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To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups whose immunity against the viruses is compromised. Therapeutic antibodies against dengue are ideally engineered to abrogate binding to Fcγ receptors (FcγRs), which can induce antibody-dependent enhancement (ADE). However, the Fc effector functions of neutralizing antibodies against SARS-CoV-2 have recently been reported to improve post-exposure therapy, while they are dispensable when administered as prophylaxis. Hence, in this report, we investigated the influence of Fc engineering on anti-virus efficacy using the anti-dengue/Zika human antibody SIgN-3C and found it affected the viremia clearance efficacy against dengue in a mouse model. Furthermore, we demonstrated that complement activation through antibody binding to C1q could play a role in anti-dengue efficacy. We also generated a novel Fc variant, which displayed the ability for complement activation but showed very low FcγR binding and an undetectable level of the risk of ADE in a cell-based assay. This Fc engineering approach could make effective and safe anti-virus antibodies against dengue, Zika and other viruses.

This retrospective multicenter study aimed to analyze the clinical features and prognosis of 24 patients diagnosed with LGMS between 2002 and 2019 in the Japanese sarcoma network. Twenty-two cases were surgically treated and two cases were treated with radical radiotherapy (RT). The pathological margin was R0 in 14 cases, R1 in 7 cases, and R2 in 1 case. The best overall response in the two patients who underwent radical RT was one complete response and one partial response. Local relapse occurred in 20.8% of patients. Local relapse-free survival (LRFS) was 91.3% at 2 years and 75.4% at 5 years. In univariate analysis, tumors of 5 cm or more were significantly more likely to cause local relapse (p < 0.01). In terms of the treatment of relapsed tumors, surgery was performed in two cases and radical RT was performed in three cases. None of the patients experienced a second local relapse. Disease-specific survival was 100% at 5 years. A wide excision aimed at the microscopically R0 margin is considered the standard treatment for LGMS. However, RT may be a viable option in unresectable cases or in cases where surgery is expected to cause significant functional impairment.

Abstract Myostatin, a member of the transforming growth factor-β superfamily, is an attractive target for muscle disease therapy because of its role as a negative regulator of muscle growth and strength. Here, we describe a novel antibody therapeutic approach that maximizes the potential of myostatin-targeted therapy. We generated an antibody, GYM329, that specifically binds the latent form of myostatin and inhibits its activation. Additionally, via “sweeping antibody technology”, GYM329 reduces or “sweeps” myostatin in the muscle and plasma. Compared with conventional anti-myostatin agents, GYM329 and its surrogate antibody exhibit superior muscle strength-improvement effects in three different mouse disease models. We also demonstrate that the superior efficacy of GYM329 is due to its myostatin specificity and sweeping capability. Furthermore, we show that a GYM329 surrogate increases muscle mass in normal cynomolgus monkeys without any obvious toxicity. Our findings indicate the potential of GYM329 to improve muscle strength in patients with muscular disorders.

Over the past thirty years, Problem Solving Therapy (PST) has been shown to be an effective treatment for many different problems and patient populations (Nezu, 2004). Among its many clinical applications, PST interventions were developed for persons with intellectually disabilities (ID), where improving problem-solving skills led to adaptive behavioral improvements (Nezu, Nezu, & Arean 1991). This article provides a rationale and description of the potential benefits of including PST as a treatment for ID sex offenders. Recommendations regarding future research directions are offered.

In this brief article, we provide relevant background concerning the prevalence, characteristics and vulnerabilities of intellectually disabled (ID) sex offenders, as well as scientifically-informed guidelines for treatment. Finally, we provide a description of Project STOP, an outpatient cognitive behavioral assessment an treatment program.

Introduction Mucinous urethral adenocarcinoma is a rare and progressive cancer of the prostatic urethra. Reports on palliative systemic treatment for mucinous urethral adenocarcinoma are few. We present a case of coexisting mucinous urethral and prostate adenocarcinomas managed with systemic treatment. Case presentation A 66‐year‐old man presented with gross hematuria and urinary retention. Prostate‐specific antigen level was elevated, at 99 ng/mL, and prostate biopsy revealed moderately to poorly differentiated adenocarcinoma. Hormone therapy and standard chemotherapy for prostate adenocarcinoma were ineffective. Prostate re‐biopsy revealed coexisting mucinous urethral and prostate adenocarcinomas. Gemcitabine + cisplatin chemotherapy and folinic acid + 5‐fluorouracil + irinotecan chemotherapy temporarily suppressed the cancer, but 14 months after presentation, he developed liver metastasis and died. Autopsy revealed metastasis of both mucinous urethral adenocarcinoma and carcinosarcoma. Conclusion Mucinous urethral adenocarcinoma is difficult to diagnose in coexistence with prostate adenocarcinoma. This was an extremely rare case showing chemoresistance due to epithelial‐mesenchymal transition.

Abstract The quality of dimension lumber (2 by 4 lumber) was preliminarily investigated in four common Mongolian softwoods: Pinus sylvestris L., Pinus sibirica Du Tour, Picea obovata Ledeb., and Larix sibirica Ledeb. to produce high quality dimension lumber for structural use. In total 61, 39, 67, and 37 pieces of lumber were prepared for Pinus sylvestris, Pinus sibirica, Picea obovata, and L. sibirica, respectively. The lumber was visually graded and then tested in static bending to obtain the 5% lower tolerance limits at 75% confidence level (f 0.05) of the modulus of elasticity (MOE) and the modulus of rupture (MOR). In addition, the effects of sawing patterns on bending properties were also analyzed. The f 0.05 of the MOE and MOR were 4.75 GPa and 15.6 MPa, 3.39 GPa and 11.0 MPa, 3.78 GPa and 11.7 MPa, and 6.07 GPa and 22.3 MPa for Pinus sylvestris, Pinus sibirica, Picea obovata, and L. sibirica, respectively. These results suggested that with a few exceptions, characteristic values of MOR in the four common Mongolian softwoods resembled those in similar commercial species already used. In visual grading, over 80% of total lumber was assigned to select structural and No. 1 grades in Pinus sylvestris and Pinus sibirica, whereas approximately 40% of total lumber in L. sibirica was No. 3 and out of grades. Sawing patterns affected bending properties in Pinus sylvestris and L. sibirica, but did not affect Pinus sibirica and Picea obovata. Dynamic Young's modulus was significantly correlated with bending properties of dimension lumber for the four species. Based on the results, it was concluded that dimension lumber for structural use can be produced from the four common Mongolian softwoods.

The propagation characteristics of backward-volume magnetostatic spin-waves in epitaxial Fe(001) films were studied by frequency-domain and time-domain spin-wave propagation spectroscopies using a vector network analyser. Due to the combination of cubic-magnetocrystalline anisotropy and anisotropic spin-wave dispersion, the backward-volume spin-wave exhibited a complicated packet propagation. For the hard-axis propagation, the group velocity of the spin wave was greatly enhanced at low external magnetic fields and propagation occurred even under no magnetic field. By analysing within a theoretical model and micromagnetic simulations, these transmission character of the backward-volume magnetostatic spin-waves in an epitaxial iron film was well reproduced. The observed characteristics are essential information to promote two-dimensional magnonic devices utilizing cubic-anisotropic materials.

Factors that influence the decision of voluntary driving cessation in patients living with Parkinson’s disease (PD) are still unclear. We aimed to reveal the factors affecting the decision of voluntary driving cessation in patients with PD. This hospital-based cross-sectional study recruited consecutive outpatients with PD. Data on sociodemographic and clinical characteristics and medication use were collected from the patients using semistructured interviews. Cognitive function was evaluated using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). We excluded patients with dementia or motor impairment (Hoehn−Yahr stage>3). We divided the patients into two groups, with and without voluntary driving cessation (D: driver; RD: retired driver), and conducted investigations using multivariate logistic regression analyses. Of the 40 patients, 8 (20.0%) voluntarily retired from driving. Patients who decided on driving cessation had a higher prevalence of freezing of gait (FOG) (D vs. RD, 25.0% vs. 87.5%; P=0.001) and tended to have lower scores for attention in the MoCA-J (D vs. RD, 5.0±1.2 vs. 4.1±1.4; P=0.086). Multivariable analysis showed that FOG was independently associated with driving cessation (odds ratio: 14.46, 95% confidence interval: 1.91–303.74). FOG was associated with voluntary driving cessation in patients with PD without dementia or severe motor impairment. Physicians should consider providing extensive social support to maintain patients’ mobility and independence, especially if the patients have these clinical factors.

Objectives: The efficacy of negative pressure wound therapy (NPWT) and its application to severely contaminated wounds sustained during surgery remain to be established. Here, we evaluated the efficacy of utilizing NPWT until delayed primary closure (DPC) by assessing the infection rates in patients with lower gastrointestinal perforations. Methods: This prospective multicenter cohort study included 56 patients that underwent abdominal surgery for lower gastrointestinal perforations in eight institutions, from February 2016 to May 2017. All patients received NPWT after surgery before attempting DPC. The extent of peritonitis was categorized according to Hinchey's classification. Patients in stages II-IV were included. Results: Five patients had surgical site infections (SSIs) during NPWT and did not receive a DPC (9%). Of the 51 patients that received DPCs, 44 had no infection (91%) and 7 developed SSIs after the DPC (13.7%). For stages II, III, and IV, the SSI rates were 0%, 22.6%, and 35.7%, respectively; the median (range) times to wound healing were 15 (10-36), 19 (11-99), and 19 (10-53) days, respectively. There were no significant differences between the stages. Conclusions: NPWT followed by DPC resulted in low infection rates in each peritonitis stage. This approach appears promising as an alternative to traditional DPC alone for treating lower gastrointestinal perforations.

Abstract The modulus of elasticity (MOE) and modulus of rupture (MOR) were evaluated for 190 pieces of dimension lumber (2 by 4 lumber, 38 by 89 mm in cross-section) produced from Larix sibirica trees grown in Mongolia. The 5% tolerance limits of the MOE and MOR were 5.70 GPa and 15.1 MPa, respectively. The value of the 5% tolerance limit of the MOR exceeded the characteristic value of 2 by 4 lumber in visual grading class No. 3 of the Japanese Agricultural Standard for the D. fir-L, Hem-Tam, JS-III and S-P-F softwood species groups. A significant positive correlation was found between the MOE and MOR, although air-dry density was weakly correlated with bending properties in L. sibirica.

Hiroki Matsuura,1 Hidemi Iwasaka,2 Satoko Nezu,3 Toyosaku Ota,4 Kosuke Okazaki,4 Kazuhiko Yamamuro,4 Yoko Nakanishi,5 Naoko Kishimoto,4 Junzo Iida,6 Toshifumi Kishimoto4 1Department of Psychiatry, Nara Prefecture General Rehabilitation Center, Shiki-Gun, Nara, Japan; 2Developmental Center for Child and Adult, Shigisan Hospital, Ikoma-Gun, Nara, Japan; 3Department of Epidemiology, Nara Medical University, Kashihara, Nara, Japan; 4Department of Psychiatry, Nara Medical University, Kashihara, Nara, Japan; 5Department of Psychiatry, Akitsu Kounoike Hospital, Gose, Nara, Japan; 6Faculty of Nursing, Nara Medical University, Kashihara, Nara, JapanCorrespondence: Toyosaku OtaDepartment of Psychiatry, Nara Medical University, 840 Shijyo-Cho, Kashihara, Nara 634-8522, JapanTel +81-744-22-3051Fax +81-744-22-3854Email toyosaku@naramed-u.ac.jpBackground: School refusal behavior (SRB), which is the refusal to attend or remain in school, has been associated with emotional, psychological, and other behavioral problems, as well as a lower health-related quality of life (HRQOL). However, the effects of self-esteem and a psychiatric diagnosis in students with SRB on HRQOL are not yet known. Understanding these relationships could help to develop more effective therapeutic interventions.Methods: A total of 175 young people (aged 8– 18 years old) who visited our medical centers and outpatient clinics participated in the study. This comprised the SRB group (n = 70) and an age- and sex-matched control group (n = 105). Information about any psychiatric diagnosis was collected from medical records, HRQOL was measured using the J-KIDSCREEN-52, SRB was assessed using the School Refusal Assessment Scale-Revised for Japanese Attendance at School, self-esteem was measured using the Rosenberg Self-Esteem Scale, children’s mental health status was measured using the Strengths and Difficulties Questionnaire, and social support was measured using the Oslo 3-item Social Support Scale. We performed between-group comparisons and multiple regression analysis.Results: The SRB had a significantly lower HRQOL than the control group in several of the KIDSCREEN-52 dimensions. In the SRB group, 35.7% had chronic disease and 35.7% of their parents had health problems and were receiving treatment. The multiple regression analysis revealed that, within the SRB group, a psychiatric diagnosis was associated with a lower HRQOL. However, this was not the case for a diagnosis of autistic spectrum disorder. Self-esteem positively affected HRQOL in six dimensions of the KIDSCREEN-52 within the SRB group.Conclusion: Our results could inform the development of support strategies for young people with SRB. Namely, support that enhances self-esteem could be used to increase HRQOL in young people with SRB. Furthermore, the presence of psychiatric disorders should be assessed as early as possible.Keywords: school refusal behavior, health-related quality of life, KIDSCREEN, Rosenberg self-esteem scale, autism spectrum disorder

Abstract Background Allergic diseases in infants have dramatically increased in developed countries during the past few decades. To date, extensive research has been done on risk factors for allergies in infancy, and preventive measures against them. However, the effect of the primary approach to preventing infantile allergy is still limited. The aim of this trial is to evaluate whether prenatal education interventions, including the latest public research results on allergic diseases, prevent the onset of infant allergies. Methods/design We designed a randomized controlled, two-arm (standard prenatal education vs our education), parallel-group, assessor-blind trial. A sample of 120 pregnant women will be recruited at Chiba Aiyu-kai Kinen Hospital and allocation is by computer-generated randomization. Pregnant women in the intervention arm participate in the childbirth education program established by the specialist and a pediatric allergy educator. The program was developed based on evidences supporting interventions on primary prevention, which are suggested to be beneficial to infantile allergies in recent studies. The primary objective of the study is to determine whether it is possible to establish effective behaviors for allergy prevention in early infancy in the children of pregnant women who participate in an educational program developed by pediatric allergy specialists. Four months after birth, their behaviors will be compared against those of pregnant women who did not participate in the program. Discussion Allergies are common in many individuals worldwide, and can be present from babyhood through the person’s lifetime. One of the strong points of this study is that it should provide pregnant women with accumulated information on preventive knowledge against allergy, that can be effective in some cases, and that women can apply a combination of these behaviors before and after pregnancy. The results of our program will be publicized to help change the behaviors of mothers, and, if the program is effective, for preventing allergies in infants, it will be disclosed worldwide as a new preventive strategy for allergy in infants. Trial registration UMIN-CTR, ID: UMIN000034730 Retrospectively registered on 1 December 2018.

Motokazu Kato,1 Keisuke Tomii,2 Kenichi Hashimoto,3 Yasuko Nezu,3 Takeo Ishii,4 C Elaine Jones,5 Sally Kilbride,6 Annette S Gross,7 Christine S Clifton,7 David A Lipson8,9 1Chest Disease Clinical and Research Institute, Kishiwada City Hospital, Kishiwada, Japan; 2Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan; 3Evidence Generation Department, GlaxoSmithKline K.K., Tokyo, Japan; 4MA Respiratory Department, GlaxoSmithKline K.K., Tokyo, Japan; 5Development, R&D, GlaxoSmithKline, Research Triangle Park, NC, USA; 6Biostatistics, GlaxoSmithKline, Uxbridge, Middlesex, UK; 7Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline R&D, Sydney, Australia; 8Clinical Sciences, GlaxoSmithKline, Collegeville, PA, USA; 9Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Yasuko NezuEvidence Generation Department, Respiratory Medical Affairs & Development GlaxoSmithKline K.K., Akasaka Intercity AIR 1-8-1 Akasaka, Minato-Ku, Tokyo 107-0052, JapanTel +81 3 4231 5064Fax +81 3 4231 5994Email yasuko.2.nezu@gsk.comPurpose: The Informing the Pathway of COPD Treatment (IMPACT) study demonstrated that single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduces moderate/severe exacerbation rates and improves lung function and health status versus FF/VI or UMEC/VI dual therapy in patients with symptomatic COPD and a history of exacerbations. This analysis evaluated the efficacy and safety of FF/UMEC/VI in patients enrolled in Japan.Patients and methods: IMPACT was a 52-week, randomized, double-blind, multicenter study comparing FF/UMEC/VI 100/62.5/25 μg with FF/VI 100/25 μg or UMEC/VI 62.5/25 μg in patients ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the previous year. Endpoints included annual rate of on-treatment moderate/severe exacerbations (primary endpoint), time-to-first on-treatment moderate/severe exacerbation and change from baseline at Week 52 in trough FEV1, post-bronchodilator FEV1, St. George’s Respiratory Questionnaire, and COPD Assessment Test score. Safety was also assessed.Results: The Japan subgroup accounted for only 4% (378/10,355) of the overall IMPACT intent-to-treat (ITT) population. In the Japan subgroup, FF/UMEC/VI reduced the annual rate of on-treatment moderate/severe exacerbations by 15% (95% CI: −20, 40) versus FF/VI (compared with 15% [10, 20] in the ITT) and 36% (95% CI: 6, 57) versus UMEC/VI (compared with 25% [19, 30] in the ITT). FF/UMEC/VI reduced moderate/severe exacerbation risk (time-to-first), improved lung function and health status at Week 52 versus both dual therapies. These results were in the same direction and of a generally similar magnitude to those seen in the overall ITT population. No new safety signals were identified in the Japan subgroup compared with the ITT population. Pneumonia incidence was higher with FF/UMEC/VI and FF/VI versus UMEC/VI.Conclusion: These results highlight the favorable benefit–risk profile of FF/UMEC/VI single-inhaler triple therapy compared with FF/VI or UMEC/VI dual therapy in patients in Japan with symptomatic COPD and ≥1 exacerbation in the prior year.Keywords: triple therapy, fluticasone furoate, Japan, umeclidinium, vilanterol, COPD exacerbation

Introduction Atypical femoral fractures are atraumatic or minimally traumatic fractures and rare side effects of bone resorption inhibitors. Bone resorption inhibitors are frequently used in the treatment of prostate cancer. Case presentation A 62‐year‐old man complained of difficulty in walking and left lower limb pain. Androgen deprivation and denosumab therapy for prostate cancer‐induced bone metastasis was initiated 27 months ago. Even though the prostate‐specific antigen level did not increase, imaging studies indicated the possibility of bone metastasis. The patient underwent bone biopsy; however, no malignancy was detected. Afterward, he had a fall, causing a complete fracture in his left femur. Conclusion Atypical femoral fractures occasionally mimic typical imaging findings and outcomes of bone metastasis. This case is important for recognizing such cases.