Postoperative evaluation of left atrial stiffness in patients with congenital heart diseases.

Left atrial (LA) stiffness is one of the most important factors involved in LA remodeling. LA stiffness has rarely been studied postoperatively in patients with congenital heart diseases (CHDs). This study aimed to evaluate LA stiffness in CHD patients postoperatively. Seventy-five patients (CHDs, 67; controls, 8; age range, 10-41 years) who underwent cardiac catheterization at our institution were included in this study. From the pulmonary artery wedge pressure waveform obtained during cardiac catheterization, the pressure range between the v wave and x trough was determined, and this value was divided by the LA reservoir strain obtained by echocardiography to calculate LA stiffness, as previously reported. LA stiffness was significantly higher in postoperative CHD patients than in controls (0.28 ± 0.17 vs. 0.13 ± 0.03, p = 0.001). Nineteen of 52 (37%) patients in their teens, 8 of 11 (73%) patients in their 20 s, and 1 of 4 (25%) patients aged > 30 years had elevated LA stiffness values. In particular, all patients with an LA reservoir strain < 20% had elevated LA stiffness. In postoperative CHD patients, LA stiffness was frequently elevated from a young age. CHD patients with elevated LA stiffness should be cautious of possible LA dysfunction in the future.

Utility of the frailty score for predicting prognosis and individualizing treatment intensity in elderly patients with diffuse large B cell lymphoma.

The optimal dose intensity of chemotherapy for elderly patients with diffuse large B cell lymphoma (DLBCL) remains controversial because of concerns about adverse events and comorbidities related to the patients' frailty. This single-center study retrospectively analyzed patients aged ≥ 70 years who were newly diagnosed with DLBCL and received chemotherapy between 2004 and 2022. Survival outcomes and treatment-related mortality (TRM) were stratified according to geriatric assessment variables, and the influence of chemotherapy dose intensity on outcomes was assessed using the frailty score with a Cox hazards model with restricted cubic spline (RCS) in patients aged 70-79 years. In total, 337 patients were included. The frailty score accurately predicted prognosis (5-year overall survival [OS]: 73.1%, 60.2%, and 29.7% in fit, unfit, and frail patients, respectively; P < 0.001) and TRM (5-year TRM: 0%, 5.4%, and 16.8 in fit, unfit, and frail patients, respectively; P < 0.001). Cox regression with RCS demonstrated a linear association between dose intensity and survival outcomes. Initial dose intensity (IDI) and relative dose intensity (RDI) had a significant impact on OS in fit patients. However, IDI and RDI had no significant effect on survival in non-fit (unfit and frail) patients. The frailty score identified non-fit patients with poorer survival and a higher risk of TRM. While fit patients were likely to benefit from full-dose R-CHOP, unfit and frail patients would likely benefit more from attenuated R-CHOP. This study suggested a potential role for the frailty score in individualizing treatment intensity in elderly patients with DLBCL.

[Polatuzumab vedotin, bendamustine, and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma, including the outcome as a bridging treatment to CAR-T cell therapy or allogeneic hematopoietic stem cell transplant].

Pola-BR (polatuzumab vedotin, bendamustine, and rituximab) therapy received approval for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in Japan in March 2021. There have been few reports on the efficacy and safety of Pola-BR therapy in Japanese clinical practice. A retrospective analysis was performed on twenty-nine patients with R/R DLBCL who received Pola-BR therapy at our institution (intent to cellular immunotherapy cohort: 20 patients, stand-alone treatment cohort: nine patients). The overall response rate was 69.0% (complete response 27.6%). The median progression-free survival was 5.1 months, with a 9.5-month median overall survival. In the intent to cellular immunotherapy cohort, 11 of 19 patients received chimeric antigen receptor T-cell (CAR-T) infusions, and one patient received allogeneic stem cell transplantation. Four patients received Pola-BR therapy, including bendamustine before leukapheresis, and all produced CAR-T products successfully. 3 of the 28 patients experienced grade3 or higher adverse events, and two required treatment discontinuation. Our single institution, a real-world cohort of R/R DLBCL patients showed high efficacy outcomes and a tolerable toxicity profile for Pola-BR therapy, which is comparable to previous studies. More cases are needed to determine its impact on CAR-T therapy and stem cell transplantation.

Anomalously High Ionic Conductivity of Li2SiS3-Type Conductors.

Solid-state electrolytes that exhibit high ionic conductivities at room temperature are key materials for obtaining the next generation of safer, higher-specific-energy solid-state batteries. However, the number of currently available crystal structures for use as superionic conductors remains limited. Here, we report a lithium superionic conductor, Li2SiS3, with tetragonal crystal symmetry, which possesses a new three-dimensional framework structure consisting of isolated edge-sharing tetrahedral dimers. This species exhibits an anomalously high ionic conductivity of 2.4 mS cm-1 at 298 K, which is 3 orders of magnitude higher than the reported ionic conductivity for its orthorhombic polymorph. The framework of this conductor consists mainly of silicon, which is abundant in natural resources, and its further optimization may lead to the development of new solid-state electrolytes for large-scale applications.

Limited effects of systemic or renal lipoprotein lipase deficiency on renal physiology and diseases.

Lipoprotein lipase (LPL) is an enzyme that catalyzes the hydrolysis of circulating triglyceride and the transport of fatty acids into cells. Its activity is positively regulated by insulin, and insulin resistance is associated with low LPL activity and subsequent hypertriglyceridemia. The involvement of hypertriglyceridemia in chronic kidney disease (CKD) is still under the debate in a clinical setting. Therefore, we aimed to study the role of hypertriglyceridemia in the disease using mice with systemic or renal-specific LPL deficiency. Systemic LPL deficiency was characterized by hypertriglyceridemia, but not renal injury or dyslipidemia-related conditions, such as fatty liver. Furthermore, the LPL deficiency-induced hypertriglyceridemia was not associated with a worsening of the CKD phenotype or atherosclerosis, even when CKD was induced by 5/6 nephrectomy. Next, because LPL-mediated fatty acid uptake may be important for energy metabolism in proximal tubular epithelial cells (PTECs), the role of renal LPL in renal physiology was studied by generating mice lacking LPL specifically in PTECs. These mice showed no abnormalities in their histology or renal reabsorption of micro molecules. These findings suggest that systemic and renal lipid abnormalities caused by LPL deficiency do not cause or worsen the development of renal injury, and provide novel insight regarding the potential role of lipotoxicity in the pathogenesis of obesity-related kidney injury.

Mechanism of Cooperative Degradation of Gum Arabic Arabinogalactan Protein by Bifidobacterium longum Surface Enzymes.

Gum arabic is an arabinogalactan protein (AGP) that is effective as a prebiotic for the growth of bifidobacteria in the human intestine. We recently identified a key enzyme in the glycoside hydrolase (GH) family 39, 3-O-α-d-galactosyl-α-l-arabinofuranosidase (GAfase), for the assimilation of gum arabic AGP in Bifidobacterium longum subsp. longum. The enzyme released α-d-Galp-(1→3)-l-Ara and ß-l-Arap-(1→3)-l-Ara from gum arabic AGP and facilitated the action of other enzymes for degrading the AGP backbone and modified sugar. In this study, we identified an α-l-arabinofuranosidase (BlArafE; encoded by BLLJ_1850), a multidomain enzyme with both GH43_22 and GH43_34 catalytic domains, as a critical enzyme for the degradation of modified α-l-arabinofuranosides in gum arabic AGP. Site-directed mutagenesis approaches revealed that the α1,3/α1,4-Araf double-substituted gum arabic AGP side chain was initially degraded by the GH43_22 domain and subsequently cleaved by the GH43_34 domain to release α1,3-Araf and α1,4-Araf residues, respectively. Furthermore, we revealed that a tetrasaccharide, α-l-Rhap-(1→4)-ß-d-GlcpA-(1→6)-ß-d-Galp-(1→6)-d-Gal, was a limited degradative oligosaccharide in the gum arabic AGP fermentation of B. longum subsp. longum JCM7052. The oligosaccharide was produced from gum arabic AGP by the cooperative action of the three cell surface-anchoring enzymes, GAfase, exo-ß1,3-galactanase (Bl1,3Gal), and BlArafE, on B. longum subsp. longum JCM7052. Furthermore, the tetrasaccharide was utilized by the commensal bacteria. IMPORTANCE Terminal galactose residues of the side chain of gum arabic arabinogalactan protein (AGP) are mainly substituted by α1,3/α1,4-linked Araf and ß1,6-linked α-l-Rhap-(1→4)-ß-d-GlcpA residues. This study found a multidomain BlArafE with GH43_22 and GH43_34 catalytic domains showing cooperative action for degrading α1,3/α1,4-linked Araf of the side chain of gum arabic AGP. In particular, the GH43_34 domain of BlArafE was a novel α-l-arabinofuranosidase for cleaving the α1,4-Araf linkage of terminal galactose. α-l-Rhap-(1→4)-ß-d-GlcpA-(1→6)-ß-d-Galp-(1→6)-d-Gal tetrasaccharide was released from gum arabic AGP by the cooperative action of GAfase, GH43_24 exo-ß-1,3-galactanase (Bl1,3Gal), and BlArafE and remained after B. longum subsp. longum JCM7052 culture. Furthermore, in vitro assimilation test of the remaining oligosaccharide using Bacteroides species revealed that cross-feeding may occur from bifidobacteria to other taxonomic groups in the gut.

Synchronous multiple primary tumors in patients with malignant lymphoma: a retrospective study.

BACKGROUND: Synchronous multiple primary malignant tumors (sMPMTs) are sometimes diagnosed in patients with malignant lymphoma. We herein investigated the prognostic impact of sMPMT in lymphoma patients and the optimal treatment strategy. METHODS: Seventy-five patients with sMPMTs (5.8%) among 1285 patients with lymphoma newly diagnosed between August 2004 and April 2020 were enrolled. RESULTS: In patients with indolent lymphoma, those with sMPMTs had a worse prognosis than those without sMPMTs (5-year overall survival [OS]: 73.4% and 87.8%, respectively; P = 0.047). Among those with high and low tumor burden, the cumulative rate of death due to solid tumors was significantly higher in patients with sMPMTs than those without sMPMTs (high tumor burden: 26.7% vs. 1.6%, P < 0.001; low tumor burden: 12.7% vs. 1.0%, P = 0.003). The presence of sMPMTs did not have a significant impact on outcomes in patients with diffuse large B-cell lymphoma (DLBCL) (5-year OS: 65.4% and 66.9%, respectively; P = 0.74; 5-year progression-free survival [PFS]: 65.5% and 59.9%, respectively; P = 0.65). However, the cumulative rate of death from solid tumor in patients with sMPMTs was significantly higher than in patients without sMPMTs (5-year cumulative rate: 7.4% and 2.1%, respectively; P = 0.004). The treatment sequence did not have a significant effect on outcomes or the relative dose intensity of chemotherapy. CONCLUSIONS: In patients with indolent lymphoma, those with sMPMTs had a significantly worse prognosis than those without sMPMTs, mainly because of high mortality due to solid tumors. The presence of sMPMTs was not a significant prognostic factor in patients with DLBCL. It is important to assess the status and need for early treatment of each type of malignancy in patients with sMPMTs.

Two α-L-arabinofuranosidases from Bifidobacterium longum subsp. longum are involved in arabinoxylan utilization.

Arabinoxylan (AX) and arabinoxylooligosaccharides (AXOs) are carbohydrate sources utilized by Bifidobacterium longum subsp. longum. However, their degradation pathways are poorly understood. In this study, we characterized two genes, BLLJ_1850 and BLLJ_1851, in the hemicellulose-degrading gene cluster (BLLJ_1836-BLLJ_1859) of B. longum subsp. longum JCM 1217. Both recombinant enzymes expressed in Escherichia coli exhibited exo-α-L-arabinofuranosidase activity toward p-nitrophenyl-α-L-arabinofuranoside. BlArafE (encoded by BLLJ_1850) contains the glycoside hydrolase family 43 (GH43), subfamily 22 (GH43_22), and GH43_34 domains. The BlArafE GH43_22 domain was demonstrated to release α1,3-linked Araf from AX, but the function of BlArafE GH43_34 could not be clearly identified in this study. BlArafD (encoded by BLLJ_1851) contains GH43 unclassified subfamily (GH43_UC) and GH43_26 domains. The BlArafD GH43_UC domain showed specificity for α1,2-linked Araf in α1,2- and α1,3-Araf double-substituted structures in AXOs, while BlArafD GH43_26 was shown to hydrolyze α1,5-linked Araf in the arabinan backbone. Co-incubation of BlArafD and BlArafE revealed that these two enzymes sequentially removed α1,2-Araf and α1,3-Araf from double-substituted AXOs in this order. B. longum strain lacking BLLJ_1850-BLLJ_1853 did not grow in the medium containing α1,2/3-Araf double-substituted AXOs, suggesting that BlArafE and BlArafD are important for the assimilation of AX. KEY POINTS: • BlArafD GH43 unclassified subfamily domain is a novel α1,2-L-arabinofuranosidase. • BlArafE GH43 subfamily 22 domain is an α1,3-L-arabinofuranosidase. • BlArafD and BlArafE cooperatively degrade α1,2/3-Araf double-substituted arabinoxylan.

Lingual Arteriovenous Malformation With Bleeding Treated With Polidocanol Foam Sclerotherapy Using Intestinal Forceps to Control Blood Flow.

ABSTRACT: Arteriovenous malformation (AVM) sometimes causes hemorrhage that can be fatal. We report a case of AVM of the tongue with bleeding that was treated by semi-emergent sclerotherapy with polidocanol. A 33-year-old woman presented with Schobinger stage III AVM of the tongue. Sclerotherapy with 3% polidocanol foam was performed under general anesthesia using curved intestinal forceps to clamp the root of the tongue for control of blood flow. Postoperatively, there was no further bleeding from the lesion. Three subsequent sclerotherapy sessions with polidocanol were performed, and there was a marked reduction in the size of the lesion. The lesion has remained well controlled in the year since the last sclerotherapy session.

[Tisagenlecleucel for relapsed/refractory diffuse large B-cell lymphoma: real-world data from single institute experience].

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the approach to patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study retrospectively analyzed patients treated with commercially available tisagenlecleucel at our hospital and evaluated its safety and effectiveness. Of the 21 patients evaluated, any grade and grade ≥3 cytokine release syndrome (CRS) occurred in 85.7% and 9.5% of the patients, respectively. A total of 66.7% received tocilizumab and 28.6% received glucocorticoids for the treatment of CRS. The complete response (CR) rate at 3 months was 61.9% (95% confidence interval [CI] 38.4-81.9). After a median follow-up of 6.3 months following CAR-T infusion, the progression-free survival (PFS) and overall survival rates at 6 months were 53.1% (95%CI 28.3-72.7) and 69.2% (95%CI 43.7-84.9), respectively. Severe cytopenia and hypogammaglobulinemia occurred frequently following CAR-T infusion. Eight patients (38.1%) had comorbidities that would have made them ineligible for leukapheresis in the JULIET trial. However, the presence of comorbidities at the time of leukapheresis had no significant effect on the rates of CR, PFS, and adverse events. Tisagenlecleucel for r/r DLBCL in the real-world setting showed high efficacy and manageable safety profile comparable with the pivotal trial.

Novel 3-O-α-d-Galactosyl-α-l-Arabinofuranosidase for the Assimilation of Gum Arabic Arabinogalactan Protein in Bifidobacterium longum subsp. longum.

Gum arabic arabinogalactan (AG) protein (AGP) is a unique dietary fiber that is degraded and assimilated by only specific strains of Bifidobacterium longum subsp. longum Here, we identified a novel 3-O-α-d-galactosyl-α-l-arabinofuranosidase (GAfase) from B. longum JCM7052 and classified it into glycoside hydrolase family 39 (GH39). GAfase released α-d-Galp-(1→3)-l-Ara and ß-l-Arap-(1→3)-l-Ara from gum arabic AGP and ß-l-Arap-(1→3)-l-Ara from larch AGP, and the α-d-Galp-(1→3)-l-Ara release activity was found to be 594-fold higher than that of ß-l-Arap-(1→3)-l-Ara. The GAfase gene was part of a gene cluster that included genes encoding a GH36 α-galactosidase candidate and ABC transporters for the assimilation of the released α-d-Galp-(1→3)-l-Ara in B. longum Notably, when α-d-Galp-(1→3)-l-Ara was removed from gum arabic AGP, it was assimilated by both B. longum JCM7052 and the nonassimilative B. longum JCM1217, suggesting that the removal of α-d-Galp-(1→3)-l-Ara from gum arabic AGP by GAfase permitted the cooperative action with type II AG degradative enzymes in B. longum The present study provides new insight into the mechanism of gum arabic AGP degradation in B. longumIMPORTANCE Bifidobacteria harbor numerous carbohydrate-active enzymes that degrade several dietary fibers in the gastrointestinal tract. B. longum JCM7052 is known to exhibit the ability to assimilate gum arabic AGP, but the key enzyme involved in the degradation of gum arabic AGP remains unidentified. Here, we cloned and characterized a GH39 3-O-α-d-galactosyl-α-l-arabinofuranosidase (GAfase) from B. longum JCM7052. The enzyme was responsible for the release of α-d-Galp-(1→3)-l-Ara and ß-l-Arap-(1→3)-l-Ara from gum arabic AGP. The presence of a gene cluster including the GAfase gene is specifically observed in gum arabic AGP assimilative strains. However, GAfase carrier strains may affect GAfase noncarrier strains that express other type II AG degradative enzymes. These findings provide insights into the bifidogenic effect of gum arabic AGP.

Protocol for an interventional study to reduce postpartum weight retention in obese mothers using the internet of things and a mobile application: a randomized controlled trial (SpringMom).

BACKGROUND: Obese pregnant women are known to experience poorer pregnancy outcomes and are at higher risk of postnatal arteriosclerosis. Hence, weight control during and after pregnancy is important for reducing these risks. The objective of our planned randomized controlled trial is to evaluate whether the rate of change in body weight in obese women before pregnancy to 12 months postpartum would be lower with the use of an intervention consisting of Internet of Things (IoT) devices and mobile applications during pregnancy to 1 year postpartum compared to a non-intervention group. METHODS: Women will be recruited during outpatient maternity checkups at four perinatal care institutions in Japan. We will recruit women at less than 30 weeks of gestation with a pre-pregnancy body mass index ≥ 25 kg/m2. The women will be randomly assigned to an intervention or non-intervention group. The intervention will involve using data (weight, body composition, activity, sleep) measured with IoT devices (weight and body composition monitor, activity, and sleep tracker), meal records, and photographs acquired using a mobile application to automatically generate advice, alongside the use of a mobile application to provide articles and videos related to obesity and pregnancy. The primary outcome will be the ratio of change in body weight (%) from pre-pregnancy to 12 months postpartum compared to before pregnancy. DISCUSSION: This study will examine whether behavioral changes occurring during pregnancy, a period that provides a good opportunity to reexamine one's habits, lead to lifestyle improvements during the busy postpartum period. We aim to determine whether a lifestyle intervention that is initiated during pregnancy can suppress weight gain during pregnancy and encourage weight loss after delivery. TRIAL REGISTRATION: UMIN: UMIN (University hospital Medical Information Network) 000,041,460. Resisted on 18th August 2020. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047278.

Working from home and dietary changes during the COVID-19 pandemic: A longitudinal study of health app (CALO mama) users.

It is plausible that the coronavirus disease pandemic and related changes in work and life patterns affected dietary patterns, but existing studies have limitations owing to a cross-sectional design. Using longitudinal data, we examined dietary changes in people due to the pandemic and work and life patterns. We conducted an online survey on changes in work and life patterns during the pandemic from April 30, 2020, to May 8, 2020, among users of a health app called CALO mama provided in Japan. We retrieved and linked the dietary data for 5929 participants from January 1, 2020, to May 13, 2020. Generalized linear mixed models were used to estimate the frequencies of food intake associated with the pandemic and work and life patterns. During the state of emergency, the frequency of intake of vegetables, beans, seaweeds, fish, meats, dairy products, and snacks increased, whereas alcohol intake decreased. Working from home was associated with increased intake of vegetables, fruits, dairy products, and snacks but decreased intake of seaweeds, meats, and alcohol. Time spent on childcare was associated with decreased intake of vegetables and fruits but increased intake of meats. Probable depressive symptoms were negatively associated with the frequency of food intake other than snacks and alcohol. We conclude that diet quality improved during the pandemic in general, but attention must be paid to overconsumption of snacks and negative factors such as increased burden of childcare and depression for healthy eating.

Clinical impact of controlling nutritional status score on the prognosis of patients with diffuse large B-cell lymphoma.

The controlling nutritional status (CONUT) score is a nutritional index calculated from serum albumin and total cholesterol levels and lymphocyte counts. Its role in predicting clinical outcomes of diffuse large B-cell lymphoma (DLBCL) has not been evaluated. In this retrospective study, data from 476 patients with DLBCL were analyzed. The cutoff value of the CONUT score was set as 4. CONUT score significantly stratified the overall survival (OS) and the progression-free-survival (PFS) (5-year OS, 49.0% vs 83.2%, P < .001; 5-year PFS, 46.1% vs 73.1%, P < .001) of the patients. Among patients at high-intermediate or high risk, as per the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), 5-year OS was lower in patients with high CONUT scores than in those with low CONUT scores (high-intermediate risk, 51.2% vs 75.5%, P < .001; high risk, 29.9% vs 63.3%, P = .007). Additionally, in patients with high CONUT scores, maintenance of relative dose intensity (RDI) of chemotherapy did not affect the 5-year OS (RDI > 80% vs RDI ≤ 80%: 59.8% vs 50.9%, P = .73). In the present study, we have demonstrated that the CONUT score is an independent prognostic factor in patients with DLBCL.

Atomic-Level Observation of Electrochemical Platinum Dissolution and Redeposition.

An understanding of electrochemical dynamics at solid-liquid interfaces is essential to develop advanced batteries and fuel cells and so on. For example, an atomic-level understanding of electrochemical Pt dissolution and redeposition behavior is crucial for optimizing the material design and operating conditions of polymer electrolyte fuel cells (PEFCs). This understanding enables the prevention of the degradation of Pt nanoparticles used as electrocatalysts. However, the mechanisms of Pt dissolution and redeposition are still not fully understood due to the lack of spatial resolution available with current observation techniques. Here, we have revealed for the first time atomic-level electrochemical Pt dissolution and redeposition behavior using in-house-developed observation techniques. We achieved atomic-level observations of closed-cell type liquid electrochemical transmission electron microscopy (TEM) by combining in-house-developed microelectromechanical system (MEMS) chips as an electrochemical cell, an aberration-corrected TEM apparatus, and an energy filter. Furthermore, accurate and stable potential control was achieved using an in-house-developed reversible hydrogen electrode (RHE) with a liquid junction connected to the outside of a TEM specimen holder. Our observation results confirmed that Pt dissolves from surface step edges layer-by-layer, as previously predicted by the density functional theory (DFT). The observation techniques developed are also applicable to other research fields concerning electrochemistry.

Degradation of plant arabinogalactan proteins by intestinal bacteria: characteristics and functions of the enzymes involved.

Arabinogalactan proteins (AGPs) are complex plant proteoglycans that function as dietary fiber utilized by human intestinal bacteria such as Bifidobacterium and Bacteroides species. However, the degradative mechanism is unknown because of the complexity of sugar chains of AGPs as well as variation among plant species and organs. Recently, AGP degradative enzymes have been characterized in Bifidobacterium and Bacteroides species. In this review, we summarize the characteristics and functions of AGP degradative enzymes in human intestinal bacteria.

Analysis of the prognostic value of BMI and the difference in its impact according to age and sex in DLBCL patients.

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B-cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R-CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (<18.5 kg/m2 ), 58 (14.3%); normal weight (≥18.5 to <25 kg/m2 ), 262 (64.5%); overweight (≥25 to <30 kg/m2 ), 75 (18.5%); and obese (≥30.0 kg/m2 ), 11 (2.7%). While the prognosis of overweight patients was good, being similar to that of normal weight, underweight, and obese patients had a worse prognosis (5-y overall survival [OS] was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight, and obese patients, respectively; P = .004). In multivariate analysis, underweight and obesity were independent prognostic factors for OS compared with normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female patients (≥70 y), patients with a low BMI (<25 kg/m2 ) had significantly inferior OS than those with a high BMI (≥25 kg/m2 ) (5-y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (<70 years), patients with a low BMI had significantly better OS than those with a high BMI (5-y OS, 88.6% vs 46.4%; P < .001). In male patients, there were no differences in the effect of BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age.

Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma.

The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI < 96.8 had significantly lower overall survival (OS) and progression-free survival (PFS) than those with a GNRI ≥ 96.8 (5-year OS, 61.2 vs. 84.4%, P < 0.001; 5-year PFS, 53.7 vs. 75.8%, P < 0.001). Multivariate analysis showed that performance status, Ann Arbor stage, serum lactate dehydrogenase, and GNRI were independent prognostic factors for OS. Among patients with high-intermediate and high-risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI < 96.8 than in those with a GNRI ≥ 96.8 (high-intermediate risk, 59.5 vs. 75.2%, P = 0.006; high risk, 37.4 vs. 64.9%, P = 0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.

Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis.

Beta-2 microglobulin as a significant prognostic factor and a new risk model for patients with diffuse large B-cell lymphoma.

Previous reports have evaluated the prognostic value of serum beta-2 microglobulin (B2MG) level in patients with non-Hodgkin lymphoma. However, its role in predicting clinical outcome of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been extensively investigated. Here, we evaluated the prognostic value of B2MG and proposed a new prognostic model including B2MG for patients with DLBCL. A total of 274 patients with newly diagnosed de novo DLBCL were retrospectively analyzed. We defined the best cutoff value as 3.2 mg/L by using a receiver operating characteristic curve. Patients with a B2MG level ≥3.2 mg/L had significantly lower overall survival (OS) and progression-free survival than those with a B2MG level <3.2 mg/L (3-year OS, 50.9% vs. 89.4%, p < 0.001; 3-year progression-free survival, 45.3% vs. 79.7%, p < 0.001). Multivariate analysis showed that B2MG, age, performance status, and Ann Arbor stage were independent prognostic factors for OS. We developed a new prognostic model consisting of these four significant factors. We stratified patients into four-risk groups: low (L, 0 factor), low-intermediate (LI, 1-2 factors), high-intermediate (HI, 3 factors), high (H, 4 factors). This new prognostic model showed better risk discrimination compared with the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 100% and 23.4% vs. 100% and 27.1%, in L and H risk groups, respectively). Our study suggested that B2MG level is a significant prognostic factor in patients with DLBCL. A new prognostic index composed of age, performance status, stage, and B2MG could stratify the outcomes of patients with DLBCL effectively and appears to be a valuable risk model for these patients. Copyright © 2016 John Wiley & Sons, Ltd.