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Cellulose nanofibers (CNFs) extracted from plant cell walls form a three-dimensional network in water and stabilize the dispersion of droplets, which are used as emulsion stabilizers. In this study, four types of alkyl-grafted CNFs (ACNFs) with different lengths of dialkyl chains (diC4, diC6, diC8, and diC10) were synthesized by the surface modification of 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized CNF (TOCNF) to improve the stability of oil-in-water Pickering emulsions (PEs). The ACNF-stabilized emulsions with a 20/80 ratio of oil/water were prepared using two different oils (olive oil and eucalyptus oil) and the ACNF 1.0 % dispersion, and the changes over time were investigated at approximately 25 °C. Compared to TOCNF, the ACNFs provided more stable olive oil-PE (o-PE) and eucalyptus oil-PE (e-PE) although the stabilization behaviors of o-PE and e-PE differed. Olive oil, which contained rich long-chain fatty acids, was more likely to interact with the ACNFs, thereby promoting the interfacial adsorption of oil droplets. On the other hand, eucalyptus oil is mainly composed of 1,8-cineole and does not have alkyl chains, so the interaction with the ACNFs was weak and therefore, sufficient interfacial adsorption could not be obtained. The results of the particle size distribution and viscosity measurements also showed that the ACNFs contributed significantly to the stabilization of o-PE. Based on the overall experimental results, it was determined that the diC6-ACNF gave the most significant stability improvement. Therefore, we designed an alkylated CNF that mimics diC6-ACNF for MD simulations. MD simulations showed that hydrophobic modification created a hydrophobic interaction between the alkyl chain and dodecane molecules as the oil, leading to the enhancing adsorption of ACNF at the oil droplet interfaces.

Spent coffee grounds (SCGs) contain abundant polysaccharides consisting of mannose (29 %), galactose (11 %), and glucose (11 %) and are a promising source of holocellulose nanofibers (HCNFs). In this study, the mannan-rich HCNFs were isolated from the SCG holocellulose in the yield of 52 % SCGs using an ultrahigh-pressure wet jet mill. The HCNF was refined by passing the suspension through a high-pressure homogenizer with a 95 μm nozzle 1–15 times. The 5-pass HCNFs were 2.4 nm wide and 0.7 μm long with 143 viscosity-average degrees of polymerization and contained mannan I crystals (5–10 nm in size) on cellulose microfibrils. The delignification process in water at 75 °C based on the Wise method allowed recrystallization of mannan on a cellulose microfibril substrate. The once-freeze-dried HCNFs had 30–50 nm widths and were not fully nanofibrillated in water when shaking the HCNF/water suspensions but exhibited comparable viscosities to those prepared by mechanical milling. The SCGs-derived HCNFs have a high potential for application in the food industry.

Abstract Background Cancer cachexia affects more than half of all cancer patients, reducing survival rates. Evidence‐based approaches are urgently needed to optimize treatment. Methods A systematic review and network meta‐analysis were conducted to assess the effectiveness and safety of different pharmacotherapies for cancer cachexia. Three databases (PubMed, Cochrane Library, and Web of Science) were searched for the period from January 1, 2000, to March 20, 2024. The netmeta package in R software was used to calculate the pooled effect, employing a random effects model. Results Seven placebo‐controlled randomized trials involving 1421 patients were analyzed. Pairwise analysis showed that body weight increases were 4.6 kg (95% confidence interval [CI] 0.83–8.37 kg) for olanzapine, 3.82 kg (95% CI 0.73–6.91 kg) for espindolol (20 mg), 2.36 kg (95% CI 1.84–2.89 kg) for anamorelin (100 mg), and 1.31 kg (95% CI 0.42–2.19 kg) for anamorelin (50 mg). In terms of safety profiles, olanzapine demonstrated the lowest odds ratio when compared to placebo, at 0.26 (95% CI 0.07–0.94), followed by anamorelin (50 mg) at 0.86 (95% CI 0.30–2.48), and anamorelin (100 mg) at 0.89 (95% CI 0.42–1.88). However, network meta‐analysis could not confirm the superiority of olanzapine over anamorelin in terms of efficacy and safety. Conclusion Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients.

Several surgical techniques have been documented for approaching and repairing superior semicircular canal dehiscence syndrome (SCDS). These techniques encompass the trans-middle cranial fossa, transmastoid, endoscopic approaches, and round window reinforcement (RWR). RWR entails the placement of connective tissue with or without cartilage and around the round window niche, restricting the round window’s movement to minimize the 3rd window effect and restore the bony labyrinth closer to its normal state. We employed the multilayer RWR technique, resulting in significant postoperative improvement and long-lasting effects for 3.7 years in 2 cases. Here, we present the clinical findings, surgical procedures, and the effectiveness of multilayer RWR. This technique can be the initial choice for surgical treatments of SCDS due to its high effectiveness, longer-lasting effect, and minimal risk of surgical complications.

Abstract Background Dacomitinib significantly improves progression‐free survival and overall survival (OS) compared with gefitinib in patients with non–small‐cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)‐activating mutations. However, dacomitinib often causes skin toxicities, resulting in treatment discontinuation. We aimed to evaluate a prophylactic strategy for skin toxicity induced by dacomitinib. Methods We performed a single‐arm, prospective, open‐label, multi‐institutional phase II trial for comprehensive skin toxicity prophylaxis. Patients with NSCLC harboring EGFR‐activating mutations were enrolled and received dacomitinib with comprehensive prophylaxis. The primary endpoint was the incidence of skin toxicity (Grade ≥2) in the initial 8 weeks. Results In total, 41 Japanese patients participated between May 2019 and April 2021 from 14 institutions (median age 70 years; range: 32–83 years), 20 were male, and 36 had a performance status of 0–1. Nineteen patients had exon 19 deletions and L858R mutation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration. Skin toxicities (Grade ≥2) occurred in 43.9% of patients (90% confidence interval [CI], 31.2%–56.7%). The most frequent skin toxicity was acneiform rash in 11 patients (26.8%), followed by paronychia in five patients (12.2%). Due to skin toxicities, eight patients (19.5%) received reduced doses of dacomitinib. The median progression‐free survival was 6.8 months (95% CI, 4.0–8.6 months) and median OS was 21.6 months (95% CI, 17.0 months–not reached). Conclusion Although the prophylactic strategy was ineffective, the adherence to prophylactic medication was quite good. Patient education regarding prophylaxis is important and can lead to improved treatment continuity.

In addition to affecting oral functions such as temporomandibular joint function, mastication, and speech, malocclusion caused by skeletal maxillary prognathism also entails sociopsychological implications. Surgical orthodontic treatment to improve occlusion and oral function and to correct esthetic disharmony is important to improve patients’ quality of life. We report the case of a 32-year-old woman who visited our hospital with a chief complaint of proclined upper front teeth. Clinical examination revealed maxillary overgrowth and severe labial inclination of the maxillary incisors with palatal gingival recession. The incisal protrusion was corrected with a maxillary anterior alveolar osteotomy—a surgical orthodontic method that could improve the overbite without causing excessive lingual inclination, while also minimizing orthodontic movement of the maxillary anterior teeth. This treatment is generally indicated in cases of maxillary prognathism with a relatively stable occlusal relationship in the molar region. As a result of the treatment, the patient’s chief complaint improved and a long-term functional occlusion was achieved. This paper outlines the pre- and posttreatment skeletal and occlusal changes.

Introduction: Necitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown. Methods: This multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs. The primary end point was progression-free survival (PFS). Results: A total of 93 patients from 35 institutions in Japan were enrolled. The median PFS, median overall survival (OS), and objective response rate were 4.4 months (95% confidence interval [CI]: 3.8–5.3), 13.3 months (95% CI: 9.6–16.5), and 27.3% (95% CI: 18.3–37.8), respectively. The median PFS, median OS, and objective response rate for second-line, third-line, and fourth-line treatment groups were 4.8 months, 3.8 months, and 4.3 months (p = 0.24); 15.7 months, 11.6 months, and 10.1 months (p = 0.06); and 31.0%, 13.6%, and 37.5% (p = 0.22), respectively. The severity of GCN-related skin disorders was associated with longer PFS (p < 0.05) and OS (p < 0.05). The frequencies of grade ≥3 skin disorders, hypomagnesemia, pneumonitis, and febrile neutropenia were 16.1%, 7.5%, 1.1%, and 4.3%, respectively. There were no treatment-related deaths. Conclusions: GCN for ICI-pretreated patients with LSqCC seems tolerable and offers promising efficacy regardless of treatment line, and ICI pretreatment might enhance GCN efficacy.

Abstract Sarcoma is a rare cancer, and little is known about the etiology, lifestyle epidemiology, and actual circumstances of treatment in hospitals in Japan. Understanding these issues is essential for the effective prevention and treatment of sarcoma. We therefore investigated the incidence of a personal and family cancer history in a total of 1320 sarcoma patients at the National Cancer Center Hospital. In addition, obesity, hypertension, dyslipidemia, diabetes mellitus, drinking, smoking, age and sex were compared in a descriptive study of 1159 of these sarcoma patients who were ≥ 20 years of age, and 7738 controls derived from the National Health and Nutrition Examination Survey in Japan. A total of 8% of sarcoma patients had a personal history of another cancer, and 30% of soft tissue sarcoma patients had a family cancer history in a first-degree relative (malignant peripheral nerve sheath tumor, 52%; leiomyosarcoma, 46%). A smoking habit was associated with the development of sarcoma (odds ratio [OR], 2.05; 95% confidence interval, 1.78–2.37; p

Réplica à Carta às Editoras de Autoria de Pablo Salomón Montes-Arcón

This paper is an extended version of a previously reported conference paper regarding a low-power design for NAND Flash. As the number of bits per NAND Flash die increases with cost scaling, the IO data path speed increases to minimize the page access time with a scaled CMOS in IOs. The power supply for IO buffers, namely, VDDQ, decreases from 3 V to 1.2 V, accordingly. In this paper, the way in which a reduction in VDDQ can contribute to power reduction in the BL path is discussed and validated. Conventionally, a BL voltage of about 0.5 V has been supplied from a supply voltage source (VDD) of 3 V. The BL path power can be reduced by a factor of VDDQ to VDD when the BL voltage is supplied by VDDQ. To maintain a sense margin at the sense amplifiers, the supply source for BLs is switched from VDDQ to VDD before sensing. As a result, power reduction and an equivalent sense margin can be realized at the same time. The overhead of implementing this operation is an increase in the BL access time of about 2% for switching the power supply from VDDQ to VDD and an increase in the die size of about 0.01% for adding the switching circuit, both of which are not significant in comparison to the significant power reduction in the BL path power of the NAND die of about 60%. The BL path is then designed in 180 nm CMOS to validate the design. When the cost for powering the SSD becomes quite significant, especially for data centers, an additional lower voltage supply, such as 0.8 V, dedicated to BL charging for read and program verifying operations may be the best option for future applications.

Background: Naldemedine, a peripherally acting opioid μ receptor antagonist, is effective for prevention of opioid-induced constipation (OIC); however, evidence on its use in children is limited. Objective: To evaluate the efficacy and safety of naldemedine in pediatric patients with OIC. Design, Setting/Subjects: Retrospective analysis of 32 pediatric patients with OIC treated with naldemedine in a single institution in Japan from June 2017 to March 2021. Measurements: Efficacy was evaluated in 13 evaluable patients with bowel movement (BM) response, defined as those with at least three BMs in the first 7 days after naldemedine initiation and an increase of at least one BM from baseline. Safety was evaluated by examining adverse events (AEs) based on the Common Terminology Criteria for AEs (v5.0). Results: BM response was recorded in 11 of the 13 patients (85%), and the number BMs per day significantly increased from 0.43 before naldemedine to 1.00 after naldemedine (p = 0.025). The most common AE was diarrhea, observed in 16 of the 32 patients (50%), and all instances were grade 1 or 2. In three of the 16 patients, naldemedine was discontinued owing to worsening diarrhea. Conclusions: In pediatric patients, naldemedine resulted in a high rate of BM response and increased the BM frequency, indicating its efficacy. In some patients, grade 2 diarrhea required naldemedine discontinuation, suggesting that it should be used with caution in pediatric patients. Further studies are warranted to determine the optimal naldemedine dose in pediatric patients. [ABSTRACT FROM AUTHOR]

Introdução: O câncer colorretal é a neoplasia mais frequente do trato gastrointestinal, sendo a segunda principal causa de morte por câncer no mundo. Objetivo: Traçar um perfil clínico-epidemiológico do câncer colorretal na Região Oeste do Paraná (Brasil), entre 2016 e 2018. Método: Estudo observacional analítico do tipo transversal, construído a partir da análise de resultados de exames anatomopatológicos, realizados entre 2016 a 2018. Realizaram-se análises por estatística descritiva, teste de associação qui-quadrado e U de Mann-Whitney. Adotou-se nível de significância de 5%. Resultados: A análise de 509 laudos positivos para câncer colorretal permitiu identificar o predomínio de pacientes do sexo masculino e a idade média de diagnóstico de 62 anos. A malignidade mostrou-se mais incidente na faixa etária de 61 a 70 anos (29,9%), e considerável número de casos ocorreu em pacientes abaixo de 50 anos (19,6%). Houve predomínio em cólon esquerdo e do tipo histológico adenocarcinoma infiltrativo moderadamente diferenciado. Verificou-se associação entre topografia da doença e sexo, com maior predominância do sexo feminino para tumores do cólon direito e do sexo masculino para tumores do cólon esquerdo (p=0,0081). Conclusão: A partir deste estudo, delineia-se um perfil clínico-epidemiológico do câncer colorretal na Região Oeste do Paraná, com maior incidência da doença em homens, sexagenários, além de predomínio de tumores em cólon esquerdo e do tipo adenocarcinoma infiltrativo moderadamente diferenciado. Tais achados são relevantes considerando a possibilidade de aplicação assertiva de protocolos internacionais de rastreio do câncer nessa população.

Background: The standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC study. Although multiple Japanese phase II studies have shown high efficacy and tolerability of CRT with cisplatin plus S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported. Objectives: We conducted a multicenter phase II study of this approach, the interim analysis of which showed a high transition rate to durvalumab consolidation therapy. Here, we report the primary analysis results. Design: In treatment-naïve LA-NSCLC, cisplatin (60 mg/m 2 , day 1) and S-1 (80–120 mg/body, days 1–14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab (10 mg/kg) every 2 weeks for up to 1 year. Methods: The primary endpoint was 1-year progression-free survival (PFS). The expected 1-year PFS and its lower limit of the 80% confidence interval (CI) were set as 63% and 47%, respectively, based on the results of TORG1018 study. Results: In all, 59 patients were enrolled, with 51 (86.4%) proceeding to durvalumab. The objective response rate throughout the study was 72.9% (95% CI: 59.7–83.6%). After median follow-up of 21.9 months, neither median PFS nor OS was reached. The 1-year PFS was 72.5% (80% CI: 64.2–79.2%, 95% CI: 59.1–82.2%), while the 1-year overall survival was 91.5% (95% CI: 80.8–96.4%). No grade 5 adverse events were observed throughout the study. The most common adverse event during the consolidation phase was pneumonitis (any grade, 78.4%; grade ⩾3, 2.0%). Eventually, 52.5% of patients completed 1-year durvalumab consolidation therapy from CRT initiation. Conclusion: This study of durvalumab after SP-based CRT met its primary endpoint and found a 1-year PFS of 73% from CRT initiation. This study provides the first prospective data on the prognosis and tolerability of durvalumab consolidation from the initiation of CRT. Trial registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127

Abstract Background A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted. Methods A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE. Results Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified. Conclusions Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.

Background: The standard of care for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC trial. Disease progression and pneumonitis were reported as the main reasons to preclude the initiation of durvalumab in multiple retrospective studies. However, the transition rate and the reasons for failure to proceed to consolidation therapy with durvalumab after CRT were not evaluated prospectively. Although phase II studies in Japan have shown high efficacy and tolerability of CRT with cisplatin + S-1 (SP), no prospective study using durvalumab after SP-based CRT has yet been reported. We therefore conducted a phase II study to verify the efficacy and safety of durvalumab following SP-based CRT. In this interim analysis, we report the transition rate and the reasons for its failure. Methods: In treatment-naïve LA-NSCLC, cisplatin (60 mg/m 2 , day 1) and S-1 (80–120 mg/body, days 1–14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab every 2 weeks for up to 12 months. The primary endpoint was 12 month progression-free survival rate. Results: Fifty-nine patients were enrolled, of whom 86.4% (51/59) proceeded to durvalumab. All of them initiated durvalumab within 42 days after CRT [median 18 days (range: 3–38)], including 27.5% (14/51) in

Background: Cancer cachexia affects more than half of all cancer patients, reducing survival rates. Evidence‐based approaches are urgently needed to optimize treatment. Methods: A systematic review and network meta‐analysis were conducted to assess the effectiveness and safety of different pharmacotherapies for cancer cachexia. Three databases (PubMed, Cochrane Library, and Web of Science) were searched for the period from January 1, 2000, to March 20, 2024. The netmeta package in R software was used to calculate the pooled effect, employing a random effects model. Results: Seven placebo‐controlled randomized trials involving 1421 patients were analyzed. Pairwise analysis showed that body weight increases were 4.6 kg (95% confidence interval [CI] 0.83–8.37 kg) for olanzapine, 3.82 kg (95% CI 0.73–6.91 kg) for espindolol (20 mg), 2.36 kg (95% CI 1.84–2.89 kg) for anamorelin (100 mg), and 1.31 kg (95% CI 0.42–2.19 kg) for anamorelin (50 mg). In terms of safety profiles, olanzapine demonstrated the lowest odds ratio when compared to placebo, at 0.26 (95% CI 0.07–0.94), followed by anamorelin (50 mg) at 0.86 (95% CI 0.30–2.48), and anamorelin (100 mg) at 0.89 (95% CI 0.42–1.88). However, network meta‐analysis could not confirm the superiority of olanzapine over anamorelin in terms of efficacy and safety. Conclusion: Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients. [ABSTRACT FROM AUTHOR]

Abstract Background Atezolizumab is a programmed death‐ligand 1 (PD‐L1) targeted monoclonal antibody that inhibits PD‐L1 interacting with its receptors PD‐1 and B7‐1, thereby enhancing anticancer immunity. Some real‐world efficacy and safety studies of anti‐PD‐1 antibody have been previously reported. However, there have been no reports investigating the efficacy of atezolizumab monotherapy in clinical practice which have focused on performance status and previous anti‐PD‐1 antibody treatment. Methods We retrospectively reviewed consecutive advanced NSCLC patients who received atezolizumab monotherapy between April 2018 and February 2019 at eight institutions. A total of 152 patients with NSCLC were enrolled in this study. Results A total of 38 patients (25%) had already been treated with anti‐PD‐1 treatment (nivolumab or pembrolizumab) before atezolizumab. The median OS and TTF was 384 days (12.8 months) (95% confidence interval [CI]: 206–424), and 42 days (1.4 months) (95% CI: 27–56) in all patients, respectively. ECOG PS 0 had significantly longer OS (median OS; not reached, p

Abstract Exosomes are involved in a wide range of biological processes in human cells. Considerable evidence suggests that engineered exosomes (eExosomes) containing therapeutic agents can attenuate the oncogenic activity of human cancer cells. Despite its biomedical relevance, no information has been available for oral squamous cell carcinoma (OSCC), and therefore the development of specific OSCC-targeting eExosomes (octExosomes) is urgently needed. We demonstrated that exosomes from normal fibroblasts transfected with Epstein–Barr Virus Induced-3 (EBI3) cDNA were electroporated with siRNA of lymphocyte cytoplasmic protein 1 (LCP1), as octExosomes, and a series of experiments were performed to evaluate the loading specificity/effectiveness and their anti-oral cancer cell activities after administration of octExosomes. These experiments revealed that octExosomes were stable, effective for transferring siLCP1 into OSCC cells and LCP1 was downregulated in OSCC cells with octExosomes as compared with their counterparts, leading to a significant tumor-suppressive effect in vitro and in vivo. Here we report the development of a new valuable tool for inhibiting tumor cells. By engineering exosomes, siLCP1 was transferred to specifically suppress oncogenic activity of OSCC cells. Inhibition of other types of human malignant cells merits further study.