bluuebunny/crossref_metadata_2025 huggingface dataset:
Carrier-free prodrug nanoparticles based on lonidamine and cisplatin for synergistic treatment of breast cancer
Authors: Yang Lu , Li Junnan , Guan Zhaoyuan , Zhang Jingwen , Wang Xin , Tang Rupei
Published: June 2022

Herein, we combined a derivative of cisplatin (CP) and the chemosensitizer lonidamine (LND) to design an amphiphilic prodrug, in which the ratio of LND to cisplatin was fixed at 2:1. Diaminedichlorodihydroxyplatinum (DH-CP) is a hydrophilic cisplatin derivative. Due to its appropriate amphiphilicity, this prodrug could self-assemble into stable nanoparticles (denoted as LNP-NPs). Under the action of excessive glutathione (GSH) in tumor cells, DH-CP could be reduced to cytotoxic cisplatin. In addition, the released LND could inhibit the metabolic process of tumor cells, and improving the sensitivity of tumor cells to cisplatin. In vitro studies demonstrated that LNP-NPs displayed significantly cytotoxicity on breast cancer cells, and the cell viability after co-incubation for 48 h (CP 16 μg/mL) were 18.77% (MCF-7) and 20.01% (EMT6), respectively. LNP-NPs could also significantly inhibit the growth of MCF-7 tumor-like spheroids, which were realized through the high coordination and cooperation between CP and LND. Therefore, the carrier-free drug delivery system based on LND and DH-CP is expected to achieve a good synergistic anti-tumor effect.
Perspectives on Engagement With Youth Physical Activity Opportunities in Low-Income, African American, Urban Neighborhoods
Authors: Suminski Richard R. , Robson Shannon M. , Kopetsky Fultz Amanda , Sundermeir Samantha M. , Jahnke Sara A.
Published: June 2022

Purpose

To identify and describe factors related to low-income, African American youth’s participation in neighborhood youth physical activity opportunities (YPAO).

Approach

Formative research.

Setting

Face-to-face focus groups in New Castle County, Delaware.

Participants

Fifty-five adults (parents/guardians of youth, YPAO providers, small business representatives) living and/or working in low-income, African American neighborhoods.

Method

Nine, 60-90 minute focus groups were conducted from December 2018 through March 2019. Focus group questions were developed a priori and included domains related to neighborhood YPAOs. The domains were awareness of YPAOs, benefits and barriers to providing YPAOs, ways to increase youth participation in YPAOs, and strategies for creating, improving, and sustaining YPAOs. Focus group recordings were transcribed, and thematic analysis was performed to identify themes related to increasing youth participation in YPAOs.

Results

Four major themes related to YPAOs emerged: 1) exposure/access, 2) parent buy-in/accountability (e.g., personal values and trust with YPAOs), 3) technology, and 4) increasing a sense of community. Three minor themes included liability, advertising, and schools. Small businesses desired to support YPAOs mainly through non-monetary means, while mutually benefitting from receiving local recognition.

Conclusion

Developing strategies to incorporate effective community partnerships, creative program ideas with advertising, and active, multisector involvement including small businesses into practice has the potential to increase engagement of low-income, African American youth in YPAOs.
Reliability of 3D planning and simulations of medial open wedge high tibial osteotomies
Authors: Jörgens Maximilian , Keppler Alexander M , Degen Nikolaus , Bachmeier Andreas T , Bergstraesser Marcel , Sass Jan , Prall Wolf Christian , Böcker Wolfgang , Fürmetz Julian
Published: June 2022

Purpose: In medial open-wedge high tibial osteotomy (HTO) hinge axis and osteotomy plane influence the resulting anatomy, but accurate angular quantifications using 3D-planning-simulations are lacking. The objectives of this study were developing a standardized and validated 3D-planning method of an HTO and to perform several simulated realignments to explain unintended anatomy changes. Methods: The cutting direction of the main osteotomy was defined parallel to the medial tibial slope and the hinge axis 1.5 cm distal to the lateral plateau. For interobserver testing, this 3D planning was performed on 13 digital models of human tibiae by two observers. In addition, four different hinge axis positions and five differently inclined osteotomy planes each were simulated. The osteotomy direction ranged from medial 0°–30° anteromedial, while the tilt of the osteotomy plane compared to the tibial plateau was −10° to +10°. All anatomic angular changes were calculated using 3D analysis. Results: Multiple HTO plannings by two medical investigators using standardized procedures showed only minimal differences. In the 3D-simulation, each 10° rotation of the hinge axis resulted in a 1.7° significant increase in slope. Tilting the osteotomy plane by 10° resulted in significant torsional changes of 2°, in addition to minor but significant changes in the medial proximal tibial angle (MPTA). Conclusion: Standardized 3D-planning of the HTO can be performed with high reliability using two-observer planning. 3D-simulations suggest that control of the osteotomy plane is highly relevant to avoid unintended changes in the resulting anatomy, but this can be a helpful tool to modify specific angles in different pathologies in the HTO.
Men in Nursing: A Qualitative Examination of Students’ Stereotypes of Male Nurses through the Framework of Social Role Theory and Stereotype Content Model
Authors: Kaur Navjotpal , Ricciardelli Rosemary , Clow Kimberley
Published: June 2022

Driven by overwhelming numerical dominance of women in the role of nurses, nursing profession over the last two centuries has been largely scripted with gendered characterizations. However, nuances that shape the language and wording choices that are evoked when describing the stereotypes targeting male nurses remain relatively unexplored. Our current research examined the way 117 female non-nursing and nursing students in Canada characterized male nurses using open-ended self-report measures and thematic qualitative analyses. We contribute to the literature on nursing, gender, and stereotypes by analyzing the personal attitudes and stereotypes held by young female students toward male nurses. Social role theory and the stereotype content model provided the theoretical underpinnings to explore and explain emergent stereotypes and stereotype content. Our findings suggest that students generate more communal, high-warmth characteristics for male nurses than agentic characteristics, suggesting possible paternalistic prejudice toward men in nursing.
Using TikTok for public and youth mental health – A systematic review and content analysis
Authors: McCashin Darragh , Murphy Colette M
Published: June 2022

Globally, TikTok is now the fastest growing social media platform among children and young people; but it remains surprisingly under-researched in psychology and psychiatry. This is despite the fact that social media platforms have been subject to intense academic and societal scrutiny regarding their potentially adverse effects on youth mental health and wellbeing, notwithstanding the inconsistent findings across the literature. In this two part study, we conducted a systematic review concerning studies that have examined TikTok for any public health or mental health purpose; and a follow-up content analysis of TikTok within an Irish context. For study 1, a predetermined search strategy covering representative public and mental health terminology was applied to six databases – PSYCINFO, Google Scholar, PUBMED, Wiley, Journal of Medical Internet Research, ACM – within the period 2016 to 2021. Included studies were limited to English-speaking publications of any design where TikTok was the primary focus of the study. The quality appraisal tool by Dunne et al., (2018) was applied to all included studies. For study 2, we replicated our search strategy from study 1, and converted this terminology to TikTok hashtags to search within TikTok in combination with Irish-specific hashtags. As quantified by the app, the top two “most liked” videos were selected for inclusion across the following three targeted groups: official public health accounts; registered Irish charities; and personal TikTok creators. A full descriptive analysis was applied in both studies. Study 1 found 24 studies that covered a range of public and mental health issues: COVID-19 ( n = 10), dermatology ( n = 7), eating disorders ( n = 1), cancer ( n = 1), tics ( n = 1), radiology ( n = 1), sexual health ( n = 1), DNA ( n = 1), and public health promotion ( n = 1). Studies were predominately from the USA, applied a content analysis design, and were of acceptable quality overall. In study 2, 29 Irish TikTok accounts were analysed, including the accounts of public health authorities ( n = 2), charity or non-profit ( n = 5), and personal TikTok creators ( n = 22). The overall engagement data from these accounts represented a significant outreach to younger populations: total likes n = 2,588,181; total comments n = 13,775; and total shares n = 21,254. TikTok has been utilised for a range of public health purposes, but remains poorly engaged by institutional accounts. The various mechanisms for connecting with younger audiences presents a unique opportunity for youth mental health practitioners to consider, yet there were distinct differences in how TikTok accounts used platform features to interact. Overall, there is an absence of high quality mixed methodological evaluations of TikTok content for public and mental health, despite it being the most used platform for children and young people.
JNJ-73763989 pharmacokinetics and safety: Liver-targeted siRNAs against hepatitis B virus, in Japanese and non-Japanese healthy adults, and combined with JNJ-56136379 and a nucleos(t)ide analogue in patients with chronic hepatitis B
Authors: Gane Ed , Yuen Man-Fung , Kakuda Thomas N , Ogawa Tetsuro , Takahashi Yasushi , Goeyvaerts Nele , Lonjon-Domanec Isabelle , Vaughan Tamisha , Schluep Thomas , Hamilton James , Njumbe Ediage Emmanuel , Hillewaert Vera , Snoeys Jan , Lenz Oliver , Talloen Willem , Biermer Michael
Published: June 2022

Background

JNJ-73763989 comprises two hepatitis B virus (HBV)-specific, liver-targeted N-galactosamine-conjugated short interfering RNA triggers, JNJ-73763976 and JNJ-73763924. JNJ-73763989 pharmacokinetics, safety and tolerability were assessed in two phase 1 studies: Japanese (NCT04002752), and non-Japanese healthy participants and chronic hepatitis B (CHB) patients also receiving the HBV capsid assembly modulator JNJ-56136379 and a nucleos(t)ide analogue (NA) (NCT03365947).

Methods

Healthy participant cohorts were double-blind and randomized to receive a single subcutaneous JNJ-73763989 dose (non-Japanese participants, 35, 100, 200, 300 or 400 mg; Japanese participants, 25, 100 or 200 mg) or placebo. JNJ-73763976 and JNJ-73763924 plasma concentrations were assessed over 48 h. CHB patients received JNJ-73763989 200 mg every 4 weeks plus daily oral JNJ-56136379 250 mg and NA in an open-label fashion. Safety and tolerability were assessed through Day 28 (healthy participants) or Day 112 (patients).

Results

Thirty non-Japanese ( n = 4/dose; placebo, n = 10) and 24 Japanese healthy participants ( n = 6/dose; placebo, n = 6) were randomized. JNJ-73763976 and JNJ-73763924 exposure generally increased in a dose-proportional manner. Mean plasma half-life was 4–9 h. No differences between pharmacokinetic parameters were apparent between non-Japanese and Japanese healthy participants. In the 12 CHB patients, mean JNJ-73763976, JNJ-73763924 and JNJ-56136379 plasma concentrations 2 h post-dose on Day 29 were 663, 269 and 14,718 ng/mL, respectively. In both studies, all adverse events were mild/moderate.

Conclusion

JNJ-73763976 and JNJ-73763924 had short plasma half-lives and exposure generally increased in a dose-proportional manner; there were no pharmacokinetic differences between Japanese and non-Japanese healthy adults. JNJ-73763989 with or without JNJ-56136379 and NA was generally safe and well tolerated.
Fake thumbs in play: A large-scale exploration of false amplification and false diminution in online news comment spaces
Authors: Kwon K Hazel , Lee Mi Hyun , Pil Han Sang , Park Sungho
Published: June 2022

This study explores how disinformation can dampen general users’ expressions of opinion online. In the context of a proven disinformation case in South Korea, this study analyzes externally validated click-logs of 1389 fake accounts and more than a million logs of 45,769 general users in a highly popular web portal. Findings show that the inflated visibility of anti-governmental opinions in the manipulated comment space was incongruent with the overall political tone that general users had spontaneously encountered from the broader media ecosystem beyond the manipulated space. Subsequently, this opinion “climate” incongruence decreased the likelihood of commenting in the manipulated space. The study concludes that false amplification (of the opinions that the manipulators promote) and false diminution (of general users’ political expressions) work in tandem to create a distorted opinion environment.
Toward a political economy of synthetic data: A data-intensive capitalism that is not a surveillance capitalism?
Authors: Steinhoff James
Published: June 2022

Surveillance of human subjects is how data-intensive companies obtain much of their data, yet surveillance increasingly meets with social and regulatory resistance. Data-intensive companies are thus seeking other ways to meet their data needs. This article explores one of these: the creation of synthetic data, or data produced artificially as an alternative to real-world data. I show that capital is already heavily invested in synthetic data. I argue that its appeal goes beyond circumventing surveillance to accord with a structural tendency within capitalism toward the autonomization of the circuit of capital. By severing data from human subjectivity, synthetic data contributes to the automation of the production of automation technologies like machine learning. A shift from surveillance to synthesis, I argue, has epistemological, ontological, and political economic consequences for a society increasingly structured around data-intensive capital.
Ringing true? The persuasiveness of Russian strategic narratives
Authors: Wagnsson Charlotte , Lundström Magnus
Published: June 2022

International Relations (IR) scholars have theorized the significance of communication and messaging across state borders, using notions such as soft power, sharp power, propaganda and illiberal communication. This study contributes to this body of research by investigating narrative persuasiveness by way of a large-scale experimental exploration of narrative reception. The projection of strategic narratives has become a central feature of modern influencing across borders. Despite the existence of a growing literature on the potentially harmful effects of such narratives, however, their persuasiveness remains under-researched. This article seeks to help fill this gap by asking what might induce people in Sweden to side with strategic narratives projected by Sputnik, the Russian state-funded news media platform. The article puts a central component of Walter Fisher’s classic narrative paradigm to the test: the notions of narrative probability (consistency and coherence) and fidelity (previous life experience). In a rare large-scale survey experiment ( N = 2,032), three narratives from Sputnik were presented to respondents to establish the potential perceived narrative probability and fidelity. Contrary to Fisher’s argument and some previous works on strategic narratives, the results show that people can be persuaded by a narrative without having personal experience of the topic, and despite regarding the text as incoherent. This indicates that information influence projected through strategic narratives can be effective regardless of the form of the message and even when introducing unfamiliar ideas. This is an interesting addition to findings in previous studies that source awareness does not negatively affect the effectiveness of strategic narratives. The article ends by highlighting contributions to previous research on persuasion and by suggesting avenues ahead.
Evaluating data quality in the Australian and New Zealand dialysis and transplant registry using administrative hospital admission datasets and data-linkage
Authors: Palamuthusingam Dharmenaan , Pascoe Elaine M , Hawley Carmel M , Johnson David W , Ratnayake Gishan , McDonald Stephen , Boudville Neil , Jose Matthew , Fahim Magid
Published: June 2022

Background: Clinical quality registries provide rich and useful data for clinical quality monitoring and research purposes but are susceptible to data quality issues that can impact their usage. Objective: This study assessed the concordance between comorbidities recorded in the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and those in state-based hospital admission datasets. Method: All patients in New South Wales, South Australia, Tasmania, Victoria and Western Australia recorded in ANZDATA as requiring chronic kidney replacement therapy (KRT) between 01/07/2000 and 31/12/2015 were linked with state-based hospital admission datasets. Coronary artery disease, diabetes mellitus, cerebrovascular disease, chronic lung disease and peripheral vascular disease recorded in ANZDATA at each annual census date were compared overall, over time and between different KRT modalities to comorbidities recorded in hospital admission datasets, as defined by the International Classification of Diseases (ICD-10-AM), using both the kappa statistic and logistic regression analysis. Results: 29, 334 patients with 207,369 hospital admissions were identified. Comparison was made at census date for every patient comparison. Overall agreement was “very good” for diabetes mellitus (92%, k = 0.84) and “poor” to “fair” (21–61%, k = 0.02–0.22) for others. Diabetes mellitus recording had the highest accuracy (sensitivity 93% (±SE 0.2) and specificity 93% (±SE 0.2)), and cerebrovascular disease had the lowest (sensitivity 54% (±SE 0.2) and specificity 21% (±SE 0.3)). The false positive rates for cerebrovascular disease, peripheral vascular disease and chronic airway disease ranged between 18 and 33%. The probability of a false positive was lowest for kidney transplant patients for all comorbidities and highest for patients on haemodialysis. Conclusions and Implications: Agreement between the clinical quality registry and hospital admission datasets was variable, with the prevalence of comorbidities being higher in ANZDATA.
A gastruloid model of the interaction between embryonic and extra-embryonic cell types
Authors: Bérenger-Currias Noémie MLP , Mircea Maria , Adegeest Esmée , van den Berg Patrick R , Feliksik Marleen , Hochane Mazène , Idema Timon , Tans Sander J , Semrau Stefan
Published: June 2022

Stem-cell derived in vitro systems, such as organoids or embryoids, hold great potential for modeling in vivo development. Full control over their initial composition, scalability, and easily measurable dynamics make those systems useful for studying specific developmental processes in isolation. Here we report the formation of gastruloids consisting of mouse embryonic stem cells (mESCs) and extraembryonic endoderm (XEN) cells. These XEN-enhanced gastruloids (XEGs) exhibit the formation of neural epithelia, which are absent in gastruloids derived from mESCs only. By single-cell RNA-seq, imaging, and differentiation experiments, we demonstrate the neural characteristics of the epithelial tissue. We further show that the mESCs induce the differentiation of the XEN cells to a visceral endoderm-like state. Finally, we demonstrate that local inhibition of WNT signaling and production of a basement membrane by the XEN cells underlie the formation of the neuroepithelial tissue. In summary, we establish XEGs to explore heterotypic cellular interactions and their developmental consequences in vitro.
The Determinants of Non-Performing Loans in the Indonesian Banking Industry: An Asymmetric Approach Before and During the Pandemic Crisis
Authors: Fakhrunnas Faaza , Nugrohowati Rindang Nuri Isnaini , Haron Razali , Anto Mohammad Bekti Hendrie
Published: June 2022

The outbreak has created an unprecedented crisis that influences macroeconomic variables. These circumstances are predicted to be contagious for banking performance. To understand the related influences, this study attempts to examine the asymmetric relationship between macroeconomic variables and non-performing loans/financing of the Indonesian banking industry before and during the COVID-19 pandemic. The nonlinear autoregressive distributed lag (NARDL) is adopted based on the time-series data from 2005Q1 to 2021Q1. The study provides evidence that an asymmetric relationship between macroeconomic variables and the banks’ non-performing loans/financing exists both before and during the pandemic. In addition, asymmetric relationships of macroeconomic variables on Islamic banks are more prominent before the pandemic even though it occurs inversely during the pandemic. As for policy implication, the financial authority needs to be prudent in implementing financial policies due to the presence of an asymmetric relationship between macroeconomic variables and the banks’ non-performing loans/financing. Moreover, the authority must ensure that all financial policies will be effective to all types of banks regardless of conventional or Islamic banks.
Linkage of Green Brand Positioning and Green Customer Value With Green Purchase Intention: The Mediating and Moderating Role of Attitude Toward Green Brand and Green Trust
Authors: Wang Yong Ming , Zaman Hafiz Muhammad Fakhar , Alvi Abdul Khaliq
Published: June 2022

Current research evaluates the mediating role of attitude toward the green brand and the moderating effect of green trust for the relationship of green brand positioning and green customer value with green purchase intention. Data was collected from the 464 University students with the help of snowball sampling technique. Results describe that green brand positioning and green customer value has noteworthy impact on green purchase intention. Results also illustrate that green brand positioning and green customer value has significant impact on attitude toward green brand. Moreover, attitude toward green brand act as partial mediator for the relationship of green brand positioning and green customer value with green purchase intention. Furthermore, green trust act as moderator for the relationship of green brand positioning and green customer value with green purchase intention. This is cross-sectional research as data is collected at single time point and this kind of research decrease the confidence about cause and effect assumptions. This research only focuses the employees at individual level. Some other potential predictors are not included in this research due to time and cost constraint. It is better to do longitudinal researches on these variables for generalization purpose. In future researches results may be compare at group as well as at network level.
Characteristics of Effective English Language Teachers: Student and Teacher Perspectives at a Thai University
Authors: Quieti Adriano , Nanni Alexander
Published: June 2022

This study investigated students’ and teachers’ perceptions of the characteristics of effective English language teachers in the Thai cultural context. A survey comprising 68 Likert-scale items was administered to students ( n = 124) and teachers ( n = 11) in the intensive English program (IEP) of a Thai university. The survey measured the participants’ perception of the characteristics of effective teachers in seven areas: general characteristics, affective variables, knowledge about students, pedagogical knowledge, content knowledge, knowledge about classroom management, and professional development. A comparison of the responses showed a statistically significant difference between the median responses of teachers and students in three areas: affective variables, knowledge of students, and professional development. In all three areas, students ascribed a higher level of importance. These findings have implications for teachers, who may underestimate the value that their students place on the personal and affective aspects of education and on professional development.
Evaluation of serum tRF-23-Q99P9P9NDD as a potential biomarker for the clinical diagnosis of gastric cancer
Authors: Zhang Yu , Gu Xinliang , Qin Xinyue , Huang Yuejiao , Ju Shaoqing
Published: June 2022

Background

Gastric cancer (GC) is one of the diseases that endanger human health with high morbidity and mortality. The positive rates of traditional biomarkers in the diagnosis of GC are low, so it is necessary to find biomarkers with high sensitivity to increase the detection rate. tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs with specific biological functions and aberrant expression in cancer. In this study, we focused on the potential of tRNA-derived small RNAs as GC biomarkers.

Methods

The differentially expressed tsRNAs in three pairs of GC tissues were screened with high-throughput sequencing and verified using the TCGA database and Quantitative real-time PCR. The methodological evaluation of tRF-23-Q99P9P9NDD was verified by agarose gel electrophoresis, RIN evaluation, and Sanger sequencing. The Chi-square test was used to evaluate the relationship between the tRF-23-Q99P9P9NDD expression and clinicopathological parameters. Kaplan–Meier survival analysis was used to evaluate the effect of the tRF-23-Q99P9P9NDD expression on survival. Additionally, the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of tRF-23-Q99P9P9NDD in GC.

Results

Differential expression of serum tRF-23-Q99P9P9NDD could distinguish GC patients from gastritis patients and healthy donors. Chi-square test showed that high expression of tRF-23-Q99P9P9NDD was significantly associated with T stage, lymph node metastasis, TNM stage, and nerve/vascular invasion. Kaplan–Meier curve showed that patients with high expression of tRF-23-Q99P9P9NDD had a lower survival rate than patients with low expression of this biomarker. ROC analysis showed that, compared with conventional biomarkers, the efficacy of tRF-23-Q99P9P9NDD was higher, which was improved by the combination of biomarkers, and even in the early stages. Finally, we preliminarily predicted the downstream of tRF-23-Q99P9P9NDD in GC cells.

Conclusions

The expression of tRF-23-Q99P9P9NDD in GC serum can identify GC patients, and it has higher efficacy than conventional biomarkers even in the early stages. Furthermore, tRF-23-Q99P9P9NDD can monitor the postoperative conditions of GC patients.
A Fuzzy-based Sliding Mode Control Approach for Acceleration Slip Regulation of Battery Electric Vehicle
Authors: Shi Qin , Wang Mingwei , He Zejia , Yao Cheng , Wei Yujiang , He Lin
Published: June 2022

Due to quick response and large quantity of electric motor torque, the traction wheels of battery electric vehicle are easy to slip during the initial phase of starting. In this paper, a sliding mode control approach of acceleration slip regulation is designed to prevent the slip of the traction wheels. The wheel slip ratio is used as the state variable for the formulation of system dynamics model. The fuzzy algorithm is utilized to adjust the switch function of sliding mode controller. After stability and robustness analysis, the sliding mode control law is transferred into C code and downloaded into vehicle control unit, which is validated under wet and dry road conditions. The experimental results with a small overshoot and a quick response during starting indicate that the sliding mode controller has good control effect on the slip ratio regulation. This article proposes an acceleration slip regulation method that improves the safety during acceleration for battery electric vehicle.
Movement Modeling and Control for Robotic Bonnet Polishing
Authors: Huang Xuepeng , Wang Zhenzhong , Lin Zewen
Published: June 2022

With the increasing demand for high-precision optical components, bonnet polishing technology is increasingly being used in the polishing process of optical components owing to its high removal efficiency and high surface accuracy. However, it is expensive and difficult to implement dedicated bonnet polishing machine tools, and their processing range is limited. This research combines bonnet polishing technology with industrial robot-assisted processing technology to propose a robotic bonnet polishing control model for large-diameter axisymmetric aspherical optical components. Using the transformation relations of the spatial coordinate system, the transformation relations of the workpiece coordinate system, local coordinate system of the polishing point, and tool coordinate system of the bonnet sphere center are established to obtain the bonnet precession polishing motion model. The polishing trajectory of large-diameter axisymmetric aspherical components and the variation in the linkage angle difference were simulated by adding an efficiency-optimal control strategy to the motion model. The robot motion was simulated in Robostudio to verify the correctness of the precession motion model and control algorithm. Lastly, the robotic bonnet polishing system was successfully applied to the polishing process of the optical components.
Experimental study of compressive properties parallel to grain of glulam
Authors: Totsuka Marina , Jockwer Robert , Kawahara Hiro , Aoki Kenji , Inayama Masahiro
Published: June 2022

This paper describes results and analysis of experiment of compression behavior parallel to grain of glulam (Norway Spruce, Japanese cedar, and Japanese cypress), especially in damage zones near loading plates and joints. To investigate the influence factors of physical properties and the mechanism of the damage zone near the loading plates or the joints, compression tests on 90 specimens and surface-measurement tests on 48 specimens were performed. As a result, it was observed that damage zones existed near the loading plates and the joints. The lengths of the damage zone of wood–wood joints are larger than that of wood–steel joints. The length of the damage zone was independent of the load and the height of the specimens. However, the length of the damage zone and its scatter increase as the width of the cross-section increases, as does the roughness on the contact surface. It was considered that the cause of the damage zone is the roughness on the contact surface and the length of the damage zone depends on the roughness on the contact surface. Therefore, the length of the damage zone depends on the processing accuracy on the contact surface and has an increasing trend as the contact-surface area increases. There was the size effect of the height of the specimens on the compressive strength because of knots.
Improving durability of cross laminated timber (CLT) with borate treatment
Authors: Bagheri Sajad , Alinejad Mona , Ohno Katie , Hasburgh Laura , Arango Rachel , Nejad Mojgan
Published: June 2022

Borate solution was used to treat two sets of Douglas-fir wood samples, one by spraying cross-laminated timbers (CLT) and another set by dip-treating wood in solutions at different retentions. A novel model was developed to explain and predict borate uptake based on dip-treatment parameters. Small-scale CLT samples were prepared using commercial emulsion polymer isocyanate (EPI) and polyurethane (PU) adhesive with dip-treated wood. The effect of adhesive and borate retention on CLT samples were evaluated through adhesion, fire, termite, and decay tests. The adhesion strength of wood was statistically unaffected by borate treatment. Statistical analysis showed that both spray- and dip-treated samples had significantly higher termite and decay resistance and fire performance than the untreated boards. Untreated CLT samples bonded with PU showed a considerably higher inherent decay and termite resistance than untreated specimens bonded with EPI adhesive.
Narrative-based medicine in headache disorders
Authors: Lampl Christian , Sacco Simona , Martelletti Paolo
Published: June 2022

In this editorial we aim to provide an overview of Narrative-based Medicine (NBM) and highlight what it may offer to the care of individuals with headache disorders.
Reversely immortalized mouse salivary gland cells presented a promising metabolic and fibrotic response upon BMP9/Gdf2 stimulation
Authors: Luo Wenping , Liang Panpan , Zhao Tianyu , Cheng Qianyu , Liu Huikai , He Liwen , Zhang Linghuan , Huang Bo , Zhang Yuxin , He Tongchuan , Yang Deqin
Published: June 2022

The submandibular gland (SMG) and the sublingual gland (SLG) are two of the three major salivary glands in mammals. In mice, they are adjacent to each other and open into the oral cavity, producing saliva to lubricate the mouth and aid in food digestion. Though salivary gland dysfunction accompanied with fibrosis and metabolic disturbance is common in clinic, in-depth mechanistic research is lacking. Currently, research on how to rescue salivary function is challenging, as it must resort to using terminally differentiated acinar cells or precursor acinar cells with unknown differentiation. In this study, we established reversely immortalized mouse primary SMG cells (iSMGCs) and SLG cells (iSLGCs) on the first postnatal day (P0). The iSMGCs and iSLGCs grew well, exhibited many salivary gland characteristics, and retained the metabolism-related genes derived from the original tissue as demonstrated using transcriptome sequencing (RNA-seq) analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these two cell lines, which overlapped with those of the SMG and SLG, were enriched in cysteine and methionine metabolism. Furthermore, we investigated the role of bone morphogenetic protein 9 (BMP9), also known as growth differentiation factor 2(Gdf2), on metabolic and fibrotic functions in the SMG and SLG. We demonstrated that iSMGCs and iSLGCs presented promising adipogenic and fibrotic responses upon BMP9/Gdf2stimulation. Thus, our findings indicate that iSMGCs and iSLGCs faithfully reproduce characteristics of SMG and SLG cells and present a promising prospect for use in future study of salivary gland metabolism and fibrosis upon BMP9/Gdf2stimulation.
Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancer
Authors: Muchlińska Anna , Nagel Anna , Popęda Marta , Szade Jolanta , Niemira Magdalena , Zieliński Jacek , Skokowski Jarosław , Bednarz-Knoll Natalia , Żaczek Anna J.
Published: June 2022

Background

Cancer-associated fibroblasts (CAFs) have been shown to support tumor development in a variety of cancers. Different markers were applied to classify CAFs in order to elucidate their impact on tumor progression. However, the exact mechanism by which CAFs enhance cancer development and metastasis is yet unknown.

Methods

Alpha-smooth muscle actin (α-SMA) was examined immunohistochemically in intratumoral CAFs of nonmetastatic breast cancers and correlated with clinicopathological data. Four CAF cell lines were isolated from patients with luminal breast cancer (lumBC) and classified according to the presence of α-SMA protein. Conditioned medium (CM) from CAF cultures was used to assess the influence of CAFs on lumBC cell lines: MCF7 and T47D cells using Matrigel 3D culture assay. To identify potential factors accounting for promotion of tumor growth by α-SMAhigh CAFs, nCounter PanCancer Immune Profiling Panel (NanoString) was used.

Results

In luminal breast cancer, presence of intratumoral CAFs expressing high level of α-SMA (13% of lumBC group) correlated with poor prognosis (p = 0.019). In in vitro conditions, conditioned medium obtained from primary cultures of α-SMA-positive CAFs isolated from luminal tumors was observed to enhance growth of lumBC cell line colonies in 3D Matrigel, in contrast to CM derived from α-SMA-negative CAFs. Multigene expression analysis indicated that osteopontin (OPN) was overexpressed in α-SMA-positive CAFs in both clinical samples and in vitro models. OPN expression was associated with higher percentage of Ki67-positive cells in clinical material (p = 0.012), while OPN blocking in α-SMA-positive CAF-derived CM attenuated growth of lumBC cell line colonies in 3D Matrigel.

Conclusions

Our findings demonstrate that α-SMA-positive CAFs might enhance tumor growth via secretion of OPN.
The importance of deep speech phenotyping for neurodevelopmental and genetic disorders: a conceptual review
Authors: Chenausky Karen V. , Tager-Flusberg Helen
Published: June 2022

Background

Speech is the most common modality through which language is communicated, and delayed, disordered, or absent speech production is a hallmark of many neurodevelopmental and genetic disorders. Yet, speech is not often carefully phenotyped in neurodevelopmental disorders. In this paper, we argue that such deep phenotyping, defined as phenotyping that is specific to speech production and not conflated with language or cognitive ability, is vital if we are to understand how genetic variations affect the brain regions that are associated with spoken language.

Speech is distinct from language, though the two are related behaviorally and share neural substrates. We present a brief taxonomy of developmental speech production disorders, with particular emphasis on the motor speech disorders childhood apraxia of speech (a disorder of motor planning) and childhood dysarthria (a set of disorders of motor execution). We review the history of discoveries concerning the KE family, in whom a hereditary form of communication impairment was identified as childhood apraxia of speech and linked to dysfunction in theFOXP2gene. The story demonstrates how instrumental deep phenotyping of speech production was in this seminal discovery in the genetics of speech and language. There is considerable overlap between the neural substrates associated with speech production and withFOXP2expression, suggesting that further genes associated with speech dysfunction will also be expressed in similar brain regions. We then show how a biologically accurate computational model of speech production, in combination with detailed information about speech production in children with developmental disorders, can generate testable hypotheses about the nature, genetics, and neurology of speech disorders.

Conclusions

Though speech and language are distinct, specific types of developmental speech disorder are associated with far-reaching effects on verbal communication in children with neurodevelopmental disorders. Therefore, detailed speech phenotyping, in collaboration with experts on pediatric speech development and disorders, can lead us to a new generation of discoveries about how speech development is affected in genetic disorders.
The Long Read Transcriptome of Rice (Oryza sativa ssp. japonica var. Nipponbare) Reveals Novel Transcripts
Authors: Hasan Sharmin , Huang Lichun , Liu Qiaoquan , Perlo Virginie , O’Keeffe Angela , Margarido Gabriel Rodrigues Alves , Furtado Agnelo , Henry Robert J.
Published: June 2022

Background

High-throughput next-generation sequencing technologies offer a powerful approach to characterizing the transcriptomes of plants. Long read sequencing has been shown to support the discovery of novel isoforms of transcripts. This approach enables the generation of full-length sequences revealing splice variants that may be important in regulating gene action. Investigation of the diversity of transcripts in the rice transcriptome including splice variants was conducted using PacBio long-read sequence data to improve the annotation of the rice genome.

Results

A cDNA library was prepared from RNA extracted from leaves, roots, seeds, inflorescences, and panicles of O. sativa ssp. japonica var Nipponbare and sequenced on a PacBio Sequel platform. This produced 346,190 non-redundant full-length non-chimeric reads (FLNC) resulting in 33,504 high-quality transcripts. Half of the transcripts were multi-exonic and entirely matched with the reference transcripts. However, 14,874 novel isoforms were also identified resulting predominantly from intron retention and at least one novel splice site. Intron retention was the prevalent alternative splicing event and exon skipping was the least observed. Of 73,659 splice junctions, 12,755 (17%) represented novel splice junctions with canonical and non-canonical intron boundaries. The complexity of the transcriptome was examined in detail for 19 starch synthesis-related genes, defining 276 spliced isoforms of which 94 splice variants were novel.

Conclusion

The data reveal the great complexity of the rice transcriptome. The novel transcripts provide new insights that may be a key input in future research to improve the annotation of the rice genome.
Primary small cell carcinoma of the ureter with associated hyponatremia and rapid progression to bladder involvement: a case report
Authors: Chuang Yu-Hsiang , Nandwani Ghulam Mustafa , Szewczyk-Bieda Magdelena , Kernohan Neil , Aslam Muhammad Zeeshan
Published: June 2022

Background

Primary small cell carcinoma (SmCCa) of the ureter is rare. The majority of patients present with visible haematuria. Diagnosis is confirmed by histopathology. Associated hyponatraemia in GU lesion can be due SmCCa can be useful for early diagnosis aggressive ureteric tumors. The current management includes radical surgery or radiotherapy with concomitant chemotherapy to improve survival and quality of life.

Case presentation

We present a case of a 77 years female who was found to have unilateral hydronephrosis with a 5 cm filling defect in the distal ureter on CT urogram. Further staging showed organ-confined disease. Serum sodium levels were low at presentation. At the time of planned nephroureterectomy (NU), cystoscopy revealed a bladder tumor obstructing the right ureteric orifice. TURBT was performed instead. After TURBT, there was marked hyponatremia and histology was small cell carcinoma (SmCCa). Paraneoplastic SIADH was the likely cause. Neoadjuvant chemotherapy (NACT) followed by radiotherapy (RT) was chosen for definitive treatment. This resulted in an excellent response supported by radiological evidence of almost complete resolution of the tumor.

Conclusion

The presence of genitourinary lesion and hyponatremia should raise suspicion of paraneoplastic SIADH. The case suggests the emphasis of histological diagnosis of the genitourinary lesion with existing hyponatraemia to provide better outcome with NACT followed by definitive treatment. We share our experience of NACT and RT in the management of ureteric SmCCa extension to the bladder.
The association between long-term night shift work and metabolic syndrome: a cross-sectional study of male railway workers in southwest China
Authors: Dong Chaohui , Zeng Honglian , Yang Bo , Zhang Yi , Li Zhitao
Published: June 2022

Objectives

Metabolic syndrome (MetS) increases the risk of new diabetes and cardiovascular disease. Night shift work (NSW) may influence metabolic disturbance and lead to MetS. This study aims to investigate the association between long-term NSW (≥ 10 years) and MetS combined with its components in male railway workers in southwest China.

Methods

11,023 male railway workers with long-term NSW of more than 10 years in the Physical Examination Center of the Affiliated Hospital of Chengdu University were enrolled. The basic data were collected by investigators and blood test results were collected. The primary outcome was the prevalence of metabolic syndrome. The results were analyzed using statistical software SPSS 22.0.

Results

In total, 11,023 people over the age of 40 with more than 10 years of working experience were enrolled, and 4759 (43.2%) participants had a diagnosis of MetS. The basic data indicated that night shift workers tended to be younger, shorter working years, but with higher body mass index and longer hip circumference (p < 0.05). The adjusted analysis revealed that there was no significant association between NSW and metabolic syndrome (OR 1.03, 95% CI 0.94–1.12, p = 0.543). NSW was associated with SBP ≥ 130 mmHg (OR 1.11, 95% CI 1.02–1.21, p < 0.001) and waist circumference ≥ 90 cm (OR 1.11, 95% CI 1.02–1.21, p < 0.001).

Conclusions

Long-term night shift workers had a higher prevalence of MetS. However, long-term NSW is not associated with a significantly increased risk of metabolic syndrome in male railway workers in southwest China. Long-term NSW is associated with elevated SBP, and waist circumference increase.
On estimation for accelerated failure time models with small or rare event survival data
Authors: Alam Tasneem Fatima , Rahman M. Shafiqur , Bari Wasimul
Published: June 2022

Background

Separation or monotone likelihood may exist in fitting process of the accelerated failure time (AFT) model using maximum likelihood approach when sample size is small and/or rate of censoring is high (rare event) or there is at least one strong covariate in the model, resulting in infinite estimates of at least one regression coefficient.

Methods

This paper investigated the properties of the maximum likelihood estimator (MLE) of the regression parameters of the AFT models for small sample and/or rare-event situation and addressed the problems by introducing a penalized likelihood approach. The penalized likelihood function and the corresponding score equation is derived by adding a penalty term to the existing likelihood function, which was originally proposed by Firth (Biometrika, 1993) for the exponential family models. Further, a post-hoc adjustment of intercept and scale parameters is discussed keeping them out of penalization to ensure accurate prediction of survival probability. The penalized method was illustrated for the widely used log-location-scale family models such as Weibull, Log-normal and Log-logistic distributions and compared the models and methods uisng an extensive simulation study.

Results

The simulation study, performed separately for each of the log-location-scale models, showed that Firth’s penalized likelihood succeeded to solve the problem of separation and achieve convergence, providing finite estimates of the regression coefficients, which are not often possible by the MLE. Furthermore, the proposed penalized method showed substantial improvement over MLE by providing smaller amount of bias, mean squared error (MSE), narrower confidence interval and reasonably accurate prediction of survival probabilities. The methods are illustrated using prostate cancer data with existence of separation, and results supported the simulation findings.

Conclusion

When sample size is small (≤ 50) or event is rare (i.e., censoring proportion is high) and/or there is any evidence of separation in the data, we recommend to use Firth’s penalized likelihood method for fitting AFT model.