bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of treatment delay due to the pandemic of COVID-19 on the efficacy of immunotherapy in head and neck cancer patients
Authors: Chen Gaili , Wu Qiuji , Jiang Huangang , Li Zheng , Hua Xinying , Hu Xiaoyan , Yu Haijun , Xie Conghua , Zhong Yahua
Published: December 2020

Immunotherapy has been a new standard for recurrent/metastatic head and neck cancers (R/M HNC). One of the prominent characteristics of cancer immunotherapy is the induction of immune memory followed by endured treatment response. However, whether and how a treatment delay would impact on the efficacy of immunotherapy has not been well determined. During the outbreak of COVID-19, a number of cancer patients in Wuhan, the epicenter of the pandemic in China, had experienced long-lasting city lockdown and delay of immunotherapies. Here, we retrospectively analyzed 24 HNC patients treated with immune checkpoint inhibitors in our cancer institute prior to the outbreak of COVID-19 who were re-evaluated after the restoration of regular medical care. Of these 24 patients, 10 patients had achieved complete response (CR) or partial response (PR), 12 patients had achieved stable disease (SD), and 2 patients had received just one cycle treatment without efficacy evaluation before treatment delay. The median delay was 3.75 months (range 1.73–8.17 months). Re-evaluation after treatment delay revealed that ten patients (10/10) who achieved CR or PR, two patients (2/2) who received just one cycle treatment without efficacy evaluation and seven patients (7/12) who achieved SD before outbreak of COVID-19 maintained tumor response after treatment delay. Among the rest five patients who had achieved SD, four patients were re-evaluated as progressive disease (PD) due to treatment delay and one patient died after treatment interruption without re-evaluation. Our results from a small cohort of R/M HNC patients showed that treatment delay of three to four months might have mild, if any, impact on the efficacy of immunotherapy for patients with controlled disease.
Reproductive technologies, female infertility, and the risk of imprinting-related disorders
Authors: Fauque Patricia , De Mouzon Jacques , Devaux Aviva , Epelboin Sylvie , Gervoise-Boyer Marie-José , Levy Rachel , Valentin Morgane , Viot Géraldine , Bergère Arianne , De Vienne Claire , Jonveaux Philippe , Pessione Fabienne
Published: December 2020

Background

Epidemiological studies suggest that singletons born from assisted reproductive technologies (ART) have a high risk of adverse perinatal outcomes, specifically for imprinting disorders. Because ART processes take place at times when epigenetic reprogramming/imprinting are occurring, there is concern that ART can affect genomic imprints. However, little is currently known about the risk of imprinting defects according to the type of ART or the type of underlying female infertility.

From the French national health database, a cohort of 3,501,495 singletons born over a 5-year period (2013–2017) following fresh embryo or frozen embryo transfers (fresh-ET or FET from in vitro fertilization), intrauterine insemination, or natural conception was followed up to early childhood. Based on clinical features, several syndromes/diseases involving imprinted genes were monitored. The effects of ART conception and the underlying cause of female infertility were assessed.

Results

Compared with infants conceived naturally, children born after fresh-ET had a higher prevalence of imprinting-related diseases, with an aOR of 1.43 [95% CI 1.13–1.81, p = 0.003]. Namely, we observed an increased risk of neonatal diabetes mellitus (1.96 aOR [95% CI 1.43–2.70], p < 0.001). There was an overall independent increase in risk of imprinting diseases for children with mothers diagnosed with endometriosis (1.38 aOR [95% CI 1.06–1.80], p = 0.02). Young and advanced maternal age, primiparity, obesity, smoking, and history of high blood pressure or diabetes were also associated with high global risk.

Conclusions

This prospective epidemiological study showed that the risk of clinically diagnosed imprinting-related diseases is increased in children conceived after fresh embryo transfers or from mothers with endometriosis. The increased perturbations in genomic imprinting could be caused by controlled ovarian hyperstimulation and potentially endometriosis through the impairment of endometrial receptivity and placentation, leading to epigenetic feto-placental changes. Further studies are now needed to improve understanding of the underlying molecular mechanisms (i.e. genetic or epigenetic causes).
Global DNA methylation pattern involved in the modulation of differentiation potential of adipogenic and myogenic precursors in skeletal muscle of pigs
Authors: Zhang Xin , Sun Wenjuan , He Linjuan , Wang Liqi , Qiu Kai , Yin Jingdong
Published: December 2020

Background

Skeletal muscle is a complex and heterogeneous tissue accounting for approximately 40% of body weight. Excessive ectopic lipid accumulation in the muscle fascicle would undermine the integrity of skeletal muscle in humans but endow muscle with marbling-related characteristics in farm animals. Therefore, the balance of myogenesis and adipogenesis is of great significance for skeletal muscle homeostasis. Significant DNA methylation occurs during myogenesis and adipogenesis; however, DNA methylation pattern of myogenic and adipogenic precursors derived from skeletal muscle remains unknown yet.

Methods

In this study, reduced representation bisulfite sequencing was performed to analyze genome-wide DNA methylation of adipogenic and myogenic precursors derived from the skeletal muscle of neonatal pigs. Integrated analysis of DNA methylation and transcription profiles was further conducted. Based on the results of pathway enrichment analysis, myogenic precursors were transfected with CACNA2D2-overexpression plasmids to explore the function of CACNA2D2 in myogenic differentiation.

Results

As a result, 11,361 differentially methylated regions mainly located in intergenic region and introns were identified. Furthermore, 153 genes with different DNA methylation and gene expression level between adipogenic and myogenic precursors were characterized. Subsequently, pathway enrichment analysis revealed that DNA methylation programing was involved in the regulation of adipogenic and myogenic differentiation potential through mediating the crosstalk among pathways including focal adhesion, regulation of actin cytoskeleton, MAPK signaling pathway, and calcium signaling pathway. In particular, we characterized a new role of CACNA2D2 in inhibiting myogenic differentiation by suppressing JNK/MAPK signaling pathway.

Conclusions

This study depicted a comprehensive landmark of DNA methylome of skeletal muscle-derived myogenic and adipogenic precursors, highlighted the critical role of CACNA2D2 in regulating myogenic differentiation, and illustrated the possible regulatory ways of DNA methylation on cell fate commitment and skeletal muscle homeostasis.
Post-translational modifications of EZH2 in cancer
Authors: Li Zhongwei , Li Minle , Wang Diandian , Hou Pingfu , Chen Xintian , Chu Sufang , Chai Dafei , Zheng Junnian , Bai Jin
Published: December 2020

Enhancer of zeste homolog 2 (EZH2), as a main component of Polycomb Repressive Complex 2, catalyzes histone H3K27me3 to silence its target gene expression. EZH2 upregulation results in cancer development and poor prognosis of cancer patients. Post-translational modifications (PTMs) are important biological events in cancer progression. PTMs regulate protein conformation and diversity functions. Recently, mounting studies have demonstrated that EZH2 stability, histone methyltransferase activity, localization, and binding partners can be regulated by PTMs, including phosphorylation,O-GlcNAcylation, acetylation, methylation and ubiquitination. However, the detailed molecular mechanisms of the EZH2-PTMs and whether other types of PTMs occur in EZH2 remain largely unclear. This review presents an overview of different roles of EZH2 modification and EZH2-PTMs crosstalk during tumorigenesis and cancer metastasis. We also discussed the therapeutic potential of targeting EZH2 modifications for cancer therapy.
Looking through the African lenses: a critical exploration of the CSR activities of Chinese International Construction Companies (CICCs) in Africa
Authors: Seriki Oluwasegun Oluwaseyi
Published: December 2020

The importance of Chinese International Construction Companies (CICCs) within the construction sector in Africa can no longer be ignored, as these firms hold a considerable amount of market share within the African continent. The construction industry is of high importance to African economic renaissance, and Corporate Social Responsibility (CSR) is becoming a key issue in business processes on the developing continent. Narratives around the implementation of CSR within construction in African economies have been largely one-sided, viewed from foreign perspectives and outsider anecdotes, without engaging locals in evaluating these initiatives. As a result, this paper explores CSR as a critical component of the continued penetration and dominance of Chinese contractors in the highly competitive African construction markets. The paper adopts a quantitative survey to explore the areas of implementation of CSR by CICCs, how they line up against current local and international counterparts and the future of these firms in Africa using CSR as a metric. Residents of Africa’s largest economy, Nigeria, who have Chinese-led projects ongoing in their communities, were surveyed for the study, and the findings used to propose solutions for future CSR policy-making in local African communities where Chinese contractors carry out business. The study found that in terms of CSR strategy implementation, CICCs were ranked highly on quality of construction and respect for local laws and customs, but ranked low in perception of employee welfare and environmental protection. The study highlighted that African governments taking responsible leadership by formulating a CSR policy for all international contractors might stem the tide of increasing anti-Chinese rhetoric within the construction sector on the African continent.
Limited not lazy: a quasi-experimental secondary analysis of evidence quality evaluations by those who hold implausible beliefs
Authors: Martire Kristy A. , Growns Bethany , Bali Agnes S. , Montgomery-Farrer Bronte , Summersby Stephanie , Younan Mariam
Published: December 2020

Past research suggests that an uncritical or ‘lazy’ style of evaluating evidence may play a role in the development and maintenance of implausible beliefs. We examine this possibility by using a quasi-experimental design to compare how low- and high-quality evidence is evaluated by those who do and do not endorse implausible claims. Seven studies conducted during 2019–2020 provided the data for this analysis (N = 746). Each of the seven primary studies presented participants with high- and/or low-quality evidence and measured implausible claim endorsement and evaluations of evidence persuasiveness (via credibility, value, and/or weight). A linear mixed-effect model was used to predict persuasiveness from the interaction between implausible claim endorsement and evidence quality. Our results showed that endorsers were significantly more persuaded by the evidence than non-endorsers, but both groups were significantly more persuaded by high-quality than low-quality evidence. The interaction between endorsement and evidence quality was not significant. These results suggest that the formation and maintenance of implausible beliefs by endorsers may result from less critical evidence evaluations rather than a failure to analyse. This is consistent with a limited rather than a lazy approach and suggests that interventions to develop analytical skill may be useful for minimising the effects of implausible claims.
Long-term results of super-selective trans-catheter embolization of the vesical arteries for the treatment of intractable bladder haematuria
Authors: Tsitskari Maria , Spiliopoulos Stavros , Konstantos Chrysostomos , Palialexis Konstantinos , Reppas Lazaros , Brountzos Elias
Published: December 2020

Purpose

To evaluate the feasibility, safety and long-term efficacy of super-selective trans-catheter arterial embolization for the management of intractable bladder bleeding.

Materials and methods

The records of 20 patients with intractable haematuria referred urgently for selective arterial embolization after failed conventional therapy, between 2013 and 2018, were retrospectively analyzed. Primary outcomes were technical (cessation of extravasation and/or stasis of flow within the target vessel) and clinical (bleeding control) success. Secondary outcomes included complication and re-intervention rates.

Results

Technical success was 90% (18/20 cases), as in 2 cases, embolization was not feasible. Super-selective embolization of the vesical arteries was feasible in 15/18 cases (83.3%). Selective proximal occlusion of the anterior division of the internal iliac artery was performed in two cases (11%) and embolization of the anterior division after coil blockage of the posterior division was performed in one case (5%). Bilateral and unilateral embolization was performed in 10 and 8 cases, respectively. Peri-procedural mortality rate was 5% (1/18 patients). One possible procedure-related death occurred due to myocardial infarction ten days following non-target embolization of the buttocks and the anterior abdominal wall. Mean time follow up was 35 ± 15 months. Bleeding reoccurred in three patients (16.6%), all successfully managed (one conservatively and two with further embolization). Clinical success was 85% (17/20 cases). During follow up 11 more patients died, due to underlying conditions not related to bleeding or the procedure.

Conclusions

Super-selective angiographic embolization is feasible, safe and effective to control refractory, life threatening bladder bleeding and should be considered as a first line treatment, as to obviate the need for emergency surgery.
Comparison of cannabidiol to citalopram in targeting fear memory in female mice
Authors: Montoya Zackary T. , Uhernik Amy L. , Smith Jeffrey P.
Published: December 2020

Background

Cannabidiol (CBD) and selective serotonin reuptake inhibitors (SSRIs) are currently used to treat post-traumatic stress disorder (PTSD). However, these drugs are commonly studied after dosing just prior to extinction training, and there are gaps in our understanding of how they affect fear memory formation, their comparative effects on various types of memory, and of sexual dimorphisms in effects. Also, more studies involving female subjects are needed to balance the gender-inequality in the literature. Therefore, the purpose of this study was to directly compare the effects of CBD to citalopram in affecting the formation of auditory cued, contextual, and generalized fear memory, and to evaluate how extinction of these different memories was altered by pre-acquisition treatment in female mice. We also evaluated the impact of the estrous cycle on each of these.

Methods

Auditory-cued trace fear conditioning was conducted shortly after dosing female C57BL/6 mice, with either CBD or citalopram (10 mg/kg each), by pairing auditory tones with mild foot shocks. Auditory-cued, contextual, and generalized fear memory was assessed by measuring freezing responses, with an automated fear conditioning system, 24 h after conditioning. Each memory type was then evaluated every 24 h, over a 4-day period in total, to create an extinction profile. Freezing outcomes were statistically compared by ANOVA with Tukey HSD post hoc analysis, N = 12 mice per experimental group. Evaluation of sexual dimorphism was by comparison to historical data from male mice.

Results

Auditory cue-associated fear memory was not affected with CBD or citalopram; however, contextual memory was reduced with CBD by 11%, p < 0.05, but not citalopram, and generalized fear memory was reduced with CBD and citalopram, 20% and 22%, respectively, p < 0.05. Extinction learning was enhanced with CBD and citalopram, but, there was considerable memory-type variability between drug effects, with freezing levels reduced at the end of training by 9 to 17% for CBD, and 10 to 12% with citalopram. The estrous cycle did not affect any outcomes.

Conclusions

Both drugs are potent modifiers of fear memory formation; however, there is considerable divergence in their targeting of different memory types which, overall, could support the use of CBD as an alternative to SSRIs for treating PTSD in females, but not males. A limitation of the study was that it compared data from experiments done at different times to evaluate sexual dimorphism. Overall, this suggests that more research is necessary to guide any therapeutic approach involving CBD.
Knowledge translation in Africa: are the structures in place?
Authors: Asamani James Avoka , Nabyonga-Orem Juliet
Published: December 2020

Background

Contextualised evidence to generate local solutions on the progressive path to universal health coverage is essential. However, this evidence must be translated into action. Knowledge translation (KT) experts have highlighted the plausible mechanisms to foster the uptake of evidence. The objective of this study was to assess the extent to which structures are in place to boost uptake of evidence, in countries of the WHO African Region.

Methods

Employing a cross-sectional survey, we collected data on the availability of structures to foster the uptake of evidence into policy in 35 out of the 47 member states of the WHO African Region. Data were analysed using a simple counting of the presence or absence of such structures.

Results

Less than half of the countries had evidence collation and synthesis mechanisms. The lack of such mechanisms presents a missed opportunity to identify comprehensive solutions that can respond to health sector challenges. Close to 50% of the countries had KT platforms in place. However, the availability of these was in several forms, as an institution-based platform, as an annual event to disseminate evidence and as a series of conferences at the national level. In some countries, KT was mainstreamed into routine health sector performance review processes. Several challenges impacted the functionality of the KT platforms including inadequate funding and lack of dedicated personnel. Regarding dissemination of evidence, sharing reports, scientific publications and one-off presentations in meetings were the main approaches employed.

Conclusion

The availability of KT platforms in the WHO African countries can be described as at best and non-existent at the worst. The current structures, where these exist, cannot adequately foster KT. Knowledge translation platforms need to be viewed as sector-wide platforms and mainstreamed in routine health sector performance reviews and policymaking processes. Funds for their functionality must be planned for as part of the health sector budget. Dissemination of evidence needs to be viewed differently to embrace the concept of “disseminate for impact”. Further, funding for dissemination activities needs to be planned for as part of the evidence generation plan.
Forcing a growth factor response – tissue-stiffness modulation of integrin signaling and crosstalk with growth factor receptors
Authors: Sarker Farhana A. , Prior Victoria G. , Bax Samuel , O'Neill Geraldine M.
Published: December 2020

Research throughout the 90s established that integrin crosstalk with growth factor receptors stimulates robust growth factor signaling. These insights were derived chiefly from comparing adherent versus suspension cell cultures. Considering the new understanding that mechanosensory inputs tune adhesion signaling, it is now timely to revisit this crosstalk in different mechanical environments. Here, we present a brief historical perspective on integrin signaling against the backdrop of the mechanically diverse extracellular microenvironment, then review the evidence supporting the mechanical regulation of integrin crosstalk with growth factor signaling. We discuss early studies revealing distinct signaling consequences for integrin occupancy (binding to matrix) and aggregation (binding to immobile ligand). We consider how the mechanical environments encountered in vivo intersect with this diverse signaling, focusing on receptor endocytosis. We discuss the implications of mechanically tuned integrin signaling for growth factor signaling, using the epidermal growth factor receptor (EGFR) as an illustrative example. We discuss how the use of rigid tissue culture plastic for cancer drug screening may select agents that lack efficacy in the soft in vivo tissue environment. Tuning of integrin signaling via external mechanical forces in vivo and subsequent effects on growth factor signaling thus has implications for normal cellular physiology and anti-cancer therapies.
Daam2 couples translocation and clustering of Wnt receptor signalosomes through Rac1
Authors: Cristobal Carlo D. , Ye Qi , Jo Juyeon , Ding Xiaoyun , Wang Chih-Yen , Cortes Diego , Chen Zheng , Lee Hyun Kyoung
Published: December 2020

Wnt signaling plays a critical role in development across species and is dysregulated in a host of human diseases. A key step in signal transduction is the formation of Wnt receptor signalosomes, during which a large number of components translocate to the membrane, cluster together and amplify downstream signaling. However, the molecular processes that coordinate these events remain poorly defined. Here, we show that Daam2 regulates canonical Wnt signaling via the PIP2–PIP5K axis through its association with Rac1. Clustering of Daam2-mediated Wnt receptor complexes requires both Rac1 and PIP5K, and PIP5K promotes membrane localization of these complexes in a Rac1-dependent manner. Importantly, the localization of Daam2 complexes and Daam2-mediated canonical Wnt signaling is dependent upon actin polymerization. These studies – in chick spinal cord and human and monkey cell lines – highlight novel roles for Rac1 and the actin cytoskeleton in the regulation of canonical Wnt signaling and define Daam2 as a key scaffolding hub that coordinates membrane translocation and signalosome clustering.
Resilience and Reproductive Health Diagnosis in Mexican Indigenous Women
Authors: Torres Patricia Elizabeth Cossio
Published: December 2020

Mental Health is a determinant of reproductive mortality and morbidity especially in the developing regions of the world with reproductive health problems. The right to sexual and reproductive health has been enunciated by the United Nations as a goal to be achieved by 2030. However, indigenous women are the most vulnerable population because of the conditions that surround them. A cross-sectional quantitative study was done in the indigenous communities of Mexico to know the resilience and reproductive health diagnosis. A Mexican Resilience Scale, gynaeco-obstetrical clinical history and a reproductive health survey were applied. A total of 180 women participated from which 34.6% and 61.4% of the women used a form of birth control method in their first and last sexual intercourse, respectively. There were statistically significant differences between the three attitudes among reproductive health and the highest levels of resilience (p<0.05). Resilience was seen to have a positive influence on the attitude of indigenous women, reducing the vulnerability among reproductive health.
The Debt-Trap Diplomacy Revisited
Authors: Gangte Lammuansiam
Published: December 2020

There is a strong case to reconsider the “debt-trap diplomacy” of China. The narrative that holds “Chinese loans are responsible for the debt-crises plaguing under developed and developing countries”(The Maritime Executive, 2019)needs a critical reexamination and, perhaps, a rethink in our geostrategic and geopolitical calculations. This paper is a case study on Sri Lanka’s Hambantota port, an asset handed over to China on lease for 99 years in the year 2017, which the dominant narrative claims to be a significant foreign policy debacle engineered by the Chinese. An inquiry into the crisis, however, traces its development back to the country’s fiscal management and macroeconomic realities that, the study argues, impelled Sri Lanka to take the tough call it did. Sri-Lanka is beset by twin deficits, among other macro-economic challenges, forcing its authorities to embark on external financing to meet fiscal expenditures, especially for the infrastructure projects. While the bulk of external capital comes from traditional creditors such as IMF and World Bank, the loan for the Hambantota project was sanctioned by China. Assessments from experts ruled out the economic potentiality of the project, owing to its commercial non-viability and logistical challenges. This decidedly prompted authorities to discontinue the project and the immediate consequence of which was difficulty in

revenue generation, translating into substantial constraints on the fiscal front resulting from the country’s soaring debt-servicing cost. Faced with a series of international sovereign debt-payment obligations lined up in the years 2020 and 2021, Sri Lanka finally gave up its non-productive asset in exchange for some extra foreign exchange reserves to meet the debt obligations lined up in the years ahead. Out of some 3000 infrastructure projects where China has invested in, the Hambantota port was the only one used as a textbook example for “the Debt-trap diplomacy.” However, drawing from objective analyses and empirical studies this case study finds no evidence for “Debt-trap diplomacy .”
An Autoethnography of Child Artists in Tamil Dance Reality Television Production
Authors: Venkatesh Sithara
Published: December 2020

Reality Television shows that revolve around the lives of children have become popular to audiences of all ages, which is evident in their success across diverse channels and various demographics (Palmer, 2013). With the increase in the number of reality shows and child participants in them, emerges a critical need of questioning the power of those in authority and are in- charge of production over the powerless group (the children) who aren’t of an age to legally possess the right to consent on their work, but have become the primary focus of almost every aspect of media commercialisation. An analysis of the conditions and effects of child participation in reality shows is extremely complex as it is difficult to make a child share his/her experience with others. It is also true that the history of children’s daily experiences are extremely difficult to trace, since children themselves have had little or no access to those public forms of expression (Holland, 2004).

This paper is an autoethnographic study that explores Tamil dance reality television's child artists during the period 2008-2020.The bodily performances of the dance reality television’s child artists and crew are studied by focusing on the intersections of body and space and with them developing in this context the concept of Biopolitics, as advanced by Michel Foucault (1979). The qualitative study covers a sample of 8 dance reality shows in five different Tamil channels with a focus on 12 child artists and how they spend their everyday lives in the shooting sets, rehearsal studios and other media production spaces. The researcher, being an insider in the reality television programmes, as a freelance floor director and coordinator for more than ten years now, provides this paper a significant leverage of the same and uses methods of memory work and self-reflexive writing along with in-depth interviews.
Optomechanical integrated optimization of a lightweight mirror for space cameras
Authors: Shao Mengqi , Zhang Lei , Jia Xuezhi
Published: December 2020

In order to improve the optical quality and lightweight ratio of a mirror, optomechanical analysis and optimization for the primary mirror of a space camera are carried out. The mirror surface performance under multiple load conditions is considered, including static gravity and uniform temperature rise load, as well as nonuniform temperature distribution loads. Sensitivities of the surface performance to the size parameters of the mirror are analyzed. The numerical simulations show that the size parameters obviously affect the performance and which parameters are key. The computed surface performance is analyzed with the help of ray-tracing software, and the contribution of size parameters to system optical performance is further evaluated. A size parameter optimization model is established to optimize the optical quality of the mirror. Finally, engineering analysis and dynamic tests are carried out. The results show that mechanical properties of the mirror are excellent, and the relative error of finite element analysis and dynamic test is within 10%. This verifies the accuracy of the model and the effectiveness of the optimization method.
The Simons Observatory: modeling optical systematics in the Large Aperture Telescope
Authors: Gudmundsson Jon E. , Gallardo Patricio A. , Puddu Roberto , Dicker Simon R. , Adler Alexandre E. , Ali Aamir M. , Bazarko Andrew , Chesmore Grace E. , Coppi Gabriele , Cothard Nicholas F. , Dachlythra Nadia , Devlin Mark , Dünner Rolando , Fabbian Giulio , Galitzki Nicholas , Golec Joseph E. , Patty Ho Shuay-Pwu , Hargrave Peter C. , Kofman Anna M. , Lee Adrian T. , Limon Michele , Matsuda Frederick T. , Mauskopf Philip D. , Moodley Kavilan , Nati Federico , Niemack Michael D. , Orlowski-Scherer John , Page Lyman A. , Partridge Bruce , Puglisi Giuseppe , Reichardt Christian L. , Sierra Carlos E. , Simon Sara M. , Teply Grant P. , Tucker Carole , Wollack Edward J. , Xu Zhilei , Zhu Ningfeng
Published: December 2020

We present geometrical and physical optics simulation results for the Simons Observatory Large Aperture Telescope. This work was developed as part of the general design process for the telescope, allowing us to evaluate the impact of various design choices on performance metrics and potential systematic effects. The primary goal of the simulations was to evaluate the final design of the reflectors and the cold optics that are now being built. We describe nonsequential ray tracing used to inform the design of the cold optics, including absorbers internal to each optics tube. We discuss ray tracing simulations of the telescope structure that allow us to determine geometries that minimize detector loading and mitigate spurious near-field effects that have not been resolved by the internal baffling. We also describe physical optics simulations, performed over a range of frequencies and field locations, that produce estimates of monochromatic far-field beam patterns, which in turn are used to gauge general optical performance. Finally, we describe simulations that shed light on beam sidelobes from panel gap diffraction.
Compact, broadband, and low-loss silicon photonic arbitrary ratio power splitter using adiabatic taper
Authors: Zhu Junbo , Chao Qiu , Huang Haiyang , Zhao Yingxuan , Li Yang , Tao Lue , She Xiaojuan , Liao Han , Huang Rui , Zhu Zijian , Liu Xiang , Sheng Zhen , Gan Fuwan
Published: December 2020

The arbitrary ratio power splitter is widely used in photonic integrated circuits (PICs), for signal monitoring, power equalization, signal feedback, and so on. Here we designed a fabrication-tolerant, compact, broadband, and low-loss arbitrary ratio power splitter. The proposed arbitrary ratio power splitter was realized with an adiabatically tapered silicon rib waveguide with 70 nm shallow etches and an

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waveguide. The fabrication analysis confirmed that both of them are robust to fabrication errors. 3D finite-difference time-domain simulations show a very low excess loss (less than 0.02 dB for

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waveguide and 0.05 dB for Si rib waveguide), and a broadband operating wavelength range (100 nm). Good fabrication tolerance and standard critical dimensions make the arbitrary ratio power splitter compatible with the standard fabrication process of commercial silicon photonic foundries.
Mapping the breeding sites of Anopheles gambiae s. l. in areas of residual malaria transmission in central western Senegal
Authors: Ndiaye Assane , Niang El Hadji Amadou , Diène Aminata Niang , Nourdine Mohamed Abderemane , Sarr Pape Cheikh , Konaté Lassana , Faye Ousmane , Gaye Oumar , Sy Ousmane
Published: December 2020

Despite the deployment of several effective control interventions in central-western Senegal, residual malaria transmission is still occurring in some hotspots. To better tailor targeted control actions, it is critical to unravel the underlying environmental and geographical factors that cause the persistence infection in hotspot villages. “Hotspots villages” were defined in our study as those reporting more than six indigenous malaria cases during the previous year. A total of ten villages, including seven hotspots and three non-hotspots, were surveyed. All potential mosquito breeding sites identified in and around the ten study villages were regularly monitored between 2013 and 2017. Monitoring comprised the detection of anopheline larvae and the collection of epidemiological, hydrogeological, topographical, and biogeographical data. The number of larval breeding sites described and monitored during the study period ranged from 50 to 62. Breeding sites were more numerous in hotspot sites in each year of monitoring, with 90.3% (56/62) in 2013, 90.9% (50/55) in 2014, 90.3% (56/62) in 2015 and 86% (43/50) in 2017 (Fisher exact test; p = 1). In the non-hotspot areas, the data for the same years were, respectively, 9.7% (6/62), 9.1% (5/55), 9.7% (6/62) and 14% (7/50) (p = 1). The Hotspot villages were characterized mostly by saline or moderately saline hydro-morphic and halomorphic soils allowing water retention and a potential larval breeding sites. By contrast, non-hotspot villages were characterized mainly by a high proportion of extremely permeable sandy-textured soils, which due to their porosity had low water retention. The annual number of confirmed malaria cases was correlated with the frequency and extent of breeding sites. Malaria cases were significantly more frequent in the hamlets located near breeding sites of An. gambiae s.l., gradually decreasing with increasing remoteness. This study shows that the characteristics of larval breeding sites, as measured by their longevity, stability, proximity to human habitation, and their positivity in Anopheles larvae are likely determining factors in the persistence of malaria hotspots in central-western Senegal. The results of this study shed more light on the environmental factors underlying the residual transmission and should make it possible to better target vector control interventions for malaria elimination in west-central Senegal.
Towards an understanding of the chemo-mechanical influences on kidney stone failure via the material point method
Authors: Raymond Samuel J. , Maragh Janille , Masic Admir , Williams John R.
Published: December 2020

This paper explores the use of the meshfree computational mechanics method, the Material Point Method (MPM), to model the composition and damage of typical renal calculi, or kidney stones. Kidney stones are difficult entities to model due to their complex structure and failure behavior. Better understanding of how these stones behave when they are broken apart is a vital piece of knowledge to medical professionals whose aim is to remove these stone by breaking them within a patient’s body. While the properties of individual stones are varied, the common elements and proportions are used to generate synthetic stones that are then placed in a digital experiment to observe their failure patterns. First a more traditional engineering model of a Brazil test is used to create a tensile fracture within the center of these stones to observe the effect of stone consistency on failure behavior. Next a novel application of MPM is applied which relies on an ultrasonic wave being carried by surrounding fluid to model the ultrasonic treatment of stones commonly used by medical practitioners. This numerical modeling of Extracorporeal Shock Wave Lithotripsy (ESWL) reveals how these different stones failure in a more real-world situation and could be used to guide further research in this field for safer and more effective treatments.
Regulation of gene transcription by thyroid hormone receptor β agonists in clinical development for the treatment of non-alcoholic steatohepatitis (NASH)
Authors: Luong Xuan G. , Stevens Sarah K. , Jekle Andreas , Lin Tse-I , Gupta Kusum , Misner Dinah , Chanda Sushmita , Mukherjee Sucheta , Williams Caroline , Stoycheva Antitsa , Blatt Lawrence M. , Beigelman Leonid N. , Symons Julian A. , Raboisson Pierre , McGowan David , Vandyck Koen , Deval Jerome
Published: December 2020

Thyroid hormones are important modulators of metabolic activity in mammals and alter cholesterol and fatty acid levels through activation of the nuclear thyroid hormone receptor (THR). Currently, there are several THRβ agonists in clinical trials for the treatment of non-alcoholic steatohepatitis (NASH) that have demonstrated the potential to reduce liver fat and restore liver function. In this study, we tested three THRβ-agonism-based NASH treatment candidates, GC-1 (sobetirome), MGL-3196 (resmetirom), and VK2809, and compared their selectivity for THRβ and their ability to modulate the expression of genes specific to cholesterol and fatty acid biosynthesis and metabolismin vitrousing human hepatic cells andin vivousing a rat model. Treatment with GC-1 upregulated the transcription ofCPT1Ain the human hepatocyte-derived Huh-7 cell line with a dose-response comparable to that of the native THR ligand, triiodothyronine (T3). VK2809A (active parent of VK2809), MGL-3196, and VK2809 were approximately 30-fold, 1,000-fold, and 2,000-fold less potent than T3, respectively. Additionally, these relative potencies were confirmed by quantification of other direct gene targets of THR, namely,ANGPTL4andDIO1. In primary human hepatocytes, potencies were conserved for every compound except for VK2809, which showed significantly increased potency that was comparable to that of its active counterpart, VK2809A. In high-fat diet fed rats, a single dose of T3 significantly reduced total cholesterol levels and concurrently increased liverDio1andMe1RNA expression. MGL-3196 treatment resulted in concentration-dependent decreases in total and low-density lipoprotein cholesterol with corresponding increases in liver gene expression, but the compound was significantly less potent than T3. In conclusion, we have implemented a strategy to rank the efficacy of THRβ agonists by quantifying changes in the transcription of genes that lead to metabolic alterations, an effect that is directly downstream of THR binding and activation.
Early serum tumor marker levels after fourteen days of tyrosine kinase inhibitor targeted therapy predicts outcomes in patients with advanced lung adenocarcinoma
Authors: Chen Hung-Jen , Tu Chih-Yen , Huang Kuo-Yang , Chien Chun-Ru , Hsia Te-Chun
Published: December 2020

Objective

Image evaluation strategy for lung cancer patients has difficulty obtaining the appropriate quantity of diffuse lung nodules and bone metastases. The study was to demonstrate whether early variations in the levels of serum 4-tumor markers (4-TMs)(carcinoembryonic antigen [CEA], cancer antigen [CA]125, CA19-9, and CA15-3) after TKI targeted therapy were associated with treatment response in patients with lung adenocarcinoma.

Methods

Patients with stage IIIB-IV lung adenocarcinoma taking epidermal growth factor receptor (EGFR) TKIs or anaplastic lymphoma kinase (ALK) inhibitors were enrolled prospectively from June 2012 to February 2015. According to the variations of the percentage of change in 4-TM levels (4-TMpc), we divided patients into ascending (increases in 4-TMpc over the 7th- 14th day) and descending (decreases in 4-TMpc over the 7th- 14th day) groups.

Results

184 patients were enrolled, and 89% had at least one of the pre-treatment evaluable TMs and were further analyzed. An excellent response to the TKI targeted therapy was accurately predicted in the descending group, as determined using receiver operating characteristic curve analysis (an area under the curve, 0.83). Multivariate Cox hazards model analyses demonstrated that the type of 4-TMpc and mutation status were the strongest predictors of progression-free survival (PFS)(descending versus ascending, hazard ratios [HR] 0.30, 95% confidence interval [CI], 0.19–0.47; sensitive mutation versus wide type, HR 0.30, 95% CI, 0.19–0.48).

Conclusions

Type of 4-TMpc 14 days after TKI targeted therapy is associated with an image response and PFS, without regarding mutation status, in patients with advanced lung adenocarcinoma.
Changes in the distribution of endogenous hormones in Phyllostachys edulis ‘Pachyloen’ during bamboo shooting
Authors: Shen Zhan , Zhang Yan-hua , Zhang Lei , Li Yuan , Sun Ya-dong , Li Zu-yao
Published: December 2020

In this study, we investigated the changes in the distribution and regulation of endogenous hormones in Phyllostachys edulis ‘Pachyloen’ during bamboo shooting. Enzyme-linked immunosorbent assay was used to measure the mass fractions of indole-3-acetic acid (IAA), gibberellic acid (GA), zeatin riboside (ZR), and abscisic acid (ABA) in rhizomes, shoots, and maternal bamboo organs during shoot sprouting, shoot growth, and new-bamboo formation. Measurements were compared among bamboo parts and developmental periods. The overall mass fractions of IAA and ABA were significantly higher than those of ZR and GA, driven by differences among bamboo parts and developmental periods. The abundance of each endogenous hormone varied among bamboo parts and developmental periods. During bamboo shooting, ABA had the highest mass fraction in all bamboo parts sampled, followed by IAA, GA, and ZR. Among bamboo parts, rhizomes had more IAA, ZR, and GA than the other parts, but significantly less ABA. Winter shoots had higher ZR: IAA and GA: IAA ratios than rhizomes and maternal bamboo organs. During shoot growth, ABA was the most abundant hormone in rhizomes and maternal bamboo organs, followed by IAA, ZR, and GA. In contrast, IAA was the most abundant hormone in spring shoots, followed by ABA, ZR, and GA. Maternal bamboo organs had a significantly higher ZR: GA ratio, and significantly lower IAA: ABA, ZR: ABA, and GA: ABA ratios than rhizomes. Spring shoots had significantly higher IAA: ABA, ZR: ABA, and GA: ABA ratios than rhizomes and maternal bamboo organs; significantly higher ZR mass fractions, and ZR: GA and ZR: IAA ratios and significantly lower ABA mass fractions than rhizomes; and significantly higher GA: IAA ratio than maternal bamboo organs. During new-bamboo formation, ABA was the most abundant hormone in rhizomes, winter shoots, and maternal bamboo organs, followed by IAA, ZR, and GA. Maternal bamboo organs had significantly lower IAA mass fractions and significantly higher ABA mass fractions than rhizomes and new bamboo tissue. IAA and ABA abundances exhibited an inverse relationship in rhizomes and maternal bamboo organs. GA: ABA and GA: IAA ratios decreased gradually and other hormone ratios exhibited parabolic trends over the bamboo-shooting period, with the highest ratios observed in new bamboo tissues. Overall, the coordination or antagonism among endogenous hormones plays a key regulatory role in bamboo shoot growth. The formation of thick walls in P. edulis ‘Pachyloen’, one of its major traits, may be partially attributed to the relatively high IAA and ZR and low GA mass fractions.
Community cervical cancer screening: Barriers to successful home-based HPV self-sampling in Dabat district, North Gondar, Ethiopia. A qualitative study
Authors: Megersa Bikila Soboka , Bussmann Hermann , Bärnighausen Till , Muche Achenef Asmamaw , Alemu Kassahun , Deckert Andreas
Published: December 2020

Objective

To explore the barriers to successful home-based human papillomavirus (HPV) self-sampling in North Gondar, Ethiopia.

Methods

The study participants were women who had previously participated in a community-wide home-based HPV self-sampling pilot study, community health workers, women’s development army leaders, and the sample collectors of the home-based HPV self-sampling pilot study. A community based qualitative descriptive study was conducted. We applied purposive and convenience sampling. In total, 47 women participated in the study (in-depth interviews n = 22, four focus group discussions n = 25, 6–7 participants each). The study employed thematic analysis for clustering the emerged themes.

Results

Husband disapproval was identified as the main barrier to the acceptance of home-based HPV self-sampling. Social influence, lack of knowledge about cervical cancer and screening, lack of health education on cervical cancer and HPV-based screening, feeling healthy, and religious influence were identified as additional barriers. Fear of using Evalyn brush® for self-sampling was found to be the main barrier to the provision of a quality sample. The inability of the sample collectors to check the proper utilization of Evalyn brush® and the difficulty in understanding the instructions did also contribute to the low-quality. Providing health education concerning cervical cancer and HPV self-sapling to women, male involvement in the screening program, and linking the screening service to existing local health facilities were suggested to guarantee the success of home-based HPV self-sampling.

Conclusions

Educating women regarding cervical cancer and HPV testing, providing clear instructions on how to collect self-sample, and male involvement in the screening program are prerequisites for a successful implementation of home-based HPV testing. Women empowerment should also be focused to overcome the identified sociocultural barriers. Furthermore, the screening program should guarantee the timely provision of the test results and offering women follow-up examinations and treatment for abnormal findings.