalent category.

A synergistic combination of in vitro electrophysiology and multicompartmental modeling of rat CA1 pyramidal neurons identified TRPM4 channels as major drivers of cholinergic modulation of the firing rate during a triangular current ramp, which emulates the bump in synaptic input received while traversing the place field. In control, fewer spikes at lower frequencies are elicited on the down-ramp compared to the up-ramp due to long-term inactivation of the NaV channel. The cholinergic agonist carbachol (CCh) removes or even reverses this spike rate adaptation, causing more spikes to be elicited on the down-ramp than the up-ramp. CCh application during Schaffer collateral stimulation designed to simulate a ramp produces similar shifts in the center of mass of firing to later in the ramp. The non-specific TRP antagonist flufenamic acid and the TRPM4-specific blockers CBA and 9-phenanthrol, but not the TRPC-specific antagonist SKF96365, reverse the effect of CCh; this implicates the Ca2+-activated nonspecific cation current, ICAN, carried by TRPM4 channels. The cholinergic shift of the center of mass of firing is prevented by strong intracellular Ca2+ buffering but not by antagonists for IP3 and ryanodine receptors, ruling out a role for known mechanisms of release from intracellular Ca2+ stores. Pharmacology combined with modeling suggest that [Ca2+] in a nanodomain near the TRPM4 channel is elevated through an unknown source that requires both muscarinic receptor activation and depolarization-induced Ca2+ influx during the ramp. Activation of the regenerative inward TRPM4 current in the model qualitatively replicates and provides putative underlying mechanisms for the experimental observations.

Abstract Acute respiratory distress syndrome is a heterogeneous pathophysiological process responsible for significant morbidity and mortality in pediatric intensive care patients. Diagnosis is defined by clinical characteristics that identify the syndrome after development. Subphenotyping patients at risk of progression to ARDS could provide the opportunity for therapeutic intervention. microRNAs, non-coding RNAs stable in circulation, are a promising biomarker candidate. We conducted a single-center prospective cohort study to evaluate random forest classification of microarray-quantified circulating microRNAs in critically ill pediatric patients. We additionally selected a sub-cohort for parallel metabolomics profiling as a pilot study for concurrent use of miRNAs and metabolites as circulating biomarkers. In 35 patients (n = 21 acute respiratory distress, n = 14 control) 15 microRNAs were differentially expressed. Unsupervised random forest classification accurately grouped ARDS and control patients with an area under the curve of 0.762, which was improved to 0.839 when subset to only patients with bacterial infection. Nine metabolites were differentially abundant between acute respiratory distress and control patients (n = 4, both groups) and abundance was highly correlated with miRNA expression. Random forest classification of microRNAs differentiated critically ill pediatric patients who developed acute respiratory distress relative to those who do not. The differential expression of microRNAs and metabolites provides a strong foundation for further work to validate their use as a prognostic biomarker.

Abstract Due to the emergence of various new infectious (viral/bacteria) diseases, the remote surveillance of infected persons has become most important, especially if hospitals need to isolate infected patients to prevent the spreading of pathogens to health care personnel. Therefore, we develop a remote health monitoring system by integrating a stretchable asymmetric supercapacitor (SASC) as a portable power source with sensors that can monitor the human physical health condition in real-time and remotely. An abnormal body temperature and breathing rate could indicate a person’s sickness/infection status. Here we integrated FePS3@graphene-based strain sensor and SASC into an all-in-one textile system and wrapped it around the abdomen to continuously monitor the breathing cycle of the person. The real body temperature was recorded by integrating the temperature sensor with the SASC. The proposed system recorded physiological parameters in real-time and when monitored remotely could be employed as a screening tool for monitoring pathogen infection status.

Abstract Background and importance Hearing loss (HL) has been sporadically described, but not well characterized, in Generalized Arterial Calcification of Infancy (GACI), a rare disease in which pathological calcification typically presents in infancy. Objectives This study aims to describe the clinical audiologic and otologic features and potential etiology of hearing impairment in GACI and gain pathophysiological insight from a murine model of GACI. Design Cross-sectional cohort study of individuals with GACI. Murine ossicle micromorphology of the ENPP1 asj/asj mutant compared to wild-type. Setting Clinical research hospital; basic science laboratory. Participants Nineteen individuals with GACI who met clinical, biochemical, and genetic criteria for diagnosis. Main outcomes and measures Clinical, biochemical, and radiologic features associated with hearing status. Results Pure-tone thresholds could be established in 15 (n = 30 ears) of the 19 patients who underwent audiological assessments. The prevalence of HL was 50% (15/30) of ears, with conductive HL in 80% and sensorineural HL in 20%. In terms of patients with HL (n = 8), seven patients had bilateral HL and one patient had unilateral HL. Degree of HL was mild to moderate for 87% of the 15 ears with hearing loss. Of those patients with sufficient pure-tone and middle ear function data, 80% (8/10) had audiometric configurations suggestive of ossicular chain dysfunction (OCD). Recurrent episodes of otitis media (ROM) requiring pressure-equalizing tube placement were common. In patients who underwent cranial CT, 54.5% (6/11) had auricular calcification. Quantitative backscattered electron imaging (qBEI) of murine ossicles supports an OCD component of auditory dysfunction in GACI, suggesting loss of ossicular osteocytes without initiation of bone remodeling. Conclusions and relevance Hearing loss is common in GACI; it is most often conductive, and mild to moderate in severity. The etiology of HL is likely multifactorial, involving dysfunction of the ossicular chain and/or recurrent otitis media. Clinically, this study highlights the importance of early audiologic and otologic evaluation in persons with GACI. Novel findings of high rates of OCD and ROM may inform management, and in cases of unclear HL etiology, dedicated temporal bone imaging should be considered.

Abstract Background Nipple fluid aspiration (NFA) is a technique to acquire nipple aspirate fluid (NAF), which is considered a rich source of breast-specific biomarkers. Originating directly from the mammary ducts, this liquid biopsy can offer insight into the process of carcinogenesis at its earliest stage and therefore could be of added value to the current imaging-based breast cancer screening tools. With that in mind, it is necessary to know how well NFA is tolerated. Aim To evaluate the participants’ tolerability of NFA compared to breast imaging screening methods and blood draws. Materials and methods Three cohorts of women underwent NFA: healthy women (n = 190), women diagnosed with breast cancer (n = 137) and women at high risk of developing breast cancer (n = 48). A 0–10 discomfort score of NFA, mammography, breast MRI and blood draws, was filled in at the study visits, which took place once or annually. Results The median discomfort rate of NFA was 1, which was significantly lower than the median discomfort of mammography and breast MRI (5 and 3, respectively, p

Abstract Background Suicide is one of the leading causes of death in children and youth. Using a sample of fatal suicides among school-aged students in Hong Kong, this study aimed to demonstrate how the classification of children and adolescent suicides into distinct subgroups using cluster analysis can alert us to the heterogeneous nature of the student suicide population and increase our understanding of multidimensional underlying causes. Methods Deaths by suicide of Hong Kong primary and secondary school students occurring between 2013–16 were identified. Reports were acquired from the Coroner’s Court, Police Force, and Education Bureau in Hong Kong. Information about students’ sociodemographic characteristics, suicide circumstances, stressors, and risk factors was extracted and organized for analysis. Based on the indicated stressors (school, family, close relationship, social challenge, finance, risk behaviour, suicide exposure, others) and risk factors (health and mental health, history of self-harm, suicidality, and psychological maladjustment), cluster analysis was conducted to derive distinct profiles of student suicides. Results A four-cluster solution was found. Patterns of stressors, risk factors, background characteristics and suicide circumstances within each cluster were examined. Four distinct and meaningful profiles of student suicides were characterised as “school distress”, “hidden”, “family and relationship”, and “numerous issues”. Conclusions Findings highlighted the need to approach student suicides in meaningfully differentiated ways. Gathering suicide report data and generating evidence that advances our knowledge of student suicide profiles are important steps towards early identification and intervention.

Abstract Background Higher levels of moderate-to-vigorous physical activity have been associated with a lower risk of diabetes, but less is known about how daily step counts (steps/day) are associated with diabetes risk. Therefore, we examined the association of steps/day and step intensity with incident diabetes. Methods We included 6634 adults from the population-based prospective cohort Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (2008–2017). Cox proportional hazard models that accounted for complex survey design and sampling weights were used to estimate the association of baseline accelerometer-assessed steps/day and step intensity with 6-year risk of incident diabetes as hazard ratios (HR) and 95% confidence intervals (CI). We further examined whether the percent of intense steps at a given accumulation of steps/day was associated with diabetes risk, and if associations were modified by specific cohort characteristics. Results The average age of cohort members was 39 years and 52% were female. Adults had an average of 8164 steps/day and spent 12 min/day in brisk ambulation (> 100 steps/min). Over 6 years of follow-up, there were 1115 cases of diabetes. There was a suggestive lower risk of diabetes with more steps/day– adults had a 2% lower risk per 1000 steps/day (HR = 0.98 (95% CI 0.95, 1.00)). Inverse associations between average steps/day and diabetes incidence were observed across many cohort characteristics, but most importantly among adults at high risk for diabetes – those who were older, or had obesity or prediabetes. Adults who accumulated 17 min/day in brisk ambulation compared to

Pesticide and heavy metal pollution in water can cause environmental and public health issues. Here, the authors report thermoresponsive magnetic nanorobots that can efficiently pick up and dispose of pollutants from water by adjusting the water temperature.

A compendium of observational studies of adults that collected accelerometry to assess physical activity and sedentary behavior (i.e., physical behaviors) could facilitate cross-study comparisons, meta-analyses, and future research collaborations. Therefore, we performed a systematic search to identify observational studies, including surveillance systems, that collected accelerometry-measured physical activity and sedentary behavior among adults. We performed a search using PubMed, Web of Science, and SPORTDiscus for studies published on or before June 1, 2021. After screening 5686 abstracts and 1027 full text articles, we included 155 unique studies that collected accelerometry on at least 500 adults 18 years or older. Most studies used one accelerometer (n=146), although eight studies used two accelerometers and one study used four accelerometers. The country of data collection, age range, and accelerometer characteristics were abstracted and checked by a second reviewer. These datasets summarizing relevant observational studies of adults can be a resource to researchers seeking to identify data sources for accelerometer-measured physical activity and sedentary behavior from around the world.

Background Few studies have investigated associations of acclerometer‐based assessments of physical activity (PA) and sedentary behavior (SB) with incidence of cardiovascular disease (CVD) and its components. This prospective cohort study assessed the associations of accelerometer‐measured PA and SB with total CVD, myocardial infarction, and ischemic stroke (IS). Methods and Results The authors included 16 031 women aged 62 years and older, free of CVD, with adherent accelerometer wear (≥10 hours/day for ≥4 days) from the Women's Health Study (mean age, 71.4 years [SD, 5.6 years]). Hip‐worn ActiGraph GT3X+ accelerometers measured total volume of PA (total average daily vector magnitude), minutes per day of high‐light PA and moderate to vigorous PA (MVPA), and SB. Women reported diagnoses of CVD, which were adjudicated using medical records and death certificates. Hazard ratios (HRs) were estimated for each exposure, and 95% CIs using Cox proportional hazards models were adjusted for accelerometer wear time, age, self‐reported general health, postmenopausal hormone therapy, smoking status, and alcohol use. The hypothetical effect of replacing 10 minutes/day of SB or high‐light PA with MVPA on CVD incidence was assessed using adjusted isotemporal substitution Cox models. Over a mean of 7.1 years (SD, 1.6 years) of follow‐up, 482 total CVD cases, 107 myocardial infarction cases, and 181 IS cases were diagnosed. Compared with the lowest quartiles of total average daily vector magnitude and MVPA (≤60 minutes), women who were in the highest quartiles (>120 minutes of MVPA) had a 43% (95% CI, 24%–58%) and 38% (95% CI, 18%–54%) lower hazard of total CVD, respectively. Estimates were similar for total average daily vector magnitude and MVPA with IS, but PA was not associated with myocardial infarction overall. High‐light PA was not associated with any CVD outcomes. Women who spent

Objective: Colorectal cancer (CRC) patients respond differently to treatments and are sub-classified by different approaches. We evaluated a deep learning model, which adopted endoscopic knowledge learnt from AI-doscopist, to characterise CRC patients by histopathological features. Results: Data of 461 patients were collected from TCGA-COAD database. The proposed framework was able to 1) differentiate tumour from normal tissues with an Area Under Receiver Operating Characteristic curve (AUROC) of 0.97; 2) identify certain gene mutations (MYH9, TP53) with an AUROC > 0.75; 3) classify CMS2 and CMS4 better than the other subtypes; and 4) demonstrate the generalizability of predicting KRAS mutants in an external cohort. Conclusions: Artificial intelligent can be used for on-site patient classification. Although KRAS mutants were commonly associated with therapeutic resistance and poor prognosis, subjects with predicted KRAS mutants in this study have a higher survival rate in 30 months after diagnoses.

IntroductionMaternal high-fat (HF) diet during gestation and lactation programs obesity in rat offspring associated with sex-dependent and tissue-specific changes of the endocannabinoid system (ECS). The ECS activation induces food intake and preference for fat as well as lipogenesis. We hypothesized that maternal HF diet would increase the lipid endocannabinoid levels in breast milk programming cannabinoid and dopamine signaling and food preference in rat offspring.MethodsFemale Wistar rats were assigned into two experimental groups: control group (C), which received a standard diet (10% fat), or HF group, which received a high-fat diet (29% fat) for 8 weeks before mating and during gestation and lactation. Milk samples were collected to measure endocannabinoids and fatty acids by mass spectrometry. Cannabinoid and dopamine signaling were evaluated in the nucleus accumbens (NAc) of male and female weanling offspring. C and HF offspring received C diet after weaning and food preference was assessed in adolescence.ResultsMaternal HF diet reduced the milk content of anandamide (AEA) (p

As the threat of antimicrobial-resistant bacteria compromises the safety and efficacy of modern healthcare practices, the search for effective treatments is more urgent than ever. For centuries, silver (Ag) has been known to have antibacterial properties and, over the past two decades, Ag-based nanoparticles have gained traction as potential antimicrobials. The antibacterial efficacy of Ag varies with structure, size, and concentration. In the present study, we examined Ag nanoparticles (AgNPs) for their antimicrobial activity and safety. We compared different commercially-available AgNPs against gram-negative Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and gram-positive Staphylococcus aureus methicillin-resistant and susceptible strains. The most effective formula of AgNPs tested had single-digit (μg/mL) minimum inhibitory concentrations against gram-negative multidrug-resistant clinical bacterial isolates with novel and emerging mechanisms of resistance. The mode of killing was assessed in E. coli and was found to be bactericidal, which is consistent with previous studies using other AgNP formulations. We evaluated cytotoxicity by measuring physiological readouts using the Caenorhabditis elegans model and found that motility was affected, but not the lifespan. Furthermore, we found that at their antibacterial concentrations, AgNPs were non-cytotoxic to any of the mammalian cell lines tested, including macrophages, stem cells, and epithelial cells. More interestingly, our experiments revealed synergy with clinically relevant antibiotics. We found that a non-toxic and non-effective concentration of AgNPs reduced the minimum inhibitory concentrations of aminoglycoside by approximately 22-fold. Because both aminoglycosides and Ag are known to target the bacterial ribosome, we tested whether Ag could also target eukaryotic ribosomes. We measured the rate of mistranslation at bactericidal concentration and found no effect, indicating that AgNPs are not proteotoxic to the host at the tested concentrations. Collectively, our results suggest that AgNPs could have a promising clinical application as a potential stand-alone therapy or antibiotic adjuvants.