bluuebunny/crossref_metadata_2025 huggingface dataset:
Reductions in biomarkers of exposure to selected harmful and potentially harmful constituents following exclusive and partial switching from combustible cigarettes to myblu™ electronic nicotine delivery systems (ENDS)
Authors: Morris Paul , McDermott Simon , Chapman Fiona , Verron Thomas , Cahours Xavier , Stevenson Matthew , Thompson Joseph , Chaudhary Nveed , O’Connell Grant
Published: August 2021

Electronic nicotine delivery systems (ENDS) offer adult combustible cigarette smokers an alternative, potentially reduced harm, mode of nicotine delivery, attributed to fewer and reduced levels of harmful and potentially harmful constituents (HPHCs) in their aerosols compared to cigarette smoke. These two identical, randomised, open label, two-part studies aimed to compare levels of 15 biomarkers of exposure (BoE) to selected HPHCs associated with tobacco smoking in healthy US adult smoker subjects (n = 72). Following 9 days of exclusive use of a range of allocated myblu™ ENDS variants, subjects’ levels of 14 non-nicotine BoE were substantially reduced compared to baseline values (combustible cigarette use), in the range of 46–97%. BoE reductions were sustained in subjects who continued myblu use exclusively (n = 25) for a further 5 days, and returned to near baseline levels in subjects who returned to exclusive combustible cigarette use (n = 21). Dual users (n = 24) demonstrated reductions in BoE to a lesser extent than with exclusive myblu use. Measured nicotine equivalents did not significantly change throughout the study. These data suggest exclusive use of ENDS provides adult smokers seeking an alternative to combustible cigarettes with substantial reductions in HPHC exposures whilst achieving satisfying levels of nicotine delivery. Dual use involving substitution of cigarettes may also provide some of this advantage, but to lesser extent. Overall, the data contribute to the weight of evidence that ENDS are an important tool in tobacco harm reduction for adult smokers unwilling to or uninterested in quitting smoking. Study 1: NCT 04430634, study 2: NCT 04429932, clinicaltrials.gov (10-06-2020).
Low sclerostin levels after long-term remission of acromegaly
Authors: Claessen Kim M. J. A. , Pelsma Iris C. M. , Kroon Herman M. , van Lierop Antoon H. , Pereira Alberto M. , Biermasz Nienke R. , Appelman-Dijkstra Natasha M.
Published: August 2021

Purpose

Bone health is compromised in acromegaly resulting in vertebral fractures (VFs), regardless of biochemical remission. Sclerostin is a negative inhibitor of bone formation and is associated with increased fracture risk in the general population. Therefore, we compared sclerostin concentrations between well-controlled acromegaly patients and healthy controls, and assessed its relationship with bone mineral density (BMD), and VFs in acromegaly.

Methods

Seventy-nine patients (mean age 58.9 ± 11.4 years, 49% women) with controlled acromegaly, and 91 healthy controls (mean age 51.1 ± 16.9 years, 59% women) were included. Plasma sclerostin levels (pg/mL) in patients were measured with an ELISA assay, whereas in controls, serum levels were converted to plasma levels by multiplication with 3.6. In patients, VFs were radiographically assessed, and BMD was assessed using dual X-ray absorptiometry.

Results

Median sclerostin concentration in controlled acromegaly patients was significantly lower than in healthy controls (104.5 pg/mL (range 45.7–234.7 pg/mL) vs 140.0 pg/mL (range 44.8–401.6 pg/mL), p < 0.001). Plasma sclerostin levels were not related to age, current growth hormone (GH) or insulin-like factor-1 (IGF-1) levels, gonadal state, treatment modality, remission duration, or BMD, VF presence, severity or progression.

Conclusion

Patients with long-term controlled acromegaly have lower plasma sclerostin levels than healthy controls, as a reflection of decreased osteocyte activity. Further longitudinal studies are needed to establish the course of sclerostin during different phases of disease and its exact effects in acromegalic osteopathy.
„Da muss man dann auch mit zurechtkommen“
Authors: Clark Zoë , Maleyka Kathrin , Wohlfarth Arne
Published: August 2021

Selbstorganisierte Interessenvertretungen junger Menschen in der Heimerziehung sollen ihnen ein selbstbestimmtes Leben durch Mitgestaltungsspielräume in ihrem Lebensumfeld ermöglichen. Deren Nutzung ist aber voraussetzungsvoll: Die Betroffenen müssen sich sowohl als Teil eines Kollektivs als auch als ein politisches Subjekt verstehen, das wirkmächtig Einfluss auf institutionelle und organisationale Prozesse nehmen kann. Die Praxis zeigt jedoch, dass die Aneignung dieser Voraussetzungen im Alltag der Heimerziehung durch Entfremdungsdynamiken verhindert wird. Der Beitrag kontextualisiert und analysiert solche Hindernisse.
In a World Where You can be Anyone: An Investigation into the Gendered Social Practices of Pakistani Facebook Users
Authors: Salam Rauha
Published: August 2021

This article investigates the construction of gender identities of Pakistani men and women Facebook users given that Facebook has emerged as the prime social media platform through which Pakistani users interact. By employing thematic analysis and taking insights from theory of performativity and intersectionality, the findings of the interview data suggest that the formation, negotiation, and expression of gender identities on Facebook occurs through complex interplay between the discourses of religion, class, culture, and tradition. In some cases, Facebook highlighted the reproduction of the prevalent cultural models of masculinity and femininity while in other cases; there was resistance to the existing socio-religious cultural norms of the society.
Improving heavy oil production rates in THAI process using wells configured in a staggered line drive (SLD) instead of in a direct line drive (DLD) configuration: detailed simulation investigations
Authors: Ado Muhammad Rabiu
Published: August 2021

As governments around the world prepare for a transition period to a decarbonised energy and economic future, petroleum is needed to smoothen that transition. Based on the analysis of the International Energy Agency’s 2020 projections, around 770 billion barrels of oil are required to meet demand from now to 2040. However, according to British Petroleum’s Statistical Review of World Energy 2020, as at the end of 2019, the global total reserves of recoverable conventional and unconventional oils is approximately 1734 billion barrels. Out of that, the conventional easy-to-produce light oil accounts for only 30% (i.e. accounts for only 520.2 billion barrels). Therefore, the remaining 249.8 billion barrels of oil needed to satisfy demand up to 2040 must come from unconventional oils, namely heavy oils and bitumen. However, these unconventional resources are very difficult to produce and the current production methods have very high environmental footprints. Consequently, in accordance with climate crisis mitigations, the vast reserves of the virtually unexploited heavy oils and bitumen must be developed using advanced and greener extraction technologies, such as the yet-to-be-fully-understood THAI process which provides partial upgrading of heavy oil/bitumen via in situ combustion. Using validated numerical models which are developed using the CMG’s reservoir thermal simulator, the STARS, which is also used in this study, field scale reservoir simulations of the THAI process were performed with the wells arranged in staggered line drive (SLD) and direct line drive (DLD). Over the 834 days of operating time, the cumulative oil recovery in SLD is 32% of oil originally in place (OOIP) which is equivalent to 26,100 m3 whilst that in DLD is 27% OOIP. This shows that more oil (i.e. an additional 5% OOIP) was cumulatively recovered in SLD compared to in DLD model. It is found that smaller reservoir volume was swept by the combustion front in DLD and thus making the heat-affected reservoir volume smaller than that in SLD model. Furthermore, in DLD, due to the nearness of the injector well to the toe of the horizontal producer (HP) well, oxygen production began much earlier, compared to in the SLD. It is also found that the temperature of the mobile oil zone is higher in the SLD model compared to that in the DLD model. This implies that higher quality oil is produced when the wells are configured in the SLD pattern. Therefore, this first-of-a-kind work has shown that SLD arrangement is far more efficient, safer, and produces higher quality oil than DLD pattern and that actual process engineering designs should use SLD wells configuration.
Psychopathology of Rare and Unusual Syndromes
Authors: Oyebode Femi
Published: August 2021

Rare and unusual psychiatric syndromes have fascinated people for centuries due to their complexity and undefined nature. Appreciating their clinical importance and relevance to understanding other conditions and experiences, this book provides an authoritative account of the rarest and most unusual psychiatric syndromes. The author, a leading authority on clinical psychopathology, delves into the history of the description of such syndromes, illustrates conditions with clinical case examples, and discusses the causes as well as the underlying explanatory mechanisms. The syndromes described draw attention to the way in which abnormal subjective experiences reflect the intersection of biomedical science, social anthropology, social sciences, evolutionary biology and the humanities. The book covers abnormalities of belief, abnormalities of perception, unusual experiences of the body and self, rare and bizarre impairments of memory, and behavioural disturbance. This is a valuable resource for psychiatrists, as well as researchers interested in the relationship between psychiatry and other disciplines.
Endoscopic decompositions and the Hausel–Thaddeus conjecture
Authors: Maulik Davesh , Shen Junliang
Published: August 2021

We construct natural operators connecting the cohomology of the moduli spaces of stable Higgs bundles with different ranks and genera which, after numerical specialisation, recover the topological mirror symmetry conjecture of Hausel and Thaddeus concerning

$\mathrm {SL}_n$

- and

$\mathrm {PGL}_n$

-Higgs bundles. This provides a complete description of the cohomology of the moduli space of stable

$\mathrm {SL}_n$

-Higgs bundles in terms of the tautological classes, and gives a new proof of the Hausel–Thaddeus conjecture, which was also proven recently by Gröchenig, Wyss and Ziegler via p-adic integration.

Our method is to relate the decomposition theorem for the Hitchin fibration, using vanishing cycle functors, to the decomposition theorem for the twisted Hitchin fibration, whose supports are simpler.
GENDER EQUALITY AND RELIGIOUS LAW: THE ORDINATION OF WOMEN AS RABBIS IN THE CONSERVATIVE MOVEMENT AS A CASE STUDY
Authors: Bloch Emmanuel
Published: August 2021

This article explores one tumultuous encounter between a religious legal tradition and the modern principle of equality—an encounter that also has the potential to shed light on a much wider cluster of questions. The author tracks the ways that the responsa written by prominent Conservative rabbis on the subject of female rabbinic ordination and gender equality implicitly (but unambiguously) reflect the push toward increased equality that weighed on the movement's trajectory, showing that the debate about the ordination of female rabbis reveals two principal trends in Conservative legal rulings, which differ in their responses to the challenge of egalitarianism and their visions of the law, and notes two outlier responsa that cannot be neatly classified within either trend. The author then examines the deep-seated historical, ideational, and sociological processes concurrent with the rise of what some have called the egalitarian age, which have produced these diverging responses and visions, and it determines an appropriate framework to understand them. The author shows that the fight for increased gender equality is situated within an intricate social context that imbues it with meaning and shapes its outcomes and modes of expression. In concluding, the author suggests applying the insights gained in the course of the analysis to other circumstances in which gender egalitarianism clashes with religious tradition. The framework by which the ordination of women in the Conservative movement is analyzed also proves useful, mutatis mutandis, in understanding and comparing the responses of other faith communities as they deal with challenges caused by the egalitarian age.
Fossil rodents in Mylodon Cave as indicators of late Pleistocene–Holocene environmental evolution in southern Chile
Authors: Pardiñas Ulyses F.J. , Borrero Luis , Martin Fabiana M. , Massone Mauricio , Fernández Fernando J.
Published: August 2021

We conducted the first taphonomic and paleoenvironmental study based on late Pleistocene–Holocene small mammal remains recovered from the famous Mylodon Cave (Cerro Benítez area, Última Esperanza, Chile). Most of the analyzed material came from the extensive excavations made by Earl Saxon in 1976. We also studied late Holocene small mammal samples of the neighboring rock shelter Dos Herraduras 1. Analyzed remains were mostly produced by owls, probably living inside the caves. In Mylodon Cave, the higher values of girdle bones are consistent with a windblown litter. We recorded nine species of rodents, seven cricetids, and two caviomorphs; almost all the identified taxa integrate recent local communities. Late Pleistocene–Holocene assemblages are characterized by the chinchilla ratEuneomys, indicating unforested areas around the caves under cold and moist climatic conditions. Middle Holocene amelioration is reflected by incremental rodent species richness, including the first record of taxa clearly associated with forest (e.g.,Abrothrix lanosa). Late Holocene assemblages are markedly stable, indicating local conditions similar to the current (historical) environment. Quaternary rodents from Cerro Benítez area do not indicate abrupt environmental changes during middle–late Holocene, but a progressive trend towards forest increase.
Associations between childhood to adulthood socio-economic mobility and adult diet quality
Authors: Wilson Johanna E. , Sugumar Dipti , McNaughton Sarah A. , Gall Seana L. , Dwyer Terence , Venn Alison J. , Smith Kylie J.
Published: August 2021

The impact of change in socio-economic status (SES) from childhood to adulthood (SES mobility) on adult diet is not well understood. This study examined associations between three SES mobility variables (area disadvantage, education, occupation) and adult diet quality. 1482 Australian participants reported childhood area-level SES in 1985 (aged 10–15 years) and retrospectively reported highest parental education and main occupation (until participant age 12) and own area-level SES, education, occupation and dietary intake in 2004–2006 (aged 26–36 years). A Dietary Guidelines Index (DGI) was calculated from food frequency and habit questionnaires. A higher score (range 0–100) indicated better diet quality. Sex-stratified linear regression models adjusted for confounders. Area-level SES mobility was not associated with diet quality. Compared with stable high (university) education, stable low (school only) was associated with lower DGI scores (males: β = –5·5, 95 % CI: −8·9, –2·1; females: β = –6·3, 95 % CI: −9·3, –3·4), as was downward educational mobility (participant’s education lower than their parents) (males: β = –5·3, 95 % CI: −8·5, –2·0; females: β = –4·5, 95 % CI: −7·2, –1·7) and stable intermediate (vocational) education among males (β = –3·9, 95 % CI: −7·0, −0·7). Compared with stable high (professional/managerial) occupation, stable low (manual/out of workforce) males (β = –4·9, 95 % CI: −7·6, –2·2), and participants with downward occupation mobility (males: β = –3·2, 95 % CI: −5·3, –1·1; females: β = –2·8, 95 % CI: −4·8, –0·8) had lower DGI scores. In this cohort, intergenerational low education and occupation, and downward educational and occupational mobility, were associated with poor adult diet quality.
Computing the fundamental group of a higher-rank graph
Authors: Kang Sooran , Pask David , Webster Samuel B.G.
Published: August 2021

We compute a presentation of the fundamental group of a higher-rank graph using a coloured graph description of higher-rank graphs developed by the third author. We compute the fundamental groups of several examples from the literature. Our results fit naturally into the suite of known geometrical results about higher-rank graphs when we show that the abelianization of the fundamental group is the homology group. We end with a calculation which gives a non-standard presentation of the fundamental group of the Klein bottle to the one normally found in the literature.
Concentrated matrix exponential distributions with real eigenvalues
Authors: Mészáros András , Telek Miklós
Published: August 2021

Concentrated random variables are frequently used in representing deterministic delays in stochastic models. The squared coefficient of variation ($\mathrm {SCV}$) of the most concentrated phase-type distribution of order $N$ is $1/N$. To further reduce the $\mathrm {SCV}$, concentrated matrix exponential (CME) distributions with complex eigenvalues were investigated recently. It was obtained that the $\mathrm {SCV}$ of an order $N$ CME distribution can be less than $n^{-2.1}$ for odd $N=2n+1$ orders, and the matrix exponential distribution, which exhibits such a low $\mathrm {SCV}$ has complex eigenvalues. In this paper, we consider CME distributions with real eigenvalues (CME-R). We present efficient numerical methods for identifying a CME-R distribution with smallest SCV for a given order $n$. Our investigations show that the $\mathrm {SCV}$ of the most concentrated CME-R of order $N=2n+1$ is less than $n^{-1.85}$. We also discuss how CME-R can be used for numerical inverse Laplace transformation, which is beneficial when the Laplace transform function is impossible to evaluate at complex points.
Cinema, colonialism, and contact zone: the movie theater and city governance in early-twentieth-century Shanghai
Authors: He Qiliang , Tan Jie
Published: August 2021

Moving away from the text-centered paradigm in film studies, the present research explores the relationship between the growing popularity of the film in Shanghai during the first two decades of the twentieth century and city governance in the International Settlement. It argues that the rise of movie halls contributed to creating a new kind of crowd that blended Chinese moviegoers with non-Chinese viewers. The emergence of the cinema as a space where people of different racial and ethnic origins encountered impelled the Shanghai Municipal Council – the governing body of the International Settlement in Shanghai – to respond by implementing new measures of public safety and altering its decades-long unspoken rules of segregation in the realm of everyday life. For Chinese enlightenment intellectuals and government officials, meanwhile, anxiety over their fellow Chinese's lack of basic decorum in public spaces arose with the intense intermingling of Chinese and non-Chinese filmgoers under the same roof. Thus, the cinema became a “contact zone” – a space of asymmetrical relations resulting not necessarily from colonists' exercise of colonial power but from the Chinese elite's wrapping of the discussion of movie theater etiquette reform within a political and ideological framework of modernization, patriotism, and anti-imperialism.
Manchukuo voices: re-interpreting a monumental space in Northeast China (1932–1945)
Authors: Dong 董钰婷 Yuting
Published: August 2021

This article revisits Japan's empire-building in Northeast China through the construction of and reactions to the Daidō hiroba 大同広場 (Plaza of Great Unity) in Shinkyō, showing how Chinese and Japanese challenged the top-down attempt for building a totalitarian empire. These re-interpretations and definitions of Hiroba unveiled the diversity, dynamics, and complexity of Manchukuo society that cannot be fully grasped in a nation-state framework. Moreover, their voices challenged the previous depiction of such imperial monumental space as the physical materialization of imperial governmentality but a contested site where individuals challenged the official vision of Manchukuo. This article examines documents ranging from governmental documents to works of literature in both Chinese and Japanese. Compared to Japanese planners' vision of the Hiroba as a site of governmentality, visitors and local residents held differing interpretations of this space: some Japanese disapproved the attempt to reframe the urban space by a totalitarian regime, and many Chinese redefined the meaning of this “utopian” urban space to accord with their own tradition and everyday life.
Morgan Rehnberg: The Making of a Museum Chief
Authors: Cartier Kimberly
Published: August 2021

From Cassini to #scicomm to showcasing science.
Characteristics of Global Ocean Abnormal Mesoscale Eddies Derived From the Fusion of Sea Surface Height and Temperature Data by Deep Learning
Authors: Liu Yingjie , Zheng Quanan , Li Xiaofeng
Published: August 2021

Recent satellite sea surface height (SSH) and sea surface temperature (SST) observations have shown that abnormal eddies, that is, warm cyclonic eddies and cold anticyclonic eddies occur sporadically in some regions, which triggers an essential question on the spatiotemporal distribution of abnormal eddies in the global ocean. In this study, a deep learning framework was developed to systematically mine information from the synergy of satellite‐sensed global SSH and SST data over the 1996–2015, 20‐year period. Abnormal eddies account for a surprising one‐third of total eddies and are active along the Equatorial Current and high unstable currents. Normal (abnormal) eddies are stronger in winter (summer) in the North Hemisphere and vice versa in the Southern Hemisphere. The annual mean amplitudes of normal eddies are larger than that of abnormal eddies. Crucially, the daily number of normal (abnormal) eddies increased (decreased) 9.68 (11.80) every year.
Decompaction Weakening as a Mechanism of Fluid Focusing in Hydrothermal Systems
Authors: Utkin Ivan , Afanasyev Andrey
Published: August 2021

We present a mathematical model of nonreactive fluid flow in a compacting porous medium. The model differs from previous formulations by considering fluid transport in the frame of reference moving with the solid phase. Such an approach guarantees material balance for the fluid and solid phases not only in the small‐porosity limit but also for large values of porosity. Using the numerical implementation of the proposed model, we simulate magmatic fluid transport in the Earth's upper crust. We account for the thermal softening of rocks, the plastic deformation of the solid matrix through decompaction weakening, and realistic fluid properties in a wide range of depths, including those above and below the brittle‐ductile transition (BDT). We show that our simulation approach can resolve the localized flow in the ductile zone and numerous hydrothermal convection cells in the brittle zone. We investigate the influence of decompaction weakening on high‐porosity channels forming in the ductile zone and their interaction with the convection in the brittle zone. We show that compaction causes magmatic fluid focusing and accumulation in high‐porosity lenses beneath the low‐porosity BDT zone. We show that magmatic fluid transfer through the BDT occurs mainly through the roofs of the lenses, which results in a plume of hydrothermal convection always sitting atop every lens. Other plumes between the lenses are associated with the convection of meteoric water that transfers only heat from the BDT to the surface. The simulations indicate that the lenses can be tracked by measuring certain parameters at the surface.
Variations in Hard‐Bedded Topography Beneath Glaciers
Authors: Woodard J. B. , Zoet L. K. , Iverson N. R. , Helanow C.
Published: August 2021

The morphology of glacier beds is a first‐order control on their slip speeds and consequent rates of subglacial erosion. As such, constraining the range of bed shapes expected beneath glaciers will improve estimates of glacier slip speeds. To estimate the variability of subglacial bed morphology, we construct 10 high‐resolution (10 cm) digital elevation models of proglacial areas near current glacier margins from point clouds produced through a combination of terrestrial laser scanning and photogrammetry techniques. The proglacial areas are located in the Swiss Alps and the Canadian Rockies and consist of predominantly debris‐free bedrock of variable lithology (igneous, sedimentary, and metamorphic). We measure eight different spatial parameters intended to describe bed morphologies generated beneath glaciers. Using probability density functions, Bhattacharyya coefficients, principal component analysis, and Bayesian statistical models we investigate the significance of these spatial parameters. We find that the parameters span similar ranges, but the means and standard deviations of the parameter probability density functions are commonly distinct. These results indicate that glacier flow over bedrock may lead to a convergence toward a common bed morphology. However, distinct properties associated with each location prevent morphologies from being uniform.
Intraspecific variation in metal tolerance modulate competition between two marine diatoms
Authors: Andersson Björn , Godhe Anna , Filipsson Helena L , Zetterholm Linda , Edler Lars , Berglund Olof , Rengefors Karin
Published: August 2021

Despite widespread metal pollution of coastal ecosystems, little is known of its effect on marine phytoplankton. We designed a co-cultivation experiment to test if toxic dose–response relationships can be used to predict the competitive outcome of two species under metal stress. Specifically, we took into account intraspecific strain variation and selection. We used 72 h dose–response relationships to model how silver (Ag), cadmium (Cd), and copper (Cu) affect both intraspecific strain selection and competition between taxa in two marine diatoms (Skeletonema marinoi and Thalassiosira baltica). The models were validated against 10-day co-culture experiments, using four strains per species. In the control treatment, we could predict the outcome using strain-specific growth rates, suggesting low levels of competitive interactions between the species. Our models correctly predicted which species would gain a competitive advantage under toxic stress. However, the absolute inhibition levels were confounded by the development of chronic toxic stress, resulting in a higher long-term inhibition by Cd and Cu. We failed to detect species differences in average Cu tolerance, but the model accounting for strain selection accurately predicted a competitive advantage for T. baltica. Our findings demonstrate the importance of incorporating multiple strains when determining traits and when performing microbial competition experiments.
OCT4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human
Authors: Huang Xin , Park Kyoung-mi , Gontarz Paul , Zhang Bo , Pan Joshua , McKenzie Zachary , Fischer Laura A. , Dong Chen , Dietmann Sabine , Xing Xiaoyun , Shliaha Pavel V. , Yang Jihong , Li Dan , Ding Junjun , Lungjangwa Tenzin , Mitalipova Maya , Khan Shafqat A. , Imsoonthornruksa Sumeth , Jensen Nick , Wang Ting , Kadoch Cigall , Jaenisch Rudolf , Wang Jianlong , Theunissen Thorold W.
Published: August 2021

Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). While the protein-protein interactions of core pluripotency factors have been identified in mouse ESCs, their interactome in human ESCs (hESCs) has not to date been explored. Here we mapped the OCT4 interactomes in naïve and primed hESCs, revealing extensive connections to mammalian ATP-dependent nucleosome remodeling complexes. In naïve hESCs, OCT4 is associated with both BRG1 and BRM, the two paralog ATPases of the BAF complex. Genome-wide location analyses and genetic studies reveal that these two enzymes cooperate in a functionally redundant manner in the transcriptional regulation of blastocyst-specific genes. In contrast, in primed hESCs, OCT4 cooperates with BRG1 and SOX2 to promote chromatin accessibility at ectodermal genes. This work reveals how a common transcription factor utilizes differential BAF complexes to control distinct transcriptional programs in naïve and primed hESCs.
PTENα functions as an immune suppressor and promotes immune resistance in PTEN-mutant cancer
Authors: Sun Yizhe , Lu Dan , Yin Yue , Song Jia , Liu Yang , Hao Wenyan , Qi Fang , Zhang Guangze , Zhang Xin , Liu Liang , Lin Zhiqiang , Liang Hui , Zhao Xuyang , Jin Yan , Yin Yuxin
Published: August 2021

PTENis frequently mutated in human cancers andPTENmutants promote tumor progression and metastasis.PTENmutations have been implicated in immune regulation, however, the underlying mechanism is largely unknown. Here, we report that PTENα, the isoform of PTEN, remains active in cancer bearing stop-gainedPTENmutations. Through counteraction of CD8+ T cell-mediated cytotoxicity, PTENα leads to T cell dysfunction and accelerates immune-resistant cancer progression. Clinical analysis further uncovers that PTENα-active mutations suppress host immune responses and result in poor prognosis in cancer as relative to PTENα-inactive mutations. Furthermore, germline deletion ofPtenαin mice increases cell susceptibility to immune attack through augmenting stress granule formation and limiting synthesis of peroxidases, leading to massive oxidative cell death and severe inflammatory damage. We propose that PTENα protects tumor from T cell killing and thus PTENα is a potential target in antitumor immunotherapy.
3D electron-beam writing at sub-15 nm resolution using spider silk as a resist
Authors: Qin Nan , Qian Zhi-Gang , Zhou Chengzhe , Xia Xiao-Xia , Tao Tiger H.
Published: August 2021

Electron beam lithography (EBL) is renowned to provide fabrication resolution in the deep nanometer scale. One major limitation of current EBL techniques is their incapability of arbitrary 3d nanofabrication. Resolution, structure integrity and functionalization are among the most important factors. Here we report all-aqueous-based, high-fidelity manufacturing of functional, arbitrary 3d nanostructures at a resolution of sub-15 nm using our developed voltage-regulated 3d EBL. Creating arbitrary 3d structures of high resolution and high strength at nanoscale is enabled by genetically engineering recombinant spider silk proteins as the resist. The ability to quantitatively define structural transitions with energetic electrons at different depths within the 3d protein matrix enables polymorphic spider silk proteins to be shaped approaching the molecular level. Furthermore, genetic or mesoscopic modification of spider silk proteins provides the opportunity to embed and stabilize physiochemical and/or biological functions within as-fabricated 3d nanostructures. Our approach empowers the rapid and flexible fabrication of heterogeneously functionalized and hierarchically structured 3d nanocomponents and nanodevices, offering opportunities in biomimetics, therapeutic devices and nanoscale robotics.
Neutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum
Authors: Bates Timothy A. , Leier Hans C. , Lyski Zoe L. , McBride Savannah K. , Coulter Felicity J. , Weinstein Jules B. , Goodman James R. , Lu Zhengchun , Siegel Sarah A. R. , Sullivan Peter , Strnad Matt , Brunton Amanda E. , Lee David X. , Adey Andrew C. , Bimber Benjamin N. , O’Roak Brian J. , Curlin Marcel E. , Messer William B. , Tafesse Fikadu G.
Published: August 2021

SARS-CoV-2 and its variants continue to infect hundreds of thousands every day despite the rollout of effective vaccines. Therefore, it is essential to understand the levels of protection that these vaccines provide in the face of emerging variants. Here, we report two demographically balanced cohorts of BNT162b2 vaccine recipients and COVID-19 patients, from which we evaluate neutralizing antibody titers against SARS-CoV-2 as well as the B.1.1.7 (alpha) and B.1.351 (beta) variants. We show that both B.1.1.7 and B.1.351 are less well neutralized by serum from vaccinated individuals, and that B.1.351, but not B.1.1.7, is less well neutralized by convalescent serum. We also find that the levels of variant-specific anti-spike antibodies are proportional to neutralizing activities. Together, our results demonstrate the escape of the emerging SARS-CoV-2 variants from neutralization by serum antibodies, which may lead to reduced protection from re-infection or increased risk of vaccine breakthrough.
Oligodendrocytic Na+-K+-Cl– co-transporter 1 activity facilitates axonal conduction and restores plasticity in the adult mouse brain
Authors: Yamazaki Yoshihiko , Abe Yoshifumi , Fujii Satoshi , Tanaka Kenji F.
Published: August 2021

The juvenile brain presents plasticity. Oligodendrocytes are the myelinating cells of the central nervous system and myelination can be adaptive. Plasticity decreases from juvenile to adulthood. The mechanisms involving oligodendrocytes underlying plasticity are unclear. Here, we show Na+-K+-Cl– co-transporter 1 (NKCC1), highly expressed in the juvenile mouse brain, regulates the oligodendrocyte activity from juvenile to adulthood in mice, as shown by optogenetic manipulation of oligodendrocytes. The reduced neuronal activity in adults was restored by Nkcc1 overexpression in oligodendrocytes. Moreover, in adult mice overexpressing Nkcc1, long-term potentiation and learning were facilitated compared to age-matched controls. These findings demonstrate that NKCC1 plays a regulatory role in the age-dependent activity of oligodendrocytes, furthermore inducing activation of NKCC1 in oligodendrocytes can restore neuronal plasticity in the adult mouse brain.
Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients
Authors: Soutome Sakiko , Otsuru Mitsunobu , Hayashida Saki , Murata Maho , Yanamoto Souichi , Sawada Shunsuke , Kojima Yuka , Funahara Madoka , Iwai Hiroshi , Umeda Masahiro , Saito Toshiyuki
Published: August 2021

Tooth extraction has been avoided since it has been considered a major risk factor for medication-related osteonecrosis of the jaw (MRONJ). However, MRONJ may also develop from tooth that is an infection source. This study aimed to clarify whether tooth extraction is a risk factor for the development of MRONJ in cancer patients receiving bone-modifying agents (BMAs). This retrospective observational study included 189 patients (361 jaws) from two hospitals. The risk factors of MRONJ were identified by comparing patient characteristics between those who did and did not develop MRONJ. Furthermore, the effect of tooth extraction during BMA therapy was analyzed after adjusting for confounding factors using the propensity score matching method. MRONJ occurred in 33 patients jaws. A longer duration of BMA administration, fewer number of teeth, presence of symptoms of local infection, and infected teeth were independent risk factors of MRONJ. However, tooth extraction during BMA therapy did not increase the risk. Propensity score matching analysis showed that tooth extraction significantly lowered the risk of MRONJ development. Teeth that can be an infection source increases the risk of MRONJ, and thus, they need to be extracted even during BMA administration.
Relationship of subjective and objective sleep measures with physical performance in advanced-stage lung cancer patients
Authors: Takemura Naomi , Cheung Denise Shuk Ting , Fong Daniel Yee Tak , Lee Anne Wing Mui , Lam Tai-Chung , Ho James Chung-Man , Kam Tsz Yeung , Chik Jeannie Yin Kwan , Lin Chia-Chin
Published: August 2021

Advanced lung cancer patients suffer from deteriorated physical function, which negatively impacts physical and psychological health. As little is known about sleep and physical function in this population, this study aimed to examine the association between subjective and objective sleep parameters and physical function among them. 164 advanced lung cancer patients were included. Objective sleep was measured by actigraphy (measured on non-dominant wrist for 72 h), and subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Performance-based physical function was measured by Timed Up and Go Test (TUGT), 6-Minute Walk Test (6MWT), Sit-to-Stand Test, and One-leg Standing Test. Univariable and multivariable regression analyses were employed to examine the association between sleep and physical function. Total sleep time (TST) was significantly associated with the 6MWT (β = 0.259; 95% CI 0.120, 0.398; P < 0.001), TUGT (β = − 0.012; 95% CI = − 0.017, − 0.008; P < 0.001) and Sit-to-Stand Test (β = 0.027; 95% CI = 0.018, 0.035; P < 0.001) after adjustment for multiple covariates. PSQI global score was only significantly associated with TUGT (β = 0.140; 95% CI = 0.000, 0.280; P = 0.050) after adjustment for multiple covariates. Shorter sleep duration significantly predicted poorer physical performance in advanced lung cancer patients, and more attention is required for those with less than 4.3 h of sleep on average.

Trial registration: ClinicalTrials.gov, NCT03482323. Registered 29 March 2018, https://clinicaltrials.gov/ct2/show/NCT03482323; ClinicalTrials.gov, NCT04119778. Registered 8 October 2019, https://clinicaltrials.gov/ct2/show/NCT04119778.
Loss of the ciliary protein Chibby1 in mice leads to exocrine pancreatic degeneration and pancreatitis
Authors: Cyge Benjamin , Voronina Vera , Hoque Mohammed , Kim Eunice N. , Hall Jason , Bailey-Lundberg Jennifer M. , Pazour Gregory J. , Crawford Howard C. , Moon Randall T. , Li Feng-Qian , Takemaru Ken-Ichi
Published: August 2021

Primary cilia protrude from the apical surface of many cell types and act as a sensory organelle that regulates diverse biological processes ranging from chemo- and mechanosensation to signaling. Ciliary dysfunction is associated with a wide array of genetic disorders, known as ciliopathies. Polycystic lesions are commonly found in the kidney, liver, and pancreas of ciliopathy patients and mouse models. However, the pathogenesis of the pancreatic phenotype remains poorly understood. Chibby1 (Cby1), a small conserved coiled-coil protein, localizes to the ciliary base and plays a crucial role in ciliogenesis. Here, we report that Cby1-knockout (KO) mice develop severe exocrine pancreatic atrophy with dilated ducts during early postnatal development. A significant reduction in the number and length of cilia was observed in Cby1-KO pancreta. In the adult Cby1-KO pancreas, inflammatory cell infiltration and fibrosis were noticeable. Intriguingly, Cby1-KO acinar cells showed an accumulation of zymogen granules (ZGs) with altered polarity. Moreover, isolated acini from Cby1-KO pancreas exhibited defective ZG secretion in vitro. Collectively, our results suggest that, upon loss of Cby1, concomitant with ciliary defects, acinar cells accumulate ZGs due to defective exocytosis, leading to cell death and progressive exocrine pancreatic degeneration after birth.
Seasonal and annual changes in the microbial communities of Ofunato Bay, Japan, based on metagenomics
Authors: Kobiyama Atsushi , Rashid Jonaira , Reza Md. Shaheed , Ikeda Yuri , Yamada Yuichiro , Kudo Toshiaki , Mizusawa Nanami , Yanagisawa Saki , Ikeda Daisuke , Sato Shigeru , Ogata Takehiko , Ikeo Kazuho , Kaga Shinnosuke , Watanabe Shiho , Naiki Kimiaki , Kaga Yoshimasa , Segawa Satoshi , Tada Yumiko , Musashi Tatsuya , Mineta Katsuhiko , Gojobori Takashi , Watabe Shugo
Published: August 2021

Five years of datasets from 2015 to 2019 of whole genome shotgun sequencing for cells trapped on 0.2-µm filters of seawater collected monthly from Ofunato Bay, an enclosed bay in Japan, were analysed, which included the 2015 data that we had reported previously. Nucleotide sequences were determined for extracted DNA from three locations for both the upper (1 m) and deeper (8 or 10 m) depths. The biotic communities analysed at the domain level comprised bacteria, eukaryotes, archaea and viruses. The relative abundance of bacteria was over 60% in most months for the five years. The relative abundance of the SAR86 cluster was highest in the bacterial group, followed by Candidatus Pelagibacter and Planktomarina. The relative abundance of Ca. Pelagibacter showed no relationship with environmental factors, and those of SAR86 and Planktomarina showed positive correlations with salinity and dissolved oxygen, respectively. The bacterial community diversity showed seasonal changes, with high diversity around September and low diversity around January for all five years. Nonmetric multidimensional scaling analysis also revealed that the bacterial communities in the bay were grouped in a season-dependent manner and linked with environmental variables such as seawater temperature, salinity and dissolved oxygen.
Exploring deep learning capabilities for surge predictions in coastal areas
Authors: Tiggeloven Timothy , Couasnon Anaïs , van Straaten Chiem , Muis Sanne , Ward Philip J.
Published: August 2021

To improve coastal adaptation and management, it is critical to better understand and predict the characteristics of sea levels. Here, we explore the capabilities of artificial intelligence, from four deep learning methods to predict the surge component of sea-level variability based on local atmospheric conditions. We use an Artificial Neural Networks, Convolutional Neural Network, Long Short-Term Memory layer (LSTM) and a combination of the latter two (ConvLSTM), to construct ensembles of Neural Network (NN) models at 736 tide stations globally. The NN models show similar patterns of performance, with much higher skill in the mid-latitudes. Using our global model settings, the LSTM generally outperforms the other NN models. Furthermore, for 15 stations we assess the influence of adding complexity more predictor variables. This generally improves model performance but leads to substantial increases in computation time. The improvement in performance remains insufficient to fully capture observed dynamics in some regions. For example, in the tropics only modelling surges is insufficient to capture intra-annual sea level variability. While we focus on minimising mean absolute error for the full time series, the NN models presented here could be adapted for use in forecasting extreme sea levels or emergency response.
Investigation of sustainability embodied in existing buildings: a case study of refurbishment adopted in a Chinese contemporary building
Authors: Huang Yi , Xu Chong , Xiao Yufan , Dewancker Bart
Published: August 2021

The Liyuan courtyard buildings are considered as contemporary architectural symbols of the spirit in Qingdao, China. The sustainability potentials embodied in the building is evaluated by building performance simulations analysis based on field investigation in this case study. Two models with optimization refurbishment were made through building simulation software. One model with façade supplemented in the insulation layers of the envelope walls and the other model with further upgrade with consideration of recycling materials mixed were discussed and estimated with building performance simulation method. The energy performance in the building and both scenarios designed can improve the energy efficiency, while the advanced model could achieve better result in the building energy behavior dramatically. Technologies innovation are proved to be good tools to improve energy performance the existing buildings by renovation actions such as insulation improvement and so on. It is concluded the sustainability regain its authentic appearance while achieve energy efficiency embodied within contemporary buildings through adaptational renovation strategies. Multicriteria considerations might influence the balanced between different factors when making decisions in the building restoration project, it is also expected to empower the fresh glory in the development of building protection and restoration.
Diagnostic usefulness of 10-step tandem gait test for the patient with degenerative cervical myelopathy
Authors: Yoo Dallah , Kang Kyung-Chung , Lee Jung-Hee , Lee Ki Young , Hwang In-Uk
Published: August 2021

Tandem gait is considered one of the most useful screening tools for gait impairment. The aim of this study is to evaluate diagnostic usefulness of 10-step tandem gait test for the patients with degenerative cervical myelopathy (DCM). Sixty-two DCM patients were compared to 55 persons without gait abnormalities as control. We counted the number of consecutive steps and graded into five according the number of steps and stability. Five grades of tandem gait were investigated for association with clinical parameters including qualitative Japanese orthopedic association (JOA) sub-score for lower extremities and Nurick scale and quantitative balance and gait assessments. The number of tandem steps were reduced and the grades of tandem gait were differently distributed in the DCM patients compared to controls (steps, 7.1 ± 3.6 versus 9.9 ± 0.4, p < 0.001; grades of 0/1/2/3/4/5, 1/13/14/15/19 versus 0/0/2/15/38, p < 0.001 in patients with DCM and control respectively). Patients with DCM showed more unstable balance and abnormal gait features including slower velocity, shorter strides, wider bases with increased stance phase of a gait cycle compared to the control group. The grades of tandem gait were correlated with JOA sub-score (r = 0.553, p < 0.001) and the Nurick scale (r = − 0.652, p < 0.001) as well as both balance and gait parameters. In DCM patients, tandem gait was impaired and correlated with severity of gait abnormality. The authors believe that 10-step tandem gait test is an objective and useful screening test for evaluating gait disturbance in patients with DCM.
Identification of key proteins in the signaling crossroads between wound healing and cancer hallmark phenotypes
Authors: López-Cortés Andrés , Abarca Estefanía , Silva Leonardo , Velastegui Erick , León-Sosa Ariana , Karolys Germania , Cabrera Francisco , Caicedo Andrés
Published: August 2021

Wound healing (WH) and cancer seem to share common cellular and molecular processes that could work in a tight balance to maintain tissue homeostasis or, when unregulated, drive tumor progression. The “Cancer Hallmarks” comprise crucial biological properties that mediate the advancement of the disease and affect patient prognosis. These hallmarks have been proposed to overlap with essential features of the WH process. However, common hallmarks and proteins actively participating in both processes have yet to be described. In this work we identify 21 WH proteins strongly linked with solid tumors by integrated TCGA Pan-Cancer and multi-omics analyses. These proteins were associated with eight of the ten described cancer hallmarks, especially avoiding immune destruction. These results show that WH and cancer's common proteins are involved in the microenvironment modification of solid tissues and immune system regulation. This set of proteins, between WH and cancer, could represent key targets for developing therapies.