bluuebunny/crossref_metadata_2025 huggingface dataset:
SLC6A8-mediated intracellular creatine accumulation enhances hypoxic breast cancer cell survival via ameliorating oxidative stress
Authors: Li Qiao , Liu Manran , Sun Yan , Jin Ting , Zhu Pengpeng , Wan Xueying , Hou Yixuan , Tu Gang
Published: May 2021

Background

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with poor prognosis and limited treatment options. Hypoxia is a key hallmark of TNBC. Metabolic adaptation promotes progression of TNBC cells that are located within the hypoxic tumor regions. However, it is not well understood regarding the precise molecular mechanisms underlying the regulation of metabolic adaptions by hypoxia.

Methods

RNA sequencing was performed to analyze the gene expression profiles in MDA-MB-231 cell line (20% O2 and 1% O2). Expressions of Slc6a8, which encodes the creatine transporter protein, were detected in breast cancer cells and tissues by quantitative real-time PCR. Immunohistochemistry was performed to detect SLC6A8 protein abundances in tumor tissues. Clinicopathologic correlation and overall survival were evaluated by chi-square test and Kaplan-Meier analysis, respectively. Cell viability assay and flow cytometry analysis with Annexin V/PI double staining were performed to investigate the impact of SLC6A8-mediated uptake of creatine on viability of hypoxic TNBC cells. TNBC orthotopic mouse model was used to evaluate the effects of creatine in vivo.

Results

SLC6A8 was aberrantly upregulated in TNBC cells in hypoxia. SLC6A8 was drastically overexpressed in TNBC tissues and its level was tightly associated with advanced TNM stage, higher histological grade and worse overall survival of TNBC patients. We found that SLC6A8 was transcriptionally upregulated by p65/NF-κB and mediated accumulation of intracellular creatine in hypoxia. SLC6A8-mediated accumulation of creatine promoted survival and suppressed apoptosis via maintaining redox homeostasis in hypoxic TNBC cells. Furthermore, creatine was required to facilitate tumor growth in xenograft mouse models. Mechanistically, intracellular creatine bolstered cell antioxidant defense by reducing mitochondrial activity and oxygen consumption rates to reduce accumulation of intracellular reactive oxygen species, ultimately activating AKT-ERK signaling, the activation of which protected the viability of hypoxic TNBC cells via mediating the upregulation of Ki-67 and Bcl-2, and the downregulation of Bax and cleaved Caspase-3.

Conclusions

Our study indicates that SLC6A8-mediated creatine accumulation plays an important role in promoting TNBC progression, and may provide a potential therapeutic strategy option for treatment of SLC6A8 high expressed TNBC.
Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
Authors: Yang Xiao , Wu Jia-shun , Li Mao , Zhang Wei-long , Gao Xiao-lei , Wang Hao-fan , Yu Xiang-hua , Pang Xin , Zhang Mei , Liang Xin-hua , Tang Ya-ling
Published: May 2021

Background

Patients were prone to have poor prognosis once dormant tumor cells being reactivated. However, the molecular mechanism of tumor cell dormancy remains poorly understood. This study aimed to investigate the function of DEC2 in the dormancy of salivary adenoid cystic carcinoma (SACC) in vitro and vivo.

Methods

The function of DEC2 in tumor dormancy of SACC was investigated in nude mice by establishing primary and lung metastasis model. Meanwhile, the interaction between hypoxia and SACC dormancy and the role of DEC2 were demonstrated through CoCl2 induced hypoxia–mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence.

Results

In the primary SACC, DEC2 overexpression inhibited cell proliferation, increased cell population arrested in G0/G1 phase, and participated in dormancy regulation, which limited tumor growth. Intriguingly, in the model of lung metastasis, the level of DEC2 was reduced significantly and resulted in dormancy exit and growth resumption of SACC cells. Then, we found that DEC2 may associate with hypoxia in contributing to tumor dormancy, which might provide a possible cue to explain the different roles of DEC2 in primary and metastasis lesions. And overexpression of DEC2 induced dormancy and promoted migration and invasion through activating EMT program. Finally, DEC2 positive expression was shown to be significantly correlated with recurrence and dormancy of SACC patients.

Conclusions

These findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.
Serial Lipocalin 2 and Oncostatin M levels reflect inflammation status and treatment response in axial spondyloarthritis
Authors: Tsui Florence W. L. , Lin Aifeng , Sari Ismail , Zhang Zhenbo , Tsui Hing Wo , Inman Robert D.
Published: May 2021

Background

Informative serum biomarkers for monitoring inflammatory activity and treatment responses in axial spondyloarthritis (axSpA) are lacking. We assessed whether Lipocalin 2 (LCN2) and Oncostatin M (OSM), both having roles in inflammation and bone remodeling, may accurately reflect chronic joint inflammation and treatment response in axSpA. Previous reports in animal models showed involvement of LCN2 and OSM in joint/gut inflammation. We asked whether they also play a role in human axSpA.

Methods

We analyzed a longitudinal observational axSpA cohort (286 patients) with yearly clinical assessments and concurrent measurements of serum LCN2 and OSM (1204 serum samples) for a mean of 4 years. Biomarker levels were correlated with MRI scoring and treatment response.

Results

Persistent and transient elevation of LCN2 and OSM were observed in axSpA patients. Persistent elevation of LCN2 or OSM, but not CRP, correlated with sacroiliac joint (SIJ) MRI SPARCC scores (Pearson’s correlation p = 0.0005 and 0.005 for LCN2 and OSM respectively), suggesting that LCN2/OSM outperforms CRP as reflective of SIJ inflammation. We observed both concordant and discordant patterns of LCN2 and OSM in relationship to back pain, the cardinal clinical symptom in axSpA. Twenty-six percent (73/286) of the patients remained both clinically and serologically active (CASA). Sixty percent (173/286) of the patients became clinically quiescent, with back pain resolved, but 53% (92/173) of them were serologically active (CQSA), indicating that pain control may not indicate control of joint inflammation, as reflected by positive MRI imaging of SIJ. With respect to treatment responses, transient elevation of LCN2 or OSM over time was predictive of better response to all treatments.

Conclusion

In axSpA, persistent LCN2 and/or OSM elevation reflects chronic SIJ inflammation and suboptimal treatment response. In our cohort, half of the currently deemed clinically quiescent patients with back pain resolved continued to demonstrate chronic joint inflammation. LCN2 and OSM profiling outperforms CRP as a predictive measure and provides an objective assessment of chronic local inflammation in axSpA patients.
Mendelian randomization: estimation of inpatient hospital costs attributable to obesity
Authors: Dick Katherine , Schneider John E. , Briggs Andrew , Lecomte Pascal , Regnier Stephane A. , Lean Michael
Published: May 2021

Background

Mendelian Randomization is a type of instrumental variable (IV) analysis that uses inherited genetic variants as instruments to estimate causal effects attributable to genetic factors. This study aims to estimate the impact of obesity on annual inpatient healthcare costs in the UK using linked data from the UK Biobank and Hospital Episode Statistics (HES).

Methods

UK Biobank data for 482,127 subjects was linked with HES inpatient admission records, and costs were assigned to episodes of care. A two-stage least squares (TSLS) IV model and a TSLS two-part cost model were compared to a naïve regression of inpatient healthcare costs on body mass index (BMI).

Results

The naïve analysis of annual cost on continuous BMI predicted an annual cost of £21.61 [95% CI £20.33 – £22.89] greater cost per unit increase in BMI. The TSLS IV model predicted an annual cost of £14.36 [95% CI £0.31 – £28.42] greater cost per unit increase in BMI. Modelled with a binary obesity variable, the naïve analysis predicted that obese subjects incurred £205.53 [95% CI £191.45 – £219.60] greater costs than non-obese subjects. The TSLS model predicted a cost £201.58 [95% CI £4.32 – £398.84] greater for obese subjects compared to non-obese subjects.

Conclusions

The IV models provide evidence for a causal relationship between obesity and higher inpatient healthcare costs. Compared to the naïve models, the binary IV model found a slightly smaller marginal effect of obesity, and the continuous IV model found a slightly smaller marginal effect of a single unit increase in BMI.
On a fractional-order p-Laplacian boundary value problem at resonance on the half-line with two dimensional kernel
Authors: Imaga O. F. , Iyase S. A.
Published: May 2021

In this work, we consider the solvability of a fractional-order p-Laplacian boundary value problem on the half-line where the fractional differential operator is nonlinear and has a kernel dimension equal to two. Due to the nonlinearity of the fractional differential operator, the Ge and Ren extension of Mawhin’s coincidence degree theory is applied to obtain existence results for the boundary value problem at resonance. Two examples are used to validate the established results.
Metagenomic analysis reveals the shared and distinct features of the soil resistome across tundra, temperate prairie, and tropical ecosystems
Authors: Qian Xun , Gunturu Santosh , Guo Jiarong , Chai Benli , Cole James R. , Gu Jie , Tiedje James M.
Published: May 2021

Background

Soil is an important reservoir of antibiotic resistance genes (ARGs), but their potential risk in different ecosystems as well as response to anthropogenic land use change is unknown. We used a metagenomic approach and datasets with well-characterized metadata to investigate ARG types and amounts in soil DNA of three native ecosystems: Alaskan tundra, US Midwestern prairie, and Amazon rainforest, as well as the effect of conversion of the latter two to agriculture and pasture, respectively.

Results

High diversity (242 ARG subtypes) and abundance (0.184–0.242 ARG copies per 16S rRNA gene copy) were observed irrespective of ecosystem, with multidrug resistance and efflux pump the dominant class and mechanism. Ten regulatory genes were identified and they accounted for 13–35% of resistome abundances in soils, among them arlR, cpxR, ompR, vanR, and vanS were dominant and observed in all studied soils. We identified 55 non-regulatory ARGs shared by all 26 soil metagenomes of the three ecosystems, which accounted for more than 81% of non-regulatory resistome abundance. Proteobacteria, Firmicutes, and Actinobacteria were primary ARG hosts, 7 of 10 most abundant ARGs were found in all of them. No significant differences in both ARG diversity and abundance were observed between native prairie soil and adjacent long-term cultivated agriculture soil. We chose 12 clinically important ARGs to evaluate at the sequence level and found them to be distinct from those in human pathogens, and when assembled they were even more dissimilar. Significant correlation was found between bacterial community structure and resistome profile, suggesting that variance in resistome profile was mainly driven by the bacterial community composition.

Conclusions

Our results identify candidate background ARGs (shared in all 26 soils), classify ARG hosts, quantify resistance classes, and provide quantitative and sequence information suggestive of very low risk but also revealing resistance gene variants that might emerge in the future.
First report of three species of Trichoderma isolated from the rhizosphere in Algeria and the high antagonistic effect of Trichoderma brevicompactum to control grey mould disease of tomato
Authors: Hammad Massinissa , Guillemette Thomas , Alem Meriem , Bastide Franck , Louanchi Meriem
Published: May 2021

Background

Grey mould caused by Botrytis cinerea Pers. (teleomorph Botryotinia fuckeliana (de Bary) Whetzel) is one of the most destructive fungal diseases of Mediterranean crops. In Algeria, few studies have been made on the economic impact of this disease. Nevertheless, it is practically present in all tomato and strawberry greenhouses, as well as in prospected vineyards in the north and south of the country. The complexity of chemical control of this disease has led to search for Trichoderma strains that are effective in biological control.

Results

Fifteen isolates of Trichoderma spp. were obtained from vigorous and healthy plants (tomatoes, strawberries, and vines) rhizosphere, and from a commercial bio-compost (Bio-composte®), then identified as T. afroharzianum (four isolates), T. gamsii (four isolates), T. longibrachiatum (three isolates), T. atroviride (one isolate), T. brevicompactum (one isolate), T. breve (one isolate), and T. lixii (one isolate) on the basis of DNA sequence analysis of four genes (ITS, tef1, rpb2, and acl1). In vitro biocontrol tests revealed that four Algerian isolates of Trichoderma spp. (TAtC11, TGS7, TGS10, and TBS1) had a high antagonistic activity against B. cinerea, the mycelial growth has been reduced by 62 to 65% in dual-culture technique, by 62.31 to 64.49% in volatile compounds test, and a high inhibition of germling growth was recorded by TBS1 isolate with 90.68% in Culture filtrates test. Biocontrol tests carried out on tomato plants with T. brevicompactum (TBS1), T. atroviride (TAtC11), and T. lixii (TLiC8) against B. cinerea (BCT04) showed that TBS1 inoculation significantly reduced the incidence of disease by 64.43 and 51.35% in preventive and curative treatment, respectively.

Conclusion

The present study revealed the first report of T. brevicompactum, T. breve, and T. lixii in Algeria, and it also contributes to the promotion of the use of native strains of Trichoderma in biological control leading to a better preservation of soil microbial diversity.
Value of information analysis in civil and infrastructure engineering: a review
Authors: Zhang Wei-Heng , Lu Da-Gang , Qin Jianjun , Thöns Sebastian , Faber Michael Havbro
Published: May 2021

The concept of Value of Information (VoI) has attracted significant attentions within the civil engineering community over especially the last decade. Triggered by the increasing focus on structural health monitoring, availability of data and emerging techniques of Big Data analysis and Artificial Intelligence, important insights on how to take benefit from VoI in structural integrity management have been gained. This literature review starts out with a summary of the historical developments and contains (1) a summary of two different VoI analysis origins, (2) a compilation of existing VoI analyses research and (3) current engineering interpretations and applications of VoI in the field of civil and infrastructure engineering. VoI analysis has roots in communication theory and Bayesian decision analysis in conjunction with utility theory. Starting point is thus taken in brief introduction of these theoretical foundations, followed by a discussion on the relevant modelling aspects such as information, probability and utility modelling. A detailed review of relevant existing research is presented, divided into the following main areas: computational methods, optimal sensor placement and engineering risk management. Finally, by way of conclusion and outlook, challenges and some promising directions for VoI analysis in the field of civil and infrastructure engineering are identified.
Current practice and adaptations being made for people with autism admitted to in-patient psychiatric services across the UK
Authors: Jones Keir , Gangadharan Satheesh , Brigham Philip , Smith Edward , Shankar Rohit
Published: May 2021

Background

A significant number of people with autism require in-patient psychiatric care. Although the requirement to adequately meet the needs of people with autism in these settings is enshrined in UK law and supported by national guidelines, little information is available on current practice.

Aims

To describe characteristics of UK in-patient psychiatric settings admitting people with autism. Also to examine psychiatric units for their suitability, and the resultant impact on admission length and restrictive interventions.

Method

Multiple-choice questions about in-patient settings and their ability to meet the needs of people with autism and the impact on their outcomes were developed as a cross-sectional study co-designed with a national autism charity. The survey was distributed nationally, using an exponential and non-discriminatory snowballing technique, to in-patient unit clinicians to provide a current practice snapshot.

Results

Eighty responses were analysed after excluding duplications, from across the UK. Significant variation between units across all enquired parameters exist. Lack of autism-related training and skills across staff groups was identified, this becoming disproportionate when comparing intellectual disability units with general mental health units particularly regarding psychiatrists working in these units (psychiatrists: 94% specialist skills in intellectual disability units versus 6% specialist skills in general mental health units). In total, 28% of survey respondents felt people with autism are more likely to be subject to seclusion and 40% believed in-patients with autism are likely to end in segregation.

Conclusions

There is no systematic approach to supporting people with autism who are admitted to in-patient psychiatric units. Significant concerns are highlighted of lack of professional training and skill sets resulting in variable clinical practice and care delivery underpinned by policy deficiency. This could account for the reported in-patient outcomes of longer stay and segregation experienced by people with autism.
Challenges in Adjuvant Therapy for Premenopausal Women Diagnosed With Luminal Breast Cancers
Authors: Vaz-Luis Ines , Francis Prudence A. , Di Meglio Antonio , Stearns Vered
Published: May 2021

More than 90% of women with newly diagnosed breast cancer present with stage I to III disease and, with optimal multidisciplinary therapy, are likely to survive their disease. Of these patients, 70% are hormone receptor–positive and candidates for adjuvant endocrine therapy. The adoption of cumulatively better adjuvant treatments contributed to improved outcomes in patients with hormone receptor–positive, early-stage breast cancer. Premenopausal women with hormone receptor–positive breast cancer often present with complex disease and have inferior survival outcomes compared with their postmenopausal counterparts. Risk stratification strategies, including classic clinicopathologic features and newer gene expression assays, can assist in treatment decisions, including adjuvant chemotherapy use and type or duration of endocrine therapy. Gene expression assays may help identify patients who can safely forgo chemotherapy, although to a lesser extent among premenopausal patients, in whom they may play a role only in node-negative disease. Patients at lower risk of recurrence can be adequately treated with tamoxifen alone, whereas higher-risk patients benefit from ovarian function suppression with tamoxifen or an aromatase inhibitor. The role of adding newer therapies such as CDK4/6 inhibitors to adjuvant endocrine therapy is not yet clear. Breast cancer treatments are associated with several side effects, with major impact on patients’ quality of life and treatment adherence, particularly in premenopausal women for whom these side effects may be more prominent as the result of the abrupt decrease in estrogen concentrations. Personalized management of treatment side effects, addressing patients' concerns, and health promotion should be an integral part of the care of premenopausal women diagnosed with luminal breast cancers.
Harnessing Nutrition and Physical Activity for Breast Cancer Prevention and Control to Reduce Racial/Ethnic Cancer Health Disparities
Authors: Bandera Elisa V. , Alfano Catherine M. , Qin Bo , Kang Dong-Woo , Friel Ciarán P. , Dieli-Conwright Christina M.
Published: May 2021

There are well-known racial/ethnic disparities in the prevalence of obesity and physical inactivity, as well as breast cancer risk and survival. However, most of the current scientific evidence that serves as a foundation for nutrition and physical activity guidelines is based on studies conducted in predominantly non-Hispanic White populations. Similarly, exercise, diet, or lifestyle intervention trials for breast cancer prevention and survivorship are scarce in racial/ethnic minority populations. We review the current evidence for racial/ethnic disparities in obesity and breast cancer risk and survival (we are focusing on obesity, because this is considered an ASCO priority, and studies conducted in the United States), discuss the evolution of nutrition/physical activity guidelines for cancer prevention and control, and provide an overview of lifestyle interventions, including barriers and facilitators in implementation and dissemination science among minority populations underrepresented in research. There is a critical need to include racially/ethnically diverse populations in cancer prevention and control research or to specifically target minority populations in which disparities are known to exist to achieve much needed health equity.
Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced Urothelial Carcinoma: Results of CALGB 90601 (Alliance)
Authors: Rosenberg Jonathan E. , Ballman Karla A. , Halabi Susan , Atherton Pamela J. , Mortazavi Amir , Sweeney Christopher , Stadler Walter M. , Teply Benjamin A. , Picus Joel , Tagawa Scott T. , Katragadda Sreedhar , Vaena Daniel , Misleh Jamal , Hoimes Christopher , Plimack Elizabeth R. , Flaig Thomas W. , Dreicer Robert , Bajorin Dean , Hahn Olwen , Small Eric J. , Morris Michael J.
Published: May 2021

PURPOSE

The combination of gemcitabine and cisplatin (GC) is a standard therapy for metastatic urothelial carcinoma. Based on data that angiogenesis plays a role in urothelial carcinoma growth and progression, a randomized placebo-controlled trial was performed with the primary objective of testing whether patients treated with GC and bevacizumab (GCB) have superior overall survival (OS) than patients treated with GC and placebo (GCP).

PATIENTS AND METHODS

Between July 2009 and December 2014, 506 patients with metastatic urothelial carcinoma without prior chemotherapy for metastatic disease and no neoadjuvant or adjuvant chemotherapy within 12 months were randomly assigned to receive either GCB or GCP. The primary end point was OS, with secondary end points of progression-free survival, objective response, and toxicity.

RESULTS

With a median follow-up of 76.3 months among alive patients, the median OS was 14.5 months for patients treated with GCB and 14.3 months for patients treated with GCP (hazard ratio for death = 0.87; 95% CI, 0.72 to 1.05; two-sided stratified log-rank P = .14). The median progression-free survival was 8.0 months for GCB and 6.7 months for GCP (hazard ratio = 0.77; 95% CI, 0.63 to 0.95; P = .016). The proportion of patients with grade 3 or greater adverse events did not differ significantly between both arms, although increased bevacizumab-related toxicities such as hypertension and proteinuria occurred in the bevacizumab-treated arm.

CONCLUSION

The addition of bevacizumab to GC did not result in improved OS. The observed median OS of about 14 months is consistent with prior phase III trials of cisplatin-based chemotherapy.
Quantum computing models for artificial neural networks
Authors: Mangini S. , Tacchino F. , Gerace D. , Bajoni D. , Macchiavello C.
Published: May 2021

Neural networks are computing models that have been leading progress in Machine Learning (ML) and Artificial Intelligence (AI) applications. In parallel, the first small-scale quantum computing devices have become available in recent years, paving the way for the development of a new paradigm in information processing. Here we give an overview of the most recent proposals aimed at bringing together these ongoing revolutions, and particularly at implementing the key functionalities of artificial neural networks on quantum architectures. We highlight the exciting perspectives in this context, and discuss the potential role of near-term quantum hardware in the quest for quantum machine learning advantage.
Hole-like Fermi surface in the overdoped non-superconducting Bi1.8 Pb0.4 Sr2CuO6+δ
Authors: Valla T. , Pervan P. , Pletikosić I. , Drozdov I. K. , Kundu Asish K. , Wu Zebin , Gu G. D.
Published: May 2021

In high-temperature cuprate superconductors, the anti-ferromagnetic spin fluctuations are thought to have a very important role in naturally producing an attractive interaction between the electrons in the d-wave channel. The connection between superconductivity and spin fluctuations is expected to be especially consequential at the overdoped end point of the superconducting dome. In some materials, that point seems to coincide with a Lifshitz transition, where the Fermi surface changes from the hole-like centered at

to the electron-like, centered at the Γ point causing a loss of large momentum anti-ferromagnetic fluctuations. Here, we study the doping dependence of the electronic structure of Bi1.8Pb0.4Sr2CuO

in angle-resolved photoemission and find that the superconductivity vanishes at lower doping than that at which the Lifshitz transition occurs. This requires a more detailed re-examination of a spin fluctuation scenario.
Surface and sub-surface investigations of the plasma influence on Cs doped Mo as surface converter for negative hydrogen ion sources for fusion(a)
Authors: Schiesko L. , Cristofaro S. , Höschen T. , Hopf C.
Published: May 2021

The influence of low-pressure and low-temperature hydrogen plasma on a pure molybdenum sample implanted with caesium is investigated by means of sputtering-XPS. A portion of the sample was exposed to the plasma, while the rest of the sample was covered by stainless steel and thus shielded from direct plasma flux. The results show that the part of the sample exposed to the plasma exhibits both on and beneath the surface an increased amount of H2O and MoO2 with respect to the covered sample part which can be explained by a chemical reduction of MoO3 oxides by the hydrogen plasma species. The XPS Cs lines show oxidation peaks. A sputtering depth of roughly 13 nm is necessary to recover an identical spectrum, indicating that the plasma changes the chemical composition of the implanted samples not only on the surface but also inside the material.
Emergency Front-of-Neck Airway Rescue Via the Cricothyroid Membrane: A High-Resolution Computed Tomography Study of Airway Anatomy in Adults
Authors: Fennessy Paul , Greco Eugene , Gelber Nicholas , Brewster David J. , Reeves John H.
Published: May 2021

BACKGROUND:

Emergency front-of-neck airway rescue is recommended in a can’t intubate, can’t oxygenate clinical scenario. Cannula cricothyroidotomy has been reported as having a high failure rate. Our primary aim was to estimate the angle of the trachea in relation to the horizontal axis in a simulated emergency front-of-neck airway rescue position. Our secondary aims were to estimate the optimal cannula angle of approach and evaluate the anatomical relationship of the cricothyroid membrane (CTM) to adjacent structures. We also assessed whether the CTM lies above or below the neck midpoint, a point equidistant from the suprasternal notch (SSN), and the chin surface landmarks. All measurements were compared between the male and female subjects.

METHODS:

Subjects having elective computed tomography of their thorax were consented to have extension of the computed tomography to include their neck. A preliminary radiation dose and risk assessment deemed the additional radiation to be of very low risk (level IIa). Subjects were positioned supinely on the computed tomography table. Standard neck extension was achieved by placing a pillow under the scapulae and a rolled towel under the neck to simulate emergency front-of-neck airway rescue positioning.

RESULTS:

Fifty-two subjects were included in this study: 31 men and 21 women. The mean angle of the trachea in relation to the horizontal axis was 25.5° (95% confidence interval [CI], 21.8–29.1) in men and 14.0° (95% CI, 11.5–16.5) in women. The mean minimum angles required for hypothetical cannula cricothyroidotomy for men and women were 55.2° (95% CI, 51.8–58.7) and 50.5° (95% CI, 45.4–55.6), respectively. The CTM was located lower in the neck in men compared to women. The CTM was located below the neck midpoint in 30 of 30 (100%) male subjects and 11 of 20 (55%) female subjects (P < .001).

CONCLUSIONS:

The trachea angulates posteriorly in a simulated emergency front-of-neck airway rescue position in supine subjects and to a greater degree in men compared to women (P < .001). The minimum angle required for hypothetical cannula cricothyroidotomy was >45° in the majority (75%) of subjects studied. A steeper cannula angle of approach may be more reliable and warrants further clinical study. If airway anatomy is indistinct and performing a vertical scalpel cricothyroidotomy, consideration should be given to performing this incision lower in the neck in men compared to women.
Agnès Varda, Jane Birkin, and Kung-fu Master!
Authors: Wilson Emma
Published: May 2021

Kung-fu Master! (Le petit amour, France, 1988) arises from a story by Jane Birkin, where an adult woman and a teenage boy fall in love. Birkin's story was meant to be realized as one of the dramatized sequences of Jane B. by Agnès V. (Jane B. par Agnès V., France, 1988), but it became its own parallel film. In prioritizing this story and pushing it to feature length, Varda opened it up for imagining with and beyond Birkin. She made it a fairy-tale, a feminist story about what women may imagine and eroticize, about the grief, pathos, damage, and beauty in this. It became a vital part of Varda's film corpus and of her feminist investigations of different subjectivities and desires, of the affective worlds of contemporary women and children. It takes shape in her tenderness for Jane Birkin, but also in light of her own clearer thinking about childhood, nostalgia, and fantasy. In this film, Varda explores female-authored fantasies in delicate, unabashed, and queer ways. This is part of her feminist legacy for the future. Kung-fu Master! is key.
She Listened: Vardian Self-Portraiture and Auto-Refrains of Sea, Wind, and Sand
Authors: Boljkovac Nadine
Published: May 2021

This article considers Vardian acts of listening and (self-)portraiture. With works that celebrate the material world in its myriad forms and scales, from a beloved button to a bottomless sea, Agnès Varda developed a method of empathetic engagement. Her encounters grasped relations extending from a person, family, or group, to a greater world-memory and duration comprising “us” all. As it heeds these foldings of the world, this article considers subjectification processes that take into a self all elements of nature. With sustained awareness of the “hundreds of thousands of people” she doesn't know, through her acts of listening and portraiture, in her later years Varda simultaneously attained a recognizable persona and an imperceptibility that gestured to an inward-outward movement her works so often foretell: that of a self's full dissolution into memory and world. In line with Varda's lifelong commitment to new forms of making visible the invisible, and her embrace of a sea as a groundless source of intersubjective relations, limits transform via her works into reflective, dissolving surfaces. A doubling of the personal and cosmic—that movement that so singularizes Varda—emanates through this weave of her art and life. As a chiasmatic double herself whose encounters brought extremes into contact, Varda demonstrated a concern for the future of the world that persisted alongside an awareness of her own mortality. Beyond the duration of her own life, Varda's works expose us to ourselves while always foregrounding the woman, and women, behind, before, and beyond the lens.
Agnès Varda and Le Collectif 50/50 en 2020: Power and Protest at the Cannes Film Festival
Authors: DeRoo Rebecca J.
Published: May 2021

This article examines how Agnès Varda used speeches and activism at the Cannes Film Festival in recent years to reveal and challenge the underrepresentation of female directors in the film industry. At the 2015 Cannes Film Festival, she accepted an honorary Palme (lifetime achievement award) in the name of other creative directors not yet in the spotlight. In 2018, Varda joined with the 50/50 en 2020 collective, a gender equity campaign, on the Cannes red carpet to call for gender parity and greater transparency in the festival's process of selecting films to screen. This article shows how Varda and 50/50 en 2020 explore social, institutional, and economic factors that may influence women's access to the highest levels of artistic success. Their actions articulate a gendered investigation of cultural institutions and the relations of power they represent, focusing on the festival and the film industry. Furthermore, this article considers dynamics of social and economic power and perceptions of cultural value in the 2019 Cannes festival tribute to Varda.
From Cannes to Cardboard: The Circulation and Promotion of Visages Villages and the Auteur on Instagram
Authors: St. John Matt
Published: May 2021

This article explores the Instagram activities of Agnès Varda and her Visages Villages (Faces Places, France, 2017) codirector JR to consider the role of social media in the film's theatrical release and awards campaign, which led to the film's nomination for Best Documentary Feature—Varda's first and only Academy Award nomination. Through analysis of Varda's posts and her appearances on JR's Instagram, the author argues that social media complemented the film's conventional promotion while extending Varda's aesthetic practices and interests, offering one of the final examples of her consistent, enthusiastic experiments with new forms of media. On Instagram, Varda recycled and recontextualized the strategies of self-presentation and formal play seen in her documentaries for a different format, as she posted images and videos involving premieres, special events, and press coverage from her perspective. Throughout the film's release and awards campaign, social media began to function as an atypical way to draw attention to the film and its directors, especially for a low-budget documentary. The Visages Villages team merged traditional methods of achieving visibility with an unusual and intentional online presence, culminating in substantial coverage from new types of outlets when JR traveled to the Academy Awards luncheon with cardboard cutouts of Varda.
Extramedullary multiple myeloma patient-derived orthotopic xenograft with a highly altered genome: combined molecular and therapeutic studies
Authors: Farre Lourdes , Sanz Gabriela , Ruiz-Xivillé Neus , Castro de Moura Manuel , Martin-Tejera Juan Francisco , Gonçalves-Ribeiro Samuel , Martinez-Iniesta Maria , Calaf Monica , Luis Mosquera Jose , Martín-Subero José Ignacio , Granada Isabel , Esteller Manel , Domingo-Domenech Eva , Climent Fina , Villanueva Alberto , Sureda Anna
Published: May 2021

Extramedullary multiple myeloma (EMM) has an overall survival of 6 months and occurs in 20% of multiple myeloma (MM) patients. Genetic and epigenetic mechanisms involved in EMM and the therapeutic role of new agents for MM are not well established. Besides, well-characterized preclinical models for EMM are not available. Herein, a patient-derived orthotopic xenograft (PDOX) was generated from a patient with an aggressive EMM to study in-depth genetic and epigenetic events, and drug responses related to extramedullary disease. A fresh punch of an extramedullary cutaneous lesion was orthotopically implanted in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ(NSG) mouse. The PDOX mimicked histologic and phenotypic features of the tumor of the patient. Cytogenetic studies revealed a hyperploid genome with multiple genetic poor-prognosis alterations. Copy number alterations (CNAs) were detected in all chromosomes. The IGH translocation t(14;16)(q32;q23)IGH/MAF was already observed at the medullary stage and a new one, t(10;14)(p?11-12;q32), was observed only with extramedullary disease and could be eventually related to EMM progression in this case. Exome sequencing showed 24 high impact single nucleotide variants and 180 indels. From the genes involved, only TP53 was previously described as a driver in MM. A rather balanced proportion of hyper/hypomethylated sites different to previously reported widespread hypomethylation in MM was also observed. Treatment with lenalidomide, dexamethasone and carfilzomib showed a tumor weight reduction of 90% versus non-treated tumors, whereas treatment with the anti-CD38 antibody daratumumab showed a reduction of 46%. The generation of PDOX from a small EMM biopsy allowed us to investigate in depth the molecular events associated with extramedullary disease in combination with drug testing.
Trim9 and Klp61F promote polymerization of new dendritic microtubules along parallel microtubules
Authors: Feng Chengye , Cleary Joseph M. , Kothe Gregory O. , Stone Michelle C. , Weiner Alexis T. , Hertzler James I. , Hancock William O. , Rolls Melissa M.
Published: May 2021

Axons and dendrites are distinguished by microtubule polarity. In Drosophila, dendrites are dominated by minus-end-out microtubules, whereas axons contain plus-end-out microtubules. Local nucleation in dendrites generates microtubules in both orientations. To understand why dendritic nucleation does not disrupt polarity, we used live imaging to analyze the fate of microtubules generated at branch points. We found that they had different rates of success exiting the branch based on orientation: correctly oriented minus-end-out microtubules succeeded in leaving about twice as often as incorrectly oriented microtubules. Increased success relied on other microtubules in a parallel orientation. From a candidate screen, we identified Trim9 and kinesin-5 (Klp61F) as machinery that promoted growth of new microtubules. In S2 cells, Eb1 recruited Trim9 to microtubules. Klp61F promoted microtubule growth in vitro and in vivo, and could recruit Trim9 in S2 cells. In summary, the data argue that Trim9 and kinesin-5 act together at microtubule plus ends to help polymerizing microtubules parallel to pre-existing ones resist catastrophe.
Enhanced Recovery After Surgery can Improve Patient Outcomes and Reduce Hospital Cost of Gastrectomy for Cancer in the West: A Propensity-Score-Based Analysis
Authors: Weindelmayer Jacopo , Mengardo Valentina , Gasparini Angela , Sacco Michele , Torroni Lorena , Carlini Mauro , Verlato Giuseppe , de Manzoni Giovanni
Published: May 2021

Background

Data on ERAS for gastrectomy are scarce, and the majority of the studies come from Eastern countries. Patients in the West are older and suffer from more advanced tumors that impair their clinical condition and often require neoadjuvant treatment. This retrospective study assessed the feasibility and safety of an Enhanced Recovery After Surgery (ERAS) protocol for gastrectomy in a Western center.

Methods

We conducted a single-center study of 351 patients operated for gastric cancer: 103, operated from January 2015 to December 2016, followed the standard pathway, while 248, operated from January 2017 to December 2019, followed the ERAS program. The primary outcomes considered were length of hospital stay (LOS) and direct costs. Secondary outcomes were 90-day morbidity and mortality, readmission rate, and compliance with ERAS items. A propensity score (PS) was built on confounding variables.

Results

Compliance with ERAS items after the program was ≥ 70%. Univariable analysis evidenced a 2-day median reduction in LOS and a median cost reduction of €826 per patient in the ERAS group. PS-based multivariable analysis confirmed a significant, 2-day decrease in median LOS and a €1097 saving after ERAS introduction. Ninety-day mortality decreased slightly in ERAS group, while complications and readmissions did not change significantly. When complications were included in the multivariable analysis, ERAS retained its significance, although the effects on LOS and cost were blunted to a median reduction of 1 day and €775, respectively.

Conclusions

ERAS for gastrectomy improved patients’ recovery and reduced hospital costs without changes in morbidity, mortality, or readmission.
A Practical Prediction of LogPo/w through Semiempirical Electronic Structure Calculations with Dielectric Continuum Model
Authors: Takahashi Teruyuki , Matsui Toru , Hengphasatporn Kowit , Shigeta Yasuteru
Published: May 2021

We examined various combinations of semiempirical and polarizable continuum methods and found that SMD/PM7 provides the highest accuracy in calculating LogPo/w. The correlation between the experimental and calculated LogPo/w is approximately R2 = 0.74. However, this result is not sufficiently accurate for achieving a practical prediction. To clarify the details of the calculation results, a linear fitting was conducted for each functional group and each atom. The results showed a large variation, indicating a large error. We then conducted a multiple regression analysis using the number of atoms in the molecule, the number of multiple bonds, the ring structure, and the indicator for aromatic nature as explanatory variables and the experimental value of LogPo/w as the objective variable; finally, we incorporated a correction to the calculated value of LogPo/w. We showed that the accuracy was significantly improved to approximately R2 = 0.95 when adopting the difference in solvation energy, along with four additional explanatory variables.
Direct Sampling Graphite Furnace Atomic Absorption Spectrometry — A Suitable Tool for the Determination of Metallic Contaminants in Pitch
Authors: Frohlich Angelica C , Pereira Leticia S F , Junges Andrizia F , Flores Erico M M , Paniz Jose N G , Duarte Fabio A
Published: May 2021

Considering the widespread use of pitch as a carbon source for manufacturing of carbon related materials, a method for the determination of Co, Cr, Cu, Mn and Ni in pitch by direct sampling graphite furnace atomic absorption spectrometry (DS-GF AAS) was proposed. The pyrolysis and atomization curves for reference solution and solid sample were evaluated. The influence of sample mass, the use of chemical modifier and the linear calibration range for each analyte were also evaluated. As advantages, the calibration with aqueous reference solutions was feasible for all the analytes and it was possible to use a relatively large sample mass, up to 3 mg directly introduced into the graphite tube. The results obtained by DS-GF AAS were compared with those from analytes determination by inductively coupled plasma mass spectrometry after pitch digestion by microwave-induced combustion and no statistical differences (Student’s t-test) were observed. The proposed method showed some advantages such as the minimum sample handling (only milling), the use of aqueous reference solutions for calibration and contrary to most work using GF AAS, Pd has been evaluated with no chemical modifier required, making the proposed method a suitable alternative for the quality control of pitch.
Construction of CF3-Containing Quaternary Chiral Centers via Michael Addition Reactions
Authors: Yamazaki Takashi , Taketsugi Masahito , Kawasaki-Takasuka Tomoko , Agou Tomohiro , Kubota Toshio
Published: May 2021

Michael addition reactions of a variety of Grignard reagents to 4,4,4-trifluorinated α,β-unsaturated carboxylic acid derivatives with 4-substituted oxazolidin-2-ones as a chiral auxiliary were found to occur smoothly in the presence of CuBr·SMe2 and TMSCl to construct the desired products with the quaternary stereocenters possessing a CF3 group in good to excellent yields.
Improvement of a Pb2Ti2O5.4F1.2 Photoanode for Solar Water Splitting by Refining the Cocatalyst and Electrolyte
Authors: Maeda Kazuhiko , Hirayama Naoki , Nakata Hiroko , Oka Kengo
Published: May 2021

Photoanode materials that are active and stable for visible-light water oxidation benefit the development of artificial photosynthesis schemes, including overall water splitting and CO2/N2 fixation. The pyrochlore-structured oxyfluoride Pb2Ti2O5.4F1.2 is an n-type semiconductor with a bandgap of 2.4 eV; it has been used as a photoanode for water oxidation. In this work, cocatalysts and electrolytes that efficiently promote photoelectrochemical water oxidation on Pb2Ti2O5.4F1.2 were investigated in an aqueous solution at pH ∼9. Among the investigated transition-metal cocatalysts, cobalt phosphate (CoPi) was found to result in the best performance. The performance of the CoPi-modified Pb2Ti2O5.4F1.2 electrode toward the photoelectrochemical oxidation of water depended on the electrolyte used. As a general trend, proton-accepting electrolytes such as tetraborate, phosphate, and bicarbonate led to higher performance. The highest photoanodic current was obtained under simulated sunlight irradiation (AM1.5G, 100 mW cm−2), accompanied by O2 evolution with a Faradaic efficiency close to unity, when potassium tetraborate was used as the electrolyte.
Cardiovascular Endurance Modifies the Link between Subjective Sleep Quality and Entorhinal Cortex Thickness in Younger Adults
Authors: WON JUNYEON , ALFINI ALFONSO J. , SMITH J. CARSON
Published: May 2021

Introduction

Poor sleep is linked to impaired cognitive function, cortical brain atrophy, and lower cortical thickness. Independently, higher cardiovascular endurance has neuroprotective effects. It remains in question, however, whether cardiovascular endurance moderates the relationship between sleep and brain health. The aims of this study included the following: 1) the association between subjective sleep quality and cognitive performance, hippocampus volume, and entorhinal cortex (EC) thickness, and 2) the moderating effects of cardiovascular endurance on the associations of sleep quality with cognitive and magnetic resonance imaging measures in healthy younger adults.

Methods

A total of 1095 younger adults (28.8 ± 3.6 yr) from the Human Connectome Project were included in the analyses. The 2-min walk test was used as a proxy of cardiovascular endurance. Self-reported sleep quality was measured using the Pittsburgh Sleep Quality Index. Composite cognitive tests were used to assess global cognition, and T1-weighted structural magnetic resonance imaging data (obtained using Siemens 3T scanner) was used to assess hippocampus volume and EC thickness. Linear regression was used to examine the moderating effects of fitness on the relationships between sleep and each of these neurocognitive outcomes after controlling for age, sex, and education year.

Results

Poorer sleep quality was associated with both a lower crystalized intelligence score (B = −0.198, P = 0.034) and lower EC thickness (B = −0.013, P = 0.003). With greater 2-min walk test score, the association between greater Pittsburgh Sleep Quality Index score and lower EC thickness was attenuated (B = 0.0008, P = 0.028).

Conclusions

Higher cardiovascular endurance may mitigate the relationship between poorer subjective sleep quality and lower EC thickness. Future longitudinal studies should examine the interactive effects of sleep and fitness on brain health among older and more vulnerable populations.