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Tumor mutation burden is an imperfect proxy of tumor foreignness and has therefore failed to consistently demonstrate clinical utility in predicting responses in the context of immunotherapy. We evaluated mutations in regions of the genome that are unlikely to undergo loss in a pan-cancer analysis across 31 tumor types (n = 9,242) and eight immunotherapy-treated cohorts of patients with non-small-cell lung cancer, melanoma, mesothelioma, and head and neck cancer (n = 524). We discovered that mutations in single-copy regions and those present in multiple copies per cell constitute a persistent tumor mutation burden (pTMB) which is linked with therapeutic response to immune checkpoint blockade. Persistent mutations were retained in the context of tumor evolution under selective pressure of immunotherapy and tumors with a high pTMB content were characterized by a more inflamed tumor microenvironment. pTMB imposes an evolutionary bottleneck that cancer cells cannot overcome and may thus drive sustained immunologic tumor control in the context of immunotherapy.

Renal cell carcinoma with inferior vena cava (IVC) thrombosis is a rare disease with a poor prognosis without surgical treatment. The presence of a tumor thrombus in the cavity of the main vessel in most cases is accompanied by massive bleeding during thrombectomy. To reduce the volume of blood loss, it is possible to use cardiopulmonary bypassto reduce the potential risks associated with blood loss and unstable hemodynamics. Sometimes tumor thrombosis can be growth into the vein wall or lead to occlusion IVC, we consider that it’s indication for resection of the IVC. Thrombectomy with laparotomy access can be performed even with type IV tumor thrombosis, if the thrombus is not fixed to the wall of the suprarenal IVC and surgeon have enough view of suprarenal segment.This article presents a variant of surgical treatment of patients with right kidney cancer, type IV IVC thrombosis, occlusion infrarenal IVC and ileofemoral thrombosis. In both cases we made resection IVC – infrarenal segment in first case and suprarenal segment in second case.

This paper provides a novel theoretical angle and robust empirical evidence demonstrating that the auction duration and the item description length are two essential auction design parameters that can function as screening mechanisms for bidder quality on online service outsourcing platforms. These outsourcing platforms use buyer-determined reverse auctions to find service providers. Using data from a major online outsourcing platform, we examine the effects of the auction duration and the item description length on both bidder entry (i.e., the number of bids and bidder quality) and contract outcomes (i.e., whether a project is contracted and the buyer’s expected utility from the winning bid) based upon the project- and bidder-level analyses. We find that auctions with longer durations and item descriptions attract more bids, but they also attract disproportionately more low-quality bidders, creating a double whammy of higher evaluation costs and adverse selection for buyers. This, in turn, leads to less successful contracting as well as lower buyer utility. Our research highlights the screening role of the auction duration and item description length for buyers on online service outsourcing platforms: by shortening auction durations and item descriptions, buyers can expect higher quality bidders, increase contracting probability, and enhance utility.

Aberrant alternative splicing can generate neoantigens, which can themselves stimulate immune responses and surveillance. Previous methods for quantifying splicing-derived neoantigens are limited by independent references and potential batch effects. Here, we introduce SpliceMutr, a bioinformatics approach and pipeline for identifying splicing derived neoantigens from tumor and normal data. SpliceMutr facilitates the identification of tumor-specific antigenic splice variants, predicts MHC-binding affinity, and estimates splicing antigenicity scores per gene. By applying this tool to genomic data from The Cancer Genome Atlas (TCGA), we generate splicing-derived neoantigens and neoantigenicity scores per sample and across all cancer types and find numerous correlations between splicing antigenicity and well-established biomarkers of anti-tumor immunity. Notably, carriers of mutations within splicing machinery genes have higher splicing antigenicity, which provides support for our approach. Further analysis of splicing antigenicity in cohorts of melanoma patients treated with mono-or combined immune checkpoint inhibition suggest that the abundance of splicing antigens is reduced post-treatment from baseline in patients who progress, likely because of an immunoediting process. We also observe increased splicing antigenicity in responders to immunotherapy, which may relate to an increased capacity to mount an immune response to splicing-derived antigens. We find the splicing antigenicity to be higher in tumor samples when compared to normal, that mutations in the splicing machinery result in increased splicing antigenicity in some cancers, and higher splicing antigenicity is associated with positive response to immune checkpoint inhibitor therapies. Further, this new computational pipeline provides novel analytical capabilities for splicing antigenicity and is openly available for further immuno-oncologic analysis.

Computational prediction of binding between neoantigen peptides and major histocompatibility complex (MHC) proteins can be used to predict patient response to cancer immunotherapy. Current neoantigen predictors focus on in silico estimation of MHC binding affinity and are limited by low predictive value for actual peptide presentation, inadequate support for rare MHC alleles, and poor scalability to high-throughput data sets. To address these limitations, we developed MHCnuggets, a deep neural network method that predicts peptide–MHC binding. MHCnuggets can predict binding for common or rare alleles of MHC class I or II with a single neural network architecture. Using a long short-term memory network (LSTM), MHCnuggets accepts peptides of variable length and is faster than other methods. When compared with methods that integrate binding affinity and MHC-bound peptide (HLAp) data from mass spectrometry, MHCnuggets yields a 4-fold increase in positive predictive value on independent HLAp data. We applied MHCnuggets to 26 cancer types in The Cancer Genome Atlas, processing 26.3 million allele–peptide comparisons in under 2.3 hours, yielding 101,326 unique predicted immunogenic missense mutations (IMM). Predicted IMM hotspots occurred in 38 genes, including 24 driver genes. Predicted IMM load was significantly associated with increased immune cell infiltration (P < 2 × 10−16), including CD8+ T cells. Only 0.16% of predicted IMMs were observed in more than 2 patients, with 61.7% of these derived from driver mutations. Thus, we describe a method for neoantigen prediction and its performance characteristics and demonstrate its utility in data sets representing multiple human cancers.

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Supplementary Figure 6 from Mammalian Target of Rapamycin Activator RHEB Is Frequently Overexpressed in Human Carcinomas and Is Critical and Sufficient for Skin Epithelial Carcinogenesis

RHEB cancer expression and clinico-pathological data from Mammalian Target of Rapamycin Activator RHEB Is Frequently Overexpressed in Human Carcinomas and Is Critical and Sufficient for Skin Epithelial Carcinogenesis

Supplementary Figure 4 from Mammalian Target of Rapamycin Activator RHEB Is Frequently Overexpressed in Human Carcinomas and Is Critical and Sufficient for Skin Epithelial Carcinogenesis

Supplementary Table 1 from Mammalian Target of Rapamycin Activator RHEB Is Frequently Overexpressed in Human Carcinomas and Is Critical and Sufficient for Skin Epithelial Carcinogenesis

Supplementary Figure 7 from Mammalian Target of Rapamycin Activator RHEB Is Frequently Overexpressed in Human Carcinomas and Is Critical and Sufficient for Skin Epithelial Carcinogenesis

Supplementary Figure 1 from Mammalian Target of Rapamycin Activator RHEB Is Frequently Overexpressed in Human Carcinomas and Is Critical and Sufficient for Skin Epithelial Carcinogenesis

Supplementary Figure 2 from Mammalian Target of Rapamycin Activator RHEB Is Frequently Overexpressed in Human Carcinomas and Is Critical and Sufficient for Skin Epithelial Carcinogenesis

Supplementary Figure 5 from Mammalian Target of Rapamycin Activator RHEB Is Frequently Overexpressed in Human Carcinomas and Is Critical and Sufficient for Skin Epithelial Carcinogenesis

Supplementary Figure 3 from Mammalian Target of Rapamycin Activator RHEB Is Frequently Overexpressed in Human Carcinomas and Is Critical and Sufficient for Skin Epithelial Carcinogenesis

We report a search for a dark photon using $14.9$~fb$^{-1}$ of $e^+e^-$ annihilation data taken at center-of-mass energies from 4.13 to 4.60~GeV with the BESIII detector operated at the BEPCII storage ring. The dark photon is assumed to be produced in the radiative annihilation process of $e^+e^-$ and to predominantly decay into light dark matter particles, which escape from the detector undetected. The mass range from 1.5 to 2.9~GeV is scanned for the dark photon candidate, and no significant signal is observed. The mass dependent upper limits at the 90$\%$ confidence level on the coupling strength parameter $\epsilon$ for a dark photon coupling with an ordinary photon vary between $1.6\times 10^{-3}$ and $5.7\times10^{-3}$., Comment: 8 pages, 3 figures

Introduction The degree to which Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is aerosolized has yet to be determined. The aim of this study is to prove methods of detection of aerosolization of SARS-CoV-2 in hospitalized patients in anticipation of testing for aerosolization in procedural and operative settings. Methods In this prospective study, inpatients with SARS-CoV-2 were identified. Demographic information was obtained, and a symptom questionnaire was completed. Polytetrafluoroethylene (PTFE) filters, which were attached to an air pump, were used to detect viral aerosolization and placed in four locations in each patient’s room. The filters were left in the rooms for a three-hour period. Results There were 10 patients who enrolled in the study, none of whom were vaccinated. Only two patients were more than a week from the onset of symptoms, and half of the patients received treatment for COVID with antivirals and steroids. Among ten RT-PCR positive and hospitalized patients, and four filters per patient, there was only one positive SARS-CoV-2 aerosol sample, and it was directly attached to one of the patients. Overall, there was no correlation between symptoms or symptom onset and aerosolized test result. Conclusions The results of this suggest that there is limited aerosolization of SARS-CoV-2 and provided proof of concept for this filter sampling technique. Further studies with increased sample size should be performed in a procedural and operative setting to provide more information about SARS-CoV-2 aerosolization.

Background Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country’s mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system. Methods Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured. Results Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes. Conclusion The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety.

At high luminosity areas, beam loss monitor with fast response and high radiation resistance is crucial for accelerator operation. In this article, we report the design and test results of a fast response and radiation-resistant scintillator detector as the beam loss monitor for high luminosity colliders, especially at low energy regions such as RFQ. The detector consists of a 2 cm*2 cm 0.5 cm LYSO crystal readout by a 6 mm*6 mm Silicon photomultiplier. Test results from various radioactive sources show that the detector has good sensitivity to photons from tens of keV to several MeV with good linearity and energy resolution (23% for 60 keV {\gamma}-ray). For the field test, two such detectors are installed outside of the vacuum chamber shell of an 800 MeV electron storage ring. The details of the test and results are introduced.

Mesothelioma is a rare and fatal cancer with limited therapeutic options until the recent approval of combination immune checkpoint blockade. Here we report the results of the phase 2 PrE0505 trial (NCT02899195) of the anti-PD-L1 antibody durvalumab plus platinum-pemetrexed chemotherapy for 55 patients with previously untreated, unresectable pleural mesothelioma. The primary endpoint was overall survival compared to historical control with cisplatin and pemetrexed chemotherapy; secondary and exploratory endpoints included safety, progression-free survival and biomarkers of response. The combination of durvalumab with chemotherapy met the pre-specified primary endpoint, reaching a median survival of 20.4 months versus 12.1 months with historical control. Treatment-emergent adverse events were consistent with known side effects of chemotherapy, and all adverse events due to immunotherapy were grade 2 or lower. Integrated genomic and immune cell repertoire analyses revealed that a higher immunogenic mutation burden coupled with a more diverse T cell repertoire was linked to favorable clinical outcome. Structural genome-wide analyses showed a higher degree of genomic instability in responding tumors of epithelioid histology. Patients with germline alterations in cancer predisposing genes, especially those involved in DNA repair, were more likely to achieve long-term survival. Our findings indicate that concurrent durvalumab with platinum-based chemotherapy has promising clinical activity and that responses are driven by the complex genomic background of malignant pleural mesothelioma., In a phase 2 trial, the combination of chemotherapy with durvalumab, an anti-PD-L1 antibody, exhibited promising clinical activity in patients with previously untreated, unresectable mesothelioma, with additional analyses providing insights into genomic and immunologic features potentially associated with response.

By analyzing 4.48 × 108 ψ(3686) events collected with the BESIII detector, we observe the decays χ cJ → nK S 0 Λ ¯ $$ {nK}_S^0\overline{\Lambda} $$ + c.c. (J = 0, 1, 2) for the first time, via the radiative transition ψ(3686) → γχ cJ . The branching fractions are determined to be (6.65 ± 0.26stat ± 0.41syst) × 10 −4, (1.66 ± 0.12stat ± 0.12syst) × 10 −4, and (3.58 ± 0.16stat ± 0.23syst) × 10 −4 for J = 0, 1, and 2, respectively.

Introduction Elective repair versus watchful waiting remains controversial in paraesophageal hernia (PEH) patients. Generation of predictive factors to determine patients at greatest risk for emergent repair may prove helpful. The aim of this study was to evaluate patients undergoing elective versus emergent PEH repair and supplement this comparison with 3D volumetric analysis of hiatal defect area (HDA) and intrathoracic hernia sac volume (HSV) to determine risk factors for increased likelihood of emergent repair. Methods A retrospective review of a prospectively enrolled, single-center hernia database was performed on all patients undergoing elective and emergent PEH repairs. Patients with adequate preoperative computed tomography (CT) imaging were analyzed using volumetric analysis software. Results Of the 376 PEH patients, 32 (8.5%) were emergent. Emergent patients had lower rates of preoperative heartburn (68.8%vs85.1%, p = 0.016) and regurgitation (21.9%vs40.2%, p = 0.04), with similar rates of other symptoms. Emergent patients more frequently had type IV PEHs (43.8%vs13.5%, p 0.05). With a formal PEH repair, there was no difference in rate or timing of recurrence. Conclusions Emergent patients are more likely to suffer complications, require ICU care, have a higher mortality, and an increased likelihood of reoperation. A graduated increase in HSV increasingly predicts the need for an emergent operation. Those patients presenting electively with a large PEH may benefit from early elective surgery.

Non-methane volatile organic compounds (NMVOCs) are important precursors of ozone (O3) and secondary organic aerosol (SOA), which play key roles in tropospheric chemistry. A huge amount of NMVOC emissions from solvent use are complicated by a wide spectrum of sources and species. This work presents a long-term NMVOC emission inventory of solvent use during 2000–2017 in China. Based on a mass (material) balance method, NMVOC emissions were estimated for six categories, including coatings, adhesives, inks, pesticides, cleaners, and personal care products. The results show that NMVOC emissions from solvent use in China increased rapidly from 2000 to 2014 then kept stable after 2014. The total emission increased from 1.6 Tg (1.2–2.2 Tg at 95 % confidence interval) in 2000 to 10.6 Tg (7.7–14.9 Tg) in 2017. The substantial growth is driven by the large demand for solvent products in both industrial and residential activities. However, increasing treatment facilities in the solvent-related factories in China restrained the continued growth of solvent NMVOC emissions in recent years. Rapidly developing and heavily industrialized provinces such as Jiangsu, Shandong, and Guangdong contributed significantly to the solvent use emissions. Oxygenated VOCs, alkanes, and aromatics were the main components, accounting for 42 %, 28 %, and 21 % of total NMVOC emissions in 2017, respectively. Our results and previous inventories are generally comparable within the estimation uncertainties (−27 %–52 %). However, there exist significant differences in the estimates of sub-categories. Personal care products were a significant and quickly rising source of NMVOCs, which were probably underestimated in previous inventories. Emissions from solvent use were growing faster compared with transportation and combustion emissions, which were relatively better controlled in China. Environmentally friendly products can reduce the NMVOC emissions from solvent use. Supposing all solvent-based products were substituted with water-based products, it would result in 37 %, 41 %, and 38 % reduction of emissions, ozone formation potential (OFP), and secondary organic aerosol formation potential (SOAP), respectively. These results indicate there is still large potential for NMVOC reduction by reducing the utilization of solvent-based products and implementation of end-of-pipe controls across industrial sectors.

Water uptake abilities of organic aerosol under sub-saturated conditions play critical roles in direct aerosol radiative effects and atmospheric chemistry; however, field characterizations of the organic aerosol hygroscopicity parameter κOA under sub-saturated conditions remain limited. In this study, a field campaign was conducted to characterize κOA at a relative humidity of 80 % with hourly time resolution for the first time in the Pearl River Delta region of China. Observation results show that, during this campaign, secondary organic aerosol (SOA) dominated total organic aerosol mass (mass fraction > 70 % on average), which provides a unique opportunity to investigate influences of SOA formation on κOA. Results demonstrate that the commonly used organic aerosol oxidation level parameter O/C was weakly correlated with κOA and failed to describe the variations in κOA. However, the variations in κOA were well reproduced by mass fractions of organic aerosol factor resolved based on aerosol mass spectrometer measurements. The more oxygenated organic aerosol (MOOA) factor, exhibiting the highest average O/C (∼ 1) among all organic aerosol factors, was the most important factor driving the increase in κOA and was commonly associated with regional air masses. The less oxygenated organic aerosol (LOOA; average O/C of 0.72) factor revealed strong daytime production, exerting negative effects on κOA. Surprisingly, the aged biomass burning organic aerosol (aBBOA) factor also formed quickly during daytime and shared a similar diurnal pattern with LOOA but had much lower O/C (0.39) and had positive effects on κOA. The correlation coefficient between κOA and mass fractions of aBBOA and MOOA in total organic aerosol mass reached above 0.8. The contrasting effects of LOOA and aBBOA formation on κOA demonstrate that volatile organic compound (VOC) precursors from diverse sources and different SOA formation processes may result in SOA with different chemical composition, functional properties and microphysical structure, consequently exerting distinct influences on κOA and rendering single oxidation level parameters (such as O/C) unable to capture those differences. Aside from that, distinct effects of aBBOA on κOA were observed during different episodes, suggesting that the hygroscopicity of SOA associated with similar sources might also differ much under different emission and atmospheric conditions. Overall, these results highlight that it is imperative to conduct more research on κOA characterization under different meteorological and source conditions and examine its relationship with VOC precursor profiles and formation pathways to formulate a better characterization and develop more appropriate parameterization approaches in chemical and climate models.

The neurosurgical management of spinal neoplasms has undergone immense development in parallel with advancements made in general spine surgery. Laminectomies were performed as the first surgical procedures used to treat spinal neoplasms. Since then, neurosurgical spinal oncology has started to incorporate techniques that have developed from recent advances in minimally invasive spine surgery. Neurosurgery has also integrated radiotherapy into the treatment of spine tumors. In this historical vignette, we present a vast timeline spanning from the Byzantine period to the current day and recount the major advancements in the management of spinal neoplasms.

The contribution of new particle formation (NPF) to cloud condensation nuclei (CCN) number concentration (NCCN) varies largely under different environments and depends on several key factors such as formation rate (J), growth rate (GR), distribution of preexisting particles, and properties of new particles during NPF events. This study investigates the contribution of NPF to the NCCN and its controlling factors based on measurements conducted at the Heshan supersite, in the Pearl River Delta (PRD) region of China during fall 2019. The size-resolved cloud condensation nuclei activity and size-resolved particle hygroscopicity were measured by a cloud condensation nuclei counter (CCNc) and a hygroscopic tandem differential mobility analyzer (HTDMA), respectively, along with a scanning mobility particle sizer (SMPS) and a diethylene glycol scanning mobility particle sizer (DEG-SMPS) for particle number size distribution (PNSD). A typical NPF event on 29 October was chosen to investigate the contribution of the NPF to NCCN under several supersaturation (SS) ratios. Two particle properties (hygroscopicity and surface tension) affect CCN activation with the latter being more important in terms of the CCN concentration (NCCN). A lower value of surface tension (i.e., 0.06 N m−1) than the pure-water assumption (0.073 N m−1) could increase the NCCN at SS = 1.0 % by about 20 % during the nonevent period and by about 40 % during the event. In addition, an earlier peak time corresponding to a lower critical diameter (D50) was also observed. The results show that high formation rate, growth rate, and low background particle concentration lead to high number concentrations of newly formed particles. The high growth rate was found to have the most significant impact on the NCCN, which can be attributed to the fact that a higher growth rate can grow particles to the CCN size in a shorter time before they are scavenged by preexisting particles. Two other NPF events (an event on 18 October in this campaign and an event on 12 December 2014 in Panyu) were chosen to perform sensitivity tests under different scenarios (growth rate, formation rate, and background particle concentration). The calculated NCCN at SS = 1.0 % on 12 December 2014 was significantly lower than that from the other two events. The event on 12 December was re-simulated using the growth rate taken from the event on 18 October which resulted in similar CCN concentrations between the two events (12 December and 18 October), implying that the growth rate is the major impact factor for CCN activation. Our results highlight the importance of growth rate and surface tension when evaluating the contribution of NPF to the NCCN.

Identifying neoepitopes that elicit an adaptive immune response is a major bottleneck to developing personalized cancer vaccines. Experimental validation of candidate neoepitopes is extremely resource intensive, and the vast majority of candidates are non-immunogenic, making their identification a needle-in-a-haystack problem. To address this challenge, we present computational methods for predicting MHC-I epitopes and identifying immunogenic neoepitopes with improved precision. The BigMHC method comprises an ensemble of seven pan-allelic deep neural networks trained on peptide-MHC eluted ligand data from mass spectrometry assays and transfer learned on data from assays of antigen-specific immune response. Compared with four state-of-the-art classifiers, BigMHC significantly improves the prediction of epitope presentation on a test set of 45,409 MHC ligands among 900,592 random negatives (AUROC=0.9733, AUPRC=0.8779). After transfer learning on immunogenicity data, BigMHC yields significantly higher precision than seven state-of-the-art models in identifying immunogenic neoepitopes, making BigMHC effective in clinical settings. All data and code are freely available athttps://github.com/KarchinLab/bigmhc.

Asthma and chronic obstructive pulmonary disease (COPD) are 2 distinct diseases with different clinical presentations. Chronic inflammation and airway obstruction are key features of asthma and COPD. Increased morbidity and mortality rates seem to be an important characteristic associated with asthma-COPD overlap (ACO).Atopy is an important clinical characteristic of patients categorized as ACO. Herein, the authors review the recent advancements in basic research, clinical assessment, and defining characteristics of ACO and the role for allergy as well as highlight future potential for disease-specific therapeutics for this asthma subtype.

Recurrent ventral hernia repairs are reported to have higher recurrence and complication rates than initial ventral hernia repairs. This is the largest analysis of outcomes for initial versus recurrent open ventral hernia repairs reported in the literature.A prospective, institutional database at a tertiary hernia center was queried for patients undergoing open ventral hernia repairs with complete fascial closure and synthetic mesh placement.A total of 1,694 open ventral hernia repairs patients were identified, including 896 (52.9%) initial ventral hernia repairs and 798 (47.1%)recurrent ventral hernia repairs. Recurrent ventral hernia repair patients were more complex: older (P = .003), higher body mass index (P.001), higher American Society of Anesthesiologists class (P.001), incidence of diabetics (P = .003), comorbidities (P.001), and larger hernia defects (133.3 ± 171.9 vs 220.2 ± 210.0; P.001). Recurrent ventral hernia repairs also had longer operative times (161.6 ± 82.4 vs 188.2 ± 68.9 minutes; P.001), increased use of preoperative botulinum toxin A injection (4.3% vs 10.1%; P = .01), components separation (19.2% vs 39.5%; P.001), and panniculectomy (20.3% vs 35.8%; P.001). The overall hernia recurrence rate was 4.4% at a mean follow-up of 36.6 ± 45.5 months. Between the initial ventral hernia repairs and recurrent ventral hernia repairs, the hernia recurrence rates were equivalent (4.2% vs 4.7%, P = .63). Rates of wound infection, seromas, hematomas, mesh infections, and wound related reoperations (P.05) were nonsignificant.At a tertiary hernia center, despite higher-risk patients, larger hernia defects, and increased components separation in recurrent ventral hernia repairs, early recurrence rates, wound complications, and reoperations are similar to initial ventral hernia repairs.

The comparative reactivity method (CRM) was developed more than a decade to measure OH reactivity (i.e., OH loss frequency) in both laboratory and field studies. However, accurate OH reactivity quantification remains challenging under real ambient conditions, especially for OH reactivity measurements in high-NOx (e.g., > 10 ppbv) environments, as ambient NO enhances the regeneration of OH radicals in the CRM reactor. To solve this problem, we design a new and improved CRM reactor (ICRM) and add NO into the system continuously so that the HO2 radical concentration is suppressed. We confirmed the appropriate level of NO by determining the maximum decrease in the pyrrole level caused by regenerated OH radicals from NO + HO2. RO2 radicals induced by volatile organic compounds (VOCs) in the ICRM reactor were also found to react with NO, which led to the regeneration of OH radicals and thus the underestimation of OH reactivity. This effect was quantified by the calibration of representative VOC species at different NO levels, and the correction coefficients obtained were used to correct the measured OH reactivity. All these efforts resulted in reducing the uncertainty of the NO-artifact correction by at least an order of magnitude compared to the original CRM system. Additionally, these technological improvements also considerably reduced the systematic errors from pyrrole photolysis in the original system. A new operation mode was proposed for the ICRM, which is able to avoid the interference resulting from OH radicals produced by photolysis of residual humidity and save time for ambient measurement. The ICRM system was employed in a field campaign to measure OH reactivity and performed well with ambient NO levels ranging from 0 to 50 ppbv, which are typically observed in the urban and suburban atmosphere.

INTRODUCTION: Tumor mutation burden (TMB) is a commonly used biomarker for cancer immunotherapy however TMB only partially captures tumor foreignness. We hypothesized that mutations in single-copy regions of the genome or mutations present in multiple copies (hereafter referred to as persistent mutations) are retained during cancer evolution and immunoediting, may render the tumor continuously visible to the immune system and promote sustained tumor control during immune checkpoint blockade (ICB). METHODS: We performed pan-cancer analyses of whole exome sequencing data across 31 tumor types in TCGA to quantify the landscape of persistent mutations (n=9,242). We then evaluated the association between persistent tumor mutation burden (pTMB) and ICB response compared to TMB in eight ICB-treated cohorts of patients with NSCLC, melanoma, mesothelioma, and head and neck cancer (n=524). To investigate the clonal evolution of persistent mutations we serially analyzed whole exome sequence data from NSCLCs prior to and at emergence of acquired resistance to ICB. Finally, we evaluated the composition of the tumor microenvironment (TME) in baseline and on-ICB melanomas by RNA sequencing differential enrichment analyses and deconvolution. RESULTS: Integration of sequence alterations in only-copy and multi-copy states for 9,242 tumors across 31 tumor types revealed a cancer lineage-dependent distribution of persistent mutations that was largely independent of the overall TMB. In evaluating differential classification based on pTMB- vs TMB-high, we found re-classification rates as high as 53% in individual tumor types, with a median reclassification rate of 33% across all tumor types (range 15% - 53%). We then evaluated the clonal composition of persistent mutations and found a wide range of correlations between pTMB and fraction of clonal mutations (Spearman ρ range: -0.11 - 0.59). In ICB-treated cohorts, pTMB better distinguished responding tumors compared to TMB, and a number of mutation and copy-number related features including tumor aneuploidy (melanoma: Mann-Whitney p=2.3e-06, NSLC: p CONCLUSIONS: Persistent mutations represent a biologically distinct subset within the overall TMB that is unlikely to be lost under selective pressure of ICB and may function as an intrinsic driver of sustained immunologic tumor control. Citation Format: Noushin Niknafs, Archana Balan, Christopher Cherry, Karlijn Hummelink, Kim Monkhorst, Xiaoshan M. Shao, Zineb Belcaid, Kristen A. Marrone, Joseph Murray, Kellie N. Smith, Benjamin Levy, Josephine Feliciano, Christine L. Hann, Vincent Lam, Drew M. Pardoll, Rachel Karchin, Tanguy Y. Seiwert, Julie R. Brahmer, Patrick M. Forde, Victor E. Velculescu, Valsamo K. Anagnostou. Persistent mutation burden drives sustained anti-tumor immune responses in human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1393.

To meet assembly requirements, carbon fiber reinforced plastics (CFRP) generally require mechanical processing, of which the most common form is drilling. As a result of the increasing quantity of use and growing structural complexity of CFRP, the demand for batch high-precision hole making is becoming increasingly urgent. However, existing research is mostly focused on the small-batch and small-thickness drilling of samples. With a customized PCD drill bit, this study investigates the effects of large-batch drilling on the failure forms of the drill bit and the quality of holes drilled. The results show that (1) chip adhesion is of great importance to the failure of the drill bit in the process of batch hole making; (2) fluid cutting facilitates the cooling, lubrication, and chip removal of the bit, thereby dramatically reducing tool wear; (3) dry cutting leads to micro hole expansion so that the holes drilled have a slightly larger diameter than the drill bit; and (4) the addition of support plates at the exit position can effectively avoid defects such as exit tear and delamination.

A variety of wave-transparent composites were prepared with multiple single-epoxy POSS and poly-epoxy POSS as modifiers, phenylene organic silicone resin as matrix, and quartz fiber as reinforcement. The effects of four epoxy POSS with different structures on the mechanical properties, dielectric properties and electromagnetic wave transmissivity of the composites were studied. Results showed that: the addition of octaepoxy POSS can significantly improve the mechanical properties of the composites, while the mechanical properties of the composites with single-epoxy POSS decline; the addition of POSS with different structures can enhance the dielectric properties of the composites; among the POSS of four structures, the glycidyl ether-based POSS can best improve the overall performance of the composites. The modified composites have a compressive strength of 140.8 MPa, bending strength of 185 MPa, and dielectric constant of about 3.0 at 8-18 GHz. Meanwhile, after comparing the effects of different glycidyl ether-based POSS additions on the properties of the composites, it is found that when the addition is 5wt%, the composites have optimal performance.

The flame-retardancy of enamelled wires was studied by using a cone calorimeter. The characteristic parameters including time to ignition, heat release rate, total smoke release and so on, were obtained. The effect of heat radiation flux on the flame retardancy was analyzed. The results show that the flame retardancy of enamelled wires is related to the content of different components in the composite insulation layer. Polyimide enamelled wires have good flame retardant performance, followed by corona resistant wire with filler, and ordinary polyamide imide composite polyester imide enamelled wire has poor flame retardant performance. In conclusion, the heat release rate measured by cone calorimeter can be used for evaluate the flame retardancy of enamelled wires and provide a reference for the development and application of flame retardant enamelled wires.

We report a search for a heavier partner of the recently observed state, denoted as , in the process , based on collision data collected at the center-of-mass energies of , 4.682 and 4.699 GeV with the BESIII detector. The is of interest as it is expected to be a candidate for a hidden-charm and open-strange tetraquark. A partial-reconstruction technique is used to isolate recoil-mass spectra, which are probed for a potential contribution from ( ). We find an excess of ( ) candidates with a significance of , after considering systematic uncertainties, at a mass of . As the data set is limited in size, the upper limits are evaluated at the 90% confidence level on the product of the Born cross sections ( ) and the branching fraction ( ) of , under different assumptions of the mass from 4.120 to 4.140 MeV and of the width from 10 to 50 MeV at the three center-of-mass energies. The upper limits of are found to be at the level of pb at each energy. Larger data samples are needed to confirm the state and clarify its nature in the coming years.

A new in-vessel water-cooled coil has been placed below the lower tungsten-covered divertor in EAST, aiming at moving the strike points in the divertor and spreading the heat flow on the targets. To achieve controlled movement of the strike points by the plasma control system (PCS) when applying the in-vessel coil, the plasma equilibrium configurations are predicted by the tokamak equilibrium (TEQ) code. The divertor coil current is involved in these calculations. The shape control parameters in the PCS are adjusted according to the predesigned equilibria from the TEQ code. The strike point movement over a wide range has been achieved in the experiment while keeping the main plasma stable. Thus, this method for divertor strike point movement with the assistance of the divertor coil is feasible.

Objective Generator site pain is a relatively common phenomenon in patients undergoing spinal cord stimulation (SCS) that complicates management and effective pain relief. This pain may be managed conservatively, with repositioning of the battery and, in some cases, with explant. Here we explore our experience with management of generator site pain (“pocket pain”) in a large single-center study. Methods All SCS permanent implants and implantable pulse generator (IPG) placements over 9 years were reviewed. Of 785 cases, we identified 43 patients with pocket pain (5.5%). Demographics and treatments of the pocket pain cohort were analyzed. Results The mean age (± SEM) of the pocket pain cohort was 46.86 ± 1.06, and there were 10/33 males/females. Females were overrepresented in pocket pain cohort (76.7%) when compared with the total SCS cohort (59.0%) (X2 = 5.93, P = 0.015). Diagnosis included failed back surgery syndrome (51.2%), complex regional pain syndrome (23.3%), and chronic neuropathic pain (25.5%). No patients improved with conservative therapy. All patients either went on to revision (n = 23) or explant (n = 20). Time from initial surgery to development of pocket pain was 7.5 months (range: 0.3–88) and from pocket pain to revision surgery was 4.5 months (range: 0.4–26). In addition, significantly more pocket pain patients (65.1%) had workers’ compensation (WC) insurance compared with patients without pocket pain (24.9%) (X2 = 33.3, P Conclusion In our institutional experience, pocket pain was inadequately managed with conservative treatments. Being female and having SCS filed under WC increased risk of pocket pain. Future work will explore the nuances in device placement based on body shape and manual activity responsibilities.

Stress has been implicated in the etiology of neurological and psychological illnesses. Chronic social isolation (SI) is a psychological stressor that provokes neurobehavioral changes associated with psychiatric disorders, including anxiety disorders. Mitochondria dysfunction and oxidative stress are hallmarks of anxiety pathogenesis. Here we demonstrate the effects of SI-induced stress on mitochondrial function, antioxidative enzymes, autophagy, and brain derivative neurotrophic factor (BDNF). SI induced a reduction in electron transport chain subunits C-I, C-II, and C-VI and an increase in hydrogen peroxide. Treatment with dihydromyricetin (DHM), extracted from Ampelopsis grossedentata, counteracted these changes. A dramatic increase in several primary mitochondrial antioxidative enzymes such as superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1), peroxiredoxin-3 (PRDX3), and glutathione peroxidase 4 (GPX4) was observed after SI and a repeated episode of SI. Both SI and repeated SI induced a reduction in sequestosome 1 (SQSTM1/p62). However, only repeated SI modulated autophagy primary protein beclin-1 (Bcl-1). In addition, SI and repeated SI modulated the BDNF-TrkB signaling pathway and the phosphorylation of the downstream extracellular signal-regulated MAP kinase1/2 (p-Erk p42 and p-Erk p44) cascade. DHM treatment ameliorated these changes. Collectively, we demonstrated that DHM treatment counteracted the effects of SI and repeated SI on antioxidative enzymes, autophagy, and the BDNF-TrkB signaling pathway. These findings highlight the molecular mechanisms that partially explain the anxiolytic effects of DHM.