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Background: Marital status has been shown to have protective effects for married patients with various cancers. We sought to determine effects of marital status on perioperative outcomes after robotic-assisted pulmonary lobectomy (RAPL). Methods: We retrospectively analyzed 709 consecutive patients who underwent RAPL between 2010 and 2022 by one surgeon. Patients were stratified by marital status at time of surgery. The Married group included married, domestically partnered, and co-habitating patients (N = 473). The Unmarried group included never married, divorced, and widowed individuals (N = 236). Demographics, preoperative comorbidities, intraoperative and postoperative complications, estimated blood loss (EBL), chest tube duration, hospital length of stay (LOS), tumor characteristics, and survival data were analyzed utilizing Student's t-test, Wilcoxon rank-sum test, Chi-square, or Fisher's exact test as appropriate, with significance at p≤0.05. Results: Unmarried patients were more likely to be female, while married patients were more likely to experience robotic-associated intraoperative complications and greater intraoperative estimated blood loss. Kaplan-Meier survival analysis revealed no difference in 5-year overall survival based on marital status. Other perioperative outcomes, intraoperative complications (except robotic-associated), postoperative complications, demographic history (except gender), and preoperative comorbidities did not significantly differ between the two groups. Conclusion: This study challenges the existing reports in the literature that marriage confers cancer treatment outcomes advantage and prolonged survival among cancer patients. Social support, in terms of a spouse or domestic partner, may be less protective in early-stage lung cancer and after minimally invasive pulmonary lobectomy compared to other cancer populations.

Background: Atrial fibrillation is a common arrhythmia previously linked to systemic inflammation, which has been correlated with leukocyte and prealbumin levels. We sought to identify predictors of postoperative atrial fibrillation (POAF) following robotic-assisted pulmonary lobectomy. Methods: This retrospective cohort study included 709 consecutive patients who underwent robotic-assisted lobectomy by one surgeon over 10.7 years. We compared demographics, preoperative comorbidities, perioperative leukocyte, prealbumin levels, complications, chest tube (CT) duration, and hospital length of stay (LOS) using Student's t-test, Chi-square (or Fisher's exact) test, or Wilcoxon rank sums test, with significance at p ≤ 0.05. Multivariable analysis investigated predictors of POAF, CT duration, hospital LOS, and overall survival (OS). Kaplan-Meier analysis estimated OS with 95% confidence intervals. Results: Preoperative atrial fibrillation or chronic steroid or immunosuppressant use excluded 131 patients, and 578 remaining patients were classified as POAF (n=76) or No POAF (n=502). Patients with new-onset POAF were older and had higher incidences of preoperative hypertension and hyperlipidemia, intraoperative complications, and postoperative anemia. The lowest postoperative prealbumin levels were reduced, and peak postoperative leukocyte counts were elevated in POAF patients. Multivariable analysis identified that patients with POAF had longer hospital LOS and lower postoperative prealbumin as factors that independently predict both POAF and increased hospital LOS. Conclusions: New-onset POAF patients had a substantial perioperative inflammatory burden characterized by preoperative hypertension, postoperative leukocytosis, and decreased prealbumin and had prolonged hospital LOS compared with patients without POAF. Postoperative leukocyte and prealbumin levels should be monitored, as these pro-inflammatory markers may forecast POAF.

Abstract Background Gene regulation is critical for proper cellular function. Next-generation sequencing technology has revealed the presence of regulatory networks that regulate gene expression and essential cellular functions. Studies investigating the epigenome have begun to uncover the complex mechanisms regulating transcription. Assay for transposase-accessible chromatin by sequencing (ATAC-seq) is quickly becoming the assay of choice for many epigenomic investigations. However, whether intervention-mediated changes in accessible chromatin determined by ATAC-seq can be harnessed to generate intervention-inducible reporter constructs has not been systematically assayed. Results We used the insulin signaling pathway as a model to investigate chromatin regions and gene expression changes using ATAC- and RNA-seq in insulin-treated Drosophila S2 cells. We found correlations between ATAC- and RNA-seq data, especially when stratifying differentially-accessible chromatin regions by annotated feature type. In particular, our data demonstrated a weak but significant correlation between chromatin regions annotated to enhancers (1-2 kb from the transcription start site) and downstream gene expression. We cloned candidate enhancer regions upstream of luciferase and demonstrate insulin-inducibility of several of these reporters. Conclusions Insulin-induced chromatin accessibility determined by ATAC-seq reveals enhancer regions that drive insulin-inducible reporter gene expression.

Abstract Assay for transposase-accessible chromatin by sequencing (ATAC-seq) is rapidly becoming the assay of choice to investigate chromatin-mediated gene regulation, largely because of low input requirements, a fast workflow, and the ability to interrogate the entire genome in an untargeted manner. Many studies using ATAC-seq use mammalian or human-derived tissues, and established protocols work well in these systems. However, ATAC-seq is not yet widely used in Drosophila. Vinegar flies present several advantages over mammalian systems that make them an excellent model for ATAC-seq studies, including abundant genetic tools that allow straightforward targeting, transgene expression, and genetic manipulation that are not available in mammalian models. Because current ATAC-seq protocols are not optimized to use flies, we developed an optimized workflow that accounts for several complicating factors present in Drosophila. We examined parameters affecting nuclei isolation, including input size, freezing time, washing, and possible confounds from retinal pigments. Then, we optimized the enzymatic steps of library construction to account for the smaller Drosophila genome size. Finally, we used our optimized protocol to generate ATAC-seq libraries that meet ENCODE quality metrics. Our optimized protocol enables extensive ATAC-seq experiments in Drosophila, thereby leveraging the advantages of this powerful model system to understand chromatin-mediated gene regulation.

This data article provides the summary data from tests comparing various Gaussian process software packages. Each spreadsheet represents a single function or type of function using a particular input sample size. In each spreadsheet, a row gives the results for a particular replication using a single package. Within each spreadsheet there are the results from eight Gaussian process model-fitting packages on five replicates of the surface. There is also one spreadsheet comparing the results from two packages performing stochastic kriging. These data enable comparisons between the packages to determine which package will give users the best results.

Céline Mirjolet,1 Julien Boudon,2 Alexis Loiseau,2 Sandy Chevrier,1 Romain Boidot,1 Alexandra Oudot,3 Bertrand Collin,3 Etienne Martin,1 Pattayil Alias Joy,4 Nadine Millot,2 Gilles Créhange1 1Department of Radiation Oncology, Center Georges-François Leclerc, Dijon, France; 2Laboratoire Interdisciplinaire Carnot de Bourgogne, Dijon, France; 3Preclinical Imaging Platform, Nuclear Medicine Department, Center Georges-François Leclerc, Dijon, France; 4CSIR-National Chemical Laboratory (CSIR-NCL), Pune, India Abstract: Around 40% of high-risk prostate cancer patients who undergo radiotherapy (RT) will experience biochemical failure. Chemotherapy, such as docetaxel (DTX), can enhance the efficacy of RT. Multidrug resistance mechanisms often limit drug efficacy by decreasing intracellular concentrations of drugs in tumor cells. It is, therefore, of interest to develop nanocarriers of DTX to maintain the drug inside cancer cells and thus improve treatment efficacy. The purpose of this study was to investigate the use of titanate nanotubes (TiONts) to develop a TiONts-DTX nanocarrier and to evaluate its radiosensitizing in vivo efficacy in a prostate cancer model. In vitro cytotoxic activity of TiONts-DTX was evaluated using an MTS assay. The biodistribution of TiONts-DTX was analyzed in vivo by single-photon emission computed tomography. The benefit of TiONts-DTX associated with RT was evaluated in vivo. Eight groups with seven mice in each were used to evaluate the efficacy of the nanohybrid combined with RT: control with buffer IT injection ± RT, free DXL ± RT, TiONts ± RT and TiONts-DXL ± RT. Mouse behavior, health status and tumor volume were monitored twice a week until the tumor volume reached a maximum of 2,000 mm3. More than 70% of nanohybrids were localized inside the tumor 96 h after administration. Tumor growth was significantly slowed by TiONts-DTX associated with RT, compared with free DTX in the same conditions (P=0.013). These results suggest that TiONts-DTX improved RT efficacy and might enhance local control in high-risk localized prostate cancer. Keywords: prostate cancer, docetaxel nanocarrier, titanate nanotubes, radiosensitivity, nanoparticle

Abstract Our understanding of the physiological and pathological functions of brain lipids is limited by the inability to analyze these molecules at cellular resolution. Here, we present a method that enables the detection of lipids in identified single neurons from live mammalian brains. Neuronal cell bodies are captured from perfused mouse brain slices by patch clamping, and lipids are analyzed using an optimized nanoflow liquid chromatography/mass spectrometry protocol. In a first application of the method, we identified more than 40 lipid species from dentate gyrus granule cells and CA1 pyramidal neurons of the hippocampus. This survey revealed substantial lipid profile differences between neurons and whole brain tissue, as well as between resting and physiologically stimulated neurons. The results suggest that patch clamp-assisted single neuron lipidomics could be broadly applied to investigate neuronal lipid homeostasis in healthy and diseased brains.

The hippocampus is thought to encode information by altering synaptic strength via synaptic plasticity. Some forms of synaptic plasticity are induced by lipid-based endocannabinoid signaling molecules that act on cannabinoid receptors (CB1). Endocannabinoids modulate synaptic plasticity of hippocampal pyramidal cells and stratum radiatum interneurons; however, the role of endocannabinoids in mediating synaptic plasticity of stratum oriens interneurons is unclear. These feedback inhibitory interneurons exhibit presynaptic long-term potentiation (LTP), but the exact mechanism is not entirely understood. We examined whether oriens interneurons produce endocannabinoids, and whether endocannabinoids are involved in presynaptic LTP. Using patch-clamp electrodes to extract single cells, we analyzed the expression of endocannabinoid biosynthetic enzyme mRNA by reverse transcription and then real-time PCR (RT-PCR). The cellular expression of calcium-binding proteins and neuropeptides were used to identify interneuron subtype. RT-PCR results demonstrate that stratum oriens interneurons express mRNA for both endocannabinoid biosynthetic enzymes and the type I metabotropic glutamate receptors (mGluRs), necessary for endocannabinoid production. Immunohistochemical staining further confirmed the presence of diacylglycerol lipase alpha, an endocannabinoid-synthesizing enzyme, in oriens interneurons. To test the role of endocannabinoids in synaptic plasticity, we performed whole-cell experiments using high-frequency stimulation to induce long-term potentiation in somatostatin-positive cells. This plasticity was blocked by AM-251, demonstrating CB1-dependence. In addition, in the presence of a fatty acid amide hydrolase inhibitor (URB597; 1 µM) and MAG lipase inhibitor (JZL184; 1 µM) that increase endogenous anandamide and 2-arachidonyl glycerol, respectively, excitatory current responses were potentiated. URB597-induced potentiation was blocked by CB1 antagonist AM-251 (2 µM). Collectively, this suggests somatostatin-positive oriens interneuron LTP is CB1-dependent.

Activity-based training and lumbosacral spinal cord epidural stimulation (scES) have the potential to restore standing and walking with self-balance assistance after motor complete spinal cord injury (SCI). However, improvements in upright postural control have not previously been addressed in this population. Here, we implemented a novel robotic postural training with scES, performed with free hands, to restore upright postural control in individuals with chronic, cervical (n?=?5) or high-thoracic (n?=?1) motor complete SCI, who had previously undergone stand training with scES using a walker or a standing frame for self-balance assistance. Robotic postural training re-enabled and/or largely improved the participants' ability to control steady standing, self-initiated trunk movements and upper limb reaching movements while standing with free hands, receiving only external assistance for pelvic control. These improvements were associated with neuromuscular activation pattern adaptations above and below the lesion. These findings suggest that the human spinal cord below the level of injury can generate meaningful postural responses when its excitability is modulated by scES, and can learn to improve these responses. Upright postural control improvements can enhance functional motor recovery promoted by scES after severe SCI.

Background: Patella baja is a known complication of total knee arthroplasty (TKA). There is a limited understanding of the association between patellar resurfacing and the incidence of patella baja. We aimed to compare rates of patella baja between unresurfaced and resurfaced patellas in patients undergoing TKA. Methods: A retrospective review of patients who underwent TKA between October 2009 and January 2020 was performed. Patients were included if they had at least one preoperative radiograph and a 1-year follow-up radiograph. Blackburne-Peel index (BPI) and Insall-Salvati ratios (ISRs) were measured on preoperative and 1-year postoperative radiographs and were used to define patella baja vs pseudopatella baja. Statistical analysis was performed using a linear model analysis of variance and the Fisher’s exact test. Results: Three hundred eighteen TKAs were included, with 176 being resurfaced and 142 unresurfaced patellas. Of the resurfaced group, 4% (7/176) had true patella baja, compared to 5.6% (8/142) of the unresurfaced patellas. Of the resurfaced patellas, 8% (14/176) had pseudopatella baja, compared to 7% (10/142) in the unresurfaced group. Patellar resurfacing was not associated with a higher incidence of patella baja (P = .60) or pseudopatella baja (P = .83). Lower preoperative ISRs (P = .04) and BPIs (0.03) were highly predictive of a higher incidence of patella baja post-TKA. Conclusions: Patellar resurfacing in TKA is not associated with a higher incidence of patella baja in TKA when compared to unresurfaced patellas. Lower preoperative ISRs and BPIs are highly predictive of a higher incidence of postoperative patella baja.

Abstract Objective Racial and ethnic disparities in arthroplasty utilization are evident, but the reasons are not known. We aimed to identify concerns that may contribute to barriers to arthroplasty from the patient’s perspective. Methods We identified patients’ concerns about arthroplasty by performing a mixed methods study. Themes identified during semi-structured interviews with Black and Hispanic patients with advanced symptomatic hip or knee arthritis were used to develop a questionnaire to quantify and prioritize their concerns. Multiple linear and logistic regression analyses were conducted to determine the association between race/ethnicity and the importance of each theme. Models were adjusted for sex, insurance, education, HOOS, JR/KOOS, JR, and discussion of joint replacement with a doctor. Results Interviews with eight participants reached saturation and provided five themes used to develop a survey answered by 738 (24%) participants; 75.5% White, 10.3% Black, 8.7% Hispanic, 3.9% Asian/Other. Responses were significantly different between groups (p

Background: Asthma is a complex disease and a severe global public health problem resulting from interactions between genetic background and environmental exposures. It has been suggested that gut microbiota may be related to asthma development; however, such relationships needs further investigation. Objective: This study aimed to characterize the gut microbiota as well as the nasal lavage cytokine profile of asthmatic and nonasthmatic individuals. Methods: Stool and nasal lavage samples were collected from 29 children and adolescents with type 2 asthma and 28 children without asthma in Brazil. Amplicon sequencing of the stool bacterial V4 region of the 16S rRNA gene was performed using Illumina MiSeq. Microbiota analysis was performed by QIIME 2 and PICRUSt2. Type 2 asthma phenotype was characterized by high sputum eosinophil counts and positive skin prick tests for house dust mite, cockroach, and/or cat or dog dander. The nasal immune marker profile was assessed using a customized multiplex panel. Results: Stool microbiota differed significantly between asthmatic and nonasthmatic participants (P = .001). Bacteroides was more abundant in participants with asthma (P < .05), while Prevotella was more abundant in nonasthmatic individuals (P < .05). In people with asthma, the relative abundance of Bacteroides correlated with IL-4 concentration in nasal lavage samples. Inference of microbiota functional capacity identified differential fatty acid biosynthesis in asthmatic compared to nonasthmatic subjects. Conclusion: The stool microbiota differed between asthmatic and nonasthmatic young people in Brazil. Asthma was associated with higher Bacteroides levels, which correlated with nasal IL-4 concentration.

The Indonesian island of Sulawesi has a unique geology and geography, which have produced an astoundingly diverse and endemic flora and fauna and a fascinating biogeographic history. Much biodiversity research has focused on the regional endemism in the island’s Central Core and on its four peninsulas, but the biodiversity of the island’s many upland regions is still poorly understood for most taxa, including amphibians and reptiles. Here, we report the first of several planned full-mountain checklists from a series of herpetological surveys of Sulawesi’s mountains conducted by our team. In more than 3 weeks of work on Gunung Galang, a 2,254 m peak west of the city of Tolitoli, Sulawesi Tengah Province, on Sulawesi’s Northern Peninsula, we recovered nearly fifty species of reptiles and amphibians, more than a dozen of which are either new to science or known but undescribed. The incompleteness of our sampling suggests that many more species remain to be discovered on and around this mountain.

Drug targets are the main focus of drug discovery due to their key role in disease pathogenesis. Computational approaches are widely applied to drug development because of the increasing availability of biological molecular datasets. Popular generative approaches can create new drug molecules by learning the given molecule distributions. However, these approaches are mostly not for target-specific drug discovery. We developed an energy-based probabilistic model for computational target-specific drug discovery. Results show that our proposed TagMol can generate molecules with similar binding affinity scores as real molecules. GAT-based models showed faster and better learning relative to Graph Convolutional Network baseline models.

Abstract Amyotrophic lateral sclerosis (ALS) is an incurable and rapidly progressive neurological disorder. Biomarkers are critical to understanding disease causation, monitoring disease progression and assessing the efficacy of treatments. However, robust peripheral biomarkers are yet to be identified. Neuroinflammation and breakdown of the blood-brain barrier (BBB) are common to familial and sporadic ALS and may produce a unique biomarker signature in peripheral blood. Using cytometric bead array (n = 15 participants per group (ALS or control)) and proteome profiling (n = 6 participants per group (ALS or control)), we assessed a total of 106 serum cytokines, growth factors, and BBB breakdown markers in the serum of control and ALS participants. Further, primary human brain pericytes, which maintain the BBB, were used as a biosensor of inflammation following pre-treatment with ALS serum. Principal components analysis of all proteome profile data showed no clustering of control or ALS sera, and no individual serum proteins met the threshold for statistical difference between ALS and controls (adjusted P values). However, the 20 most changed proteins between control and ALS sera showed a medium effect size (Cohen’s d = 0.67) and cluster analysis of their levels together identified three sample subsets; control-only, mixed control-ALS, and ALS-only. These 20 proteins were predominantly pro-angiogenic and growth factors, including fractalkine, BDNF, EGF, PDGF, Dkk-1, MIF and angiopoietin-2. S100β, a protein highly concentrated in glial cells and therefore a marker of BBB leakage when found in blood, was unchanged in ALS serum, suggesting that serum protein profiles were reflective of peripheral rather than CNS biofluids. Finally, primary human brain pericytes remained proliferative and their secretome was unchanged by chronic exposure to ALS serum. Our exploratory study suggests that individual serum cytokine levels may not be robust biomarkers in small studies of ALS, but that larger studies using multiplexed analysis of pro-angiogenic and growth factors may identify a peripheral signature of ALS pathogenesis.

Objective: To assess the effectiveness of telemedicine video visits in the management of hypertensive patients at home during the first year of the COVID-19 pandemic. Methods: A quantitative analysis was performed of all home video visits coded with a diagnosis of essential hypertension during the first 12 months of the COVID-19 pandemic (March 2020 through February 2021). A total of 10,634 patients with 16,194 hypertension visits were present in our national telemedicine practice database during this time. Among this population, a total of 569 patients who had 1785 hypertension visits met the criteria of having 2 or more blood pressure (BP) readings, with the last BP reading occurring in the report period. We analyzed baseline characteristics and BP trends of these 569 patients during the study period. Voluntarily submitted patient satisfaction ratings, which were systematically requested at the end of each visit, were also analyzed. Results: The mean age of the patients in this study cohort of 569 patients was 43.9 years, and 48.3% (275) were women. More than 62% (355) of the patients had an initial systolic BP (SBP) above 140 mm Hg, and 25.3% (144) had an initial SBP of greater than 160 mm Hg. The average number of visits during the study period was 3.1 visits per patient; an average of 6.4 BP measurements per patient were available. During the study period, 77% (438) of the patients experienced an improvement in either SBP or diastolic BP (DBP), with mean reductions of −9.7 mm Hg and −6.8 mm Hg in SBP and DBP, respectively. A total of 416 patients in the cohort started with a BP above 140/90 mm Hg. For this subset of patients, 55.7% (232) achieved a BP of 140/90 mm Hg or lower by the end of the study period, and the average reductions in SBP and DBP were −17.9 mm Hg and −12.8 mm Hg, respectively, which corresponded to improvements of 11.2% and 12.4%. These improvements did not vary significantly when patients were stratified by age, sex, or geographic region of residence (rural vs urban/suburban). Voluntarily submitted patient surveys indicated a high degree of patient satisfaction, with a mean satisfaction score of 4.94 (5-point scale). Conclusion: Clinician-patient relationships established in a video-first telemedicine model were broadly effective for addressing suboptimally controlled hypertension. Patient satisfaction with these visits was high.

Improved energy efficiency and the associated cost savings is critical for environmental stewardship. In heating, ventilation, and cooling (HVAC) systems, occupancy sensors play an important role in system control for energy conservation. This paper introduces an integrated plenoptic device/people occupancy counting sensor for time-of-flight (ToF) measurements based on grating-coupled-waveguide, angularly resolved detection. Light from a 940 nm laser source is scattered from objects up to 5-m distant. The acceptance angle for scattered light is determined by the period of the detector grating and the waveguide properties. As a consequence of the narrow-band optical coupling, the plenoptic sensor demonstrates a good immunity to background light sources, such as sunlight and incandescent room illumination. The conical acceptance angles (azimuth and altitude) of this device are measured and confirm the device model. Importantly, the device is realized on a commercial silicon-based integrated-photonics foundry line, providing a pathway to volume manufacturing.

Challenges arise to the crime scene investigators when dealing with dead body investigation. The body posture may cause confusion to explain even during natural disasters like flood, lightning and storm. Suspicious death, more than traditional foul play is suspected in which the circumstances of death strongly suggest murder. The present crime scene report, as investigated by the corresponding author (hereafter as TN) in Tamil Nadu, India, during his crime scene investigator career, wherein a middle-aged village woman found dead in an open land with bleedings from nose and ear. The relatives and the villagers have alleged murder and demanded the police for the immediate arrest of the accused. The police registered a case under “suspicious death” and investigated by then forensic crime scene investigator and assisted the police investigation. The method of investigation was a keen scientific observation on dead body, crime scene and reconstruction to identify the case of death. The examination of the deceased revealed a linear burned marks on the thigh region, charred mark in a dried palm leaf that used to cover the head from rain, and charred grasses on the soil near the dead body that clearly indicated the death due to lightning. The present investigation concluded with a finding, based on crime scene, crime reconstruction and autopsy examination that the cause of death was due to lightning and not by homicide, thus unravelled the mystery.

Background: Primary care physicians (PCPs) are often gatekeepers to specialist care. This study assessed the relationship between PCP density and total knee (TKA) and total hip arthroplasty (THA) outcomes. Methods: We obtained patient-level data from an institutional registry on patients undergoing elective primary TKA and THA for osteoarthritis, including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores at baseline and 2 years. Using geocoding, we identified the number of PCPs in the patient’s census tract (communities). We used Augmented Inverse Probability Weighting and Cross-validated Targeted Minimum Loss-Based Estimation to compare provider density and outcomes adjusting for potential confounders. Results: Our sample included 3606 TKA and 4295 THA cases. The median number of PCPs in each community was similar for both procedures: TKA 2 (interquartile range 1, 6) and for THA 2 (interquartile range 1, 7). Baseline and 2-year follow-up WOMAC pain, function, and stiffness scores were not statistically significantly different comparing communities with more than median number of PCPs to those with less than median number of PCPs. In sensitivity analyses, adding 1 PCP to a community with zero PCPs would not have statistically significantly improved baseline or 2-year follow-up WOMAC pain, function, and stiffness scores. Conclusions: In this sample of patients who underwent elective TKA or THA for osteoarthritis, we found no statistically significant association between PCP density and pain, function, or stiffness outcomes at baseline or 2 years. Further studies should examine what other provider factors affect access and outcomes in THA and TKA.

Background: Distal tibia allograft reconstruction of the glenoid in shoulder instability has garnered significant attention over the last decade. Prior studies demonstrate significant improvement in all reported patient outcomes albeit the approach is through a subscapularis split. There have not been prior studies evaluating outcomes after lesser tuberosity osteotomy which provides excellent exposure to the anterior glenoid.We hypothesize there is significant improvement in functional outcomes and no deleterious effects after lesser tuberosity osteotomy for distal tibia allograft reconstruction of the glenoid for shoulder instability. Methods: A retrospective review was performed from 2016 of 2019 of patients undergoing distal tibia allograft reconstruction of the glenoid through a lesser tuberosity osteotomy. Patients were indicated if they had recurrent anterior shoulder instability with >20% glenoid bone loss and evidence of an off-track lesion. Clinical, imaging, and operative data were evaluated. Objective follow-up data evaluated at minimum 2 years included radiographs, range of motion, DASH, SANE, VAS, SST, ASES, and Constant scores. Results: A total of 12 patients were available with average follow-up 28 months, average age 26 years old, and average glenoid bone loss of 33%. The patients demonstrated significant improvement in their clinical outcomes at final follow-up: DASH 42.9-8.9 (P = .004), SANE 32.2-85 (P = .00005), VAS 4.6-1.1 (P = .003), SST 7-11.4 (P = .01), ASES 50.2-90.5 (P = .001), and Constant 37.6-86.2 (P = .01). Range of motion at final follow-up was forward flexion to 161.4° (135-170°), external rotation 49.5° (40-65°), and internal rotation to T12-L1 (T7-L2) vertebral body. Conclusion: The present study demonstrates the effectiveness of a lesser tuberosity osteotomy in exposure of the glenoid for reconstruction with a distal tibia allograft. The functional integrity of the subscapularis is maintained and the patient-reported outcomes are comparable with current literature.

BackgroundThe genomic frontier continues to revolutionize the practice of oncology. Advances in cancer biology from tumorigenesis to treatment resistance are driven by the molecular underpinnings of malignancy. The framing of precision oncology as both a clinical and research tool is constantly evolving and directly influences conversations between oncologists and their patients. Prior research has shown that patient-participants often have unmet or unrealistic expectations regarding the clinical utility of oncology research and genomic sequencing. This indicates the need for more in-depth investigation of how and why patients choose to participate in such research. ObjectiveThis study presents a qualitative ethical analysis to better understand patient and provider perspectives on enrollment in precision oncology research. MethodsPaired semistructured interviews were conducted with patient-participants enrolled in a prospective head and neck precision oncology research platform, along with their oncology providers, at a National Cancer Institute–designated academic cancer center. ResultsThere were three major themes that emerged from the analysis. (1) There are distinct and unique challenges with informed consent to precision medicine, chiefly involving the ability of both patient-participants and providers to effectively understand the science underlying the research. (2) The unique benefits of precision medicine enrollment are of paramount importance to patients considering enrollment. (3) Patient-participants have little concern for the risks of research enrollment, particularly in the context of a low-burden protocol. ConclusionsPatient-participants and their providers offer complementary and nuanced perspectives on their motivation to engage in precision oncology research. This reflects both the inherent promise and enthusiasm within the field, as well as the limitations and challenges of ensuring that both patient-participants and clinicians understand the complexities of the science involved.

Background: Acromioclavicular (AC) separations are commonly seen shoulder injuries. Numerous surgical reconstruction techniques have been described. In this study, we present a series of patients who underwent an anatomic reconstruction using a synthetic ligament and allograft construct. Methods: We performed a retrospective review of patients with type IV or V AC separations who underwent primary or revision AC reconstruction with a luggage-tag synthetic ligament and a semitendinosus allograft placed through the anatomic insertion sites of the coracoclavicular ligaments. Patient-reported outcomes, as well as complication rates, were recorded at a minimum 2-year follow-up. Results: Ten patients with a mean age of 44.2 ± 14.9 years were included in the study. The mean Disabilities of the Arm, Shoulder and Hand score was 15.5 ± 15.4; mean Single Assessment Numeric Evaluation score, 81.8 ± 12.1; mean Simple Shoulder Test score, 11.4 ± 1.1; mean American Shoulder and Elbow Surgeons score, 84.6 ± 15.7; mean Constant score, 82.5 ± 11.6; and mean visual analog scale score, 2 ± 2.6. Conclusion: The technique using a luggage-tag synthetic ligament along with an anatomic allograft coracoclavicular ligament reconstruction is a safe, effective alternative to other techniques described in the literature.

Dust-exposed construction workers have an increased risk of respiratory symptoms, but the efficacy of dust-control measures remains unclear. This study compared respiratory symptoms, using a modified European Community Respiratory Health Survey questionnaire, between construction workers (n = 208) and a reference group of bus drivers and retail workers (n = 142). Within the construction workers, we assessed the effect of collective (on-tool vacuum/'wet-cut' systems) and personal (respirators) exposure controls on symptom prevalence. Logistic regression assessed differences between groups, adjusted for age, ethnicity, and smoking status. Construction workers were more likely to cough with phlegm at least once a week (OR 2.4, 95% CI 1.2-4.7) and cough with phlegm ≥3 months/year for ≥2 years (OR 2.8, CI 1.2-7.0), but they had similar or fewer asthma symptoms. Construction workers who had worked for 11-20 years reported more cough/phlegm symptoms (OR 5.1, 1.7-15.0 for cough with phlegm ≥3 months/year for ≥2 years) than those who had worked 10 years. Use of collective dust exposure controls might protect against these symptoms, but this requires confirmation in a larger study.

Background: This study aimed to evaluate the role of intravenous lidocaine as a supplemental pain control modality in patients undergoing spine surgery. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) involving the use of supplemental intravenous lidocaine in spine surgery. We developed a comprehensive search strategy to adequately screen for randomized controlled trials involving intravenous lidocaine in spine surgery. Continuous outcomes included postoperative opiate consumption and postoperative pain scores. Dichotomous outcomes included nausea, vomiting, pneumonia, delirium, and wound infection. Results: A total of 3 RCTs comprising 235 patients were selected for inclusion in the meta-analysis. Cumulative morphine consumption at 48 h was not statistically significant between lidocaine and control groups. Postoperative pain was not statistically significant at any measured time points in the first and second day postoperatively. There was no statistical difference in postoperative complications including nausea, vomiting, pneumonia, delirium, or surgical site infection. Conclusion: Our results indicated that current literature does not support the use of intravenous lidocaine as an adjunctive measure of pain management after spine surgery. Given the relatively few numbers of studies in this field, further randomized controlled trials are needed to make a definitive conclusion on the effectiveness of lidocaine in spine surgery patients.

Automorphisms of shift spaces and the Higman--Thompson groups: the one-sided case, Discrete Analysis 2021:15, 35 pp. Symbolic dynamics is the study of dynamical systems of the following kind, known as _shift spaces_. One takes an alphabet $\Sigma$ of "symbols" and a closed (in the product topology) shift-invariant subset $X$ of $\Sigma^{\mathbb Z}$ or $\Sigma^{\mathbb N}$ and looks at iterations of the shift applied to $X$. An important particular case is to take a single infinite sequence $x$ and to let $X$ be the closure of the orbit of $x$. Another case, more relevant to this paper, is the _full shift_, where one takes $X$ to consist of all sequences. An _automorphism_ of a shift space is a shift-invariant homeomorphism of $X$ to itself. Typically, such homeomorphisms are quite hard to construct, so the automorphism groups of shift spaces tend to be "small" in some sense. For example, the automorphism group of the space $\{0,1\}^{\mathbb N}$ is the cyclic group of order 2, with the two shift-invariant automorphisms being the identity and the map that interchanges 0s and 1s. (That said, once the alphabet is larger than this, the groups contain free groups, but they are nevertheless much smaller than the group of all homeomorphisms of $\{0,1\}^{\mathbb N}$. For example, they have to be countable.) However, determining the automorphism groups is quite hard (even the result just mentioned is a genuine theorem and not simply an exercise), and this has led to an active research area. This paper concerns automorphims of the full shift in the one-sided case (the authors have a companion paper that deals with the two-sided case, which is genuinely different in various ways). Something of the flavour of the paper is conveyed by the following non-trivial example of a shift-invariant automorphism of the space $\{0,1,2\}^{\mathbb N}$, which it is more convenient to think of as $\{0,1,2\}^{-\mathbb N}$ -- that is, as the space of sequences $(\dots,x_{-2},x_{-1},x_0)$. To any such sequence one applies a _synchronous transducer_, which is a finite-state automaton that works as follows. At any one moment it is looking at some term $x_{-n}$ and is in some state $q$ that belongs to a set $Q=\{q_1,\dots,q_r\}$. It then sets $y_{-n}$ to be equal to $\phi(x_{-n},q)$, changes to a new state $\pi(x_{-n},q)$, and turns its attention to the next term $x_{-(n-1)}$. As soon as one tries to imagine using this idea, one runs into a problem: how does the process start? Or rather, since it doesn't really start -- it has always been going on -- how do we ever know what state it is in? The answer is that some transducers have a special property, one that is definitely not shared by an arbitrary transducer, which is that for some $k$ the state that they are in by the time they reach $x_{-n}$ depends only on the terms $x_{-n-1},x_{-n-2},\dots,x_{-n-k}$ and not on the state they were in when they were looking at $x_{-n-k}$. Such transducers are called _strongly synchronizing_. Given a strongly synchronizing transducer, one obtains a well-defined map, and if its inverse is also strongly synchronizing, in which case it is called _bi-synchronizing_, then it is then easy to see that it is a shift-invariant homeomorphism. A concrete example of such a transducer is the following. Write $(q,a)\to (r,b)$ to mean that if the transducer is in state $q$ and sees $a$, then it will change state to $r$ and write $b$ (and then move to the next term). Then the instructions are $(q_0,0)\to(q_0,0)$ $(q_0,1)\to(q_2,1)$ $(q_0,2)\to(q_1,2)$ $(q_1,0)\to(q_0,1)$ $(q_1,1)\to(q_2,0)$ $(q_1,2)\to(q_1,2)$ $(q_2,0)\to(q_1,2)$ $(q_2,1)\to(q_2,1)$ $(q_2,2)\to(q_0,0)$ One can check that this is strongly synchronizing. For instance, if it ever encounters a 1, it will go into state $q_2$. Less trivially, if it encounters 00 then it will go into state $q_0$ and if it encounters 02, then it will go into state $q_1$. One of the main results of this paper is to show that the group of automorphisms of the one-sided shift on $X_n^{\mathbb N}$ (where $X_n$ is a set of size $n$) embeds naturally into the outer automorphism group of any one of the _Higman-Thompson groups_ $G_{n,r}$, which can be defined as follows. Let $1\leq r

Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor CRTC1/3-MAML2 gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillomavirus (HPV) as a potential driver of mucoepidermoid carcinoma. Bioinformatics analysis was performed on 48 MEC transcriptomes. Subsequent targeted capture DNA sequencing was used to annotate HPV content and integration status in the host genome. HPV of any type was only identified in 1/48 (2%) of the MEC transcriptomes analyzed. Importantly, the one HPV16+ tumor expressed high levels of p16, had high expression of HPV16 oncogenes E6 and E7, and displayed a complex integration pattern that included breakpoints into 13 host genes including PIK3AP1, HIPI, OLFM4,SIRT1, ARAP2, TMEM161B-AS1, and EPS15L1 as well as 9 non-genic regions. In this cohort, HPV is a rare driver of MEC but may have a substantial etiologic role in cases that harbor the virus. Genetic mechanisms of host genome integration are similar to those observed in other head and neck cancers.

Accelerated idioventricular rhythm (AIVR) is an uncommon but benign rhythm, seen most commonly in children. It is associated with reperfusion injury after myocardial infarction in adults. In children, it is usually seen as an idiopathic finding in the absence of heart disease. We present a case of AIVR in an adolescent associated with acute presentation of inflammatory bowel disease. Prompt treatment of the systemic inflammation led to the remission of both inflammatory bowel disease and AIVR. This report emphasizes the diverse causes of AIVR in children and our limited understanding of its pathophysiology. Treatment of the underlying condition resolved the arrhythmia. Résumé: Le rythme idioventriculaire accéléré (RIVA) est un rythme rarement rencontré mais bénin, observé le plus souvent chez les enfants. Il est associé à des lésions de reperfusion après un infarctus du myocarde chez l'adulte. Chez l'enfant, il est généralement catégorisé comme idiopathique en absence de maladie cardiaque. Nous présentons le cas d’un adolescent ayant un RIVA associé à une forme aiguë de maladie intestinale inflammatoire. Un traitement rapide de l'inflammation systémique a conduit à la rémission de la maladie intestinale inflammatoire et du RIVA. Ce rapport met en lumière les diverses causes du RIVA chez les enfants et notre compréhension limitée de sa physiopathologie. Le traitement de la condition sous-jacente a permis de résoudre l'arythmie.

Background Neural mechanisms may play an important role in non-eosinophilic asthma (NEA). This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic asthma (EA) and NEA and non-asthmatics.Methods Thirty-eight asthmatics and 19 non-asthmatics (aged 14–21 years) underwent combined hypertonic saline challenge/sputum induction, fractional exhaled nitric oxide, atopy and spirometry tests, followed by capsaicin challenge. EA and NEA were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity was defined as a ≥15% drop in FEV1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs.Results Non-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared with non-asthmatics (n=19) (geometric mean C5: 58.3 µM, 95% CI 24.1 to 141.5 vs 193.6 µM, 82.2 to 456.0; p

Condensed Matter Physics: nematic order does not exist in FeS Low energy spin excitations show no sign of nematic order existing in FeS, a structure-similar material of FeSe, without direct coupling to superconductivity. An international team led by Pengcheng Dai at the Rice University and Beijing Normal University carried out transport, neutron scattering, quantum oscillation measurements combined with theoretical calculations to study single crystals of FeS. They found that the spin excitations below 100 meV reveal only stripe-type spin fluctuations without direct coupling to superconductivity, suggesting FeS being a tetragonal paramagnet without nematic order and with a reduced quasiparticle mass compared to that of FeSe. These results not only suggest that FeS is a weakly correlated analog of FeSe, but also shed a light to understand the nematic order in FeSe, which is due to the competing spin fluctuations driven by frustrated magnetic interactions.

Double steal phenomenon is a rare condition where occlusion of the innominate (brachiocephalic) artery leads to hemodynamic changes in which blood flow is shunted from the intracranial circulation down the right vertebral artery and subsequently up the right carotid and subclavian circulation. This is a case of a 67-year-old female presenting emergently with recurrent transient ischemic attacks due to double steal phenomenon. Emergency department recognition of the double steal phenomenon and large vessel occlusion by computed tomography angiogram of the head and neck allowed for early treatment, which was critical in avoiding irreversible cerebral infarction.

The emergence of Zika virus (ZIKV) in the New World has led to more than 200,000 human infections. Perinatal infection can cause severe neurological complications, including fetal and neonatal microcephaly, and in adults there is an association with Guillain-Barré syndrome (GBS). ZIKV is transmitted to humans by Aedes sp. mosquitoes, yet little is known about its enzootic cycle in which transmission is thought to occur between arboreal Aedes sp. mosquitos and non-human primates. In the 1950s and '60s, several bat species were shown to be naturally and experimentally susceptible to ZIKV with acute viremia and seroconversion, and some developed neurological disease with viral antigen detected in the brain. Because of ZIKV emergence in the Americas, we sought to determine susceptibility of Jamaican fruit bats (Artibeus jamaicensis), one of the most common bats in the New World. Bats were inoculated with ZIKV PRVABC59 but did not show signs of disease. Bats held to 28 days post-inoculation (PI) had detectable antibody by ELISA and viral RNA was detected by qRT-PCR in the brain, saliva and urine in some of the bats. Immunoreactivity using polyclonal anti-ZIKV antibody was detected in testes, brain, lung and salivary glands plus scrotal skin. Tropism for mononuclear cells, including macrophages/microglia and fibroblasts, was seen in the aforementioned organs in addition to testicular Leydig cells. The virus likely localized to the brain via infection of Iba1+ macrophage/microglial cells. Jamaican fruit bats, therefore, may be a useful animal model for the study of ZIKV infection. This work also raises the possibility that bats may have a role in Zika virus ecology in endemic regions, and that ZIKV may pose a wildlife disease threat to bat populations.

In marathon running, maintenance of body temperature is critical for peak performance. Race apparel should maximize ventilation yet current fabric permeability standards are based on airflow rates that are not generated during running. A novel flow measurement device was used to measure airflow through textiles and the effects of fabric hole size, coverage area and standoff distance between a simulated torso and fabric at velocities of 3.3, 5.3 and 10 m.s−1. Fluorescent dye injection in a tow tank or flume permitted visualization of flow through fabrics. Ventilation is constrained by the low flow velocity in the stagnation area over the chest of an athlete, with freestream airflows of 3.3 and 10 m.s−1 reduced to 1.31 +/− 0.10 m/s (39.6%) and 3.51 +/− 0.27 m.s−1 (35.0%), respectively at a yaw angle of 20°. The initial low flow velocity precludes improvements in airflow despite changes in the standoff distance, fabric hole size or coverage area.

Introduction. The aim of the study was to use trajectory analysis to categorise high-impact users based on their long-term readmission rate and identify their predictors following AAA (abdominal aortic aneurysm) repair. Methods. In this retrospective cohort study, group-based trajectory modelling (GBTM) was performed on the patient cohort (2006-2009) identified through national administrative data from all NHS English hospitals. Proc Traj software was used in SAS program to conduct GBTM, which classified patient population into groups based on their annual readmission rates during a 5-year period following primary AAA repair. Based on the trends of readmission rates, patients were classified into low- and high-impact users. The high-impact group had a higher annual readmission rate throughout 5-year follow-up. Short-term high-impact users had initial high readmission rate followed by rapid decline, whereas chronic high-impact users continued to have high readmission rate. Results. Based on the trends in readmission rates, GBTM classified elective AAA repair (n=16,973) patients into 2 groups: low impact (82.0%) and high impact (18.0%). High-impact users were significantly associated with female sex (P=0.001) undergoing other vascular procedures (P=0.003), poor socioeconomic status index (P

Category: Bunion, Trauma, Other Introduction/Purpose: Immobilization is required for management of acute and chronic pathologic states of the hallux metatarsophalangeal (MTP) joint. Traditionally, this was performed using physician applied custom splint or cast and achieved a high degree of immobilization. Braces and orthotics are becoming less expensive and have several advantages, such as light weight and convenience in removal. However, this may come at the expense of ability to restrict movement. We hypothesize that generic braces will provide as much immobilization as custom applied plaster splints. Methods: Healthy volunteers were instrumented with electromagnetic sensors over bony prominences of the right foot. Range of motion exercises and activities of daily living were performed without an immobilization device. The same procedure was repeated with each of three immobilization devices: a post-operative shoe, a walking boot, and a custom applied plaster splint. Position and angular data were collected to determine range of motion primarily of the hallux MTP joint. This study was approved by the hospital IRB Results: Compared to baseline, all three immobilization devices significantly reduced range of motion at the MTP joint in non- weight bearing with the ankle in dorsiflexion and plantarflexion (p

Category: Trauma Introduction/Purpose: Pre-operative serum albumin levels have routinely been utilized to assess nutritional status. Malnutrition, as defined by serum albumin levels < 3.5 g/dL, has been associated with worse post-operative outcomes in multiple surgical settings. The effect of hypo-albuminemia on 30-day post-operative outcomes after operative fixation of ankle fractures has not been well delineated. Methods: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, 1,526 patients who had undergone surgical fixation of ankle fractures were identified using Current Procedural Terminology (CPT) codes. Perioperative complications and length of hospital stay were compared between patients with and without hypoalbuminemia (serum albumin concentration

OBJECTIVES/SPECIFIC AIMS: Our objective was to assess and compare the attitudes of patients with head and neck cancer and their clinicians regarding the commercialization of genetic research data. We explored whether such opinions changed when profits from such transactions were used to fund 1) cancer research, 2) academic research generally, or 3) if patients were given personalized genetic information in return. METHODS/STUDY POPULATION: This qualitative analysis was nested within a prospective precision oncology genomic sequencing study in an NCI-designated cancer center. We conducted paired, semi-structured interviews with enrolled participants with head & neck cancer and with their doctors (medical oncologists, surgical oncologists, and radiation oncologists). Interviews were recorded, transcribed, and coded for analysis. Codes were developed through an iterative process until saturation was reached, and all transcripts were double-coded (and discrepancies reconciled) to ensure reliability. RESULTS/ANTICIPATED RESULTS: We identified three main themes from the patients and clinicians: (1) Both clinicians and their patients were unclear about how the study protocol and informed consent form authorized patients’ genetic data to be used and commercialized in the future. (2) Patients with cancer were generally more comfortable than their clinician thought they were regarding the ongoing research use of their genetic data and commercialization thereof. (3) There is a strong interest among patients and clinicians in focusing academic medical center profits from commercialization back into the research program from which the data was acquired, rather than being invested into academic research more broadly. DISCUSSION/SIGNIFICANCE OF IMPACT: Given patients’ strong feelings about the commercialization of their data, our results highlight the need for greater transparency—both with patients and with their clinicians—about potential future use of research data. Clinicians appear inclined to be particularly cautious regarding access to and commercialization of patients’ data, however patients generally hope that their data may be used to help future cancer patients. Explicit discussions with patients about specific future uses of profits derived from commercialization of research data can ensure both transparency and participation in future primary and secondary precision health research programs.

We report an 85-year-old female patient who presented with an erythematous keratotic lesion on her temple suspicious of squamous cell carcinoma. Histological evaluation revealed actinic keratosis, but the underlying atypical infiltrate contained atypical myeloid forms consistent with acute myelogenous leukemia (AML). Upon further questioning, it was determined that the patient had a history of myelodysplastic syndrome. Her skin biopsy provided the first evidence of progression to AML. This case serves as an important reminder of the role the dermatopathologist plays in identifying serious systemic disease.

Central centrifugal cicatricial alopecia is a common cause of progressive permanent apical alopecia. This unique form of alopecia includes entities previously know as "hot comb alopecia," "follicular degeneration syndrome," "pseudopelade" in African Americans and "central elliptical pseudopelade" in Caucasians. The etiology appears to be multifactorial and the condition occurs in all races.