Wide bandgap semiconductor nanomembranes as a long-term biointerface for flexible, implanted neuromodulator.

Electrical neuron stimulation holds promise for treating chronic neurological disorders, including spinal cord injury, epilepsy, and Parkinson's disease. The implementation of ultrathin, flexible electrodes that can offer noninvasive attachment to soft neural tissues is a breakthrough for timely, continuous, programable, and spatial stimulations. With strict flexibility requirements in neural implanted stimulations, the use of conventional thick and bulky packages is no longer applicable, posing major technical issues such as short device lifetime and long-term stability. We introduce herein a concept of long-lived flexible neural electrodes using silicon carbide (SiC) nanomembranes as a faradic interface and thermal oxide thin films as an electrical barrier layer. The SiC nanomembranes were developed using a chemical vapor deposition (CVD) process at the wafer level, and thermal oxide was grown using a high-quality wet oxidation technique. The proposed material developments are highly scalable and compatible with MEMS technologies, facilitating the mass production of long-lived implanted bioelectrodes. Our experimental results showed excellent stability of the SiC/silicon dioxide (SiO2) bioelectronic system that can potentially last for several decades with well-maintained electronic properties in biofluid environments. We demonstrated the capability of the proposed material system for peripheral nerve stimulation in an animal model, showing muscle contraction responses comparable to those of a standard non-implanted nerve stimulation device. The design concept, scalable fabrication approach, and multimodal functionalities of SiC/SiO2 flexible electronics offer an exciting possibility for fundamental neuroscience studies, as well as for neural stimulation-based therapies.

Integrated Sensors for Soft Medical Robotics.

Minimally invasive procedures assisted by soft robots for surgery, diagnostics, and drug delivery have unprecedented benefits over traditional solutions from both patient and surgeon perspectives. However, the translation of such technology into commercialization remains challenging. The lack of perception abilities is one of the obstructive factors paramount for a safe, accurate and efficient robot-assisted intervention. Integrating different types of miniature sensors onto robotic end-effectors is a promising trend to compensate for the perceptual deficiencies in soft robots. For example, haptic feedback with force sensors helps surgeons to control the interaction force at the tool-tissue interface, impedance sensing of tissue electrical properties can be used for tumor detection. The last decade has witnessed significant progress in the development of multimodal sensors built on the advancement in engineering, material science and scalable micromachining technologies. This review article provides a snapshot on common types of integrated sensors for soft medical robots. It covers various sensing mechanisms, examples for practical and clinical applications, standard manufacturing processes, as well as insights on emerging engineering routes for the fabrication of novel and high-performing sensing devices.

Mesoporous Gold: Substrate-Dependent Growth Dynamics, Strain Accumulation, and Electrocatalytic Activity for Biosensing.

Understanding the growth of mesoporous crystalline materials, such as mesoporous metals, on different substrates can provide valuable insights into the crystal growth dynamics and the redox reactions that influence their electrochemical sensing performance. Herein, it is demonstrated how the amorphous nature of the glass substrate can suppress the typical <111> oriented growth in mesoporous Au (mAu) films. The suppressed <111> growth is manifested as an accumulation of strain, leading to the generation of abundant surface defects, which are beneficial for enhancing the electrochemical activity. The fine structuring attained enables dramatically accelerated diffusion and enhances the electrochemical sensing performance for disease-specific biomolecules. As a proof-of-concept, the as-fabricated glass-grown mAu film demonstrates high sensitivity in electrochemical detection of SARS-CoV-2-specific RNA with a limit of detection (LoD) as low as 1 attomolar (aM).

A machine learning-based choledocholithiasis prediction tool to improve ERCP decision making: a proof-of-concept study.

BACKGROUND: Previous studies demonstrated limited accuracy of existing guidelines for predicting choledocholithiasis, leading to overutilization of endoscopic retrograde cholangiopancreatography (ERCP). More accurate stratification may improve patient selection for ERCP and allow use of lower-risk modalities. METHODS: A machine learning model was developed using patient information from two published cohort studies that evaluated performance of guidelines in predicting choledocholithiasis. Prediction models were developed using the gradient boosting model (GBM) machine learning method. GBM performance was evaluated using 10-fold cross-validation and area under the receiver operating characteristic curve (AUC). Important predictors of choledocholithiasis were identified based on relative importance in the GBM. RESULTS: 1378 patients (mean age 43.3 years; 61.2% female) were included in the GBM and 59.4% had choledocholithiasis. Eight variables were identified as predictors of choledocholithiasis. The GBM had accuracy of 71.5% (SD 2.5%) (AUC 0.79 [SD 0.06]) and performed better than the 2019 American Society for Gastrointestinal Endoscopy (ASGE) guidelines (accuracy 62.4% [SD 2.6%]; AUC 0.63 [SD 0.03]) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines (accuracy 62.8% [SD 2.6%]; AUC 0.67 [SD 0.02]). The GBM correctly categorized 22% of patients directed to unnecessary ERCP by ASGE guidelines, and appropriately recommended as the next management step 48% of ERCPs incorrectly rejected by ESGE guidelines. CONCLUSIONS: A machine learning-based tool was created, providing real-time, personalized, objective probability of choledocholithiasis and ERCP recommendations. This more accurately directed ERCP use than existing ASGE and ESGE guidelines, and has the potential to reduce morbidity associated with ERCP or missed choledocholithiasis.

Mesoporous Semiconductive Bi2Se3 Films.

Bi2Se3 is a semiconductive material possessing a bandgap of 0.3 eV, and its unique band structure has paved the way for diverse applications. Herein, we demonstrate a robust platform for synthesizing mesoporous Bi2Se3 films with uniform pore sizes via electrodeposition. Block copolymer micelles act as soft templates in the electrolyte to create a 3D porous nanoarchitecture. By controlling the length of the block copolymer, the pore size is adjusted to 9 and 17 nm precisely. The nonporous Bi2Se3 film exhibits a tunneling current in a vertical direction of 52.0 nA, but upon introducing porosity (9 nm pores), the tunneling current increases significantly to 684.6 nA, suggesting that the conductivity of Bi2Se3 films is dependent on the pore structure and surface area. The abundant porous architecture exposes a larger surface area of Bi2Se3 to the surrounding air within the same volume, thereby augmenting its metallic properties.

Mesoporous Metastable CuTe2 Semiconductor.

Binary metastable semiconductor materials offer exciting possibilities in the field of optoelectronics, such as photovoltaics, tunable photosensors, and detectors. However, understanding their properties and translating them into practical applications can sometimes be challenging, owing to their thermodynamic instability. Herein, we report a temperature-controlled crystallization technique involving electrochemical deposition to produce metastable CuTe2 thin films that can reliably function under ambient conditions. A series of in situ heating/cooling cycle tests from room temperature to 200 °C followed by spectral, morphological, and compound analyses (such as ultraviolet-visible light spectroscopy, X-ray diffraction (XRD) analysis, and X-ray photoelectron spectroscopy (XPS)) suggest that the seeding electrodes play a key role in the realization of the metastable phase in CuTe2 films. In particular, CuTe2 films deposited on Al electrodes exhibit superior crystallinity and long-term stability compared with those grown on a Au substrate. The XRD data of thermally annealed CuTe2 thin films deposited on Al show a markedly sharp peak, indicating significantly increased crystal-domain sizes. Our method can be used to achieve the metastable phase of CuTe2 with a bandgap of 1.67 eV and offers outstanding photoresponsivity under different illumination conditions.

Flexible Nanoarchitectonics for Biosensing and Physiological Monitoring Applications.

Flexible and implantable electronics hold tremendous promises for advanced healthcare applications, especially for physiological neural recording and modulations. Key requirements in neural interfaces include miniature dimensions for spatial physiological mapping and low impedance for recognizing small biopotential signals. Herein, a bottom-up mesoporous formation technique and a top-down microlithography process are integrated to create flexible and low-impedance mesoporous gold (Au) electrodes for biosensing and bioimplant applications. The mesoporous architectures developed on a thin and soft polymeric substrate provide excellent mechanical flexibility and stable electrical characteristics capable of sustaining multiple bending cycles. The large surface areas formed within the mesoporous network allow for high current density transfer in standard electrolytes, highly suitable for biological sensing applications as demonstrated in glucose sensors with an excellent detection limit of 1.95 µm and high sensitivity of 6.1 mA cm-2  µM-1 , which is approximately six times higher than that of benchmarking flat/non-porous films. The low impedance of less than 1 kΩ at 1 kHz in the as-synthesized mesoporous electrodes, along with their mechanical flexibility and durability, offer peripheral nerve recording functionalities that are successfully demonstrated in vivo. These features highlight the new possibilities of our novel flexible nanoarchitectonics for neuronal recording and modulation applications.

Expeditious Electrochemical Synthesis of Mesoporous Chalcogenide Flakes: Mesoporous Cu2 Se as a Potential High-Rate Anode for Sodium-Ion Battery.

Nanostructured copper selenide (Cu2 Se) attracts much interest as it shows outstanding performance as thermoelectric, photo-thermal, and optical material. The mesoporous structure is also a promising morphology to obtain better performance for electrochemical and catalytic applications, thanks to its high surface area. A simple one-step electrochemical method is proposed for mesoporous chalcogenides synthesis. The synthesized Cu2 Se material has two types of mesopores (9 and 18 nm in diameter), which are uniformly distributed inside the flakes. These materials are also implemented for sodium (Na) ion battery (NIB) anode as a proof of concept. The electrode employing the mesoporous Cu2 Se exhibits superior and more stable specific capacity as a NIB anode compared to the non-porous samples. The electrode also exhibits excellent rate tolerance at each current density, from 100 to 1000 mA g-1 . It is suggested that the mesoporous structure is advantageous for the insertion of Na ions inside the flakes. Electrochemical analysis indicates that the mesoporous electrode possesses more prominent diffusion-controlled kinetics during the sodiation-desodiation process, which contributes to the improvement of Na-ion storage performance.

Morphologic Severity of Acute Pancreatitis on Imaging Is Independently Associated with Opioid Dose Requirements in Hospitalized Patients.

BACKGROUND: Prior studies have evaluated clinical characteristics associated with opioid dose requirements in hospitalized patients with acute pancreatitis (AP) but did not incorporate morphologic findings on CT imaging. AIMS: We sought to determine whether morphologic severity on imaging is independently associated with opioid dose requirements in AP. METHODS: Adult inpatients with a diagnosis of AP from 2006 to 2017 were reviewed. The highest modified CT severity index (MCTSI) score and the daily oral morphine equivalent (OME) for each patient over the first 7 days of hospitalization were used to grade the morphologic severity of AP and calculate mean OME per day(s) of treatment (MOME), respectively. Multiple regression analysis was used to evaluate the association of MOME with MCSTI. RESULTS: There were 249 patients with AP, of whom 196 underwent contrast-enhanced CT. The mean age was 46 ± 13.6 years, 57.9% were male, and 60% were black. The mean MOME for the patient cohort was 60 ± 52.8 mg/day. MCTSI (ß = 3.5 [95% CI 0.3, 6.7], p = 0.03), early hemoconcentration (ß = 21 [95% CI 4.6, 39], p = 0.01) and first episode of AP (ß = - 17 [95% CI - 32, - 2.7], p = 0.027) were independently associated with MOME. Among the 19 patients undergoing ≥ 2 CT scans, no significant differences in MOME were seen between those whose MCTSI score increased (n = 12) versus decreased/remained the same (n = 7). CONCLUSION: The morphologic severity of AP positively correlated with opioid dose requirements. No difference in opioid dose requirements were seen between those who did versus those who did not experience changes in their morphologic severity.

Plasma-Induced Nanocrystalline Domain Engineering and Surface Passivation in Mesoporous Chalcogenide Semiconductor Thin Films.

The synthesis of highly crystalline mesoporous materials is key to realizing high-performance chemical and biological sensors and optoelectronics. However, minimizing surface oxidation and enhancing the domain size without affecting the porous nanoarchitecture are daunting challenges. Herein, we report a hybrid technique that combines bottom-up electrochemical growth with top-down plasma treatment to produce mesoporous semiconductors with large crystalline domain sizes and excellent surface passivation. By passivating unsaturated bonds without incorporating any chemical or physical layers, these films show better stability and enhancement in the optoelectronic properties of mesoporous copper telluride (CuTe) with different pore diameters. These results provide exciting opportunities for the development of long-term, stable, and high-performance mesoporous semiconductor materials for future technologies.

Provider Response to Critical Action Values for Hypoglycemia in the Ambulatory Setting: a Retrospective Cohort Study.

BACKGROUND: The blood glucose level triggering a critical action value (CAV) for hypoglycemia is not standardized, and associated outcomes are unknown. OBJECTIVE: To evaluate the clinical consequences of, and provider responses to, CAVs for hypoglycemia. DESIGN: Retrospective cohort study at Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center between April 1, 2013, and January 31, 2017. PARTICIPANTS: Patients with an ambulatory serum glucose < 50 mg/dL. Point-of-care capillary glucose and whole blood glucose samples were excluded. MAIN MEASURES: Electronic medical record (EMR) review for providers' documented response to CAV, associated patient symptoms, and serious adverse events. KEY RESULTS: We analyzed 209 CAVs for hypoglycemia from 154 patients. The median age (IQR) was 59 years (46, 69), 89 (57.8%) were male, and 96 (62.3%) were black. Provider-to-patient contact occurred in 128 of 209 (61.2%) episodes, among which no documented etiology was observed for 81 of 128 (63.3%), no recommendations were provided in 32 of 128 (25.0%), and no patient-reported hypoglycemic symptoms were documented in 103 of 128 (80.5%). Serious adverse events were documented in 4 of 128 episodes (3.1%), two required glucagon administration, and three required an ED visit. Provider-to-patient contact was associated with the patient having malignant neoplasm (adjusted OR 3.63, p = 0.045) or a hypoglycemic disorder (adjusted OR 7.70, p = 0.018) and inversely associated with a longer time from specimen collection to EMR result (adjusted OR 0.90 per hour, p = 0.016). CONCLUSIONS: There is inconsistent provider-to-patient contact following CAVs for hypoglycemia, and the etiology and symptoms of hypoglycemia were infrequently documented. There were few serious documented adverse events associated with hypoglycemia, although undocumented events may have occurred, and the incidence of serious adverse events in non-contacted patients remains unknown. These findings demonstrate a need to standardize provider response to CAVs for hypoglycemia. Decreasing the lag time between sample collection and laboratory result reporting may increase provider-to-patient contact.

Universal Electrochemical Synthesis of Mesoporous Chalcogenide Semiconductors: Mesoporous CdSe and CdTe Thin Films for Optoelectronic Applications.

Here we report the soft-template-assisted electrochemical deposition of mesoporous semiconductors (CdSe and CdTe). The resulting mesoporous films are stoichiometrically equivalent and contain mesopores homogeneously distributed over the entire surface. To demonstrate the versatility of the method, two block copolymers with different molecular weights are used, yielding films with pores of either 9 or 18 nm diameter. As a proof of concept, the mesoporous CdSe film-based photodetectors show a high sensitivity of 204 mW-1 cm2 at 680 nm wavelength, which is at least two orders of magnitude more sensitive than the bulk counterpart. This work presents a new synthesis route for nanostructured semiconductors with optical band gaps active in the visible spectrum.

On the physics of dispersive electron transport characteristics in SnO2 nanoparticle-based dye sensitized solar cells.

The present study elucidates dispersive electron transport mediated by surface states in tin oxide (SnO2) nanoparticle-based dye sensitized solar cells (DSSCs). Transmission electron microscopic studies on SnO2 show a distribution of ∼10 nm particles exhibiting (111) crystal planes with inter-planar spacing of 0.28 nm. The dispersive transport, experienced by photo-generated charge carriers in the bulk of SnO2, is observed to be imposed by trapping and de-trapping processes via SnO2 surface states present close to the band edge. The DSSC exhibits 50% difference in performance observed between the forward (4%) and reverse (6%) scans due to the dispersive transport characteristics of the charge carriers in the bulk of the SnO2. The photo-generated charge carriers are captured and released by the SnO2 surface states that are close to the conduction band-edge resulting in a very significant variation; this is confirmed by the hysteresis observed in the forward and reverse scan current-voltage measurements under AM1.5 illumination. The hysteresis behavior assures that the charge carriers are accumulated in the bulk of electron acceptor due to the trapping, and released by de-trapping mediated by surface states observed during the forward and reverse scan measurements.

Tuberculosis presenting as uncontrolled hypertension.

We analyzed the issue of a young woman who wanted our opinion regarding uncontrolled hypertension. Her hypertension was discovered to have a highly unusual origin, but it is fairly prevalent in nations like India. A 19-year-old woman who complained of blurred vision was presented to an ophthalmologist, who diagnosed her with grade IV hypertensive retinopathy. Her 2D ECHO was normal, hence a thorough screening for secondary hypertension was carried out. A left paravertebral tumor that may have squeezed the left renal artery and contributed to her hypertension was discovered during the workup by a CECT chest and abdomen scan. She also exhibited widespread lymphadenopathy; a condition known as granulomatous pathology. She was started on anti-TB medication, and after six months of treatment, her radiological and clinical conditions improved. This case highlights a rare instance of TB causing excessively elevated blood pressure.

A case of tracheobronchopathia ostochondorplastica.

Tracheobronchopathia osteochondroplastica (TO) is a disorder caused by the accumulation of calcium phosphate in the submucosa of large airways. Benign proliferation of bone and cartilage lead to the narrowing of airways. Bronchoscopy is the diagnostic test for TO. It shows characteristic smooth nodules emerging from tracheal rings that never involves the posterior membranous wall.

Study on factors associated with post bronchodilator reversibility among patients presenting with dyspnea: An experience at a tertiary care academic hospital in Kerala.

Background: The change in FEV1 after administration of a short-acting bronchodilator has been widely used for diagnosis of obstructive airway diseases. Many factors can influence the post bronchodilator reversibility. Aim: The aim of the present study was to estimate the presence of reversibility among the patients of obstructive airway disease and to identify the factors affecting it. Methods: Patients who presented to the department of respiratory medicine with symptoms of dyspnea were evaluated with spirometry. Spirometry and post bronchodilator reversibility (BDR) was defined as per international guidelines. SPSS 17 was used for statistical analysis and P < 0.05 was considered significant. Results: Out of 100 patients studied, 33 had BDR. Median age of the population was 58 ± 17 years. There were 72 non-smokers and 58 men. A total of 32 had chronic obstructive pulmonary disease (COPD), 56 had asthma, and 12 had normal spirometry. The median pre and post bronchodilator FEV1 was 1.34L/Sec and 1.46 L/sec respectively. Twenty-seven of asthma (41%) and 6 of COPD (19%) had BDR (P = 0.05). Other factors associated with BDR were smoking (P = 0.035). There was no statistically significant correlation found between eosinophilia, gender, severity of obstruction, BMI, height, weight and age. Conclusion: The prevalence of post BDR in the study population was 33%. The factors affecting BDR were smoking status, and asthma. The study did not show any significant correlation between BDR and eosinophilia, gender, height and age.

MOF-derived nanoporous carbons with diverse tunable nanoarchitectures.

Metal-organic frameworks (MOFs), or porous coordination polymers, are crystalline porous materials formed by coordination bonding between inorganic and organic species on the basis of the self-assembly of the reacting units. The typical characteristics of MOFs, including their large specific surface areas, ultrahigh porosities and excellent thermal and chemical stabilities, as well as their great potential for chemical and structural modifications, make them excellent candidates for versatile applications. Their poor electrical conductivity, however, has meant that they have not been useful for electrochemical applications. Fortuitously, the direct carbonization of MOFs results in a rearrangement of the carbon atoms of the organic units into a network of carbon atoms, which means that the products have useful levels of conductivity. The direct carbonization of zeolitic imidazolate framework (ZIF)-type MOFs, particularly ZIF-8, has successfully widened the scope of possible applications of MOFs to include electrochemical reactions that could be used in, for example, energy storage, energy conversion, electrochemical biosensors and capacitive deionization of saline water. Here, we present the first detailed protocols for synthesizing high-quality ZIF-8 and its modified forms of hollow ZIF-8, core-shell ZIF-8@ZIF-67 and ZIF-8@mesostuctured polydopamine. Typically, ZIF-8 synthesis takes 27 h to complete, and subsequent nanoarchitecturing procedures leading to hollow ZIF-8, ZIF-8@ZIF-67 and ZIF-8@mPDA take 6, 14 and 30 h, respectively. The direct-carbonization procedure takes 12 h. The resulting nanoporous carbons are suitable for electrochemical applications, in particular as materials for supercapacitors.

Integrated, Transparent Silicon Carbide Electronics and Sensors for Radio Frequency Biomedical Therapy.

The integration of micro- and nanoelectronics into or onto biomedical devices can facilitate advanced diagnostics and treatments of digestive disorders, cardiovascular diseases, and cancers. Recent developments in gastrointestinal endoscopy and balloon catheter technologies introduce promising paths for minimally invasive surgeries to treat these diseases. However, current therapeutic endoscopy systems fail to meet requirements in multifunctionality, biocompatibility, and safety, particularly when integrated with bioelectronic devices. Here, we report materials, device designs, and assembly schemes for transparent and stable cubic silicon carbide (3C-SiC)-based bioelectronic systems that facilitate tissue ablation, with the capability for integration onto the tips of endoscopes. The excellent optical transparency of SiC-on-glass (SoG) allows for direct observation of areas of interest, with superior electronic functionalities that enable multiple biological sensing and stimulation capabilities to assist in electrical-based ablation procedures. Experimental studies on phantom, vegetable, and animal tissues demonstrated relatively short treatment times and low electric field required for effective lesion removal using our SoG bioelectronic system. In vivo experiments on an animal model were conducted to explore the versatility of SoG electrodes for peripheral nerve stimulation, showing an exciting possibility for the therapy of neural disorders through electrical excitation. The multifunctional features of SoG integrated devices indicate their high potential for minimally invasive, cost-effective, and outcome-enhanced surgical tools, across a wide range of biomedical applications.

KOH-Activated Hollow ZIF-8 Derived Porous Carbon: Nanoarchitectured Control for Upgraded Capacitive Deionization and Supercapacitor.

Herein, the synergistic effects of hollow nanoarchitecture and high specific surface area of hollow activated carbons (HACs) are reported with the superior supercapacitor (SC) and capacitive deionization (CDI) performance. The center of zeolite imidazolate framework-8 (ZIF-8) is selectively etched to create a hollow cavity as a macropore, and the resulting hollow ZIF-8 (HZIF-8) is carbonized to obtain hollow carbon (HC). The distribution of nanopores is, subsequently, optimized by KOH activation to create more nanopores and significantly increase specific surface area. Indeed, as-prepared hollow activated carbons (HACs) show significant improvement not only in the maximum specific capacitance and desalination capacity but also capacitance retention and mean desalination rates in SC and CDI, respectively. As a result, it is confirmed that well-designed nanoarchitecture and porosity are required to allow efficient diffusion and maximum electrosorption of electrolyte ions.