bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival Analysis and Risk Factors in COVID-19 Patients
Authors: Lu Wen , Yu Shuhui , Liu Hailing , Suo Lihua , Tang Kuanyin , Hu Jitao , Shi Yantong , Hu Ke
Published: March 2021

Objective:

The aim of this study is to evaluate the clinical characteristics and outcomes in 2019 coronavirus disease (COVID-19) patients and to help clinicians perform correct treatment and evaluate prognosis and guide the treatment.

Methods:

Patients totaling 239 were diagnosed with COVID-19 and were included in this study. Patients were divided into the improvement group and the death group according to their outcome (improvement or death). Clinical characteristics and laboratory parameters were collected from medical records. Continuous variables were tested by an independent sample T test, and categorical variables were analyzed by the chi-square test or Fisher’s exact test. The Cox proportional hazard regression model was used for survival analysis in death patients. The time-dependent area under curves (AUC) based on white blood cell count, lymphocyte count, neutrophil count by age, blood urea nitrogen, and C-reactive protein were plotted.

Results:

Efficacy evaluation indicated that 99 (41.4%) patients had deteriorated, and 140 (58.6%) patients had improved. Oxygen saturation, hemoglobin levels, infection-related indicators, lymphocyte and platelet counts, C-reactive protein, serum albumin, liver and kidney function, and lactate dehydrogenase in improvement group were statistically significant between the improvement and death groups. A survival analysis revealed that comorbidities, lymphocyte counts, platelet count, serum albumin, C-reactive protein level, and renal dysfunction may be risk factors in patients with COVID-19.

Conclusion:

Patients with comorbidities, lower lymphocyte counts in hemogram, platelet count and serum albumin, high C-reactive protein level, and renal dysfunction may have higher risk for death. More attention should be given to risk management in the progression of COVID-19.
Stigma Associated with COVID-19 Among Health Care Workers in Indonesia
Authors: Yufika Amanda , Pratama Rovy , Anwar Samsul , Winardi Wira , Librianty Nurfanida , Prashanti Nyoman Ananda Putri , Sari Tri Novita Wulan , Utomo Prattama Santoso , Dwiamelia Theresia , Natha Putu Pangestu Cendra , Salwiyadi Salwiyadi , Asrizal Febrivan Wahyu , Ikram Ikram , Wulandari Irma , Haryanto Sotianingsih , Fenobilire Nice , Wagner Abram L , Jamil Kurnia Fitri , Mudatsir Mudatsir , Harapan Harapan
Published: March 2021

Objective:

The aim of this study was to assess the stigma associated with coronavirus disease - 2019 (COVID-19) among health care workers (HCWs) in Indonesia during the early phase of the pandemic.

Methods:

A cross-sectional study was conducted in 12 hospitals across the country in March, 2020. A logistic regression was employed to assess the association between stigma and explanatory variables.

Results:

In total, 288 HCWs were surveyed, of which 93.4% had never experienced any outbreaks. Approximately 21.9% of the respondents had stigma associated with COVID-19. HCWs who were doctors, had not participated in trainings related to COVID-19, worked in the capital of the province, worked at private hospitals, or worked at a hospital with COVID-19 triage protocols were likely to have no stigma associated with COVID-19.

Conclusions:

The stigma associated with COVID-19 is relatively high among HCWs in the early phase of the COVID-19 pandemic in Indonesia. Adequate dissemination of knowledge and adequate protection are necessary to reduce stigma among HCWs.
From World War II to COVID-19: A Historical Perspective on the American Medical Supply Chain
Authors: Bechtold Hunter D , Cruz Andrea T , Kaziny Brent D
Published: March 2021

COVID-19 is the latest episode of shortages of critical medical supplies. Historically and to the present day, medical supplies have been sourced from single regions in the world, thus rendering the supply chain vulnerable to a myriad of harmful circumstances. We argue that shortages in medications related and unrelated to COVID have illustrated the need for the United States to diversify its medical supply sources before future pandemics, political crises, or natural disasters occur.
Instability of a shear-imposed flow down a vibrating inclined plane
Authors: Samanta Arghya
Published: March 2021

A linear stability of a shear-imposed viscous liquid flowing down a vibrating inclined plane is deciphered for disturbances of arbitrary wavenumbers. The main purpose of this study is to expand the model of Woods & Lin (J. Fluid Mech., vol. 294, 1995, pp. 391–407) for a shear-imposed flow (Smith, J. Fluid Mech., vol. 217, 1990, pp. 469–485) when the inclined plane oscillates in streamwise and cross-stream directions, respectively. The time-dependent Orr–Sommerfeld-type boundary value problem is derived and solved numerically based on the Chebyshev spectral collocation method along with Floquet theory. Numerical results corresponding to the cross-stream oscillation disclose that there exist three different types of instabilities, the so-called gravitational, subharmonic and harmonic instabilities, which can be resonated in separate unstable ranges of wavenumber by varying the amplitude of cross-stream oscillation. In fact, the subharmonic and harmonic resonances occur once the forcing amplitude exceeds the respective critical amplitudes for the subharmonic and harmonic instabilities. At low Reynolds number, the subharmonic resonance excited at low forcing amplitude intensifies but attenuates in the presence of imposed shear stress when the forcing amplitude is high. However, the harmonic resonance excited solely at high forcing amplitude intensifies in the presence of imposed shear stress. In contrast, at moderate Reynolds number, the subharmonic resonance excited at low forcing amplitude can be weakened by incorporating an imposed shear stress at the liquid surface. Furthermore, at high Reynolds number, a new instability, the so-called shear instability, arises along with the aforementioned three instabilities and becomes stronger in the presence of imposed shear stress. However, the gravitational and shear instabilities become weaker as soon as the forcing amplitude of cross-stream oscillation increases. On the other hand, numerical results for a streamwise oscillatory flow reveal that there exist three distinct unstable zones separated by stable ranges of Reynolds number. The resonated unstable zone induced by the streamwise oscillation attenuates, but the unstable zone responsible for the gravitational instability enhances in the presence of imposed shear stress. As soon as the Reynolds number is large and the inclination angle is sufficiently small, a new instability, the so-called shear instability, occurs in the finite wavenumber regime along with the resonated and gravitational instabilities. Further, the shear instability also intensifies in the presence of imposed shear stress for a streamwise oscillatory flow.
Ancient Maya Patolli from Gallon Jug, Belize
Authors: Novotny Claire , Houk Brett A.
Published: March 2021

Recent excavations at the site of Gallon Jug, a minor center in northwestern Belize, revealed multiple patolli boards incised into a well-preserved plaster floor in an unvaulted platform. A significant artifact deposit was placed directly on top of the patolli boards. In this report we describe the architectural context, associated artifact deposit, and the patolli boards themselves.
Does adaptive thermogenesis occur after weight loss in adults? A systematic review
Authors: Nunes Catarina L. , Casanova Nuno , Francisco Ruben , Bosy-Westphal Anja , Hopkins Mark , Sardinha Luís B. , Silva Analiza M.
Published: March 2021

Adaptive thermogenesis (AT) has been proposed to be a compensatory response that may resist weight loss (WL) and promote weight regain. This systematic review examined the existence of AT in adults after a period of negative energy balance (EB) with or without a weight stabilisation phase. Studies published until 15 May 2020 were identified from PubMed, Cochrane Library, EMBASE, MEDLINE, SCOPUS and Web of Science. Inclusion criteria included statistically significant WL, observational with follow-up or experimental studies, age > 18y, sample size ≥10 participants, intervention period ≥ 1week, published in English, objective measures of total daily energy expenditure (EE) (TDEE), resting EE (REE) and sleeping EE(SEE). The systematic review was registered at PROSPERO (2020 CRD42020165348). A total of thirty-three studies comprising 2528 participants were included. AT was observed in twenty-seven studies. Twenty-three studies showed significant values for AT for REE (82·8 %), four for TDEE (80·0 %) and two for SEE (100 %). A large heterogeneity in the methods used to quantify AT and between subjects and among studies regarding the magnitude of WL and/or of AT was reported. Well-designed studies reported lower or non-significant values for AT. These findings suggest that although WL may lead to AT in some of the EE components, these values may be small or non-statistically significant when higher-quality methodological designs are used. Furthermore, AT seems to be attenuated, or non-existent, after periods of weight stabilisation/neutral EB. More high-quality studies are warranted not only to disclose the existence of AT but also to understand its clinical implications on weight management outcomes.
Colony and Empire, Colonialism and Imperialism: A Meaningful Distinction?
Authors: Kumar Krishan
Published: March 2021

Colony and empire, colonialism and imperialism, are often treated as synonyms.This can be acceptable for many purposes. But there may be also good reasons to distinguish between them. This article considers in detail one important attempt in that direction by the classicist Moses Finley. It argues that there is considerable strength in that approach, putting the stress as it does on the distinctiveness of the settler community. It is also valuable in suggesting that early-modern Western colonialism marked a new departure in an older history of imperialism, thus once again suggesting the need for a conceptual separation of the two. But the article concludes that ultimately more may be lost than gained by insisting on the distinction. In particular, it inhibits wide-ranging comparisons between ancient and modern, and Western and non-Western, empires, which can often suggest illuminating connections and parallels. The field of empire studies gains by drawing on the rich store of examples provided by the whole history of empire, from the earliest times to now. Western colonialism is part of that story; to separate it out is to impoverish the field.
Decentering Egyptian Historiography: Provincializing Geographies, Methodologies, and Sources
Authors: Carminati Lucia , Gamal-Eldin Mohamed
Published: March 2021

“They say the city never sleeps, they say it bursts at the seams. The city rotates and revolves. The city branches out. The city beats, the city bleeds.” This unnamed city is Cairo, Umm al-Dunya or “mother of the world,” at once a vibrant character and the pulsating backdrop of Ahmed Naji's scandal-rousing Istikhdam al-Hayat (Using Life) and countless other works in Egyptian literature. Cairo, Amitav Ghosh has argued in his autobiographical chronicle of historical research and anthropological fieldwork in the Egyptian Delta in 1980 and beyond, is “Egypt's own metaphor for itself.” If that is the case, what does this sprawling and pervasive synecdoche reveal and what does it obscure?
Iceberg disturbance to benthic communities in McMurdo Sound, Antarctica
Authors: Kim Stacy , Collins Clint A.
Published: March 2021

On the continental shelf of the Antarctic the major disturbance to benthic ecosystems is from iceberg scouring; however, this is based on observations from the Peninsula region. We combine observation and experimentation in the McMurdo Sound region of the Ross Sea to determine if community recovery patterns there are similar to those in better-studied Antarctic regions, and if local immigration is an important factor in recovery dynamics. We found that regardless of habitat differences in depth, substrate, and oceanographic setting, iceberg disturbance strongly impacted benthic communities in McMurdo Sound. Notably, in shallow water (<30 m) where anchor ice is an annual disturbance, both the benthic communities and recovery processes were more variable than at deeper locations. A manipulative experiment performed in a shallow area indicated that recruitment might be more important than immigration to infaunal community recovery. We conclude that whilst disturbance frequency influences dominant epifauna, recovery from iceberg disturbance is a slow ecological progression that is dependent on the extremely inconsistent recruitment processes of the high Antarctic benthic ecosystem.
The proposer or the proposal? An experimental analysis of constitutional beliefs
Authors: McElwain Kenneth Mori , Eshima Shusei , Winkler Christian G.
Published: March 2021

In many countries, constitutional amendments require the direct approval of voters, but the consequences of fundamental changes to the powers and operations of the state are difficult to anticipate. The referendums literature suggests that citizens weigh their prior beliefs about the merits of proposals against the heuristic provided by the partisanship of the proposer, but the relative salience of these factors across constitutional issue areas remains underexplored. This paper examines the determinants of citizen preferences on 12 diverse constitutional issues, based on a novel survey experiment in Japan. We show that support for amendments is greater when its proposer is described as non-partisan. However, constitutional ideology moderates this effect. Those who prefer idealistic constitutions that elevate national traditions tend to value proposals that expand government powers, compared to those who prefer pragmatic constitutions that constrain government authority. These results highlight the significance of constitutional beliefs that are independent of partisanship.
Bayesian Unsupervised Machine Learning Approach to Segment Arctic Sea Ice Using SMOS Data
Authors: Herbert Christoph , Camps Adriano , Wellmann Florian , Vall‐llossera Mercedes
Published: March 2021

Microwave radiometry at L‐band is sensitive to sea ice thickness (SIT) up to ∼ 60 cm. Current methods to infer SIT depend on ice‐physical properties and data provided by the ESA’s Soil Moisture and Ocean Salinity (SMOS) mission. However, retrieval accuracy is limited due to seasonally and regionally variable surface conditions during the formation and melting of sea ice. In this work, Arctic sea ice is segmented using a Bayesian unsupervised learning algorithm aiming to recognize spatial patterns by harnessing multi‐incidence angle brightness temperature observations. The approach considers both statistical characteristics and spatial correlations of the observations. The temporal stability and separability of classes are analyzed to distinguish ambiguous from well‐determined regions. Model uncertainty is quantified from class membership probabilities using information entropy. The presented approach opens up a new scope to improve current SIT retrieval algorithms, and can be particularly beneficial to investigate merged satellite products.
A Successful Model for Interdisciplinary Research
Authors: F�rot Ana�s
Published: March 2021

Over the past decade, the GeoPRISMS program has greatly expanded understanding of shoreline-spanning Earth systems processes and fostered a vibrant and increasingly diverse community of researchers.
Earth’s Volatile Balancing Act
Authors: Muirhead James , Naif Samer , Fischer Tobias , Shillington D.
Published: March 2021

How do greenhouse gases and water circulate from minerals deep below Earth’s surface into the atmosphere and oceans—and then back again? Our understanding continues to evolve.
Glycolysis reprogramming in cancer-associated fibroblasts promotes the growth of oral cancer through the lncRNA H19/miR-675-5p/PFKFB3 signaling pathway
Authors: Yang Jin , Shi Xueke , Yang Miao , Luo Jingjing , Gao Qinghong , Wang Xiangjian , Wu Yang , Tian Yuan , Wu Fanglong , Zhou Hongmei
Published: March 2021

As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.
A protective role for autophagy in vitiligo
Authors: Bastonini Emanuela , Kovacs Daniela , Raffa Salvatore , delle Macchie Marina , Pacifico Alessia , Iacovelli Paolo , Torrisi Maria Rosaria , Picardo Mauro
Published: March 2021

A growing number of studies supports the existence of a dynamic interplay between energetic metabolism and autophagy, whose induction represents an adaptive response against several stress conditions. Autophagy is an evolutionarily conserved and a highly orchestrated catabolic recycling process that guarantees cellular homeostasis. To date, the exact role of autophagy in vitiligo pathogenesis is still not clear. Here, we provide the first evidence that autophagy occurs in melanocytes and fibroblasts from non-lesional skin of vitiligo patients, as a result of metabolic surveillance response. More precisely, this study is the first to reveal that induction of autophagy exerts a protective role against the intrinsic metabolic stress and attempts to antagonize degenerative processes in normal appearing vitiligo skin, where melanocytes and fibroblasts are already prone to premature senescence.
Immune memory in convalescent patients with asymptomatic or mild COVID-19
Authors: Long Quan-Xin , Jia Yan-Jun , Wang Xin , Deng Hai-Jun , Cao Xiao-Xia , Yuan Jun , Fang Liang , Cheng Xu-Rong , Luo Chao , He An-Ran , Tang Xiao-Jun , Hu Jie-li , Hu Yuan , Tang Ni , Cai Xue-Fei , Wang De-Qiang , Hu Jie , Qiu Jing-Fu , Liu Bei-Zhong , Chen Juan , Huang Ai-long
Published: March 2021

It is important to evaluate the durability of the protective immune response elicited by primary infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we systematically evaluated the SARS-CoV-2-specific memory B cell and T cell responses in healthy controls and individuals recovered from asymptomatic or symptomatic infection approximately 6 months prior. Comparatively low frequencies of memory B cells specific for the receptor-binding domain (RBD) of spike glycoprotein (S) persisted in the peripheral blood of individuals who recovered from infection (median 0.62%, interquartile range 0.48-0.69). The SARS-CoV-2 RBD-specific memory B cell response was detected in 2 of 13 individuals who recovered from asymptomatic infection and 10 of 20 individuals who recovered from symptomatic infection. T cell responses induced by S, membrane (M), and nucleocapsid (N) peptide libraries from SARS-CoV-2 were observed in individuals recovered from coronavirus disease 2019 (COVID-19), and cross-reactive T cell responses to SARS-CoV-2 were also detected in healthy controls.
Retraction Note: Reduction of carbon dioxide to oxalate by a binuclear copper complex
Authors: Pokharel Uttam R. , Fronczek Frank R. , Maverick Andrew W.
Published: March 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1038/s41467-021-21951-5
Model-based deep embedding for constrained clustering analysis of single cell RNA-seq data
Authors: Tian Tian , Zhang Jie , Lin Xiang , Wei Zhi , Hakonarson Hakon
Published: March 2021

Clustering is a critical step in single cell-based studies. Most existing methods support unsupervised clustering without the a priori exploitation of any domain knowledge. When confronted by the high dimensionality and pervasive dropout events of scRNA-Seq data, purely unsupervised clustering methods may not produce biologically interpretable clusters, which complicates cell type assignment. In such cases, the only recourse is for the user to manually and repeatedly tweak clustering parameters until acceptable clusters are found. Consequently, the path to obtaining biologically meaningful clusters can be ad hoc and laborious. Here we report a principled clustering method named scDCC, that integrates domain knowledge into the clustering step. Experiments on various scRNA-seq datasets from thousands to tens of thousands of cells show that scDCC can significantly improve clustering performance, facilitating the interpretability of clusters and downstream analyses, such as cell type assignment.
A molecular timescale for eukaryote evolution with implications for the origin of red algal-derived plastids
Authors: Strassert Jürgen F. H. , Irisarri Iker , Williams Tom A. , Burki Fabien
Published: March 2021

In modern oceans, eukaryotic phytoplankton is dominated by lineages with red algal-derived plastids such as diatoms, dinoflagellates, and coccolithophores. Despite the ecological importance of these groups and many others representing a huge diversity of forms and lifestyles, we still lack a comprehensive understanding of their evolution and how they obtained their plastids. New hypotheses have emerged to explain the acquisition of red algal-derived plastids by serial endosymbiosis, but the chronology of these putative independent plastid acquisitions remains untested. Here, we establish a timeframe for the origin of red algal-derived plastids under scenarios of serial endosymbiosis, using Bayesian molecular clock analyses applied on a phylogenomic dataset with broad sampling of eukaryote diversity. We find that the hypotheses of serial endosymbiosis are chronologically possible, as the stem lineages of all red plastid-containing groups overlap in time. This period in the Meso- and Neoproterozoic Eras set the stage for the later expansion to dominance of red algal-derived primary production in the contemporary oceans, which profoundly altered the global geochemical and ecological conditions of the Earth.
Manipulating Weyl quasiparticles by orbital-selective photoexcitation in WTe2
Authors: Guan Meng-Xue , Wang En , You Pei-Wei , Sun Jia-Tao , Meng Sheng
Published: March 2021

Optical control of structural and electronic properties of Weyl semimetals allows development of switchable and dissipationless topological devices at the ultrafast scale. An unexpected orbital-selective photoexcitation in type-II Weyl material WTe2 is reported under linearly polarized light (LPL), inducing striking transitions among several topologically-distinct phases mediated by effective electron-phonon couplings. The symmetry features of atomic orbitals comprising the Weyl bands result in asymmetric electronic transitions near the Weyl points, and in turn a switchable interlayer shear motion with respect to linear light polarization, when a near-infrared laser pulse is applied. Consequently, not only annihilation of Weyl quasiparticle pairs, but also increasing separation of Weyl points can be achieved, complementing existing experimental observations. In this work, we provide a new perspective on manipulating the Weyl node singularity and coherent control of electron and lattice quantum dynamics simultaneously.
Structure-based design of a Cortistatin analogue with immunomodulatory activity in models of inflammatory bowel disease
Authors: Rol Álvaro , Todorovski Toni , Martin-Malpartida Pau , Escolà Anna , Gonzalez-Rey Elena , Aragón Eric , Verdaguer Xavier , Vallès-Miret Mariona , Farrera-Sinfreu Josep , Puig Eduard , Fernández-Carneado Jimena , Ponsati Berta , Delgado Mario , Riera Antoni , Macias Maria J.
Published: March 2021

Ulcerative colitis and Crohn’s disease are forms of inflammatory bowel disease whose incidence and prevalence are increasing worldwide. These diseases lead to chronic inflammation of the gastrointestinal tract as a result of an abnormal response of the immune system. Recent studies positioned Cortistatin, which shows low stability in plasma, as a candidate for IBD treatment. Here, using NMR structural information, we design five Cortistatin analogues adopting selected native Cortistatin conformations in solution. One of them, A5, preserves the anti-inflammatory and immunomodulatory activities of Cortistatin in vitro and in mouse models of the disease. Additionally, A5 displays an increased half-life in serum and a unique receptor binding profile, thereby overcoming the limitations of the native Cortistatin as a therapeutic agent. This study provides an efficient approach to the rational design of Cortistatin analogues and opens up new possibilities for the treatment of patients that fail to respond to other therapies.
Clonal analysis and dynamic imaging identify multipotency of individual Gallus gallus caudal hindbrain neural crest cells toward cardiac and enteric fates
Authors: Tang Weiyi , Li Yuwei , Li Ang , Bronner Marianne E.
Published: March 2021

Neural crest stem cells arising from caudal hindbrain (often called cardiac and posterior vagal neural crest) migrate long distances to form cell types as diverse as heart muscle and enteric ganglia, abnormalities of which lead to common congenital birth defects. Here, we explore whether individual caudal hindbrain neural crest precursors are multipotent or predetermined toward these particular fates and destinations. To this end, we perform lineage tracing of chick neural crest cells at single-cell resolution using two complementary approaches: retrovirally mediated multiplex clonal analysis and single-cell photoconversion. Both methods show that the majority of these neural crest precursors are multipotent with many clones producing mesenchymal as well as neuronal derivatives. Time-lapse imaging demonstrates that sister cells can migrate in distinct directions, suggesting stochasticity in choice of migration path. Perturbation experiments further identify guidance cues acting on cells in the pharyngeal junction that can influence this choice; loss of CXCR4 signaling results in failure to migrate to the heart but no influence on migration toward the foregut, whereas loss of RET signaling does the opposite. Taken together, the results suggest that environmental influences rather than intrinsic information govern cell fate choice of multipotent caudal hindbrain neural crest cells.
Membrane type 1 matrix metalloproteinase promotes LDL receptor shedding and accelerates the development of atherosclerosis
Authors: Alabi Adekunle , Xia Xiao-Dan , Gu Hong-Mei , Wang Faqi , Deng Shi-Jun , Yang Nana , Adijiang Ayinuer , Douglas Donna N. , Kneteman Norman M. , Xue Yazhuo , Chen Li , Qin Shucun , Wang Guiqing , Zhang Da-Wei
Published: March 2021

Plasma low-density lipoprotein (LDL) is primarily cleared by LDL receptor (LDLR). LDLR can be proteolytically cleaved to release its soluble ectodomain (sLDLR) into extracellular milieu. However, the proteinase responsible for LDLR cleavage is unknown. Here we report that membrane type 1-matrix metalloproteinase (MT1-MMP) co-immunoprecipitates and co-localizes with LDLR and promotes LDLR cleavage. Plasma sLDLR and cholesterol levels are reduced while hepatic LDLR is increased in mice lacking hepatic MT1-MMP. Opposite effects are observed when MT1-MMP is overexpressed. MT1-MMP overexpression significantly increases atherosclerotic lesions, while MT1-MMP knockdown significantly reduces cholesteryl ester accumulation in the aortas of apolipoprotein E (apoE) knockout mice. Furthermore, sLDLR is associated with apoB and apoE-containing lipoproteins in mouse and human plasma. Plasma levels of sLDLR are significantly increased in subjects with high plasma LDL cholesterol levels. Thus, we demonstrate that MT1-MMP promotes ectodomain shedding of hepatic LDLR, thereby regulating plasma cholesterol levels and the development of atherosclerosis.
Author Correction: Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways
Authors: Howard David M. , Adams Mark J. , Shirali Masoud , Clarke Toni-Kim , Marioni Riccardo E. , Davies Gail , Coleman Jonathan R. I. , Alloza Clara , Shen Xueyi , Barbu Miruna C. , Wigmore Eleanor M. , Gibson Jude ,   23andMe Research Team, Agee Michelle , Alipanahi Babak , Auton Adam , Bell Robert K. , Bryc Katarzyna , Elson Sarah L. , Fontanillas Pierre , Furlotte Nicholas A. , Hinds David A. , Huber Karen E. , Kleinman Aaron , Litterman Nadia K. , McCreight Jennifer C. , McIntyre Matthew H. , Mountain Joanna L. , Noblin Elizabeth S. , Northover Carrie A. M. , Pitts Steven J. , Sathirapongsasuti J. Fah , Sazonova Olga V. , Shelton Janie F. , Shringarpure Suyash , Tian Chao , Tung Joyce Y. , Vacic Vladimir , Wilson Catherine H. , Hagenaars Saskia P. , Lewis Cathryn M. , Ward Joey , Smith Daniel J. , Sullivan Patrick F. , Haley Chris S. , Breen Gerome , Deary Ian J. , McIntosh Andrew M.
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22411-w
Author Correction: Pharmacophore hybridisation and nanoscale assembly to discover self-delivering lysosomotropic new-chemical entities for cancer therapy
Authors: Ma Zhao , Li Jin , Lin Kai , Ramachandran Mythili , Zhang Dalin , Showalter Megan , De Souza Cristabelle , Lindstrom Aaron , Solano Lucas N. , Jia Bei , Urayama Shiro , Duan Yuyou , Fiehn Oliver , Lin Tzu-yin , Li Minyong , Li Yuanpei
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22419-2
The effect of SARS-CoV-2 D614G mutation on BNT162b2 vaccine-elicited neutralization
Authors: Zou Jing , Xie Xuping , Fontes-Garfias Camila R. , Swanson Kena A. , Kanevsky Isis , Tompkins Kristin , Cutler Mark , Cooper David , Dormitzer Philip R. , Shi Pei-Yong
Published: March 2021

Initial COVID-19 vaccine candidates were based on the original sequence of SARS-CoV-2. However, the virus has since accumulated mutations, among which the spike D614G is dominant in circulating virus, raising questions about potential virus escape from vaccine-elicited immunity. Here, we report that the D614G mutation modestly reduced (1.7–2.4-fold) SARS-CoV-2 neutralization by BNT162b2 vaccine-elicited mouse, rhesus, and human sera, concurring with the 95% vaccine efficacy observed in clinical trial.
EORNA, a barley gene and transcript abundance database
Authors: Milne Linda , Bayer Micha , Rapazote-Flores Paulo , Mayer Claus-Dieter , Waugh Robbie , Simpson Craig G.
Published: March 2021

A high-quality, barley gene reference transcript dataset (BaRTv1.0), was used to quantify gene and transcript abundances from 22 RNA-seq experiments, covering 843 separate samples. Using the abundance data we developed a Barley Expression Database (EORNA*) to underpin a visualisation tool that displays comparative gene and transcript abundance data on demand as transcripts per million (TPM) across all samples and all the genes. EORNA provides gene and transcript models for all of the transcripts contained in BaRTV1.0, and these can be conveniently identified through either BaRT or HORVU gene names, or by direct BLAST of query sequences. Browsing the quantification data reveals cultivar, tissue and condition specific gene expression and shows changes in the proportions of individual transcripts that have arisen via alternative splicing. TPM values can be easily extracted to allow users to determine the statistical significance of observed transcript abundance variation among samples or perform meta analyses on multiple RNA-seq experiments. * Eòrna is the Scottish Gaelic word for Barley.
Polypill eligibility and equivalent intake in a Swiss population-based study
Authors: Castioni Julien , Abolhassani Nazanin , Vollenweider Peter , Waeber Gérard , Marques-Vidal Pedro
Published: March 2021

The polypill has been advocated for cardiovascular disease (CVD) management. The fraction of the population who could benefit from the polypill in Switzerland is unknown. Assess (1) the prevalence of subjects (a) eligible for the polypill and (b) already taking a polypill equivalent; and (2) the determinants of polypill intake in the first (2009–2012) and second follow-ups (2014–2017) of a population-based prospective study conducted in Lausanne, Switzerland. The first and the second follow-ups included 5038 and 4596 participants aged 40–80 years, respectively. Polypill eligibility was defined as having a high CVD risk as assessed by an absolute CVD risk ≥ 5% with the SCORE equation for Switzerland and/or presenting with CVD. Four polypill equivalents were defined: statin + any antihypertensive with (A) or without (B) aspirin; statin + calcium channel blocker (CCB) (C); and statin + CCB + angiotensin-converting enzyme inhibitor (D). The prevalence of polypill eligibility was 20.6% (95% CI 19.5–21.8) and 27.7% (26.5–29.1) in the first and second follow-up, respectively. However, only around one-third of the eligible 29.5% (95% CI 26.7–32.3) and 30.4% (27.9–33.0) respectively, already took the polypill equivalents. All polypill equivalents were more prevalent among men, elderly and in presence of CVD. After multivariable adjustment, in both periods, male gender was associated with taking polypill equivalent A (OR: 1.93; 95% CI 1.45–2.55 and OR: 1.67; 95% CI 1.27–2.19, respectively) and polypill equivalent B (OR: 1.52; 95% CI 1.17–1.96 and OR: 1.41; 95% CI 1.07–1.85, respectively). Similarly, in both periods, age over 70 years, compared to middle-age, was associated with taking polypill equivalent A (OR: 11.71; CI 6.74–20.33 and OR: 9.56; CI 4.13–22.13, respectively) and equivalent B (OR: 13.22; CI 7.27–24.07 and OR: 20.63; CI 6.51–56.36, respectively). Former or current smoking was also associated with a higher likelihood of taking polypill equivalent A in both periods. A large fraction of the population is eligible for the polypill, but only one-third of them actually benefits from an equivalent, and this proportion did not change over time.
A 3D analysis of growth trajectory and integration during early human prenatal facial growth
Authors: Katsube Motoki , Yamada Shigehito , Utsunomiya Natsuko , Yamaguchi Yutaka , Takakuwa Tetsuya , Yamamoto Akira , Imai Hirohiko , Saito Atsushi , Vora Siddharth R. , Morimoto Naoki
Published: March 2021

Significant shape changes in the human facial skeleton occur in the early prenatal period, and understanding this process is critical for studying a myriad of congenital facial anomalies. However, quantifying and visualizing human fetal facial growth has been challenging. Here, we applied quantitative geometric morphometrics (GM) to high-resolution magnetic resonance images of human embryo and fetuses, to comprehensively analyze facial growth. We utilized non-linear growth estimation and GM methods to assess integrated epigenetic growth between masticatory muscles and associated bones. Our results show that the growth trajectory of the human face in the early prenatal period follows a curved line with three flexion points. Significant antero-posterior development occurs early, resulting in a shift from a mandibular prognathic to relatively orthognathic appearance, followed by expansion in the lateral direction. Furthermore, during this time, the development of the zygoma and the mandibular ramus is closely integrated with the masseter muscle.
Classification of unlabeled online media
Authors: Prakash Sakthi Kumar Arul , Tucker Conrad
Published: March 2021

This work investigates the ability to classify misinformation in online social media networks in a manner that avoids the need for ground truth labels. Rather than approach the classification problem as a task for humans or machine learning algorithms, this work leverages user–user and user–media (i.e.,media likes) interactions to infer the type of information (fake vs. authentic) being spread, without needing to know the actual details of the information itself. To study the inception and evolution of user–user and user–media interactions over time, we create an experimental platform that mimics the functionality of real-world social media networks. We develop a graphical model that considers the evolution of this network topology to model the uncertainty (entropy) propagation when fake and authentic media disseminates across the network. The creation of a real-world social media network enables a wide range of hypotheses to be tested pertaining to users, their interactions with other users, and with media content. The discovery that the entropy of user–user and user–media interactions approximate fake and authentic media likes, enables us to classify fake media in an unsupervised learning manner.
Generalized chest CT and lab curves throughout the course of COVID-19
Authors: Kassin Michael T. , Varble Nicole , Blain Maxime , Xu Sheng , Turkbey Evrim B. , Harmon Stephanie , Yang Dong , Xu Ziyue , Roth Holger , Xu Daguang , Flores Mona , Amalou Amel , Sun Kaiyun , Kadri Sameer , Patella Francesca , Cariati Maurizio , Scarabelli Alice , Stellato Elvira , Ierardi Anna Maria , Carrafiello Gianpaolo , An Peng , Turkbey Baris , Wood Bradford J.
Published: March 2021

A better understanding of temporal relationships between chest CT and labs may provide a reference for disease severity over the disease course. Generalized curves of lung opacity volume and density over time can be used as standardized references from well before symptoms develop to over a month after recovery, when residual lung opacities remain. 739 patients with COVID-19 underwent CT and RT-PCR in an outbreak setting between January 21st and April 12th, 2020. 29 of 739 patients had serial exams (121 CTs and 279 laboratory measurements) over 50 ± 16 days, with an average of 4.2 sequential CTs each. Sequential volumes of total lung, overall opacity and opacity subtypes (ground glass opacity [GGO] and consolidation) were extracted using deep learning and manual segmentation. Generalized temporal curves of CT and laboratory measurements were correlated. Lung opacities appeared 3.4 ± 2.2 days prior to symptom onset. Opacity peaked 1 day after symptom onset. GGO onset was earlier and resolved later than consolidation. Lactate dehydrogenase, and C-reactive protein peaked earlier than procalcitonin and leukopenia. The temporal relationships of quantitative CT features and clinical labs have distinctive patterns and peaks in relation to symptom onset, which may inform early clinical course in patients with mild COVID-19 pneumonia, or may shed light upon chronic lung effects or mechanisms of medical countermeasures in clinical trials.
Containment efficiency and control strategies for the corona pandemic costs
Authors: Gros Claudius , Valenti Roser , Schneider Lukas , Valenti Kilian , Gros Daniel
Published: March 2021

The rapid spread of the Coronavirus (COVID-19) confronts policy makers with the problem of measuring the effectiveness of containment strategies, balancing public health considerations with the economic costs of social distancing measures. We introduce a modified epidemic model that we name the controlled-SIR model, in which the disease reproduction rate evolves dynamically in response to political and societal reactions. An analytic solution is presented. The model reproduces official COVID-19 cases counts of a large number of regions and countries that surpassed the first peak of the outbreak. A single unbiased feedback parameter is extracted from field data and used to formulate an index that measures the efficiency of containment strategies (the CEI index). CEI values for a range of countries are given. For two variants of the controlled-SIR model, detailed estimates of the total medical and socio-economic costs are evaluated over the entire course of the epidemic. Costs comprise medical care cost, the economic cost of social distancing, as well as the economic value of lives saved. Under plausible parameters, strict measures fare better than a hands-off policy. Strategies based on current case numbers lead to substantially higher total costs than strategies based on the overall history of the epidemic.
Epidemiology and prognosis in young lung cancer patients aged under 45 years old in northern China
Authors: Shi Jin , Li Daojuan , Liang Di , He Yutong
Published: March 2021

To explore the epidemiological characteristics and prognosis of lung cancer in patients aged under 45 years old in northern China. The population-based database about lung cancer cases aged under 45y selected form the Hebei Provincial Cancer Registry Center from 2010–2015. Mortality data of young death from 1973 to 1975, 1990 to 1992, and 2004 to 2005 were extracted from the national retrospective survey of death. Mortality rates were calculated by the mortality database above in this analysis. Consecutive, 954 non-selected younger patients (< 45 years) and 2261 selected older patients (≥ 45 years) with pathologically diagnosed lung cancer treated at the Fourth Hospital of Hebei Medical University were included as the hospital-based database. Epidemiological, treatment outcomes and prognosis status from 2010 to 2017 were documented. A comparison with younger and older patients was also made. Multivariate analysis with young lung cancer patients was calculated by Cox regression model. The younger lung cancer mortality rate tended to slightly increase in Hebei Province, from 1.04 per100 000 in 1973 to 2.01 per 100 000 in 2015, but the PDR tended to decrease over the last 40 years. There were 954 younger and 2261 older lung cancer patients included in the hospital-based database. The proportions of patients who were female (50.84% vs 34.85%), family history of cancer (12.37% vs 6.32%), advanced stage at diagnosis (65.46% vs 60.77%) and adenocarcinoma (65.27% vs 61.11%) were relatively higher in the younger group than in the older group. The median OS were 23.0 months and 27.0 months between younger and older, the OS difference existed between the two groups (P = 0.001). In the younger patients, Cox regression showed that a family history of cancer, symptoms at diagnosis, pathology, stage at diagnosis and surgery were confirmed as independent factors affecting the prognosis. Mortality rates among younger lung cancer patients showed an increasing trend in northern China. The younger account for small but have unique characteristics, with higher proportions of female, family history of cancer, adenocarcinoma and advanced stages than the older group and had a trend of worse OS.
In silico studies reveal structural deviations of mutant profilin-1 and interaction with riluzole and edaravone in amyotrophic lateral sclerosis
Authors: Sadr Ahmad Shahir , Eslahchi Changiz , Ghassempour Alireza , Kiaei Mahmoud
Published: March 2021

This study aimed to investigate four of the eight PFN-1 mutations that are located near the actin-binding domain and determine the structural changes due to each mutant and unravel how these mutations alter protein structural behavior. Swapaa’s command in UCSF chimera for generating mutations, FTMAP were employed and the data was analyzed by RMSD, RMSF graphs, Rg, hydrogen bonding analysis, and RRdisMaps utilizing Autodock4 and GROMACS. The functional changes and virtual screening, structural dynamics, and chemical bonding behavior changes, molecular docking simulation with two current FDA-approved drugs for ALS were investigated. The highest reduction and increase in Rg were found to exist in the G117V and M113T mutants, respectively. The RMSF data consistently shows changes nearby to this site. The in silico data described indicate that each of the mutations is capable of altering the structure of PFN-1 in vivo. The potential effect of riluzole and edaravone two FDA approved drugs for ALS, impacting the structural deviations and stabilization of the mutant PFN-1 is evaluated using in silico tools. Overall, the analysis of data collected reveals structural changes of mutant PFN-1 protein that may explain the neurotoxicity and the reason(s) for possible loss and gain of function of PFN-1 in the neurotoxic model of ALS.
Frontolimbic alpha activity tracks intentional rest BCI control improvement through mindfulness meditation
Authors: Jiang Haiteng , Stieger James , Kreitzer Mary Jo , Engel Stephen , He Bin
Published: March 2021

Brain–computer interfaces (BCIs) are capable of translating human intentions into signals controlling an external device to assist patients with severe neuromuscular disorders. Prior work has demonstrated that participants with mindfulness meditation experience evince improved BCI performance, but the underlying neural mechanisms remain unclear. Here, we conducted a large-scale longitudinal intervention study by training participants in mindfulness-based stress reduction (MBSR; a standardized mind–body awareness training intervention), and investigated whether and how short-term MBSR affected sensorimotor rhythm (SMR)-based BCI performance. We hypothesize that MBSR training improves BCI performance by reducing mind wandering and enhancing self-awareness during the intentional rest BCI control, which would mainly be reflected by modulations of default-mode network and limbic network activity. We found that MBSR training significantly improved BCI performance compared to controls and these behavioral enhancements were accompanied by increased frontolimbic alpha activity (9–15 Hz) and decreased alpha connectivity among limbic network, frontoparietal network, and default-mode network. Furthermore, the modulations of frontolimbic alpha activity were positively correlated with the duration of meditation experience and the extent of BCI performance improvement. Overall, these data suggest that mindfulness allows participant to reach a state where they can modulate frontolimbic alpha power and improve BCI performance for SMR-based BCI control.
Audiotactile interactions in the mouse cochlear nucleus
Authors: Ansorge Josephine , Wu Calvin , Shore Susan E. , Krieger Patrik
Published: March 2021

Multisensory integration of auditory and tactile information occurs already at the level of the cochlear nucleus. Rodents use their whiskers for tactile perception to guide them in their exploration of the world. As nocturnal animals with relatively poor vision, audiotactile interactions are of great importance for this species. Here, the influence of whisker deflections on sound-evoked spiking in the cochlear nucleus was investigated in vivo in anesthetized mice. Multichannel, silicon-probe electrophysiological recordings were obtained from both the dorsal and ventral cochlear nucleus. Whisker deflections evoked an increased spiking activity in fusiform cells of the dorsal cochlear nucleus and t-stellate cells in ventral cochlear nucleus, whereas bushy cells in the ventral cochlear nucleus showed a more variable response. The response to broadband noise stimulation increased in fusiform cells and primary-like bushy cells when the sound stimulation was preceded (~ 20 ms) by whisker stimulation. Multi-sensory integration of auditory and whisker input can thus occur already in this early brainstem nucleus, emphasizing the importance of early integration of auditory and somatosensory information.