Is the Importance of Achieving Stable Disease Different between Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Cytotoxic Agents in the Second-Line Setting for Advanced Non-small Cell Lung Cancer?

BackgroundIt is controversial whether achieving stable disease leads to a survival benefit and whether the importance of achieving stable disease differs between cytotoxic agents and molecular targeted agents. To examine these questions, the authors retrospectively reviewed phase II and III studies in the second-line setting for advanced non-small cell lung cancer using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic agents separately.MethodsThe authors chose 45 trials for the chemotherapy group and nine for the EGFR TKI group by searching the PubMed database. All nine trials in the EGFR TKI group concern gefitinib and erlotinib.ResultsThe median survival time increased 0.0375 month with each 1% increase in stable disease rate (p = 0.039), and each 1% increase in response rate resulted in 0.0744 (p < 0.001) month of median survival time in the analysis combined with both cytotoxic agents and EGFR TKIs. Main and interaction terms for EGFR TKI treatment were not statistically significant. With respect to time to progression, only response rate showed a statistically significant relationship with survival.ConclusionsTo obtain response seems to be more important than to achieve stable disease for both cytotoxic agents and EGFR TKIs, although achieving stable disease is still valuable. The relationship between survival and response or stable disease appears similar for cytotoxic agents and EGFR TKIs

KUS121, a VCP modulator, has an ameliorating effect on acute and chronic heart failure without calcium loading via maintenance of intracellular ATP levels

KUS121は新規の心不全治療薬となる --Ca2+負荷なしに血行動態を改善--. 京都大学プレスリリース. 2023-12-15.[Aims] As heart failure (HF) progresses, ATP levels in myocardial cells decrease, and myocardial contractility also decreases. Inotropic drugs improve myocardial contractility but increase ATP consumption, leading to poor prognosis. Kyoto University Substance 121 (KUS121) is known to selectively inhibit the ATPase activity of valosin-containing protein, maintain cellular ATP levels, and manifest cytoprotective effects in several pathological conditions. The aim of this study is to determine the therapeutic effect of KUS121 on HF models. [Methods and results] Cultured cell, mouse, and canine models of HF were used to examine the therapeutic effects of KUS121. The mechanism of action of KUS121 was also examined. Administration of KUS121 to a transverse aortic constriction (TAC)-induced mouse model of HF rapidly improved the left ventricular ejection fraction and improved the creatine phosphate/ATP ratio. In a canine model of high frequency-paced HF, administration of KUS121 also improved left ventricular contractility and decreased left ventricular end-diastolic pressure without increasing the heart rate. Long-term administration of KUS121 to a TAC-induced mouse model of HF suppressed cardiac hypertrophy and fibrosis. In H9C2 cells, KUS121 reduced ER stress. Finally, in experiments using primary cultured cardiomyocytes, KUS121 improved contractility and diastolic capacity without changing peak Ca²⁺ levels or contraction time. These effects were not accompanied by an increase in cyclic adenosine monophosphate or phosphorylation of phospholamban and ryanodine receptors. [Conclusions] KUS121 ameliorated HF by a mechanism totally different from that of conventional catecholamines. We propose that KUS121 is a promising new option for the treatment of HF

Development and validation of questionnaires for eating‐related distress among advanced cancer patients and families

Background: Eating‐related distress (ERD) is one type of psychosocial distress among advanced cancer patients and family caregivers. Its alleviation is a key issue in palliative care; however, there is no validated tool for measuring ERD. Methods: The purpose of this study was to validate tools for evaluating ERD among patients and family caregivers. The study consisted of a development and validation/retest phase. In the development phase, we made preliminary questionnaires for patients and family caregivers. After face validity and content validity, we performed an exploratory factor analysis and discussed the final adoption of items. In the validation/retest phase, we examined factor validity with an exploratory factor analysis. We calculated Pearson's correlation coefficients between the questionnaire for patients, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia Cachexia Subscale (FAACT ACS) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Cachexia 24 (EORTC QLQ‐CAX24) and Pearson's correlation coefficients between the questionnaire for family caregivers and the Caregiver Quality of Life Index‐Cancer (CQOLC) for concurrent validity. We calculated Cronbach's alpha coefficients (Cronbach's alpha) and intraclass correlation coefficients (ICCs) for internal consistency and test–retest reliability. We performed the Mann–Whitney U test between the questionnaires and cancer cachexia based on criteria from the international consensus for known‐group validity. Results: In the development phase, 162 pairs of patients and family caregivers were asked to participate, and 144 patients and 106 family caregivers responded. In the validation/retest phase, 333 pairs of patients and family caregivers were asked to participate, and 234 patients and 152 family caregivers responded. Overall, 183 patients and 112 family caregivers did the retest. Seven conceptual groups were extracted for the ERD among patients and family caregivers, respectively. Patient factors 1–7 correlated with FAACT ACS (r = −0.63, −0.43, −0.55, −0.40, −0.38, −0.54, −0.38, respectively) and EORTC QLQ‐CAX24 (r = 0.58, 0.40, 0.60, 0.49, 0.38, 0.59, 0.42, respectively). Family factors 1–7 correlated with CQOLC (r = −0.34, −0.30, −0.37, −0.37, −0.46, −0.42, −0.40, respectively). The values of Cronbach's alpha and ICC of each factor and all factors of patients ranged from 0.84 to 0.96 and 0.67 to 0.83, respectively. Those of each factor and all factors of family caregivers ranged from 0.84 to 0.96 and 0.63 to 0.84, respectively. The cachexia group of patients had significantly higher scores than the non‐cachexia group for each factor and all factors. Conclusions: Newly developed tools for measuring ERD experienced by advanced cancer patients and family caregivers have been validated

A pirate site Sci-Hub: Recent trend and usage analytics from Japan.

Sci-Hubとは，6,450万件以上もの学術論文のフルテキスト（全文）を誰もが無料でダウンロードできる論文海賊サイトである。Sci-Hubからダウンロードできる論文には，学術雑誌に掲載された有料論文の約85%が含まれており，Sci-Hubは学術出版社の著作権を侵害する違法サイトである。大学図書館の契約する電子ジャーナル，OAジャーナル，機関リポジトリ，プレプリントサーバーなど法的に問題ない論文サイトが在る中で，世界中から1日に35万件以上の論文がSci-Hubを通じてダウンロードされている。本稿では先ずSci-Hubの概要・仕組み・世界的な動向について述べる。次いで2017年にSci-Hubからダウンロードされた論文のログデータを分析し，国内におけるSci-Hub利用実態の調査結果を報告する。栗山による2016年調査と比較すると，Sci-Hubの利用数やSci-Hubの利用が確認された都市数は増加していた。また，Sci-Hubでダウンロードされているのは有料論文だけではなくOA論文が約20%を占めていること，クッキーの情報から約80%のユーザーは1回のみSci-Hubを利用している状況も明らかになった。Sci-Hub is a pirate site for academic articles. Sci-Hub provides more 64 million academic articles for free. About 85% of the articles that can be downloaded for free from Sci-Hub otherwise require paid access. Sci-Hub therefore infringes upon academic publisher’s copyright. Yet despite the existence of legitimate academic article databases, users from around the world download over 350,000 articles each day from Sci-Hub; almost 3,800 of those daily downloads originate in Japan. In this paper, we first outline the trends pertaining to Sci-Hub. Next, we analyze the Sci-Hub download log data from 2017 and investigate the Sci-Hub Usage in Japan. Comparison of the results with Kuriyama’s (2016) survey reveals that the number of downloads and citations confirmed that Sci-Hub use has increased. We revealed that Open Access articles account for about 20% of Sci-Hub downloads and that about 80% of users use Sci-Hub only once by cookie

Successful treatment for patients with chronic orchialgia following inguinal hernia repair by means of meshoma removal, orchiectomy and triple-neurectomy

Introduction: Orchialgia following inguinal hernia repair is rare complication and still challenging since there has been no established surgical treatment because of complexity of nerve innervation to the testicular area. Herein we report a case of postoperative orchialgia following Lichtenstein repair, which was successfully treated by mesh removal, orchiectomy and triple neurectomy. Case presentation: A 65-year-old man was referred to our department because of chronic right orchialgia following Lichtenstein hernia repair. He walked with a limp and was unable to walk a long distance. Physical examination revealed the presence of meshoma in the groin area and hypoesthesia in the anterior skin of the right scrotum. His right testis was completely atrophic and located not in the scrotum but in the subcutaneous regions of right groin. He was diagnosed as both neuropathic and nociceptive orchialgia and underwent meshoma removal, triple-neurectomy, and orchiectomy to address these issues. Pathological examination revealed that meshoma was integrated with the structures of the spermatic cord, leading to foreign-body reaction and fibrosis around the genital branch of genitofemoral nerve. The resected right testis was completely-scarred without ischemic changes. Orchialgia disappeared immediately after operation and he was able to walk without a limp. Discussions: It is important to distinguish between nociceptive and neuropathic orchialgia. Neuroanatomic understanding is essential to guide treatment options. Orchiectomy is an option but should be reserved for refractory cases with evidence of nociceptive pain accompanied by anatomical changes. Conclusions: Triple neurectomy should be considered in patients with neuropathic orchialgia

Waveguide Embedding of a Double-Metal 1.9-THz Quantum Cascade Laser: Design, Manufacturing, and Results

We present the details of a coupling structure to embed a 1.9-THz double-metal quantum cascade lasers (QCLs) into a 120-mu m-wide full-height rectangular waveguide. We describe the split-block manufacturing of the waveguide coupler together with a diagonal feed horn and present power and beam shape measurements of two different devices. The two devices differ in coupling factor, which can be chosen in a wide range by the mounting position of the QCL. Our waveguide embedding allows coupling of a large fraction of the laser power into the waveguide and the subsequent horn antenna emitting with a large Gaussian mode content, enabling efficient integration into a diffraction limited optics setup. This is illustrated by a self-mixing experiment and by using the embedded QCL as a local oscillator in a heterodyne receiver

Data from: Mixed mating system are regulated by fecundity in Shorea curtisii (Dipterocarpaceae) as revealed by comparison under different pollen limited conditions

The maintenance of mixed mating was studied in Shorea curtisii, a dominant and widely distributed dipterocarp species in Southeast Asia. Paternity and hierarchical Bayesian analyses were used to estimate the parameters of pollen dispersal kernel, male fecundity and self-pollen affinity. We hypothesized that partial self incompatibility and/or inbreeding depression reduce the number of selfed seeds if the mother trees receive sufficient pollen, whereas reproductive assurance increases the numbers of selfed seeds under low amounts of pollen. Comparison of estimated parameters of self-pollen affinity between high density undisturbed and low density selectively logged forests indicated that self-pollen was selectively excluded from mating in the former, probably due to partial self incompatibility or inbreeding depression until seed maturation. By estimating the self-pollen affinity of each mother tree in both forests, mother trees with higher amount of self-pollen indicated significance of self-pollen affinity with negative estimated value. The exclusion of self-fertilization and/or inbreeding depression during seed maturation occurred in the mother trees with large female fecundity, whereas reproductive assurance increased self-fertilization in the mother trees with lower female fecundity