bluuebunny/crossref_metadata_2025 huggingface dataset:
Well-Differentiated Liposarcoma of the Hypopharynx Exhibiting Myxoid Liposarcoma-like Morphology with MDM2 and DDIT3 Co-Amplification
Authors: Murshed Khaled A. , Abo Samra Hayan , Ammar Adham
Published: June 2021

Well-differentiated liposarcoma (WDL) is one of the most common soft tissue sarcomas in adults. It has a predilection for middle-aged males and arises in deep-seated locations such as retroperitoneum, mediastinum, and spermatic cord. Its occurrence in young individuals at the hypopharyngeal region is an exceedingly rare event. Myxoid liposarcoma (ML)-like changes can seldom occur in some cases of WDL, which makes the diagnosis of WDL more challenging. Amplification of DDIT3 gene in a subset of cases of WDL has shown to be associated with such unique morphology. Herein, we present a case of a 36-year-old gentleman who presented with difficulty in breathing and swallowing for 3 months duration. CT scan of the neck revealed a lesion along the posterior wall of the hypopharynx measuring 3.5 cm. Histopathologic examination revealed a tumor composed of lobules of oval to spindle cells in a prominent myxoid stroma with delicate chicken-wire vasculature. In the vicinity, there were lobules composed of variably sized adipocytes separated by thick fibrous septa that contains atypical hyperchromatic spindle cells. By immunohistochemistry, the tumor cells in both components were immunoreactive for CDK4, but negative for MDM2. Fluorescence in-situ hybridization (FISH) confirmed the presence of MDM2 gene amplification. There was no evidence of FUS-DDIT3 gene rearrangement, however, DDIT3 gene was also amplified. The diagnosis of well-differentiated liposarcoma with prominent myxoid stroma was rendered. This is the first documentation of WDL with ML-like morphology harboring co-amplification of MDM2 and DDIT3 in the hypopharynx.
Taking Time Seriously: Biographical Circumstance and Immigrant Labor Integration Experience
Authors: Gubrium Erika , Leirvik Mariann Stærkebye
Published: June 2021

The article offers a re-conceptualization of the labor integration process which takes temporality into account as a relevant feature that, rather than following patterned frames of reference, is actively referenced through narratively and socially constructed formations of understanding. The European policy strategy regarding immigrants has shifted in the past decades from a focus on social integration to a predominant focus on labor market integration, due in part to the relatively high unemployment rates of immigrants entering and migrating within Europe. A personalized approach used throughout Europe to “empower” and move immigrants into the labor market has not been realized in practice. Norway, a “best case scenario” for a more personalized approach through comprehensive labor integration and activation measures, has also had limited success with the sustained labor integration of immigrants. We suggest that a source of the problem lies in the conceptualization of labor integration, which, in contrast to true personalization, follows a patterned notion of the process. We argue that such a conceptualization does not provide the means to explore and untangle potentially significant processes and mechanisms relevant to the labor integration experience. We introduce the concept of biographical circumstance to demonstrate how immigrant participants in a Norwegian labor activation program draw on different references from their personal histories as they make meaning of their labor integration—and how meaning-making is dialectically shaped and delimited by the structural effects of changing policy opportunities, rules, and regulations. We conducted 14 qualitative interviews with immigrants involved in the Norwegian Qualification Program, a national labor activation program. We select four participants to present as illustrative cases of biographical circumstance and meaning making. The four differently make meaning of and respond to their labor integration experiences through active reference to specific personal histories and changing policy encounters over time. The data demonstrate that accounting for biographical circumstance enables us to better understand the actions, rationalizations, and motivations of immigrants participating in labor integration and activation measures.
Typifications and combinations in the Ebenaceae of Peninsular Malaysia and Singapore
Authors: de Kok R. P. J. , Puglisi C.
Published: June 2021

Many of the current and synonymous names applied to the species of Diospyros L. (Ebenaceae) from Peninsular Malaysia and Singapore lack a type. Here we designate lectotypes and two neotypes and establish the correct combinations for the taxa belonging to the species hitherto known as Diospyros pilosanthera.
Recognizing Indigenous peoples’ and local communities’ rights and agency in the post-2020 Biodiversity Agenda
Authors: Reyes-García Victoria , Fernández-Llamazares Álvaro , Aumeeruddy-Thomas Yildiz , Benyei Petra , Bussmann Rainer W. , Diamond Sara K. , García-del-Amo David , Guadilla-Sáez Sara , Hanazaki Natalia , Kosoy Nicolas , Lavides Margarita , Luz Ana C. , McElwee Pamela , Meretsky Vicky J. , Newberry Teresa , Molnár Zsolt , Ruiz-Mallén Isabel , Salpeteur Matthieu , Wyndham Felice S. , Zorondo-Rodriguez Francisco , Brondizio Eduardo S.
Published: June 2021

The Convention on Biological Diversity is defining the goals that will frame future global biodiversity policy in a context of rapid biodiversity decline and under pressure to make transformative change. Drawing on the work of Indigenous and non-Indigenous scholars, we argue that transformative change requires the foregrounding of Indigenous peoples’ and local communities’ rights and agency in biodiversity policy. We support this argument with four key points. First, Indigenous peoples and local communities hold knowledge essential for setting realistic and effective biodiversity targets that simultaneously improve local livelihoods. Second, Indigenous peoples’ conceptualizations of nature sustain and manifest CBD’s 2050 vision of “Living in harmony with nature.” Third, Indigenous peoples’ and local communities’ participation in biodiversity policy contributes to the recognition of human and Indigenous peoples’ rights. And fourth, engagement in biodiversity policy is essential for Indigenous peoples and local communities to be able to exercise their recognized rights to territories and resources.
The Applied Sports Science and Medicine of Netball: A Systematic Scoping Review
Authors: Whitehead Sarah , Weakley Jonathon , Cormack Stuart , Alfano Helen , Kerss Jim , Mooney Mitch , Jones Ben
Published: June 2021

Background

Netball is the one of the most popular women’s sports in the world. Since gaining professional status in 2008 there has been a rapid growth in research in the applied sports science and medicine of the sport. A scoping review of the area would provide practitioners and researchers with an overview of the current scientific literature to support on-court performance, player welfare and reduce injury.

Objective

The primary objective was to identify the current research on the applied sports science and medicine of netball. Additionally, the article provides a brief summary of the research in each topic of sports science and medicine in netball and identifies gaps in the current research.

Methods

Systematic searches of PubMed, SPORTDiscus, MEDLINE and CINAHL were undertaken from earliest record to Dec 2020 and reference lists were manually searched. The PRISMA-ScR protocol was followed. Studies were eligible for inclusion if they investigated netball as a sport or the applied sport science and medicine of netball athletes.

Results

962 studies were identified in the initial search, 150 of which met the inclusion criteria. Injury was the most highly investigated sport science and medicine topic (n = 45), followed by physical qualities (n = 37), match characteristics (n = 24), biomechanics (n = 15), psychology (n = 13), fatigue and recovery (n = 9), training load (n = 4) and nutrition (n = 3). A range of cohorts were used from school to elite and international standards. All cohorts were female netballers, except for one study. A rapid growth in studies over recent years was demonstrated with 65% of studies published in the last decade. There still remains gaps in the literature, with a low evidence base for nutrition, training load and fatigue and recovery.

Conclusion

This scoping review summarises the current evidence base and key findings that can be used in practice to enhance the applied sport science and medical support to netball athletes across a range of playing standards, and support the growth of the sport. It is evident that netball as a sport is still under-researched.
Sexuelle Unlust – Wirkmechanismen des natürlichen Aphrodisiakums Damiana (Turnera diffusa)
Authors: Kuchernig Jennifer-Christin
Published: June 2021

Sexuelle Unlust bei Frauen ist eine häufig auftretende und meist multifaktorielle Symptomatik in jedem Alter. Entsteht daraus ein individueller Leidensdruck, einhergehend mit einer schlechten Lebensqualität, dann leiden Frauen daran umfassender und möglicherweise schwerwiegender als Männer. Ihre sexuellen Probleme werden jedoch im klinischen Umfeld oft nicht erkannt und bleiben unbehandelt, denn nur 20–34 % der Betroffenen suchen aktiv Hilfe bei einem Arzt. Die Auslöser mangelnder Libido können vielfältig sein und neben stressigen Lebensphasen auch an bestehende Medikationen, den demografischen Hintergrund, Probleme in der Partnerschaft oder Umstellungen der Hormone z. B. in den Wechseljahren gekoppelt sein. Pharmakotherapeutisch stehen jedoch nur relativ wenige Optionen für die Behandlung zur Verfügung. Neben einer nur in der Off-Label-Anwendung möglichen Verabreichung von transdermalem Testosteron oder Dehydroepiandrosteron, der Überweisung an andere Fachgebiete oder einer interdisziplinären Zusammenarbeit kann ein möglicher Baustein der Behandlung in der Verwendung geeigneter Phytopharmaka liegen. Durch eine Gesamtwirkung der beobachteten Einzelwirkungen von Inhaltsstoffen der Pflanze Damiana (Turnera diffusa) aus der Familie der Safranmalven (Turneraceae) können daraus hergestellte Arzneimittel eine gute Behandlungsoption mit einem positiven Einfluss auf eine verminderte Libido darstellen.
The Intellectual Property of Nations
Authors: Ford Laura R.
Published: June 2021

Drawing on macro-historical sociological theories, this book traces the development of intellectual property as a new type of legal property in the modern nation-state system. In its current form, intellectual property is considered part of an infrastructure of state power that incentivizes innovation, creativity, and scientific development, all engines of economic growth. To show how this infrastructure of power emerged, Laura Ford follows macro-historical social theorists, including Michael Mann and Max Weber, back to antiquity, revealing that legal instruments very similar to modern intellectual property have existed for a long time and have also been deployed for similar purposes. Using comparative and historical evidence, this groundbreaking work reflects on the role of intellectual property in our contemporary political communities and societies; on the close relationship between law and religion; and on the extent to which law's obliging force depends on ancient, written traditions.
Manners Make a Nation
Authors: Shutt Allison K.
Published: June 2021

Shortlisted for the inaugural award of the ASAUK Fage & Oliver Prize Tells the story of how people struggled to define, refine, reform, and ultimately overturn racial etiquette as a social guide for Southern Rhodesian politics.
No Easy Occupation
Authors: Long Bronson
Published: June 2021

After 1945, France and West Germany were involved in a bitter dispute over the Saar, a small, coal-rich, culturally German territory bordering France's Lorraine region that France had occupied at war's end. French officials and the Saar's political elite attempted to wrest the territory from Germany and make it an independent nation oriented culturally towards France. Although France's occupation officially ended in 1947 with the ratification of a new constitution and elections, the new Saar state was not fully sovereign, as French control persisted until 1955. The Saar's status was an increasing concern for West Germany, partly due to its implications for the division of Germany. After lengthy negotiations, France and West Germany agreed to turn the Saar into a European territory and the seat of European institutions, much as today's Brussels. Saarlanders, however, saw this as a French ploy to maintain control, and in a heated 1955 referendum voted against it, leading to the territory's reunification with West Germany. This is the first study in English dealing with the German research of recent decades and citing original French and German sources.

Bronson Long is Associate Professor of History at Georgia Highlands College.
APPLYING ECONOMIC MEASURES TO LAPSE RISK MANAGEMENT WITH MACHINE LEARNING APPROACHES
Authors: Loisel Stéphane , Piette Pierrick , Tsai Cheng-Hsien Jason
Published: June 2021

Modeling policyholders’ lapse behaviors is important to a life insurer, since lapses affect pricing, reserving, profitability, liquidity, risk management, and the solvency of the insurer. In this paper, we apply two machine learning methods to lapse modeling. Then, we evaluate the performance of these two methods along with two popular statistical methods by means of statistical accuracy and profitability measure. Moreover, we adopt an innovative point of view on the lapse prediction problem that comes from churn management. We transform the classification problem into a regression question and then perform optimization, which is new to lapse risk management. We apply the aforementioned four methods to a large real-world insurance dataset. The results show that Extreme Gradient Boosting (XGBoost) and support vector machine outperform logistic regression (LR) and classification and regression tree with respect to statistic accuracy, while LR performs as well as XGBoost in terms of retention gains. This highlights the importance of a proper validation metric when comparing different methods. The optimization after the transformation brings out significant and consistent increases in economic gains. Therefore, the insurer should conduct optimization on its economic objective to achieve optimal lapse management.
Predicted Number of Pregnant Women in Aichi Prefecture, Japan: Estimation by Machine Learning Database Construction for Disaster Preparation
Authors: Hattori Kanetoshi , Hattori Ritsuko
Published: June 2021

Aichi prefecture, Japan is predicted to be hit by Mega-earthquake. Aichi Prefectural Association of Midwives has been making efforts to improve disaster preparedness for pregnant women. This project aims to acquire area data of pregnant women for simulated studies of rescue activities. Number of women in census survey areas in Nagoya City was acquired from nationwide data of pregnant women by machine learning (Cascade-Correlation Learning Architecture). Quite high correlation coefficients between actual data and estimation data were observed. Rescue simulations have been carried out based on the data acquired by this study.
On the temporal evolution of turbopause altitude, 1996–2021, 70°N, 19°E
Authors: Hall C. M. , Nozawa S.
Published: June 2021

Medium frequency radars with multiple receivers are able to track the movement of the interference pattern on the ground from echoes from irregularities in refractive index. In particular, refractive index in the mesosphere is determined by electron density – commonly known as the ionospheric D-region. Thus using this technique it is possible to determine winds in the height regime 70-90 km, depending on the degree of ionization throughout the year. In addition, by examining the fading times of the passage of these structures, it is possible to deduce metrics pertaining to neutral air turbulence. Here, we employ a well-established method to this effect. Thereafter, comparing the turbulent intensity to the kinematic viscosity of the neutral atmosphere, we determine the turbopause altitude. Above this height, atmospheric constituents behave independently, whereas below, all components are mixed. Contrary to earlier analyses, we present evidence the turbopause altitude has been constant since approximately 2004.
Is ‘conversion therapy’ tortious?
Authors: Purshouse Craig , Trispiotis Ilias
Published: June 2021

So-called ‘conversion therapy’ involves therapeutic attempts to change an individual's sexual orientation or gender identity. It is widely considered to be harmful to sexual minorities and there have been calls for it to be banned in the UK. In this paper, we examine whether victims of the practice could bring tort claims against ‘therapists’ for mental harm. Focusing on talking therapies, we assess tort doctrine in the law of negligence, the rule in Wilkinson v Downton, the Protection from Harassment Act 1997 and deceit. We conclude that while some forms of conversion therapy will be tortious, others will not and so this area of law may fail to assist many victims of the practice.
Hypothalamic regulation of energy homoeostasis when consuming diets of different energy concentrations: comparison between Tibetan and Small-tailed Han sheep
Authors: Jing Xiaoping , Guo Yamin , Degen Allan , Wang Wenji , Kang Jingpeng , Ding Luming , Shang Zhanhuan , Long Ruijun , Zhou Jianwei
Published: June 2021

Seasonal energy intake of Tibetan sheep on the harsh Qinghai-Tibetan Plateau (QTP) fluctuates greatly and is often well below maintenance requirements. The aim of this study was to gain insight into how the hypothalamus regulates energy homoeostasis in Tibetan sheep. We compared Tibetan and Small-tailed Han sheep (n 24 of each breed), which were each allocated randomly into four groups and offered one of four diets that differed in digestible energy densities: 8·21, 9·33, 10·45 and 11·57 MJ/kg DM. Sheep were weighed every 2 weeks, and it was assumed that the change in body weight (BW) reflected the change in energy balance. The arcuate nucleus of the hypothalamus in Tibetan sheep had greater protein expressions of neuropeptide Y (NPY) and agouti-related peptide (AgRP) when in negative energy balance, but lesser protein expressions of proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) when in positive energy balance than Small-tailed Han sheep. As a result, Tibetan sheep had a lesser BW loss when in negative energy balance and stored more energy and gained more BW when in positive energy balance than Small-tailed Han sheep with the same dietary intake. Moreover, in the hypothalamic adenosine monophosphate-activated protein kinase (AMPK) regulation pathway, Tibetan sheep had greater adenosine monophosphate-activated protein kinase-α 2 protein expression than Small-tailed Han sheep, which supported the premise of a better ability to regulate energy homoeostasis and better growth performance. These differences in the hypothalamic NPY/AgRP, POMC/CART and AMPK pathways between breeds conferred an advantage to the Tibetan over Small-tailed Han sheep to cope with low energy intake on the harsh QTP.
Smooth parameterizations of power-subanalytic sets and compositions of Gevrey functions
Authors: Van Hille Siegfried
Published: June 2021

We show that if $X$ is an $m$-dimensional definable set in $\mathbb {R}_\text {an}^\text{pow}$, the structure of real subanalytic sets with real power maps added, then for any positive integer $r$ there exists a $C^{r}$-parameterization of $X$ consisting of $cr^{m^{3}}$ maps for some constant $c$. Moreover, these maps are real analytic and this bound is uniform for a definable family.
The Last Hump: The Lahore Elementary Flying Training School, the Chinese Civil War, and the final days of the British Raj
Authors: CAO YIN
Published: June 2021

This article centres on the evacuation of the Lahore Elementary Flying Training School, which was built in 1943 to train Chinese pilots and mechanics. It details the British and Chinese authorities’ concerns over the school and how the chaotic situation in India during the final days of the British Raj influenced its evacuation back to China. This article locates the story within the broad context of the British withdrawal from India and the Chinese Civil War, and it uses this case to uncover the links between the two most significant events in the history of modern India and China. In so doing, it puts forward an integrated framework for studying modern Indian and Chinese history.
Nearly modern IPE? Insights from IPE at mid-century
Authors: Germain Randall
Published: June 2021

Disciplinary debates within IPE often leave as an open question how contemporary scholars may build on and incorporate insights from its rich intellectual history. In this article I examine the work of three scholars who are rarely grouped together, but who should be recognised today as engaged in an IPE-inflected debate: Karl Polanyi, E. H. Carr, and David Mitrany. They advanced distinct IPE-centred ways of framing the central problems of the post-1945 world, which are remarkable for how they prefigure important themes in modern IPE scholarship. By assembling and considering their work collectively, I make two arguments: (1) we should recognise their contributions as a precursor to modern IPE; and (2) their work, with certain caveats, provides valuable intellectual resources for contemporary scholars. Their combined work should be considered as part of the common heritage of IPE.
A prenatal diagnosis of unusual aortopulmonary communication: tubular aortopulmonary window
Authors: Babaoğlu Kadir , Başar Eviç Zeynep , Türköz Rıza
Published: June 2021

We described a very rare case of aorto-pulmonary communication with right aortic arch and crossed pulmonary artery that cannot be placed in the typical anatomic classification of aortopulmonary window. At 23 weeks gestation, fetal echocardiography revealed a large tunnel-like communication connecting the great vessels proximal to the main pulmonary artery bifurcation, rather than a classic aortopulmonary window between the ascending aorta and the main pulmonary artery.
Characterising and monitoring preconception health in England: a review of national population-level indicators and core data sources
Authors: Schoenaker Danielle A.J.M. , Stephenson Judith , Connolly Anne , Shillaker Sally , Fishburn Sarah , Barker Mary , Godfrey Keith M. , Alwan Nisreen A. ,   the UK Preconception Partnership
Published: June 2021

Initiatives to optimise preconception health are emerging following growing recognition that this may improve the health and well-being of women and men of reproductive age and optimise health in their children. To inform and evaluate such initiatives, guidance is required on indicators that describe and monitor population-level preconception health. We searched relevant databases and websites (March 2021) to identify national and international preconception guidelines, recommendations and policy reports. These were reviewed to identify preconception indicators. Indicators were aligned with a measure describing the prevalence of the indicator as recorded in national population-based data sources in England. From 22 documents reviewed, we identified 66 indicators across 12 domains. Domains included wider (social/economic) determinants of health; health care; reproductive health and family planning; health behaviours; environmental exposures; cervical screening; immunisation and infections; mental health, physical health; medication and genetic risk. Sixty-five of the 66 indicators were reported in at least one national routine health data set, survey or cohort study. A measure of preconception health assessment and care was not identified in any current national data source. Perspectives from three (healthcare) professionals described how indicator assessment and monitoring may influence patient care and inform awareness campaign development. This review forms the foundation for developing a national surveillance system for preconception health in England. The identified indicators can be assessed using national data sources to determine the population’s preconception needs, improve patient care, inform and evaluate new campaigns and interventions and enhance accountability from responsible agencies to improve preconception health.
Sub‐Ice Platelet Layer Physics: Insights From a Mushy‐Layer Sea Ice Model
Authors: Wongpan P. , Vancoppenolle M. , Langhorne P. J. , Smith I. J. , Madec G. , Gough A. J. , Mahoney A. R. , Haskell T. G.
Published: June 2021

The sub‐ice platelet layer (SIPL) is a highly porous, isothermal, friable layer of ice crystals and saltwater, that can develop to several meters in thickness under consolidated sea ice near Antarctic ice shelves. While the SIPL has been comprehensively described, details of its physics are rather poorly understood. In this contribution we describe the halo‐thermodynamic mechanisms driving the development and stability of the SIPL in mushy‐layer sea ice model simulations, forced by thermal atmospheric and oceanic conditions in McMurdo Sound, Ross Sea, Antarctica. The novelty of these simulations is that they predict a realistic model analogue for the SIPL. Two aspects of the model are essential: (a) a large initial brine fraction is imposed on newly forming ice, and (b) brine rejection via advective desalination. The SIPL appears once conductive heat fluxes become insufficient to remove latent heat required to freeze the highly porous new ice. Favorable conditions for SIPL formation include cold air, supercooled waters, and consolidated ice and snow that are thick enough to provide sufficient thermal insulation. Thermohaline properties resulting from large liquid fractions stabilize the SIPL, in particular a low thermal diffusivity. Intense convection within the isothermal SIPL generates the SIPL‐consolidated ice contrast without transporting heat. Using standard physical constants and free parameters, the model successfully predicts the SIPL and consolidated ice thicknesses at six locations. While most simulations were performed with 50 layers, an SIPL emerged with moderate accuracy in thickness for three layers proving a low‐cost representation of the SIPL in large‐scale climate models.
Bitter receptor TAS2R138 facilitates lipid droplet degradation in neutrophils during Pseudomonas aeruginosa infection
Authors: Pu Qinqin , Guo Kai , Lin Ping , Wang Zhihan , Qin Shugang , Gao Pan , Combs Colin , Khan Nadeem , Xia Zhenwei , Wu Min
Published: June 2021

Bitter receptors function primarily in sensing taste, but may also have other functions, such as detecting pathogenic organisms due to their agile response to foreign objects. The mouse taste receptor type-2 member 138 (TAS2R138) is a member of the G-protein-coupled bitter receptor family, which is not only found in the tongue and nasal cavity, but also widely distributed in other organs, such as the respiratory tract, gut, and lungs. Despite its diverse functions, the role of TAS2R138 in host defense against bacterial infection is largely unknown. Here, we show that TAS2R138 facilitates the degradation of lipid droplets (LDs) in neutrophils during Pseudomonas aeruginosa infection through competitive binding with PPARG (peroxisome proliferator-activated receptor gamma) antagonist: N-(3-oxododecanoyl)-l-homoserine lactone (AHL-12), which coincidently is a virulence-bound signal produced by this bacterium (P. aeruginosa). The released PPARG then migrates from nuclei to the cytoplasm to accelerate the degradation of LDs by binding PLIN2 (perilipin-2). Subsequently, the TAS2R138–AHL-12 complex targets LDs to augment their degradation, and thereby facilitating the clearance of AHL-12 in neutrophils to maintain homeostasis in the local environment. These findings reveal a crucial role for TAS2R138 in neutrophil-mediated host immunity against P. aeruginosa infection.
Ecological significance of extracellular vesicles in modulating host-virus interactions during algal blooms
Authors: Schatz Daniella , Schleyer Guy , Saltvedt Marius R , Sandaa Ruth-Anne , Feldmesser Ester , Vardi Assaf
Published: June 2021

Extracellular vesicles are produced by organisms from all kingdoms and serve a myriad of functions, many of which involve cell-cell signaling, especially during stress conditions and host-pathogen interactions. In the marine environment, communication between microorganisms can shape trophic level interactions and population succession, yet we know very little about the involvement of vesicles in these processes. In a previous study, we showed that vesicles produced during viral infection by the ecologically important model alga Emiliania huxleyi, could act as a pro-viral signal, by expediting infection and enhancing the half-life of the virus in the extracellular milieu. Here, we expand our laboratory findings and show the effect of vesicles on natural populations of E. huxleyi in a mesocosm setting. We profile the small-RNA (sRNA) cargo of vesicles that were produced by E. huxleyi during bloom succession, and show that vesicles applied to natural assemblages expedite viral infection and prolong the half-life of this major mortality agent of E. huxleyi. We subsequently reveal that exposure of the natural assemblage to E. huxleyi-derived vesicles modulates not only host-virus dynamics, but also other components of the microbial food webs, thus emphasizing the importance of extracellular vesicles to microbial interactions in the marine environment.
Smac-mimetic enhances antitumor effect of standard chemotherapy in ovarian cancer models via Caspase 8-independent mechanism
Authors: Hernandez Lidia F. , Dull Angie B. , Korrapati Soumya , Annunziata Christina M.
Published: June 2021

Ovarian cancer is the most lethal gynecological cancer in the US. Standard treatment consists of surgery followed by chemotherapies relying on apoptotic tumor cell death. Most women with advanced stage disease will relapse, suggesting that this disease is characterized by primary and acquired resistance to chemotherapy, and novel approaches to treatment are greatly needed. Low Caspase 8 expression levels in ovarian cancers correlate with resistance to apoptotic chemotherapy, and a subpopulation of patients with low Caspase 8 levels exhibit poorer overall survival after standard-of-care treatment. We hypothesized that low Caspase 8 function reduces the ability of cancer cells to undergo apoptosis when exposed to standard chemotherapy and that second mitochondria-derived activator of caspases (Smac)-mimetics could increase cell death in combination with chemotherapy. Here we show that combination treatment with a Smac-mimetic can target tumor cells with low Caspase 8 and induce necroptotic cell death. We investigated the in vitro effect of Smac-mimetic added to carboplatin and paclitaxel treatment of ovarian cancer cells expressing wild type and low Caspase 8 levels, which resulted in a 2–4-fold enhancement of cell death. Mice bearing subcutaneous or intraperitoneal ovarian xenografts showed greater aggressiveness of Caspase 8-deficient versus wild-type tumors; combined in vivo treatment with chemotherapy and Smac-mimetic resulted in >50% decrease in low Caspase 8 xenograft growth, as well as significantly enhanced overall survival, especially when given simultaneously with paclitaxel. Surprisingly, Smac-mimetic on the same day as carboplatin decreased mouse survival compared to when it was given on a sequential day of treatment. The antagonism was associated with a decrease in DNA damage markers, emphasizing the importance of optimizing timing of drug administration. Clinical validation of such approaches is needed to increase the effectiveness of current standard ovarian cancer treatment.
Robust estimation of SARS-CoV-2 epidemic in US counties
Authors: Li Hanmo , Gu Mengyang
Published: June 2021

The COVID-19 outbreak is asynchronous in US counties. Mitigating the COVID-19 transmission requires not only the state and federal level order of protective measures such as social distancing and testing, but also public awareness of time-dependent risk and reactions at county and community levels. We propose a robust approach to estimate the heterogeneous progression of SARS-CoV-2 at all US counties having no less than 2 COVID-19 associated deaths, and we use the daily probability of contracting (PoC) SARS-CoV-2 for a susceptible individual to quantify the risk of SARS-CoV-2 transmission in a community. We found that shortening by $$5\%$$

5
%

of the infectious period of SARS-CoV-2 can reduce around $$39\%$$

39
%

(or 78 K, $$95\%$$

95
%

CI: [66 K , 89 K ]) of the COVID-19 associated deaths in the US as of 20 September 2020. Our findings also indicate that reducing infection and deaths by a shortened infectious period is more pronounced for areas with the effective reproduction number close to 1, suggesting that testing should be used along with other mitigation measures, such as social distancing and facial mask-wearing, to reduce the transmission rate. Our deliverable includes a dynamic county-level map for local officials to determine optimal policy responses and for the public to better understand the risk of contracting SARS-CoV-2 on each day.
Inhibition of epithelial–mesenchymal transition in retinal pigment epithelial cells by a retinoic acid receptor-α agonist
Authors: Kobayashi Yuka , Tokuda Kazuhiro , Yamashiro Chiemi , Higashijima Fumiaki , Yoshimoto Takuya , Ota Manami , Ogata Tadahiko , Ashimori Atsushige , Hatano Makoto , Kobayashi Masaaki , Uchi Sho-Hei , Wakuta Makiko , Kimura Kazuhiro
Published: June 2021

Epithelial–mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells plays a key role in proliferative retinal diseases such as age-related macular degeneration by contributing to subretinal fibrosis. To investigate the potential role of retinoic acid receptor-α (RAR-α) signaling in this process, we have now examined the effects of the RAR-α agonist Am580 on EMT induced by transforming growth factor-β2 (TGF-β2) in primary mouse RPE cells cultured in a three-dimensional type I collagen gel as well as on subretinal fibrosis in a mouse model. We found that Am580 inhibited TGF-β2-induced collagen gel contraction mediated by RPE cells. It also attenuated the TGF-β2-induced expression of the mesenchymal markers α-smooth muscle actin, fibronectin, and collagen type I; production of pro-matrix metalloproteinase 2 and interleukin-6; expression of the focal adhesion protein paxillin; and phosphorylation of SMAD2 in the cultured RPE cells. Finally, immunofluorescence analysis showed that Am580 suppressed both the TGF-β2-induced translocation of myocardin-related transcription factor-A (MRTF-A) from the cytoplasm to the nucleus of cultured RPE cells as well as subretinal fibrosis triggered by laser-induced photocoagulation in a mouse model. Our observations thus suggest that RAR-α signaling inhibits EMT in RPE cells and might attenuate the development of fibrosis associated with proliferative retinal diseases.
Multi-isotope evidence of population aggregation in the Natufian and scant migration during the early Neolithic of the Southern Levant
Authors: Santana Jonathan , Millard Andrew , Ibáñez-Estevez Juan J. , Bocquentin Fanny , Nowell Geoffrey , Peterkin Joanne , Macpherson Colin , Muñiz Juan , Anton Marie , Alrousan Mohammad , Kafafi Zeidan
Published: June 2021

Human mobility and migration are thought to have played essential roles in the consolidation and expansion of sedentary villages, long-distance exchanges and transmission of ideas and practices during the Neolithic transition of the Near East. Few isotopic studies of human remains dating to this early complex transition offer direct evidence of mobility and migration. The aim of this study is to identify first-generation non-local individuals from Natufian to Pre-Pottery Neolithic C periods to explore the scope of human mobility and migration during the Neolithic transition in the Southern Levant, an area that is central to this historical process. The study adopted a multi-approach resorting to strontium (87Sr/86Sr), oxygen (δ18OVSMOW) and carbon (δ13C) isotope ratio analyses of tooth enamel of 67 human individuals from five sites in Jordan, Syria, and Israel. The isotope ratios point both to a significant level of human migration and/or mobility in the Final Natufian which is compatible with early sedentarism and seasonal mobility and with population aggregation in early sedentary hamlets. The current findings, in turn, offer evidence that most individuals dating to the Pre-Pottery Neolithic were local to their respective settlements despite certain evidence of non-locals. Interestingly, isotopic data suggest that two possible non-local individuals benefitted from particular burial practices. The results underscore a decrease in human mobility and migration as farming became increasingly dominant among the subsistence strategies throughout the Neolithic transition of the Southern Levant.
A spatio-temporal analysis of dengue spread in a Brazilian dry climate region
Authors: Filho Aloísio S. Nascimento , Murari Thiago B. , Ferreira Paulo , Saba Hugo , Moret Marcelo A.
Published: June 2021

We investigated the relation between the spread, time scale, and spatial arrangement of dengue in Bahia, a Brazilian dry climate region, for the period 2000 to 2009. The degree of cross-correlation is calculated for 15 economic regions. We propose a multiscale statistical analysis to datasets of dengue cases in order to verify the effect of infection dispersal on the economic regions from the metropolitan region of Salvador. Our empirical results support a significant and persistent cross-correlation between most regions, reinforcing the idea that economic regions or climatic conditions are non-statistically significant in the spread of dengue in the State of Bahia. Our main contribution lies in the cross-correlation results revealing multiple aspects related to the propagation of dengue in dry climate regions.
Slight reduction in SARS-CoV-2 exposure viral load due to masking results in a significant reduction in transmission with widespread implementation
Authors: Goyal Ashish , Reeves Daniel B. , Thakkar Niket , Famulare Mike , Cardozo-Ojeda E. Fabián , Mayer Bryan T. , Schiffer Joshua T.
Published: June 2021

Masks are a vital tool for limiting SARS-CoV-2 spread in the population. Here we utilize a mathematical model to assess the impact of masking on transmission within individual transmission pairs and at the population level. Our model quantitatively links mask efficacy to reductions in viral load and subsequent transmission risk. Our results reinforce that the use of masks by both a potential transmitter and exposed person substantially reduces the probability of successful transmission, even if masks only lower exposure viral load by ~ 50%. Slight increases in mask adherence and/or efficacy above current levels would reduce the effective reproductive number (Re) substantially below 1, particularly if implemented comprehensively in potential super-spreader environments. Our model predicts that moderately efficacious masks will also lower exposure viral load tenfold among people who get infected despite masking, potentially limiting infection severity. Because peak viral load tends to occur pre-symptomatically, we also identify that antiviral therapy targeting symptomatic individuals is unlikely to impact transmission risk. Instead, antiviral therapy would only lower Re if dosed as post-exposure prophylaxis and if given to ~ 50% of newly infected people within 3 days of an exposure. These results highlight the primacy of masking relative to other biomedical interventions under consideration for limiting the extent of the COVID-19 pandemic prior to widespread implementation of a vaccine. To confirm this prediction, we used a regression model of King County, Washington data and simulated the counterfactual scenario without mask wearing to estimate that in the absence of additional interventions, mask wearing decreased Re from 1.3–1.5 to ~ 1.0 between June and September 2020.
Meta-QTL analysis and identification of candidate genes for quality, abiotic and biotic stress in durum wheat
Authors: Soriano Jose Miguel , Colasuonno Pasqualina , Marcotuli Ilaria , Gadaleta Agata
Published: June 2021

The genetic improvement of durum wheat and enhancement of plant performance often depend on the identification of stable quantitative trait loci (QTL) and closely linked molecular markers. This is essential for better understanding the genetic basis of important agronomic traits and identifying an effective method for improving selection efficiency in breeding programmes. Meta-QTL analysis is a useful approach for dissecting the genetic basis of complex traits, providing broader allelic coverage and higher mapping resolution for the identification of putative molecular markers to be used in marker-assisted selection. In the present study, extensive QTL meta-analysis was conducted on 45 traits of durum wheat, including quality and biotic and abiotic stress-related traits. A total of 368 QTL distributed on all 14 chromosomes of genomes A and B were projected: 171 corresponded to quality-related traits, 127 to abiotic stress and 71 to biotic stress, of which 318 were grouped in 85 meta-QTL (MQTL), 24 remained as single QTL and 26 were not assigned to any MQTL. The number of MQTL per chromosome ranged from 4 in chromosomes 1A and 6A to 9 in chromosome 7B; chromosomes 3A and 7A showed the highest number of individual QTL (4), and chromosome 7B the highest number of undefined QTL (4). The recently published genome sequence of durum wheat was used to search for candidate genes within the MQTL peaks. This work will facilitate cloning and pyramiding of QTL to develop new cultivars with specific quantitative traits and speed up breeding programs.
Country distancing increase reveals the effectiveness of travel restrictions in stopping COVID-19 transmission
Authors: Zhong Lu , Diagne Mamadou , Wang Weiping , Gao Jianxi
Published: June 2021

Despite a number of successful approaches in predicting the spatiotemporal patterns of the novel coronavirus (COVID-19) pandemic and quantifying the effectiveness of non-pharmaceutical interventions starting from data about the initial outbreak location, we lack an intrinsic understanding as outbreak locations shift and evolve. Here, we fill this gap by developing a country distance approach to capture the pandemic’s propagation backbone tree from a complex airline network with multiple and evolving outbreak locations. We apply this approach, which is analogous to the effective resistance in series and parallel circuits, to examine countries’ closeness regarding disease spreading and evaluate the effectiveness of travel restrictions on delaying infections. In particular, we find that 63.2% of travel restrictions implemented as of 1 June 2020 are ineffective. The remaining percentage postponed the disease arrival time by 18.56 days per geographical area and resulted in a total reduction of 13,186,045 infected cases. Our approach enables us to design optimized and coordinated travel restrictions to extend the delay in arrival time and further reduce more infected cases while preserving air travel.
Interfacing non-enzymatic catalysis with living microorganisms
Authors: Sadler Joanna C. , Dennis Jonathan A. , Johnson Nick W. , Wallace Stephen
Published: June 2021

This review highlights recent advances in the field of biocompatible chemistry. It focusses on the combined use of non-enzymatic catalysis and microbial metabolism to support cellular function and to synthesise high value chemicals.
Dual mechanoluminescence system comprising a solid-state di-copper(i) complex containing N-heterocyclic carbene ligands
Authors: Ogawa Shigesaburo , Katsuragi Haruka , Ikeda Tsukasa , Oshima Kazumasa , Satokawa Shigeo , Yamazaki Yasuomi , Tsubomura Taro
Published: June 2021

Multi-chromic luminescence in a di-copper(i) complex containing NHC ligands, which exhibited dual tribochromism and chronochromism, was observed.
A review on metal–organic framework-derived anode materials for potassium-ion batteries
Authors: Xie Qiongyi , Ou Hong , Yang Qingyun , Lin Xiaoming , Zeb Akif , Li Kang , Chen Xinli , Ma Guozheng
Published: June 2021

Research progress of MOF-derived anode materials for potassium ion batteries has been presented based on different organic ligands.
Bis(imino)carbazolate lead(ii) fluoride and related halides
Authors: Chapple Peter M. , Hamdoun Ghanem , Roisnel Thierry , Carpentier Jean-François , Oulyadi Hassan , Sarazin Yann
Published: June 2021

A soluble lead(ii) fluoride and homologous halide, amide and hydrocarbyl complexes have been characterised by X-ray diffraction and 207Pb NMR spectroscopy.
Polymer-coated TiO2 nanoparticles bioaccumulate, immunoactivate and suppress pathogenic Mycobacterium chelonae clearance when intravenously injected into goldfish (Carassius auratus L.)
Authors: Ortega Van A. , Boyle David , Hodgkinson Jordan W. , Simmons Denina B. D. , Belosevic Miodrag , Stafford James L. , Goss Greg G.
Published: June 2021

We examined goldfish immunotoxicological responses to intravenously injected PAA-TiO2 NPs by determining organ accumulation, depuration, tissue damage, and immune responsiveness in the kidneys, spleen, and isolated primary kidney neutrophils.
Apple consumption reduces markers of postprandial inflammation following a high fat meal in overweight and obese adults: A randomized, crossover trial
Authors: Liddle Danyelle M. , Lin Xinjie , Ward Emily M. , Cox Liam C. , Wright Amanda J. , Robinson Lindsay E.
Published: June 2021

Whole apples in combination with a high fat meal mitigated plasma and peripheral blood mononuclear cell markers of postprandial inflammation in individuals with overweight and obesity.
Pancreatic lipase inhibitory activity of Bambusa multiplex cv. Fernleaf leaf extract in vitro and in vivo
Authors: Li Ying , Chen Bo , Cao Hai-Yan , Li Jing-En , Chen Ling-Li , Zhang Qing-Feng
Published: June 2021

Bambusa multiplex cv Fernleaf (B. multiplex) is a species of bamboo.
The medicinal chemistry of mitochondrial dysfunction: a critical overview of efforts to modulate mitochondrial health
Authors: Lee Maximillian Taro William , Mahy William , Rackham Mark David
Published: June 2021

This manuscript reviews the compounds historically used to modulate mitochondria, and offers a perspective on which targets have been convincingly (in)validated with high quality chemical matter and those which remain untested.
Transition-metal-free nucleophilic 211At-astatination of spirocyclic aryliodonium ylides
Authors: Matsuoka Keitaro , Obata Honoka , Nagatsu Kotaro , Kojima Masahiro , Yoshino Tatsuhiko , Ogawa Mikako , Matsunaga Shigeki
Published: June 2021

The transition-metal-free nucleophilic 211At-astatination of aryliodonium ylides, involving those derived from multi-functionalized molecules and heteroarenes, proceeded with good to excellent radiochemical yields.
Ag–Cu copromoted direct C2–H bond thiolation of azoles with Bunte salts as sulfur sources
Authors: Wang Rui , Xu Hongyan , Zhang Ying , Hu Yuntao , Wei Yingsu , Du Xiao , Zhao Huaiqing
Published: June 2021

A direct C2–H thiolation of azoles with Bunte salts was achieved under the combined action of copper and silver salts, furnishing various substituted 2-thioazoles in moderate to good yields.
Two novel oxetane containing lignans and a new megastigmane from Paronychia arabica and in silico analysis of them as prospective SARS-CoV-2 inhibitors
Authors: Elshamy Abdelsamed I. , Mohamed Tarik A. , Ibrahim Mahmoud A. A. , Atia Mohamed A. M. , Yoneyama Tatsuro , Umeyama Akemi , Hegazy Mohamed-Elamir F.
Published: June 2021

The hydromethanolic extract of Paronychia arabica aerial parts afforded two oxetane containing lignans, paronychiarabicine A (1) and B (2), and one new megastigmane, paronychiarabicastigmane A (3), alongside a known secondary metabolites (4–14).
Probing the effect of straight chain fatty acids on the properties of lead-containing plexiglass
Authors: Zhang Yujuan , Wang Chunhong , Wu Defeng , Guo Xintao , Yu Lei , Zhang Ming
Published: June 2021

By adding saturated straight chain fatty acids into the reaction system of Pb(MAA)2 with MMA, the prepared lead-containing plexiglass possessed excellent optical properties. It may provide key techniques for fabricating γ-ray shielding plexiglasses.