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Abstract Terrestrial groundwater travels through subterranean estuaries before reaching the sea. Groundwater‐derived nutrients drive coastal water quality, primary production, and eutrophication. We determined how dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), and dissolved organic nitrogen (DON) are transformed within subterranean estuaries and estimated submarine groundwater discharge (SGD) nutrient loads compiling > 10,000 groundwater samples from 216 sites worldwide. Nutrients exhibited complex, nonconservative behavior in subterranean estuaries. Fresh groundwater DIN and DIP are usually produced, and DON is consumed during transport. Median total SGD (saline and fresh) fluxes globally were 5.4, 2.6, and 0.18 Tmol yr−1 for DIN, DON, and DIP, respectively. Despite large natural variability, total SGD fluxes likely exceed global riverine nutrient export. Fresh SGD is a small source of new nutrients, but saline SGD is an important source of mostly recycled nutrients. Nutrients exported via SGD via subterranean estuaries are critical to coastal biogeochemistry and a significant nutrient source to the oceans.

Abstract Considering that nearly 39% of the total CO2 emission released into the atmosphere today are thought to be due to the energy consumed by buildings, the importance of taking measures through buildings to combat global warming is evident. Therefore, the concept of nearly zero‐energy buildings (NZEB) is come to the forefront. Building integrated photovoltaic thermal (BIPV/T) systems are used to enable buildings to generate their own energy. However, buildings have limited facade and roof areas required for BIPV/T systems. Therefore, in this study, various configurations of bifacial (double‐sided) and monofacial (single‐sided) panels were compared to investigate ways to enhance the efficiency of BIPV/T systems. Different air flow velocities and varying air gap distances were tested for both panel types. By placing a reflective surface on the wall behind the bifacial panel, the electrical efficiency of the bifacial panel was increased and proven through PVsyst analysis. Both panels provided maximum heat efficiency at the shortest air gap distance under high air flow conditions. In addition, it was shown in both the experimental setup and Comsol CFD analysis that it provides significant benefit in the thermal energy load of the building when heating the interior environment in winter. In terms of electrical power production surplus, the bifacial panel outperformed the monofacial panel in all configurations, with a minimum advantage of 8.33% and a maximum of 12.73%. Additionally, the maximum electrical efficiency was obtained from the bifacial panel in configurations with the longest air gap distance. Using the bifacial panel in the BIPV/T system with the shortest air gap distance during the heating season and the longest air gap distance during other seasons can provide the highest efficiency for the building throughout the year.

Background Overweight and obesity are increasing globally with aging, as are life expectancy and aging‐associated disorders, including calcific aortic stenosis (AS). Studies investigating the correlation between high body mass index (BMI) and AS are contradictory and inconclusive. This study examines a potential association between BMI and AS in women. Methods and Results By linking the Swedish Medical Birth Register and the Swedish National Patient Register, we included women aged 18 to 55 years with a first childbirth from 1981 to 2020. Diagnosis of AS and comorbidities were defined according to the International Classification of Diseases (ICD) codes. The women were divided into groups on the basis of BMI. Cox proportional hazards regression models were used to investigate the difference in the risk of being diagnosed with AS, with reference BMI 20 to

Abstract With wireless multimodal locomotion capabilities, magnetic soft millirobots have emerged as potential minimally invasive medical robotic platforms. Due to their diverse shape programming capability, they can generate various locomotion modes, and their locomotion can be adapted to different environments by controlling the external magnetic field signal. Existing adaptation methods, however, are based on hand‐tuned signals. Here, a learning‐based adaptive magnetic soft millirobot multimodal locomotion framework empowered by sim‐to‐real transfer is presented. Developing a data‐driven magnetic soft millirobot simulation environment, the periodic magnetic actuation signal is learned for a given soft millirobot in simulation. Then, the learned locomotion strategy is deployed to the real world using Bayesian optimization and Gaussian processes. Finally, automated domain recognition and locomotion adaptation for unknown environments using a Kullback‐Leibler divergence‐based probabilistic method are illustrated. This method can enable soft millirobot locomotion to quickly and continuously adapt to environmental changes and explore the actuation space for unanticipated solutions with minimum experimental cost.

Abstract Seminal plasma induces immune tolerance towards paternal allogenic antigens within the female reproductive tract and during foetal development. Recent evidence suggests a role for extracellular vesicles in seminal plasma (spEVs). We isolated spEVs from seminal plasma that was donated by vasectomized men, thereby excluding any contributions from the testis or epididymis. Previous analysis demonstrated that such isolated spEVs originate mainly from the prostate. Here we observed that when isolated fluorescently labelled spEVs were mixed with peripheral blood mononuclear cells, they were endocytosed predominantly by monocytes, and to a lesser extent also by T‐cells. In a mixed lymphocyte reaction, T‐cell proliferation was inhibited by spEVs. A direct effect of spEVs on T‐cells was demonstrated when isolated T cells were activated by anti‐CD3/CD28 coated beads. Again, spEVs interfered with T cell proliferation, as well as with the expression of CD25 and the release of IFN‐γ, TNF, and IL‐2. Moreover, spEVs stimulated the expression of Foxp3 and IL‐10 by CD4+CD25+CD127‐ T cells, indicating differentiation into regulatory T‐cells (Tregs). Prior treatment of spEVs with proteinase K revoked their effects on T‐cells, indicating a requirement for surface‐exposed spEV proteins. The adenosine A2A receptor‐specific antagonist CPI‐444 also reduced effects of spEVs on T‐cells, consistent with the notion that the development of Tregs and their immune suppressive functions are under the influence of adenosine‐A2A receptor signalling. We found that adenosine is highly enriched in spEVs and propose that spEVs are targeted to and endocytosed by T‐cells, after which they may release their adenosine content into the lumen of endosomes, thus allowing endosome‐localized A2A receptor signalling in spEVs targeted T‐cells. Collectively, these data support the idea that spEVs can prime T cells directly for differentiation into Tregs.

Abstract Aims The use of guideline‐directed medical therapy (GDMT) among patients with heart failure (HF) with reduced ejection fraction (HFrEF) remains suboptimal. The SMYRNA study aims to identify the clinical factors for the non‐use of GDMT and to determine the prognostic significance of GDMT in patients with HFrEF in a real‐life setting. Methods and results The SMYRNA study is a prospective, multicentre, and observational study that included outpatients with HFrEF. Patients were divided into three groups according to the status of GDMT at the time of enrolment: (i) patients receiving all classes of HF medications including renin‐angiotensin system (RAS) inhibitors, beta‐blockers, and mineralocorticoid receptor antagonists (MRAs); (ii) patients receiving any two classes of HF medications (RAS inhibitors and beta‐blockers, or RAS inhibitors and MRAs, or beta‐blockers and MRAs); and (iii) either patients receiving class of HF medications (only one therapy) or patients not receiving any class of HF medications. The primary outcome was a composite of hospitalization for HF or cardiovascular death. The study population consisted of 1062 patients with HFrEF, predominantly men (69.1%), with a median age of 68 (range: 20–96) years. RAS inhibitors, beta‐blockers, and MRAs were prescribed in 76.0%, 89.4%, and 55.1% of the patients, respectively. The proportions of patients receiving target doses of guideline‐directed medications were 24.4% for RAS inhibitors, 11.0% for beta‐blockers, and 11.1% for MRAs. Overall, 491 patients (46.2%) were treated with triple therapy, 353 patients (33.2%) were treated with any two classes of HF medications, and 218 patients (20.6%) were receiving only one class of HF medication or not receiving any HF medication. Patient‐related factors comprising older age, New York Heart Association functional class, rural living, presence of hypertension, and history of myocardial infarction were independently associated with the use or non‐use of GDMT. During the median 24‐month period, the primary composite endpoint occurred in 362 patients (34.1%), and 177 of 1062 (16.7%) patients died. Patients treated with two or three classes of HF medications had a decreased risk of hospitalization for HF or cardiovascular death compared with those patients receiving ≤1 class of HF medication [hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.49–0.85; P = 0.002, and HR: 0.61; 95% CI: 0.47–0.79; P

Abstract Even after decades of research, pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease and responses to conventional treatments remain mostly poor. Subclassification of PDAC into distinct biological subtypes has been proposed by various groups to further improve patient outcome and reduce unnecessary side effects. Recently, an immunohistochemistry (IHC)‐based subtyping method using cytokeratin‐81 (KRT81) and hepatocyte nuclear factor 1A (HNF1A) could recapitulate some of the previously established molecular subtyping methods, while providing significant prognostic and, to a limited degree, also predictive information. We refined the KRT81/HNF1A subtyping method to classify PDAC into three distinct biological subtypes. The prognostic value of the IHC‐based method was investigated in two primary resected cohorts, which include 269 and 286 patients, respectively. In the second cohort, we also assessed the predictive effect for response to erlotinib + gemcitabine. In both PDAC cohorts, the new HNF1A‐positive subtype was associated with the best survival, the KRT81‐positive subtype with the worst, and the double‐negative with an intermediate survival (p

Abstract Although hypertension is considered high intravascular pressure, impairing circadian blood pressure (BP) has been shown to potentially contribute to poor clinical outcomes. Systemic immune‐inflammation index (SII), based on platelet, neutrophil, and lymphocyte counts, has been established as a strong prognostic marker in cardiovascular disease. The role of inflammation in the pathogenesis of hypertension is a well‐known issue and inflammatory markers are associated with BP variability. We aimed to investigate whether there is a relationship between circadian BP changes and SII in newly diagnosed hypertensive patients. The study population consisted of 196 newly diagnosed hypertensive patients without LVH. In total, 76 (38%) patients had a dipper BP pattern, 60 (31%) patients had a non‐dipper BP pattern, and 60 (31%) patients had a reverse‐dipper BP pattern. SII was calculated according to Multivariate logistic regression analysis revealed SII and HDL‐C as an independent predictors of reverse‐dipper circadian pattern in newly diagnosed hypertensive patients. The cut‐off value of the SII for reverse‐dipper hypertension in a ROC curve analysis was >639.73 with 63.3% sensitivity and 84.2% specificity. Our study showed that the SII level was higher in the reverse‐dipper hypertension patient group than in the dipper and non‐dipper hypertension groups. Furthermore, SII was an independent predictor of newly diagnosed reverse‐dipper hypertensive patients. The high SII value in newly diagnosed hypertensive patients can be used as an early warning parameter to identify reverse‐dipper hypertension patients.

Abstract Background Determination of control level in recurrent angioedema (RAE) is necessary to guide management. Here, we validated a Turkish version of the angioedema control test (AECT) for 4‐week (AECT‐4wk) and for 3‐month (AECT‐3mth) and assessed their utility in monitoring RAE. Method The recommended structured translation process for patient‐reported outcome measures was completed. The final versions were administered to 51 patients with mast cell‐mediated angioedema (MMAE) and 38 patients with hereditary angioedema, and the minimal clinically important difference (MCID) was determined. Additionally, anchor surveys comprising angioedema activity score for 28 days (AAS‐28 day), visual analog score for angioedema control, Likert scale for the control level from the patient's perspective (LS‐AEC), angioedema quality of life, short form‐12 (SF‐12) and patients' assessment of treatment sufficiency were applied. Results The Turkish AECT versions showed good convergent validity with a substantial correlation with anchor tools and known‐group validity. Excellent internal consistency and reproducibility were observed. Equal or more than 10 of 16 points scored with the AECT‐4wk and AECT‐3mth identified patients with well‐controlled disease. The disease activity, control and burden parameters were consistent with the disease control level defined depending on the cut‐off point 10 of AECT. Three‐point changes in AECT‐4wk and ‐3 mt could detect MCID in disease control in all patients. Conclusions Turkish AECT versions are valid and reliable tools for assessing and monitoring disease control in patients with RAE. The use of the Turkish versions of the AECT in routine patient care, clinical trials and angioedema research is recommended.

Abstract Background In ovo application is the process of administering some nutrients or components into the egg. The main purpose of this application is to ensure that some nutrients are provided to chicks with a short incubation period. Few studies were conducted with taurine in fertile eggs; especially, no observation of hatchability and chick quality has been found. In addition, taurine has an anti‐stress impact that fights oxidative factors. Objective To assess the hatchability and chick quality after in ovo taurine administration. To determine the stress that may occur as a result of in ovo application and whether taurine has a stress‐reducing effect. Methods A total of 1200 fertile eggs from a 34‐week‐old broiler breeder (Ross 308) flock were categorized into 4 groups with 75 eggs per replicate: control (uninjected), taurine group (0.30 mL dissolved taurine in distilled water), sham control (sterile distilled water) and perforation (eggs perforated and then waxed). On day 14 of incubation, an in ovo injection was administered to the albumen. Data on hatching parameters and hepatic HSP70 levels were obtained using relevant formulas and western blotting, respectively. Results Control chicks exhibited higher hatchability than other groups, with the taurine group showing the lowest hatchability. The HSP70 levels were the highest in the perforation group compared to the control group. An increase of 21.37% in the taurine group and 83.45% in the sham control group was observed compared to the control group. Conclusions The findings suggest that in ovo application may induce increased stress, whereas taurine may have positive effects in mitigating the stress caused by in ovo application.

Abstract Background In ruminants, fibrous feedstuffs must be included in the ration to ensure normal rumen physiology and to prevent the occurrence of rumen‐related metabolic diseases. In addition to being a source of fibrous feedstuffs, they contain energy depending on the level of digestion and protein, minerals, fatty acids, minerals, and secondary compounds. Objectives This study aimed to determine the nutrient matter, fatty acid, mineral and in vitro rumen fermentation values of the pennyroyal (Mentha pulegium L.) plant. Methods The pennyroyal plant samples were collected at different phenological stages (vegetative, full flowering, and seed bulking) from the natural meadow. The samples were analysed for core nutrients, condensed tannins, minerals, fatty acids, and in vitro ruminal fermentation parameters. Results The calcium (Ca) and iron (Fe) contents and in vitro ruminal fermentation parameters (total gas production and methane production, organic matter digestion (OMd), and the ammonia‐nitrogen) decreased with increasing phenological stage (p < 0.05). The percentages of linoleic, α‐linolenic, ω‐3, ω‐6 and polyunsaturated fatty (PUFA) acids of the pennyroyal plant linearly increased with the phenological stages (p < 0.05). However, butyric acid (BA) concentration in the in vitro ruminal fermentation fluid in the full flowering stage was lower than that of other stages (p < 0.05). Conclusions Pennyroyal plant is a functional plant in terms of high values of ether extract (EE), α‐linolenic acid, linoleic acid, ∑ω‐3 fatty acids, Ca, Fe and Zn contents. For this plant to be used as animal feed, the stage when it has the highest values for Ca, Mg, S and Zn minerals and in vitro OMd were vegetative and full flowering. The stage with good potential as animal feed for ∑ω‐3 and ∑ω‐6 fatty acids and core nutrients (CP and EE) is the seed bulking stage.

Abstract Purpose The number of studies conducted on the role of neuroinflammation in the etiopathogenesis of bipolar disorder has been increasing in recent years. The role of Galectin‐1, Galectin‐9, and YKL‐40, which are considered to play roles in neuroinflammation and the etiopathogenesis of bipolar disorder, and the relationship of these parameters with cognitive functions were investigated in the present study. Method Serum Galectin‐1, Galectin‐9, and YKL‐40 levels were measured with the ELISA Method in 64 bipolar euthymic patients and 64 healthy controls. The Stroop and trail‐making tests were administered to assess cognitive functions in all participants. Results Serum Galectin‐1, Galectin‐9, and YKL‐40 levels were statistically and significantly lower in the patient group when compared to the healthy control group. The scores of the Stroop test and trail‐making tests were statistically higher in the patient group than in the healthy control group. There was a weak and positive correlation between serum Galectin‐1, Galectin‐9, and YKL‐40 levels and cognitive performance in all participants. Discussion and conclusion Statistically significant low levels of serum Galectin‐1, Galectin‐9, and YKL‐40 detected in the patient group suggest that these parameters have important roles in neuroinflammation. The statistically higher Stroop and trail‐making test scores of the patient group compared to the control group indicates that the cognitive performance of the patient group was weaker. Also, the positive correlation between Galectin‐1, Galectin‐9, and YKL‐40 levels and cognitive performance suggests that these molecules may have a neuroprotective role. We think that the present study will contribute to this field where there is very limited data in the literature.

Abstract Environmental DNA (eDNA) analysis has matured to the point that it is ready for deployment in many applications, particularly in aquatic environments. But public agencies have yet to adopt eDNA methods into their environmental decision making routines at scale, even when eDNA offers clear advantages to those now in use. This article provides a perspective on this gap by considering adoption of a new technology as a path‐dependent, social process in which some paths lead to outcomes that provide far greater benefits than others. We use the diffusion of innovations to investigate eDNA adoption by government agencies, in an effort to (1) identify likely paths toward institutionalized uptake, and (2) suggest ways of avoiding societally inefficient adoption outcomes. Because—as in any scientific endeavor—the best eDNA practices will continue to change, public agencies must remain open to improvements while building a useful and validated array of methods for routine eDNA application. Here we suggest one mechanism for doing so, which we call collaborative governance.

Abstract Environmental DNA (eDNA) data make it possible to measure and monitor biodiversity at unprecedented resolution and scale. As use‐cases multiply and scientific consensus grows regarding the value of eDNA analysis, public agencies have an opportunity to decide how and where eDNA data fit into their mandates. Within the United States, many federal and state agencies are individually using eDNA data in various applications and developing relevant scientific expertise. A national strategy for eDNA implementation would capitalize on recent scientific developments, providing a common set of next‐generation tools for natural resource management and public health protection. Such a strategy would avoid patchwork and possibly inconsistent guidelines in different agencies, smoothing the way for efficient uptake of eDNA data in management. Because eDNA analysis is already in widespread use in both ocean and freshwater settings, we focus here on applications in these environments. However, we foresee the broad adoption of eDNA analysis to meet many resource management issues across the nation because the same tools have immediate terrestrial and aerial applications.

Abstract Introduction Cognitive impairment (CI) is a significant non‐motor symptoms in Parkinson's disease (PD) that often precedes the emergence of motor symptoms by several years. Patients with PD hypothetically progress from stages without CI (PD‐normal cognition [NC]) to stages with Mild CI (PD‐MCI) and PD dementia (PDD). CI symptoms in PD are linked to different brain regions and neural pathways, in addition to being the result of dysfunctional subcortical regions. However, it is still unknown how functional dysregulation correlates to progression during the CI. Neuroimaging techniques hold promise in discriminating CI stages of PD and further contribute to the biomarker formation of CI in PD. In this study, we explore disparities in the clinical assessments and resting‐state functional connectivity (FC) among three CI stages of PD. Methods We enrolled 88 patients with PD and 26 healthy controls (HC) for a cross sectional clinical study and performed intra‐ and inter‐network FC analysis in conjunction with comprehensive clinical cognitive assessment. Results Our findings underscore the significance of several neural networks, namely, the default mode network (DMN), frontoparietal network (FPN), dorsal attention network, and visual network (VN) and their inter–intra‐network FC in differentiating between PD‐MCI and PDD. Additionally, our results showed the importance of sensory motor network, VN, DMN, and salience network (SN) in the discriminating PD‐NC from PDD. Finally, in comparison to HC, we found DMN, FPN, VN, and SN as pivotal networks for further differential diagnosis of CI stages of PD. Conclusion We propose that resting‐state networks (RSN) can be a discriminating factor in distinguishing the CI stages of PD and progressing from PD‐NC to MCI or PDD. The integration of clinical and neuroimaging data may enhance the early detection of PD in clinical settings and potentially prevent the disease from advancing to more severe stages.

Abstract Endoscopic retrograde cholangiopancreatography (ERCP), is an invasive procedure with a high complication rate used in the diagnosis and treatment of pancreaticobiliary system diseases. A system that grading the difficulty and complexity of the ERCP procedure has been developed by the American Society of Gastrointestinal Endoscopy (ASGE). The aim of the study is to evaluate the degree of difficulty of ERCP procedures according to the ASGE grading system and its effectiveness in predicting the success and complications of the procedure. A total of 600 patients who underwent ERCP were evaluated retrospectively. Of all ERCP procedures, 5.5% were classified as ASGE 1, 46.8% as ASGE 2, 39% as ASGE 3, and 8.6% as ASGE 4. In all procedures, the successful cannulation rate was 96.3%, the technical success rate was 96%, and the clinical success rate was 94.8%. The procedure's success decreased linearly and the need for repetition increased linearly as the ASGE grade increased (p > .05). In terms of complications, there was no statistical difference between ASGE 1–3 and 4. We believe that the ASGE grading system will be useful in clinical practice, particularly for less experienced endoscopists in ERCP procedures.

Abstract Background Pleural mesothelioma (PM) is typically diagnosed late during the disease. Earlier detection can increase the chance of effective therapy. Recurrent pleural effusions are the earliest symptoms displaying an array of cytomorphological changes from reactive atypia to malignancy. Diagnosis is possible on effusion cytology by applying molecular and immunocytochemical markers, the main difficulty being when to suspect PM and to differentiate PM from metastatic adenocarcinoma and reactive mesothelial proliferations. Methods We evaluated the diagnostic performance of two immunocytochemical dual stains (BerEp4/Calretinin and Desmin/Epithelial Membrane Antigen (EMA)) on 149 ethanol‐fixed cytospin preparation as an initial step to solve the mentioned diagnostic difficulty. The immunocytochemical reactivity pattern was evaluated by two independent investigators. The final diagnosis corresponded to PM (n = 20), metastatic adenocarcinoma (n = 83), and mesotheliosis (n = 46) in these cases. Results Calretinin had 99% specificity and 98% sensitivity for indicating a mesothelial phenotype, while BerEp4 distinguished the adenocarcinoma cases with 98% specificity and 99% sensitivity. EMA displayed 96% specificity and 99% sensitivity in malignant cases, while Desmin without EMA present showed 99% specificity and 96% sensitivity for indicating benign mesothelial proliferation. Conclusions Interpretation of the four immunoreactions is improved when performed as dual stains. The dual staining is a useful tool in the initial handling of atypical effusions and guides the subsequent choice of antibody panels for more detailed subclassification of malignant effusions.

Abstract Snow depth on sea ice is an Essential Climate Variable and a major source of uncertainty in satellite altimetry‐derived sea ice thickness. During winter of the MOSAiC Expedition, the “KuKa” dual‐frequency, fully polarized Ku‐ and Ka‐band radar was deployed in “stare” nadir‐looking mode to investigate the possibility of combining these two frequencies to retrieve snow depth. Three approaches were investigated: dual‐frequency, dual‐polarization and waveform shape, and compared to independent snow depth measurements. Novel dual‐polarization approaches yielded r2 values up to 0.77. Mean snow depths agreed within 1 cm, even for data sub‐banded to CryoSat‐2 SIRAL and SARAL AltiKa bandwidths. Snow depths from co‐polarized dual‐frequency approaches were at least a factor of four too small and had a r2 0.15 or lower. r2 for waveform shape techniques reached 0.72 but depths were underestimated. Snow depth retrievals using polarimetric information or waveform shape may therefore be possible from airborne/satellite radar altimeters.

Abstract Aims Left ventricular non‐compaction cardiomyopathy (LVNC) is a poorly understood entity resulting in heart failure. Whether it is a distinct form of cardiomyopathy or an anatomical phenotype is a subject of discussion. The current diagnosis is based on morphologic findings by comparing the compacted to non‐compacted myocardium. The study aimed to compare demographic and prognostic variables of patients with dilated cardiomyopathy (DCM) and LVNC. Emphasis was given to cardiac magnetic resonance (CMR) imaging analysis. Data on survival were also assessed. Methods and results We retrospectively evaluated the characteristics and outcomes of 262 non‐ischaemic cardiomyopathy patients with LVNC and DCM phenotypes. Petersen's CMR criteria of non‐compacted to the compacted myocardial ratio 2.3 were used to diagnose LVNC. The primary endpoint was a composite endpoint of major adverse cardiovascular events comprising cardiovascular‐related death, left ventricular assisted device implantation, or heart transplantation. A total of 262 patients with CMR data were included in the study. One hundred fifty‐five patients who fulfilled CMR criteria were diagnosed as LVNC. CMR findings revealed that LVNC patients had higher left ventricular end‐diastolic (137.2 ± 51.6, 116.8 ± 44.6, P = 0.002) and systolic volume index (98.4 ± 49.5, 85.9 ± 42.7, P = 0.049). Cardiac haemodynamics, cardiac output (5.61 ± 2.03, 4.96 ± 1.83; P = 0.010), stroke volume (73.9 ± 28.8, 65.1 ± 25.1; P = 0.013), and cardiac index (2.85 ± 1.0, 2.37 ± 0.72; P

Abstract To navigate in complex and unstructured real‐world environments, soft miniature robots need to possess multiple functions, including autonomous environmental sensing, self‐adaptation, and multimodal locomotion. However, to achieve multifunctionality, artificial soft robots should respond to multiple stimuli, which can be achieved by multimaterial integration using facile and flexible fabrication methods. Here, a multimaterial integration strategy for fabricating soft millirobots that uses electrodeposition to integrate two inherently non‐adherable materials, superhydrophilic hydrogels and superhydrophobic elastomers, together via gel roots is proposed. This approach enables the authors to electrodeposit sodium alginate hydrogel onto a laser‐induced graphene‐coated elastomer, which can then be laser cut into various shapes to function as multi‐stimuli‐responsive soft robots (MSRs). Each MSR can respond to six different stimuli to autonomously transform their shapes, and mimic flowers, vines, mimosas, and flytraps. It is demonstrated that MSRs can climb slopes, switch locomotion modes, self‐adapt between air‐liquid environments, and transport cargo between different environments. This multimaterial integration strategy enables creating untethered soft millirobots that have multifunctionality, such as environmental sensing, self‐propulsion, and self‐adaptation, paving the way for their future operation in complex real‐world environments.

Smart materials respond to environmental signals by changing their microstructure and physical properties. Programming multiple behaviors and functions into a single material could increase its utility and adaptability to ever‐changing environmental conditions. A swellable and stretchable metamaterial hydrogel or “metasponge” engineered to morph into customized sizes and shapes that dynamically tune its physical properties and functions is reported. Multiple case studies that take advantage of the morphing properties of the metasponge, including robotic actuation, light guidance, optical and sonic invisibility (“cloaking”), adaptation of propulsion mode, sampling, and multiple biomedical applications, are illustrated. Developing multifunctional smart materials in which logic is programmed into the materials rather than electronic components could pave a new path to autonomy and dynamic responses in soft robots, sensors, and actuators.

Abstract Background Chronic spontaneous urticaria (CSU) is a common and disabling disease. Assessments of IgE and C‐reactive protein (CRP) are recommended in the diagnostic work‐up, but the role and clinical relevance of these biomarkers are not well characterized. Moreover, it remains unknown if elevated levels of IgE or CRP are linked to CSU microRNA (miRNA) signatures or interleukin 31 (IL‐31). Methods We measured IgE and CRP serum levels in 47 CSU patients (and 45 healthy controls) and determined CSU disease activity using the urticaria activity score (UAS7). Expression levels of miR‐155 and miR‐221 were assessed by RT‐PCR, and IL‐31 levels were determined by ELISA. Results Total IgE and CRP levels were independently increased in CSU patients. IgE and CRP levels were highest and lowest in patients with high and mild disease activity. IgE levels correlated with miR‐155 levels, whereas CRP levels correlated with miR‐221 levels. miR‐155 and miR‐221 were significantly overexpressed in CSU patients. ROC analyses linked miRNA‐155 and CSU with a sensitivity of 79% and specificity of 87%, and miRNA‐221 and CSU with a sensitivity of 75% and specificity of 91%. High CRP and miR‐221 expression levels were linked to elevated levels of IgG anti‐TPO and IL‐31. Conclusion IgE and CRP are useful biomarkers for disease activity in CSU, with distinct miRNA profiles. High CRP and miR‐221 levels may point to autoimmune CSU and a role for IL‐31.

Background Coronary heart disease remains the dominant cause of death worldwide. To improve cardiovascular disease prevention, knowledge of early key risk factors, especially those that are modifiable, is essential. The ongoing global obesity epidemic is of particular concern. We aimed to determine whether body mass index at conscription predicts early acute coronary events among men in Sweden. Methods and Results This was a population‐based Swedish cohort study of conscripts (n=1 668 921; mean age, 18.3 years; 1968–2005), with follow‐up through linkage to the nationwide Swedish patient and death registries. Risk of a first acute coronary event (hospitalization for acute myocardial infarction or coronary death) during follow‐up (1–48 years) was calculated with generalized additive models. Objective baseline measures of fitness and cognition were included in the models in secondary analyses. During follow‐up, there were 51 779 acute coronary events, of which 6457 (12.5%) were fatal within 30 days. Compared with men at the lowest end of the normal body mass index spectrum (body mass index, 18.5 kg/m2), an increasing risk for a first acute coronary event was observed, with hazard ratios (HRs) peaking at 40 years of age. After multivariable adjustments, men with a body mass index of 35 kg/m2 had an HR of 4.84 (95% CI, 4.29–5.46) for an event before the age of 40 years. Conclusions An increased risk of an early acute coronary event was detectable within normal levels of body weight at the age of 18 years, increasing to almost 5‐fold in the highest weight category at 40 years of age. Given increasing levels of body weight and prevalence of overweight and obesity in young adults, the current decrease in coronary heart disease incidence in Sweden may flatten or even reverse in the near future.

Background Guidelines recommend that coronary slow flow phenomenon (CSFP), defined as corrected thrombolysis in myocardial infarction frame count (CTFC) >$$ > $$27, can diagnose coronary microvascular dysfunction (CMD) in patients with angina and nonobstructed coronary arteries. CSFP has also historically been regarded as a sign of coronary endothelial dysfunction (CED). We sought to validate the utility of CTFC, as a binary classifier of CSFP and as a continuous variable, to diagnose CMD and CED. Methods and Results Patients with angina and nonobstructed coronary arteries had simultaneous coronary pressure and flow velocity measured using a dual sensor‐tipped guidewire during rest, adenosine‐mediated hyperemia, and intracoronary acetylcholine infusion. CMD was defined as the inability to augment coronary blood flow in response to adenosine (coronary flow reserve

Abstract Introduction Many studies have attempted to link multifidus (MF) fat infiltration with muscle quality and chronic low back pain (cLBP), but there is no consensus on these relationships. Methods In this cross‐sectional cohort study, 39 cLBP patients and 18 asymptomatic controls were included. The MF muscle was manually segmented at each lumbar disc level and fat fraction (FF) measurements were taken from the corresponding advanced imaging water‐fat images. We assessed the distribution patterns of MF fat from L1L2 to L5S1 and compared these patterns between groups. The sample was stratified by age, sex, body mass index (BMI), subject‐reported pain intensity (VAS), and subject‐reported low back pain disability (oswestry disability index, ODI). Results Older patients had significantly different MF FF distribution patterns compared to older controls (p

Background We sought to determine the role of obesity in adolescent men on development of atrial fibrillation (AF) and subsequent associated clinical outcomes in subjects diagnosed with AF. Methods and Results We conducted a nationwide, register‐based, cohort study of 1 704 467 men (mean age, 18.3±0.75 years) enrolled in compulsory military service in Sweden from 1969 through 2005. Height and weight, blood pressure, fitness, muscle strength, intelligence quotient, and medical disorders were recorded at baseline. Records obtained from the National Inpatient Registry and the Cause of Death Register were used to determine incidence and clinical outcomes of AF. During a median follow‐up of 32 years (interquartile range, 24–41 years), 36 693 cases (mean age at diagnosis, 52.4±10.6 years) of AF were recorded. The multivariable‐adjusted hazard ratio (HR) for AF increased from 1.06 (95% CI, 1.03–1.10) in individuals with body mass index (BMI) of 20.0 to 30 kg/m2 compared with those with BMI

Abstract In many malaria‐endemic regions, current detection tools are inadequate in diagnostic accuracy and accessibility. To meet the need for direct, phenotypic, and automated malaria parasite detection in field settings, a portable platform to process, image, and analyze whole blood to detect Plasmodium falciparum parasites, is developed. The liberated parasites from lysed red blood cells suspended in a magnetic field are accurately detected using this cellphone‐interfaced, battery‐operated imaging platform. A validation study is conducted at Ugandan clinics, processing 45 malaria‐negative and 36 malaria‐positive clinical samples without external infrastructure. Texture and morphology features are extracted from the sample images, and a random forest classifier is trained to assess infection status, achieving 100% sensitivity and 91% specificity against gold‐standard measurements (microscopy and polymerase chain reaction), and limit of detection of 31 parasites per µL. This rapid and user‐friendly platform enables portable parasite detection and can support malaria diagnostics, surveillance, and research in resource‐constrained environments.

Abstract Transarterial chemoembolization (TACE) is a therapeutic option for patients with intermediate‐stage hepatocellular carcinoma (HCC) or metastatic liver cancers. Identifying those patients who particularly benefit from TACE remains challenging. Macrophage migration inhibitory factor (MIF) represents is an inflammatory protein described in patients with liver cancer, but no data on its prognostic relevance in patients undergoing TACE exist. Here, we evaluate MIF serum concentrations as a potential biomarker in patients undergoing TACE for primary and secondary hepatic malignancies. MIF serum concentrations were measured by multiplex immunoassay in 50 patients (HCC: n = 39, liver metastases: n = 11) before and 1 day after TACE as well as in 51 healthy controls. Serum concentrations of MIF did not differ between patients and healthy controls. Interestingly, in the subgroup of patients with larger tumor size, significantly more patients had increased MIF concentrations. Patients with an objective tumor response to TACE therapy showed comparable concentrations of serum MIF compared to patients who did not respond. MIF concentrations at day 1 after TACE were significantly higher compared to baseline concentrations. Importantly, baseline MIF concentrations above the optimal cutoff value (0.625 ng/ml) turned out as a significant and independent prognostic marker for a reduced overall survival (OS) following TACE: patients with elevated MIF concentrations showed a significantly reduced median OS of only 719 days compared to patients below the cutoff value (median OS: 1430 days, p = 0.021). Baseline MIF serum concentrations are associated with tumor size of intrahepatic malignancies and predict outcome of patients with liver cancer receiving TACE.

Abstract Background Birch pollen‐related apple allergy is the most frequent IgE‐mediated food allergy in Central‐Northern Europe with Mal d 1 as major allergen. Its concentration in apples varies with the cultivar and storage time. Year‐round appealing, hypoallergenic cultivars still are needed to satisfy the nutritional needs of affected individuals. We characterized three promising cultivars by multidisciplinary in vitro assays including long‐term storage and by clinical challenges of allergic individuals before and after the birch pollen season. Methods Proteins were extracted from fruits of ‘Santana’, ‘Golden Delicious’ (GD), and three genuine cultivars in November 2018 and April 2019. Mal d 1‐levels were analysed by mass spectrometry, SDS‐PAGE, immunoblotting, competitive ELISA, and basophil activation tests. Twenty‐eight allergic individuals underwent single‐blinded open food challenges and skin testing with the cultivars and birch pollen in November 2018 and May 2019. Allergen‐specific IgE‐levels were determined. Results After storage all cultivars except ‘Santana’ were of appealing appearance and taste. Their Mal d 1 content had increased, also reflected by significantly amplified basophil activation and stronger reactions in clinical challenges. Besides, individuals showed boosted reactivity after pollen exposure indicated by enhanced allergen‐specific IgE‐levels and skin reactions to birch pollen. Still, all cultivars remained significantly less allergenic than GD and comparable to Santana in November 2018 in all assessments except for skin testing. Conclusions Combined expertise in pomology and allergology identified promising new cultivars for allergic consumers. The evaluation of hypoallergenic apples should incorporate long‐term storage and birch pollen exposure. Basophil activation tests may be suitable in the selection of promising cultivars for oral challenges.