bluuebunny/crossref_metadata_2025 huggingface dataset:
A Mathematical Study of the Influence of Hypoxia and Acidity on the Evolutionary Dynamics of Cancer
Authors: Fiandaca Giada , Delitala Marcello , Lorenzi Tommaso
Published: June 2021

Hypoxia and acidity act as environmental stressors promoting selection for cancer cells with a more aggressive phenotype. As a result, a deeper theoretical understanding of the spatio-temporal processes that drive the adaptation of tumour cells to hypoxic and acidic microenvironments may open up new avenues of research in oncology and cancer treatment. We present a mathematical model to study the influence of hypoxia and acidity on the evolutionary dynamics of cancer cells in vascularised tumours. The model is formulated as a system of partial integro-differential equations that describe the phenotypic evolution of cancer cells in response to dynamic variations in the spatial distribution of three abiotic factors that are key players in tumour metabolism: oxygen, glucose and lactate. The results of numerical simulations of a calibrated version of the model based on real data recapitulate the eco-evolutionary spatial dynamics of tumour cells and their adaptation to hypoxic and acidic microenvironments. Moreover, such results demonstrate how nonlinear interactions between tumour cells and abiotic factors can lead to the formation of environmental gradients which select for cells with phenotypic characteristics that vary with distance from intra-tumour blood vessels, thus promoting the emergence of intra-tumour phenotypic heterogeneity. Finally, our theoretical findings reconcile the conclusions of earlier studies by showing that the order in which resistance to hypoxia and resistance to acidity arise in tumours depend on the ways in which oxygen and lactate act as environmental stressors in the evolutionary dynamics of cancer cells.
Volatile metabolites of willows determining host discrimination by adult Plagiodera versicolora
Authors: Ling Jiahao , Li Xiaoping , Yang Guo , Yin Tongming
Published: June 2021

Plagiodera versicolora Laicharting is a highly damaging leaf beetle foraging on willow leaves. In willow germplasm collections, observation has shown that Salix suchowensis Cheng was severely foraged by this leaf beetle while Salix triandra L. was damage free or only slightly damaged. Results of olfactometer bioassays show that the headspace volatiles from leaves of S. triandra significantly repelled adult beetles, suggesting that this species produces volatile repellents against P. versicolora. S. suchowensis had no effect on the beetles. Gas chromatography-mass spectrometry was carried out to profile the headspace volatile organic compounds and 23 compounds from leaves of the alternate species in significantly different concentrations were detected. The effects of 20 chemical analogs on host discrimination were examined. Olfactory response to these chemicals showed that o-cymene, a S. suchowensis specific constituent, significantly attracted adult P. versicolora. In contrast, cis-3-hexenyl acetate, a constituent concentrated more in S. triandra than in S. suchowensis, significantly repelled beetles. Mixing o-cymene and cis-3-hexenyl acetate in comparable concentrations as in the volatiles of S. suchowensis demonstrated that the latter could mask the attracting effect of the former, causing a neutral response by adult beetles to leaves of S. suchowensis against clean air. In addition, chemical analogs have the same effect as plants when resembling volatile organic compounds in real samples. Two volatile metabolites were detected triggering host discrimination by one of the most damaging insect pests to host and non-host willows. The two metabolites are of considerable potential for use as olfactory signs in managing the beetles.
Maternal obesity and depression reported at the first antenatal visit
Authors: Tuthill Emma H. , Reynolds Ciara M. E. , McKeating Aoife , O’Malley Eimer G. , Kennelly Mairead M. , Turner Michael J.
Published: June 2021

Background

Maternal obesity and depression are common and both have been associated with adverse pregnancy outcomes.

Aims

The aim of this observational study was to examine the relationship between maternal body mass index (BMI) category and self-reported depression at the first antenatal visit.

Methods

Women who delivered a baby weighing ≥ 500 g over nine years 2009–2017 were included. Self-reported sociodemographic and clinical details were computerised at the first antenatal visit by a trained midwife, and maternal BMI was calculated after standardised measurement of weight and height.

Results

Of 73,266 women, 12,304 (16.7%) had obesity, 1.6% (n = 1126) reported current depression and 7.5% (n = 3277) multiparas reported a history of postnatal depression. The prevalence of self-reported maternal depression was higher in women who had obesity, > 35 years old, were socially disadvantaged, smokers, had an unplanned pregnancy and used illicit drugs. After adjustment for confounding variables, obesity was associated with an increased odds ratio (aOR) for current depression in both nulliparas (aOR 1.7, 95% CI 1.3–2.3, p < 0.001) and multiparas (aOR 1.8, 95% CI 1.5–2.1, p < 0.001) and postnatal depression in multiparas (aOR 1.4, 95% CI 1.3–1.5, p < 0.001). The prevalence of current depression was higher in women with moderate/severe obesity than in women with mild obesity (both p < 0.001).

Conclusions

We found that self-reported maternal depression in early pregnancy was independently associated with obesity. The prevalence of depression increased with the severity of obesity. Our findings highlight the need for implementation of strategies and provision of services for the prevention and treatment of both obesity and depression.
Automated Brain Masking of Fetal Functional MRI with Open Data
Authors: Rutherford Saige , Sturmfels Pascal , Angstadt Mike , Hect Jasmine , Wiens Jenna , van den Heuvel Marion I. , Scheinost Dustin , Sripada Chandra , Thomason Moriah
Published: June 2021

Fetal resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a critical new approach for characterizing brain development before birth. Despite the rapid and widespread growth of this approach, at present, we lack neuroimaging processing pipelines suited to address the unique challenges inherent in this data type. Here, we solve the most challenging processing step, rapid and accurate isolation of the fetal brain from surrounding tissue across thousands of non-stationary 3D brain volumes. Leveraging our library of 1,241 manually traced fetal fMRI images from 207 fetuses, we trained a Convolutional Neural Network (CNN) that achieved excellent performance across two held-out test sets from separate scanners and populations. Furthermore, we unite the auto-masking model with additional fMRI preprocessing steps from existing software and provide insight into our adaptation of each step. This work represents an initial advancement towards a fully comprehensive, open-source workflow, with openly shared code and data, for fetal functional MRI data preprocessing.
The digital transformation of healthcare - An interview with Werner Dorfmeister
Authors: Alt Rainer , Zimmermann Hans-Dieter
Published: June 2021

In this interview, Werner Dorfmeister, a Vice President at DasLab and a former Global Sales Director at Karl Storz, reports on the current developments of digital technologies in the field of medical instruments and services. It is a sector where digitalization affects all processes within hospitals as well as pre- and post-surgical activities. Due to the many actors involved, who use different information systems, and the strong regulation of the entire healthcare sector, crafting digital solutions is complex, but nevertheless promising and necessary. Among the key areas mentioned in the interview are telemedicine, hospital and patient management and a sector-wide digital infrastructure. Digital platforms are described as important enablers to address current inefficiencies and to leverage future potentials towards patient-orientation, such as digital patient pathways.
Role of thyroid hormone therapy in depressive disorders
Authors: Bauer M. , Whybrow P. C.
Published: June 2021

Purpose

The close association among thyroid metabolism, mood disorders and behavior has long been known. The old and modern uses of thyroid hormones to modulate the expression of depression and bipolar disorder and to improve clinical outcome when used in conjunction with psychotropic medications.

Methods

A literature search was performed to identify studies investigating the effects of thyroid hormone treatment in patient s with mood disorders.

Results

The successful modification of mood disorders with thyroid hormone underscores the association between endocrine and cerebral systems in these disorders. Thyroid hormones have a profound influence on behavior and appear to be capable of modulating the phenotypic expression of major mood disorders. In fact, there is evidence that triiodothyronine (LT3) may accelerate the antidepressant response to antidepressants, and studies suggest that LT3 also may augment the response to antidepressants in refractory depression. Add-on treatment with supraphysiologic doses of levothyroxine (LT4) has shown efficacy in open-label and in placebo-controlled studies, including in rapid cycling and prophylaxis-resistant bipolar disorder, and with acute refractory uni- or bipolar depression. Functional brain-imaging studies (PET) demonstrated that administration of supraphysiologic LT4 improves depressive symptoms in patients with bipolar depression by modulating cerebral activity in the anterior limbic network.

Conclusion

The add-on administration of supraphysiologic doses of LT4 is a promising strategy in patients with refractory bipolar and depressive mood disorders.
The Dangers Associated with Female Adolescents Consuming Nyaope Drug in Butterworth, South Africa
Authors: Bala Samkelo , Kang’ethe Simon M.
Published: June 2021

Nyaope is a potent drug that is currently challenging South Africa; its ramifications have destroyed the country’s youth. The study described in this paper sought to explore the dangers associated with the consumption of Nyaope in Butterworth, South Africa. This study adopted an explorative and descriptive qualitative approach that involved the facilitation of focus group discussions and one-on-one interviews with twenty-six participants. An analysis of the findings of the study revealed the health hazards associated with consuming Nyaope and the tendency of Nyaope consumption to induce hallucinations and delusions in young people. Moreover, the study showed that Nyaope stimulated mood swings among female adolescents, its consumption created a fertile ground for conflict, and the addiction to Nyaope led to the destruction of the future of female adolescents. The researchers recommend the application of multiple approaches to preventing the initiation of Nyaope consumption. These approaches include attempts to control the peddling of Nyaope in schools and communities as well as the introduction of pro-active educational interventions regarding the dangers of Nyaope on the part of relevant institutions and government.
Theoretical and practical, but rarely integrated: Norwegian primary school teachers’ intentions and practices of teaching outside the classroom
Authors: Winje Øystein , Løndal Knut
Published: June 2021

This study investigates teachers’ intentions and practices related to teaching outside the classroom. We report on three months of fieldwork consisting of participatory observations and qualitative interviews of teachers in two Norwegian primary schools practising weekly uteskole [outdoor school]. We find that the teachers’ intentions for uteskole are to facilitate first-hand experiences for their pupils. The teachers organise and teach uteskole in two distinct ways: 1) friluftsliv activities [outdoor living activities] and 2) theoretical learning activities. The connections between friluftsliv activities and theoretical learning activities are seldom emphasised. Furthermore, the teachers rarely organise theoretical learning activities that entail pupils’ transacting with their surroundings. We discuss how the teachers’ work can be understood through the Romantic and the Pragmatist perspectives of experiential education and through the representational epistemology of traditional schooling. We outline how a transactional epistemology, operationalised as the “multi-modal model of knowing”, can support teachers in facilitating transaction between the pupils and the environment outdoors and aid in establishing continuity between learning activities outdoors and indoors. We argue that these are important factors that can enhance uteskole as a teaching method for facilitating deep learning in Norwegian primary education.
Remediation scenario of the abandoned Kettara mine site (Morocco): acid mine drainage (AMD) transport modeling
Authors: Lghoul Meriem , Sbihi Karim , Maqsoud Abdelkabir , Hakkou Rachid , Kchikach Azzouz
Published: June 2021

In this study, we present the efficiency of remediation scenario to attenuate the impact of acid mine drainage (AMD) contamination in the Kettara abandoned mine site. The study focuses on the AMD groundwater contamination of the Sarhlef shists aquifer. To predict the evolution of AMD groundwater contamination in the Kettara mine site under remediation scenario, a model of groundwater flow and AMD transport was performed.

Piezometric heads were measured at the dry and wet periods from eleven wells located downstream of mine wastes. To elaborate a conceptual groundwater flow model, we faced with to the heterogeneity and anisotropy of fractured Sarhlef shists aquifer. Consequently, the study focused on the use of various approaches: 1. The inverse modeling by the CMA-ES algorithm is adopted as an alternative approach to determine hydraulic parameters indirectly, and 2. the model is treated as an equivalent porous media (EPM). The groundwater flow model was carried out in steady-state and transient conditions in the dry and wet periods using the PMWIN interface. The obtained results are satisfactory and show an excellent correlation between measured and computed heads. Contaminant transport model is used to solve the advection–dispersion equation and to generate the AMD concentration by MT3D via the PMWIN interface. A sensitivity analysis of the dispersivity coefficient is carried out. The AMD transport simulation was computed during periods of 1, 5 and 10 years, and the performed model indicates that the simulated concentrations under remediation scenario are reduced 1000 times comparing to the current concentrations. The study revealed a necessary approach in addressing an environmental issue for the AMD contamination. The results of the study will be a start-up for further research work in the study area and implementing it for the prevention of AMD propagation plume.
Elevated Anti-Müllerian Hormone Levels in Newborns of Women with Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis Based on Observational Studies
Authors: Zhou Siyu , Lu Danhua , Wen Shu , Sheng Yongcheng , Kang Deying , Xu Liangzhi
Published: June 2021

We performed this updated systematic review and meta-analysis to evaluate anti-Müllerian hormone levels (AMH) in newborns of mothers with polycystic ovary syndrome (PCOS) compared with healthy controls. A search of the literature was conducted in the PubMed, MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, WANFANG, and VIP for articles to assess AMH levels in offspring of PCOS and non-PCOS mothers irrespective of language. These databases were searched from their inception to December 7, 2020. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) scoring system. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were adopted to calculate the overall estimates with random-effects models. A total of 6 studies with 846 participants were included. The pooled analysis found an increased AMH level in the umbilical cord blood in newborns of PCOS mothers (SMD =0.62, 95% CI [0.28, 0.95]). Subgroup analyses revealed an elevation of AMH concentrations in female neonates, neonates born to American and Asian PCOS mothers. In addition, higher AMH levels were also found in studies diagnosed by the National Institute of Health (NIH) criteria, maternal clinical/biochemical hyperandrogenism, or maternal body mass index (BMI) >30 kg/m2. Meta-regression analysis suggested that diagnostic criterion contributed mostly to the high heterogeneity. We demonstrated that AMH levels in neonates born to PCOS mothers were essentially higher, which indicates that AMH may act as an enigmatic role in the pathogenesis of PCOS which inhibits folliculogenesis in the fetal stage.
Non-State Actors' Rights in Maritime Delimitation
Authors: Pappa Marianthi
Published: June 2021

Most of the world's maritime boundary disputes involve privately held rights - relating to such matters as fishing, petroleum exploration and scientific research - that states have unilaterally granted to non-state actors in areas of overlapping national claims. An international lawyer would typically investigate the legality of a state's decision to create such rights without notifying or consulting its neighbour, and the legal consequences this action would have for the interests of the states concerned. Departing from this approach, Dr Marianthi Pappa examines such situations from the perspective of the non-state actors: what will happen to private rights in a disputed maritime area if it changes hands from state A to state B due to a subsequent delimitation treaty or judgment? Does the legal framework of maritime delimitation protect those rights effectively against a potential reallocation? To address these questions, the book considers the place that private rights have in land boundary-making.
Moving-mass-based station keeping of stratospheric airships
Authors: Chen L. , Gao Q. , Deng Y. , Liu J.
Published: June 2021

Stratospheric airships are lighter-than-air vehicles that work at an altitude of 20km in the lower calm portion of the stratosphere. They can be used as real-time surveillance platforms for environment monitoring and civil communication. Solar energy is the ideal power choice for long-endurance stratospheric airships. Attitude control is important for airships so that they can point at a target for observation or adjust the attitude to improve the output performance of solar panels. Stratospheric airships have a large volume and semi-flexible structure. The typical actuators used are aerodynamic surfaces, vectored thrust and ballonets. However, not all these actuators can work well under special working conditions, such as low density and low speed. In this study, moving-mass control is introduced to stratospheric airships because its control efficiency is independent of airspeed and atmospheric density. A nonlinear feedback controller based on generalised inverse with a nonlinear mapping module is designed to implement moving-mass control. Such a new station keeping scheme with moving masses is proposed for airships with different working situations.
On arithmetic progressions in non-periodic self-affine tilings
Authors: NAGAI YASUSHI , AKIYAMA SHIGEKI , LEE JEONG-YUP
Published: June 2021

We study the repetition of patches in self-affine tilings in
${\mathbb {R}}^d$
. In particular, we study the existence and non-existence of arithmetic progressions. We first show that an arithmetic condition of the expansion map for a self-affine tiling implies the non-existence of certain one-dimensional arithmetic progressions. Next, we show that the existence of full-rank infinite arithmetic progressions, pure discrete dynamical spectrum, and limit-periodicity are all equivalent for a certain class of self-affine tilings. We finish by giving a complete picture for the existence or non-existence of full-rank infinite arithmetic progressions in the self-similar tilings in
${\mathbb {R}}^d$
.
The effect of drone strikes on civilian communication: evidence from Yemen
Authors: Christia Fotini , Zoumpoulis Spyros I. , Freedman Michael , Yao Leon , Jadbabaie Ali
Published: June 2021

Although covert warfare does not readily lend itself to scientific inquiry, new technologies are increasingly providing scholars with tools that enable such research. In this note, we examine the effects of drone strikes on patterns of communication in Yemen using big data and anomaly detection methods. The combination of these analytic tools allows us to not only quantify some of the effects of drone strikes, but also to compare them to other shocks. We find that on average drone strikes leave a footprint in their aftermath, spurring significant but localized spikes in communication. This suggests that drone strikes are not a purely surgical intervention, but rather have a disruptive impact on the local population.
Gender, Power, and Cricket Spectators in Calcutta, 1960s–1990s
Authors: Naha Souvik
Published: June 2021

Historians of modern India have emphasized the reflexivity of men and women in the making of womanhood, paying attention to notions of gender difference emerging from both primordial, restrictive codes of behaviour and contrarian impulses towards what was popularly called progress. There have been relatively few attempts to trace gender interaction in outdoor leisure activities, public displays of femininity, and male regulatory anxieties in the post-colonial context. By studying the symbolism of women's presence in the Eden Gardens, the international cricket stadium in Calcutta, from the 1960s to the 1990s, this article reflects on the nature of power, authority, and gender hierarchy in urban Indian society. This study of questions of gender hierarchy, women's mannerisms, social identity, and informal resistance through a historical lens will enable us to understand the trajectory of women's outsider status in urban public spaces. Through a reading of the mediated parti pris impressions of female spectators, it will also map the transition in society's approach to sport from a structured homosocial community activity to a relatively unstructured field of shared experience.
Bruce Smith and Anglo-Australian Liberalism
Authors: Paynter Alastair
Published: June 2021

Bruce Smith (1851–1937) was the most prominent Australian exponent of classical or ‘old’ liberalism in the late nineteenth and early twentieth century. Although his political career was not particularly successful, he was notable as the foremost defender of individualism as the authentic liberal creed, exemplified by his 1887 work Liberty and liberalism. He consistently attacked new liberalism, with its acceptance of extensive state interference, and socialism, as inimical to individual liberty and national prosperity. Although he is now recognized as an important figure in the Australian liberal pantheon, there has been relatively little attention to his thought outside Australia itself, despite his extensive connections to Britain. The general trajectory of Australian liberalism from ‘individualism’ to ‘collectivism’ was mirrored in Britain from the 1880s, especially during Prime Minister William Gladstone's second and third administrations, when the radicals within the Liberal party grew in influence and the aristocratic whig moderates waned. Smith maintained close links with the British Liberty and Property Defence League, which dedicated itself to fighting against collectivism, as well as with his personal hero, the philosopher Herbert Spencer, from whom his own politics derived much influence. This article considers Smith's thought through the prism of Anglo-Australian politics.
Crafting Idiosyncrasies. Early Social Complexity, Ivory and Identity-Making in Copper Age Iberia
Authors: Luciañez-Triviño Miriam , García Sanjuán Leonardo , Schuhmacher Thomas
Published: June 2021

As a raw material, ivory has been used to manufacture a wide range of objects, normally associated with sumptuous material culture. In this article we explore the role played by ivory and ivory artefacts among early complex societies, and particularly its importance in the definition of identities among emergent elites. To this end, we make a thorough examination of the evidence from Copper Age Iberia, focusing on the mega-site of Valencina, in southern Spain. This site has provided what to date is the largest assemblage of prehistoric ivory in western Europe, with an estimated total of 8.8 kg, including finely crafted artefacts of unrivalled beauty and sophistication. Our study looks carefully at the technological, morphological and contextual dimensions of Copper Age ivory. As a result, we contend that the broad morphological variability together with the technological uniformity of this assemblage suggest that, while belonging to a common technological tradition, objects were deliberately crafted as unique and unrepeatable so that they could be used to create and maintain socio-cultural idiosyncrasies and ideological legitimation.
Political Professors and the Perception of Bias in the College Classroom
Authors: Liebertz Scott , Giersch Jason
Published: June 2021

This article addresses three related questions. Does voicing a political ideology in class make a professor less appealing to students? Does voicing an ideology in class make a professor less appealing to students with opposing views? Does the intensity of professors’ ideology affect their appeal? We conducted survey experiments in two public national universities to provide evidence of the extent to which students may tolerate or even prefer that professors share their political views and under which conditions these preferences may vary. Results from the experiments indicate that expressing a political opinion did not make a professor less appealing to students—and, in fact, made the professor more appealing to some students—but the perception that a professor’s ideology is particularly intense makes the class much less favorable for students with opposing views. Students are indifferent between moderately political and nonpolitical professors.
Moderation Effects of Coping Flexibility on the Association Between Depressive Symptoms and Suicidal Risk
Authors: Kato Tsukasa
Published: June 2021

Abstract. Background: This study focused on poor coping flexibility, which involves the perseveration of a failed coping strategy, as a moderator of the association between depression and suicidal risk; no study has previously examined the association between coping flexibility and suicidal risk. Aims: This study examined whether individuals with lower coping flexibility would have a stronger suicidal risk when experiencing depression above a certain level. Method: Participants, who were 682 college students, answered questionnaires regarding coping flexibility, depressive symptoms, and suicidal risk. Results: Hierarchical multiple regression analyses showed that in individuals with greater depressive symptoms, lower coping flexibility was associated with higher suicidal risk, but this was not the case in individuals without depressive symptoms. Our hypothesis was supported. Limitations: Our findings cannot indicate the causal direction of the association between coping flexibility and depressive symptoms and suicidal risk. Conclusion: Our findings may be useful in understanding the association between depression and suicidal risk through coping flexibility and contribute to reductions in suicidal risk, as coping flexibility can be improved through training.
Improving Solar Wind Forecasting Using Data Assimilation
Authors: Lang Matthew , Witherington Jake , Turner Harriet , Owens Mathew J. , Riley Pete
Published: June 2021

Data Assimilation (DA) has enabled huge improvements in the skill of terrestrial operational weather forecasting. In this study, we use a variational DA scheme with a computationally efficient solar wind model and in situ observations from STEREO‐A, STEREO‐B and ACE. This scheme enables solar‐wind observations far from the Sun, such as at 1 AU, to update and improve the inner boundary conditions of the solar wind model (at 30 solar radii). In this way, observational information can be used to improve estimates of the near‐Earth solar wind, even when the observations are not directly downstream of the Earth. This allows improved initial conditions of the solar wind to be passed into forecasting models. To this effect, we employ the HUXt solar wind model to produce 27‐day forecasts of the solar wind during the operational lifetime of STEREO‐B (November 01, 2007–September 30, 2014). In near‐Earth space, we compare the accuracy of these DA forecasts with both non‐DA forecasts and simple corotation of STEREO‐B observations. We find that 27‐day root mean square error (RMSE) for STEREO‐B corotation and DA forecasts are comparable and both are significantly lower than non‐DA forecasts. However, the DA forecast is shown to improve solar wind forecasts when STEREO‐B's latitude is offset from the Earth, which is an issue for corotation forecasts. And the DA scheme enables the representation of the solar wind in the whole model domain between the Sun and the Earth to be improved, which will enable improved forecasting of CME arrival time and speed.
Magma Pockets Lie Stacked Beneath Juan de Fuca Ridge
Authors: Stanley Sarah
Published: June 2021

Analysis of new imaging data suggests that vertically stacked magma chambers are short-lived and contribute to eruptions.
Maternal exposure to polycyclic aromatic hydrocarbons in South Texas, evaluation of silicone wristbands as personal passive samplers
Authors: Mendoza-Sanchez Itza , Uwak Inyang , Myatt Louise , Van Cleve Allison , Pulczinski Jairus C. , Rychlik Kristal A. , Sweet Stephen , Ramani Tara , Zietsman Josias , Zamora Misti Levy , Koehler Kirsten , Carrillo Genny , Johnson Natalie M.
Published: June 2021

Background

Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health effects in children. Valid exposure assessment methods with accurate spatial and temporal resolution across pregnancy is a critical need for advancing environmental health studies.

Objective

The objective of this study was to quantify maternal PAH exposure in pregnant women residing in McAllen, Texas where the prematurity rate and childhood asthma prevalence rates are high. A secondary objective was to compare PAH levels in silicone wristbands deployed as passive samplers with concentrations measured using standardized active air-sampling techniques.

Methods

Participants carried a backpack that contained air-sampling equipment (i.e., filter and XAD sorbent) and a silicone wristband (i.e., passive sampler) for three nonconsecutive 24-h periods. Filters, XAD tubes, and wristbands were analyzed for PAHs.

Results

The median level of exposure for the sum of 16 PAHs measured via active sampling over 24 h was 5.54 ng/m3 (filters) and 43.82 ng/m3 (XADs). The median level measured in wristbands (WB) was 586.82 ng/band. Concentrations of the PAH compounds varied across sampling matrix type. Phenanthrene and fluorene were consistently measured for all participants and in all matrix types. Eight additional volatile PAHs were measured in XADs and WBs; the median level of exposure for the sum of these eight PAHs was 342.98 ng/m3 (XADs) and 632.27 ng/band. The silicone wristbands (WB) and XAD sorbents bound 1-methynaphthalyne, 2-methylnaphthalene, biphenyl following similar patterns of detection.

Significance

Since prior studies indicate linkages between PAH exposure and adverse health outcomes in children at the PAH levels detected in our study, further investigation on the associated health effects is needed. Data reflect the ability of silicone wristbands to bind smaller molecular weight, semivolatile PAHs similar to XAD resin. Application of wristbands as passive samplers may be useful in studies evaluating semivolatile PAHs.
Thermally-actuated microfluidic membrane valve for point-of-care applications
Authors: Sesen Muhsincan , Rowlands Christopher J.
Published: June 2021

Microfluidics has enabled low volume biochemistry reactions to be carried out at the point-of-care. A key component in microfluidics is the microfluidic valve. Microfluidic valves are not only useful for directing flow at intersections but also allow mixtures/dilutions to be tuned real-time and even provide peristaltic pumping capabilities. In the transition from chip-in-a-lab to lab-on-a-chip, it is essential to ensure that microfluidic valves are designed to require less peripheral equipment and that they are transportable. In this paper, a thermally-actuated microfluidic valve is presented. The valve itself is fabricated with off-the-shelf components without the need for sophisticated cleanroom techniques. It is shown that multiple valves can be controlled and operated via a power supply and an Arduino microcontroller; an important step towards transportable microfluidic devices capable of carrying out analytical assays at the point-of-care. It is been calculated that a single actuator costs less than $1, this highlights the potential of the presented valve for scaling out. The valve operation is demonstrated by adjusting the ratio of a water/dye mixture in a continuous flow microfluidic chip with Y-junction channel geometry. The power required to operate one microfluidic valve has been characterised both theoretically and experimentally. Cyclical operation of the valve has been demonstrated for 65 h with 585 actuations. The presented valve is capable of actuating rectangular microfluidic channels of 500 μm × 50 μm with an expected temperature increase of up to 5 °C. The fastest actuation times achieved were 2 s for valve closing (heating) and 9 s for valve opening (cooling).
Individualized lncRNA differential expression profile reveals heterogeneity of breast cancer
Authors: Zhao Zhangxiang , Guo YingYing , Liu Yaoyao , Sun Lichun , Chen Bo , Wang Chengyu , Chen Tingting , Wang Yuquan , Li Yawei , Dong Qi , Ai Liqiang , Wang Ran , Gu Yunyan , Li Xia
Published: June 2021

Long non-coding RNAs (lncRNAs) play key regulatory roles in breast cancer. However, population-level differential expression analysis methods disregard the heterogeneous expression of lncRNAs in individual patients. Therefore, we individualized lncRNA expression profiles for breast invasive carcinoma (BRCA) using the method of LncRNA Individualization (LncRIndiv). After evaluating the robustness ofLncRIndiv, we constructed an individualized differentially expressed lncRNA (IDElncRNA) profile for BRCA and investigated the subtype-specific IDElncRNAs. The breast cancer subtype-specific IDElncRNA showed frequent co-occurrence with alterations of protein-coding genes, including mutations, copy number variation and differential methylation. We performed hierarchical clustering to subdivide TNBC and revealed mesenchymal subtype and immune subtype for TNBC. The TNBC immune subtype showed a better prognosis than the TNBC mesenchymal subtype. LncRNAPTOV1-AS1was the top differentially expressed lncRNA in the mesenchymal subtype. And biological experiments validated that the upregulation ofPTOV1-AS1could downregulateTJP1(ZO-1) and E-Cadherin, and upregulate Vimentin, which suggestsPTOV1-AS1may promote epithelial-mesenchymal transition and lead to migration and invasion of TNBC cells. The mesenchymal subtype showed a higher fraction of M2 macrophages, whereas the immune subtype was more associated with CD4 + T cells. The immune subtype is characterized by genomic instability and upregulation of immune checkpoint genes, thereby suggesting a potential response to immunosuppressive drugs. Last, drug response analysis revealed lncRNA ENSG00000230082 (PRRT3-AS1) is a potential resistance biomarker for paclitaxel in BRCA treatment. Our analysis highlights that IDElncRNAs can characterize inter-tumor heterogeneity in BRCA and the new TNBC subtypes indicate novel insights into TNBC immunotherapy.
Neuroprotective effects of bone marrow Sca-1+ cells against age-related retinal degeneration in OPTN E50K mice
Authors: Liu Xinna , Hou Mingying , Zhang Shiqi , Zhao Yutong , Wang Qi , Jiang Menglu , Du Mengxian , Shao Zhengbo , Yuan Huiping
Published: June 2021

Glaucoma is characterized by retinal ganglion cell (RGC) death, the underlying mechanisms of which are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal-tension glaucoma (NTG), which directly affects RGCs in the absence of high intraocular pressure and causes severe glaucomatous symptoms in patients. Bone marrow (BM) stem cells have been demonstrated to play a key role in regenerating damaged tissue during ageing and disease through their trophic effects and homing capability. Here, we separated BM stem cells into Sca-1+ and Sca-1- cells and transplanted them into lethally irradiated aged OPTN E50K mice to generate Sca-1+ and Sca-1− chimaeras, respectively. After 3 months of BM repopulation, we investigated whether Sca-1+ cells maximized the regenerative effects in the retinas of NTG model mice with the OPTN E50K mutation. We found that the OPTN E50K mutation aggravated age-related deficiency of neurotrophic factors in both retinas and BM during NTG development, leading to retinal degeneration and BM dysfunction. Sca-1+ cells from young healthy mice had greater paracrine trophic effects than Sca-1− cells and Sca-1+ cells from young OPTN E50K mice. In addition, Sca-1+ chimaeras demonstrated better visual functions than Sca-1− chimaeras and untreated OPTN E50K mice. More Sca-1+ cells than Sca-1− cells were recruited to repair damaged retinas and reverse visual impairment in NTG resulting from high expression levels of neurotrophic factors. These findings indicated that the Sca-1+ cells from young, healthy mice may have exhibited an enhanced ability to repair retinal degeneration in NTG because of their excellent neurotrophic capability.
USP35, regulated by estrogen and AKT, promotes breast tumorigenesis by stabilizing and enhancing transcriptional activity of estrogen receptor α
Authors: Cao Jiawei , Wu Du , Wu Guang , Wang Yaqi , Ren Tianhao , Wang Yang , Lv Yingshuai , Sun Wei , Wang Jieyi , Qian Changrui , He Licai , Yang Kaiyan , Li Hongzhi , Gu Haihua
Published: June 2021

Although endocrine therapies targeting estrogen receptor α (ERα) are effective in managing ER positive (+) breast cancer, many patients have primary resistance or develop resistance to endocrine therapies. In addition, ER+ breast cancer with PIK3CA activating mutations and 11q13-14 amplification have poor survival with unclear mechanism. We uncovered that higher expression of deubiquitinase USP35, located in 11q14.1, was associated with ER+ breast cancer and poor survival. Estrogen enhanced USP35 protein levels by downregulating USP35-targeting miRNA-140-3p and miRNA-26a-5p. USP35 promoted the growth of ER+ breast cancer in vitro and in vivo, and reduced the sensitivity of ER+ breast cancer cells to endocrine therapies such as tamoxifen and fulvestrant. Mechanistically, USP35 enhanced ERα stability by interacting and deubiquitinating ERα, and transcriptional activity of ERα by interacting with ERα in DNA regions containing estrogen response element. In addition, AKT, a key effector of PI3K, phosphorylated USP35 at Serine613, which promoted USP35 nuclear translocation, ERα transcriptional activity, and the growth of ER+ breast cancer cells. Our data indicate that USP35 and ERα form a positive feedback loop in promoting the growth of ER+ breast cancer. USP35 may be a treatment target for ER+ breast cancer with endocrine resistance or with PIK3CA mutations or hyperactivation of the PI3K pathway.
MiR-103a promotes tumour growth and influences glucose metabolism in hepatocellular carcinoma
Authors: Liu Yuling , Zhang Yuanzhou , Xiao Bowen , Tang Ning , Hu Jingying , Liang Shunshun , Pang Yechun , Xu Huili , Ao Junping , Yang Juan , Liang Xiaofei , Wei Lin , Wang Yunfeng , Luo Xiaoying
Published: June 2021

Hepatocellular carcinoma (HCC) is a common and high-mortality cancer worldwide. Numerous microRNAs have crucial roles in the progression of different cancers. However, identifying the important microRNAs and the target biological function of the microRNA in HCC progression is difficult. In this study, we selected highly expressed microRNAs with different read counts as candidate microRNAs and then tested whether the microRNAs were differentially expressed in HCC tumour tissues, and we found that their expression was related to the HCC prognosis. Then, we investigated the effects of microRNAs on the cell growth and mobility of HCC using a real-time cell analyser (RTCA), colony formation assay and subcutaneous xenograft models. We further used deep-sequencing technology and bioinformatic analyses to evaluate the main functions of the microRNAs. We found that miR-103a was one of the most highly expressed microRNAs in HCC tissues and that it was upregulated in HCC tissue compared with the controls. In addition, high miR-103a expression was associated with poor patient prognosis, and its overexpression promoted HCC cell growth and mobility. A functional enrichment analysis showed that miR-103a mainly promoted glucose metabolism and inhibited cell death. We validated this analysis, and the data showed that miR-103a promoted glucose metabolism-likely function and directly inhibited cell death via ATP11A and EIF5. Therefore, our study revealed that miR-103a may act as a key mediator in HCC progression.
Adipose tissue function in healthy pregnancy, gestational diabetes mellitus and pre-eclampsia
Authors: Trivett Cara , Lees Zoe J. , Freeman Dilys J.
Published: June 2021

Gestational diabetes mellitus (GDM) is a common disorder of pregnancy with short- and long-term consequences for mother and baby. Pre-eclampsia is of major concern to obstetricians due to its sudden onset and increased morbidity and mortality for mother and baby. The incidence of these conditions continues to increase due to widespread maternal obesity. Maternal obesity is a risk factor for GDM and pre-eclampsia, yet our understanding of the role of adipose tissue and adipocyte biology in their aetiology is very limited. In this article, available data on adipose tissue and adipocyte function in healthy and obese pregnancy and how these are altered in GDM and pre-eclampsia are reviewed. Using our understanding of adipose tissue and adipocyte biology in non-pregnant populations, a role for underlying adipocyte dysfunction in the pathological pathways of these conditions is discussed.
An l-2-hydroxyglutarate biosensor based on specific transcriptional regulator LhgR
Authors: Kang Zhaoqi , Zhang Manman , Gao Kaiyu , Zhang Wen , Meng Wensi , Liu Yidong , Xiao Dan , Guo Shiting , Ma Cuiqing , Gao Chao , Xu Ping
Published: June 2021

l-2-Hydroxyglutarate (l-2-HG) plays important roles in diverse physiological processes, such as carbon starvation response, tumorigenesis, and hypoxic adaptation. Despite its importance and intensively studied metabolism, regulation of l-2-HG metabolism remains poorly understood and none of regulator specifically responded to l-2-HG has been identified. Based on bacterial genomic neighborhood analysis of the gene encoding l-2-HG oxidase (LhgO), LhgR, which represses the transcription of lhgO in Pseudomonas putida W619, is identified in this study. LhgR is demonstrated to recognize l-2-HG as its specific effector molecule, and this allosteric transcription factor is then used as a biorecognition element to construct an l-2-HG-sensing FRET sensor. The l-2-HG sensor is able to conveniently monitor the concentrations of l-2-HG in various biological samples. In addition to bacterial l-2-HG generation during carbon starvation, biological function of the l-2-HG dehydrogenase and hypoxia induced l-2-HG accumulation are also revealed by using the l-2-HG sensor in human cells.
Neuronal variability reflects probabilistic inference tuned to natural image statistics
Authors: Festa Dylan , Aschner Amir , Davila Aida , Kohn Adam , Coen-Cagli Ruben
Published: June 2021

Neuronal activity in sensory cortex fluctuates over time and across repetitions of the same input. This variability is often considered detrimental to neural coding. The theory of neural sampling proposes instead that variability encodes the uncertainty of perceptual inferences. In primary visual cortex (V1), modulation of variability by sensory and non-sensory factors supports this view. However, it is unknown whether V1 variability reflects the statistical structure of visual inputs, as would be required for inferences correctly tuned to the statistics of the natural environment. Here we combine analysis of image statistics and recordings in macaque V1 to show that probabilistic inference tuned to natural image statistics explains the widely observed dependence between spike count variance and mean, and the modulation of V1 activity and variability by spatial context in images. Our results show that the properties of a basic aspect of cortical responses—their variability—can be explained by a probabilistic representation tuned to naturalistic inputs.
iPLA2β-mediated lipid detoxification controls p53-driven ferroptosis independent of GPX4
Authors: Chen Delin , Chu Bo , Yang Xin , Liu Zhaoqi , Jin Ying , Kon Ning , Rabadan Raul , Jiang Xuejun , Stockwell Brent R. , Gu Wei
Published: June 2021

Here, we identify iPLA2β as a critical regulator for p53-driven ferroptosis upon reactive oxygen species (ROS)-induced stress. The calcium-independent phospholipase iPLA2β is known to cleave acyl tails from the glycerol backbone of lipids and release oxidized fatty acids from phospholipids. We found that iPLA2β-mediated detoxification of peroxidized lipids is sufficient to suppress p53-driven ferroptosis upon ROS-induced stress, even in GPX4-null cells. Moreover, iPLA2β is overexpressed in human cancers; inhibition of endogenous iPLA2β sensitizes tumor cells to p53-driven ferroptosis and promotes p53-dependent tumor suppression in xenograft mouse models. These results demonstrate that iPLA2β acts as a major ferroptosis repressor in a GPX4-independent manner. Notably, unlike GPX4, loss of iPLA2β has no obvious effect on normal development or cell viability in normal tissues but iPLA2β plays an essential role in regulating ferroptosis upon ROS-induced stress. Thus, our study suggests that iPLA2β is a promising therapeutic target for activating ferroptosis-mediated tumor suppression without serious toxicity concerns.
Broadband decoupling of intensity and polarization with vectorial Fourier metasurfaces
Authors: Song Qinghua , Baroni Arthur , Wu Pin Chieh , Chenot Sébastien , Brandli Virginie , Vézian Stéphane , Damilano Benjamin , de Mierry Philippe , Khadir Samira , Ferrand Patrick , Genevet Patrice
Published: June 2021

Intensity and polarization are two fundamental components of light. Independent control of them is of tremendous interest in many applications. In this paper, we propose a general vectorial encryption method, which enables arbitrary far-field light distribution with the local polarization, including orientations and ellipticities, decoupling intensity from polarization across a broad bandwidth using geometric phase metasurfaces. By revamping the well-known iterative Fourier transform algorithm, we propose “à la carte” design of far-field intensity and polarization distribution with vectorial Fourier metasurfaces. A series of non-conventional vectorial field distribution, mimicking cylindrical vector beams in the sense that they share the same intensity profile but with different polarization distribution and a speckled phase distribution, is demonstrated. Vectorial Fourier optical metasurfaces may enable important applications in the area of complex light beam generation, secure optical data storage, steganography and optical communications.