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Patrick Oellers,1,* Inês Laíns,1,2,* Steven Mach,1 Shady Garas,1 Ivana K Kim,1 Demetrios G Vavvas,1 Joan W Miller,1 Deeba Husain,1 John B Miller1 1Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA; 2Faculty of Medicine, University of Coimbra, Coimbra, Portugal *These authors contributed equally to this work Purpose: Eyes with age-related macular degeneration (AMD) often harbor pathological changes in the retinal periphery and perimacular region. These extramacular changes have not been well classified, but may be phenotypically and functionally relevant. The purpose of this study was to demonstrate a novel grid to systematically study peripheral retinal abnormalities in AMD using geometric distortion-corrected ultra-widefield (UWF) imaging.Methods: This is a cross-sectional observational case series. Consecutive patients with AMD without any other coexisting vitreoretinal disease and control patients over age 50 without AMD or any other vitreoretinal disease were imaged using Optos 200 Tx. Captured 200° UWF images were corrected for peripheral geometric distortion using Optos transformation software. A newly developed grid to study perimacular and peripheral abnormalities in AMD was then projected onto the images.Results: Peripheral and perimacular changes such as drusen, retinal pigment epithelium changes and atrophy were found in patients with AMD. The presented grid in conjunction with geometric distortion-corrected UWF images allowed for systematic study of these peripheral changes in AMD.Conclusion: We present a novel grid to study peripheral and posterior pole changes in AMD. The grid is unique in that it adds a perimacular zone, which may be important in characterizing certain phenotypes in AMD. Our UWF images were corrected for geometric peripheral distortion to accurately reflect the anatomical dimensions of the retina. This grid offers a reliable and reproducible foundation for the exploration of peripheral retinal pathology associated with AMD. Keywords: ultra-widefield, autofluorescence, macular degeneration, grid, periphery, drusen, retinal pigment epithelium changes

Minchul Kim,1 Jinma Ren,1 William Tillis,2,3 Carl V Asche,1,4 Inkyu K Kim,5 Carmen S Kirkness1 1Department of Internal Medicine, Center for Outcomes Research, University of Illinois College of Medicine at Peoria, 2OSF St Francis Medical Center, 3Department of Internal Medicine, University of Illinois College of Medicine at Peoria, Peoria, 4Department of Pharmacy Systems, Outcomes and Policy, University of Illinois at Chicago College of Pharmacy, Chicago, IL, 5Battelle Memorial Institute, Atlanta, GA, USA Background: Limited accessibility to health care may be a barrier to obtaining good care. Few studies have investigated the association between access-to-care factors and COPD hospitalizations. The objective of this study is to estimate the association between access-to-care factors and health care utilization including hospital/emergency department (ED) visits and primary care physician (PCP) office visits among adults with COPD utilizing a nationally representative survey data. Methods: We conducted a pooled cross-sectional analysis based upon a bivariate probit model, utilizing datasets from the 2011–2012 Behavioral Risk Factor Surveillance System linked with the 2014 Area Health Resource Files among adults with COPD. Dichotomous outcomes were hospital/ED visits and PCP office visits. Key covariates were county-level access-to-care factors, including the population-weighted numbers of pulmonary care specialists, PCPs, hospitals, rural health centers, and federally qualified health centers. Results: Among a total of 9,332 observations, proportions of hospital/ED visits and PCP office visits were 16.2% and 44.2%, respectively. Results demonstrated that access-to-care factors were closely associated with hospital/ED visits. An additional pulmonary care specialist per 100,000 persons serves to reduce the likelihood of a hospital/ED visit by 0.4 percentage points (pp) (P=0.028). In contrast, an additional hospital per 100,000 persons increases the likelihood of hospital/ED visit by 0.8 pp (P=0.008). However, safety net facilities were not related to hospital utilizations. PCP office visits were not related to access-to-care factors. Conclusion: Pulmonary care specialist availability was a key factor in reducing hospital utilization among adults with COPD. The findings of our study implied that an increase in the availability of pulmonary care specialists may reduce hospital utilizations in counties with little or no access to pulmonary care specialists and that since availability of hospitals increases hospital utilization, directing patients with COPD to pulmonary care specialists may decrease hospital utilizations. Keywords: pulmonary specialist, COPD, hospital utilization

Irene K Kim, Ashley Vo, Stanley C Jordan Transplant Immunotherapy Program, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Despite better understanding of the impact of development of the human leukocyte antigen (HLA) antibody and numerous advancements in immunosuppressive therapy, the ability to successfully transplant highly sensitized patients remains a significant challenge. As the percentage of the waiting list becomes increasingly populated with highly sensitized patients, there is a growing demand for effective strategies to manage these patients. Over the past 20 years, desensitization therapies have been modified and developed, and are mainly utilized at transplant centers that have developed expertise. In addition, recognition that the highly sensitized patient population is disadvantaged on the transplant waiting list has led to recent changes in national kidney allocation policy. Furthermore, creative strategies, such as enrollment of sensitized patients into paired kidney exchange programs, have been developed to find compatible matches for these patients. The goal of this article is to address some of the specific challenges related to transplanting the highly sensitized patient at a high-volume transplant center with experience in desensitization and to review established and emerging solutions to help this patient population. Keywords: human leukocyte antigen, antibodies, desensitization, high-dose intravenous immunoglobulin, rituximab

SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a putative binding partner of Nsp14. SIRT5 is an NAD-dependent protein deacylase critical for cellular metabolism that removes succinyl and malonyl groups from lysine residues. Here we investigated the nature of this interaction and the role of SIRT5 during SARS-CoV-2 infection. We showed that SIRT5 interacts with Nsp14, but not with Nsp10, suggesting that SIRT5 and Nsp10 are parts of separate complexes. We found that SIRT5 catalytic domain is necessary for the interaction with Nsp14, but that Nsp14 does not appear to be directly deacylated by SIRT5. Furthermore, knock-out of SIRT5 or treatment with specific SIRT5 inhibitors reduced SARS-CoV-2 viral levels in cell-culture experiments. SIRT5 knock-out cells expressed higher basal levels of innate immunity markers and mounted a stronger antiviral response, independently of the Mitochondrial Antiviral Signaling Protein MAVS. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions.

Abstract Situs inversus totalis (SIT) is not itself a premalignant condition, however, rare synchronous or metachronous multiple primary malignancies have been reported. Herein we present a case of synchronous transverse and sigmoid colon cancers and a case of metachronous rectosigmoid colon and gastric cancers in patients with SIT. A 66-year-old male with SIT was referred for a two-month history of hematochezia. Synchronous colonic tumors were found on the proximal transverse and sigmoid colon. The patient underwent open total colectomy and was discharged without incident. A 71-year-old female with rectosigmoid colon cancer and SIT underwent laparoscopy-assisted low anterior resection. Fourteen months after the surgery, the patient developed a single hepatic metastasis and underwent hepatic segmentectomy (S6). Forty-six months after laparoscopy-assisted low anterior resection, the patient developed metachronous early gastric cancer on the antrum and underwent radical subtotal gastrectomy with gastroduodenostomy. The patient is doing well without recurrence for 28 months.

Autophagy is a catabolic process through which cytoplasmic components are degraded and recycled in response to various stresses including starvation. Recently, transcriptional and epigenetic regulations of autophagy have emerged as essential mechanisms for maintaining homeostasis. Here, we identify that coactivator-associated arginine methyltransferase 1 (CARM1) methylates Pontin chromatin-remodeling factor under glucose starvation, and methylated Pontin binds Forkhead Box O 3a (FOXO3a). Genome-wide analyses and biochemical studies reveal that methylated Pontin functions as a platform for recruiting Tip60 histone acetyltransferase with increased H4 acetylation and subsequent activation of autophagy genes regulated by FOXO3a. Surprisingly, CARM1-Pontin-FOXO3a signaling axis can work in the distal regions and activate autophagy genes through enhancer activation. Together, our findings provide a signaling axis of CARM1-Pontin-FOXO3a and further expand the role of CARM1 in nuclear regulation of autophagy.

This paper introduces the VDR decomposition of Chebyshev-Vandermonde matrices, where V represents an ordinary Vandermonde matrix, D is diagonal, and R is upper triangular. Our motivation for this work stems from the study by Brubeck et al. [Vandermonde with Arnoldi. SIAM Rev. 2021;63(2):405–415]. We explore the VDR decomposition and combine it with a QR decomposition of V for Chebyshev-Vandermonde matrices. Furthermore, we demonstrate that the upper triangular factor in the QR decomposition can be recursively obtained from the upper Hessenberg matrix in the Arnoldi process. To compare our approach with the results obtained using the default QR code in Matlab, we present experimental results. Finally, we provide an algorithm for solving linear systems with Chebyshev-Vandermonde matrices as coefficient matrices, and experimental results for an upper bound on the relative error by applying an a posteriori error analysis for the computed solutions of the systems. [ABSTRACT FROM AUTHOR]

Copper (Cu) is widely used as an industrial electrode due to its high electrical conductivity, mechanical properties, and cost‐effectiveness. However, Cu is susceptible to corrosion, which degrades device performance over time. Although various methods (alloying, physical passivation, surface treatment, etc.) are introduced to address the corrosion issue, they can cause decreased conductivity or vertical insulation. Here, using the nitrogen‐doped amorphous carbon (a‐C:N) thin film is proposed as a substrate on which Cu is directly deposited. This simple method significantly inhibits corrosion of ultrathin Cu (<20 nm) films in humid conditions, enabling the fabrication of ultrathin electronic circuit boards without corrosion under ambient conditions. This study investigates the origin of corrosion resistance through comprehensive microscopic/spectroscopic characterizations and density‐functional theory (DFT) calculations: i) diffusion of Cu atoms into the a‐C:N driven by stable C‐Cu‐N bond formation, ii) diffusion of N atoms from the a‐C:N to the Cu layer heading the top surface, which is the thermodynamically preferred location for N, and iii) the doped N atoms in Cu layer suppress the inclusion of O into the Cu lattice. By leveraging the ultrathinness and deformability of the circuit board, a transparent electrode and a crumpleable LED lighting device are demonstrated. [ABSTRACT FROM AUTHOR]