bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the anti-hyperglycemic and antioxidant effects of wheat bread supplemented with onion peel extract and onion powder in diabetic rats
Authors: Masood Sara , Rehman Attiq ur , Bashir Shahid , El Shazly Mohamed , Imran Muhammad , Khalil Palwasha , Ifthikar Faiza , Jaffar Hafiza Madiha , Khursheed Tara
Published: March 2021

Aim

Onion is one of the commonly cultivated and consumed vegetables rich in nutrients and phytochemicals. Various nutraceuticals are found in the outer fleshy layers and dry peel of onion which usually is treated as a common biowaste. Diabetes mellitus is a leading non communicable disease causing hyperglycemia and increased production of free radicals that potentially disrupts antioxidant enzymatic activity. Considering global consumption of wheat, the present study was designed to evaluate the anti-hyperglycemic and antioxidant effects of wheat bread supplemented with onion peel extract (OPE) or onion powder (OP) on diabetic rats.

Methods

In this study, ethanolic extract of onion peel and onion bulb were prepared separately. Male Sprague Dawley rats were divided into 6 groups (n = 7). Different regimens of supplemented wheat bread (OPE (1% and 3%) and OP (5% and 7%)) were given to diabetic rats for eight weeks, plain bread was used as the control. Blood glucose level, body weight and activities of SOD, CAT, GPx, GR, GSH and MDA in the liver and kidney tissues were evaluated. Statistical analysis was performed using SPSS Version (25) and Dunnett’s multiple comparison test.

Results

Bread supplemented with 1% and 3% onion peel extract and 7% onion powder significantly reduced blood glucose levels and MDA in the treated rats compared with the control group diabetic rats. Body weight of diabetic rats was reduced for control group, while onion supplemented diet improved the body weight of treated rats. Onion supplementation also brought significant improvement in antioxidant enzyme activities among the treated diabetic rats.

Conclusion

These findings suggested that onion supplementation is effective in lowering blood glucose and could potentially aid in protecting organs from oxidative stress.
Pregnancy outcomes in women with immunoglobulin A nephropathy: a nationwide population-based cohort study
Authors: Jarrick Simon , Lundberg Sigrid , Stephansson Olof , Symreng Adina , Bottai Matteo , Höijer Jonas , Ludvigsson Jonas F.
Published: March 2021

Background

Immunoglobulin A nephropathy (IgAN) incidence peaks in childbearing age. Data on pregnancy outcomes in women with IgAN are limited.

Methods

We performed a register-based cohort study in a nationwide cohort of women with biopsy-verified IgAN in Sweden, comparing 327 pregnancies in 208 women with biopsy-verified IgAN and 1060 pregnancies in a matched reference population of 622 women without IgAN, with secondary comparisons with sisters to IgAN women. Adverse pregnancy outcomes, identified by way of the Swedish Medical Birth Register, were compared through multivariable logistic regression and presented as adjusted odds ratios (aORs). Main outcome was preterm birth (< 37 weeks). Secondary outcomes were preeclampsia, small for gestational age (SGA), low 5-min Apgar score (< 7), fetal or infant loss, cesarean section, and gestational diabetes.

Results

We found that IgAN was associated with an increased risk of preterm birth (13.1% vs 5.6%; aOR = 2.69; 95% confidence interval [CI] = 1.52–4.77), preeclampsia (13.8% vs 4.2%; aOR = 4.29; 95%CI = 2.42–7.62), SGA birth (16.0% vs 11.1%; aOR = 1.84; 95%CI = 1.17–2.88), and cesarean section (23.9% vs 16.2%; aOR = 1.74, 95%CI = 1.14–2.65). Absolute risks were low for intrauterine (0.6%) or neonatal (0%) death and for low 5-min Apgar score (1.5%), and did not differ from the reference population. Sibling comparisons suggested increased risks of preterm birth, preeclampsia, and SGA in IgAN, but not of cesarean section.

Conclusion

We conclude that although most women with IgAN will have a favorable pregnancy outcome, they are at higher risk of preterm birth, preeclampsia and SGA. Intensified supervision during pregnancy is warranted.
Highly Concentrated, Conductive, Defect-free Graphene Ink for Screen-Printed Sensor Application
Authors: Kim Dong Seok , Jeong Jae-Min , Park Hong Jun , Kim Yeong Kyun , Lee Kyoung G. , Choi Bong Gill
Published: March 2021

Highlights

Ultrathin and defect-free graphene ink is prepared through a high-throughput fluid dynamics process, resulting in a high exfoliation yield (53.5%) and a high concentration (47.5 mg mL−1).

A screen-printed graphene conductor exhibits a high electrical conductivity of 1.49 × 104 S m−1 and good mechanical flexibility.

An electrochemical sodium ion sensor based on graphene ink exhibits an excellent potentiometric sensing performance in a mechanically bent state.

Real-time monitoring of sodium ion concentration in sweat is demonstrated.

Conductive inks based on graphene materials have received significant attention for the fabrication of a wide range of printed and flexible devices. However, the application of graphene fillers is limited by their restricted mass production and the low concentration of their suspensions. In this study, a highly concentrated and conductive ink based on defect-free graphene was developed by a scalable fluid dynamics process. A high shear exfoliation and mixing process enabled the production of graphene at a high concentration of 47.5 mg mL−1 for graphene ink. The screen-printed graphene conductor exhibits a high electrical conductivity of 1.49 × 104 S m−1 and maintains high conductivity under mechanical bending, compressing, and fatigue tests. Based on the as-prepared graphene ink, a printed electrochemical sodium ion (Na+) sensor that shows high potentiometric sensing performance was fabricated. Further, by integrating a wireless electronic module, a prototype Na+-sensing watch is demonstrated for the real-time monitoring of the sodium ion concentration in human sweat during the indoor exercise of a volunteer. The scalable and efficient procedure for the preparation of graphene ink presented in this work is very promising for the low-cost, reproducible, and large-scale printing of flexible and wearable electronic devices.
Correction to: Investigating friction spin welding of thermoplastics in shear joint configuration
Authors: Bindal Tarun , Saxena Ravindra K. , Pandey Sunil
Published: March 2021

Figure parts d and f were incorrectly labelled in Fig. 2 in the initial online publication. The original article has been corrected.
Active fault segments along the North Anatolian Fault system in the Sea of Marmara: implication for seismic hazard
Authors: Gasperini Luca , Stucchi Massimiliano , Cedro Vincenzo , Meghraoui Mustapha , Ucarkus Gulsen , Polonia Alina
Published: March 2021

A new analysis of high-resolution multibeam and seismic reflection data, collected during several oceanographic expeditions starting from 1999, allowed us to compile an updated morphotectonic map of the North Anatolian Fault below the Sea of Marmara. We reconstructed kinematics and geometries of individual fault segments, active at the time scale of 10 ka, an interval which includes several earthquake cycles, taking as stratigraphic marker the base of the latest marine transgression. Given the high deformation rates relative to sediment supply, most active tectonic structures have a morphological expression at the seafloor, even in presence of composite fault geometries and/or overprinting due to mass-wasting or turbidite deposits. In the frame of the right-lateral strike-slip domain characterizing the North Anatolian fault system, three types of deformation are observed: almost pure strike-slip faults, oriented mainly E–W; NE/SW-aligned axes of transpressive structures; NW/SE-oriented trans-tensional depressions. Fault segmentation occurs at different scales, but main segments develop along three major right-lateral oversteps, which delimit main fault branches, from east to west: (i) the transtensive Cinarcik segment; (ii) the Central (East and West) segments; and (iii) the westernmost Tekirdag segment. A quantitative morphometric analysis of the shallow deformation patterns observed by seafloor morphology maps and high-resolution seismic reflection profiles along the entire basin allowed to determine nature and cumulative lengths of individual fault segments. These data were used as inputs for empirical relationships, to estimate maximum expected Moment Magnitudes, obtaining values in the range of 6.8–7.4 for the Central, and 6.9–7.1 for the Cinarcik and Tekirdag segments, respectively. We discuss these findings considering analyses of historical catalogues and available paleoseismological studies for the Sea of Marmara region to formulate reliable seismic hazard scenarios.
The Israel-Palestine Conflict
Authors: Gelvin James L.
Published: March 2021

Now in its fourth edition, James L. Gelvin's award-winning account of the conflict between Israel and Palestine offers a compelling, accessible and current introduction for students and general readers. The book traces the struggle from the emergence of nationalism among the Jews of Europe and the Arab inhabitants of Ottoman Palestine through to the present, exploring the external pressures and internal logic that have propelled it. Placing events in Palestine within the framework of global history, The Israel-Palestine Conflict: A History skilfully interweaves biographical sketches, eyewitness accounts, poetry, fiction, and official documentation into its narrative. This updated edition features new material on the fate of the two-state solution during the Trump/Netanyahu era, alongside an expanded glossary and suggestions for further reading.
A Life Lived Across Continents: The Global Microhistory of an Armenian Agent of the Compagnie des Indes Orientales, 1666–1688
Authors: Aslanian Sebouh David
Published: March 2021

In 1666, French finance minister Jean-Baptiste Colbert hired Martin di Marcara Avachinz, an Armenian merchant who had lived in Iran and India, as an agent for his newly established Compagnie des Indes orientales. In 1669, shortly after the Armenian had secured a royal edict from the sultan Of Golconda to set up a French trading center in the port of Masulipatam, he was summarily arrested, tortured, and sent to France by his superior François Caron. This article provides a close reading of the legal briefs or factums produced during the sensational trial that followed Marcara’s release from prison in 1675. In tracing a “global microhistory” of his life across continents, it seeks to contribute to a deeper understanding of early modern long-distance trade in the Indian Ocean, comparing the network of the CIO and other joint-stock corporations with the “stateless” nature of the trade diaspora of Armenian merchants from the township of New Julfa on the outskirts of the Safavid capital Isfahan. Finally, the article considers the role of factums in early modern France and explores how the “exceptionally normal” story of Marcara’s life provides a useful window onto French perceptions of the Orient and the fear induced by communities such as Armenian and Indian merchants, bankers, and brokers.
Integration of sociocultural and behavioral factors into the clinical framework of cardiovascular studies in Hispanic/Latino populations: Relevance during the SARS-COV-2 pandemic
Authors: Suglia Shakira F. , Abraido-Lanza Ana F. , Guerrero-Preston Rafael E. , Ramos Kenneth S.
Published: March 2021

Recent reports on the burden of cardiovascular disease (CVD) in the USA indicate that despite significant declines in CVD mortality in the late 20th century, this decline is now decelerating and may be worsened by inequalities in health care. Social factors contribute to most of the cardiovascular health disparities documented to date. Hispanics/Latinos and African-Americans share a higher prevalence of cardiovascular risk factors and experience higher rates of poverty and social stressors than non-Hispanic Whites. We propose that the use of social and behavioral data beyond basic and sometimes loose identifiers of race/ethnicity, educational attainment, and occupation would inform clinical practice and greatly facilitate the provision of adequate guidance and support to patients regarding continuity of care, adherence to medications and treatment plans, and engagement of participants in future research. This perspective briefly highlights factors deemed to be critical for the advancement of Hispanic/Latino health and delineates pathways toward future applications.
Divestiture and Its Market Reaction in a Consolidating Industry: The Global Brewing Industry
Authors: Erl Ludwig , Kiesel Florian
Published: March 2021

This study provides a perspective on the market performance of divestitures in the global brewing industry. In 2018, the five largest players accounted for 60% of the global beer volume. We analyze to what extent the capital market values divestitures in an industry where players usually seek efficiency gains and growth through mergers and acquisitions. Based on a sample of 61 divestiture intent announcements in the period from 1999–2018, this study shows that publicly listed brewing groups experience significant positive abnormal returns of about 1.4%. We measure the influential effect of success determinants concerning the underlying industry, the divested business, the divestiture structure, and the divestor itself. (JEL Classifications: G14, G34, L25, Q14)
The Political Economy of Governance Quality
Authors: TING MICHAEL M.
Published: March 2021

This paper develops a dynamic theory of the social and political foundations of governance quality. In the model, groups of citizens have different expected needs for a public service, and citizens choose whether to demand service when the need arises. Politicians representing these groups can determine policy benefits and delegate to bureaucrats the ability to invest in long-run service quality. The main feature of the theory is its foundation for citizen–government interactions, which draws from well-known queueing models of organizational service provision. The model provides a framework for characterizing the effectiveness and durability of government programs. A main implication is that politicized bureaucracies improve program survivability and increase the frequency of investment, while insulated bureaucracies increase the intensity of investment; overall service quality trades off between these two factors. Other results examine the implications of cross-group inequality, electoral conditions, and decentralization.
Challenges to the Liberal Order: Reflections onInternational Organization
Authors: Lake David A. , Martin Lisa L. , Risse Thomas
Published: March 2021

AsInternational Organizationcommemorates its seventy-fifth anniversary, the Liberal International Order (LIO) that authors in this journal have long analyzed is under challenge, perhaps as never before. The articles in this issue explore the nature of these challenges by examining how the Westphalian order and the LIO have co-constituted one another over time; how both political and economic dynamics internal to the LIO threaten its core aspects; and how external threats combine with these internal dynamics to render the LIO more fragile than ever before. This introduction begins by defining and clarifying what is “liberal,” “international,” and “orderly” about the LIO. It then discusses some central challenges to the LIO, illustrated by the contributors to this issue as well as other sources. Finally, we reflect on the analytical lessons we have learned—or should learn—as the study of the LIO, represented by scholarship inInternational Organization, has sometimes overlooked or marginalized dynamics that now appear central to the functioning, and dysfunction, of the order itself.
Variation and determinants of early initiation of breastfeeding in high and low neonatal mortality settings in India
Authors: Yadav Jeetendra , Shekhar Chander , Bharati Kusum
Published: March 2021

Early initiation of breastfeeding (EIBF) is considered one of the most cost-effective interventions for infant survival and well-being. This study aimed to examine the variations in, and determinants of, early initiation of breastfeeding among women in high and low neonatal mortality rate (NMR) settings in India using data from the fourth round of the National Family Health Survey conducted in 2015–16. At 35%, EIBF was found to be disproportionately low in the high NMR group of states compared with 52% in the low NMR group, with the national average being 44%. The chance of EIBF significantly increased if childbirth was vaginal, delivery took place in a health institution, the mother received breastfeeding advice and the birth was a planned one in both high and low NMR settings. In the high NMR group of states, the probability of initiating breastfeeding immediately after birth improved to a great extent if childbirth was assisted by a trained person and if the mother was exposed to any type of mass media. There is an urgent need to increase the access of mothers to breastfeeding advice during pregnancy and to increase their exposure to mass media, particularly in high NMR states. In addition, achieving universal access to institutional deliveries and deliveries assisted by a skilled birth attendant, especially in high NMR settings, and promoting early breastfeeding, especially in the case of Caesarean deliveries, would further improve the level of EIBF in the country as a whole. These interventions can potentially increase the prevalence of early initiation of breastfeeding and help India attain the neonatal mortality rate target of Sustainable Development Goal 3.
Evaluation of the Baermann–Wetzel method for detecting lungworm larvae in wild ruminants from faecal samples
Authors: Carrau T. , Martínez-Carrasco C. , Garijo M.M. , Alonso F. , Ruiz de Ybáñez R. , Tizzani P.
Published: March 2021

Lungworms can exert a negative impact on wild ruminant fitness; for this reason, the diagnosis of the associated diseases is an important prevention measure. The Baerman–Wetzel technique is the most usual method for the diagnosis of bronchopulmonary nematodes and is based on the active migration and movement of their first-stage larvae. Pulmonary tissue samples are frequently used for the post-mortem diagnosis of these parasites, but this kind of sample is not always available and easy to obtain. Faecal samples represent a more accessible choice for parasite monitoring. This work aimed to evaluate the agreement between the results obtained by the Baermann–Wetzel technique when samples of lung parenchyma or faeces from wild ruminants are used. A good level of agreement as well as a similar sensitivity between the two types of sample were observed, validating the use of faecal samples as a less invasive and cost-effective alternative for the monitoring of lungworm in wild ruminant populations.
Beta and phylogenetic diversities tell complementary stories about ecological networks biogeography
Authors: Higino Gracielle T. , Poisot Timothée
Published: March 2021

The beta-diversity of interactions between communities does not necessarily correspond to the differences related to their species composition because interactions show greater variability than species co-occurrence. Additionally, the structure of species interaction networks can itself vary over spatial gradients, thereby adding constraints on the dissimilarity of communities in space. We used published data on the parasitism interaction between fleas and small mammals in 51 regions of the Palearctic to investigate how beta-diversity of networks and phylogenetic diversity are related. The networks could be separated in groups based on the metrics that best described the differences between them, and these groups were also geographically structured. We also found that each network beta-diversity index relates in a particular way with phylogenetically community dissimilarity, reinforcing that some of these indexes have a strong phylogenetic component. Our results clarify important aspects of the biogeography of hosts and parasites communities in Eurasia, while suggesting that networks beta-diversity and phylogenetic dissimilarity interact with the environment in different ways.
Does grandparental child-care provision affect number, satisfaction and with whom leisure activities are done?
Authors: Ates Merih , Bordone Valeria , Arpino Bruno
Published: March 2021

This study investigates the impact of non-intensive and intensive supplementary grandparental child care on grandparents’ involvement in leisure activities. Three aspects of leisure activities are investigated: the number/frequency of activities, with whom they are carried out and the subjective satisfaction with them. Beside the possibility of a cumulation effect, the literature suggests that providing grandparental child care might compete with other activities, especially for women. Thus, we consider role enhancement and role strain theories to derive our hypotheses. We use longitudinal data from the German Ageing Survey (DEAS) which contains rich information on the leisure activities of people aged 40 and older. To account for selection into the provision of grandparental child care, we use a within-unit estimation approach (fixed-effects panel models). Our results show that both grandfathers and grandmothers tend to engage in more leisure activities when they provide grandparental child care. While care-giving grandfathers become more likely to engage in activities with family members without changing their engagement outside the family, we found no effect for women in this respect. Nevertheless, grandparental child-care provision modifies satisfaction with leisure activities only for women, reducing it, independently from with whom leisure activities are carried out. These findings suggest that a higher quantity of leisure activities does not necessarily imply higher quality.
Re-conceptualizing the role(s) of science in biodiversity conservation
Authors: Evans Megan C
Published: March 2021

Science, as both a body of knowledge and a process of acquiring new knowledge, is widely regarded as playing a central role in biodiversity conservation. Science undoubtedly enhances our understanding of the drivers of biodiversity loss and assists in the formulation of practical and policy responses, but it has not yet proved sufficiently influential to reverse global trends of biodiversity decline. This review seeks to critically examine the science of biodiversity conservation and to identify any hidden assumptions that, once interrogated and explored, may assist in improving conservation science, policy and practice. By drawing on existing reviews of the literature, this review describes the major themes of the literature and examines the historical shifts in the framing of conservation. It highlights the dominance of research philosophies that view conservation through a primarily ecological lens, changes in the goal(s) of conservation and a lack of clarity over the role(s) of science in biodiversity conservation. Finally, this review offers a simple framework to more clearly and consistently conceptualize the role(s) of science in biodiversity conservation in the future. Greater critical reflection on how conservation science might better accommodate multiple knowledges, goals and values could assist in ‘opening up’ new, legitimate pathways for biodiversity conservation.
Off-pump direct hepatic veins-to-hemiazygos vein anastomosis after primary Kawashima operation: long-term result
Authors: Kaulitz Renate , Ziemer Gerhard , Hofbeck Michael
Published: March 2021

Direct hepatic veins-to-hemiazygos connection offers the balanced distribution of hepatic venous blood to both lungs, not requiring anticoagulation. We report a 13-year follow-up after this type of off-pump Fontan completion. Patient’s hepatic veins-to-hemiazygos confluence increased with growth to allow for unobstructed flow. This unique technique can be recommended in heterotaxy patients, if atrial hepatic venous drainage and hemiazygos vein are in close proximity.
Bovine respiratory disease treatment failure: definition and impact
Authors: Booker Calvin W.
Published: March 2021

Bovine respiratory disease (BRD) treatment failure occurs when animals receiving a treatment regimen for BRD fail to directly return to health, resulting in chronic illness and a requirement for repeated treatments, sale for salvage slaughter, euthanasia or death. BRD treatment failure has both direct and indirect impacts. Direct impacts include costs to manage chronically ill animals, including those associated with BRD relapse treatment; reduced returns from animals sent for salvage slaughter, loss of the initial investment to purchase the animal and feed and other accumulated expenses to death, and costs associated with carcass disposal. Indirect impacts include costs of infrastructure requirements, and negative effects on animal welfare and employee morale.
Improving resistance of cattle to BRD through genomics
Authors: Parker Gaddis Kristen L.
Published: March 2021

Bovine respiratory disease (BRD) is of considerable economic importance to the dairy industry, specifically among young animals. Several studies have demonstrated that BRD has a significant genetic component, with heritabilities ranging from 0.04 up to 0.22, which could be utilized to select more resistant animals. Taking advantage of available genomic data will allow more accurate genetic predictions to be made earlier in an animal's life. The availability of genomic data does not negate the necessity of quality phenotypes, in this case, records of BRD incidence. Evidence has shown that genetic selection is possible through the use of producer-recorded health information. The national dairy cooperator database currently has minimal records on respiratory problems. There is an existing pipeline for these data to flow from events recorded by producers on the farm to the national database used for genetic evaluation. Additional data could also be collected through the expansion of currently utilized termination codes and used in conjunction with the records of direct health events. Selection for animals with improved BRD resistance is possible at the national level; however, collection of additional phenotypes remains a significant hurdle.
Genes, Ideology, and Sophistication
Authors: Kalmoe Nathan P. , Johnson Martin
Published: March 2021

Twin studies function as natural experiments that reveal political ideology’s substantial genetic roots, but how does that comport with research showing a largely nonideological public? This study integrates two important literatures and tests whether political sophistication – itself heritable – provides an “enriched environment” for genetic predispositions to actualize in political attitudes. Estimates from the Minnesota Twin Study show that sociopolitical conservatism is extraordinarily heritable (74%) for the most informed fifth of the public – much more so than population-level results (57%) – but with much lower heritability (29%) for the public’s bottom half. This heterogeneity is clearest in the Wilson–Patterson (W-P) index, with similar patterns for individual index items, an ideological constraint measure, and ideological identification. The results resolve tensions between two key fields by showing that political knowledge facilitates the expression of genetic predispositions in mass politics.
Lithospheric Structure and Flat‐Slab Subduction in the Northern Appalachians: Evidence From Rayleigh Wave Tomography
Authors: Bagherpur Mojaver Omid , Darbyshire Fiona , Dave Riddhi
Published: March 2021

A billion years of tectonic history makes southeastern Canada and the northeastern United States an exciting area to investigate the evolution of continental lithosphere. Our study area comprises terranes with either Laurentian or Gondwanan provenance that accreted to eastern North America at different times. With the aim of resolving the isotropic velocity variations across the northern Phanerozoic Appalachians and the southeastern Proterozoic Grenville Province, we adopted a Rayleigh wave tomography technique that takes multipathing, scattering, and finite frequency effects into account. Our data sets include records of teleseismic earthquakes recorded by 71 broadband seismic stations over a 2‐year period. Our high‐resolution tomography models indicate significant (±3.5%) variations in shear wave velocity across different lithospheric domains, enabling us to discuss tectonic implications. In contrast to the Peri‐Laurentian zones, seismic signatures in the Peri‐Gondwanan domains are more complex and variable. Although systematic variations of seismic velocities across different tectonic zones are observed, we find no simple relation between the lithospheric thicknesses of different tectonic zones and their age. We interpret the lithosphere‐asthenosphere boundary in our study area, located at 70–120 km depth, with the thickest and fastest lithosphere beneath New Brunswick. We suggest that this relatively thicker lithosphere is due to a slab stacking process that occurred after flat subduction of a younger domain in the Late Silurian. Occurrence of flat subduction in the Late Silurian in the northern Appalachians is also supported by geochemical and paleomagnetic evidence.
Molecular biology of Hodgkin lymphoma
Authors: Weniger Marc A. , Küppers Ralf
Published: March 2021

Classical Hodgkin lymphoma (cHL) is unique among lymphoid malignancies in several key biological features. (i) The Hodgkin and Reed-Sternberg (HRS) tumor cells are rare among an extensive and complex microenvironment. (ii) They derive from B cells, but have largely lost the B-cell typical gene expression program. (iii) Their specific origin appears to be pre-apoptotic germinal center (GC) B cells. (iv) They consistently develop bi- or multinucleated Reed-Sternberg cells from mononuclear Hodgkin cells. (v) They show constitutive activation of numerous signaling pathways. Recent studies have begun to uncover the basis of these specific features of cHL: HRS cells actively orchestrate their complex microenvironment and attract many distinct subsets of immune cells into the affected tissues, to support their survival and proliferation, and to create an immunosuppressive environment. Reed-Sternberg cells are generated by incomplete cytokinesis and refusion of Hodgkin cells. Epstein-Barr virus (EBV) plays a major role in the rescue of crippled GC B cells from apoptosis and hence is a main player in early steps of lymphomagenesis of EBV+cHL cases. The analysis of the landscape of genetic lesions in HRS cells so far did not reveal any highly recurrent HRS cell-specific lesions, but major roles of genetic lesions in members of the NF-κB and JAK/STAT pathways and of factors of immune evasion. It is perhaps the combination of the genetic lesions and the peculiar cellular origin of HRS cells that are disease defining. A combination of such genetic lesions and multiple cellular interactions with cells in the microenvironment causes the constitutive activation of many signaling pathways, often interacting in complex fashions. In nodular lymphocyte predominant Hodgkin lymphoma, the GC B cell-derived tumor cells have largely retained their typical GC B-cell expression program and follicular microenvironment. For IgD-positive cases, bacterial antigen triggering has recently been implicated in early stages of its pathogenesis.
Creation and control of high-dimensional multi-partite classically entangled light
Authors: Shen Yijie , Nape Isaac , Yang Xilin , Fu Xing , Gong Mali , Naidoo Darryl , Forbes Andrew
Published: March 2021

Vector beams, non-separable in spatial mode and polarisation, have emerged as enabling tools in many diverse applications, from communication to imaging. This applicability has been achieved by sophisticated laser designs controlling the spin and orbital angular momentum, but so far is restricted to only two-dimensional states. Here we demonstrate the first vectorially structured light created and fully controlled in eight dimensions, a new state-of-the-art. We externally modulate our beam to control, for the first time, the complete set of classical Greenberger–Horne–Zeilinger (GHZ) states in paraxial structured light beams, in analogy with high-dimensional multi-partite quantum entangled states, and introduce a new tomography method to verify their fidelity. Our complete theoretical framework reveals a rich parameter space for further extending the dimensionality and degrees of freedom, opening new pathways for vectorially structured light in the classical and quantum regimes.
COVID-19 in early 2021: current status and looking forward
Authors: Wang Chengdi , Wang Zhoufeng , Wang Guangyu , Lau Johnson Yiu-Nam , Zhang Kang , Li Weimin
Published: March 2021

Since the first description of a coronavirus-related pneumonia outbreak in December 2019, the virus SARS-CoV-2 that causes the infection/disease (COVID-19) has evolved into a pandemic, and as of today, >100 million people globally in over 210 countries have been confirmed to have been infected and two million people have died of COVID-19. This brief review summarized what we have hitherto learned in the following areas: epidemiology, virology, and pathogenesis, diagnosis, use of artificial intelligence in assisting diagnosis, treatment, and vaccine development. As there are a number of parallel developments in each of these areas and some of the development and deployment were at unprecedented speed, we also provided some specific dates for certain development and milestones so that the readers can appreciate the timing of some of these critical events. Of note is the fact that there are diagnostics, antiviral drugs, and vaccines developed and approved by a regulatory within 1 year after the virus was discovered. As a number of developments were conducted in parallel, we also provided the specific dates of a number of critical events so that readers can appreciate the evolution of these research data and our understanding. The world is working together to combat this pandemic. This review also highlights the research and development directions in these areas that will evolve rapidly in the near future.
Stability of person-specific blood-based infrared molecular fingerprints opens up prospects for health monitoring
Authors: Huber Marinus , Kepesidis Kosmas V. , Voronina Liudmila , Božić Maša , Trubetskov Michael , Harbeck Nadia , Krausz Ferenc , Žigman Mihaela
Published: March 2021

Health state transitions are reflected in characteristic changes in the molecular composition of biofluids. Detecting these changes in parallel, across a broad spectrum of molecular species, could contribute to the detection of abnormal physiologies. Fingerprinting of biofluids by infrared vibrational spectroscopy offers that capacity. Whether its potential for health monitoring can indeed be exploited critically depends on how stable infrared molecular fingerprints (IMFs) of individuals prove to be over time. Here we report a proof-of-concept study that addresses this question. Using Fourier-transform infrared spectroscopy, we have fingerprinted blood serum and plasma samples from 31 healthy, non-symptomatic individuals, who were sampled up to 13 times over a period of 7 weeks and again after 6 months. The measurements were performed directly on liquid serum and plasma samples, yielding a time- and cost-effective workflow and a high degree of reproducibility. The resulting IMFs were found to be highly stable over clinically relevant time scales. Single measurements yielded a multiplicity of person-specific spectral markers, allowing individual molecular phenotypes to be detected and followed over time. This previously unknown temporal stability of individual biochemical fingerprints forms the basis for future applications of blood-based infrared spectral fingerprinting as a multiomics-based mode of health monitoring.
Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain
Authors: Kupari Jussi , Usoskin Dmitry , Parisien Marc , Lou Daohua , Hu Yizhou , Fatt Michael , Lönnerberg Peter , Spångberg Mats , Eriksson Bengt , Barkas Nikolaos , Kharchenko Peter V. , Loré Karin , Khoury Samar , Diatchenko Luda , Ernfors Patrik
Published: March 2021

Distinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain. However, molecular insights into the primate sensory neurons are missing. Here we classify non-human primate dorsal root ganglion sensory neurons based on their transcriptome and map human pain heritability to neuronal types. First, we identified cell correlates between two major datasets for mouse sensory neuron types. Machine learning exposes an overall cross-species conservation of somatosensory neurons between primate and mouse, although with differences at individual gene level, highlighting the importance of primate data for clinical translation. We map genomic loci associated with chronic pain in human onto primate sensory neuron types to identify the cellular origin of chronic pain. Genome-wide associations for chronic pain converge on two different neuronal types distributed between pain disorders that display different genetic susceptibilities, suggesting both unique and shared mechanisms between different pain conditions.
Specific inhibition of the Survivin–CRM1 interaction by peptide-modified molecular tweezers
Authors: Meiners Annika , Bäcker Sandra , Hadrović Inesa , Heid Christian , Beuck Christine , Ruiz-Blanco Yasser B. , Mieres-Perez Joel , Pörschke Marius , Grad Jean-Noël , Vallet Cecilia , Hoffmann Daniel , Bayer Peter , Sánchez-García Elsa , Schrader Thomas , Knauer Shirley K.
Published: March 2021

Survivin’s dual function as apoptosis inhibitor and regulator of cell proliferation is mediated via its interaction with the export receptor CRM1. This protein–protein interaction represents an attractive target in cancer research and therapy. Here, we report a sophisticated strategy addressing Survivin’s nuclear export signal (NES), the binding site of CRM1, with advanced supramolecular tweezers for lysine and arginine. These were covalently connected to small peptides resembling the natural, self-complementary dimer interface which largely overlaps with the NES. Several biochemical methods demonstrated sequence-selective NES recognition and interference with the critical receptor interaction. These data were strongly supported by molecular dynamics simulations and multiscale computational studies. Rational design of lysine tweezers equipped with a peptidic recognition element thus allowed to address a previously unapproachable protein surface area. As an experimental proof-of-principle for specific transport signal interference, this concept should be transferable to any protein epitope with a flanking well-accessible lysine.
Antarctic Peninsula warm winters influenced by Tasman Sea temperatures
Authors: Sato Kazutoshi , Inoue Jun , Simmonds Ian , Rudeva Irina
Published: March 2021

The Antarctic Peninsula of West Antarctica was one of the most rapidly warming regions on the Earth during the second half of the 20th century. Changes in the atmospheric circulation associated with remote tropical climate variabilities have been considered as leading drivers of the change in surface conditions in the region. However, the impacts of climate variabilities over the mid-latitudes of the Southern Hemisphere on this Antarctic warming have yet to be quantified. Here, through observation analysis and model experiments, we reveal that increases in winter sea surface temperature (SST) in the Tasman Sea modify Southern Ocean storm tracks. This, in turn, induces warming over the Antarctic Peninsula via planetary waves triggered in the Tasman Sea. We show that atmospheric response to SST warming over the Tasman Sea, even in the absence of anomalous tropical SST forcing, deepens the Amundsen Sea Low, leading to warm advection over the Antarctic Peninsula.
Immune cell profiling of the cerebrospinal fluid enables the characterization of the brain metastasis microenvironment
Authors: Rubio-Perez Carlota , Planas-Rigol Ester , Trincado Juan L. , Bonfill-Teixidor Ester , Arias Alexandra , Marchese Domenica , Moutinho Catia , Serna Garazi , Pedrosa Leire , Iurlaro Raffaella , Martínez-Ricarte Francisco , Escudero Laura , Cordero Esteban , Cicuendez Marta , Ruiz Sara , Parra Genís , Nuciforo Paolo , Gonzalez Josep , Pineda Estela , Sahuquillo Juan , Tabernero Josep , Heyn Holger , Seoane Joan
Published: March 2021

Brain metastases are the most common tumor of the brain with a dismal prognosis. A fraction of patients with brain metastasis benefit from treatment with immune checkpoint inhibitors (ICI) and the degree and phenotype of the immune cell infiltration has been used to predict response to ICI. However, the anatomical location of brain lesions limits access to tumor material to characterize the immune phenotype. Here, we characterize immune cells present in brain lesions and matched cerebrospinal fluid (CSF) using single-cell RNA sequencing combined with T cell receptor genotyping. Tumor immune infiltration and specifically CD8+ T cell infiltration can be discerned through the analysis of the CSF. Consistently, identical T cell receptor clonotypes are detected in brain lesions and CSF, confirming cell exchange between these compartments. The analysis of immune cells of the CSF can provide a non-invasive alternative to predict the response to ICI, as well as identify the T cell receptor clonotypes present in brain metastasis.
Prioritizing non-coding regions based on human genomic constraint and sequence context with deep learning
Authors: Vitsios Dimitrios , Dhindsa Ryan S. , Middleton Lawrence , Gussow Ayal B. , Petrovski Slavé
Published: March 2021

Elucidating functionality in non-coding regions is a key challenge in human genomics. It has been shown that intolerance to variation of coding and proximal non-coding sequence is a strong predictor of human disease relevance. Here, we integrate intolerance to variation, functional genomic annotations and primary genomic sequence to build JARVIS: a comprehensive deep learning model to prioritize non-coding regions, outperforming other human lineage-specific scores. Despite being agnostic to evolutionary conservation, JARVIS performs comparably or outperforms conservation-based scores in classifying pathogenic single-nucleotide and structural variants. In constructing JARVIS, we introduce the genome-wide residual variation intolerance score (gwRVIS), applying a sliding-window approach to whole genome sequencing data from 62,784 individuals. gwRVIS distinguishes Mendelian disease genes from more tolerant CCDS regions and highlights ultra-conserved non-coding elements as the most intolerant regions in the human genome. Both JARVIS and gwRVIS capture previously inaccessible human-lineage constraint information and will enhance our understanding of the non-coding genome.
Oxidation inhibits autophagy protein deconjugation from phagosomes to sustain MHC class II restricted antigen presentation
Authors: Ligeon Laure-Anne , Pena-Francesch Maria , Vanoaica Liliana Danusia , Núñez Nicolás Gonzalo , Talwar Deepti , Dick Tobias P. , Münz Christian
Published: March 2021

LC3-associated phagocytosis (LAP) contributes to a wide range of cellular processes and notably to immunity. The stabilization of phagosomes by the macroautophagy machinery in human macrophages can maintain antigen presentation on MHC class II molecules. However, the molecular mechanisms involved in the formation and maturation of the resulting LAPosomes are not completely understood. Here, we show that reactive oxygen species (ROS) produced by NADPH oxidase 2 (NOX2) stabilize LAPosomes by inhibiting LC3 deconjugation from the LAPosome cytosolic surface. NOX2 residing in the LAPosome membrane generates ROS to cause oxidative inactivation of the protease ATG4B, which otherwise releases LC3B from LAPosomes. An oxidation-insensitive ATG4B mutant compromises LAP and thereby impedes sustained MHC class II presentation of exogenousCandida albicansantigens. Redox regulation of ATG4B is thereby an important mechanism for maintaining LC3 decoration of LAPosomes to support antigen processing for MHC class II presentation.
Flexible thermoelectric generator with liquid metal interconnects and low thermal conductivity silicone filler
Authors: Padmanabhan Ramesh Viswanath , Sargolzaeiaval Yasaman , Neumann Taylor , Misra Veena , Vashaee Daryoosh , Dickey Michael D. , Ozturk Mehmet C.
Published: March 2021

Harvesting body heat using thermoelectricity provides a promising path to realizing self-powered, wearable electronics that can achieve continuous, long-term, uninterrupted health monitoring. This paper reports a flexible thermoelectric generator (TEG) that provides efficient conversion of body heat to electrical energy. The device relies on a low thermal conductivity aerogel–silicone composite that secures and thermally isolates the individual semiconductor elements that are connected in series using stretchable eutectic gallium-indium (EGaIn) liquid metal interconnects. The composite consists of aerogel particulates mixed into polydimethylsiloxane (PDMS) providing as much as 50% reduction in the thermal conductivity of the silicone elastomer. Worn on the wrist, the flexible TEGs present output power density figures approaching 35 μWcm−2 at an air velocity of 1.2 ms−1, equivalent to walking speed. The results suggest that these flexible TEGs can serve as the main energy source for low-power wearable electronics.
How COVID-19 will boost remote exercise-based treatment in Parkinson’s disease: a narrative review
Authors: Langer Agnes , Gassner Lucia , Flotz Anna , Hasenauer Sebastian , Gruber Jakob , Wizany Laurenz , Pokan Rochus , Maetzler Walter , Zach Heidemarie
Published: March 2021

The lack of physical exercise during the COVID-19 pandemic-related quarantine measures is challenging, especially for patients with Parkinson’s disease (PD). Without regular exercise not only patients, but also nursing staff and physicians soon noticed a deterioration of motor and non-motor symptoms. Reduced functional mobility, increased falls, increased frailty, and decreased quality of life were identified as consequences of increased sedentary behavior. This work overviews the current literature on problems of supplying conventional physiotherapy and the potential of telerehabilitation, allied health services, and patient-initiated exercise for PD patients during the COVID-19 period. We discuss recent studies on approaches that can improve remote provision of exercise to patients, including telerehabilitation, motivational tools, apps, exergaming, and virtual reality (VR) exercise. Additionally, we provide a case report about a 69-year-old PD patient who took part in a 12-week guided climbing course for PD patients prior to the pandemic and found a solution to continue her climbing training independently with an outdoor rope ladder. This case can serve as a best practice example for non-instructed, creative, and patient-initiated exercise in the domestic environment in difficult times, as are the current. Overall, many recent studies on telemedicine, telerehabilitation, and patient-initiated exercises have been published, giving rise to optimism that facilitating remote exercise can help PD patients maintain physical mobility and emotional well-being, even in phases such as the COVID-19 pandemic. The pandemic itself may even boost the need to establish comprehensive and easy-to-do telerehabilitation programs.