Efficiency in Matching Markets with Regional Caps: The Case of the Japan Residency Matching Program

In an attempt to increase the placement of medical residents to rural hospitals, the Japanese government recently introduced "regional caps" which restrict the total number of residents matched within each region of the country. The government modified the deferred acceptance mechanism incorporating the regional caps. This paper shows that the current mechanism may result in avoidable ineffciency and instability and proposes a better mechanism that improves upon it in terms of effciency and stability while meeting the regional caps. More broadly, the paper contributes to the general research agenda of matching and market design to address practical problems.medical residency matching, regional caps, the rural hospital theorem, sta- bility, strategy-proofness, matching with contracts

Regression of Necrotic Lesions after Methotrexate Withdrawal in Patients with Methotrexate-Associated Lymphoproliferative Disorders: A Retrospective CT Study

This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD

Life Style Factors Influencing Serum Pepsinogen Levels in Healthy Japanese: a Prospective Study

Background: Gastric cancer mass screening using serum pepsinogen has been recognized and several advantages of this methods over photofluorography have been shown by previous study. Aims: To determine the factors influence the serum pepsinogen levels in healthy subjects. Subjects &amp; Methods: One thousand and one hundred fourteen subjects who were screened for gastric cancer as part of a periodic health check. Blood samples were taken after fasting and stored below –20 ° C, until pepsinogen levels were assayed. Results: The subjects consist of 338 males (mean age 52.6+14.0) and 776 females (mean age 49.0+11.9). Age ranges from 19 to 81 years. The overall prevalence of chronic atrophic gastritis using a criterion PG I £ 70 hg/ml and PG I/II ratio £ 3.0 was 21.99 % in 1996 and 23.97 % in 2000. Bivariate analysis revealed a significant association between age, more salt consumption, fish favorable over meat and less than three time meal intake covariates with the lowering of PG I/II ratio. Smoking, drinking, BMI, weight and gender did not affect the changes of PG I/II ratio. Conclusion: Age and more salt consumption covariates have a strongest association with the decreased of PG I/II by multivariate analysis

Expression of Cyclooxygenase Enhances Tumor Invasion and Metastasis in Human Gastric Carcinoma

Background: Expression of COX-2 in vitro has been shown to have a number of cellular effects including increasing proliferation, reducing apoptosis promoting angiogenesis, decreasing E-cadherin expression and increasing invasive/metastatic potential. Aims: To determine the role of COX-2 in the development and metastasis potential of gastric carcinoma in human subjects. Methods: Tissue samples were obtained from surgically removed specimens of 48 patients with primary gastric adenocarcinoma who underwent gastrectomy from January 1998 to December 1999. The specimens were stained for HE while COX-2 expressions in cancer fold and antrum site were evaluated immunohistochemically. Expression of COX-2 was defined as positive when either one of cancer lesion or antrum site showed immunoreactivity. Results: Preliminary result from 12 out of 48 cases, COX-2 immunoreactivity was detected in 50% (6 of 12 specimens). Expression of COX-2 were more frequent in tumor with serosal invasion (5 of 6 specimens), lymph node metastases (3 of 3 specimens), tumor size more than 4 cm and were significant, statistically (p&lt;0.05). The expression of COX-2 in well differential carcinoma type was similar with in poorly differentiated carcinoma type. Conclusion: COX-2 expression in gastric carcinoma tissue is correlated closely with tumor size, serosal invasion and lymph node metastases, indicating that COX-2 is involved in the growth and metastases of gastric carcinoma

Influence of muscle fiber type composition on early fat accumulation under high-fat diet challenge

Objective: To investigate whether differences in muscle fiber types affect early-stage fat accumulation, under high fat diet challenge in mice. Methods: Twelve healthy male C57BL/6 mice experienced with short-term (6 weeks) diet treatment for the evaluation of early pattern changes in muscular fat. The mice were randomly divided into two groups: high fat diet (n = 8) and normal control diet (n = 4). Extra- and intra-myocellular lipid (EMCL and IMCL) in lumbar muscles (type I fiber predominant) and tibialis anterior (TA) muscle (type II fiber predominant) were determined using magnetic resonance spectroscopy (MRS). Correlation of EMCL, IMCL and their ratio between TA and lumbar muscles was evaluated. Results: EMCL increased greatly in both muscle types after high fat diet. IMCL in TA and lumbar muscles increased to a much lower extent, with a slightly greater increase in TA muscles. EMCLs in the 2 muscles were positively correlated (r = 0.84, p = 0.01), but IMCLs showed a negative relationship (r = -0.84, p = 0.01). In lumbar muscles, high fat diet significantly decreased type I fiber while it increased type II fiber (all p≤0.001). In TA muscle, there was no significant fiber type shifting (p>0.05). Conclusions: Under short-time high fat diet challenge, lipid tends to initially accumulate extra-cellularly. In addition, compared to type II dominant muscle, Type I dominant muscle was less susceptible to IMCL accumulation but more to fiber type shifting. These phenomena might reflect compensative responses of skeletal muscle to dietary lipid overload in order to regulate metabolic homeostasis

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)