Rapid patient-specific FEM meshes from 3D smart-phone based scans.

Objective.The objective of this study was to describe and evaluate a smart-phone based method to rapidly generate subject-specific finite element method (FEM) meshes. More accurate FEM meshes should lead to more accurate thoracic electrical impedance tomography (EIT) images.Approach.The method was evaluated on an iPhone®that utilized an app called Heges, to obtain 3D scans (colored, surface triangulations), a custom belt, and custom open-source software developed to produce the subject-specific meshes. The approach was quantitatively validated via mannequin and volunteer tests using an infrared tracker as the gold standard, and qualitatively assessed in a series of tidal-breathing EIT images recorded from 9 subjects.Main results.The subject-specific meshes can be generated in as little as 6.3 min, which requires on average 3.4 min of user interaction. The mannequin tests yielded high levels of precision and accuracy at 3.2 ± 0.4 mm and 4.0 ± 0.3 mm root mean square error (RMSE), respectively. Errors on volunteers were only slightly larger (5.2 ± 2.1 mm RMSE precision and 7.7 ± 2.9 mm RMSE accuracy), illustrating the practical RMSE of the method.Significance.Easy-to-generate, subject-specific meshes could be utilized in the thoracic EIT community, potentially reducing geometric-based artifacts and improving the clinical utility of EIT.

15NRORC: An Azine Labeling Protocol.

A practical method for the synthesis of 15N-labeled azines with a high degree of isotopic enrichment is described. Activation of azine heterocycles with an electron-deficient arene allows for the facile substitution of the nitrogen atom with a specifically designed 15N-labeled reagent that undergoes a canonical ANRORC-type mechanism. A wide range of azines can be converted to their corresponding 15N isotopologs using this method, and it also allows for dearomative access to reduced heterocyclic congeners. A short dearomative formal synthesis of 15N-solifenacin is accomplished as well to demonstrate a practical application of this method for generating labeled pharmaceuticals.

EEG electrode localization with 3D iPhone scanning using point-cloud electrode selection (PC-ES).

Objective.Electroencephalography source imaging (ESI) is a valuable tool in clinical evaluation for epilepsy patients but is underutilized in part due to sensitivity to anatomical modeling errors. Accurate localization of scalp electrodes is instrumental to ESI, but existing localization devices are expensive and not portable. As a result, electrode localization challenges further impede access to ESI, particularly in inpatient and intensive care settings.Approach.To address this challenge, we present a portable and affordable electrode digitization method using the 3D scanning feature in modern iPhone models. This technique combines iPhone scanning with semi-automated image processing using point-cloud electrode selection (PC-ES), a custom MATLAB desktop application. We compare iPhone electrode localization to state-of-the-art photogrammetry technology in a human study with over 6000 electrodes labeled using each method. We also characterize the performance of PC-ES with respect to head location and examine the relative impact of different algorithm parameters.Main Results.The median electrode position variation across reviewers was 1.50 mm for PC-ES scanning and 0.53 mm for photogrammetry, and the average median distance between PC-ES and photogrammetry electrodes was 3.4 mm. These metrics demonstrate comparable performance of iPhone/PC-ES scanning to currently available technology and sufficient accuracy for ESI.Significance.Low cost, portable electrode localization using iPhone scanning removes barriers to ESI in inpatient, outpatient, and remote care settings. While PC-ES has current limitations in user bias and processing time, we anticipate these will improve with software automation techniques as well as future developments in iPhone 3D scanning technology.

Dearomative Access to (-)-Thebaine and Derivatives.

A synthesis of the natural product thebaine is reported in eight steps from commercially available starting materials, hinging on the dearomatization and coupling of simple aromatic starting materials. This provides divergent access to two unnatural opioid derivatives and is aimed at the long-term development of synthetic opioid analogs of the "wonderdrug" Naloxone. Additionally, a formal enantioselective synthesis of all reported targets is disclosed that leverages a catalytic asymmetric dearomatization via anion-pairing catalysis.

Air-Knife-Assisted Spray Coating of Organic Solar Cells.

The power conversion efficiencies (PCEs) of organic solar cells (OSCs) have risen dramatically since the introduction of the "Y-series" of non-fullerene acceptors. However, the demonstration of rapid scalable deposition techniques to deposit such systems is rare. Here, for the first time, we demonstrate the deposition of a Y-series-based system using ultrasonic spray coating─a technique with the potential for significantly faster deposition speeds than most traditional meniscus-based methods. Through the use of an air-knife to rapidly remove the casting solvent, we can overcome film reticulation, allowing the drying dynamics to be controlled without the use of solvent additives, heating the substrate, or heating the casting solution. The air-knife also facilitates the use of a non-halogenated, low-toxicity solvent, resulting in industrially relevant, spray-coated PM6:DTY6 devices with PCEs of up to 14.1%. We also highlight the obstacles for scalable coating of Y-series-based solar cells, in particular the influence of slower drying times on blend morphology and crystallinity. This work demonstrates the compatibility of ultrasonic spray coating, and use of an air-knife, with high-speed, roll-to-roll OSC manufacturing techniques.

Associations between symptoms and functional capacity in patients after COVID-19 infection and community controls.

BACKGROUND: Post-acute sequelae of COVID-19 (PASC or 'long COVID') reflect ongoing symptoms, but these are non-specific and common in the wider community. Few reports of PASC have been compared with a control group. AIMS: To compare symptoms and objective impairment of functional capacity in patients with previous COVID-19 infection with uninfected community controls. METHODS: In this community-based, cross-sectional study of functional capacity, 562 patients from Western Melbourne who had recovered from COVID-19 infections in 2021 and 2022 were compared with controls from the same community and tested for functional capacity pre-COVID-19. Functional impairment (<85% of the predicted response) was assessed using the Duke Activity Status Index (DASI) and 6-min walk distance (6MWD) test. A subgroup underwent cardiopulmonary exercise testing before and after exercise training. RESULTS: Of 562 respondents (age 54 ± 12 years, 69% women), 389 were symptomatic. Functional impairment (<85% predicted metabolic equivalent of tasks) was documented by DASI in 149 participants (27%), and abnormal 6MWD (<85% predicted) was observed in 14% of the symptomatic participants. Despite fewer risk factors and younger age, patients with COVID-19 had lower functional capacity by 6MWD (P < 0.001) and more depression (P < 0.001) than controls. In a pilot group of seven participants (age 58 ± 12 years, two women, VO2 18.9 ± 5.7 mL/kg/min), repeat testing after exercise training showed a 20% increase in peak workload. CONCLUSIONS: Although most participants (69%) had symptoms consistent with long COVID, significant subjective functional impairment was documented in 27% and objective functional impairment in 14%. An exercise training programme might be beneficial for appropriately selected patients.

Prospects for Tin-Containing Halide Perovskite Photovoltaics.

Tin-containing metal halide perovskites have enormous potential as photovoltaics, both in narrow band gap mixed tin-lead materials for all-perovskite tandems and for lead-free perovskites. The introduction of Sn(II), however, has significant effects on the solution chemistry, crystallization, defect states, and other material properties in halide perovskites. In this perspective, we summarize the main hurdles for tin-containing perovskites and highlight successful attempts made by the community to overcome them. We discuss important research directions for the development of these materials and propose some approaches to achieve a unified understanding of Sn incorporation. We particularly focus on the discussion of charge carrier dynamics and nonradiative losses at the interfaces between perovskite and charge extraction layers in p-i-n cells. We hope these insights will aid the community to accelerate the development of high-performance, stable single-junction tin-containing perovskite solar cells and all-perovskite tandems.

Chloride-Based Additive Engineering for Efficient and Stable Wide-Bandgap Perovskite Solar Cells.

Metal halide perovskite based tandem solar cells are promising to achieve power conversion efficiency beyond the theoretical limit of their single-junction counterparts. However, overcoming the significant open-circuit voltage deficit present in wide-bandgap perovskite solar cells remains a major hurdle for realizing efficient and stable perovskite tandem cells. Here, a holistic approach to overcoming challenges in 1.8 eV perovskite solar cells is reported by engineering the perovskite crystallization pathway by means of chloride additives. In conjunction with employing a self-assembled monolayer as the hole-transport layer, an open-circuit voltage of 1.25 V and a power conversion efficiency of 17.0% are achieved. The key role of methylammonium chloride addition is elucidated in facilitating the growth of a chloride-rich intermediate phase that directs crystallization of the desired cubic perovskite phase and induces more effective halide homogenization. The as-formed 1.8 eV perovskite demonstrates suppressed halide segregation and improved optoelectronic properties.

Understanding the Degradation of Methylenediammonium and Its Role in Phase-Stabilizing Formamidinium Lead Triiodide.

Formamidinium lead triiodide (FAPbI3) is the leading candidate for single-junction metal-halide perovskite photovoltaics, despite the metastability of this phase. To enhance its ambient-phase stability and produce world-record photovoltaic efficiencies, methylenediammonium dichloride (MDACl2) has been used as an additive in FAPbI3. MDA2+ has been reported as incorporated into the perovskite lattice alongside Cl-. However, the precise function and role of MDA2+ remain uncertain. Here, we grow FAPbI3 single crystals from a solution containing MDACl2 (FAPbI3-M). We demonstrate that FAPbI3-M crystals are stable against transformation to the photoinactive δ-phase for more than one year under ambient conditions. Critically, we reveal that MDA2+ is not the direct cause of the enhanced material stability. Instead, MDA2+ degrades rapidly to produce ammonium and methaniminium, which subsequently oligomerizes to yield hexamethylenetetramine (HMTA). FAPbI3 crystals grown from a solution containing HMTA (FAPbI3-H) replicate the enhanced α-phase stability of FAPbI3-M. However, we further determine that HMTA is unstable in the perovskite precursor solution, where reaction with FA+ is possible, leading instead to the formation of tetrahydrotriazinium (THTZ-H+). By a combination of liquid- and solid-state NMR techniques, we show that THTZ-H+ is selectively incorporated into the bulk of both FAPbI3-M and FAPbI3-H at ∼0.5 mol % and infer that this addition is responsible for the improved α-phase stability.

An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity.

Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase that plays an oncogenic role in breast, gastric and other solid tumors. However, anti-HER2 therapies are only currently approved for the treatment of breast and gastric/gastric esophageal junction cancers and treatment resistance remains a problem. Here, we engineer an anti-HER2 IgG1 bispecific, biparatopic antibody (Ab), zanidatamab, with unique and enhanced functionalities compared to both trastuzumab and the combination of trastuzumab plus pertuzumab (tras + pert). Zanidatamab binds adjacent HER2 molecules in trans and initiates distinct HER2 reorganization, as shown by polarized cell surface HER2 caps and large HER2 clusters, not observed with trastuzumab or tras + pert. Moreover, zanidatamab, but not trastuzumab nor tras + pert, elicit potent complement-dependent cytotoxicity (CDC) against high HER2-expressing tumor cells in vitro. Zanidatamab also mediates HER2 internalization and downregulation, inhibition of both cell signaling and tumor growth, antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP), and also shows superior in vivo antitumor activity compared to tras + pert in a HER2-expressing xenograft model. Collectively, we show that zanidatamab has multiple and distinct mechanisms of action derived from the structural effects of biparatopic HER2 engagement.

Open-circuit and short-circuit loss management in wide-gap perovskite p-i-n solar cells.

In this work, we couple theoretical and experimental approaches to understand and reduce the losses of wide bandgap Br-rich perovskite pin devices at open-circuit voltage (VOC) and short-circuit current (JSC) conditions. A mismatch between the internal quasi-Fermi level splitting (QFLS) and the external VOC is detrimental for these devices. We demonstrate that modifying the perovskite top-surface with guanidinium-Br and imidazolium-Br forms a low-dimensional perovskite phase at the n-interface, suppressing the QFLS-VOC mismatch, and boosting the VOC. Concurrently, the use of an ionic interlayer or a self-assembled monolayer at the p-interface reduces the inferred field screening induced by mobile ions at JSC, promoting charge extraction and raising the JSC. The combination of the n- and p-type optimizations allows us to approach the thermodynamic potential of the perovskite absorber layer, resulting in 1 cm2 devices with performance parameters of VOCs up to 1.29 V, fill factors above 80% and JSCs up to 17 mA/cm2, in addition to a thermal stability T80 lifetime of more than 3500 h at 85 °C.

Six-Step Synthesis of (±)-Lysergic Acid.

This article describes a concise synthesis of lysergic acid from simple aromatic precursors. The successful strategy relies on the coupling, dearomatization, and cyclization of a halopyridine with a 4-haloindole derivative in 6 total synthetic steps from commercial starting materials. In addition to highlighting the advantages of employing dearomative retrosynthetic analysis, the design is practical and anticipated to enable the synthesis of novel neuroactive compounds as exemplified by the synthesis of a novel natural product derivative, 12-chlorolysergic acid.

Revisiting the manzamine biosynthetic hypothesis.

Covering: up to 2023The marine environment represents a rich yet challenging source of novel therapeutics. These challenges are best exemplified by the manzamine class of alkaloids, featuring potent bioactivities, difficult procurement, and a biosynthetic pathway that has eluded characterization for over three decades. This review highlights postulated biogenic pathways toward the manzamines, evaluated in terms of current biosynthetic knowledge and metabolic precedent.

Synergistic Surface Modification of Tin-Lead Perovskite Solar Cells.

Interfaces in thin-film photovoltaics play a pivotal role in determining device efficiency and longevity. In this work, the top surface treatment of mixed tin-lead (≈1.26 eV) halide perovskite films for p-i-n solar cells is studied. Charge extraction is promoted by treating the perovskite surface with piperazine. This compound reacts with the organic cations at the perovskite surface, modifying the surface structure and tuning the interfacial energy level alignment. In addition, the combined treatment with C60 pyrrolidine tris-acid (CPTA) reduces hysteresis and leads to efficiencies up to 22.7%, with open-circuit voltage values reaching 0.90 V, ≈92% of the radiative limit for the bandgap of this material. The modified cells also show superior stability, with unencapsulated cells retaining 96% of their initial efficiency after >2000 h of storage in N2 and encapsulated cells retaining 90% efficiency after >450 h of storage in air. Intriguingly, CPTA preferentially binds to Sn2+ sites at film surface over Pb2+ due to the energetically favored exposure of the former, according to first-principles calculations. This work provides new insights into the surface chemistry of perovskite films in terms of their structural, electronic, and defect characteristics and this knowledge is used to fabricate state-of-the-art solar cells.

Trochlear Lesion Caused by Suprapatellar Intramedullary Nailing and Treated with Autologous Chondrocytes Implant.

Introduction: Intramedullary nailing remains the most common method of treatment for tibial shaft fractures. The suprapatellar technique has proven to be useful in gaining and maintaining alignment, especially in proximal one-third tibia shaft fractures. It has been adopted by many surgeons taking trauma call, because it requires less set-up time and allows the surgery to be done with less assistance. We present a case of a femoral trochlea lesion following the placement of a reamed suprapatellar intramedullary nail for fixation of a tibial shaft fracture. Case Presentation: An active 33-year-old male with no prior history of knee pain sustained a distal tibial shaft fracture and was treated with suprapatellar intramedullary nail fixation. Five months later, he underwent revision surgery with exchange nail placement and reaming via an infrapatellar technique for delayed healing of the fracture with subsequent successful healing. The patient, otherwise healthy, continued to experience persistent anterior knee pain with clunking and inability to arise from a flexed knee position approximately 18 months post-surgery. Magnetic resonance imaging and arthroscopic evaluation of the joint were performed, and a full-thickness cartilage lesion was identified in the central portion of the femoral trochlear groove. Conclusion: The purpose of the present case is to bring awareness to the fact that the suprapatellar approach to intramedullary nailing tibial shaft fracture fixation can be accompanied by trochlear articular cartilage damage, which can be successfully treated with cartilage restoration.

Controlling anisotropic properties by manipulating the orientation of chiral small molecules.

Chiral π-conjugated molecules bring new functionality to technological applications and represent an exciting, rapidly expanding area of research. Their functional properties, such as the absorption and emission of circularly polarized light or the transport of spin-polarized electrons, are highly anisotropic. As a result, the orientation of chiral molecules critically determines the functionality and efficiency of chiral devices. Here we present a strategy to control the orientation of a small chiral molecule (2,2'-dicyano[6]helicene) by the use of organic and inorganic templating layers. Such templating layers can either force 2,2'-dicyano[6]helicene to adopt a face-on orientation and self-assemble into upright supramolecular columns oriented with their helical axis perpendicular to the substrate, or an edge-on orientation with parallel-lying supramolecular columns. Through such control, we show that low- and high-energy chiroptical responses can be independently 'turned on' or 'turned off'. The templating methodologies described here provide a simple way to engineer orientational control and, by association, anisotropic functional properties of chiral molecular systems for a range of emerging technologies.

Regiodivergent Asymmetric Pyridinium Additions: Mechanistic Insight and Synthetic Applications.

A practical protocol for the first regiodivergent asymmetric addition of aryl and alkenyl organometallic reagents to substituted N-alkyl pyridinium heterocycles is described. The couplings proceed with high regiochemical and stereochemical selectivities, and provide access to chiral 1,2,3- and 1,3,4-trisubstituted dihydropyridine products, controlled by judicious choice of nitrogen activating agent. To this end, a correlation was found between the parameterized size of the activating group and the C2/C4 regioselectivity in the couplings. The utility of the described chemistry was demonstrated in two concise asymmetric syntheses of (+)-N-methylaspidospermidine and (-)-paroxetine.