Overview and Discussion of the Competition on Legal Information, Extraction/Entailment (COLIEE) 2023.

We summarize the 10th Competition on Legal Information Extraction and Entailment. In this tenth edition, the competition included four tasks on case law and statute law. The case law component includes an information retrieval task (Task 1), and the confirmation of an entailment relation between an existing case and a selected unseen case (Task 2). The statute law component includes an information retrieval task (Task 3), and an entailment/question-answering task based on retrieved civil code statutes (Task 4). Participation was open to any group based on any approach. Ten different teams participated in the case law competition tasks, most of them in more than one task. We received results from 8 teams for Task 1 (22 runs) and seven teams for Task 2 (18 runs). On the statute law task, there were 9 different teams participating, most in more than one task. 6 teams submitted a total of 16 runs for Task 3, and 9 teams submitted a total of 26 runs for Task 4. We describe the variety of approaches, our official evaluation, and analysis of our data and submission results.

Adiponectin Paradox More Evident in Non-Obese Than in Obese Patients with Diabetic Microvascular Complications.

Aims/Introduction: Adiponectin is generally regarded as a beneficial molecule, protecting against insulin resistance and atherosclerosis, and its serum levels are low in individuals with obesity as well as in those with type 2 diabetes (T2DM). However, several clinical studies have shown associations between high adiponectin values and major health concerns. These conflicting findings are termed the "adiponectin paradox". Similarly, these paradoxical adiponectin elevations were observed in patients with diabetic microvascular complications. This cross-sectional study aimed to identify differences in factors, including adiponectin, related to diabetic vascular complications between non-obese and obese patients. Materials and Methods: Study patients with T2DM were non-obese (n=197) or obese (n=197), matched by a propensity score model adjusted with age and gender. Independent factors for each of the microvascular complications were determined using multivariate logistic regression analyses. Results: The prevalence of nephropathy was high in obese T2DM patients. In addition to long diabetes duration, elevated adiponectin was a common characteristic of patients with microvascular complications. Logistic regression analyses for microvascular complications revealed adiponectin to be highly related to retinopathy (odds ratio [OR], 1.138; 95%confidence intervals [CI], 1.004-1.289, p<0.001), nephropathy (OR, 1.192; CI, 1.077-1.319, p<0.001) and neuropathy (OR, 1.217; CI, 1.071-1.384, p<0.001), in non-obese patients. In contrast, the association between adiponectin values and complications was modest in obese patients. Conclusion: Adiponectin regulation in response to vascular damage differed between non-obese and obese patients, suggesting that adiponectin regulation is compromised by fat accumulation. Assuming that paradoxical elevation of adiponectin in vascular damage is a compensatory response, we speculate that responsive upregulation might be insufficient in obese patients. These newly-recognized differences in adiponectin values might lead to novel insights into adiponectin regulation and our understanding of the adiponectin paradox.

[A Long-Term Survival Case of Liver Metastasis from Remnant Gastric Cancer Treated by CapeOX, S-1, and Surgery].

A 70-year-old man, who had undergone distal gastrectomy for early gastric cancer at 63-year-old, had multiple liver metastases from remnant gastric cancer, which was diagnosed as cT3(SS), N0, M1, cStage Ⅳ. After a regimen consisting of 8 courses of capecitabine plus oxaliplatin and 2 courses of S-1 was administered, clinical CR was confirmed for the remnant gastric cancer and multiple liver metastases. Chemotherapy was administered for 10 months and discontinued for side effects and the needs of the patient. Anticoagulant drugs were administered for the onset of cerebral infarction after he vomited blood. A gastric ulcer in the oral side of the anastomotic portion was detected and diagnosed as poorly differentiated adenocarcinoma. Multiple liver metastases could not be detected by PET-CT, and we performed a total gastrectomy of the remnant stomach. The patient remains relapse-free 4 years and 10 months after chemotherapy(3 years and 10 months after discontinuing chemotherapy).

Survivability Prediction of Colorectal Cancer Patients: A System with Evolving Features for Continuous Improvement.

Prediction in health care is closely related with the decision-making process. On the one hand, accurate survivability prediction can help physicians decide between palliative care or other practice for a patient. On the other hand, the notion of remaining lifetime can be an incentive for patients to live a fuller and more fulfilling life. This work presents a pipeline for the development of survivability prediction models and a system that provides survivability predictions for years one to five after the treatment of patients with colon or rectal cancer. The functionalities of the system are made available through a tool that balances the number of necessary inputs and prediction performance. It is mobile-friendly and facilitates the access of health care professionals to an instrument capable of enriching their practice and improving outcomes. The performance of survivability models was compared with other existing works in the literature and found to be an improvement over the current state of the art. The underlying system is capable of recalculating its prediction models upon the addition of new data, continuously evolving as time passes.

Diagnostic accuracy of real-time tissue elastography for the staging of liver fibrosis: a meta-analysis.

OBJECTIVE: To evaluate the overall accuracy of real-time tissue elastography (RTE) for the staging of liver fibrosis. METHODS: We systematically reviewed 15 studies (1,626 subjects) in which sensitivity and specificity of RTE for liver fibrosis are available. For each cut-off stage of fibrosis, i.e., F ≥ 1, F ≥ 2, F ≥ 3, and F ≥ 4, summary sensitivity and specificity were estimated using a bivariate random-effects model. Publication bias was assessed using funnel plots and Egger's test. RESULTS: Summary sensitivity and specificity were 0.79 and 0.76 for F ≥ 2, 0.82 and 0.81 for F ≥ 3, and 0.74 and 0.84 for F ≥ 4, respectively. Meta-regressions revealed scoring methods of RTE and liver diseases in the samples might not influence sensitivity and specificity of RTE. However, the estimated accuracy of RTE might be overestimated due to publication bias (p = 0.004 for F ≥ 2, p < 0.001 for F ≥ 3, and p = 0.002 for F ≥ 4). CONCLUSIONS: RTE is not highly accurate for any cut-off stage of fibrosis. Compared with findings of meta-analyses on Transient Elastography and Acoustic Radiation Force Impulse imaging, the overall accuracy of RTE seems to be nearly identical for the evaluation of significant liver fibrosis, but less accurate for the evaluation of cirrhosis. KEY POINTS: • Non-invasive methods for evaluating liver fibrosis are necessary to replace liver biopsy. • ARFI is as accurate as TE for evaluating liver fibrosis. • RTE may be as accurate as TE and ARFI for fibrosis. • RTE may be less accurate than TE and ARFI for cirrhosis. • The estimated accuracy of RTE may be overestimated by publication bias.

Assisting the diagnosis of overt hypothyroidism with pattern recognition methods, making use of a set of routine tests, and their multiple correlation with total T4.

In our previous papers we proposed a novel screening method that assists the diagnosis of patients with overt Graves' hyperthyroidism by making use of routine test data and pattern recognition methods. This method can be applied by non-specialists during physical check-ups at low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists, that is, to improve patients' QOL. In this report, we investigate whether a similar screening method is also applicable for overt hypothyroidism. Fifty-six subjects with 12 routine test data with a known diagnosis (30 patients with overt hypothyroidism and 52 healthy female volunteers, and 26 patients with overt hypothyroidism and 48 healthy male volunteers) were used as training data. Then, test samples of patients who had also undergone the same routine tests at the Tohoku university hospital were screened by our method for overt hypothyroidism. The present examination of the screening method showed its high screening ability with the set of four parameters used (lactate dehydrogenase [LDH], total cholesterol [TC], red blood cell [RBC] and serum creatinine [S-Cr]). It was found that there was a strong multiple correlation between the set of routine test parameters and serum total thyroxine (TT4) in the patients with overt hypothyroidism, which supports the usefulness of our screening method.

[Management of tuberculosis (TB) cases from view points of public health].

Tuberculosis control law was enacted in 1951 and has been the basis for the management of TB cases over the long post-war period. This law has legalized the use of public founds for the treatment of TB patients for the first time and has provided the authentic basis for mandatory hospitalization, routine health examination, vaccination, notification and registration of TB cases. However, this law was abrogated in 2001 and was joined to the comprehensive infectious diseases control law, in order to facilitate a prophylactic measure against TB infection and to protect human rights of TB patients. Concurrently the medical care system and the formalities connected to hospitalization treatment of TB patients were reviewed. The purpose of the present overview is to explain how TB cases are managed under the newly-enacted law.

Assisting the diagnosis of Graves' hyperthyroidism with pattern recognition methods and a set of three routine tests parameters, and their correlations with free T4 levels: Extension to male patients.

In our previous paper, we proposed a novel screening method that aids the diagnosis of female patients with Graves' hyperthyroidism via two types of neural networks and the use of routine test data. This method can be applied by non-specialists during physical checkups at a low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists; i.e., to improve patients' QOL. In this report, we investigate whether the screening method is also applicable to males since sex differences exist in routine test data. The values of 14 routine test parameters for 78 subjects with definite diagnoses (31 patients with Graves' hyperthyroidism and 48 healthy volunteers) were adopted as training data, and 133 individuals who had also undergone the same routine tests at Tohoku University Hospital were screened for Graves' hyperthyroidism using our method. The present examination of our screening method in males showed its high screening ability with the set of parameters used (low serum creatinine, elevated alkaline phosphatase, and low total cholesterol). It was also found that there is strong multiple correlation between a set of three parameters and serum free thyroxine (FT4) in male patients with Graves' hyperthyroidism. A formula for FT4 consisting of three parameters was obtained, and this can be utilized in place of the true FT4 value. This result also supports the usefulness of our screening method.

Features of distinct contractions induced with a high and a low concentration of KCl, noradrenaline, and histamine in swine lingual artery.

We investigated the features of swine lingual artery contraction induced with different strengths of stimulation. Endothelium-denuded artery rings were contracted with two concentrations of KCl, noradrenaline, and histamine with or without Y-27632, sodium nitroprusside (SNP), 2,2-diphenyl-1,3,2-oxaza-borolidine internal salt (2- APB), and extracellular Ca2+. While stored at 5 degrees C up to 3 days, artery rings remained active to strong stimulation but became inactive to weak stimulation if prior warming was lacking. Artery rings contracted slowly and progressively to weak stimulation but rapidly to strong stimulation and then kept a plateau or slightly relaxed. Y-27632, SNP, and 2-APB, irrespective of extracellular Ca2+, attenuated weak-stimulation-induced contractions to much greater extents except that 2-APB similarly diminished contractions to both noradrenaline concentrations. Without extracellular Ca2+, transitory contractions occurred with one peak to strong stimulation and two small peaks to weak stimulation, though one full peak to both noradrenaline concentrations. Artery rings lost stimulant responsiveness when extracellular Ca2+ was absent, but subsequent Ca2+ reintroduction without coexisting stimulant triggered transient contractions, which were as large as contractions to weak stimulation with extracellular Ca2+ and ceased with Y-27632, SNP, and 2-APB. These results collectively suggest that, in the lingual artery, its contraction properties shift coupling with strengths of both receptor- and voltage-mediated stimulation, with the tonic-like component being dominant in weak-stimulation-induced contraction.

Reversible methotrexate-associated lymphoproliferative disorder resembling advanced gastric cancer in a patient with rheumatoid arthritis.

A 73-year-old woman with rheumatoid arthritis had been treated with weekly low-dose methotrexate (MTX) for 5 years. She suffered from epigastric discomfort. Endoscopic examination revealed a tumor resembling advanced gastric cancer. Biopsy specimens showed atypical lymphoid cell infiltration. Immunohistological studies showed that these cells were positive for CD30 and CD79a, but not for CD15 or CD20. In situ hybridization identified Epstein-Barr virus latency-associated RNA expression in these cells. Clonally rearranged immunoglobulin heavy chain JH gene was not detected by Southern blot analysis. She was diagnosed with Epstein-Barr virus-associated polymorphic lymphoproliferative disorder (LPD) due to immunodeficiency caused by MTX administration. Cessation of MTX therapy led to complete regression of the tumor. To our knowledge, this is the first case of spontaneous remission of MTX-associated gastric LPD after discontinuation of MTX therapy. Increased awareness is needed on the possible occurrence of LPD resembling gastric cancer in rheumatoid arthritis patients treated with MTX.

Four-week pegylated interferon alpha-2a monotherapy for chronic hepatitis C with genotype 2 and low viral load: a pilot, randomized study.

AIM: To assess the efficacy and advantages of 4-wk pegylated interferon alpha-2a (peg-IFN-alpha 2a) monotherapy for chronic hepatitis C patients with strong predictors of sustained virologic response (SVR). METHODS: Patients (n = 33) with genotype 2 and low viral load (< 100 KIU/mL), who became HCV RNA negative after 1 wk of IFN treatment, were randomly allocated to receive a 4- or 12-wk treatment course at a ratio of 2:1, respectively, with a subsequent 24-wk follow-up period. Peg-IFN-alpha 2a was administered subcutaneously at a dose of 180 microg or 90 microg once weekly. SVR was defined as absence of serum HCV RNA at the end of the follow-up period. RESULTS: All patients completed the treatment schedule, and more than half were symptom-free during the treatment. In the 4-wk treatment group, 20 of 22 (91%) patients achieved SVR. Two patients relapsed, but achieved SVR following re-treatment with peg-IFN-alpha 2a alone. In the 12-wk treatment group, 11 of 11 (100%) patients attained SVR. CONCLUSION: Our results show that a 4-wk course of peg-IFN-alpha 2a monotherapy can achieve a high SVR rate in "IFN-sensitive" patients, without negatively affecting outcome.

Effects of decorin on the expression of alpha-smooth muscle actin in a human myofibroblast cell line.

Myofibroblasts are metabolically and morphologically distinctive fibroblasts expressing alpha-smooth muscle actin (alpha-SMA), and their activation plays a key role in development of the fibrotic response. In an activated state, myofibroblasts cease to proliferate and start to synthesize large amounts of extracellular component proteins. The expression of alpha-SMA correlates with the activation of myofibroblasts. Decorin, a member of the small leucine-rich proteoglycan gene family, has been implicated in the negative control of cell proliferation primarily by upregulating the expression of p21, a potent inhibitor of cyclin-dependent kinase. In order to examine the effect of decorin on myofibroblast cell growth, we rendered a human lung myofibroblast cell line, MRC-5, quiescent by either cell-cell contact or serum starvation, and examined the relationship between decorin and alpha-SMA expression in these cells. The expression of decorin in cells made quiescent by serum starvation was lower than that in cells made quiescent by cell-cell contact. In contrast, the expression of alpha-SMA in cells made quiescent by cell-cell contact was lower than that in cells made quiescent by serum starvation. Furthermore, forced expression of decorin was accompanied by a suppression of alpha-SMA expression, whereas knocking down of decorin expression by RNA interference increased the expression of alpha-SMA.

A phase I study and pharmacokinetics of irinotecan (CPT-11) and paclitaxel in patients with advanced non-small cell lung cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of irinotecan and paclitaxel in this two-drug combination, and to investigate a sequence-dependent effect in the pharmacokinetics of these drugs, we conducted a phase I study in chemo-naïve patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were enrolled in this study. Both irinotecan and paclitaxel were administered on days 1 and 8, and repeated every 3 weeks. The starting dose of both drugs was 40 mg/m2 which was then alternately increased by 10 mg/m2 increments. In the first cycle, irinotecan was initially administered and followed by paclitaxel infusion, while the sequence of drug administration was reversed in the second cycle. Blood samples for pharmacokinetic analysis were obtained on day 1 of the first and second cycles. RESULTS: Nine patients received a total of 12 cycles, which were evaluated for toxicity and efficacy. The main hematological toxicity was neutropenia. Grades 3 or more neutropenia was observed in 67% of cycles at dose level 2. The main non-hematological toxicities were grade 3 febrile neutropenia, supraventricular arrhythmia, and grade 2 hepatic dysfunction. The MTD of irinotecan and paclitaxel were 40 and 50 mg/m2, respectively. In the pharmacokinetic analysis, the maximum concentration of paclitaxel was elevated in a dose-dependent manner. There was a trend toward elevation of the area under the plasma concentration-time curve (AUC) of irinotecan and a decline of the AUC of paclitaxel in cycle 1 (irinotecan followed by paclitaxel), compared with those in cycle 2 (paclitaxel followed by irinotecan). Hepatic toxicity was strongly associated with the AUC of irinotecan (r = 0.894, P < 0.0001). The objective response was not observed in the nine patients. CONCLUSION: The combination of irinotecan and paclitaxel with this schedule produced considerable toxicities without any antitumor effect for advanced NSCLC. The different schedule of administration or other combinations should be investigated.

Leucine-rich repeat region of decorin binds to filamin-A.

Decorin is a member of the family of small leucine-rich proteoglycans found in the extracellular matrix and has an important role in promoting fiber formation and in controlling cell proliferation. Here, we have investigated whether the leucine-rich repeat (LRR) region of decorin interacts with proteins from human lung fibroblasts by using a yeast two-hybrid assay. We report that the LRR region of decorin interacts with the cytoskeletal protein, filamin-A (ABP-280), a peripheral cytoplasmic protein. This interaction is dependent on the 288 carboxyl-terminal amino acids of filamin-A, which correspond to repeats 22-24 of its conserved beta-sheet structure. We also show that the recombinant LRR region of decorin binds to filamin-A in vitro, and that the deglycosylated core protein of decorin coprecipitates with filamin-A, whereas intact decorin does not. Together, these results suggest that proteins containing the LRR motif that interact with filamin-A may be present in the cytoplasm or at the plasma membrane.