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This nested case-control study in the NIH-AARP Diet and Health Study was carried out to prospectively investigate the relationship of oral microbiome with head and neck cancer (HNC).56 incident HNC cases were identified, and 112 controls were incidence-density matched to cases. DNA extracted from pre-diagnostic oral wash samples was whole-genome shotgun metagenomic sequenced to measure the overall oral microbiome. ITS2 gene qPCR was used to measure the presence of fungi. ITS2 gene sequencing was performed on ITS2 gene qPCR positive samples. We computed taxonomic and functional alpha-diversity and beta-diversity metrics. The presence and relative abundance of groups of red-complex (e.g., Porphyromonas gingivalis) and/or orange-complex (e.g., Fusobacterium nucleatum) periodontal pathogens were compared between cases and controls using conditional logistic regression models and MiRKAT.Participants with higher taxonomic microbial alpha-diversity had a non-statistically significant decreased risk of HNC. No case-control differences were found for beta diversity by MiRKAT model (all p 0.05). A greater relative abundance of red-complex periodontal pathogens (OR = 0.51, 95 % CI = 0.26-1.00), orange-complex (OR = 0.38, 95 % CI = 0.18-0.83), and both complexes' pathogens (OR = 0.32, 95 % CI = 0.14-0.75), were associated with reduced risk of HNC. The presence of oral fungi was also strongly associated with reduced risk of HNC compared with controls (OR = 0.39, 95 % CI = 0.17-0.92).Greater taxonomic alpha-diversity, the presence of oral fungi, and the presence or relative abundance of multiple microbial species, including the red- and orange-complex periodontal pathogens, were associated with reduced risk of HNC. Future studies with larger sample sizes are needed to evaluate these associations.

Purpose Mutations in hereditary breast cancer genes play an important role in the risk for cancer. Methods Cancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome. Results A total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6. The high ratio of BRCA1/BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P P = 0.038) or breast cancer (33% vs 15%, P Conclusions Hereditary breast cancer mutations were observed among Guatemalan women, and these women are more likely to have early age at diagnosis and family history of cancer. These data suggest the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

It is challenging to identify somatic variants from high-throughput sequence reads due to tumor heterogeneity, sub-clonality, and sequencing artifacts. In this study, we evaluated the performance of eight primary somatic variant callers and multiple ensemble methods using both real and synthetic whole-genome sequencing, whole-exome sequencing, and deep targeted sequencing datasets with the NA12878 cell line. The test results showed that a simple consensus approach can significantly improve performance even with a limited number of callers and is more robust and stable than machine learning based ensemble approaches. To fully exploit the multi-callers, we also developed a software package, SomaticCombiner, that can combine multiple callers and integrates a new variant allelic frequency (VAF) adaptive majority voting approach, which can maintain sensitive detection for variants with low VAFs.

Abstract Background: Mutations in hereditary breast cancer genes play an essential role in cancer risk. Little is known of the type and frequency of mutations in Hispanic populations in the United States and Central American countries, including Guatemala. Methods: We used exome sequencing to identify mutations in blood DNA from unselected Hispanic breast cancer cases from community recruitment and from two hospitals each in Texas and Guatemala. Data from a structured questionnaire was used to compare mutation carriers of medium and high penetrance genes. Variants were annotated with ClinVar and VarSome. Results: We recruited 262 Hispanic US women, 37 (14%) from community-based recruitment and 225 (86%) from hospitals in Texas. In addition, we ascertained 633 patients from two hospitals in Guatemala City. A total of 91 out of 895 subjects (10%) had a variant classified as pathogenic in a gene with known high or medium penetrance for inherited breast cancer. The most frequently mutated genes were the high penetrance BRCA1 (44/895, 4.9%) followed by BRCA2 (23/895, 2.6%), PALB2 (5/895, 0.6%), CHEK2 (5/895 0.6%), ATM (6/895, 0.7%) and TP53 (6/895, 0.7%). Pathogenic variants were also detected in the moderate penetrance genes BARD1 and MSH6, and rare pathogenic variants detected in the low penetrance genes AXIN2, FH, MLH1, MSH2, MUTYH, NF1, and SDHB. The high ratio of BRCA1/BRCA2 mutations is due to the presence of two potential founder mutations, BRCA1 c.212+1G>A splice mutation (18 cases) and BRCA1 c.799delT (9 cases) in Guatemala. Compared to all others, cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs. 52 years, P Conclusions: Guatemalan women have rates of hereditary breast cancer mutations like other populations, and these women are more likely to have early age at diagnosis, triple-negative disease, and family history. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Hispanic women. Citation Format: Jesica Godinez Paredes, Isabel Rodriguez, Megan Ren, Anali Orozco, Jeremy Ortiz, Anaseidy Albanez, Catherine Jones, Zeina Nahleh, Lilian Barreda, Lisa Garland, Dongjing Wu, Jiahui Wang, Victor Argueta, Roberto Orozco, Eduardo Gharzouzi, Michael Dean. Germline mutations in breast cancer genes are associated with early age of diagnosis and triple negative disease in Guatemalan and US Hispanic women [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 1938.

PURPOSE Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all pediatric cancer. In this study, we investigated germline sequence and structural variation in a broad set of genes in two large, independent RMS cohorts. MATERIALS AND METHODS Genome sequencing of the discovery cohort (n = 273) and exome sequencing of the secondary cohort (n = 121) were conducted on germline DNA. Analyses were performed on 130 cancer susceptibility genes (CSG). Pathogenic or likely pathogenic (P/LP) variants were predicted using the American College of Medical Genetics and Genomics (ACMG) criteria. Structural variation and survival analyses were performed on the discovery cohort. RESULTS We found that 6.6%-7.7% of patients with RMS harbored P/LP variants in dominant-acting CSG. An additional approximately 1% have structural variants ( ATM, CDKN1C) in CSGs. CSG variants did not influence survival, although there was a significant correlation with an earlier age of tumor onset. There was a nonsignificant excess of P/LP variants in dominant inheritance genes in the patients with FOXO1 fusion–negative RMS patients versus the patients with FOXO1 fusion–positive RMS. We identified pathogenic germline variants in CSGs previously ( TP53, NF1, DICER1, mismatch repair genes), rarely ( BRCA2, CBL, CHEK2, SMARCA4), or never ( FGFR4) reported in RMS. Numerous genes ( TP53, BRCA2, mismatch repair) were on the ACMG Secondary Findings 2.0 list. CONCLUSION In two cohorts of patients with RMS, we identified pathogenic germline variants for which gene-specific therapies and surveillance guidelines may be beneficial. In families with a proband with an RMS-risk P/LP variant, genetic counseling and cascade testing should be considered, especially for ACMG Secondary Findings genes and/or with gene-specific surveillance guidelines.

BackgroundMutations in hereditary breast cancer genes play an important role in the risk for cancer, however, little is known of the type and frequency of mutations in Central American populations, including Guatemala.MethodsTwo separate panels of known cancer susceptibility genes were used to sequence blood DNA from 664 unselected breast cancer cases from two large hospitals in Guatemala. Variants were annotated with ClinVar and VarSome. Data from a structured questionnaire was used to compare mutation carriers of medium and high penetrance genes.ResultsA total of 73 out of 664 subjects (11%) had a variant classified as pathogenic in a gene with known high or medium penetrance for inherited breast cancer. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%) and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6, and rare pathogenic variants detected in the low penetrance genes AXIN2, FH, MLH1, MSH2, MUTYH, NF1, and SDHB. The high ratio of BRCA1/BRCA2 mutations is due to the presence of two potential founder mutations, BRCA1 c.212+1G>A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Compared to all others, cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, PConclusionsGuatemalan women have rates of hereditary breast cancer mutations similar to other populations, and these women are more likely to have early age at diagnosis and family history. This data supports the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

Mutations in hereditary breast cancer genes play an important role in the risk for cancer. Cancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome. A total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6. The high ratio of BRCA1/BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P

Optical vortices carrying orbital angular momentum (OAM) have attracted extensive attention in recent decades because of their interesting applications in optical trapping, optical machining, optical communication, quantum information, and optical microscopy. Intriguing effects induced by OAMs, such as angular momentum conversion, spin Hall effect of light (SHEL), and spin–orbital interaction, have also gained increasing interest. In this article, we provide an overview of the modulations of OAMs on the propagation dynamics of scalar and vector fields in free space. First, we introduce the evolution of canonical and noncanonical optical vortices and analyze the modulations by means of local spatial frequency. Second, we review the Pancharatnam–Berry (PB) phases arising from spin–orbital interaction and reveal the control of beam evolution referring to novel behavior such as spindependent splitting and polarization singularity conversion. Finally, we discuss the propagation and focusing properties of azimuthally broken vector vortex beams.

Background and aims Guatemala has the highest incidence of hepatocellular carcinoma (HCC) in the Western hemisphere. The major risk factors in Guatemala are not well characterized, but the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) appears to be low, while the prevalence of aflatoxin (AFB1) exposure appears to be high. To examine whether AFB1 may contribute to the elevated incidence of HCC in Guatemala, this study examined the frequency of the AFB1‐signature mutation in the TP53 gene (R249S) as well as other somatic mutations. In addition, we assessed whether the frequency of the TP53 mutation differed by sex. Methods Formalin‐fixed, paraffin‐embedded (FFPE) HCC tissues were obtained from three hospitals in Guatemala City between 2016 and 2017. In addition, tumor tissues preserved in RNAlater were also obtained. Sociodemographic and clinical information including HBV and HCV status were collected. Targeted sequencing of TP53 was performed in the FFPE samples, and a panel of 253 cancer‐related genes was sequenced in the RNAlater samples. Results Ninety‐one FFPE tissues were examined, from 52 men and 39 women. Median (IQR) age at diagnosis was 62 (51‐70). Among those with known HBV and HCV status, two were HBV+ and three were HCV+. Overall, 47% of the HCCs had a TP53 mutation. The AFB1‐signature R249S mutation was present in 24%. No overlap between the R249S mutation and HBV+ was observed in this cohort. Among 18 RNAlater samples examined, 44% had any TP53 mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes. Conclusions The presence of the TP53 R249S mutation in the samples studied suggests that AFB1 may contribute to the high incidence of HCC in Guatemala. The proportion of HBV+ tumors was low, suggesting that AFB1 may be associated with HCC in the absence of concomitant HBV infection. Further investigation of AFB1 and other risk factors for HCC in Guatemala is warranted.

Background: Epidemiological data regarding the regional differences in chronic pancreatitis (CP) from the mainland of China is lacking. We aimed to gather and combine the information concerning the regional distribution, diagnosis and treatment of CP, in addition to the risk factors associated with pancreatic cancer (PaCa) and death from published articles. Methods: Case articles on CP published in three English and four Chinese databases from January 1979 to December 2018 were analysed. Findings: A total of 4,452 cases articles (containing 161,243 CP cases) were included. Almost all relevant departments of 1,557 hospitals participated in the writing of CP articles and approximately 67.2% of hospitals wrote only one article. The etiologies, symptoms, treatments, and number of cases with PaCa varied from region to region. Surgical treatment was more common in underdeveloped areas. Endoscopic therapy was mainly concentrated in developed areas and was also associated with non-alcoholic CP. PaCa detected during hospitalization was mainly related to jaundice (r = 0.35, P = 0.000), pain (r = 0.31, P = 0.000), diabetes (r = 0.20, P = 0.000), biliary diseases (r = 0.36, P = 0.000), alcoholic CP (r = 0.30, P = 0.000), conservative treatment (r = 0.37, P = 0.000) and surgical treatment (r = 0.21, P = 0.000). PaCa detected during follow-up was primarily associated with idiopathic CP (r = 0.26, P = 0.000), alcoholic CP (r = 0.23, P = 0.000), endoscopy therapy (r = 0.3, P = 0.000) and surgical treatment (r = 0.24, P = 0.000). Death during hospitalization was only related to surgery. Interpretation: Many regions have gradually formed their own unique characteristics in terms of the diagnosis and treatment of CP. However, the level of diagnosis and treatment of CP in many areas still needs to be improved. The problem of uneven distribution of medical resources needs to be resolved. Funding Statement: None. Declaration of Interests: The authors declare that there are no competing interests associated with the manuscript.

Simultaneously controlling the spatial distribution of multiple parameters of a light field in a three-dimensional (3D) space is highly desirable because of its prominent applications in the areas of optical imaging, microscopy, and manipulation. Phase-only encoding techniques that use a phase-only computer-generated hologram (CGH) to reshape and efficiently reconstruct target fields have fostered substantial interests. In this paper, we propose a convenient encoding method to construct vector fields with spatially structured multiple parameters in a 3D space by integrating the Fourier phase-only encoding technique into a modified Sagnac polarization conversion system. Without spatial filtering, various vector fields are constructed instantly at the image plane. Furthermore, utilizing a macro-pixel encoding approach, we demonstrate the possibility of a simultaneous and an independent construction of multiple vector fields in a 3D space. This method can also benefit the design of a metasurface to implement a polarization hologram.

Background Guatemala has the highest incidence of hepatocellular carcinoma (HCC), the dominant type of liver cancer, in the Western Hemisphere. The major risk factors in Guatemala are not well-characterized, but the prevalence of hepatitis B (HBV) and hepatitis C virus (HCV) appear to be low, while the prevalence of aflatoxin (AFB 1 ) exposure appears to be high. To examine whether AFB 1 could be a risk factor for HCC in Guatemala, this study examined the frequency of the AFB 1 -signature mutation in the TP53 gene (R249S) as well as other somatic mutations.Methods Ninety-one formalin-fixed, paraffin-embedded (FFPE) HCC tissues were obtained from three hospitals in Guatemala City. An additional, eighteen tumor tissues preserved in RNAlater were also obtained. Targeted sequencing of TP53 was successfully performed in 89 of the FFPE samples, and a panel of 245 genes were sequenced in the RNAlater samples.Results Overall, 47% of HCCs had a TP53 mutation. The AFB 1 -signature R249S mutation was present in 24%. Among the RNAlater samples, 44% had any TP53 mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes such as ARID1A , ARID2 , and CTNNB1 .Conclusions The presence of the TP53 R249S mutation indicates that AFB 1 is a risk factor for HCC in Guatemala. The proportion of HBV positive tumors was low, suggesting that AFB 1 is associated with HCC in the absence of concomitant HBV infection. To decrease the risk of HCC in Guatemala, AFB 1 abatements efforts are warranted.

Optical activity (OA) is the rotation of the polarization orientation of the linearly polarized light as it travels through certain materials that are of mirror asymmetry, including gases or solutions of chiral molecules such as sugars and proteins, as well as metamaterials. The necessary condition for achieving OA is the birefringence of two circular polarizations in material. Here, we propose a new kind of self-accelerated OA in free space, based on the intrinsic Gouy phase induced mode birefringence of two kinds of quasi-non-diffracting beams. We provide a detailed insight into this kind of self-accelerated OA by analyzing angular parameters, including angular direction, velocity, acceleration, and even the polarization transformation trajectory. As the Gouy phase exists for any wave, this kind of self-accelerated OA can be implemented in other waves beyond optics, from acoustic and elastic waves to matter waves.

At present, LLC resonant converters are mostly used in step-down situations. The reason why LLC resonant converters are not used in high step-up situations is that parasitic parameters caused by high turn-to-turn ratio of transformers affect the circuit and the large current stress of switching devices and resonant components on the input side. In this paper, a new type of LLC resonant converter circuit, i.e. input parallel output series subside resonant LLC resonant converter, is designed. It can not only reduce the current stress borne by the switching devices on the input side and the resonant components, but also reduce the turn-to-turn ratio of the transformer under the same output voltage. Therefore, it can be used in boost occasion to output high voltage. In this paper, a new type of circuit is used in high boost situation, and the final output is stable 2KV high voltage.

Optical singularities, including phase and polarization singularities that are prevalent in vortex beams, cylindrical vector beams, and cylindrical vector vortex beams, were widely investigated in the past few decades because of their physical and application interest. Here, we propose a method for measuring the singularities within these cylindrically structured light beams by using a radial grating (RG), which is fabricated by etching patterns on the chrome plated soda-lime glass and exhibits a broadband performance. We demonstrate the versatility and compatibility of the measuring method by obtaining the topological charge and polarization order that characterize the phase and polarization singularity, respectively. The reliability of the RG was also inspected by analyzing the grating period and the illumination location of the input field on it.

Polarization oscillating beams, namely, polarization standing waves, commonly formed by a pair of coherent counterpropagating light waves with orthogonal polarizations, oscillate their states of polarization periodically within a wavelength interval, offering conceptual and practical interests in light-matter interactions such as the nonreciprocal magnetoelectric effect, and impressive applications in optical imaging, sensing, and chirality detection. Here, we propose a new class of polarization oscillating beams that longitudinally vary states of polarization with spatial intervals within centimeters via the superposition of two copropagating optical frozen waves with preshaped longitudinal intensity profiles and transverse phase structures. The flexibility and manipulability are demonstrated by creating several polarization oscillating beams with different polarization structures. This work paves a new way to manipulate other waves and may be useful for applications of optical standing waves in optical manipulation, light guiding of atoms, polarization-sensitive sensing, etc.

We propose an efficient and robust method to generate tunable vector beams by employing a single phase-type spatial light modulator (SLM). With this method, a linearly polarized Gaussian beam can be converted into a vector beam with arbitrarily controllable polarization state, phase, and amplitude. The energy loss during the conversion is greatly reduced and depends mainly on the reflectivity of the SLM. We experimentally demonstrate that conversion efficiency of about 47% is achieved by using an SLM with reflectivity of 62%. Several typical vector beams, including cylindrical vector beams, vector beams on higher order Poincare spheres, and arbitrary vector beams attached with phases and with tunable amplitude, are generated and verified experimentally. This method is also expected to create high-power vector beams and play important roles in optical fabrication and light trapping.

We propose a generalized model for the creation of vector Bessel-Gauss (BG) beams having state of polarization (SoP) varying along the propagation direction. By engineering longitudinally varying Pancharatnam-Berry (PB) phases of two constituent components with orthogonal polarizations, we create zeroth- and higher-order vector BG beams having (i) uniform polarizations in the transverse plane that change along z following either the equator or meridian of the Poincaré sphere and (ii) inhomogeneous polarizations in the transverse plane that rotate during propagation along z. Moreover, we evaluate the self-healing capability of these vector BG beams after two disparate obstacles. The self-healing capability of spatial SoP information may enrich the application of BG beams in light-matter interaction, polarization metrology and microscopy.

As an official rule for healthcare privacy and security, Health Insurance Portability and Accountability Act (HIPAA) requires security services supporting implementation features: Access control; Audit controls; Authorization control; Data authentication; and Entity authentication. Audit controls proposed by HIPPA Security Standards are audit trails, which audit activities, to assess compliance with a secure domain's policies, to detect instances of non-compliant behavior, and to facilitate detection of improper creation, access, modification and deletion of Protected Health Information (PHI). Although current medical imaging systems generate activity logs, there is a lack of regular description to integrate these large volumes of log data into generating HIPPA compliant auditing trails. The paper outlines the design of a HIPAA's compliant auditing system for medical imaging system such as PACS and RIS and discusses the development of this security monitoring system based on the Supplement 95 of the DICOM standard: Audit Trail Messages.