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An unconventional yet facile low-energy method for uniquely synthesizing neat poly(vinylidene fluoride) (PVDF) films for energy harvesting applications by utilizing nanoelectromechanical vibration through a 'piezo-to-piezo' (P2P) mechanism is reported. In this concept, the nanoelectromechanical energy from a piezoelectric substrate is directly coupled into another polarizable material ( i.e. , PVDF) during its crystallization to produce an optically transparent micron-thick film that not only exhibits strong piezoelectricity, but is also freestanding-properties ideal for its use for energy harvesting, but which are difficult to achieve through conventional synthesis routes. We show, particularly through in situ characterization, that the unprecedented acceleration associated with the nanoelectromechanical vibration in the form of surface reflected bulk waves (SRBWs) facilitates preferentially-oriented nucleation of the ferroelectric PVDF β-phase, while simultaneously aligning its dipoles to pole the material through the SRBW's intense native evanescent electric field . The resultant neat (additive-free) homopolymer film synthesized through this low voltage method, which requires only -orders-of-magnitude lower than energy-intensive conventional poling methods utilizing high kV electric potentials, is shown to possess a 76% higher macroscale piezoelectric charge coefficient d 33 , together with a similar improvement in its power generation output, when compared to gold-standard commercially-poled PVDF films of similar thicknesses.

Background: Cardiovascular dysfunction is a significant factor contributing to weaning failure in mechanically ventilated children. Understanding the cardiopulmonary pathophysiological changes that occur during weaning is a prerequisite for the early recognition of weaning failure of cardiovascular origin. This study aimed to assess the effect of weaning trials on central hemodynamics and to identify the indices predictive of cardiac-related weaning failure., Methods: This prospective observational study was conducted in the Pediatric Intensive Care Unit (PICU) and included mechanically ventilated patients aged between 2 and 30 months who were on minimal ventilatory settings and ready for weaning. Patients who were hemodynamically unstable, diagnosed with neuromuscular diseases, or diagnosed with cardiac diseases were excluded. Hemodynamic parameters were evaluated during weaning from ventilation via echocardiography and noninvasive cardiometry during pressure support (PS) ventilation and at the end of the spontaneous breathing trial (SBT)., Results: The study included 50 patients, comprising 30 males (60%) and 20 females (40%) with ages ranging from 2 to 30 months. Echocardiography revealed a significant increase in the cardiac index (CI), tricuspid annular plane systolic excursion (TAPSE), and the E/A ratio at the end of SBT. Moreover, right ventricular systolic pressure (RVSP) significantly decreased. Noninvasive cardiometry revealed a significant increase in the index of contractility (ICON) and CI at the end of SBT (p-value = 0.023 and < 0.001, respectively). Of the 12 (25%) patients who failed their first extubation trial, they exhibited a significantly lower CI and TAPSE (p values = 0.001 and 0.001, respectively)., Conclusion: This study identified that weaning from mechanical ventilation in children is associated with hemodynamic changes, which can impact weaning success and reveal potential ventricular dysfunction. Bedside echocardiography was found to detect cardiac dysfunctions during weaning, and noninvasive cardiometry was considered a reliable tool that supports echocardiography for detecting changing trends in CI in PICUs. However, accurate values should be confirmed by echocardiography., (© 2024. The Author(s).)

Background: Globally, approximately 70 million people suffer from epilepsy. Infants constitute a significant percentage of these cases. Hence, there is a significant need for better understanding of the pathophysiology of epilepsy through laboratory and radiological methods for early detection and optimized management. Interleukin enhancer binding factor 3 antisense RNA l (ILF3AS1) is a long non-coding RNA (lncRNA) that enhances the expressions of matrix metalloproteinase 3 (MMP3) and matrix metalloproteinase 9 (MMP9), which are considered to be epileptogenic., Aim: We aimed to assess the serum expressions of the lncRNAs ILF3AS1, MMP3, and MMP9 along with microRNA-212 (miRNA-212) as predictive biomarkers in children with epilepsy; we also assessed their correlations with magnetic resonance imaging (MRI) findings., Subjects and Methods: Fifty children with epilepsy and fifty healthy controls were considered in this study. Serum expressions of the lncRNA ILF3AS1 and miRNA-212 were estimated by quantitative real-time polymerase chain reaction (qPCR). Serum concentrations of MMP3 and MMP9 were estimated by enzyme-linked immunosorbent assay (ELISA) in parallel with MRI findings and different baseline biochemical parameters of all the subjects., Results: The results showed significantly higher levels of lncRNAs ILF3AS1, MMP3, and MMP9 as well as lower levels of miRNA-212 in children with epilepsy compared to the controls. The fold-change of miRNA-212 was a significant negative predictor (odds ratio = 0.153, p = 0.000). The receiver operating characteristic curves (Roc) showed that the areas under the curves for MMP3, MMP9, and lncRNA ILF3AS1 as well as the fold-change for miRNA-212 were 0.659, 0.738, 0.656, and 0.965, respectively. Brain lesions were detected in 15 patients (30%) with epilepsy, whereas the remaining 35 patients (70%) had normal results., Conclusion: Serum levels of the lncRNA ILF3AS1 among children with epilepsy were higher than those in the control group and were associated with upregulation of both MMP3 and MMP9 as well as downregulation of miRNA-212 expressions, suggesting their predictive utility in monitoring the development of epilepsy; this also means that a treatment plan focusing on the ILF3AS1/miRNA-212/MMP3/MMP9 axis could be an effective strategy for treating epilepsy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mohammed, Emam, Mohammed, Abd Elalim, Mansour, Nasr, Ghamry, Alkhawagah, Fathy, Elattar, Abish, Hussein, Zaghloul, Khairallah, Alharbi, Seif Eldin, Dawood, Sabet, Gamea, Elshishtawy Ibrahim, Mosa and Dahpy.)

Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple genes. miRNA-375 and the Calpin-10 gene are potential genetic biomarkers for the early prediction of diabetic nephropathy (DN). 128 healthy controls and 129 type 2 diabetic (T2DM) participants were matched for age and sex. Three subgroups were identified from the T2DM group: 39 patients had microalbuminuria, 41 had macroalbuminuria, and 49 patients had renal problems. Circulating miR-375 expression levels were measured via qPCR. Calpain-10 SNP 19 (rs3842570) genotyping was assessed with allele-specific PCR in all the included participants. Spectrophotometry was used to measure the concentrations of serum copper, zinc, and magnesium, while ELISA was used to measure the levels of TGF-β and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-β, IL-17, Cu, and the Cu/Zn ratio, whereas, in contrast to the control group, the Zn and Mg levels were lower in the T2DM group. The DN groups had significantly lower miR-375, TGF-β, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-β, IL-17, and miRNA-375, there were notable correlations. Calpain-10 SNP 19 genotype 22 and allele 2 were linked to a higher incidence of T2DM and DN. Significant TGF-β, Cu, Cu/Zn ratio, HbAc1, and creatinine levels, but insignificant miRNA-375 levels, were associated with genotype 22 of Calpain-10 SNP 19. interactions between the Calpain-10 SNP 19 genotype 22 and IL-17, TGF-β, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.

Two-dimensional (2D) layered metal dichalcogenides constitute a promising class of materials for photodetector applications due to their excellent optoelectronic properties. The most common photodetectors, which work on the principle of photoconductive or photovoltaic effects, however, require either the application of external voltage biases or built-in electric fields, which makes it challenging to simultaneously achieve high responsivities across broad-band wavelength excitation─especially beyond the material's nominal band gap─while producing low dark currents. In this work, we report the discovery of an intricate phonon-photon-electron coupling─which we term the acoustophotoelectric effect─in SnS 2 that facilitates efficient photodetection through the application of 100 MHz order propagating surface acoustic waves (SAWs). This effect not only reduces the band gap of SnS 2 but also provides the requisite momentum for indirect band gap transition of the photoexcited charge carriers, to enable broad-band photodetection beyond the visible light range, while maintaining pA-order dark currents─ without the need for any external voltage bias. More specifically, we show in the infrared excitation range that it is possible to achieve up to 8 orders of magnitude improvement in the material's photoresponsivity compared to that previously reported for SnS 2 -based photodetectors, in addition to exhibiting superior performance compared to most other 2D materials reported to date for photodetection.

Aims/introduction: Peripheral artery disease (PAD) serves as a risk factor for diabetic foot ulcers (DFUs). PAD pathology involves atherosclerosis and impaired immunity. Non-classical monocytes are believed to have an anti-inflammatory role. 1,25-Dihydroxy vitamin D (vitamin D 3 ) is claimed to have immune-modulating and lipid-regulating roles. Vitamin D receptor is expressed on monocytes. We aimed to investigate if circulating non-classical monocytes and vitamin D 3 were implicated in DFUs associated with PAD., Materials and Methods: There were two groups of DFU patients: group 1 (n = 40) included patients with first-degree DFUs not associated with PAD, and group 2 (n = 50) included patients with DFU with PAD. The monocyte phenotypes were detected using flow cytometry. Vitamin D 3 was assessed by enzyme-linked immunosorbent assay., Results: DFU patients with PAD showed a significant reduction in the frequency of non-classical monocytes and vitamin D 3 levels, when compared with DFU patients without PAD. The percentage of non-classical monocytes positively correlated with vitamin D 3 level (r = 0.4, P < 0.01) and high-density lipoprotein (r = 0.5, P < 0.001), whereas it was negatively correlated with cholesterol (r = -0.5, P < 0.001). Vitamin D 3 was negatively correlated with triglyceride/high-density lipoprotein (r = -0.4, P < 0.01). Regression analysis showed that a high vitamin D 3 serum level was a protective factor against PAD occurrence., Conclusions: Non-classical monocytes frequency and vitamin D 3 levels were significantly reduced in DFU patients with PAD. Non-classical monocytes frequency was associated with vitamin D 3 in DFUs patients, and both parameters were linked to lipid profile. Vitamin D 3 upregulation was a risk-reducing factor for PAD occurrence., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

A way through which the properties of metal-organic frameworks (MOFs) can be tuned is by engineering defects into the crystal structure. Given its intrinsic stability and rigidity, however, it is difficult to introduce defects into zeolitic imidazolate frameworks (ZIFs)-and ZIF-8, in particular-without compromising crystal integrity. In this work, it is shown that the acoustic radiation pressure as well as the hydrodynamic stresses arising from the oscillatory flow generated by coupling high frequency (MHz-order) hybrid surface and bulk acoustic waves into a suspension of ZIF-8 crystals in a liquid pressure transmitting medium is capable of driving permanent structural changes in their crystal lattice structure. Over time, the enhancement in the diffusive transport of guest molecules into the material's pores as a consequence is shown to lead to expansion of the pore framework, and subsequently, the creation of dangling-linker and missing-linker defects, therefore offering the possibility of tuning the type and extent of defects engineered into the MOF through the acoustic exposure time. Additionally, the practical utility of the technology is demonstrated for one-pot, simultaneous solvent-assisted ligand exchange under ambient conditions, for sub-micron-dimension ZIF-8 crystals and relatively large ligands-more specifically 2-aminobenzimidazole-without compromising the framework porosity or overall crystal structure., (© 2023 The Authors. Small Methods published by Wiley-VCH GmbH.)

Background: Severe bronchial asthma (BA) affects 5-10% of children, which imposes socioeconomic burden. Therefore, it is crucial to identify biomarkers for risk stratification in children with BA. T regulatory cells (Tregs) play a balancing role in allergic response regulation. We aimed to investigate the relationship between Treg, miR-210-3p, and miR-146a-5p in relation to asthma phenotypes in search of novel biomarkers of disease severity., Methods: This study included 50 children with BA classified into Group 1 (n = 25) children with mild to moderate asthma and Group 2 (n = 25) children with severe asthma. In addition to 26 control subjects. Flow cytometry was used to detect Tregs. Plasma miR-210-3p and miR-146a levels were determined using quantitative real-time PCR. Patients' FEV1 (Forced Expiratory Volume in the first second) was measured., Results: miR-210-3p level correlated negatively with Treg frequency (r = -0.828, P < 0.001) and FEV1 (r = -0.621, P < 0.001). The level of miR-146a-5p positively correlated positively with Treg% (r = 0.303, P = 0.032). ROC curve analysis revealed that miR-210-3p was the most sensitive biomarker of severity, with the area under curve (AUC) = 0.923, 96% sensitivity, and 60% specificity. According to multivariate analysis, miR-210-3p is an independent risk factor for BA severity [OR =3.119, P = 0.030], while miR-146a-5p is a protective factor [OR =0.811, P = 0.049]., Conclusion: Treg frequency is linked to FEV1, miR-146a-5p and miR-210-3p in childhood BA. Upregulation of miR-210-3p is a sensitive biomarker and an independent risk factor for BA severity in Egyptian children., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Eldosoky et al.)

Cardiac arrest causes primary and secondary brain injuries. We evaluated the association between neuron-specific enolase (NSE), serum S-100B (S100B), electroencephalogram (EEG) patterns, and post-cardiac arrest outcomes in pediatric patients. A prospective observational study was conducted in the pediatric intensive care unit and included 41 post-cardiac arrest patients who underwent EEG and serum sampling for NSE and S100B. The participants were aged 1 month to 18 years who experienced cardiac arrest and underwent CPR after a sustained return of spontaneous circulation for ≥48 h. Approximately 19.5% ( n = 8) of patients survived until ICU discharge. Convulsions and sepsis were significantly associated with higher mortality (relative risk: 1.33 [95% CI = 1.09-1.6] and 1.99 [95% CI = 0.8-4.7], respectively). Serum NSE and S100B levels were not statistically associated with the outcome ( p = 0.278 and 0.693, respectively). NSE levels were positively correlated with the duration of CPR. EEG patterns were significantly associated with the outcome ( p = 0.01). Non-epileptogenic EEG activity was associated with the highest survival rate. Post-cardiac arrest syndrome is a serious condition with a high mortality rate. Management of sepsis and convulsions affects prognosis. We believe that NSE and S100B may have no benefit in survival evaluation. EEG can be considered for post-cardiac arrest patients.

MXenes hold immense potential given their superior electrical properties. The practical adoption of these promising materials is, however, severely constrained by their oxidative susceptibility, leading to significant performance deterioration and lifespan limitations. Attempts to preserve MXenes have been limited, and it has not been possible thus far to reverse the material's performance. In this work, we show that subjecting oxidized micron or nanometer thickness dry MXene films-even those constructed from nanometer-order solution-dispersed oxidized flakes-to just one minute of 10 MHz nanoscale electromechanical vibration leads to considerable removal of its surface oxide layer, whilst preserving its structure and characteristics. Importantly, electrochemical performance is recovered close to that of their original state: the pseudocapacitance, which decreased by almost 50% due to its oxidation, reverses to approximately 98% of its original value, with good capacitance retention ( ≈ 93%) following 10,000 charge-discharge cycles at 10 A g -1 . These promising results allude to the exciting possibility for rejuvenating the material for reuse, therefore offering a more economical and sustainable route that improves its potential for practical translation., (© 2023. The Author(s).)

Lung ultrasound (LUS) is a crucial diagnostic tool for identifying pneumonia in the pediatric age group. However, it plays a limited role in the early distinction between viral and bacterial pneumonia in children. The objectives of our study were to determine if LUS and the neutrophil-lymphocyte ratio (NLR) were useful in identifying and distinguishing between viral and bacterial pneumonia in Egyptian children under the age of two. Within the first 12 h of being admitted to our department, 52 children with clinical symptoms and signs suggestive of community-acquired pneumonia (CAP) underwent LUS and the NLR. LUS and the NLR strongly differentiated children with viral from those with bacterial pneumonia. For the early diagnosis and differentiation between viral and bacterial pneumonia in young Egyptian children, LUS was proven to be a noninvasive and reliable method. Combining the NLR with LUS increased the diagnostic accuracy when evaluating children suspected of having pneumonia.

Objectives. This study was carried out to delineate the patients' characteristics and the imaging findings and their relation to some biochemical markers of 31 critically ill patients with MIS-C. Design. A retrospective cross-sectional study including all critically ill MIS-C patients admitted to the PICU from June 23rd to July 22nd, 2020. Results. Eighteen males and 13 females, with a median age of 9 years (interquartile range 6-11) presented mainly with fever (100%) and hypotension (100%). Abnormalities in the chest computed tomography were detected in 22 cases (71%). Consolidation and architecture distortion were detected in 58.1% of patients; bilateral lesions and lower lobe infiltrates, each, was evident in 64.5% of patients, while the peripheral distribution of lesions was seen in 71% of the cases. Pleural thickening and effusion, each, was found in 51.6% of the patients. In this small case series, the presence of high ferritin was significantly associated with the bilaterality of the lesions. Elevated C-reactive protein was associated with the peripheral distribution of the lesions. Thrombocytopenia and hypoalbuminemia were significantly correlated with the CT disease stage and CT severity score respectively. Conclusions. Although a few children in this group of MIS-C patients presented with respiratory manifestations, yet, most of them demonstrated significant radiological lung involvement, which necessitates a longer-term follow-up., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objective: To report and describe cases of children presenting with coronavirus disease 2019 (COVID-19)-related multisystem inflammatory syndrome in children (MIS-C) with new-onset type 1 diabetes mellitus (T1DM) in severe diabetic ketoacidosis (DKA)., Research Design and Methods: This prospective observational study was conducted to characterize children with COVID-19-related MIS-C and new-onset T1DM who were in DKA. MIS-C was diagnosed if Centers for Disease Control and Prevention and World Health Organization criteria were fulfilled., Results: Six cases were identified. The patients were critically ill and in nonfluid responsive shock (combined hypovolemic and cardiogenic or distributive shock). All had cardiac involvement. One patient had a Kawasaki shock-like presentation. All needed aggressive treatment with careful monitoring of fluid balance (because of associated cardiac dysfunction), early institution of vasoactive/inotropic supports, and use of methylprednisolone and intravenous immunoglobulins. The latter are better administered after DKA resolution to avoid undue volume overload and fluid shifts while the patients are in DKA., Conclusions: Awareness of MIS-C coexistence with DKA at T1DM onset is crucial for rapid proper management., (© 2022 by the American Diabetes Association.)

Metal-organic frameworks (MOFs) have recently been shown to be effective antimicrobial agents, particularly if they comprise pathogenicidal metal ions. Nevertheless, the accessibility of these active metal sites to the pathogen, and hence the MOFs' antimicrobial activity itself, is often poor since the metal nodes are usually embedded deep within its three-dimensional (3D) structure. We show that a unique copper-based (copper(II)-benzene-1,3,5-tricarboxylate) MOF, whose quasi-two-dimensional (quasi-2D) swordlike structure facilitates exposure of the metal ions along its surface, exhibits enhanced antimicrobial properties against three representative plant pathogens: a bacterium ( Pseudomonas syringae ), a fungus ( Fusarium solani ), and a virus ( Odontoglossum ringspot virus (ORSV)). Such superior antimicrobial activity results in low minimum inhibitory concentrations (MICs)─half that of a commercial pesticide and an eighth of its conventional 3D cubic MOF counterpart (HKUST-1)─and hence low phytotoxicity, which can be attributed to the accessibility of the surface copper sites to the pathogen, thereby facilitating their adhesion and physical contact with the MOF. Additionally, we observed that orchids treated with the quasi-2D MOF showed negligible phytotoxicity and 80% decreased viral load. This work constitutes the first study to demonstrate the antimicrobial properties of this novel MOF against bacterial, fungal, and viral plant pathogens, and the first chemical control of ORSV.

Diamond nitrogen-vacancy (NV) centers constitute a promising class of quantum nanosensors owing to the unique magneto-optic properties associated with their spin states. The large surface area and photostability of diamond nanoparticles, together with their relatively low synthesis costs, make them a suitable platform for the detection of biologically relevant quantities such as paramagnetic ions and molecules in solution. Nevertheless, their sensing performance in solution is often hampered by poor signal-to-noise ratios and long acquisition times due to distribution inhomogeneities throughout the analyte sample. By concentrating the diamond nanoparticles through an intense microcentrifugation effect in an acoustomicrofluidic device, we show that the resultant dense NV ensembles within the diamond nanoparticles give rise to an order-of-magnitude improvement in the measured acquisition time. The ability to concentrate nanoparticles under surface acoustic wave (SAW) microcentrifugation in a sessile droplet is, in itself, surprising given the well-documented challenge of achieving such an effect for particles below 1 μm in dimension. In addition to a demonstration of their sensing performance, we thus reveal in this work that the reason why the diamond nanoparticles readily concentrate under the SAW-driven recirculatory flow can be attributed to their considerably higher density and hence larger acoustic contrast compared to those for typical particles and cells for which the SAW microcentrifugation flow has been shown to date.

Neonatal pneumonia is a serious respiratory infectious disease with a high rate of case fatality in developing countries. Salivary cytokines could serve as interesting noninvasive markers in the diagnosis of neonatal pneumonia. The aim was to assess the diagnostic role of salivary and serum interleukin-6 (IL-6), C-reactive protein/mean platelet volume (CRP/MPV) ratio, and the combination of these markers in the diagnosis of late-onset neonatal pneumonia in full-term neonates. Seventy full-term neonates, 35 with late-onset neonatal pneumonia and 35 controls, were enrolled in this prospective case-control study. Complete blood count (CBC), salivary and serum IL-6, and CRP concentrations were measured for all the study subjects. The sensitivity, specificity, positive predictive value, and negative predictive value of salivary IL-6, serum IL-6, and CRP/MPV ratio for the diagnosis of late-onset neonatal pneumonia were determined. At the cutoff point of >34 pg/ml, salivary IL-6 showed 82.86% sensitivity and 91.43% specificity. CRP/MPV ratio showed a sensitivity of 97.14% and specificity of 85.71% at a cutoff value > 0.88. The combination of salivary IL-6 and CRP/MPV ratio improved the sensitivity and specificity to 100%. The current study shows for the first time that both salivary IL-6 and CRP/MPV ratio are suitable markers for the diagnosis of late-onset neonatal pneumonia in full-term neonates., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Ahmed Omran et al.)

Salivary markers could serve as potential noninvasive markers in the diagnosis of neonatal infections. We aimed to investigate the diagnostic role of salivary and serum interleukin 10 (IL-10), C-reactive protein (CRP), mean platelet volume (MPV), and CRP/MPV ratio in the diagnosis of late-onset neonatal sepsis in full-term neonates. Seventy full-term neonates were enrolled in this prospective case-control study, 35 with late-onset neonatal sepsis, and 35 controls. Salivary IL-10, serum IL-10, and CRP concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Complete blood (CBC) count was measured by an automated blood cell counter. The salivary IL-10, serum IL-10, CRP, MPV, and CRP/MPV ratio levels were much higher in neonates with late-onset sepsis than in control (220 ± 150 vs. 18 ± 9 pg/ml, P < 0.001), (316 ± 198 vs. 23.7 ± 14 pg/ml, P < 0.001), (78.2 ± 34 vs. 3.3 ± 1.7 mg/L, P < 0.001), (11.2 ± 0.9 vs. 8.6 ± 0.4 fL), and (7.08 ± 3.3 vs. 0.4 ± 0.2, P < 0.001), respectively. At the cutoff point of >31 pg/ml, salivary IL-10 showed 97.1% sensitivity and 94.3% specificity. Serum IL-10 at a cutoff value of ≥33.6 pg/ml had a sensitivity of 97.1% and specificity of 80%. MPV showed a sensitivity of 100% and specificity of 94.4% at a cutoff value ≥ 9.2 fL. CRP/MPV ratio showed a sensitivity of 100% and specificity of 97.1% at a cutoff value > 0.9. Salivary and serum IL-10 showed a positive correlation with CRP and CRP/MPV ratio in septic neonates. The current study shows for the first time that both salivary IL-10 and CRP/MPV showed statistically significant differences between neonates with late-onset sepsis and controls. Accordingly, salivary IL-10 could serve as a potential noninvasive biomarker for the diagnosis of late-onset sepsis in full-term neonates., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ahmed Omran et al.)

Septic shock is a major public health concern. However, the clinical and laboratory criteria for sepsis overlap with those for hemophagocytic lymphohistiocytosis (HLH), and their differentiation can be challenging. The aim of this study was to compare HLH criteria among patients diagnosed with neonatal sepsis and childhood sepsis and to study the outcomes in patients fulfilling the diagnostic criteria for HLH. A cross-sectional study included 50 neonates and children with severe sepsis and/or septic shock. Clinical and laboratory data and HLH diagnostic criteria were studied in relation to patients outcome. Of all patients, 18% fulfilled three of the eight HLH diagnostic criteria, 2% fulfilled four criteria, and 4% fulfilled five criteria. All patients who fulfilled three or more of the criteria died. Mortality was higher in the presence of more positive HLH criteria and in pediatric age groups. However, the distributions of the HLH criteria were comparable for pediatric and neonatal patients with severe sepsis/septic shock, and their mortality rates were not significantly different when based on the criteria.

The conversion of layered transition metal carbides and/or nitrides (MXenes) into zero-dimensional structures with thicknesses and lateral dimensions of a few nanometers allows these recently discovered materials with exceptional electronic properties to exploit the additional benefits of quantum confinement, edge effects, and large surface area. Conventional methods for the conversion of MXene nanosheets and quantum dots, however, involve extreme conditions such as high temperatures and/or harsh chemicals that, among other disadvantages, lead to significant degradation of the material as a consequence of their oxidation. Herein, we show that the large surface acceleration-on the order of 10 million g 's-produced by high-frequency (10 MHz) nanometer-order electromechanical vibrations on a chip-scale piezoelectric substrate is capable of efficiently nebulizing, and consequently dimensionally reducing, a suspension of multilayer Ti 3 C 2 T z (MXene) into predominantly monolayer nanosheets and quantum dots while, importantly, preserving the material from any appreciable oxidation. As an example application, we show that the high-purity MXene quantum dots produced using this room-temperature chemical-free synthesis method exhibit superior performance as electrode materials for electrochemical sensing of hydrogen peroxide compared to the highly oxidized samples obtained through conventional hydrothermal synthesis. The ability to detect concentrations as low as 5 nM is a 10-fold improvement to the best reported performance of Ti 3 C 2 T z MXene electrochemical sensors to date.

Background: We sought to screen for clinical and laboratory features of hemophagocytic lymphohistiocytosis among pediatric patients with severe sepsis., Methods: We conducted a retrospective study that analyzed the clinical and laboratory data of 70 pediatric patients who died of severe sepsis. Medical records were revised for the presence of fever, splenomegaly, pancytopenia, hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia. Soluble CD25 was measured in stored samples., Results: Patients' ages ranged between 0.5 and 11 years with median (interquartile range) 2 (1-5). All patients had fever (≥38.5 °C) and pancytopenia, 58 (82.9%) hepatosplenomegaly, 36 (51.4%) lymphadenopathy, 37 (52.9%) had ferritin >500 ng/ml, 20 (28.6%) had fibrinogen <1.5 mg/ml, 14 (20%) had fasting triglycerides >264 mg/dl while 5 (7.1%) had soluble CD25 >2400 U/ml. Twenty-five (35.7%) patients fulfilled at least 5/6 of the hemophagocytic lymphohistiocytosis-2004 diagnostic criteria. Multivariate backward binary logistic regression analysis revealed lymphadenopathy as an independent predictor for hemophagocytic lymphohistiocytosis criteria fulfilment with odds ratio of 23.9. Fibrinogen had the best performance in discriminating hemophagocytic lymphohistiocytosis fulfilling from non-fulfilling groups (cut-off value: <1.8 mg/ml), followed by ferritin/erythrocyte sedimentation rate ratio (cut-off value: >17)., Conclusion: There is a significant clinical and laboratory overlap between hemophagocytic lymphohistiocytosis and severe sepsis, making the syndromes difficult to distinguish. The use of current hemophagocytic lymphohistiocytosis-2004 diagnostic criteria should be applied cautiously in those patients.

The generation of cavitation-free radicals through evanescent electric field and bulk-streaming was reported when micro-volumes of a liquid were subjected to 10 MHz surface acoustic waves (SAW) on a piezoelectric substrate [Rezk et al., J. Phys. Chem. Lett. 2020, 11, 4655-4661; Rezk et al., Adv. Sci. 2021, 8, 2001983]. In the current study, we have tested a similar hypothesis with PZT-based ultrasonic units (760 kHz and 2 MHz) with varying dissolved gas concentrations, by sonochemiluminescence measurement and iodide dosimetry, to correlate radical generation with dissolved gas concentrations. The dissolved gas concentration was adjusted by controlling the over-head gas pressure. Our study reveals that there is a strong correlation between sonochemical activity and dissolved gas concentration, with negligible sonochemical activity at near-vacuum conditions. We therefore conclude that radical generation is dominated by acoustic cavitation in conventional PZT-based ultrasonic reactors, regardless of the excitation frequency., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Light-driven directional motion is common in nature but remains a challenge for synthetic microparticles, particularly regarding collective motion on a macroscopic scale. Successfully engineering microparticles with light-driven collective motion could lead to breakthroughs in drug delivery, contaminant sensing, environmental remediation, and artificial life. Herein, metal-phenolic particle microswimmers capable of autonomously sensing and swimming toward an external light source are reported, with the speed regulated by the wavelength and intensity of illumination. These microswimmers can travel macroscopic distances (centimeters) and can remain illuminated for hours without degradation of motility. Experimental and theoretical analyses demonstrate that motion is generated through chemical transformations of the organic component of the metal-phenolic complex. Furthermore, cargos with specific spectral absorption profiles can be loaded into the particles and endow the particle microswimmers with activated motion corresponding to these spectral characteristics. The programmable nature of the light navigation, tunable size of the particles, and versatility of cargo loading demonstrate the versatility of these metal-phenolic particle microswimmers., (© 2021 Wiley-VCH GmbH.)

The current quest for two-dimensional transition metal carbides and nitrides (MXenes) has been to circumvent the slow, hazardous, and laborious multistep synthesis procedures associated with conventional chemical MAX phase exfoliation. Here, we demonstrate a one-step synthesis method with local Ti 3 AlC 2 MAX to Ti 3 C 2 T z MXene conversion on the order of milliseconds, facilitated by proton production through solution dissociation under megahertz frequency acoustic excitation. These protons combined with fluorine ions from LiF to selectively etch the MAX phase into MXene, whose delamination is aided by the acoustic forcing. These results have important implications for the future applicability of MXenes, which crucially depend on the development of more efficient synthesis procedures. For proof-of-concept, we show that flexible electrodes fabricated by this method exhibit comparable electrochemical performance to that previously reported.

The internalization of therapeutic molecules into cells-a critical step in enabling a suite of autologous ex vivo gene and cell therapies-is highly regulated by the lipid barrier imposed by the cell membrane. Strategies to increase the efficiency of delivering these exogenous payloads into the cell, while maintaining the integrity of both the therapeutic molecules to be delivered as well as the host cells they are delivered to, are therefore required. This is especially the case for suspension cells that are particularly difficult to transfect. In this work, we show that it is possible to enhance the uptake of short interfering RNA (siRNA) into nonadherent Jurkat and HuT 78 cells with a rapid poration-free method involving high-frequency (MHz order) acoustic excitation. The 2-fold enhancement in gene knockdown is almost comparable with that obtained with conventional nucleofection, which is among the most widely used intracellular delivery methods, but with considerably higher cell viabilities (>91% compared to approximately 76%) owing to the absence of pore formation. The rapid and effective delivery afforded by the platform, together with its low cost and scalability, therefore renders it a potent tool in the cell engineering pipeline.

Ultrasound constitutes a powerful means for materials processing. Similarly, a new field has emerged demonstrating the possibility for harnessing sound energy sources at considerably higher frequencies (10 MHz to 1 GHz) compared to conventional ultrasound (⩽3 MHz) for synthesizing and manipulating a variety of bulk, nanoscale, and biological materials. At these frequencies and the typical acoustic intensities employed, cavitation-which underpins most sonochemical or, more broadly, ultrasound-mediated processes-is largely absent, suggesting that altogether fundamentally different mechanisms are at play. Examples include the crystallization of novel morphologies or highly oriented structures; exfoliation of 2D quantum dots and nanosheets; polymer nanoparticle synthesis and encapsulation; and the possibility for manipulating the bandgap of 2D semiconducting materials or the lipid structure that makes up the cell membrane, the latter resulting in the ability to enhance intracellular molecular uptake. These fascinating examples reveal how the highly nonlinear electromechanical coupling associated with such high-frequency surface vibration gives rise to a variety of static and dynamic charge generation and transfer effects, in addition to molecular ordering, polarization, and assembly-remarkably, given the vast dimensional separation between the acoustic wavelength and characteristic molecular length scales, or between the MHz-order excitation frequencies and typical THz-order molecular vibration frequencies., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley‐VCH GmbH.)

Preconcentrating particulate and cellular matter for their isolation or detection is often a necessary and critical sample preparation or purification step in many lab-on-a-chip diagnostic devices. While surface acoustic wave (SAW) microcentrifugation has been demonstrated as a powerful means to drive efficient particle concentration, this has primarily been limited to micron dimension particles. When the particle size is around 1 μm or below, studies on SAW microcentrifugation to date have shown that particle ring-like aggregates can only be obtained in contrast to the localized concentrated clusters that are obtained with larger particles. Considering the importance of submicron particles and bioparticles that are common in many real-world samples, we elucidate why previous studies have not been able to achieve the concentration of these smaller particles to completion, and we present a practical solution involving a novel closed chamber configuration that minimizes sample heating and eliminates evaporation to show that it is indeed possible to drive submicron particle and cell concentration down to 200 nm diameters with SAW microcentrifugation over longer durations.

Owing to their large surface area and high uptake capacity, metal-organic frameworks (MOFs) have attracted considerable attention as potential materials for gas storage, energy conversion, and electrocatalysis. Various strategies have recently been proposed to manipulate the MOF surface chemistry to facilitate exposure of the embedded metal centers at the crystal surface to allow more effective binding of target molecules to these active sites. Nevertheless, such strategies remain complex, often requiring strict control over the synthesis conditions to avoid blocking pore access, reduction in crystal quality, or even collapse of the entire crystal structure. In this work, we exploit the hydrodynamics and capillary resonance associated with acoustically-driven dynamically spreading and nebulizing thin films as a new method for ultrafast synthesis of swordlike Cu 3 (1,3,5-benzenetricarboxylate) n (Cu-BTC) MOFs with unique monoclinic crystal structures (P2 1 /n) distinct to that obtained via conventional bulk solvothermal synthesis, with 'swordlike' morphologies whose lengths far exceed their thicknesses. Through pulse modulation and taking advantage of the rapid solvent evaporation associated with the high nebulisation rates, we are also able to control the thicknesses of these large aspect ratio (width and length with respect to the thickness) crystals by arresting their vertical growth, which, in turn, allows exposure of the metal active sites at the crystal surface. An upshot of such active site exposure on the crystal surface is the concomitant enhancement in the conductivity of the MOF, evident from the improvement in its current density by two orders of magnitude.

We reveal a unique mechanism by which pure water can be dissociated to form free radicals without requiring catalysts, electrolytes, or electrode contact by means of high-frequency nanometer-amplitude electromechanical surface vibrations in the form of surface acoustic waves (SAWs) generated on a piezoelectric substrate. The physical undulations associated with these mechanical waves, in concert with the evanescent electric field arising from the piezoelectric coupling, constitute half-wavelength "nanoelectrochemical cells" in which liquid is trapped within the SAW potential minima with vertical dimensions defined by the wave amplitude (∼10 nm), thereby forming highly confined polarized regions with intense electric field strengths that enable the breakdown of water. The ions and free radicals that are generated rapidly electromigrate under the high field intensity in addition to being convectively transported away from the cells by the bulk liquid recirculation generated by the acoustic excitation, thereby overcoming mass transport limitations that lead to ion recombination.

Introduction: Respiratory distress (RD) in children is a life-threatening condition. Delay in diagnosis has a deleterious effect on morbidity and mortality. The bedside lung ultrasound in emergency (BLUE) is a fast method that aims to accelerate the diagnosis with minimal radiological exposure. We targeted to evaluate the efficacy of BLUE protocol to speed and increase the precision of recognizing the cause of RD compared with chest X-ray (CXR) in the emergency department., Materials and Methods: A cross-sectional study on 63 children with RD attended the emergency of a tertiary, university-affiliated, pediatric medical center between January 2017 and January 2018., Results: Most cases were males 52.4%. We designed to estimate the value of BLUE as a diagnostic tool for RD and comparing it with CXR. Pneumonia with or without pleural effusion was the main etiology of RD detected by BLUE in 47.7% of studied children, pulmonary edema in 22.2%, bronchiolitis and asthma in 17.4%, and pneumothorax in 12.7%. Lung ultrasound (LUS) was superior to CXR in the diagnosis of RD cause, and most cases, 47.7% were diagnosed with pneumonia with a sensitivity of 93.5% and specificity 96.9%., Conclusion: Bedside lung ultrasound in emergency is an effective tool for identifying the cause of RD which is more sensitive and specific compared with CXR., How to Cite This Article: Hegazy LM, Rezk AR, Sakr HM, Ahmed AS. Comparison of Efficacy of LUS and CXR in the Diagnosis of Children Presenting with Respiratory Distress to Emergency Department. Indian J Crit Care Med 2020;24(6):459-464., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)

Microcentrifugation constitutes an important part of the microfluidic toolkit in a similar way that centrifugation is crucial to many macroscopic procedures, given that micromixing, sample preconcentration, particle separation, component fractionation, and cell agglomeration are essential operations in small scale processes. Yet, the dominance of capillary and viscous effects, which typically tend to retard flow, over inertial and gravitational forces, which are often useful for actuating flows and hence centrifugation, at microscopic scales makes it difficult to generate rotational flows at these dimensions, let alone with sufficient vorticity to support efficient mixing, separation, concentration, or aggregation. Herein, the various technologies-both passive and active-that have been developed to date for vortex generation in microfluidic devices are reviewed. Various advantages or limitations associated with each are outlined, in addition to highlighting the challenges that need to be overcome for their incorporation into integrated microfluidic devices., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The ability to spatially organise the microenvironment of tissue scaffolds unlocks the potential of many scaffold-based tissue engineering applications. An example application is to aid the regeneration process of peripheral nerve injuries. Herein, we present a promising approach for three-dimensional (3D) micropatterning of nerve cells in tissue scaffolds for peripheral nerve repair. In particular, we demonstrate the 3D micropatterning of PC12 cells in a gelatin-hydroxyphenylpropionic acid (Gtn-HPA) hydrogel using ultrasound standing waves (USWs). PC12 cells were first aligned in 3D along nodal planes by the USWs in Gtn-HPA hydrogel precursor solution. The precursor was then crosslinked using horseradish peroxidase (HRP) and diluted hydrogen peroxide (H 2 O 2 ), thus immobilising the aligned cells within 90-120 s. This micropatterning process is cost effective and can be replicated easily without the need for complex and expensive specialised equipment. USW-aligned PC12 cells showed no adverse effect in terms of viability or ability to proliferate. To our best knowledge, this is the first report on the effect of USW alignment on neural cell differentiation. Differentiated and USW-aligned PC12 cells showed directional uniformity after 20 d, making this technique a promising alternative approach to guide the nerve regeneration process.

Despite advances in two-dimensional (2D) transition metal dichalcogenide research owing to their outstanding physical properties, the synthesis of large micron-dimension single-layer sheets of these materials remains a challenge. Here, we present a novel and unique method to rapidly and flexibly exfoliate bulk molybdenum disulphide (MoS2) into either small nanometre-dimension quantum dots (QDs) or large micron-dimension sheets comprising predominantly single- or few-layers. The exfoliation process is conducted in dry phase, i.e., without liquid, by exploiting nanometer-amplitude MHz-order surface vibrations in the form of surface acoustic waves (SAWs). To produce the small QDs, we take advantage of the unprecedentedly large surface acceleration-on the order of 108 m s-2-to induce an iterative impaction mechanism involving successive ejection and collision of the bulk MoS2 aggregates within a miniature enclosure in order to progressively thin and break their lateral dimensions into single- and few-layer QDs. In contrast, we suppress the impaction in the zero-height enclosure limit by confining the bulk MoS2 under adhesive tape such that the shear that arises due to the travelling SAW on the substrate progressively thins the material whilst preserving their lateral dimension such that large, predominantly-monolayer, micron-sized sheets are produced with high substrate coverage up to around 80%. This fast, additive-free and dry exfoliation platform potentially presents a simple yet scalable micromechanical exfoliation method towards viable commercial production of 2D transition metal dichalcogenides.

The high surface area and porosity, and limitless compound and network combinations between the metal ions and organic ligands making up metal-organic frameworks (MOFs) offer tremendous opportunities for their use in many applications. While numerous methods have been proposed for the synthesis of MOF powders, it is often difficult to obtain oriented crystals with these techniques. Further, the need for additional post-synthesis steps to activate the crystals and release them from the substrate presents a considerable production challenge. Here, we report an acoustically-driven microcentrifugation platform that facilitates fast convective solutal transport, allowing the synthesis of MOF crystals in as short as five minutes. The crystals are not only oriented due to long-range out-of-plane superlattice ordering aided by molecular dipole polarization under the acoustoelectric coupling, but also simultaneously activated during the synthesis process.

Tactile haptic feedback is an important consideration in the design of advanced human-machine interfaces, particularly in an age of increasing reliance on automation and artificial intelligence. In this work, we show that the typical nanometer-order surface displacement amplitudes of piezoelectric transducers-which are too small to be detectable by the human touch, and constitute a significant constraint in their use for tactile haptic surface actuation-can be circumvented by coupling the vibration into a liquid to drive the deflection of a thermoplastic membrane. In particular, transmission of the sound energy from the standing wave vibration generated along a piezoelectric transducer into a microfluidic chamber atop which the membrane is attached is observed to amplify the mechanical vibration signalling through both the acoustic radiation pressure and the viscous normal stress acting on the membrane-the latter arising due to the acoustic streaming generated as the sound wave propagates through the liquid-to produce 100 μm-order static deflections of the membrane, upon which approximately 0.5 μm dynamic vibrations at frequencies around 1 kHz are superimposed; both these static and dynamic responses are within the perception range for human finger sensation. The large static deformation, the relatively fast response time, and the ability to incorporate a dynamic vibrotactile response together with the small size and potential for integration of the device into large scale arrays make this mechanism well suited for driving actuation in devices which require tactile haptic responses.

We seek to demonstrate a robust, low-cost, and user-friendly acoustomicrofluidic platform that facilitates rapid, reproducible, and precise nanoliter sample dispensing. The solid-state chipscale platform exploits the unprecedented acceleration arising from high-frequency nanoelectromechanical vibrations, on the order of 10 million g, to jet the sample and hence generate a liquid bridge that spans across the substrate, on which the vibrations are generated and from which the sample originates, to a top target plate before rapidly pinching off to deposit the sample on the target with precise and reproducible volumes that can be tuned down to 0.22 μL with a standard error of 6.5% and coefficient of variation of 11.3%. The entire process occurs within approximately 10 ms. In addition to explicating the fundamental physical mechanism that underpins the technology, we demonstrate its use for serial dilution and concentration and, in particular, a cell-based drug toxicology assay. Moreover, we also show that multiple drop dispensing in an array, without requiring repositioning of the chip between dispensing steps, can be achieved through a simple but yet effective sequential directional jetting strategy, therefore allowing significant reduction in the total dispensing time in the case of massive-scale microarray operation. Given its low cost and compact size, the platform can easily be automated and parallelized, thus offering the prospect for introducing large-scale efficiencies in the laboratory workflow.

The majority of infectious diseases enter the body through mucosal membranes that line the ocular, nasal, oral, vaginal and rectal surfaces. As infections can be effectively prevented by instigating a local immune response in the immunocyte-rich regions of the mucosa, an efficacious route of vaccine administration is to directly target their delivery to these surfaces. It is nevertheless challenging to provide sufficient driving force to penetrate both the mucus lining as well as the epithelial barrier of the mucosal surfaces, which are designed to effectively keep foreign entities out, but not excessively such that the therapeutic agent penetrates deeper into the vascularised submucosal regions where they are mostly taken up by the systemic circulation, thus resulting in a far weaker immune response. In this work, we demonstrate the possibility of controllably localising and hence maximising the delivery of both small and large molecule model therapeutic agents in the mucosa of a porcine buccal model using high frequency acoustics. Unlike their low (kHz order) frequency bulk ultrasonic counterpart, these high frequency (>10 MHz) surface waves do not generate cavitation, which leads to large molecular penetration depths beyond the 100 μm order thick mucosal layer, and which has been known to cause considerable cellular/tissue damage and hence scarring. Through system parameters such as the acoustic irradiation frequency, power and exposure duration, we show that it is possible to tune the penetration depth such that over 95% of the delivered drug are localised within the mucosal layer, whilst preserving their structural integrity.

We report a miniaturised platform for continuous production of single or multiple liquid droplets with diameters between 60 and 500 μm by interfacing a capillary-driven self-replenishing liquid feed with pulsed excitation of focussed surface acoustic waves (SAWs). The orifice-free operation circumvents the disadvantages of conventional jetting systems, which are often prone to clogging that eventuates in rapid degradation of the operational performance. Additionally, we show the possibility for flexibly tuning the ejected droplet size through the pulse width duration, thus avoiding the need for a separate device for every different droplet size required, as is the case for systems in which the droplet size is set by nozzles and orifices, as well as preceding ultrasonic jetting platforms where the droplet size is controlled by the operating frequency. Further, we demonstrate that cells can be jetted and hence printed onto substrates with control over the cell density within the droplets down to single cells. Given that the jetting does not lead to significant loss to the cell's viability or ability to proliferate, we envisage that this versatile jetting method can potentially be exploited with further development for cell encapsulation, dispensing and 3D bioprinting applications.

Recent breakthroughs in gene editing have necessitated practical ex vivo methods to rapidly and efficiently re-engineer patient-harvested cells. Many physical membrane-disruption or pore-forming techniques for intracellular delivery, however, result in poor cell viability, while most carrier-mediated techniques suffer from suboptimal endosomal escape and hence cytoplasmic or nuclear targeting. In this work, we show that short exposure of cells to high frequency (>10 MHz) acoustic excitation facilitates temporal reorganisation of the lipid structure in the cell membrane that enhances translocation of gold nanoparticles and therapeutic molecules into the cell within just ten minutes. Due to its transient nature, rapid cell self-healing is observed, leading to high cellular viabilities (>97%). Moreover, the internalised cargo appears to be uniformly distributed throughout the cytosol, circumventing the need for strategies to facilitate endosomal escape. In the case of siRNA delivery, the method is seen to enhance gene silencing by over twofold, demonstrating its potential for enhancing therapeutic delivery into cells.

While the remarkable properties of 2D crystalline materials offer tremendous opportunities for their use in optics, electronics, energy systems, biotechnology, and catalysis, their practical implementation largely depends critically on the ability to exfoliate them from a 3D stratified bulk state. This goal nevertheless remains elusive, particularly in terms of a rapid processing method that facilitates high yield and dimension control. An ultrafast multiscale exfoliation method is reported which exploits the piezoelectricity of stratified materials that are noncentrosymmetric in nature to trigger electrically-induced mechanical failure across weak grain boundaries associated with their crystal domain planes. In particular, it is demonstrated that microfluidic nebulization using high frequency acoustic waves exposes bulk 3D piezoelectric crystals such as molybdenum disulphide (MoS 2 ) and tungsten disulphide (WS 2 ) to a combination of extraordinarily large mechanical acceleration (≈10 8 m s -2 ) and electric field (≈10 7 V m -1 ). This results in the layered bulk material being rapidly cleaved into pristine quasi-2D-nanosheets that predominantly comprise single layers, thus constituting a rapid and high throughput chip-scale method that opens new possibilities for scalable production and spray coating deposition., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

While many microfluidic devices have been developed for sensing and others for actuation, few devices can perform both tasks effectively and simultaneously on the same platform. In piezoelectric sensors and actuators, this is due to the opposing operating requirements for sensing and actuation. Sensing ideally requires narrow resonant peaks characterized by high quality factors, such as those found in quartz crystals. However, these materials usually have poor electromechanical coupling coefficients that are not ideal for actuation. In this work, we show that it is possible to achieve both sensing and actuation simultaneously on a shared device by exploiting the distinct advantages of both bulk waves for effective mass sensing and surface waves for highly efficient microfluidic actuation through a unique hybrid surface and bulk acoustic wave platform. In light of the recent resurgence of interest in portable inhaled insulin devices for personalized diabetes management, we demonstrate the use of this technology for efficient aerosolization of insulin for inhalation without denaturing the protein, while being able to concurrently detect the residual mass of the un-nebulized insulin remaining on the device such that the actual dose delivered to the patient can be determined in real time.

The microarray titre plate remains a fundamental workhorse in genomic, proteomic and cellomic analyses that underpin the drug discovery process. Nevertheless, liquid handling technologies for sample dispensing, processing and transfer have not progressed significantly beyond conventional robotic micropipetting techniques, which are not only at their fundamental sample size limit, but are also prone to mechanical failure and contamination. This is because alternative technologies to date suffer from a number of constraints, mainly their limitation to carry out only a single liquid operation such as dispensing or mixing at a given time, and their inability to address individual wells, particularly at high throughput. Here, we demonstrate the possibility for true sequential or simultaneous single- and multi-well addressability in a 96-well plate using a reconfigurable modular platform from which MHz-order hybrid surface and bulk acoustic waves can be coupled to drive a variety of microfluidic modes including mixing, sample preconcentration and droplet jetting/ejection in individual or multiple wells on demand, thus constituting a highly versatile yet simple setup capable of improving the functionality of existing laboratory protocols and processes.

Thread-based microfluidics offer a simple, easy to use, low-cost, disposable and biodegradable alternative to conventional microfluidic systems. While it has recently been shown that such thread networks facilitate manipulation of fluid samples including mixing, flow splitting and the formation of concentration gradients, the passive capillary transport of fluid through the thread does not allow for precise control due to the random orientation of cellulose fibres that make up the thread, nor does it permit dynamic manipulation of the flow. Here, we demonstrate the use of high frequency sound waves driven from a chip-scale device that drives rapid, precise and uniform convective transport through the thread network. In particular, we show that it is not only possible to generate a stable and continuous concentration gradient in a serial dilution and recombination network, but also one that can be dynamically tuned, which cannot be achieved solely with passive capillary transport. Additionally, we show a proof-of-concept in which such spatiotemporal gradient generation can be achieved with the entire thread network embedded in a three-dimensional hydrogel construct to more closely mimic the in vivo tissue microenvironment in microfluidic chemotaxis studies and cell culture systems, which is then employed to demonstrate the effect of such gradients on the proliferation of cells within the hydrogel.

We report a simple method for on-demand continuous processing of composite liquid marbles with the aid of a 3D printed slide platform, which offers the potential for engineering novel functional surfaces for the production of combination drug therapies, particle-based barcode biomarkers and smart membranes, among other applications. Unlike other attempts at producing such liquid marbles, this novel technique not only facilitates controllable and reproducible production of the liquid marbles but also allows the selection of different morphologies such as banded, patchy, and Janus structures by controlling the coalescence conditions, with the possibility for tunable symmetric and asymmetric patterns, the latter by varying the particle species partitioning ratio.

Infection by hepatitis C virus (HCV) and its subsequent complications are a major cause of mortality worldwide. The water extract of the wild Egyptian artichoke (WEA) (Cynara cardunculus L. var. sylvestris (Lam.) Fiori) leaves is a freely available herbal product that is used for treatment of HCV-infection complications such as jaundice and ascites. The purpose of this study was to evaluate whether WEA exhibits activity against HCV, identify bioactive chemicals in its extract and to tentatively examine the potential inhibitory interactions of WEA with human drug-metabolizing enzymes. The current pilot clinical trial revealed that the water extract of a WEA plant decreased the HCV viral load below the detection level in 12 out of 15 patients. Furthermore, the liver enzymes ALT and AST, as well as the level of bilirubin were normalized. The total WEA extract inhibited CYP2B6 (OH-BUP) and CYP2C19 (5-OH-OME) with high affinity, IC50 ∼ 20 μg ml(-1), while moderate inhibitory interactions were observed for CYP1A2, CYP2D6, CYP2E1 and CYP3A4. Results presented herein suggest that the WEA exhibits strong antiviral activity against HCV and may be useful for its treatment. Compared to the artichoke product "Hepar SL Forte(®)", WEA was found to be more enriched in sesquiterpenes versus the abundance of phenolic compounds, especially flavonoids in Hepar SL Forte(®) as revealed via UPLC-MS analysis coupled to chemometrics.

Surface acoustic wave (SAW), a nanometer amplitude electroelastic wave generated and propagated on low-loss piezoelectric substrates (such as LiNbO3), is an extremely efficient solid-fluid energy transfer mechanism. The present study explores the use of SAW nebulization as a solution for effective pulmonary peptide delivery. In vitro deposition characteristics of the nebulized peptides were determined using a Next Generation Cascade Impactor. 70% of the peptide-laden aerosols generated were within a size distribution favorable for deep lung distribution. The integrity of the nebulized peptides was found to be retained, as shown via mass spectrometry. The anti-mycobacterial activity of the nebulized peptides was found to be uncompromised compared with their non-nebulized counterparts, as demonstrated by the minimum inhibition concentration and the colony forming inhibition activity. The peptide concentration and volume recoveries for the SAW nebulizer were significantly higher than 90% and found to be insensitive to variation in the peptide sequences. These results demonstrate the potential of the SAW nebulization platform as an effective delivery system of therapeutic peptides through the respiratory tract to the deep lung.

The existence of what is termed here as a surface-reflected bulk wave is unraveled and elucidated, and it is shown, quite counterintuitively, that it is possible to obtain an order-of-magnitude improvement in microfluidic manipulation efficiency, and, in particular, nebulization, through a unique combination of surface and bulk waves without increasing complexity or cost., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

By exploiting the very recent discovery of the piezoelectricity in odd-numbered layers of two-dimensional molybdenum disulfide (MoS2), we show the possibility of reversibly tuning the photoluminescence of single and odd-numbered multilayered MoS2 using high frequency sound wave coupling. We observe a strong quenching in the photoluminescence associated with the dissociation and spatial separation of electrons-holes quasi-particles at low applied acoustic powers. At the same applied powers, we note a relative preference for ionization of trions into excitons. This work also constitutes the first visual presentation of the surface displacement in one-layered MoS2 using laser Doppler vibrometry. Such observations are associated with the acoustically generated electric field arising from the piezoelectric nature of MoS2 for odd-numbered layers. At larger applied powers, the thermal effect dominates the behavior of the two-dimensional flakes. Altogether, the work reveals several key fundamentals governing acousto-optic properties of odd-layered MoS2 that can be implemented in future optical and electronic systems.