A journey in the world of DNA rings and beyond.

I was born in China and would have remained there but for the tumultuous events that led many of my generation to the United States for graduate studies. Norman Davidson introduced me to DNA when I became a postdoctoral fellow in his group at the California Institute of Technology in 1964, and a fortuitous conversation there ignited my interest in DNA ring formation, which later led me to study different topological forms of DNA rings-catenanes, knots, and supercoils. In 1968, a chance observation led me to identify a new enzyme capable of converting one DNA ring form to another, an enzyme now known as a DNA topoisomerase. My interest in DNA rings and DNA topoisomerases continued throughout my years at the University of California, Berkeley, and Harvard. The fascinating ability of the topoisomerases in passing DNA strands or double helices through one another and their importance in cellular processes have kept me and many others excited in their studies.

SHMT2 inhibition disrupts the TCF3 transcriptional survival program in Burkitt lymphoma.

Burkitt lymphoma (BL) is an aggressive lymphoma type that is currently treated by intensive chemoimmunotherapy. Despite the favorable clinical outcome for most patients with BL, chemotherapy-related toxicity and disease relapse remain major clinical challenges, emphasizing the need for innovative therapies. Using genome-scale CRISPR-Cas9 screens, we identified B-cell receptor (BCR) signaling, specific transcriptional regulators, and one-carbon metabolism as vulnerabilities in BL. We focused on serine hydroxymethyltransferase 2 (SHMT2), a key enzyme in one-carbon metabolism. Inhibition of SHMT2 by either knockdown or pharmacological compounds induced anti-BL effects in vitro and in vivo. Mechanistically, SHMT2 inhibition led to a significant reduction of intracellular glycine and formate levels, which inhibited the mTOR pathway and thereby triggered autophagic degradation of the oncogenic transcription factor TCF3. Consequently, this led to a collapse of tonic BCR signaling, which is controlled by TCF3 and is essential for BL cell survival. In terms of clinical translation, we also identified drugs such as methotrexate that synergized with SHMT inhibitors. Overall, our study has uncovered the dependency landscape in BL, identified and validated SHMT2 as a drug target, and revealed a mechanistic link between SHMT2 and the transcriptional master regulator TCF3, opening up new perspectives for innovative therapies.

A multiprotein supercomplex controlling oncogenic signalling in lymphoma.

B cell receptor (BCR) signalling has emerged as a therapeutic target in B cell lymphomas, but inhibiting this pathway in diffuse large B cell lymphoma (DLBCL) has benefited only a subset of patients1. Gene expression profiling identified two major subtypes of DLBCL, known as germinal centre B cell-like and activated B cell-like (ABC)2,3, that show poor outcomes after immunochemotherapy in ABC. Autoantigens drive BCR-dependent activation of NF-κB in ABC DLBCL through a kinase signalling cascade of SYK, BTK and PKCß to promote the assembly of the CARD11-BCL10-MALT1 adaptor complex, which recruits and activates IκB kinase4-6. Genome sequencing revealed gain-of-function mutations that target the CD79A and CD79B BCR subunits and the Toll-like receptor signalling adaptor MYD885,7, with MYD88(L265P) being the most prevalent isoform. In a clinical trial, the BTK inhibitor ibrutinib produced responses in 37% of cases of ABC1. The most striking response rate (80%) was observed in tumours with both CD79B and MYD88(L265P) mutations, but how these mutations cooperate to promote dependence on BCR signalling remains unclear. Here we used genome-wide CRISPR-Cas9 screening and functional proteomics to determine the molecular basis of exceptional clinical responses to ibrutinib. We discovered a new mode of oncogenic BCR signalling in ibrutinib-responsive cell lines and biopsies, coordinated by a multiprotein supercomplex formed by MYD88, TLR9 and the BCR (hereafter termed the My-T-BCR supercomplex). The My-T-BCR supercomplex co-localizes with mTOR on endolysosomes, where it drives pro-survival NF-κB and mTOR signalling. Inhibitors of BCR and mTOR signalling cooperatively decreased the formation and function of the My-T-BCR supercomplex, providing mechanistic insight into their synergistic toxicity for My-T-BCR+ DLBCL cells. My-T-BCR supercomplexes characterized ibrutinib-responsive malignancies and distinguished ibrutinib responders from non-responders. Our data provide a framework for the rational design of oncogenic signalling inhibitors in molecularly defined subsets of DLBCL.

huARdb: human Antigen Receptor database for interactive clonotype-transcriptome analysis at the single-cell level.

T-cell receptors (TCRs) and B-cell receptors (BCRs) are critical in recognizing antigens and activating the adaptive immune response. Stochastic V(D)J recombination generates massive TCR/BCR repertoire diversity. Single-cell immune profiling with transcriptome analysis allows the high-throughput study of individual TCR/BCR clonotypes and functions under both normal and pathological settings. However, a comprehensive database linking these data is not yet readily available. Here, we present the human Antigen Receptor database (huARdb), a large-scale human single-cell immune profiling database that contains 444 794 high confidence T or B cells (hcT/B cells) with full-length TCR/BCR sequence and transcriptomes from 215 datasets. All datasets were processed in a uniform workflow, including sequence alignment, cell subtype prediction, unsupervised cell clustering, and clonotype definition. We also developed a multi-functional and user-friendly web interface that provides interactive visualization modules for biologists to analyze the transcriptome and TCR/BCR features at the single-cell level. HuARdb is freely available at https://huarc.net/database with functions for data querying, browsing, downloading, and depositing. In conclusion, huARdb is a comprehensive and multi-perspective atlas for human antigen receptors.

The Influence of Etiology and Stimulation Target on the Outcome of Deep Brain Stimulation for Chronic Neuropathic Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: Deep brain stimulation (DBS) to treat chronic neuropathic pain has shown variable outcomes. Variations in pain etiologies and DBS targets are considered the main contributing factors, which are, however, underexplored owing to a paucity of patient data in individual studies. An updated meta-analysis to quantitatively assess the influence of these factors on the outcome of DBS for chronic neuropathic pain is warranted, especially considering that the anterior cingulate cortex (ACC) has emerged recently as a new DBS target. MATERIALS AND METHODS: A comprehensive literature review was performed in PubMed, Embase, and Cochrane data bases to identify studies reporting quantitative outcomes of DBS for chronic neuropathic pain. Pain and quality of life (QoL) outcomes, grouped by etiology and DBS target, were extracted and analyzed (α = 0.05). RESULTS: Twenty-five studies were included for analysis. Patients with peripheral neuropathic pain (PNP) had a significantly greater initial stimulation success rate than did patients with central neuropathic pain (CNP). Both patients with CNP and patients with PNP with definitive implant, regardless of targets, gained significant follow-up pain reduction. Patients with PNP had greater long-term pain relief than did patients with CNP. Patients with CNP with ACC DBS gained less long-term pain relief than did those with conventional targets. Significant short-term QoL improvement was reported in selected patients with CNP after ACC DBS. However, selective reporting bias was expected, and the improvement decreased in the long term. CONCLUSIONS: Although DBS to treat chronic neuropathic pain is generally effective, patients with PNP are the preferred population over patients with CNP. Current data suggest that ACC DBS deserves further investigation as a potential way to treat the affective component of chronic neuropathic pain.

Deep learning classification of reading disability with regional brain volume features.

Developmental reading disability is a prevalent and often enduring problem with varied mechanisms that contribute to its phenotypic heterogeneity. This mechanistic and phenotypic variation, as well as relatively modest sample sizes, may have limited the development of accurate neuroimaging-based classifiers for reading disability, including because of the large feature space of neuroimaging datasets. An unsupervised learning model was used to reduce deformation-based data to a lower-dimensional manifold and then supervised learning models were used to classify these latent representations in a dataset of 96 reading disability cases and 96 controls (mean age: 9.86 ± 1.56 years). A combined unsupervised autoencoder and supervised convolutional neural network approach provided an effective classification of cases and controls (accuracy: 77%; precision: 0.75; recall: 0.78). Brain regions that contributed to this classification accuracy were identified by adding noise to the voxel-level image data, which showed that reading disability classification accuracy was most influenced by the superior temporal sulcus, dorsal cingulate, and lateral occipital cortex. Regions that were most important for the accurate classification of controls included the supramarginal gyrus, orbitofrontal, and medial occipital cortex. The contribution of these regions reflected individual differences in reading-related abilities, such as non-word decoding or verbal comprehension. Together, the results demonstrate an optimal deep learning solution for classification using neuroimaging data. In contrast with standard mass-univariate test results, results from the deep learning model also provided evidence for regions that may be specifically affected in reading disability cases.

Feasibility of [18F]fluoropivalate hybrid PET/MRI for imaging lower and higher grade glioma: a prospective first-in-patient pilot study.

PURPOSE: MRI and PET are used in neuro-oncology for the detection and characterisation of lesions for malignancy to target surgical biopsy and to plan surgical resections or stereotactic radiosurgery. The critical role of short-chain fatty acids (SCFAs) in brain tumour biology has come to the forefront. The non-metabolised SCFA radiotracer, [18F]fluoropivalate (FPIA), shows low background signal in most tissues except eliminating organs and has appropriate human dosimetry. Tumour uptake of the radiotracer is, however, unknown. We investigated the uptake characteristics of FPIA in this pilot PET/MRI study. METHODS: Ten adult glioma subjects were identified based on radiological features using standard-of-care MRI prior to any surgical intervention, with subsequent histopathological confirmation of glioma subtype and grade (lower-grade - LGG - and higher-grade - HGG - patients). FPIA was injected as an intravenous bolus injection (range 342-368 MBq), and dynamic PET and MRI data were acquired simultaneously over 66 min. RESULTS: All patients tolerated the PET/MRI protocol. Three patients were reclassified following resection and histology. Tumour maximum standardised uptake value (SUVmax,60) increased in the order LGG (WHO grade 2) < HGG (WHO grade 3) < HGG (WHO grade 4). The net irreversible solute transfer, Ki, and influx rate constant, K1, were significantly higher in HGG (p < 0.05). Of the MRI variables studied, DCE-MRI-derived extravascular-and-extracellular volume fraction (ve) was high in tumours of WHO grade 4 compared with other grades (p < 0.05). SLC25A20 protein expression was higher in HGG compared with LGG. CONCLUSION: Tumoural FPIA PET uptake is higher in HGG compared to LGG. This study supports further investigation of FPIA PET/MRI for brain tumour imaging in a larger patient population. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04097535.

Unlocking the Emotional World of Visual Media: An Overview of the Science, Research, and Impact of Understanding Emotion: Drawing Insights From Psychology, Engineering, and the Arts, This Article Provides a Comprehensive Overview of the Field of Emotion Analysis in Visual Media and Discusses the Latest Research, Systems, Challenges, Ethical Implications, and Potential Impact of Artificial Emotional Intelligence on Society.

The emergence of artificial emotional intelligence technology is revolutionizing the fields of computers and robotics, allowing for a new level of communication and understanding of human behavior that was once thought impossible. While recent advancements in deep learning have transformed the field of computer vision, automated understanding of evoked or expressed emotions in visual media remains in its infancy. This foundering stems from the absence of a universally accepted definition of "emotion," coupled with the inherently subjective nature of emotions and their intricate nuances. In this article, we provide a comprehensive, multidisciplinary overview of the field of emotion analysis in visual media, drawing on insights from psychology, engineering, and the arts. We begin by exploring the psychological foundations of emotion and the computational principles that underpin the understanding of emotions from images and videos. We then review the latest research and systems within the field, accentuating the most promising approaches. We also discuss the current technological challenges and limitations of emotion analysis, underscoring the necessity for continued investigation and innovation. We contend that this represents a "Holy Grail" research problem in computing and delineate pivotal directions for future inquiry. Finally, we examine the ethical ramifications of emotion-understanding technologies and contemplate their potential societal impacts. Overall, this article endeavors to equip readers with a deeper understanding of the domain of emotion analysis in visual media and to inspire further research and development in this captivating and rapidly evolving field.

Impact of Expanding Telephonic Codes in a State Medicaid Program During COVID-19.

Background: The recent pandemic caused by the 2019 novel coronavirus (COVID-19) resulted in declaration of a national emergency (NE) in March 2020. The Centers for Medicare and Medicaid Services quickly responded with temporary expansion of telehealth coverage policies. Aim: To determine the impact of implementing a temporary telephonic code set in a state Medicaid population by comparing the utilization patterns of telehealth claims before and after a NE announcement. Methods: This was a retrospective cohort study conducted with the Arizona Medicaid program, the Arizona Health Care Cost Containment System (AHCCCS). Data include telehealth claims submitted to AHCCCS between January and May 2020 by contracted managed care organizations. Results: Approximately 2.3 million telehealth claims were analyzed in this study. Utilization of the audio-visual (A/V) modality increased 1,610% and telephonic visits increased 408% compared with pre-NE. Compared with pre-NE, three provider type groups increased their utilization of telephonic visits from 1.8% to 50.8% as a result of the temporary telephonic set post-NE. Rural counties had higher rates of telephonic modality adoption, whereas urban counties adopted the A/V modality more readily. Ten telephonic codes constituted 87% of all telehealth claims, with the majority of those codes used for behavioral health and established office visit types. Conclusion: The telephonic modality was adopted more frequently in rural areas and the A/V modality in urban areas. There were several new provider types utilizing telehealth as a result of the temporary telephonic code set implementation.

Effects of Essential Oils on Scars and Wound Healing: A Systematic Review.

Essential oils (EOs) have been considered as a potential alternative therapy for wound healing and scar reduction. The aim of this article was to provide a comprehensive review examining the effects of EOs on wound healing and scars. PubMed, Cochrane, Ovid, and Embase computerized searches were performed through June 2020. Two independent reviewers conducted data extraction, with search results reviewed by the senior author following the PRISMA protocol. Three manuscripts examining three different EO-containing topical agents were analyzed. Outcomes include healing rate, erythema, pain, pruritus, patient discomfort, physician satisfaction, percent wound reduction, wound/scar surface perimeter area, and qualitative dermatological evaluation. All articles concluded that the EO-containing topical agents resulted in either superior or noninferior outcomes in comparison with controls. Hypericum-Calendula oil obtained lower wound surface perimeter area. Erythema (p = 0.001) was significantly decreased by the peppermint EO-containing topical agent. Physicians also reported greater satisfaction (p < 0.001) in wound appearance with use of the peppermint EO-containing topical agent. A paucity of studies have examined EO use for wound healing and scar reduction. Treatment with EO-containing topical agents resulted in decreased erythema with increased physician satisfaction of wound appearance. Future studies should assess what level of purity is needed for improved results and which EO, or combination of EOs, is most beneficial.

Exercise Training Decreases Hepatic Injury and Metastases Through Changes in Immune Response to Liver Ischemia/Reperfusion in Mice.

BACKGROUND AND AIMS: Liver ischemia/reperfusion injury (IRI) induces local and systemic inflammation in which neutrophil extracellular traps (NETs) are major drivers. IRI markedly augments metastatic growth, which is consistent with the notion that the liver IRI can serve as a premetastatic niche. Exercise training (ExT) confers a sustainable protection, reducing IRI in some animal models, and has been associated with improved survival in patients with cancer; however, the impact of ExT on liver IRI or development of hepatic metastases is unknown. APPROACH AND RESULTS: Mice were randomized into exercise (ExT) and sedentary groups before liver IRI and tumor injection. Computerized dynamic network analysis of 20 inflammatory mediators was used to dissect the sequence of mediator interactions after ischemia/reperfusion (I/R) that induce injury. ExT mice showed a significant decrease in hepatic IRI and tissue necrosis. This coincided with disassembly of complex networks among inflammatory mediators seen in sedentary mice. Neutrophil infiltration and NET formation were decreased in the ExT group, which suppressed the expression of liver endothelial cell adhesion molecules. Concurrently, ExT mice revealed a distinct population of infiltrating macrophages expressing M2 phenotypic genes. In a metastatic model, fewer metastases were present 3 weeks after I/R in the ExT mice, a finding that correlated with a marked increase in tumor-suppressing T cells within the tumor microenvironment. CONCLUSIONS: ExT preconditioning mitigates the inflammatory response to liver IRI, protecting the liver from injury and metastases. In light of these findings, potential may exist for the reduction of liver premetastatic niches induced by liver IRI through the use of ExT as a nonpharmacologic therapy before curative surgical approaches.

Comparison of cervical neck strain in common otolaryngology surgeries.

BACKGROUND: Cervical neck strain and surgical ergonomics is an increasingly important topic being addressed in this time and age. With new technologies, visualizations, and approaches to surgeries, there are now different strains and duration of strains to the cervical neck. Recently the effect of chronic cell phone use has been described as "text neck." In a similar fashion we understand that certain otolaryngology surgeries can also impart chronic strain to the cervical neck. We aim to quantitatively describe strain for different types of surgeries by looking at posture, duration of surgery, and anatomic ergonomics of specific surgeries. METHODS: Lateral photo documentation of posture during 6 common otolaryngology procedures, used to estimate cervical neck angle and calculate force and impulse to cervical neck. RESULTS: Six common otolaryngology procedures show various cervical neck angles ranging from around 0° to 60° of neck flexion, with subsequent forces ranging from 16 lb to 60 lb of force. When accounting for surgical time, bigger differences arose with impulses ranging from 270,000 N∗s to 3,300,000 N∗s. Noticeably, thyroidectomy and cleft palate showed much higher impulses than the other four types of surgeries. CONCLUSION: Both cervical neck flexion and duration of surgery play important roles in total neck theoretical strain. Variance exists between neck strains of common otolaryngology surgeries. There is a necessity for continued study and improvement in surgical ergonomics.

A Report on the Use of Telehealth in Otolaryngology in the Pre COVID-19 Era.

Objective: To investigate the integration of and barriers to the utilization of telehealth technology and its components (telemedicine, e-Health, m-health) in daily otolaryngologic practice before the SARS CoV-2 (COVID-19) pandemic. Methods: This cross-sectional study was conducted at a tertiary academic center. A national survey of members of the American Academy of Otolaryngology-Head and Neck Surgery was administered. Descriptive analyses were performed to determine how telehealth was employed in otolaryngologists' practices. Results: A total of 184 surveys were completed. Telehealth technology was used by 50% of otolaryngologists surveyed. Regions with the largest percentage of physicians using telehealth were the Mid-Atlantic region (84%) and West Coast (67%). Most otolaryngologists indicated that they were familiar with telehealth or any of its components and how it is used in practice (52-83%), they had heard of telehealth or any of its components but were unsure what the terms specifically entailed (17-42%); 53% were satisfied with their current use of telehealth and electronic medical record (EMR); and 72% were comfortable utilizing smart devices for patient care. Most otolaryngologists (65%) indicated reimbursement as the biggest limitation to implementing telehealth, and 67% believed that typing was a hindrance to EMR utility. Conclusion: Half of the surveyed otolaryngologists used some form of telehealth at the time of the survey. The most commonly cited obstacle to physician adoption of telehealth was reimbursement. Although the adoption of telehealth technology was still limited in the field of otolaryngology based on this study, we are now seeing significant change due to the COVID-19 pandemic.

Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. METHODS: We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. RESULTS: We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. CONCLUSIONS: We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).

Characterization of the structure, vascularity, and stem/progenitor cell populations in porcine Achilles tendon (PAT).

This study aimed to characterize porcine Achilles tendon (PAT) in terms of its structural components, vascularity, and resident tendon cells. We found that PAT is composed of a paratenon sheath, a core of fascicles, and an endotenon/interfascicular matrix (IFM) that encases the fascicle bundles. We analyzed each of these three tendon components structurally using tissue sections and by isolating cells from each component and analyzing in vitro. Many blood vessel-like tissues were present in the paratenon and IFM but not in fascicles, and the vessels in the paratenon and IFM appeared to be inter-connected. Cells isolated from the paratenon and IFM displayed characteristics of vascular stem/progenitor cells expressing the markers CD105, CD31, with α-smooth muscle actin (α-SMA) localized surrounding blood vessels. The isolated cells from paratenon and IFM also harbored abundant stem/progenitor cells as evidenced by their ability to form colonies and express stem cell markers including CD73 and CD146. Furthermore, we demonstrate that both paratenon and IFM-isolated cells were capable of undergoing multi-differentiation. In addition, both paratenon and IFM cells expressed elastin, osteocalcin, tubulin polymerization promoting protein (TPPP), and collagen IV, whereas fascicle cells expressed none of these markers, except collagen I. The neurotransmitter substance P (SP) was also found in the paratenon and IFM-localized surrounding blood vessels. The findings of this study will help us to better understand the vascular and cellular mechanisms of tendon homeostasis, injury, healing, and regeneration.

Reporting of Demographic Variables in Neuropsychological Research: An Update of O'Bryant et al.'s Trends in the Current Literature.

OBJECTIVE: Demographic trends and the globalization of neuropsychology have led to a push toward inclusivity and diversity in neuropsychological research in order to maintain relevance in the healthcare marketplace. However, in a review of neuropsychological journals, O'Bryant et al. found systematic under-reporting of sample characteristics vital for understanding the generalizability of research findings. We sought to update and expand the findings reported by O'Bryant et al. METHOD: We evaluated 1648 journal articles published between 2016 and 2019 from 7 neuropsychological journals. Of these, 1277 were original research or secondary analyses and were examined further. Articles were coded for reporting of age, sex/gender, years of education, ethnicity/race, socioeconomic status (SES), language, and acculturation. Additionally, we recorded information related to sample size, country, and whether the article focused on a pediatric or adult sample. RESULTS: Key variables such as age and sex/gender (both over 95%) as well as education (71%) were frequently reported. Language (20%) and race/ethnicity (36%) were modestly reported, and SES (13%), and acculturation (<1%) were more rarely reported. SES was more commonly reported in pediatric than adult samples, and the opposite was true for education. There were differences between the present results and those of O'Bryant et al., though the same general trends remained. CONCLUSIONS: Reporting of demographic data in neuropsychological research appears to be slowly changing toward greater comprehensiveness, though clearly more work is needed. Greater systematic reporting of such data is likely to be beneficial for the generalizability and contextualization of neurocognitive function.

The influence of electrokinetic bioremediation on subsurface microbial communities at a perchloroethylene contaminated site.

There is an increased interest in finding remedies for contamination in low permeability and advection-limited aquifers. A technology applicable at these sites, electrokinetic-enhanced bioremediation (EK-BIO), combines traditional bioremediation and electrokinetic technologies by applying direct current to transport bioremediation amendments and microbes in situ. The effect of this technology on the native soil microbial community has only been previously investigated at the bench scale. This research explored the influence of EK-BIO on subsurface microbial communities at a field-scale demonstration site. The results showed that, similar to the findings in laboratory studies, alpha diversity decreased and beta diversity differed temporally, based on treatment phase. Enrichments in specific taxa were linked to the bioaugmentation culture and electron donor. Overall, findings from our study, one of the first field-scale investigations of the influence of electrokinetic bioremediation on subsurface microbial communities, are very similar to bench-scale studies on the topic, suggesting good correlation between laboratory and field experiments on EK-BIO and showing that lessons learned at the benchtop are important and relevant to field-scale implementation. KEY POINTS: • Microbial community analysis of field samples validates laboratory study results • Bioaugmentation cultures and electron donors have largest effect on microbial community.

The Use of Remote Programming for Spinal Cord Stimulation for Patients With Chronic Pain During the COVID-19 Outbreak in China.

OBJECTIVES: Due to the impact of COVID-19 epidemic, face-to-face follow-up treatments for patients with chronic pain and implanted spinal cord stimulation (SCS) devices are forced to be delayed or stopped. This has led to more follow ups being done remotely. Meanwhile, with the development of 4G/5G networks, smartphones, and novel devices, remote programming has become possible. Here, we investigated the demand and utility of remote follow-ups including remote programming for SCS for patients with chronic pain. MATERIALS AND METHODS: A questionnaire including questions on demographic characteristics, pain history, postimplantation life quality, standard follow-up experience, remote follow-up, and remote programming experience was sent to patients diagnosed as chronic intractable pain and treated with SCS during January 2019 to January 2020. RESULTS: A total of 64 participants completed the questionnaire. About 70% of participants expressed demands for remote follow-ups due to the inconvenience, high costs, and time consumption of traditional follow-up visits. Nearly 97% of participants have attempted remote follow-ups, and about 81% of participants have further tried remote programming. Approximately, 96% of them recognized the benefits. CONCLUSIONS: The remote programming was in high demand among participants. Most of the participants have tried remote follow-ups or even remote programming. The remote programming appeared to be more efficient, economic and were widely recognized among participants.

Advancements in Therapeutics via 3D Printed Multifunctional Architectures from Dispersed 2D Nanomaterial Inks.

2D nanomaterials (2DNMs) possess fascinating properties and are found in multifarious devices and applications including energy storage devices, new generation of battery technologies, sensor devices, and more recently in biomedical applications. Their use in biomedical applications such as tissue engineering, photothermal therapy, neural regeneration, and drug delivery has opened new horizons in treatment of age-old ailments. It is also a rapidly developing area of advanced research. A new approach of integrating 3D printing (3DP), a layer-by-layer deposition technique for building structures, along with 2DNM multifunctional inks, has gained considerable attention in recent times, especially in biomedical applications. With the ever-growing demand in healthcare industry for novel, efficient, and rapid technologies for therapeutic treatment methods, 3DP structures of 2DNMs provide vast scope for evolution of a new generation of biomedical devices. Recent advances in 3DP structures of dispersed 2DNM inks with established high-performance biomedical properties are focused on. The advantages of their 3D structures, the sustainable formulation methods of such inks, and their feasible printing methods are also covered. Subsequently, it deals with the therapeutic applications of some already researched 3DP structures of 2DNMs and concludes with highlighting the challenges as well as the future directions of research in this area.

POLYGALACTURONASE INVOLVED IN EXPANSION3 Functions in Seedling Development, Rosette Growth, and Stomatal Dynamics in Arabidopsis thaliana.

Plant cell separation and expansion require pectin degradation by endogenous pectinases such as polygalacturonases, few of which have been functionally characterized. Stomata are a unique system to study both processes because stomatal maturation involves limited separation between sister guard cells and stomatal responses require reversible guard cell elongation and contraction. However, the molecular mechanisms for how stomatal pores form and how guard cell walls facilitate dynamic stomatal responses remain poorly understood. We characterized POLYGALACTURONASE INVOLVED IN EXPANSION3 (PGX3), which is expressed in expanding tissues and guard cells. PGX3-GFP localizes to the cell wall and is enriched at sites of stomatal pore initiation in cotyledons. In seedlings, ablating or overexpressing PGX3 affects both cotyledon shape and the spacing and pore dimensions of developing stomata. In adult plants, PGX3 affects rosette size. Although stomata in true leaves display normal density and morphology when PGX3 expression is altered, loss of PGX3 prevents smooth stomatal closure, and overexpression of PGX3 accelerates stomatal opening. These phenotypes correspond with changes in pectin molecular mass and abundance that can affect wall mechanics. Together, these results demonstrate that PGX3-mediated pectin degradation affects stomatal development in cotyledons, promotes rosette expansion, and modulates guard cell mechanics in adult plants.