Objective Measures of Gaze Behaviors and the Visual Environment during Near-Work Tasks in Young Adult Myopes and Emmetropes.

Purpose: To objectively quantify near-work gaze behaviors and the visual environment during reading tasks performed on a smartphone and on paper in both indoor and outdoor environments in myopes and emmetropes. Methods: A novel wearable gaze and viewing distance tracking device was used to quantify near-work gaze behaviors (focusing demand) and the visual environment (20° peripheral scene relative defocus) during a series of reading tasks. Data from nine myopes (mean age, 21 ± 1.4 years) and 10 emmetropes (21 ± 0.8 years) were analyzed. Five-minute reading tasks (matched for font type and size) were performed under four conditions: reading from a smartphone indoors, paper indoors, smartphone outdoors, and paper outdoors. Results: A significantly greater focusing demand (closer viewing distance) was found with smartphone-based reading (mean, 3.15 ± 0.74 D) compared to paper-based reading (2.67 ± 0.48 D) (P < 0.001), with the differences being greatest for myopic participants (P = 0.04). Smartphone reading was also associated with greater peripheral scene relative myopic defocus (P < 0.001). Although near-work behaviors were similar between environments, significantly more relative myopic defocus was found at the start of the paper-based task when performed outdoors compared to indoors (P = 0.02). Conclusions: Significant differences in focusing demand and scene relative defocus within a 20° field were found to be associated with reading tasks performed on a smartphone and paper in indoor and outdoor environments. Translational Relevance: These findings highlight the complex interaction between near-work behaviors and the visual environment and demonstrate that factors of potential importance to myopia development vary between paper-based and smartphone-based near tasks.

Genetic Predisposition to Persistent Human Papillomavirus-Infection and Virus-Induced Cancers.

Human papillomaviruses (HPVs) are the most common sexually transmitted pathogens worldwide and among the more than 200 identified HPV types, approximately 15 high risk (HR-HPV) types are oncogenic, being strongly associated with the development of cervical cancer, anogenital cancers and an increasing fraction of head and neck squamous cell carcinomas (HNSCC). HPV-associated cervix cancer accounts for 83% of HPV-attributable cancers, and more than two-thirds of those cases occur in developing countries. Despite the high frequency of HPV infections, in most cases, the virus is cleared by the host immune response and only a small proportion of infected individuals develop persistent infections that can result in malignant transformation, indicating that other elements, including biological, genetic and environmental factors may influence the individual susceptibility to HPV-associated cancers. Previous studies have quantified that heritability, in the form of genetic variants, common in the general population, is implicated in nearly 30% of cervical cancers and a large number of studies conducted across various populations have identified genetic variants that appear to be associated with genes that predispose or protect the host to HPV infections thereby affecting individual susceptibility to HPV-associated cancers. In this article, we provide an overview of gene association studies on HPV-associated cancers with emphasis on genome-wide association study (GWAS) that have identified novel genetic factors linked to HPV infection or HPV-associated cancers.

Fear-Related Reasons for Avoiding Sexual Intercourse in Early Pregnancy: A Cross-Sectional Study.

INTRODUCTION: Several studies have reported women's worry that sexual intercourse may harm the course of pregnancy. This worry might lead to avoidance of sexual intercourse during pregnancy. AIM: To assess if fears about harming the pregnancy are associated with avoidance of sexual intercourse during pregnancy. METHODS: A cross-sectional study was conducted on 250 Vietnamese pregnant women in the first or second trimester who visited our hospital for antenatal care. We explored 5 types of fears including miscarriage/preterm labor, premature rupture of membranes, bleeding, infection, and injury to the fetus. Fears were measured by modified questions from the Reasons For Not Engaging in Sexual Activity During Pregnancy questionnaire. Using the total fear score, pregnant women were categorized into having low, moderate, and high fear. MAIN OUTCOME MEASURE: Not having sexual intercourse during the past 4 weeks. RESULTS: 72 (28.8%) pregnant women had no sexual intercourse for the past 4 weeks. All types of fear were considered important among pregnant women; the more important fears were infection and injury to the fetus. In multivariable regression analysis, the prevalence of not having sexual intercourse was higher in both women who had moderate (adjusted prevalence ratio = 2.84, 95% CI 1.42-5.67) and high fear (adjusted prevalence ratio = 4.39, 95% CI 2.28-8.44). CONCLUSION: Avoidance of sexual intercourse was common among Vietnamese pregnant women and was associated with the fears about harming the pregnancy. This can be a target in the health education programs for pregnancy couples. Thanh C. Phan, Long B. Hoang, Thanh K. Tran, et al. Fear-Related Reasons for Avoiding Sexual Intercourse in Early Pregnancy: A Cross-Sectional Study. Sex Med 2021;9:100430.

Bimetallic Ag-Zn-BTC/GO composite as highly efficient photocatalyst in the photocatalytic degradation of reactive yellow 145 dye in water.

Agx-Zn100-x-BTC/GO composites (BTC: benzene-1,3,5-tricarboxylic, GO: graphene oxide) with different Ag/Zn molar ratios were synthesized using microwave-assisted hydrothermal treatment. The Agx-Zn100-x-BTC/GO exhibited excellent photocatalytic performance in the reactive yellow 145 dye (RY-145) degradation under irradiation of visible light with nearly 100% of RY-145 removal after 35 min, as compared to Zn-BTC/GO and Ag-BTC/GO. Reactive oxygen species scavenging assays have shown that the holes (h+) and superoxide radical anion (O2-•) play a primary role in RY-145 degradation. Based on the band structure of materials, the Z-scheme photocatalytic mechanism was suggested. The effect of catalyst dosage, pH and dye concentration on the efficiency of photocatalytic activity of bimetallic Ag50-Zn50-BTC/GO was also investigated. The improvement in photocatalytic activity of bimetallic Ag50-Zn50-BTC/GO could be given by the synergism of (i) absorption of visible light confirmed by UV-Vis diffuse reflectance spectra; (ii) the increased lifetime as evidenced by photoluminescence spectra and transient photocurrent response; (iii) the increased oxygen vacancy defects as confirmed by X-ray photoelectron spectroscopy results. The degradation pathway of RY-145 dye was also predicted based on liquid chromatography-mass spectrometer analysis. The removed chemical oxygen demand, biological oxygen demand, total organic carbon outcomes indicated the high mineralization ability for RY-145 degradation over Ag50-Zn50-BTC/GO.

Phenomic screen identifies a role for the yeast lysine acetyltransferase NuA4 in the control of Bcy1 subcellular localization, glycogen biosynthesis, and mitochondrial morphology.

Cellular metabolism is tightly regulated by many signaling pathways and processes, including lysine acetylation of proteins. While lysine acetylation of metabolic enzymes can directly influence enzyme activity, there is growing evidence that lysine acetylation can also impact protein localization. As the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 has been implicated in a variety of metabolic processes, we have explored whether NuA4 controls the localization and/or protein levels of metabolic proteins. We performed a high-throughput microscopy screen of over 360 GFP-tagged metabolic proteins and identified 23 proteins whose localization and/or abundance changed upon deletion of the NuA4 scaffolding subunit, EAF1. Within this, three proteins were required for glycogen synthesis and 14 proteins were associated with the mitochondria. We determined that in eaf1Δ cells the transcription of glycogen biosynthesis genes is upregulated resulting in increased proteins and glycogen production. Further, in the absence of EAF1, mitochondria are highly fused, increasing in volume approximately 3-fold, and are chaotically distributed but remain functional. Both the increased glycogen synthesis and mitochondrial elongation in eaf1Δ cells are dependent on Bcy1, the yeast regulatory subunit of PKA. Surprisingly, in the absence of EAF1, Bcy1 localization changes from being nuclear to cytoplasmic and PKA activity is altered. We found that NuA4-dependent localization of Bcy1 is dependent on a lysine residue at position 313 of Bcy1. However, the glycogen accumulation and mitochondrial elongation phenotypes of eaf1Δ, while dependent on Bcy1, were not fully dependent on Bcy1-K313 acetylation state and subcellular localization of Bcy1. As NuA4 is highly conserved with the human Tip60 complex, our work may inform human disease biology, revealing new avenues to investigate the role of Tip60 in metabolic diseases.

Correlation of ultra-high field MRI with histopathology for evaluation of rectal cancer heterogeneity.

Current clinical MRI techniques in rectal cancer have limited ability to examine cancer stroma. The differentiation of tumour from desmoplasia or fibrous tissue remains a challenge. Standard MRI cannot differentiate stage T1 from T2 (invasion of muscularis propria) tumours. Diffusion tensor imaging (DTI) can probe tissue structure and organisation (anisotropy). The purpose of this study was to examine DTI-MRI derived imaging markers of rectal cancer stromal heterogeneity and tumour extent ex vivo. DTI-MRI at ultra-high magnetic field (11.7 tesla) was used to examine the stromal microstructure of malignant and normal rectal tissue ex vivo, and the findings were correlated with histopathology. Images obtained from DTI-MRI (A0, apparent diffusion coefficient and fractional anisotropy (FA)) were used to probe rectal cancer stromal heterogeneity. FA provided the best discrimination between cancer and desmoplasia, fibrous tissue and muscularis propria. Cancer had relatively isotropic diffusion (mean FA 0.14), whereas desmoplasia (FA 0.31) and fibrous tissue (FA 0.34) had anisotropic diffusion with significantly higher FA than cancer (p < 0.001). Tumour was distinguished from muscularis propria (FA 0.61) which was highly anisotropic with higher FA than cancer (p < 0.001). This study showed that DTI-MRI can assist in more accurately defining tumour extent in rectal cancer.

Proteomic analysis defines kinase taxonomies specific for subtypes of breast cancer.

Multiplexed small molecule inhibitors covalently bound to Sepharose beads (MIBs) were used to capture functional kinases in luminal, HER2-enriched and triple negative (basal-like and claudin-low) breast cancer cell lines and tumors. Kinase MIB-binding profiles at baseline without perturbation proteomically distinguished the four breast cancer subtypes. Understudied kinases, whose disease associations and pharmacology are generally unexplored, were highly represented in MIB-binding taxonomies and are integrated into signaling subnetworks with kinases that have been previously well characterized in breast cancer. Computationally it was possible to define subtypes using profiles of less than 50 of the more than 300 kinases bound to MIBs that included understudied as well as metabolic and lipid kinases. Furthermore, analysis of MIB-binding profiles established potential functional annotations for these understudied kinases. Thus, comprehensive MIBs-based capture of kinases provides a unique proteomics-based method for integration of poorly characterized kinases of the understudied kinome into functional subnetworks in breast cancer cells and tumors that is not possible using genomic strategies. The MIB-binding profiles readily defined subtype-selective differential adaptive kinome reprogramming in response to targeted kinase inhibition, demonstrating how MIB profiles can be used in determining dynamic kinome changes that result in subtype selective phenotypic state changes.

Characteristic expression of fukutin in gastric cancer among atomic bomb survivors.

Approximately 70 years have passed since the atomic bombs were dropped on Nagasaki and Hiroshima. To elucidate potential biomarkers and possible mechanisms of radiation-induced cancer, the expression of FKTN, which encodes fukutin protein and causes Fukuyama-type congenital muscular dystrophy, was analyzed in gastric cancer (GC) tissue samples from atomic bomb survivors. Expression of cluster of differentiation (CD) 10 was also evaluated, as it has previously been observed that positive fukutin expression was frequently noted in CD10-positive GC cases. In the first cohort from Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital (Hiroshima, Japan; n=92), 102 (53%) of the GC cases were positive for fukutin. Expression of fukutin was not associated with exposure status, but was associated with CD10 expression (P=0.0001). The second cohort was from Hiroshima University Hospital (Hiroshima, Japan; n=86), and these patients were also in the Life Span Study cohort, in which atomic bomb radiation doses were precisely estimated using the DS02 system. Expression of fukutin was detected in 58 (67%) of GC cases. GC cases positive for fukutin were observed more frequently in the low dose-exposed group than in the high dose-exposed group (P=0.0001). Further studies with a larger cohort, including precise radiation dose estimation, may aid in clarifying whether fukutin could serve as a potential biomarker to define radiation-induced GC in atomic-bomb survivors.

Functional MRI for quantitative treatment response prediction in locally advanced rectal cancer.

Despite advances in multimodality treatment strategies for locally advanced rectal cancer and improvements in locoregional control, there is still a considerable variation in response to neoadjuvant chemoradiotherapy (CRT). Accurate prediction of response to neoadjuvant CRT would enable early stratification of management according to good responders and poor responders, in order to adapt treatment to improve therapeutic outcomes in rectal cancer. Clinical studies in diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have shown promising results for the prediction of therapeutic response in rectal cancer. DWI allows for assessment of tumour cellularity. DCE-MRI enables evaluation of factors of the tumour microvascular environment and changes in perfusion in response to treatment. Studies have demonstrated that predictors of good response to CRT include lower tumour pre-CRT apparent diffusion coefficient (ADC), greater percentage increase in ADC during and post CRT, and higher pre-CRT Ktrans. However, the mean ADC and Ktrans values do not adequately reflect tumour heterogeneity. Multiparametric MRI using quantitative DWI and DCE-MRI in combination, and a histogram analysis technique can assess tumour heterogeneity and its response to treatment. This strategy has the potential to improve the accuracy of therapeutic response prediction in rectal cancer and warrants further investigation.

A functional polymorphism in the NKG2D gene modulates NK-cell cytotoxicity and is associated with susceptibility to Human Papilloma Virus-related cancers.

Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide and is etiologically linked to several cancers, including cervical and genital cancers. NKG2D, an activating receptor expressed by NK cells, plays an important role in cancer immune-surveillance. We analyzed the impact of a NKG2D gene variant, rs1049174, on the incidence of HPV-related cancers in Vietnamese patients and utilized various molecular approaches to elucidate the mechanisms of NKG2D receptor regulation by rs1049174. In a group of 123 patients with HPV+ anogenital cancers, the low cytotoxicity allele LNK was significantly associated with increased cancer susceptibility (p = 0.016). Similar results were also observed in a group of 153 women with cervical cancer (p = 0.05). In functional studies, NK cells from individuals with LNK genotype showed a lower NKG2D expression and displayed less efficient NKG2D-mediated functions than NK cells with HNK genotype. Notably, the rs1049174 variant occurs within a targeting site for miR-1245, a negative regulator of NKG2D expression. Compared with the higher cytotoxicity allele HNK, the LNK allele was more efficiently targeted by miR-1245 and thus determined lower NKG2D expression in NK cells with the LNK genotype. The NKG2D variants may influence cancer immunosurveillance and thus determine susceptibility to various malignancies, including HPV-induced cancers.

Induction of KIFC1 expression in gastric cancer spheroids.

Gastric cancer (GC) is one of the most common human cancers. Spheroid colony formation is an effective model for characterization of cancer stem cells. However, gene expression profiles of spheroid colonies obtained from GC cells have not been examined. We performed microarray analyses by Human Genome U133 Plus 2.0 Array in spheroid body-forming and parental cells from MKN-45 and MKN-74 GC cell lines. Kinesin family member C1 (KIFC1) was expressed >2-fold higher in spheroid body-forming cells than in parental cells in both GC lines. Both the number and size of spheres from MKN-45 cells were significantly reduced upon KIFC1 siRNA-transfection compared with negative control siRNA-transfection. Immunohistochemical analysis of 114 GC tissue samples revealed that 42 (37%) of GC cases were positive for KIFC1 expression. GC cases positive for KIFC1 were found more frequently in stage III/IV cases than in stage I/II cases. GC cases positive for KIFC1 were found more frequently in intestinal type GC cases than in diffuse type GC cases. Furthermore, KIFC1-positive GC cases showed high Ki-67 labeling index. Kaplan-Meier analysis demonstrated that KIFC1 expression was not associated with survival. We found positive expression of KIFC1 in CD44­positive GC and aldehyde dehydrogenase 1 (ALDH1)-positive GC cells. Our results showed that KIFC1 is overexpressed in GC. Since knockdown of KIFC1 inhibited sphere formation, KIFC1 likely plays an important role in cancer stem cells.

Left-sided breast cancer loco-regional radiotherapy with deep inspiration breath-hold: Does volumetric-modulated arc radiotherapy reduce heart dose further compared with tangential intensity-modulated radiotherapy?

INTRODUCTION: Left-sided breast cancer radiotherapy has been associated with an increase in cardiac mortality. This study investigated the potential heart-sparing effect of volumetric-modulated arc radiotherapy (VMAT). We compared VMAT to tangential intensity-modulated radiotherapy (t-IMRT) in the loco-regional treatment of left-sided breast cancer, including internal mammary nodal irradiation, based on deep inspiration breath-hold (DIBH) and free-breathing (FB). METHODS: Radiotherapy for 15 patients was re-planned. Four plans were compared: t-IMRT-DIBH; VMAT-DIBH; t-IMRT-FB; VMAT-FB. Prescribed dose was 50 Gy in 25 fractions. T-IMRT plans were generated using tangentially orientated fields. VMAT plans were generated using two partial arcs (average arc 190°). RESULTS: Mean heart dose (MHD) was 5 ± 2.4 Gy, 5.7 ± 1.4 Gy, 9.7 ± 3.3 Gy and 8.1 ± 2.0 Gy for t-IMRT-DIBH, VMAT-DIBH, IMRT-FB and VMAT-FB respectively. The difference in MHD between IMRT-DIBH and VMAT-DIBH was not significant (P = 0.14). VMAT-DIBH significantly spared the volume of heart irradiated to doses of 20 Gy and above (p < 0.05), however, resulted in a significantly higher V5 Gy (P < 0.001), compared to t-IMRT-DIBH. VMAT-DIBH resulted in higher combined lung mean (11 ± 0.8 Gy vs. 8.8 ± 1.1 Gy, P < 0.001) and higher contralateral breast mean dose (5 ± 1 Gy vs. 1.6 ± 1.2 Gy, P < 0.001) compared with t-IMRT-DIBH. CONCLUSIONS: On average, there was no significant difference in MHD between VMAT-DIBH and t-IMRT-DIBH. However, VMAT-DIBH was found to benefit a select group of patients. For patients in whom the MHD was >6.3 Gy with t-IMRT-DIBH, the use of VMAT-DIBH resulted in a benefit in reducing the MHD.

Characteristic miR-24 Expression in Gastric Cancers among Atomic Bomb Survivors.

OBJECTIVE: To elucidate the mechanism of radiation-induced cancers, we analyzed the expression profiles of microRNAs extracted from formalin-fixed paraffin-embedded (FFPE) gastric cancer (GC) tissue samples from atomic bomb survivors. METHODS: The expression levels of miR-21, miR-24, miR-34a, miR-106a, miR-143, and miR-145 were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The expression of microRNAs was measured by qRT-PCR in a Hiroshima University Hospital cohort comprising 32 patients in the high-dose-exposed group and 18 patients in the low-dose-exposed group who developed GC after the bombing. The GC cases showing high expression of miR-24, miR-143, and miR-145 were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. We next performed qRT-PCR of miR-24, miR-143, and miR-145 in a cohort from the Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital comprising 122 patients in the high-dose-exposed group and 48 patients in the low-dose-exposed group who developed GC after the bombing. High expressions of miR-24 and miR-143 were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. Multivariate analysis demonstrated that only high expression of miR-24 was an independent predictor for the exposure status. CONCLUSION: These results suggest that the measurement of miR-24 expression from FFPE samples is useful to identify radiation-associated GC.

MAP3K1: Genomic Alterations in Cancer and Function in Promoting Cell Survival or Apoptosis.

MAP3K1 is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family of serine/threonine kinases. MAP3K1 regulates JNK activation and is unique among human kinases in that it also encodes an E3 ligase domain that ubiquitylates c-Jun and ERK1/2. Full length MAP3K1 regulates cell migration and contributes to pro-survival signaling while its caspase 3-mediated cleavage generates a C-terminal kinase domain that promotes apoptosis. The critical function of MAP3K1 in cell fate decisions suggests that it may be a target for deregulation in cancer. Recent large-scale genomic studies have revealed that MAP3K1 copy number loss and somatic missense or nonsense mutations are observed in a significant number of different cancers, being most prominent in luminal breast cancer. The alteration of MAP3K1 in diverse cancer types demonstrates the importance of defining phenotypes for possible therapeutic targeting of tumor cell vulnerabilities created when MAP3K1 function is lost or gained.

The carbonic anhydrase isoforms of Chlamydomonas reinhardtii: intracellular location, expression, and physiological roles.

Aquatic photosynthetic organisms, such as the green alga Chlamydomonas reinhardtii, respond to low CO(2) conditions by inducing a CO(2) concentrating mechanism (CCM). Carbonic anhydrases (CAs) are important components of the CCM. CAs are zinc-containing metalloenzymes that catalyze the reversible interconversion of CO(2) and HCO(3)(-). In C. reinhardtii, there are at least 12 genes that encode CA isoforms, including three alpha, six beta, and three gamma or gamma-like CAs. The expression of the three alpha and six beta genes has been measured from cells grown on elevated CO(2) (having no active CCM) versus cells growing on low levels of CO(2) (with an active CCM) using northern blots, differential hybridization to DNA chips and quantitative RT-PCR. Recent RNA-seq profiles add to our knowledge of the expression of all of the CA genes. In addition, protein content for some of the CA isoforms was estimated using antibodies corresponding to the specific CA isoforms: CAH1/2, CAH3, CAH4/5, CAH6, and CAH7. The intracellular location of each of the CA isoforms was elucidated using immunolocalization and cell fractionation techniques. Combining these results with previous studies using CA mutant strains, we will discuss possible physiological roles of the CA isoforms concentrating on how these CAs might contribute to the acquisition and retention of CO(2) in C. reinhardtii.

Desmoplastic neurotropic melanoma: a clinicopathologic analysis of 128 cases.

BACKGROUND: Several studies have suggested that desmoplastic neurotropic melanoma (DNM) is associated with higher local recurrence rates than other types of melanoma. The authors investigated the local recurrence rates for patients with DNM after surgery alone or surgery followed by radiotherapy (RT). METHODS: One hundred twenty-eight patients with DNM were treated at the Sydney Melanoma Unit and the Sydney Cancer Center from 1996 to 2007. All patients underwent local excision, 27 patients also received RT. For both groups, clinical and pathologic features, treatment details, and local recurrence data were analyzed. RESULTS: The median age at diagnosis was 65.5 years. The ratio of men to women was 2.7:1. The head and neck was the most common location (51%). The median Breslow thickness was 4 mm, and 99% of patients had Clark Level IV or V primary tumors. Patients who received adjuvant RT had thicker tumors (P = .003), deeper Clark level invasion (P < .001), and narrower excision margins (P < .001). There were 8 local recurrences, including 6 (6%) in the surgery only group and 2 (7%) in the adjuvant RT group. A positive margin (P < .001) and head and neck location (P = .03) were significant predictors of local recurrence. CONCLUSIONS: The local recurrence rate in this series was lower than the rates reported in historic control groups and in the authors' previous temporal cohort. The results indicated that clear surgical margins are of paramount importance in minimizing local recurrence; when margins are compromised, the addition of RT may reduce local recurrence rates compared with historic controls. A prospective randomized trial is needed to quantify the risk reduction with adjuvant RT.