A Thread In Japan’s History: The Historical Journey Of Japanese Christianity to the Brink of Modern Japan

A Jesuit missionary named Francis Xavier pioneered the Christian faith in Japan in 1549. Japan was open to the gospel, and many missionaries followed Francis Xavier. Japanese people from a wide range of social standings supported Christianity for a variety of reasons. The Tokugawa government soon viewed Christianity as a threat to the authority of the Japanese government. Japan persecuted the Christians and the Japanese church was driven underground. Over two hundred years later during the Meiji Restoration, Japan altered its policies towards the West and tolerated Christianity in Japan. Despite never being fully welcomed, the Christian belief resonated with many well-educated Japanese men. Some of the most well educated men in Japan became Christians and their work influenced the formation of Japan during a crucial time in its history. These men’s goal to develop Christianity in Japan helped shape Japan as a nation and develop Modern Japan

The Effects of Superovulation and Embryo Culture on Genomic Imprinting in a Mouse Model System

Genomic imprinting is a specialized transcriptional mechanism resulting in the unequal expression of alleles based on their parent-of-origin. Imprinted genes are critical for embryonic and fetal development and their dysregulation is linked to a group of human diseases called imprinting disorders, including Beckwith-Wiedemann Syndrome, Angelman Syndrome and Silver-Russell Syndrome. Two critical phases of genomic imprinting exist. The acquisition phase occurs in developing germ cells, asynchronously for different imprinted loci, while the maintenance phase takes place during preimplantation development, while the rest of the genome is undergoing demethylation. Increased frequencies of human imprinting disorders are observed in children following the use of assisted reproductive technologies (ARTs). The timing of ARTs during the critical periods of imprint acquisition and maintenance provides a mechanism for their disruption. At the onset of this project, I hypothesized that superovulation alone, and embryo culture alone, disrupt imprinting acquisition and maintenance mechanisms, respectively, and that disruption of genomic imprinting correlates with rates of preimplantation embryo development. I have determined the effects of superovulation, and embryo culture using five commercially available media, on the key imprinted loci H19, Snrpn, Peg3, Kcnq1ot1 and Peg1/Mest, and correlated rates of preimplantation development with loss of genomic imprinting. Superovulation alone disrupted genomic imprinting, in a dose-dependent manner. Embryo culture in all media was sub-optimal in maintaining genomic imprints. Embryos developing at a moderate pace showed levels of imprinted methylation most similar to in vivo-derived controls. In addition, these studies suggest that superovulation does not affect the acquisition of imprinted methylation, but rather maintenance throughout preimplantation development. Data presented in this thesis suggests that superovulation disrupts one or more key maternal-effects genes necessary for imprint maintenance, and that superovulation and embryo culture disrupt the same pathway. Future studies delineating the mechanisms mediating embryonic adaptation to the environmental insult caused by ARTs, and improving current techniques to minimize the amount of adaptation required for embryo growth and survival outside the female reproductive tract, will lead to a decreased incidence of disease and improve the long term health of children born following ARTs

Do cheerfulness, exhilaration, and humor production moderate pain tolerance? A FACS study

Prior studies have shown that watching a funny film leads to an increase in pain tolerance. The present study aimed at separating three factors considered potentially essential (mood, behavior, and cognition related to humor) and examined whether they are responsible for this effect. Furthermore, the study examined whether trait cheerfulness and trait seriousness, as measured by the State-Trait-Cheerfulness-Inventory (STCI; Ruch et al. 1996), moderate changes in pain tolerance. Fifty-sixty female subjects were assigned randomly to three groups, each having a different task to pursue while watching a funny film: (1) get into a cheerful mood without smiling or laughing ("Cheerfulness"); (2) smile and laugh extensively ("Exhilaration"); and (3) produce a humorous commentary to the film ("Humor production"). Pain tolerance was measured using the cold pressor test before, immediately after, and twenty minutes after the film. Results indicated that pain tolerance increased for participants from before to after watching the funny film and remained high for the twenty minutes. This effect was moderated by facial but not verbal indicators of enjoyment of humor. Participants low in trait seriousness had an overall higher pain tolerance. Subjects with a high score in trait cheerfulness showed an increase in pain tolerance after producing humor while watching the film whereas subjects low in trait cheerfulness showed a similar increase after smiling and laughter during the film

Red blood cell transfusion practices for patients with cervical cancer undergoing radiotherapy

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma

We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n = 178). An independent validation cohort (n = 79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR = 4.01, 95% CI 2.10–7.67, Cox P = 2.63e−05) and PFS (HR = 3.72, 95% CI 2.06–6.73, Cox P = 1.38e−05) in univariate analysis. In multivariate analysis, the association of hypoalbuminemia with PFS was independent of serum LDH, IFN-γ signature expression, TMB, age, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR = 2.76, 95% CI 1.24–6.13, Cox P = 0.0131). Our validation cohort confirmed the prognostic power of hypoalbuminemia for OS (HR = 1.98, 95% CI 1.16–3.38; Cox P = 0.0127) and was complementary to serum LDH in analyses for both OS (LDH-adjusted HR = 2.12, 95% CI 1.2–3.72, Cox P = 0.00925) and PFS (LDH-adjusted HR = 1.91, 95% CI 1.08–3.38, Cox P = 0.0261). In conclusion, pretreatment hypoalbuminemia was a powerful predictor of outcome in ICI in melanoma and showed remarkable complementarity to previously established biomarkers, including high LDH.</p

Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma

We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n = 178). An independent validation cohort (n = 79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR = 4.01, 95% CI 2.10–7.67, Cox P = 2.63e−05) and PFS (HR = 3.72, 95% CI 2.06–6.73, Cox P = 1.38e−05) in univariate analysis. In multivariate analysis, the association of hypoalbuminemia with PFS was independent of serum LDH, IFN-γ signature expression, TMB, age, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR = 2.76, 95% CI 1.24–6.13, Cox P = 0.0131). Our validation cohort confirmed the prognostic power of hypoalbuminemia for OS (HR = 1.98, 95% CI 1.16–3.38; Cox P = 0.0127) and was complementary to serum LDH in analyses for both OS (LDH-adjusted HR = 2.12, 95% CI 1.2–3.72, Cox P = 0.00925) and PFS (LDH-adjusted HR = 1.91, 95% CI 1.08–3.38, Cox P = 0.0261). In conclusion, pretreatment hypoalbuminemia was a powerful predictor of outcome in ICI in melanoma and showed remarkable complementarity to previously established biomarkers, including high LDH.</p

A Flow Induced Autoimmune Response and Accelerated Senescence of Red Blood Cells in Cardiovascular Devices

Red blood cells (RBCs) passing through heart pumps, prosthetic heart valves and other cardiovascular devices undergo early senescence attributed to non-physiologic forces. We hypothesized that mechanical trauma accelerates aging by deformation of membrane proteins to cause binding of naturally occurring IgG. RBCs isolated from blood of healthy volunteers were exposed to high shear stress in a viscometer or microfluidics channel to mimic mechanical trauma and then incubated with autologous plasma. Increased binding of IgG was observed indicating forces caused conformational changes in a membrane protein exposing an epitope(s), probably the senescent cell antigen of band 3. The binding of immunoglobulin suggests it plays a role in the premature sequestration and phagocytosis of RBCs in the spleen. Measurement of IgG holds promise as a marker foreshadowing complications in cardiovascular patients and as a means to improve the design of medical devices in which RBCs are susceptible to sublethal trauma.Research in this publication was supported by the National Institutes of Health Small Business Innovation Research program under award number R44HL114246 as a subcontract to the University of Oklahoma from VADovations and NIH grant R21HL132286 to DWS and TAS. Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

Assisted reproduction treatment and epigenetic inheritance

Background: The subject of epigenetic risk of assisted reproduction treatment (ART), initiated by reports on an increase of children with the Beckwith–Wiedemann imprinting disorder, is very topical. Hence, there is a growing literature, including mouse studies. Methods: In order to gain information on transgenerational epigenetic inheritance and epigenetic effects induced by ART, literature databases were searched for papers on this topic using relevant keywords. Results: At the level of genomic imprinting involving CpG methylation, ART-induced epigenetic defects are convincingly observed in mice, especially for placenta, and seem more frequent than in humans. Data generally provide a warning as to the use of ovulation induction and in vitro culture. In human sperm from compromised spermatogenesis, sequence-specific DNA hypomethylation is observed repeatedly. Transmittance of sperm and oocyte DNA methylation defects is possible but, as deduced from the limited data available, largely prevented by selection of gametes for ART and/or non-viability of the resulting embryos. Some evidence indicates that subfertility itself is a risk factor for imprinting diseases. As in mouse, physiological effects from ART are observed in humans. In the human, indications for a broader target for changes in CpG methylation than imprinted DNA sequences alone have been found. In the mouse, a broader range of CpG sequences has not yet been studied. Also, a multigeneration study of systematic ART on epigenetic parameters is lacking. Conclusions: The field of epigenetic inheritance within the lifespan of an individual and between generations (via mitosis and meiosis, respectively) is growing, driven by the expansion of chromatin research. ART can induce epigenetic variation that might be transmitted to the next generation