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The enhanced liver fibrosis (ELF) test is a noninvasive method for diagnosing hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). This multicenter cohort study aimed to evaluate the accuracy of the ELF test and compare it with other noninvasive tests in Japan.We analyzed 371 Japanese patients with biopsy-proven NAFLD. We constructed area under the receiver operator characteristics curves (AUROC) to determine the diagnostic accuracies of the ELF test, the Mac-2-binding protein glycosylation isomer (M2BPGi), the FIB-4 index, and combinations of these indices.In patients with F0/F1/F2/F3/F4 fibrosis, the median respective values of the ELF test were 8.98/9.56/10.39/10.92/11.41. The AUROCs of the ELF test for patients with F0 vs F1-4, F0-1 vs F2-4, F0-2 vs F3-4, and F0-3 vs F4 fibrosis were 0.825/0.817/0.802/0.812, respectively. The AUROCs of the ELF test were greater than those of the FIB-4 index and M2BPGi at each fibrosis stage. Respective low and high cutoff values yielded sensitivities and specificities for predicting advanced fibrosis (≥F3) of 91.1% and 50.8% and 38.5% and 92.8%, respectively. For F3 or F4 fibrosis, the combined values from the ELF test and FIB-4 index showed a sensitivity of 98.5%, and the combined values from the ELF test and M2BPGi assay showed a specificity of 97.5%.In Japan, the ELF test predicts NAFLD-related fibrosis from its early stages. The diagnostic ability of the ELF test was not inferior to that of other indices, and the combined values of ELF plus other indices were more accurate. This article is protected by copyright. All rights reserved.

Study Design: Clinical case series.Purpose: This study aimed to report dynamization–posterior lumbar interbody fusion (PLIF), our surgical treatment for hemodialysisrelated spondyloarthropathy (HSA), and investigate patients’ postoperative course within 2 years.Overview of Literature: HSA often requires lumbar fusion surgery. Conventional PLIF for HSA may cause progressive destructive changes in the vertebral endplate, leading to progressive cage subsidence, pedicle screw loosening, and pseudoarthrosis. A dynamic stabilization system might be effective in patients with a poor bone quality. Thus, we performed “dynamization–PLIF” in hemodialysis patients with destructive vertebral endplate changes.Methods: We retrospectively examined patients with HSA who underwent dynamization–PLIF at our hospital between April 2010 and March 2018. The radiographic measurements included lumbar lordosis and local lordosis in the fused segment. The evaluation points were before surgery, immediately after surgery, 1 year after surgery, and 2 years after surgery. The preoperative and postoperative radiographic findings were compared using a paired t-test. A p-value of less than 0.05 was considered significant.Results: We included 50 patients (28 males, 22 females). Lumbar lordosis and local lordosis were significantly improved through dynamization– PLIF (lumbar lordosis, 28.4°–35.5°; local lordosis, 2.7°–12.8°; pp=0.07, respectively). Solid fusion was achieved in 59 (89%) of 66 fused segments. Solid fusion of all fixed segments was achieved in 42 cases (84%). Within 2 years postoperatively, only six cases (12%) were reoperated (two, surgical debridement for surgical site infection; two, reoperation for pedicle screw loosening; one, laminectomy for epidural hematoma; one, additional fusion for adjacent segment disease).Conclusions: Dynamization–PLIF showed local lordosis improvement, a high solid fusion rate, and a low reoperation rate within 2 years of follow-up.

Cheeger's inequality states that a tightly connected subset can be extracted from a graph $G$ using an eigenvector of the normalized Laplacian associated with $G$. More specifically, we can compute a subset with conductance $O(\sqrt{\phi_G})$, where $\phi_G$ is the minimum conductance of a set in $G$. It has recently been shown that Cheeger's inequality can be extended to hypergraphs. However, as the normalized Laplacian of a hypergraph is no longer a matrix, we can only approximate to its eigenvectors; this causes a loss in the conductance of the obtained subset. To address this problem, we here consider the heat equation on hypergraphs, which is a differential equation exploiting the normalized Laplacian. We show that the heat equation has a unique solution and that we can extract a subset with conductance $\sqrt{\phi_G}$ from the solution. An analogous result also holds for directed graphs., Comment: 22 pages

We present a polynomial-time online algorithm for maximizing the conditional value at risk (CVaR) of a monotone stochastic submodular function. Given $T$ i.i.d. samples from an underlying distribution arriving online, our algorithm produces a sequence of solutions that converges to a ($1-1/e$)-approximate solution with a convergence rate of $O(T^{-1/4})$ for monotone continuous DR-submodular functions. Compared with previous offline algorithms, which require $\Omega(T)$ space, our online algorithm only requires $O(\sqrt{T})$ space. We extend our online algorithm to portfolio optimization for monotone submodular set functions under a matroid constraint. Experiments conducted on real-world datasets demonstrate that our algorithm can rapidly achieve CVaRs that are comparable to those obtained by existing offline algorithms., Comment: Full version of our paper in IJCAI 2021

Patients with ossification of the posterior longitudinal ligament (OPLL) are often reported to have increased bone mineral density (BMD). The bone strength of the proximal femur measured by quantitative computed tomography-based finite element analysis (QCT/FEA) is reportedly comparable between healthy subjects with and without OPLL. However, the bone strength in symptomatic OPLL patients remains unknown.To investigate bone strength measured by QCT/FEA in symptomatic patients with OPLL.A single-center prospective observational study.A total of 157 patients with cervical or thoracic compressive myelopathy were included in the study.We analyzed patients' characteristics, Japanese Orthopedic Association (JOA) score, serum laboratory tests including calcium (Ca), inorganic phosphate (Pi), and bone turnover markers, BMD of the proximal femur and lumbar spine measured using dual-energy X-ray absorptiometry, and predicted bone strength (PBS) of the proximal femur and lumbar spine measured using QCT/FEA.Eligible patients were divided into the non-OPLL and OPLL groups. We compared the patients' characteristics, JOA scores, laboratory data, BMD, and PBS of the proximal femur and lumbar spine between the non-OPLL and OPLL groups among total, male, and female patients by performing Fisher's exact test for categorical variables and the unpaired t test for continuous variables. Then, we used the inverse probability weighted logistic regression model after calculating propensity scores to compare the bone metabolism-associated markers, BMD, and PBS measurements between the groups.Among the eligible 157 patients, 68 were in the non-OPLL group and 89 were in the OPLL group. Compared with the non-OPLL group, the OPLL group had a significantly younger age and higher BMI in the total, male, and female patients. The JOA scores in the total and female patients were significantly higher in the OPLL group than in the non-OPLL group. The OPLL group showed significantly lower Ca levels in the female patients and significantly lower Pi levels in the total or male patients compared with the non-OPLL group in the inverse probability weighting method. The BMD of the proximal femur and lumbar spine and the PBS of the proximal femur were significantly higher in the OPLL group than in the non-OPLL group. There were no significant differences in the PBS and BMD between the male subgroups. However, the BMD and PBS of the proximal femur and lumbar spine were significantly higher in the OPLL females than in the non-OPLL females.Hyperostosis of the posterior longitudinal ligament in OPLL was associated with higher bone strength by QCT/FEA, especially in female OPLL patients.

Hepatocellular carcinoma (HCC) after sustained virologic response (SVR) has been observed even in hepatitis C virus (HCV) patients without advanced liver fibrosis. Identifying predictors for HCC incidence in patients without advanced liver fibrosis will enable efficient post-SVR HCC surveillance. This study aimed to develop a scoring system to predict the incidence of HCC after SVR in HCV patients without advanced liver fibrosis.A total of 1682 HCV patients without advanced liver fibrosis (defined as Fibrosis-4 index3.25) with no history of HCC who initiated direct-acting antiviral treatment between September 2014 and October 2020 at 26 institutions, and achieved SVR24, were included. We divided 1682 patients into training (1122) and validation (560) cohorts.In the multivariate analysis, baseline age ≥ 65 years (p = 0.030), alanine aminotransferase (ALT) levels at SVR24 ≥ 30 U/l (p = 0.001), and α-fetoprotein (AFP) levels at SVR24 ≥ 5.0 ng/ml (p = 0.001) were independent predictors for HCC incidence in the training cohort. We developed a scoring system to predict HCC incidence after SVR24 using these three factors (1 point was added for each factor). The cumulative HCC incidence rates at 5 years were 7.1% in patients who scored 2 or 3, and no patients developed HCC in those who scored 0 in the validation cohort.Our scoring system using the three factors of baseline age, ALT levels at SVR, and AFP levels at SVR is useful for post-SVR HCC surveillance of patients without advanced liver fibrosis.

OBJECTIVE The aim of this study was to compare perioperative complications and postoperative outcomes between patients with lumbar recurrent stenosis without lumbar instability and radiculopathy who underwent decompression surgery and those who underwent decompression with fusion surgery. METHODS For this retrospective study, the authors identified 2606 consecutive patients who underwent posterior surgery for lumbar spinal canal stenosis at eight affiliated hospitals between April 2017 and June 2019. Among these patients, those with a history of prior decompression surgery and central canal restenosis with cauda equina syndrome were included in the study. Those patients with instability or radiculopathy were excluded. The patients were divided between the decompression group and decompression with fusion group. The demographic characteristics, numerical rating scale score for low-back pain, incidence rates of lower-extremity pain and lower-extremity numbness, Oswestry Disability Index score, 3-level EQ-5D score, and patient satisfaction rate were compared between the two groups using the Fisher’s exact probability test for nominal variables and the Student t-test for continuous variables, with p < 0.05 as the level of statistical significance. RESULTS Forty-six patients met the inclusion criteria (35 males and 11 females; 19 patients underwent decompression and 27 decompression and fusion; mean ± SD age 72.5 ± 8.8 years; mean ± SD follow-up 18.8 ± 6.0 months). Demographic data and perioperative complication rates were similar. The percentages of patients who achieved the minimal clinically important differences for patient-reported outcomes or satisfaction rate at 1 year were similar. CONCLUSIONS Among patients with central canal stenosis who underwent revision, the short-term outcomes of the patients who underwent decompression were comparable to those of the patients who underwent decompression and fusion. Decompression surgery may be effective for patients without instability or radiculopathy.

Severe hypertension in pregnancy is a hypertensive crisis that requires urgent and intensive care due to its high maternal and fetal mortality. However, there is still a conflict of opinion on the recommendations of antihypertensive therapy. This study aimed to identify the optimal blood pressure (BP) levels to prevent severe hypertension in pregnant women with nonsevere hypertension. Ovid MEDLINE and the Cochrane Library were searched, and only randomized controlled trials (RCTs) were included if they compared the effects of antihypertensive drugs and placebo/no treatment or more intensive and less intensive BP-lowering treatments in nonsevere hypertensive pregnant patients. A random effects model meta-analysis was performed to estimate the pooled risk ratio (RR) for the outcomes. Forty RCTs with 6355 patients were included in the study. BP-lowering treatment significantly prevented severe hypertension (RR, 0.46; 95% CI, 0.37-0.56), preeclampsia (RR, 0.82; 95% CI, 0.69-0.98), severe preeclampsia (RR, 0.38; 95% CI, 0.17-0.84), placental abruption (RR, 0.52; 95% CI, 0.32-0.86), and preterm birth ( 37 weeks; RR, 0.81; 95% CI, 0.71-0.93), while the risk of small for gestational age infants was increased (RR, 1.25; 95% CI, 1.02-1.54). An achieved systolic blood pressure (SBP) of 130 mmHg reduced the risk of severe hypertension to nearly one-third compared with an SBP of ≥ 140 mmHg, with a significant interaction of the BP levels achieved with BP-lowering therapy. There was no significant interaction between the subtypes of hypertensive disorders of pregnancy and BP-lowering treatment, except for placental abruption. BP-lowering treatment aimed at an SBP 130 mmHg and accompanied by the careful monitoring of fetal growth might be recommended to prevent severe hypertension.

Background Primary aldosteronism (PA) is a common cause of secondary hypertension, whereas pheochromocytoma is a rare cause of it. Thus, concomitant PA and pheochromocytoma is a very rare condition. Case presentation A 52-year-old woman was admitted to our hospital with suspected PA based on the presence of hypertension, spontaneous hypokalemia, and a high aldosterone-to-renin ratio. She had no catecholamine excess symptoms other than hypertension. Abdominal computed tomography (CT) showed a right lipid-rich adrenal mass and a left lipid-poor adrenal mass. PA was diagnosed by the captopril challenge test. The 24-h urinary fractionated metanephrines were slightly elevated. Adrenal vein sampling (AVS) confirmed that the right adrenal gland was responsible for aldosterone hypersecretion. Medical therapy with eplerenone was started because the patient refused surgery. Five years later, she requested surgery for PA. The second AVS confirmed right unilateral hyperaldosteronism, as expected. Repeated abdominal CT showed the enlargement of the left adrenal mass. The 24-h urinary fractionated metanephrines had risen to the diagnostic level. 123I- metaiodobenzylguanidine (MIBG) scintigraphy showed a marked tracer uptake in the left adrenal mass with no metastatic lesion. After preoperative management with α-blockade, laparoscopic left partial adrenalectomy was performed. Immunohistochemical examination of the tumor showed chromogranin A positivity leading to the diagnosis of left pheochromocytoma. Conclusions We report an extremely rare case of concomitant unilateral PA and contralateral pheochromocytoma. When diagnosing unilateral PA by AVS, especially in cases with a lipid-poor adrenal mass, clinicians should rule out the possibility of the presence of pheochromocytoma before proceeding to undergo unilateral adrenalectomy. Although there is no standard treatment for this rare condition, it is essential to select personalized treatment from the perspective of conserving the adrenal gland.

For a size parameter s: ℕ → ℕ, the Minimum Circuit Size Problem (denoted by MCSP[s(n)]) is the problem of deciding whether the minimum circuit size of a given function f : {0,1}ⁿ → {0,1} (represented by a string of length N : = 2ⁿ) is at most a threshold s(n). A recent line of work exhibited "hardness magnification" phenomena for MCSP: A very weak lower bound for MCSP implies a breakthrough result in complexity theory. For example, McKay, Murray, and Williams (STOC 2019) implicitly showed that, for some constant μ₁ > 0, if MCSP[2^{μ₁⋅ n}] cannot be computed by a one-tape Turing machine (with an additional one-way read-only input tape) running in time N^{1.01}, then P≠NP. In this paper, we present the following new lower bounds against one-tape Turing machines and branching programs: 1) A randomized two-sided error one-tape Turing machine (with an additional one-way read-only input tape) cannot compute MCSP[2^{μ₂⋅n}] in time N^{1.99}, for some constant μ₂ > μ₁. 2) A non-deterministic (or parity) branching program of size o(N^{1.5}/log N) cannot compute MKTP, which is a time-bounded Kolmogorov complexity analogue of MCSP. This is shown by directly applying the Nečiporuk method to MKTP, which previously appeared to be difficult. 3) The size of any non-deterministic, co-non-deterministic, or parity branching program computing MCSP is at least N^{1.5-o(1)}. These results are the first non-trivial lower bounds for MCSP and MKTP against one-tape Turing machines and non-deterministic branching programs, and essentially match the best-known lower bounds for any explicit functions against these computational models. The first result is based on recent constructions of pseudorandom generators for read-once oblivious branching programs (ROBPs) and combinatorial rectangles (Forbes and Kelley, FOCS 2018; Viola 2019). En route, we obtain several related results: 1) There exists a (local) hitting set generator with seed length Õ(√N) secure against read-once polynomial-size non-deterministic branching programs on N-bit inputs. 2) Any read-once co-non-deterministic branching program computing MCSP must have size at least 2^Ω̃(N)., LIPIcs, Vol. 187, 38th International Symposium on Theoretical Aspects of Computer Science (STACS 2021), pages 23:1-23:19

Let G = ( V , E ) be an undirected graph, L G ∈ R V × V be the associated Laplacian matrix, and b ∈ R V be a vector. Solving the Laplacian system L G x = b has numerous applications in theoretical computer science, machine learning, and network analysis. Recently, the notion of the Laplacian operator L F : R V → 2 R V for a submodular transformation F : 2 V → R + E was introduced, which can handle undirected graphs, directed graphs, hypergraphs, and joint distributions in a unified manner. In this study, we show that the submodular Laplacian system L F ( x ) ∋ b can be solved in polynomial time. Furthermore, we prove that even when the submodular Laplacian system has no solution, we can solve its regression form in polynomial time. Finally, we discuss potential applications of submodular Laplacian systems in machine learning and network analysis.

BACKGROUND Several factors associated with hepatocellular carcinoma (HCC) occurrence after sustained virological response (SVR) in patients with hepatitis C have been reported. However, few validation studies have been performed in the era of direct-acting anti-virals (DAAs). AIMS To develop a prediction model for HCC occurrence after DAA-mediated SVR and validate its usefulness. METHODS We analysed 2209 patients with SVR and without a history of HCC who initiated DAA treatment at 24 Japanese hospitals. These patients were divided into a training set (1473 patients) and a validation set (736 patients). RESULTS In the training set, multivariate Cox proportional hazards analysis showed that the baseline BMI (≥25.0 kg/m2 , P = 0.024), baseline fibrosis-4 (FIB-4) index (≥3.25, P = 0.001), albumin level at SVR (

Objective To compare the clinical and radiographic outcomes and complications in patients undergoing multilevel posterior cervical fusion surgery, ending at C7 or crossing the cervicothoracic junction (CTJ). Methods A total of 96 patients undergoing multilevel posterior cervical fusion surgery ending at C7, T1, or T2 were screened. The patients who fulfilled the inclusion criteria were divided into 2 groups based on the lower instrumented vertebra (LIV) level: group C7 (ending at C7) and group T1-T2 (crossing the CTJ). The radiographic and clinical outcomes were compared between the 2 groups, and the risk factors for instrument failure at LIV were investigated. Results In total, 73 patients (76%) completed at least 1 year follow-up and divided into group C7 (n = 43) and group T1-T2 (n = 30). Preoperative and postoperative radiographic parameters, the Japanese Orthopaedic Association score, and patient-reported outcomes were not significantly different between the 2 groups. Significantly longer surgical time, increased blood loss, and higher incidence rates of perioperative or postoperative complications were noted in group T1-T2. On the other hand, the incidence of instrument failures at LIV was significantly higher in group C7. Multivariate analysis showed that ending at C7, skipping screw insertion at the proximal vertebra adjacent to LIV, and a large postoperative cervical sagittal vertical axis (>40 mm) were risk factors for instrument failure at LIV. Conclusions Crossing the CTJ during multilevel posterior cervical fusion surgery reduced instrument failures at LIV, but increased the surgical invasiveness and perioperative and postoperative complications.

Background: The relationship between baseline serum albumin level and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) remains unknown. Methods:This is a sub-analysis of the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) study. The main outcomes were: death or orthotopic liver transplantation (OLT), liver-related death, and liver-related events (hepatocellular carcinoma [HCC], decompensated cirrhosis, and gastroesophageal varices/bleeding). Results:1,383 Japanese patients with biopsy-confirmed NAFLD were analyzed. They were divided into 3 groups based on serum albumin: high (>4.0 g/dL), intermediate (3.5–4.0 g/dL), and low (P< 0.001; low vs high albumin group: HR 22.9, 95% CI 8.21–63.9, P< 0.001). Conclusions: Among biopsy-confirmed NAFLD patients, those with intermediate or low serum albumin had a significantly higher risk of death or OLT than those with high serum albumin.

Congestive hepatopathy often leads to liver fibrosis and hepatocellular carcinoma. Imaging modalities provided clinical evidence that elevation of liver stiffness and tumor occurrence are mainly induced in liver periphery of patients with congestive hepatopathy. However, clinical relevance of liver stiffness and liver fibrosis is unclear because liver congestion itself increases liver stiffness in congestive hepatopathy. It also unclear which factors configure such regional disparity of tumor development in patients with congestive hepatopathy. To answer these questions, we evaluated the macroscopic spatial distribution of liver fibrosis and tumors in murine model of congestive hepatopathy.Chronic liver congestion was induced by partial ligation of the suprahepatic inferior vena cava (pIVCL). Distribution of liver congestion, fibrosis, and tumors in pIVCL mice was assessed by histological findings, laser microdissection (LMD)-based qPCR and enhanced computed tomography. LMD-based RNA-seq was performed to identify causal factors which promotes tumor development in congestive hepatopathy.Liver fibrosis was mainly induced in liver periphery and co-localized with distribution of liver congestion. Liver tumors were also induced in liver periphery where liver congestion and fibrosis occurred. LMD-based RNA-seq revealed the upregulation of extracellular matrix/collagen fibril related-, wound healing related-, angiogenesis related-, morphogenesis related-, and cell motility-related signaling pathways in liver periphery compared to liver center.Our findings showed experimental relevance of liver congestion, fibrosis and tumor development in congestive hepatopathy, and may provide important locational information. Macroscopic regional disparity observed in this murine model should be considered to manage patients with congestive hepatopathy. This article is protected by copyright. All rights reserved.

CAP biosynthesis in the pericarp of chili pepper fruits occurs with an ambiguous boundary in the placental septum and pericarp. Capsaicinoid (CAP) is a pungent ingredient of chili pepper fruits. Generally, CAP biosynthesis is limited to the placental septum of fruits, but it has been reported that its biosynthesis occurs even in the pericarp of some extremely pungent varieties, resulting in a substantial increase in total content. To examine the mechanism of CAP biosynthesis in the pericarp, comparative transcriptome analysis of a variety that produces CAP in the pericarp (MY) and a variety that does not (HB) was carried out. RNA-seq revealed that 2264 genes were differentially expressed in the MY pericarp compared with the HB pericarp. PCA analysis and GO enrichment analysis indicated that the MY pericarp has a gene expression profile more like placental septum than the HB pericarp. The gene expression of CAP biosynthesis-related genes in the MY pericarp changed coordinately with the placental septum during fruit development. In most Capsicum accessions including HB, the distribution of slender epidermal cells producing CAP was limited to the placental septum, and the morphological boundary between the placental septum and pericarp was clear. In some extremely pungent varieties such as MY, slender epidermal cells ranged from the placental septum to the pericarp region, and the pericarp was morphologically similar to the placental septum, such as the absence of large sub-epidermal cells and abundant spaces in the parenchymal tissue. Our data suggest that CAP biosynthesis in the pericarp occurred with an ambiguous boundary in the placental septum and pericarp. These findings contribute to further enhancement of CAP production in chili pepper fruits.

Grb2-associated binder 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction by receptor tyrosine kinases that are receptors for various growth factors and plays an important role in rapid liver regeneration after partial hepatectomy and during acute hepatitis. On the other hand, mild liver regeneration is induced in livers of individuals with chronic hepatitis, where hepatocyte apoptosis is persistent; however, the impact of Gab1 on such livers remains unclear. We examined the role of Gab1 in chronic hepatitis. Gab1 knockdown enhanced the decrease in cell viability and apoptosis induced by ABT-737, a Bcl-2/-xL/-w inhibitor, in BNL.CL2 cells, while cell viability and caspase activity were unchanged in the absence of ABT-737. ABT-737 treatment induced Gab1 cleavage to form p35-Gab1. p35-Gab1 was also detected in the livers of mice with hepatocyte-specific Mcl-1 knockout (KO), which causes persistent hepatocyte apoptosis. Gab1 deficiency exacerbated hepatocyte apoptosis in Mcl-1 KO mice with posttranscriptional downregulation of Bcl-XL. In BNL.CL2 cells treated with ABT-737, Gab1 knockdown posttranscriptionally suppressed Bcl-xL expression, and p35-Gab1 overexpression enhanced Bcl-xL expression. Gab1 deficiency in Mcl-1 KO mice activated STAT3 signaling in hepatocytes, increased hepatocyte proliferation, and increased the incidence of liver cancer with the exacerbation of liver fibrosis. In conclusion, Gab1 is cleaved in the presence of apoptotic stimuli and forms p35-Gab1 in hepatocytes. In chronic liver injury, the role of Gab1 in suppressing apoptosis and reducing liver damage, fibrosis, and tumorigenesis is more important than its role in liver regeneration.

Although the survival rate after living-donor liver transplantation (LDLT) is improving, sepsis still limits the prognosis. Immune dysfunction and sarcopenia are often observed in LDLT patients, and increase susceptibility to infection. Brain-derived neurotrophic factor (BDNF) is a myokine produced by immune cells and skeletal muscle. We aimed to determine whether serum BDNF could be a feasible biomarker for sepsis of LDLT patients.We measured serum samples from 124 patients who underwent LDLT and 9 healthy volunteers for BDNF. We examined its correlation with incidence rate of sepsis. To clarify the source of BDNF, we examined its expression in lymphocytes, skeletal muscle cells, and hepatocytes.Patients who experienced sepsis showed worse short-term survival. Preoperative serum BDNF was lower in LDLT patients compared with healthy volunteers, and was also lower in Child-Pugh C compared with Child-Pugh A or B. Serum BDNF was inversely correlated with Model for End-Stage Liver Disease and controlling nutritional status (CONUT) scores, but had a weak positive correlation with skeletal muscle mass index (SMI). Multivariate analysis revealed that serum BDNF was independently associated with sepsis. Preoperative serum BDNF was a better predictor of sepsis in LDLT patients than CONUT score or SMI. Serum BDNF was positively correlated with lymphocyte counts, especially T cells. In vitro, T cells and skeletal muscle cells produced BDNF.Preoperative serum BDNF could be a predictive biomarker for sepsis after LDLT, by reflecting the systemic condition including hepatic function, nutritional status, and immune status.

We measured dietary salt intake in 26 patients with primary aldosteronism treated with mineralocorticoid receptor antagonists and evaluated whether plasma renin levels were affected by dietary salt intake pre-treatment and post 6 months of mineralocorticoid receptor antagonist treatment. The dietary salt intake level was calculated using spot urine sodium and creatinine concentrations, body weight, height, and age. The clinical parameters pre- and post- treatment were compared. The systolic and diastolic blood pressure levels decreased, and the serum potassium and active renin concentration increased significantly. Although the dietary salt intake did not change after treatment, the differences in dietary salt intake and active renin concentration pre- and post- treatment were inversely correlated (r = -0.418, p = 0.03). The 26 patients were divided into two groups with active renin concentration levels ≥5 pg/mL (Group 1) and5 pg/mL (Group 2) after treatment. The Group parameters did not differ pre- and post- treatment. Group 1 evidenced improvements in systolic and diastolic blood pressures, and the potassium level and active renin concentration over time; Group 2 did not. Group 1 evidenced no significant correlation between the differences in dietary salt intake and active renin concentration levels (r = -0.481, p = 0.11) but Group 2 showed a strong inverse correlation (r = -0.7599, p = 0.01). In conclusion, we found that an active renin concentration level5 pg/mL post-mineralocorticoid receptor antagonist treatment may indicate that salt sensitivity has not adequately improved, emphasizing the importance of measuring plasma renin levels after such treatment.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Recently, the prognosis of NAFLD/NASH has been reported to be dependent on liver fibrosis degree. Liver biopsy remains the gold standard, but it has several issues that must be addressed, including its invasiveness, cost, and inter-observer diagnosis variability. To solve these issues, a variety of noninvasive tests (NITs) have been in development for the assessment of NAFLD progression, including blood biomarkers and imaging methods, although the use of NITs varies around the world. The aim of the Japan NASH NIT (JANIT) Forum organized in 2020 is to advance the development of various NITs to assess disease severity and/or response to treatment in NAFLD patients from a scientific perspective through multi-stakeholder dialogue with open innovation, including clinicians with expertise in NAFLD/NASH, companies that develop medical devices and biomarkers, and professionals in the pharmaceutical industry. In addition to conventional NITs, artificial intelligence will soon be deployed in many areas of the NAFLD landscape. To discuss the characteristics of each NIT, we conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis in this study with the 36 JANIT Forum members (16 physicians and 20 company representatives). Based on this SWOT analysis, the JANIT Forum identified currently available NITs able to accurately select NAFLD patients at high risk of NASH for HCC surveillance/therapeutic intervention and evaluate the effectiveness of therapeutic interventions.

This paper proposes an analytical method for calculating rocking responses of unanchored tanks during seismic ground motion. Some researchers have proposed the analytical methods to calculate seismic responses of unanchored tanks without considering the rotational inertia of content liquid. In other words, most of method for a time-history analysis of tank rocking responses are assumed that an equilibrium equation in direction of rotation can be formulated as a static equilibrium equation in which the overturning moment and the restoring moment are equal. Even a model that considers rotational inertia of content liquid was proposed in the past, the definition of moment of inertia is ambiguous. On the other hand, there a study that derives moment of inertia from a physical background and alleges the importance of the moment of inertia in the tank rocking response. In this study, an analytical method of a time history analysis of tank rocking motion considering the rotational inertia of content liquid is proposed. Furthermore, results of the proposed method are compared with results of the FEM dynamic analysis to validate the accuracy of the proposed method. Finally, comparisons with results of the conventional calculation method are also conducted.

Chili peppers are important as vegetables and ornamental crops, because of the variety of fruit shapes and colors. Understanding of flower and fruit development in Capsicum is limited compared with closely related Solanaceae crops such as tomato. This study reports a novel malformed fruit mutant named malformed fruit-1 (maf-1), which was isolated from an ethyl methanesulfonate–induced mutant population of chili pepper. maf-1 exhibited homeotic changes in the floral bud, which were characterized by conversion of petals and stamens into sepal-like and carpel-like organs, respectively. In addition, the indeterminate formation of carpel-like tissue was observed. Genetic analysis demonstrated that the causative gene in maf-1 is a nonsense mutation in CaLFY. This is the first characterization of an lfy mutant in Capsicum. Unlike tomatoes, the CaLFY mutation did not affect the architecture of sympodial unit or flowering time but mainly affected the formation of flower organs. Gene expression analysis suggested that a nonsense mutation in CaLFY led to decreased expression of multiple class B genes, resulting in homeotic changes in the flower and fruit. This maf-1 mutant may provide new insights at the molecular level in understanding flower organ formation and the genetic manipulation of fruit shape in chili peppers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11032-022-01304-w.

Background The impact of the T1 slope minus cervical lordosis (T1S-CL) on surgical outcomes in patients with degenerative cervical myelopathy undergoing laminoplasty (LP) remain uncertain. Methods One hundred patients who underwent cervical LP were retrospectively reviewed. Radiographic measurements included C2–C7 lordosis (CL), T1 slope (T1S), and C2–C7 sagittal vertical axis (SVA). Additionally, pain numeric rating scale, neck disability index (NDI), 12-Item Short-Form Health Survey, Euro QOL 5 dimensions (EQ5D), and Japanese Orthopedic Association score were investigated. According to past reports, T1S–CL > 20° was defined as mismatched. Then, based on T1S-CL mismatching, patients were divided into 2 groups. Results This research understudied 67 males and 33 females with a mean age of 67 y. Preoperatively, only eight patients showed a T1S-CL mismatch. While the C2–7 Cobb angles did not change significantly after surgery, the T1 slope (T1S) angle increased, increasing the T1S-CL as a result. As we compared the clinical outcomes based on the preoperative T1S-CL mismatching, there were no significant differences between the two groups. On the other hand, the number of patients in the mismatched group increased to 21 patients postoperatively. As we compared clinical outcomes based on the postoperative T1S-CL mismatching, the postoperative NDI score and preop/postop EQ5D score were significantly worse in the mismatch group. Conclusions Although cervical LP showed inferior outcomes in patients with postoperative T1S-CL mismatch even in the absence of severe preoperative kyphosis (> 10°), preoperative T1S-CL mismatch was not adversely prognostic.

Neurofibromatosis 1 (NF1) is a genetic disorder characterized by various symptoms including dermatological, neurological, and osseous manifestations. These complications often cause cosmetic or functional disturbances, resulting in a significant impact on quality of life (QOL). However, there are limited data on QOL of individuals with NF1 in Japan. Therefore, we studied health-related QOL in patients with NF1 compared with that in general populations and the association with severity grade using EQ-5D. A cross-sectional study was conducted for 73 adult NF1 patients (26 males and 47 females; mean age, 44.16 years). The EQ-5D-5L values and visual analog scale (VAS) in patients with NF1 were 0.738 ± 0.137 and 69.93 ± 19.14, respectively. Both scores were significantly lower in patients with NF1 than in healthy volunteers (p 0.0001). The score for anxiety/depression was the highest among the five items of EQ-5D. Although we investigated differences in the index value and VAS between stage 2 or less and stage 3 or higher, there was no difference in the scores between groups related to certification criteria for the public medical expenses subsidy system. EQ-5D-5L is a valuable assessment tool for health-related QOL in patients with NF1, but it might not be sufficient for severity certification of NF1 in Japan. We would need the revision of the current certification based on the patients' demand in the future. Our findings might be useful for assessment of therapeutic effects and appropriate resource allocation in the care of patients with NF1.

In 2021, 217 excellent manuscripts were published in Hypertension Research. Editorial teams greatly appreciate the authors' contribution to hypertension research progress. Here, our editorial members have summarized twelve topics from published work and discussed current topics in depth. We hope you enjoy our special feature, "Update on Hypertension Research in 2021".

AIM In patients with liver cirrhosis, high levels of serum myostatin are associated with poor prognosis. We aimed to clarify the influence of myostatin on the prognosis of patients with non-alcoholic fatty liver disease-hepatocellular carcinoma (NAFLD-HCC) without cirrhosis and on the progression of liver fibrosis. METHODS Serum myostatin levels were evaluated in 234 patients who underwent primary surgical resection for single HCC. To clarify the impact of myostatin on liver fibrosis, we established human primary liver fibroblasts from resected livers, and cultured them in the presence of myostatin. RESULTS The median age was 67.4 years, the median L3 skeletal muscle mass index was 44.4 cm2 /m2 , and the median body mass index was 23.4 kg/m2 . Eighty-two (35.0%) patients had sarcopenia (L3 skeletal muscle mass index: men

Purpose Long-term effects on patient health-related quality of life (HRQoL) after direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) are unknown. We assessed the impact of DAA-mediated HCV clearance on HRQoL from DAA initiation to 1 year after confirmed sustained virological response at 24 weeks post-treatment (SVR24). Methods HRQoL was evaluated using the eight-item Short Form Health Survey (SF-8). Chronic HCV-infected patients were treated for 12 weeks with sofosbuvir-based DAAs. SF-8 was administered at baseline, treatment cessation, SVR24, and 1-year post-SVR24. Results A total of 109 chronic HCV-infected patients were enrolled. The average SF-8 scores were higher than the Japanese national standard values for bodily pain (BP) and mental health at baseline and for general health at 1-year post-SVR24. None of the SF-8 scores differed significantly between baseline and 1-year post-SVR24. Regarding age, sex, liver status, and treatment regimen, the SF-8 scores at 1-year post-SVR24 were affected by only age; individuals aged Conclusion Upon long-term assessment, although more factors trended higher than national standard values at 1-year post-SVR24 than at baseline, there were no significant changes within factors. As PCS tended to be associated with age, patients aged ≥ 65 years should be carefully monitored for PCS.