Clinical significance of the estimation of pulmonary-right ventricular uncoupling in patients with transthyretin amyloid cardiomyopathy.

Aims: There are few data on the prognostic impact of pulmonary-right ventricular (RV) uncoupling in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM).

Methods And Results: Among the 174 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from 2002 to 2021, 143 patients who met the current Japanese guideline and had sufficient information for two-dimensional speckle tracking echocardiography were retrospectively analysed. During a median follow-up of 1209 days, 39 cardiac deaths occurred.

An orally available P1'-5-fluorinated M inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier.

We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.

A machine learning model to predict neurological deterioration after mild traumatic brain injury in older adults.

Objective: Neurological deterioration after mild traumatic brain injury (TBI) has been recognized as a poor prognostic factor. Early detection of neurological deterioration would allow appropriate monitoring and timely therapeutic interventions to improve patient outcomes. In this study, we developed a machine learning model to predict the occurrence of neurological deterioration after mild TBI using information obtained on admission.

A single-arm, phase II study of sotorasib plus carboplatin/pemetrexed in advanced non-squamous non-small cell lung cancer patients with KRAS G12C mutation (WJOG14821L, SCARLET).

Background: The efficacy and safety of sotorasib plus platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous non-small cell lung cancer (non-Sq NSCLC) were previously reported with limited follow-up period.

Method: SCARLET was a single-arm phase II study of chemotherapy-naïve patients with KRAS G12C-mutated non-Sq NSCLC. Participants received sotorasib 960 mg daily plus four cycles of carboplatin (area under the curve, 5)/pemetrexed 500 mg/m, followed by sotorasib/pemetrexed until disease progression.

Low survival due to higher risk of relapse and non-relapse mortality after allogeneic HSCT in ATL compared with AML and ALL.

Background: Patients with adult T-cell leukemia/lymphoma (ATL) are considered to have worse outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) than patients with other hematological malignancies, owing to high risk of relapse and immunocompromised status. However, no studies have compared transplant outcomes between patients with ATL and those with other hematological malignancies using a large-scale database.

Objectives: To compare transplant outcomes between patients with ATL and those with other leukemias and to identify factors contributing to worse transplant outcomes in ATL patients.

Biology-inspired dynamic microphysiological system approaches to revolutionize basic research, healthcare and animal welfare.

The regular workshops held by the Center for Alternatives to Animal Testing (CAAT) on biology-inspired microphysiological systems (MPS) taking place every four years, have become a reliable measure to assess fundamental scientific, industrial and regulatory trends for translational science in the MPS-field from a bird's eye view. The 2023 workshop participants at that time concluded that the technology as used within academia has matured significantly, underlined by the broad use of MPS and the steadily increasing number of high quality research publications - yet, broad industry adoption of MPS has been slow, despite strong interest. Academic research using MPS primarily aims to accurately recapitulate human biology in MPS-based organ models in areas where traditional models have been lacking key elements of human physiology, thereby enabling breakthrough discoveries for life sciences.

Impact of Altered Graft Position During Living Donor Liver Retransplantation and its Outcomes.

Introduction: Liver retransplantation (reLT), which is the only treatment for liver graft failure, remains challenging not only because of its technical nature but also because it is performed in high-risk patients.

Methods: Nineteen patients who underwent reLT (second LT, n = 18; third LT, n = 1) between 1999 and 2021 were divided into two groups according to the graft laterality between prior transplantation and reLT (ipsilateral group, n = 9; contralateral group, n = 10). The aim of this study was to evaluate the short- and the long-term outcomes of patients who underwent living donor reLT and compared graft survival between ipsilateral and contralateral grafts.

Betagenin ameliorates diabetes by inducing insulin secretion and β-cell proliferation.

Recent success with the use of glucagon-like peptide-1 (GLP-1) receptor analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of patients with diabetes has highlighted the role of the intestine as an endocrine organ. Gut-derived hormones, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and ghrelin, have important roles in the control of energy metabolism and food intake, and are associated with the metabolic syndrome. In this study, we isolated and identified a new intestine-derived hormone, betagenin, and showed that it stimulates insulin secretion and β-cell proliferation and suppresses β-cell apoptosis.

Non-canonical imprinting, manifesting as post-fertilization placenta-specific parent-of-origin dependent methylation, is not conserved in humans.

Genomic imprinting is the parent-of-origin dependent monoallelic expression of genes often associated with regions of germline-derived DNA methylation that are maintained as differentially methylated regions (gDMRs) in somatic tissues. This form of epigenetic regulation is highly conserved in mammals and is thought to have co-evolved with placentation. Tissue-specific gDMRs have been identified in human placenta, suggesting that species-specific imprinting dependent on unorthodox epigenetic establishment or maintenance may be more widespread than previously anticipated.

Prognostic Analysis of Pathological Stage I Lung Adenocarcinoma Harboring Major EGFR Mutations.

Background: While Epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LUAD) has favorable outcomes with targeted therapy, early-stage prognosis remains influenced by pathological factors and central nervous system (CNS) recurrence. The study aimed to clarify prognostic factors in pathological stage (pStage) I EGFR mutation-positive LUAD.

Methods: Between 2015 and 2018, 2,191 pStage I LUAD cases with known EGFR status (excluding EGFR testing after recurrence) who received anatomical resection were included from multiple institutions in Japan.

Dispersion behavior of Fukushima-derived Cs over the North Pacific with emphasis on its sensitivity to vertical velocity and diffusion.

This study simulated the dispersion of Cs in the North Pacific using a Lagrangian particle model, incorporating basin-wide atmospheric deposition and direct release from the Fukushima accident. Three experiments examined the impact of vertical diffusion and velocity on dispersion behavior. EXP01 and EXP02 assumed zero vertical velocity with different vertical diffusion coefficients (1 × 10 and 2 × 10 m/s, respectively), while EXP03 used a 3-day average vertical velocity and the same diffusion coefficient as EXP01.

Hydrogel coils in intracranial aneurysm treatment: a multicenter, prospective, randomized open-label trial.

Objective: Studies have demonstrated the effectiveness of hydrogel-coated coils (HGCs) to achieve the composite endpoint of decreased recanalization rates and greater safety. Herein, the authors aimed to assess the true ability of second-generation HGCs to prevent recanalization.

Methods: This randomized controlled study, the HYBRID (Hydrocoil Versus Bare Platinum Coil in Recanalization Imaging Data) trial, comparing HGCs with bare platinum coils (BPCs), was conducted in 43 Japanese institutions.

Plasma galectin-9 levels correlate with blood monocyte turnover and predict simian/human immunodeficiency virus disease progression.

Background: Late-stage human immunodeficiency virus (HIV) infection is typically characterized by low CD4 + T-cell count. We previously showed that profound changes in the monocyte turnover (MTO) rate in rhesus macaques infected by the simian immunodeficiency virus (SIV) outperforms declining CD4 + T-cell counts in predicting rapid health decline associated with progression to terminal disease. High MTO is associated with increased tissue macrophage death.

FAM136A depletion induces mitochondrial stress and reduces mitochondrial membrane potential and ATP production.

FAM136A deficiency has been associated with Ménière's disease. However, the underlying mechanism of action of this protein remains unclear. We hypothesized that FAM136A functions in maintaining mitochondria, even in HepG2 cells.

Influence of Worsening Renal Function and Baseline Chronic Kidney Disease on Clinical Outcomes in Patients With Chronic Coronary Syndromes: Insights From the REAL-CAD Study.

Background: The effect of worsening renal function and baseline chronic kidney disease (CKD) on outcomes in patients with chronic coronary syndrome in the setting of optimal medical therapy remains unknown.

Methods And Results: The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease) study is a prospective, multicenter, randomized trial of high-dose (pitavastatin 4 mg/day) or low-dose (pitavastatin 1 mg/day) statin therapy in 12 118 patients with chronic coronary syndrome. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or unstable angina requiring hospitalization (major adverse cardiac and cerebral events [MACCE]).

Alginate-Based Hydrogels with Amniotic Membrane Stem Cells for Wound Dressing Application.

Objective: Chronic wounds are a common clinical problem that necessitate the exploration of novel regenerative therapies. We report a method to investigate the in vitro wound healing capacity of an innovative biomaterial, which is based on amniotic membrane-derived stem cells (AMSCs) embedded in an alginate hydrogel matrix. The aim of this study was to prepare an sodium alginate-based hydrogel, cross-linked calcium chloride (CaCl with the active ingredient AMSC (AMSC/Alg-H) and to evaluate its in vitro effectiveness for wound closure.

Impact of aspirin on biochemical recurrence of prostate cancer after robot assisted radical prostatectomy in a multicenter retrospective cohort study.

This study evaluated the impact of aspirin on the biochemical recurrence (BCR) rate following robot-assisted radical prostatectomy (RARP) in patients. A database search identified patients who underwent RARP for pT2-3N0M0 disease at any of 25 centers between 2011 and 2022, categorized into aspirin (n = 350) and control groups (n = 5857). Adjustment by 1:1 propensity score matching (PSM) and Mahalanobis distance matching (MDM) created 350 matched pairs.

Heart failure treatment and serum carnitines in HFpEF and HFrEF with or without hypertension - a pilot study.

The ratio of serum acylcarnitines to free carnitines (AC/FC) reflects impaired cardiomyocyte β-oxidization. The effect of heart failure (HF) treatment on AC/FC remained unclear. This pilot study retrospectively examined treatment-induced AC/FC changes in patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) in 148 consecutive inpatients undergoing echocardiography and carnitine measurement at admission and discharge.

Effectiveness of Data-Driven Gating FDG PET/CT for Abdominal Region.

This study aimed to validate the effectiveness of MotionFree (MF) in the abdominal region using 2 different PET/CT scanners to determine how to use MF efficiently. All 198 patients underwent respiratory-gated F-FDG PET/CT with MF. Imaging was performed using Discovery MI (DMI) and Discovery IQ (DIQ) PET/CT scanners, and all data were divided into 2 groups in each category (abdominal: upper and lower abdomen, lesion size, <20 mm and ≥20 mm; scanner group: DMI and DIQ).

Prognostic value of left atrial stiffness in patients undergoing transcatheter aortic valve implantation.

Aim: This study was performed to evaluate the association between left atrial (LA) stiffness and outcomes in patients undergoing transcatheter aortic valve implantation (TAVI).

Methods And Results: This study involved 279 patients with aortic stenosis (AS) who underwent TAVI at Kumamoto University Hospital between 2015 and 2023. During a median follow-up of 468 days (interquartile range: 258-825 days), 42 deaths occurred.

Artificial dural regeneration matrix as a substitute for autologous tissue in indirect bypass in Moyamoya disease: Investigation of a rat model of chronic cerebral hypoperfusion.

Indirect bypass using autologous tissue is effective in Moyamoya disease, especially among pediatric patients. This study aimed to evaluate the effectiveness of indirect bypass using DuraGen (absorbable artificial dura mater composed of collagen matrix), as a substitute for autologous tissue in a rat model of chronic cerebral hypoperfusion. Male Wistar rats were subjected to bilateral internal carotid artery occlusion and divided into three groups: a control group without bypass surgery, a group wherein indirect bypass was performed using the temporalis muscle (encephalo-myo-synangiosis [EMS] group), and a group wherein DuraGen was used (Dura group).

HIF1α Plays a Crucial Role in the Development of TFE3-Rearranged Renal Cell Carcinoma by Orchestrating a Metabolic Shift Toward Fatty Acid Synthesis.

Tumor development often requires cellular adaptation to a unique, high metabolic state; however, the molecular mechanisms that drive such metabolic changes in TFE3-rearranged renal cell carcinoma (TFE3-RCC) remain poorly understood. TFE3-RCC, a rare subtype of RCC, is defined by the formation of chimeric proteins involving the transcription factor TFE3. In this study, we analyzed cell lines and genetically engineered mice, demonstrating that the expression of the chimeric protein PRCC-TFE3 induced a hypoxia-related signature by transcriptionally upregulating HIF1α and HIF2α.

Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy: A Randomized Clinical Trial With Open-Label Extension.

Importance: There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN.

Objective: To present the long-term efficacy and safety of patisiran in adults with hATTR-PN.