Maintaining Electrochemical Performance of Flexible ITO-PET Electrodes under High Strain.

Flexible electrode materials, particularly indium tin oxide (ITO)-coated polyethylene terephthalate (PET), have attracted the attention of researchers for a wide variety of applications. However, there has been limited attention to the effects of electrode flexibility during electrochemical processes. In this research article, we studied how bending commercially available ITO-PET electrodes impacts the electrodeposition process of polyaniline (PANI). Thicker ITO layers start cracking at a normalized strain of 0.10 (bending radius of 10 mm), and cracking becomes detrimental to full deposition at a normalized strain of 0.16 or higher (bending radius of 6 mm or lower). Thinner ITO layers were evaluated as electrodes in electrochemical applications; however, the higher resistance of these electrodes prevented uniform electrodeposition of PANI. In order to overcome the issues of cracking, conductive thin films and copper tape were explored as low-cost methods for electrically bridging cracks in the electrode. While conductive thin films reduced the resistance effect, copper tape was found to fully restore the original electrochemical activity as measured by chronoamperometry and enable uniform electrodeposition at a bending radius as low as 3 mm. This strategy was then demonstrated by performing electrochromic bleaching of PANI under high-strain conditions. These studies illustrate some of the limitations of ITO-PET electrodes and strategies for overcoming these limitations for future applications that require a high degree of flexibility in a transparent electrode substrate.

On Demand Bioorthogonal Switching of an Antibody-Conjugated SPECT Probe to a Cytotoxic Payload: from Imaging to Therapy.

Antibody-drug conjugates (ADCs) for the treatment of cancer aim to achieve selective delivery of a cytotoxic payload to tumor cells while sparing normal tissue. In vivo, multiple tumor-dependent and -independent processes act on ADCs and their released payloads to impact tumor-versus-normal delivery, often resulting in a poor therapeutic window. An ADC with a labeled payload would make synchronous correlations between distribution and tissue-specific pharmacological effects possible, empowering preclinical and clinical efforts to improve tumor-selective delivery; however, few methods to label small molecules without destroying their pharmacological activity exist. Herein, we present a bioorthogonal switch approach that allows a radiolabel attached to an ADC payload to be removed tracelessly at will. We exemplify this approach with a potent DNA-damaging agent, the pyrrolobenzodiazepine (PBD) dimer, delivered as an antibody conjugate targeted to lung tumor cells. The radiometal chelating group, DOTA, was attached via a novel trans-cyclooctene (TCO)-caged self-immolative para-aminobenzyl (PAB) linker to the PBD, stably attenuating payload activity and allowing tracking of biodistribution in tumor-bearing mice via SPECT-CT imaging (live) or gamma counting (post-mortem). Following TCO-PAB-DOTA reaction with tetrazines optimized for extra- and intracellular reactivity, the label was removed to reveal the unmodified PBD dimer capable of inducing potent tumor cell killing in vitro and in mouse xenografts. The switchable antibody radio-drug conjugate (ArDC) we describe integrates, but decouples, the two functions of a theranostic given that it can serve as a diagnostic for payload delivery in the labeled state, but can be switched on demand to a therapeutic agent (an ADC).

Bigtools: a high-performance BigWig and BigBed library in Rust.

MOTIVATION: The BigWig and BigBed file formats were originally designed for the visualization of next-generation sequencing data through a genome browser. Due to their versatility, these formats have long since become ubiquitous for the storage of processed sequencing data and regularly serve as the basis for downstream data analysis. As the number and size of sequencing experiments continues to accelerate, there is an increasing demand to efficiently generate and query BigWig and BigBed files in a scalable and robust manner, and to efficiently integrate these functionalities into data analysis environments and third-party applications. RESULTS: Here, we present Bigtools, a feature-complete, high-performance, and integrable software library for generating and querying both BigWig and BigBed files. Bigtools is written in the Rust programming language and includes a flexible suite of command line tools as well as bindings to Python. AVAILABILITY AND IMPLEMENTATION: Bigtools is cross-platform and released under the MIT license. It is distributed on Crates.io, Bioconda, and the Python Package Index, and the source code is available at https://github.com/jackh726/bigtools.

Using random forests to uncover the predictive power of distance-varying cell interactions in tumor microenvironments.

Tumor microenvironments (TMEs) contain vast amounts of information on patient's cancer through their cellular composition and the spatial distribution of tumor cells and immune cell populations. Exploring variations in TMEs between patient groups, as well as determining the extent to which this information can predict outcomes such as patient survival or treatment success with emerging immunotherapies, is of great interest. Moreover, in the face of a large number of cell interactions to consider, we often wish to identify specific interactions that are useful in making such predictions. We present an approach to achieve these goals based on summarizing spatial relationships in the TME using spatial K functions, and then applying functional data analysis and random forest models to both predict outcomes of interest and identify important spatial relationships. This approach is shown to be effective in simulation experiments at both identifying important spatial interactions while also controlling the false discovery rate. We further used the proposed approach to interrogate two real data sets of Multiplexed Ion Beam Images of TMEs in triple negative breast cancer and lung cancer patients. The methods proposed are publicly available in a companion R package funkycells.

Pediatric Mandibular Fracture Management: Intraoperative Thermoplastic Splint Fabrication and Circummandibular Wires, without Maxillomandibular Fixation.

Management of mandibular fractures often involves the use of maxillomandibular fixation (MMF) to attain immobility of the fractured segments. This can be used as a primary treatment modality or as an adjunct in fracture management. This technique, however, has its drawbacks due to the great burden of care imposed on patients. In the following case, fixation of a pediatric open mandibular body fracture was attained without the use of MMF, and bone union was achieved. Due to age, safety concerns, long-distance travel, and parent's preference, the routine management of this type of fracture with MMF using piriform aperture drop wires and circummandibular wires was not done. Instead, the fracture was reduced, and an intraoral mandibular impression was taken in the operating room, which was used to create a stone model. A 2-mm acrylic splint was designed and fabricated from the stone model, and two circummandibular wires were placed. The wires were tightened over the acrylic splint to achieve stabilization of the mandibular reduction. At 4 weeks postoperatively, the splint was removed, and the patient was maintained on a soft diet. At 6 weeks, bone union was appreciated clinically by immobility of the mandibular segments, and the patient was advanced to a regular diet. Occlusion was corrected to premorbid state by clinical findings and 6 months postoperative imaging. This technique represents an effective approach in managing pediatric mandibular fractures when MMF cannot be used.

An improved method to assess the encapsulation response in arthropods.

Ecoimmunology explores how ecological factors and evolutionary processes influence immune responses across various taxa and how immune responses trade-off with other traits. Studying immune responses requires biologically meaningful immunoassays applicable to a broad range of taxa and are sensitive enough to detect changes in the immune response. Useful immunoassays should also correlate with immunocompetence and fitness. The encapsulation response, a complex immune mechanism in arthropods, serves as a robust method for ecoimmunological investigations. However, traditional methods to test the encapsulation response can require long training. This study introduces an innovative, cost-effective method for assessing the encapsulation immune response in arthropods, which simplifies the procedure by reducing the training time and skill required. Our modified device utilizes a pen and syringe assembly for inserting monofilaments into arthropod larvae. We compared our device against traditional methods. Despite the new method being 22% faster, it did not compromise the accuracy or effectiveness of the encapsulation response when compared with traditional techniques, demonstrating similar degrees of melanization and encapsulation. Our method allowed for more accessible participation by less experienced researchers, such as undergraduates, facilitating their involvement in ecoimmunological research.

The Fisher Subunit Anatomical Approach for Cleft Lip Revisions: An Evolution and Case Series.

ABSTRACT: Many techniques exist to reapproximate a cleft lip but can leave unsatisfactory results with nonanatomic scars and a short upper lip, creating a need for revision. Many revisions focus on adjacent tissue transfers and realignment of landmarks, but in the senior authors' experience, recreating the defect and utilizing the Fisher repair for revision have led to aesthetically pleasing results and less noticeable scars. A database was collected that included all cleft lip revisions performed at a large, comprehensive children's hospital from October 2018 to July 2021. Inclusion criteria included any cleft patient with a cleft lip revision performed by two craniofacial surgeons. Data collected included sex, characteristics of the cleft lip, age at initial and index repair, type of initial repair, previous revisions, type of revision with any additional tissue rearrangement, and any nose repair. Sixty-five patients were included in the study for analysis. The type of initial repair was known in sixty-four cases (98%), and fifty-four were Millard repairs (83%). Twenty-two patients (33%) had a previous revision prior to their index revision. Sixty patients (92%) underwent the Fisher repair technique for their index revision and forty-six patients (70%) underwent nasal revision. In follow-up, all patients demonstrated an improvement in lip aesthetics. This study demonstrates a large subset of patients that have undergone cleft lip revision using the Fisher technique. In the senior surgeons' experience, the Fisher repair technique in the setting of cleft lip revision is an ideal way to address the shortcomings of historical repair techniques.

Development and validation of the Telepsychology Facilitators Scale: A national study.

This study developed and validated the Telepsychology Facilitators Scale (TFS), a novel measure that uses the theory of reasoned action and technology acceptance model as frameworks to assess factors that influence psychologists' openness to using telepsychology. At the beginning of the COVID-19 pandemic, an online sample of 2,619 psychologists completed initial items considered for the TFS, along with a measure assessing their actual use of telepsychology. The sample was split in half, with a preliminary exploratory factor analysis ultimately revealing a 13-item general scale with four distinct subscales (Positive Attitudes, Facilitating Infrastructure, Organizational Support, and External Policies). Higher scores on each subscale positively correlated with psychologists' percentage of patient treatment conducted with telepsychology. The exploratory factor analysis subscale structure was subsequently supported via confirmatory factory analyses of a four-factor structure and bifactor structure (tested separately) with the other half of the sample, revealing adequate model fit for both models and similar convergent validity. The TFS may help the field assess the potential barriers and drivers of telepsychology use among psychologists and be used to inform future organizational and policy efforts to increase telepsychology implementation and use across health service settings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Adipose and skin distribution of African trypanosomes in natural animal infections.

BACKGROUND: Animal African trypanosomiasis, which is caused by different species of African trypanosomes, is a deadly disease in livestock. Although African trypanosomes are often described as blood-borne parasites, there have been recent reappraisals of the ability of these parasites to reside in a wide range of tissues. However, the majority of those studies were conducted on non-natural hosts infected with only one species of trypanosome, and it is unclear whether a similar phenomenon occurs during natural animal infections, where multiple species of these parasites may be present. METHODS: The infective trypanosome species in the blood and other tissues (adipose and skin) of a natural host (cows, goats and sheep) were determined using a polymerase chain reaction-based diagnostic. RESULTS: The animals were found to harbour multiple species of trypanosomes. Different patterns of distribution were observed within the host tissues; for instance, in some animals, the blood was positive for the DNA of one species of trypanosome and the skin and adipose were positive for the DNA of another species. Moreover, the rate of detection of trypanosome DNA was highest for skin adipose and lowest for the blood. CONCLUSIONS: The findings reported here emphasise the complexity of trypanosome infections in a natural setting, and may indicate different tissue tropisms between the different parasite species. The results also highlight the need to include adipose and skin tissues in future diagnostic and treatment strategies.

Rhizobium determinants of rhizosphere persistence and root colonization.

Bacterial persistence in the rhizosphere and colonization of root niches are critical for the establishment of many beneficial plant-bacteria interactions including those between Rhizobium leguminosarum and its host legumes. Despite this, most studies on R. leguminosarum have focused on its symbiotic lifestyle as an endosymbiont in root nodules. Here, we use random barcode transposon sequencing to assay gene contributions of R. leguminosarum during competitive growth in the rhizosphere and colonization of various plant species. This facilitated the identification of 189 genes commonly required for growth in diverse plant rhizospheres, mutation of 111 of which also affected subsequent root colonization (rhizosphere progressive), and a further 119 genes necessary for colonization. Common determinants reveal a need to synthesize essential compounds (amino acids, ribonucleotides, and cofactors), adapt metabolic function, respond to external stimuli, and withstand various stresses (such as changes in osmolarity). Additionally, chemotaxis and flagella-mediated motility are prerequisites for root colonization. Many genes showed plant-specific dependencies highlighting significant adaptation to different plant species. This work provides a greater understanding of factors promoting rhizosphere fitness and root colonization in plant-beneficial bacteria, facilitating their exploitation for agricultural benefit.

Treatment of vaginitis caused by non-albicans Candida species.

INTRODUCTION: In the face of increased frequency of non-albicans Candida vulvovaginitis (VVC) reported worldwide, there is a paucity of effective oral and topical antifungal drugs available. Drug selection is further handicapped by an absence of data of clinical efficacy of available antifungal drugs for these infections. AREAS COVERED: In this review, attention is directed at the cause of drug shortage as well as increased frequency of non-albicans Candida (NAC) vulvovaginitis. There is widespread recognition of reduced in vitro azole drug susceptibility in NAC species. Moreover, antifungal susceptibility tests have not been standardized or validated for NAC isolates, hence clinicians rely on an element of empiricism especially given the absence of randomized controlled comparative studies targeting NAC species. Clinical spectrum of NAC species isolates is highly variable with ongoing difficulty in determining a causal role in symptomatic patients. EXPERT OPINION: We have entered the era of demand for Candida species-specific therapy and although consensus treatment guidelines are emerging, new antifungal agents that target these multiple-azole resistant or relatively resistant vaginal NAC species are urgently needed.

The use of collective variables and enhanced sampling in the simulations of existing and emerging microporous materials.

Microporous materials, including zeolites, metal-organic frameworks, and cage compounds, offer diverse functionalities due to their unique dynamics and guest confinement properties. These materials play a significant role in separation, catalysis, and sensing, but their complexity hinders exploration using traditional atomistic simulations. This review explores collective variables (CVs) paired with enhanced sampling as a powerful approach to enable efficient investigation of key features in microporous materials. We highlight successful applications of CVs in studying adsorption, diffusion, phase transitions, and mechanical properties, demonstrating their crucial role in guiding material design and optimisation. The future of CVs lies in integration with techniques like machine learning, allowing for enhanced efficiency and accuracy. By tailoring CVs to specific materials and developing multi-scale approaches we can further unlock the intricacies of these fascinating materials. Simulations are a cornerstone in unravelling the complexities of microporous materials and are crucial for our future understanding.

FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy.

Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of haematological malignancies such as acute lymphoblastic leukaemia, B cell lymphoma and multiple myeloma1-4, but the efficacy of CAR T cell therapy in solid tumours has been limited5. This is owing to a number of factors, including the immunosuppressive tumour microenvironment that gives rise to poorly persisting and metabolically dysfunctional T cells. Analysis of anti-CD19 CAR T cells used clinically has shown that positive treatment outcomes are associated with a more 'stem-like' phenotype and increased mitochondrial mass6-8. We therefore sought to identify transcription factors that could enhance CAR T cell fitness and efficacy against solid tumours. Here we show that overexpression of FOXO1 promotes a stem-like phenotype in CAR T cells derived from either healthy human donors or patients, which correlates with improved mitochondrial fitness, persistence and therapeutic efficacy in vivo. This work thus reveals an engineering approach to genetically enforce a favourable metabolic phenotype that has high translational potential to improve the efficacy of CAR T cells against solid tumours.

Peripheral direct current reduces naturally evoked nociceptive activity at the spinal cord in rodent models of pain.

Objective.Electrical neuromodulation is an established non-pharmacological treatment for chronic pain. However, existing devices using pulsatile stimulation typically inhibit pain pathways indirectly and are not suitable for all types of chronic pain. Direct current (DC) stimulation is a recently developed technology which affects small-diameter fibres more strongly than pulsatile stimulation. Since nociceptors are predominantly small-diameter Aδand C fibres, we investigated if this property could be applied to preferentially reduce nociceptive signalling.Approach.We applied a DC waveform to the sciatic nerve in rats of both sexes and recorded multi-unit spinal activity evoked at the hindpaw using various natural stimuli corresponding to different sensory modalities rather than broad-spectrum electrical stimulus. To determine if DC neuromodulation is effective across different types of chronic pain, tests were performed in models of neuropathic and inflammatory pain.Main results.We found that in both pain models tested, DC application reduced responses evoked by noxious stimuli, as well as tactile-evoked responses which we suggest may be involved in allodynia. Different spinal activity of different modalities were reduced in naïve animals compared to the pain models, indicating that physiological changes such as those mediated by disease states could play a larger role than previously thought in determining neuromodulation outcomes.Significance.Our findings support the continued development of DC neuromodulation as a method for reduction of nociceptive signalling, and suggests that it may be effective at treating a broader range of aberrant pain conditions than existing devices.

Self-Sorting of Interfacial Compatibility in MOF-Based Mixed Matrix Membranes.

Metal-organic framework (MOF)-based mixed matrix membranes (MMMs) have shown great promises to overcome the performance upper limit of polymeric membranes for various gas separation processes. However, the gas separation properties of the MMMs largely depend on the MOF-polymer interfacial compatibility which is a metric difficult to quantify. In most cases, whether a MOF filler and a polymer matrix make a good pair is not revealed until the gas transport experiments are performed. This is because there is a lack of characterization techniques to directly probe the MOF-polymer interfacial compatibility. In this work, we demonstrate a self-sorting method to rank the interface compatibility among several MOF-polymer pairs. By mixing one MOF with two polymers in an MMM, the demixing of two polymers will form two polymer domains. The MOF particles will preferably partition into the "preferred" polymer domain due to their higher interfacial affinity. By scanning different polymer pairs, a rank of MOF-polymer interfacial compatibility from high to low can be obtained. Moreover, based on this ranking, it was also found that a highly compatible MOF-polymer pair suggested by this method also corresponds to a more predictable MMM gas separation performance.

Design of Efficient Artificial Enzymes Using Crystallographically Enhanced Conformational Sampling.

The ability to create efficient artificial enzymes for any chemical reaction is of great interest. Here, we describe a computational design method for increasing the catalytic efficiency of de novo enzymes by several orders of magnitude without relying on directed evolution and high-throughput screening. Using structural ensembles generated from dynamics-based refinement against X-ray diffraction data collected from crystals of Kemp eliminases HG3 (kcat/KM 125 M-1 s-1) and KE70 (kcat/KM 57 M-1 s-1), we design from each enzyme ≤10 sequences predicted to catalyze this reaction more efficiently. The most active designs display kcat/KM values improved by 100-250-fold, comparable to mutants obtained after screening thousands of variants in multiple rounds of directed evolution. Crystal structures show excellent agreement with computational models, with catalytic contacts present as designed and transition-state root-mean-square deviations of ≤0.65 Å. Our work shows how ensemble-based design can generate efficient artificial enzymes by exploiting the true conformational ensemble to design improved active sites.

A device for magnetic-field angle control in magneto-optical filters using a solenoid-permanent magnet pair.

Atomic bandpass filters are used in a variety of applications due to their narrow bandwidths and high transmission at specific frequencies. Predominantly, these filters are in the Faraday (Voigt) geometry, using an applied axial (transverse) magnetic field with respect to the laser propagation direction. Recently, there has been interest in filters realized with arbitrary-angle magnetic fields, which have been made by rotating permanent magnets with respect to the k-vector of the interrogating laser beam. However, the magnetic field angle achievable with this method is limited as field uniformity across the cell decreases as the rotation angle increases. In this work, we propose and demonstrate a new method of generating an arbitrary-angle magnetic field, using a solenoid to produce a small, and easily alterable, axial field, in conjunction with fixed permanent magnets to produce a large transverse field. We directly measure the fields produced by both methods, finding them to be very similar over the length of the vapor cell. We then compare the transmission profiles of filters produced using both methods, again finding excellent agreement. Finally, we demonstrate the sensitivity of the filter profile to changing magnetic field angle (solenoid current), which becomes easier to exploit with the much improved angle control and precision offered by our new design.

Disparities between Native Americans and Whites in trajectories of functional independence and life satisfaction over the 5 years after traumatic brain injury.

PURPOSE: Traumatic brain injury (TBI) can lead to impairments in motor and cognitive function and reduced life satisfaction. TBI is one of the leading causes of death and disability worldwide and disproportionately affects Native Americans, who have the highest rates of TBI among all races in the United States and elevated likelihood for fatality and severe complications. This study investigated whether disparities in functional and life satisfaction outcomes exist longitudinally over the 5 years after complicated mild, moderate, or severe TBI between Native Americans and White individuals; it further explored which demographic and injury-related covariates account for them. RESEARCH METHOD: The current study used a subsample of the national TBI Model Systems Database of 80 demographically and injury-severity matched Native American and White pairs (total n = 160). RESULTS: A series of longitudinal hierarchical linear models found that Native Americans experienced significantly lower Functional Independence Measure Cognitive and Motor trajectories than Whites; however, life satisfaction was comparable. Native Americans had declining cognitive function over time relative to a slight increase in White individuals. This differential movement dissipated with the addition of employment status at the time of injury and type of health insurance. CONCLUSIONS: These results demonstrate a profound need to further investigate the cultural and contextual variables unique to Native Americans that underlie these differences and highlight the importance of culturally responsive treatment and rehabilitation in bridging the gap in recovery. (PsycInfo Database Record (c) 2024 APA, all rights reserved).