Dexamethasone-sparing on days 2-4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial).

BACKGROUND: This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy. METHODS: Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%. RESULTS: A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life. CONCLUSION: DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation. CLINICAL TRIALS REGISTRY NUMBER: UMIN000032269.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13). CONCLUSIONS: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I.

Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.

C-terminus of serine-arginine protein kinase-like protein, SrpkF, is involved in conidiophore formation and hyphal growth under salt stress in Aspergillus aculeatus.

The serine-arginine protein kinase-like protein, SrpkF, was identified as a regulator for the cellulose-responsive induction of cellulase genes in Aspergillus aculeatus. To analyze various aspects of SrpkF function, we examined the growth of the control strain (MR12); C-terminus deletion mutant, which produced SrpkF1-327 (ΔCsrpkF); whole gene-deletion mutant of srpkF (ΔsrpkF), srpkF overexpressing strain (OEsprkF); and the complemented strain (srpkF+) under various stress conditions. All test strains grew normally on minimal medium under control, high salt (1.5 M KCl), and high osmolality (2.0 M sorbitol and 1.0 M sucrose). However, only ΔCsrpkF showed reduced conidiation on 1.0 M NaCl media. Conidiation of ΔCsrpkF on 1.0 M NaCl media was reduced to 12% compared with that of srpkF+. Further, when OEsprkF and ΔCsrpkF were pre-cultured under salt stress conditions, germination under salt stress conditions was enhanced in both strains. By contrast, deletion of srpkF did not affect hyphal growth and conidiation under the same conditions. We then quantified the transcripts of the regulators involved in the central asexual conidiation pathway in A. aculeatus. The findings revealed that the expression of brlA, abaA, wetA, and vosA was reduced in ΔCsrpkF under salt stress. These data suggest that in A. aculeatus, SrpkF regulates conidiophore development. The C-terminus of SrpkF seems to be important for regulating SrpkF function in response to culture conditions such as salt stress.

Perceptions regarding the concept and definition of patient-reported outcomes among healthcare stakeholders in Japan with relation to quality of life: a cross-sectional study.

Patient-reported outcomes (PROs) are frequently used in a variety of settings, including clinical trials and clinical practice. The definition of PRO and quality of life (QOL) and their relationship have been concluded through discussions among experts that has been the premise of PRO guidelines are not clearly stated in the guidelines. Therefore, the definition of PRO, especially in relation to QOL, is sometimes explained simply, as "PRO includes QOL," but this complicated matters. This study investigated the perceptions of PRO among various stakeholders (including patients and their families, the industry, clinicians, regulatory or health technology assessment personnel, and academic researchers) in Japan to clarify its definitions and that of QOL, including their relationship.We conducted a two-step survey: a qualitative interview survey and a web-based survey to ensure the validity of the survey. During the interviews, eight stakeholders described their perceptions and thoughts on PRO and its relationship to QOL, and their experience of using PRO. Overall 253 clinicians, 249 company employees, and 494 patients participated in the web survey to confirm how the findings of the interview survey supported the results.In the interview survey, patient advocates described various perspectives of PRO and QOL, including unexpected dynamic relationships, while the most other stakeholders explained PRO and QOL with the language used in the guidelines, but their responses were split. The web-based survey revealed that all stakeholders had a lower awareness of PRO than QOL. The most common perception of PRO, especially in the relationship to QOL, was "they did not fully overlap." Although there were differences in perceptions of the relationship between PRO and QOL among clinicians, company employees, and patients, all perceived PRO as a tool to facilitate communication in clinical practice.The present results are inconsistent with the simplified explanation of PRO, but consistent with the original PRO guideline definitions, which also considered the role of PRO in clinical practice. To make PRO a more potent tool, all stakeholders using PRO should confirm its definition and how it differs from QOL, have a unified recognition in each PRO use, and avoid miscommunication.

Independent, cooperative regulation of cellulolytic genes by paralogous transcription factors ClbR and ClbR2 in Aspergillus aculeatus.

The cellobiose-responsive regulator ClbR, a Zn(II)2Cys6 binuclear-cluster transcription factor, is a positive regulator of carbohydrate-active enzyme (CAZyme) genes responsive to cellulose in Aspergillus aculeatus. Because Zn(II)2Cys6 transcription factors tend to dimerize with proteins of the same family, we searched for a counterpart of ClbR and identified ClbR2, which is 42% identical to ClbR, as an interacting partner of ClbR by yeast two-hybrid screening. Genetic analyses suggested that ClbR and ClbR2 cooperatively regulate the expression of CAZyme genes in response to cellulose and 1,4-ß-mannobiose in A. aculeatus. CAZyme genes under the control of the transcription factor ManR were regulated by ClbR and ClbR2, whereas those controlled by the transcription factor XlnR were regulated by ClbR, but not ClbR2. These findings suggest that ClbR participates in multiple regulatory pathways in A. aculeatus by altering an interacting factor.

How to select and understand guidelines for patient-reported outcomes: a scoping review of existing guidance.

BACKGROUND: Over the past few decades, patient-reported outcomes (PROs) have been used to understand patient health conditions better. Therefore, numerous PRO measures (questionnaires) and guidelines or guidance have been developed. However, it is challenging to select target guidance from among the many available guidance and to understand the chosen guidance. This study comprehensively collected the existing PRO guidance for clinical trials or studies and practices to support novice PRO users in academia, industry, clinical practice, and regulatory and reimbursement decision-making. METHODS: For the scoping review, we searched the MEDLINE, Embase, Google Books, WorldCat, and the National Library of Medicine (NLM) Bookshelf databases from 2009 to 2023. The eligibility criteria were PRO guidance for clinical trials, clinical practice, or application such as health technology assessment. Those guidance cover aspects such as quality of life (QOL), PRO, health-related QOL, health state utilities, psychometric requirements, implementation methods, analysis and interpretation, or clinical practice applications. After the systematic search, three researchers individually reviewed the collected data, and the reviewed articles and books were scrutinized using the same criteria. RESULTS: We collected the PRO guidance published in articles and books between 2009 and 2023. From the database searches, 1,455 articles and 387 books were identified, of which one book and 33 articles were finally selected. The collected PRO guidance was categorized into the adoption of PRO measures, design and reporting of trials or studies using PROs, implementation of PRO evaluation in clinical trials or studies or clinical practice, analysis and interpretation of PROs, and application of PRO evaluation. Based on this categorization, we suggest the following for novices: When selecting guidance, novices should clarify the "place" and "purpose" where the guidance will be used. Additionally, they should know that the terminology related to PRO and the scope and expectations of PROs vary by "places" and "purposes". CONCLUSIONS: From this scoping review of existing PRO guidance, we provided summaries and caveats to assist novices in selecting guidance that fits their purpose and understanding it.

Association between hypogammaglobulinaemia and severe infections during induction therapy in ANCA-associated vasculitis: from J-CANVAS study.

OBJECTIVES: To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections. METHODS: We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine-Gray model to assess the association between low IgG (the minimum IgG levels <500 mg/dl) and severe infections. In addition, the association was expressed as a restricted cubic spline (RCS) and analysed by treatment subgroups. RESULTS: Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03-3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens. CONCLUSION: Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation.

Protocol for a confirmatory trial of the effectiveness and safety of palliative arterial embolization for painful bone metastases.

BACKGROUND: Transcatheter arterial embolization (TAE) has long been used for hemostasis of traumatic or postoperative hemorrhage and embolization of tumors. Previous retrospective studies of TAE for painful bone metastases showed 60%-80% pain reduction with a median time to response of 1-2 days. Compared with radiotherapy and bisphosphonates, time to response appeared earlier than that of radiotherapy or bone-modifying agents. However, few prospective studies have examined TAE for this indication. Here, we describe the protocol for a confirmatory study designed to clarify the efficacy and safety profile of TAE. METHODS: This study will be a multicenter, single-arm confirmatory study (phase 2-3 design). Patients with painful bone metastases from any primary tumor are eligible for enrollment. TAE will be the main intervention. Following puncture of the femoral artery under local anesthesia and insertion of an angiographic sheath, angiography will confirm that the injected region includes tumor vasculature. Catheter position will be adjusted so that the embolization range does not include non-target tissues. Spherical embolic material will then be slowly injected into the artery to embolize it. The primary endpoint (efficacy) is the proportion of subjects with pain relief at 72 h after TAE and the secondary endpoint (safety) is the incidence of all NCI Common Terminology Criteria for Adverse Events version 5.0 Grade 4 adverse events and Grade ≥ 3 necrosis of the central nervous system. DISCUSSION: If the primary and secondary endpoints are met, TAE can be a treatment choice for painful bone metastases. Trial registry number is UMIN-CTR ID: UMIN000040794. TRIAL REGISTRATION: The study is ongoing, and patients are currently being enrolled. Enrollment started in March 2021. A total of 36 patients have participated as of Aug 2022. PROTOCOL VERSION: Ver1.4, 13/07/2022.

A new function of a putative UDP-glucose 4-epimerase on the expression of glycoside hydrolase genes in Aspergillus aculeatus.

In order to figure out the induction mechanisms of glycoside hydrolase genes in Aspergillus aculeatus, we screened approximately 9,000 transfer DNA (T-DNA)-inserted mutants for positive regulators involved in the induction. Since the mutants possess the orotidine 5'-monophosphate decarboxylase gene as a reporter gene to monitor the cellulose-responsive expression of the cellobiohydrolase I gene (cbhI), candidate strains were isolated by counterselection against 5-fluoroorotic acid (5-FOA). One 5-FOA-resistant mutant harboring the T-DNA at the uge5 locus showed reduced cellulose utilization and cbhI expression. A. aculeatus Uge5 is homologous to Aspergillus fumigatus uge5 (Afu5g10780; E-value, 0.0; identities, 93%), which catalyzes the conversion of uridine diphosphate (UDP)-glucose to UDP-galactopyranose. The uge5 deletion mutant in A. aculeatus (Δuge5) showed reduced conidium formation on minimal media supplemented with galactose, locust bean gum (LBG), and guar gum as a carbon source. ß-1,4-Endoglucanase and ß-1,4-mannanase production in submerged culture containing LBG was reduced to 10% and 6% of the control strain at day 5, respectively, but no difference was observed in cultures containing wheat bran. The expression of major cellulolytic and mannolytic genes in the presence of mannobiose in Δuge5 was reduced to less than 15% of the control strain, while cellobiose-responsive expression was only modestly reduced at early inducing time points. Since all test genes were controlled by a transcription factor ManR, these data demonstrate that Uge5 is involved in inducer-dependent selective expression of genes controlled via ManR. KEY POINTS: • UDP-glucose 4-epimerase (Uge5) regulates expression of glycosyl hydrolase genes. • ManR regulates both cellobiose- and mannobiose-responsive expression. • Uge5 plays a key role in mannobiose-responsive expression.

Optimal Dose of Intravenous Cyclophosphamide during remission induction therapy in ANCA-associated vasculitis: a retrospective cohort study of J-CANVAS.

OBJECTIVES: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We retrospectively assessed patients with AAV who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes were also evaluated. RESULTS: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly. CONCLUSION: Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg).

Serine-arginine protein kinase-like protein, SrpkF, stimulates both cellobiose-responsive and D-xylose-responsive signaling pathways in Aspergillus aculeatus.

Aspergillus aculeatus produces cellulolytic enzymes in the presence of their substrates. We screened a library of 12,000 A. aculeatus T-DNA-inserted mutants to identify a regulatory factor involved in the expression of their enzyme genes in response to inducers. We found one mutant that reduced the expression of FIII-avicelase (chbI) in response to cellulose. T-DNA was inserted into a putative protein kinase gene similar to AN10082 in A. nidulans, serine-arginine protein kinase F, SrpkF. Fold increases in srpkF gene expression in response to various carbon sources were 2.3 (D-xylose), 44 (Avicel®), 59 (Bacto™ Tryptone), and 98 (no carbon) compared with D-glucose. Deletion of srpkF in A. aculeatus resulted in a significant reduction in cellulose-responsive expression of chbI, hydrocellulase (cel7b), and FIb-xylanase (xynIb) genes at an early induction phase. Further, the srpkF-overexpressing strain showed upregulation of the srpkF gene from four- to nine-fold higher than in the control strain. srpkF overexpression upregulated cbhI and cel7b in response to cellobiose and the FI-carboxymethyl cellulase gene (cmc1) and xynIb in response to D-xylose. However, the srpkF deletion did not affect the expression of xynIb in response to D-xylose due to the less expression of srpkF under the D-xylose condition. Our data demonstrate that SrpkF is primarily involved in cellulose-responsive expression, though it has a potential to stimulate gene expression in response to both cellobiose and D-xylose in A. aculeatus.

Parenting experiences of cancer patients with minor children and their conversations about the possibility of death: a cross-sectional web-based survey for an online cancer community.

PURPOSE: Many cancer patients with minor children experience difficulty talking about their illness with their children. This study aimed to investigate the parenting experiences of cancer patients with minor children and their conversations about the possibility of death. METHODS: A cross-sectional web-based survey was conducted between April and May 2019. Cancer patients with at least one child aged < 18 years were recruited from an online peer support group called "Cancer Parents." The participants were asked to complete a questionnaire about their experiences of talking about their illnesses with their children. The participants were classified into those who disclosed their cancer to their children ("disclosing group"), and those who did not disclose ("non-disclosing group"). The association between whether they talked with their children about their cancer, and whether it included conversations about the possibility of death, was examined. RESULTS: A total of 370 parents participated (with 80.8% female parents, with a median age of 43.0 years). The disclosing group (n = 274, 74.1%) wanted to know what their child felt, more than the non-disclosing group did (p < 0.001). Members of the non-disclosing group had a greater tendency than those in the disclosing group to report that they did not want their children to see their suffering (p = 0.002) and did not know how to explain their disease status (p < 0.002). Some members of both the disclosing (42.1%) and non-disclosing (6.5%) groups told their children about the possibility of death. CONCLUSION: This study showed that 74.1% of the patients with minor children disclosed their cancer to their children. The parents' feelings when thinking about interacting with their children differed significantly between the disclosing and non-disclosing groups. It is important for healthcare professionals treating patients with cancer to provide appropriate multidisciplinary support for discussing their diagnosis and prognosis with their children.

Effect of paracentesis on the survival of patients with terminal cancer and ascites: a propensity score-weighted analysis of the East Asian Collaborative Cross-cultural Study to Elucidate the Dying Process.

PURPOSE: Paracentesis is among the most widely utilized treatments for malignant ascites (MA). However, paracentesis in patients with MA has the potential to be associated with life-shortening effects. Thus, this study aimed to investigate whether paracentesis affected the duration of survival in such patients. METHODS: We performed a post hoc analysis of a prospective multicenter observational study investigating the dying process and end-of-life care in patients with terminal cancer, admitted to 23 palliative care units in Japan. Survival duration was compared between patients who did (paracentesis group) and did not undergo paracentesis (non-paracentesis group). We used inverse probability of treatment weighting (IPTW) to control for baseline covariates between groups. RESULTS: Among the 1896 initially enrolled patients, 568 with ascites were included in the study cohort. Eighty-five (15.0%) patients underwent paracentesis. The primary tumor site was the pancreas (51.9%, n = 295), followed by the gastrointestinal tract (22.7%, n = 129). Non-adjusted median durations of survival were 22 days (95% confidence interval [CI]: 16-25) and 12 days (95% CI: 11-13) in the paracentesis and non-paracentesis groups, respectively (hazard ratio [HR]: 0.69, 95% CI: 0.54-0.88; p = 0.003). The IPTW-adjusted median survival durations were 22 (95% CI: 16-25) and 16 days (95% CI: 12-22) in the paracentesis and non-paracentesis groups, respectively (HR: 0.89, 95% CI: 0.64-1.24; p = 0.492). No serious adverse events occurred in the paracentesis group. CONCLUSIONS: Paracentesis does not negatively affect the survival of patients with cancer and MA and can be a standard treatment in palliative care settings.

Palliative care physicians' recognition of patients after immune checkpoint inhibitors and immune-related adverse events.

PURPOSE: This study investigated the experience of palliative care physicians (PCPs) and their knowledge and recognition of immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs) in clinical practice as well as the need to provide palliative care services for patients after ICI treatments. METHODS: A cross-sectional survey with self-administered questionnaires was conducted between February and April 2020. A total of 759 questionnaires were sent to PCPs in Japan. The changes in the PCPs' knowledge and recognition of ICIs and irAEs due to the increased experiences of treating patients after ICI treatments were analyzed. RESULTS: Four hundred ninety-two responses (64.8%) were analyzed. Only 15.0% of respondents had no experience of patients after ICI treatments, while 53.9% had experience of more than six patients. On the other hand, 40% of respondents had no experience of patients with suspected irAEs, while only 13.4% had experience of more than six patients. Respondents with more experience of patients after ICI treatments or those with suspected irAEs had extensive knowledge of ICIs and irAEs, were more confident in treating these patients, and tended to consider irAEs as therapeutic indications. The majority of respondents required guidelines and efficient consultation systems with oncologists. CONCLUSION: This study demonstrated that PCPs with experience had extensive knowledge and confidence of ICIs and irAEs and tended to recognize irAEs as therapeutic indications. The establishment of a more intimate relationship between PCPs and oncologists is important for providing better treatment for these patients.

An observational study on nutrition status in gastric cancer patients receiving ramucirumab plus taxane: BALAST study.

Limited data are available regarding the efficacy of nutrition support in advanced gastric cancer (AGC) patients receiving a standard second-line combination chemotherapy. The BALAST study is conducted as a prospective, multicenter observational study to evaluate the efficacy of nutrition support for patients with AGC treated with ramucirumab plus taxane as second-line treatment. As part of the routine care, patients who are malnourished or at risk of malnutrition will receive nutrition support from dietitians. We will enroll a total of 26 patients to estimate weight control rate at 12 weeks as primary end point. This study will generate valuable data reinforcing the role of nutrition support therapy for AGC patients receiving second-line chemotherapy.

Lay abstract Various guidelines recommend that nutrition support therapy should be considered if cancer patients are malnourished or at risk of malnutrition. Several studies have revealed that body weight loss, which is an important factor in determining the nutrition status, may predict survival during second-line standard chemotherapy with ramucirumab and a taxane for advanced gastric cancer (AGC) patients. However, limited data are available regarding the efficacy of nutrition support in AGC patients receiving ramucirumab and a taxane. This study is conducted as a prospective, multicenter observational study to evaluate the efficacy of nutrition support for Japanese patients with AGC treated with ramucirumab and a taxane. This study will generate valuable data reinforcing the role of nutrition support therapy for AGC patients in second-line treatment. Clinical trial registration: UMIN000037867.

Smallest Organic Tetracation in the Gas Phase: Stability of Multiply Charged Diiodoacetylene Produced in Intense Femtosecond Laser Fields.

Coulomb explosion imaging, which is the reconstruction of a molecular structure by measuring the three-dimensional momenta of atomic ions formed by a Coulomb explosion of multiply charged molecular cations (MMCs), has been utilized widely. In contrast, intact MMCs, whose properties and reactions are interesting from both fundamental and applied scientific perspectives, themselves have been little explored to date. This study demonstrates that the four-atom molecule diiodoacetylene (DIA) can survive as a long-lived species in the gas phase after the removal of four electrons in intense femtosecond laser fields. The electron configurations of the equilibrium structures of the electronic ground states calculated by the complete active space self-consistent field (CASSCF) method reveal the stability of multiply charged DIA. The dissociation energies are estimated to be 3.01, 3.59, 2.57, 1.82, and 1.61 eV for neutral, cation radical, dication, trication radical, and tetracation, respectively. A fairly deep potential well suggests that a DIA tetracation is metastable toward dissociation, whereas the repulsive potential of a pentacation radical confirms its absence in the mass spectrum. With their sufficiently long lifetimes, minimum number of atoms, and simple dissociation paths, DIA MMCs are promising candidates for further experimental and theoretical investigations of multiply charged ion chemistry.

A component of the septation initiation network complex, AaSepM, is involved in multiple cellulose-responsive signaling pathways in Aspergillus aculeatus.

Various carbohydrate-active enzymes in Aspergillus are produced in response to physiological inducers, which is regulated at the transcriptional level. To elucidate the induction mechanisms in Aspergillus, we screened for new regulators involved in cellulose-responsive induction from approximately 10,000 Aspergillus aculeatus T-DNA-inserted mutants. We constructed the T-DNA-inserted mutant library using the host strain harboring the orotidine 5'-monophosphate decarboxylase gene (pyrG) under the control of the FIII-avicelase gene (cbhI) promoter. Thus, candidate mutants deficient in cellulose-responsive induction were positively screened via counter selection against 5-fluoroorotic acid (5-FOA). Among less than two hundred 5-FOA-resistant mutants, one mutant that the T-DNA inserted into the AasepM locus reduced the cbhI expression in response to cellulose. Since AaSepM is similar to Schizosaccharomyces pombe Cdc14p (E-value, 2e-20; identities, 33%), which is a component of the septation initiation network (SIN)-complex, we constructed an AasepM deletion mutant (ΔAasepM). We analyzed the expression of cellulase and xylanase genes in response to cellulose, septation, and conidiation in ΔAasepM. The AasepM deletion leads to delayed septation and decreased formation of the conidium chain in A. aculeatus but does not affect hyphal growth on minimal media. We also confirmed AaSepM's involvement in multiple cellulose-responsive signaling pathways of cellulase and xylanase genes under the control of the ManR-dependent, XlnR-dependent, and ManR- and XlnR-independent signaling pathways. KEY POINTS : • A new regulator for cellulolytic gene expression has been identified. • AaSepM is involved in septation and conidiation in A. aculeatus. • AasepM is involved in multiple cellulose-responsive signaling pathways.

Developing a Japanese version of the 'scale of attitudes toward pharmacist-physician collaboration'.

There are many reports that pharmacotherapy has been optimized to ensure collaboration between physicians and pharmacists. Various scales assess the relationship between physicians and pharmacists as well as medical students and pharmacy students. The Scale of Attitudes Toward Physician-Pharmacist Collaboration (SATP2C) can be applied not only to the physician-pharmacist relationship but also to the medical-pharmacy student relationship. As there is no Japanese version of the SATP2C, we developed one and examined its psychometric properties. SATP2C scores were measured before and after interprofessional education (IPE) to verify responsiveness. The scale showed confirmed reliability: Cronbach's alphas were 0.79 for Responsibility and Accountability, 0.68 for Shared Authority, and 0.67 for Interdisciplinary Education. Pre and post-IPE, each mean subscale score increased: Responsibility and Accountability, 0.7 ± 0.4; Shared Authority, 0.2 ± 0.3; and Interdisciplinary Education, 0.3 ± 0.2. Although the total score increased (1.2 ± 0.7), this was non-significant. The Japanese version of the SATP2C can be considered, at least initially, to have reached an acceptable level of reliability and validity. The new measure is currently the only scale in Japan that can evaluate attitudes toward physician-pharmacist collaboration regarding IPE. Further studies are needed to confirm responsiveness pre- and post-IPE.

The association between health-related quality of life and achievement of personalized symptom goal.

PURPOSE: The aim of study was to explore the potential association between patient's self-reported physical symptom management goals as personalized symptom goal (PSGs) and health-related quality of life (HRQOL) in cancer patients. The secondary outcome was to investigate the relationship between number of physical symptoms not achieving the PSGs and HRQOL in cancer patients. METHODS: This single-center prospective observational study comprised 140 consecutive outpatients. We evaluated the PSGs and HRQOL using the Functional Assessment of Cancer Therapy-General (FACT-G). Patients were administered a self-report questionnaire, including reports on their physical symptom intensity and PSGs using Edmonton Symptom Assessment System-revised (ESAS-r) scores. We investigated the correlation between PSGs achievement (ESAS-r score ≤ PSG score) and FACT-G total scores, and relationship between and number of physical symptoms not achieving the PSGs (ESAS-r score > PSG score) and FACT-G total scores. RESULTS: The patients who did not achieve PSGs of pain, tiredness, lack of appetite, and shortness of breath had a lower FACT-G total score (p < 0.05). Multivariate linear regression showed that higher number of physical symptoms not achieving the PSGs correlated with lower FACT-G scores (decreasing by 1.826 points for each such symptom, p < 0.01). Predictors of increased number of physical symptoms not achieving the PSGs were younger age and a higher symptom intensity of anxiety. CONCLUSION: PSGs achievement was associated with HRQOL in cancer patients. Additionally, the number of unachieved PSGs were independent determinant of poor HRQOL, particularly in younger cancer patients and those with higher symptom intensity of anxiety.