bluuebunny/crossref_metadata_2025 huggingface dataset:
Small cell lung cancer stem cells display mesenchymal properties and exploit immune checkpoint pathways in activated cytotoxic T lymphocytes
Authors: Kursunel M. Alper , Taskiran Ekim Z. , Tavukcuoglu Ece , Yanik Hamdullah , Demirag Funda , Karaosmanoglu Beren , Ozbay Feyza Gul , Uner Aysegul , Esendagli Dorina , Kizilgoz Derya , Yilmaz Ulku , Esendagli Gunes
Published: July 2021

Small cell lung cancer (SCLC) is an aggressive tumor type with early dissemination and distant metastasis capacity. Even though optimal chemotherapy responses are observed initially in many patients, therapy resistance is almost inevitable. Accordingly, SCLC has been regarded as an archetype for cancer stem cell (CSC) dynamics. To determine the immune-modulatory influence of CSC in SCLC, this study focused on the characterization of CD44+CD90+ CSC-like subpopulations in SCLC. These cells displayed mesenchymal properties, differentiated into different lineages and further contributed to CD8+ cytotoxic T lymphocytes (CTL) responses. The interaction between CD44+CD90+ CSC-like cells and T cells led to the upregulation of checkpoint molecules PD-1, CTLA-4, TIM-3, and LAG3. In the patient-derived lymph nodes, CD44+ SCLC metastases were also observed with T cells expressing PD-1, TIM-3, or LAG3. Proliferation and IFN-γ expression capacity of TIM-3 and LAG3 co-expressing CTLs are adversely affected over long-time co-culture with CD44+CD90+ CSC-like cells. Moreover, especially through IFN-γ secreted by the T cells, the CSC-like SCLC cells highly expressed PD-L1 and PD-L2. Upon a second encounter with immune-experienced, IFN-γ-stimulated CSC-like SCLC cells, both cytotoxic and proliferation capacities of T cells were hampered. In conclusion, our data provide evidence for the superior potential of the SCLC cells with stem-like and mesenchymal properties to gain immune regulatory capacities and cope with cytotoxic T cell responses. With their high metastatic and immune-modulatory assets, the CSC subpopulation in SCLC may serve as a preferential target for checkpoint blockade immunotherapy
.
Bayesian inversion of a diffusion model with application to biology
Authors: Croix Jean-Charles , Durrande Nicolas , Alvarez Mauricio A.
Published: July 2021

A common task in experimental sciences is to fit mathematical models to real-world measurements to improve understanding of natural phenomenon (reverse-engineering or inverse modelling). When complex dynamical systems are considered, such as partial differential equations, this task may become challenging or ill-posed. In this work, a linear parabolic equation is considered as a model for protein transcription from MRNA. The objective is to estimate jointly the differential operator coefficients, namely the rates of diffusion and self-regulation, as well as a functional source. The recent Bayesian methodology for infinite dimensional inverse problems is applied, providing a unique posterior distribution on the parameter space continuous in the data. This posterior is then summarized using a Maximum a Posteriori estimator. Finally, the theoretical solution is illustrated using a state-of-the-art MCMC algorithm adapted to this non-Gaussian setting.
Genetic analysis of human parainfluenza virus type 4 associated with severe acute respiratory infection in children in Luohe City, Henan Province, China, during 2017–2018
Authors: Zhou Shanshan , Mao Naiying , Zhang Yan , Cui Aili , Zhu Zhen , Hu Ruiping , Xu Jin , Xu Wenbo
Published: July 2021

During 2017–2018, nasopharyngeal aspirates (NPAs) from 627 hospitalized patients with severe acute respiratory infection at Luohe Center Hospital were tested by RT-PCR for human parainfluenza virus 4 (HPIV-4). Fourteen (2.2%) of the 627 samples were positive for HPIV-4. The complete HN gene was amplified from nine positive samples and sequenced. Sequence comparisons showed that the HPIV-4 strains circulating in the city of Luohe are closely related to HPIV-4A strains. Our study indicated that there were multiple lineages of HPIV-4 circulating in Henan Province in China during the study period. This will improve our understanding of the epidemiological and clinical characteristics of HPIV-4.
The effects of psychological treatment of perinatal depression: an overview
Authors: Cuijpers Pim , Karyotaki Eirini
Published: July 2021

Perinatal depression is an important public health problem. Psychological interventions play an essential role in the treatment of depression. In the current paper, we will present the results of a series of meta-analyses on psychological treatments of perinatal depression. We report the results of a series of meta-analyses on psychological treatments of depression, including perinatal depression. The meta-analyses are based on a database of randomized trials on psychotherapies for depression that has been systematically developed and updated every year. Psychological interventions are effective in the treatment of perinatal depression with a moderate effect size of g = 0.67, corresponding with a NNT of about 4. These effects were still significant at 12 months after the start of the treatment. These interventions also have significant effects on social support, anxiety, functional impairment, parental stress, and marital stress. Possibly the effects are overestimated because of the use of waiting list control groups, the low quality of the majority of trials and publication bias. Research on psychotherapies for depression in general has shown that there are no significant differences between the major types of therapy, except for non-directive counseling that may have somewhat smaller effects. CBT can also be delivered in individual, group, telephone, and guided self-help format. Interventions in subthreshold depression are also effective and may prevent the onset of a full-blown depressive disorder, while therapies may be less effective in chronic depression. Psychological interventions are effective and deserve their place as first-line treatment of perinatal depression.
The probabilistic model checker Storm
Authors: Hensel Christian , Junges Sebastian , Katoen Joost-Pieter , Quatmann Tim , Volk Matthias
Published: July 2021

We present the probabilistic model checker Storm. Storm supports the analysis of discrete- and continuous-time variants of both Markov chains and Markov decision processes. Storm has three major distinguishing features. It supports multiple input languages for Markov models, including the Jani and Prism modeling languages, dynamic fault trees, generalized stochastic Petri nets, and the probabilistic guarded command language. It has a modular setup in which solvers and symbolic engines can easily be exchanged. Its Python API allows for rapid prototyping by encapsulating Storm’s fast and scalable algorithms. This paper reports on the main features of Storm and explains how to effectively use them. A description is provided of the main distinguishing functionalities of Storm. Finally, an empirical evaluation of different configurations of Storm on the QComp 2019 benchmark set is presented.
Safety and efficacy of Tolvaptan in real-world patients with autosomal dominant polycystic kidney disease- interim results of SLOW-PKD surveillance
Authors: Mochizuki Toshio , Muto Satoru , Miyake Masateru , Tanaka Toshiki , Wang Wenchyi
Published: July 2021

Background

Tolvaptan is a vasopressin type 2 receptor antagonist and has been used to treat autosomal dominant polycystic kidney disease (ADPKD) since 2014. There has been limited real-world data on the safety and efficacy of tolvaptan.

Methods

This post-marketing surveillance was conducted to evaluate the long-term safety and the efficacy of tolvaptan in Japanese patients with ADPKD in real-world clinical settings. The baseline characteristics of 1630 patients treated with tolvaptan are reported. Safety analysis comprises evaluation of adverse drug reactions (ADRs). The efficacy evaluation includes percent change in total kidney volume (TKV) and change in estimated glomerular filtration rate (eGFR) before and after tolvaptan treatment.

Results

Mean age was 49.7 ± 11.2 years and 843 (51.7%) patients were male. Baseline TKV was 2158 ± 1346 mL and eGFR was 44.4 ± 21.7 mL/min/1.73 m2. The majority of CKD patients were stage G3b (27.0%) and G4 (30.1%). Frequently reported ADRs were hepatic function abnormal (8.3%), thirst (8.2%), and hyperuricaemia (6.9%). The frequency of ALT elevation (> 30 and > 90 IU/L) was slightly high (32.9 and 8.3%) to previous studies. After tolvaptan treatment, the annual rate of percentage change in TKV reduced from 11.68%/year to 2.73%/year (P < 0.0001). Similar results were also obtained for the effect on change in eGFR from − 3.31 to − 2.28 mL/min/1.73 m2/year after initiation of tolvaptan treatment (P = 0.0403).

Conclusion

There were no major problems with safety of tolvaptan treatment and comparable efficacy for TKV and eGFR was observed in relation to the previous pivotal two randomized control trials in this post-marketing surveillance.
Faculty Attitudes Towards Article Processing Charges for Open Access Articles
Authors: Halevi Gali , Walsh Samantha
Published: July 2021

Article Processing Charges (APCs) are significant charges for publishing Open Access (OA), and have no accepted standards for authors to source the funds or negotiate the charges. While there is a growing body of literature exploring academic authors’ perceptions of OA publishing, there is little data on how authors pay for APCs. The aim of this study was to examine how authors prepare for and fund APCs, as well as their perceptions of these charges. In early 2021 the authors deployed a survey to Icahn School of Medicine at Mount Sinai faculty members via email. The survey was completed by 310 faculty, representing 10.6% of the active researcher population. Our findings show that about 50% of respondents include anticipated APC costs in grant applications, and that 16% of faculty will pay APCs using personal funds. Questions evaluating perception of APCs show that while the majority of respondents support the concept of Open Access, most believe that charges are too high and should not fall on authors.
Experimental research on water chemistry evolution in case of inadequate conservation protocols: application on surface and groundwater
Authors: Dib Dounia , Ababsa Nawel , Addad Dalila , Kadi Kenza , Khiari Abdelkader , Oualdjaoui Mounia
Published: July 2021

The objective of this study conducted from October to December 2020 in the Natural Resources and Sensitive Environment Development Laboratory was to demonstrate the importance of conservation protocols respect throw evolution of water chemistry. Ninety-nine samples representing three water types (tap, spring and mineral water) were analyzed. Storage was at laboratory temperature with no conservation protocol. Studied parameters (temperature, pH, CE, dissolved oxygen, oxydo-reduction potential, total dissolved solids, HCO3−, Ca2+, Mg2+, SO42−and Cl−) were determined using standard methods. The data registered from physico-chemical parameters were subjected to different analytical methods to assess the time affect on their values compared with initial state. The results indicate that pH and alkalinity (exprimed in HCO3−) are the most vulnerable to evolution processes with highly significant time factor effect, while the concentrations of chlorides and sulfates with conductivity levels are statistically less evolved. PCA analysis accounting 71.43% of the total variance examines contribution of water type composition as a second variation factor. Projection through F1*F2 plan demonstrates clearly two groups with surface waters (tap water) which are excessively mineralized and groundwaters (spring and bottled waters) in which pH and magnesium parameters variations are the best illustrated.
Psathyrellins A–E, Antibacterial Guanacastane Diterpenoids from Mushroom Psathyrella candolleana
Authors: Wu Han , Yang Hui-Xiang , Li Zheng-Hui , Feng Tao , Liu Ji-Kai
Published: July 2021

Five previously undescribed guanacastane diterpenoids, namely psathyrellins A–E (1–5), were obtained from cultures of the mushroom Psathyrella candolleana. Their structures with absolute configurations were elucidated by extensive spectroscopic methods. Compounds 1–3 showed antibacterial activity against four strains with MIC values in a range of 16–128 μg/mL.

Graphic Abstract
Food and alcohol disturbance among young adults during the COVID-19 lockdown in Italy: risk and protective factors
Authors: Pompili Sara , Di Tata Daniele , Bianchi Dora , Lonigro Antonia , Zammuto Marta , Baiocco Roberto , Longobardi Emiddia , Laghi Fiorenzo
Published: July 2021

Purpose

The COVID-19 lockdown measures have had a significant impact on risk behaviors as alcohol use and disordered eating. However, little is known about a serious health-risk-behavior named “food and alcohol disturbance” (FAD), characterized by engaging in dysfunctional eating on days of planned alcohol consumption. The aim of the present study was to investigate potential factors that may have put young adults at risk or protected against FAD during the COVID-19 lockdown.

Methods

A sample of 447 young adults (280 females, 167 males; range 18–26) completed an online survey during the country’s nationwide lockdown composed of self-reported measures assessing FAD behaviors, alcohol consumption, compensatory behaviors, eating and weight concerns, social support, emotion regulation strategies, and living arrangement.

Results

Our findings showed that FAD was significantly and positively correlated to alcohol consumption, use of laxatives, self-induced vomiting, eating and weight concerns, and expressive suppression, and negatively correlated to social support and living with family. Hierarchical regression analysis revealed that alcohol consumption, eating concern, and expression suppression positively predicted FAD, while social support and living with family were negative predictors.

Conclusions

Our results suggest that during the COVID-19 lockdown, preoccupation with eating and the use of expressive suppression may have increased vulnerability to FAD; conversely, perceived social support and living with family may have been a source of protection against this dysfunctional behavior.

Level of evidence

Level V, descriptive study.
Detection of pre-existing SARS-CoV-2-reactive T cells in unexposed renal transplant patients
Authors: Anft Moritz , Blazquez-Navarro Arturo , Stervbo Ulrik , Skrzypczyk Sarah , Witzke Oliver , Wirth Rainer , Choi Mira , Hugo Christian , Reinke Petra , Meister Toni Luise , Steinmann Eike , Pfaender Stephanie , Schenker Peter , Viebahn Richard , Westhoff Timm H. , Babel Nina
Published: July 2021

Background

Recent data demonstrate potentially protective pre-existing T cells reactive against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in samples of healthy blood donors, collected before the SARS-CoV-2 pandemic. Whether pre-existing immunity is also detectable in immunosuppressed patients is currently not known.

Methods

Fifty-seven patients were included in this case–control study. We compared the frequency of SARS-CoV-2-reactive T cells in the samples of 20 renal transplant (RTx) patients to 20 age/gender matched non-immunosuppressed/immune competent healthy individuals collected before the onset of the SARS-CoV-2 pandemic. Seventeen coronavirus disease 2019 (COVID-19) patients were used as positive controls. T cell reactivity against Spike-, Nucleocapsid-, and Membrane- SARS-CoV-2 proteins were analyzed by multi-parameter flow cytometry. Antibodies were analyzed by neutralization assay.

Results

Pre-existing SARS-CoV-2-reactive T cells were detected in the majority of unexposed patients and healthy individuals. In RTx patients, 13/20 showed CD4+ T cells reactive against at least one SARS-CoV-2 protein. CD8+ T cells reactive against at least one SARS-CoV-2 protein were demonstrated in 12/20 of RTx patients. The frequency and Th1 cytokine expression pattern of pre-formed SARS-CoV-2 reactive T cells did not differ between RTx and non-immunosuppressed healthy individuals.

Conclusions

This study shows that the magnitude and functionality of pre-existing SARS-CoV-2 reactive T cell in transplant patients is non-inferior compared to the immune competent cohort. Although several pro-inflammatory cytokines were produced by the detected T cells, further studies are required to prove their antiviral protection.

Graphic abstract
The Wold-Type Decomposition for m-Isometries
Authors: Kośmider Jakub
Published: July 2021

The aim of this paper is to study the Wold-type decomposition in the class ofm-isometries. One of our main results establishes an equivalent condition for an analyticm-isometry to admit the Wold-type decomposition for$$m\ge 2$$m≥2. In particular, we introduce thek-kernel condition which we use to characterize analyticm-isometric operators which are unitarily equivalent to unilateral operator valued weighted shifts for$$m\ge 2$$m≥2. As a result, we also show thatm-isometric composition operators on directed graphs with one circuit containing only one element are not unitarily equivalent to unilateral weighted shifts. We also provide a characterization ofm-isometric unilateral operator valued weighted shifts with positive and commuting weights.
A Fully-Automatic Segmentation of the Carpal Tunnel from Magnetic Resonance Images Based on the Convolutional Neural Network-Based Approach
Authors: Yang Tai-Hua , Yang Cheng-Wei , Sun Yung-Nien , Horng Ming-Huwi
Published: July 2021

Purpose

Carpal tunnel syndrome is one of the common peripheral neuropathies. For magnetic resonance imaging, segmentation of the carpal tunnel and its contents, including flexor tendons and the median nerve for magnetic resonance images is an important issue. In this study, a convolutional neural network (CNN) model, which was modified by the original DeepLabv3 + model to segment three primary structures of the carpal tunnel: the carpal tunnel, flexor tendon, and median nerve.

Methods

To extract important feature maps for segmentation of the carpal tunnel, flexor tendon, and median nerve, the proposed CNN model termed modified DeepLabv3 + uses DenseNet-121 as a backbone and adds dilated convolution to the original spatial pyramid pooling module. A MaskTrack method was used to refine the segmented results generated by modified DeepLabv3 + , which have a small and blurred appearance. For evaluation of the segmentation results, the average Dice similarity coefficients (ADSC) were used as the performance index.

Results

Sixteen MR images corresponding to different subjects were obtained from the National Cheng Kung University Hospital. Our proposed modified DeepLabv3 + generated the following ADSCs: 0.928 for carpal tunnel, 0.872 for flexor tendons and 0.785 for the median nerve. The ADSC value of 0.8053 generated the MaskTrack that 0.22 ADSC measure were improved for measuring the median nerve.

Conclusions

The experimental results showed that the proposed modified DeepLabv3 + model can promote segmentations of the carpal tunnel and its contents. The results are superior to the results generated by original DeepLabv3 + . Additionally, MaskTrack can also effectively refine median nerve segmentations.
On the Hodge conjecture for quasi-smooth intersections in toric varieties
Authors: Bruzzo Ugo , Montoya William
Published: July 2021

We establish the Hodge conjecture for some subvarieties of a class of toric varieties. First we study quasi-smooth intersections in a projective simplicial toric variety, which is a suitable notion to generalize smooth complete intersection subvarieties in the toric environment, and in particular quasi-smooth hypersurfaces. We show that under appropriate conditions, the Hodge conjecture holds for a very general quasi-smooth intersection subvariety, generalizing the work on quasi-smooth hypersurfaces of the first author and Grassi in Bruzzo and Grassi (Commun Anal Geom 28: 1773–1786, 2020). We also show that the Hodge Conjecture holds asymptotically for suitable quasi-smooth hypersurface in the Noether–Lefschetz locus, where “asymptotically” means that the degree of the hypersurface is big enough, under the assumption that the ambient variety $${{\mathbb {P}}}_\Sigma ^{2k+1}$$

P
Σ

2
k
+
1

has Picard group $${\mathbb {Z}}$$
Z
. This extends to a class of toric varieties Otwinowska’s result in Otwinowska (J Alg Geom 12: 307–320, 2003).
Indus river estuary: an assessment of potential risk of contaminants and ecosystem susceptibility
Authors: Mairaj Mushaiyada , Panhwar Sher Khan , Qamar Nazia , Rashid Shahnaz
Published: July 2021

The Indus River is proclaimed  as second most plastic-polluted rivers of the world. This river is the principal river of Pakistan and supplies freshwater for agriculture and human consumption. Its terminus into the northern Arabian Sea creates a unique ecosystem that supports a variety of aquatic organisms. In this study we have evaluate the heavy metal concentration in fishes sampled from the IRE. Muscle tissues from five fish species of ecologically and economically important were sampled and the concentrations of cadmium (0.125‒1.025 µg g−1, 0.93 ± 0.33), lead (0.250‒2.560 µg g−1, 0.92 ± 0.86), arsenic (4.178‒6.337 µg g−1, 4.24 ± 2.13) and mercury (BDL‒0.116 µg g−1, 0.05 ± 0.04) were found to be beyond optimum level. We determined the pollution load index which indicated that the IRE pollution exhibits significant seasonal oscillations. In addition to the heavy metal assay we note the frequent appearance of abnormal fishes caught in the IRE, which validates the pollution load. Multivariate approaches, canonical correspondence analysis and cluster analysis, were used to evaluate the relationships among environmental variables that influence metal concentration. This study is the first to document heavy metals detected from fishes inhabiting in IRE and highlights concerns regarding the need for management measures.

Highlights

We examined heavy metals in commercial and ecological valuable fishes in the Indus River Estuary (IRE) for the first time.

Multivariate approaches were used to determine the efficacy of environmental parameters to predict heavy metal concentration.

We described the presence of fish abnormalities as a result of contamination in the IRE.

We observe that the mechanism of action of organism health and food contamination in the IRE is poorly understood.
Law and Administration
Authors: Harlow Carol , Rawlings Richard
Published: July 2021

Law and Administration takes a contextual approach to administrative law, setting law and legal rules in the context of the social, political and economic forces that shape the law, and of the complex constitutional framework in which contemporary administrative law operates. This book contains a full account of judicial review, the traditional heartland of administrative law, and adds to this by taking into account the concerns of government, officials and agencies who operate and shape the law. It also looks at the possible future of administrative law in an increasingly automated and digitalised world. A fully revised and updated new edition, this book includes new case studies of regulatory agencies and government contracting to develop understanding of law in practice.
Citizen of the Staatsoper: Erich Kleiber's Musical Migration
Authors: Orzoff Andrea
Published: July 2021

Conductor Erich Kleiber was born in Vienna, made his reputation in Berlin, fled Nazism for Latin America, and tried briefly to return to postwar East Berlin before dying in 1956. His life illustrates the wide diversity in mid-century migratory stories. For so many of Kleiber's fellow migrants, flight disrupted established structures, contexts and networks. More recently, scholars have emphasized refugees' creative self-reinvention. Kleiber's story illustrates both these outcomes while embodying neither; his narrative is one of musical and political continuity, involving a particular kind of Habsburg cultural nostalgia, insulated by his wealth and fame.
AUTONOMY TO SET THE LEVEL OF REGULATORY PROTECTION IN INTERNATIONAL INVESTMENT LAW
Authors: Paine Joshua
Published: July 2021

This article argues that State autonomy in setting the level of protection for permissible regulatory aims can be better operationalised in the investment treaty regime. The article draws on comparative insights from WTO law, where it is established that WTO members have the right to determine the level of protection for permissible regulatory aims, although significant disciplines are placed on the means used to achieve those aims. It is then argued that investment treaties are, properly interpreted, consistent with the idea that States retain autonomy to determine the level of protection for permissible regulatory aims. Finally, the article proposes removing from the fair and equitable treatment and indirect expropriation standards proportionality balancingstricto sensu, as this undermines State autonomy in setting the level of protection. Overall, this article argues for a partial reorientation of investment law, in which non-discriminatory measures that pursue a permissible regulatory aim, including at a particular level, should not amount to a breach of a treaty where a State uses the means that involve the least possible restriction of the competing interests protected by relevant investment treaty obligations.
Profitable partnerships: The Chinese business elite and Dutch lawyers in the making of Semarang
Authors: Post Peter
Published: July 2021

This article examines the collaboration between the law firm of C.W. Baron van Heeckeren from Semarang and the Oei Tiong Ham Concern (OTHC). From the 1880s this Dutch law firm became the centre of a close-knit group of Dutch lawyer-entrepreneurs who through interlocking business directorships developed important sectors of the Javanese economy and the city of Semarang. In doing so Van Heeckeren and his associates teamed up with the Chinese business elite of the port-city. In particular they worked with the foremost Overseas Chinese capitalist, Major Oei Tiong Ham, developing profitable partnerships. The Dutch lawyers acted not only as his legal advisors, but developed his sugar empire as directors-shareholders, held major stakes in his shipping business and coolie trade, and profited from his opium trade. They moreover helped Oei Tiong Ham to acquire real estate and enterprises formerly belonging to powerful Chinese opium farmers and collaborated with him in developing infrastructural and housing projects. This article provides new and revealing details about how the business world of colonial Java worked during the early phase of Dutch economic imperialism and how the Chinese business elite seized the opportunities provided by the Dutch colonial state to advance their business interests.
Crystal structure of donepezil hydrochloride form III, C24H29NO3⋅HCl
Authors: Reid Joel W. , Kaduk James A.
Published: July 2021

The crystal structure of donepezil hydrochloride, form III, has been solved with FOX using laboratory powder diffraction data previously submitted to and published in the Powder Diffraction File. Rietveld refinement with GSAS yielded monoclinic lattice parameters of a = 14.3662(9) Å, b = 11.8384(6) Å, c = 13.5572(7) Å, and β = 107.7560(26)° (C24H30ClNO3, Z = 4, space group P21/c). The Rietveld-refined structure was compared to a density functional theory (DFT)-optimized structure, and the structures exhibit excellent agreement. Layers of donepezil molecules parallel to the (101) planes are maintained by columns of chloride anions along the b-axis, where each chloride anion hydrogen bonds to three donepezil molecules each.
Continuous phase transitions on Galton–Watson trees
Authors: Johnson Tobias
Published: July 2021

Distinguishing between continuous and first-order phase transitions is a major challenge in random discrete systems. We study the topic for events with recursive structure on Galton–Watson trees. For example, let
$\mathcal{T}_1$
be the event that a Galton–Watson tree is infinite and let
$\mathcal{T}_2$
be the event that it contains an infinite binary tree starting from its root. These events satisfy similar recursive properties:
$\mathcal{T}_1$
holds if and only if
$\mathcal{T}_1$
holds for at least one of the trees initiated by children of the root, and
$\mathcal{T}_2$
holds if and only if
$\mathcal{T}_2$
holds for at least two of these trees. The probability of
$\mathcal{T}_1$
has a continuous phase transition, increasing from 0 when the mean of the child distribution increases above 1. On the other hand, the probability of
$\mathcal{T}_2$
has a first-order phase transition, jumping discontinuously to a non-zero value at criticality. Given the recursive property satisfied by the event, we describe the critical child distributions where a continuous phase transition takes place. In many cases, we also characterise the event undergoing the phase transition.
Death Anxiety and Intrusive Thinking During the COVID-19 Pandemic
Authors: Or Gigi , Levi-Belz Yossi , Aisenberg Daniela
Published: July 2021

Abstract. COVID-19 has expanded into a life-threatening global pandemic. We examined COVID-19 effects on trauma measures, loneliness, and death anxiety in senior Israelis. Young and old adults ( N = 277) were recruited through social media. They completed online questionnaires assessing mental status during the crisis. The findings yielded correlations between trauma reactions, death anxiety, and loneliness, age-related change in rates of death anxiety and traumatic symptoms, but not in perceived loneliness. Trauma-related intrusive thinking was predicted by age, loneliness, death anxiety, and being in isolation. Traumatic reactions, as indicated by DSM-V, were observed for young adults, while grandchildren were found to be protective for older adults. Conclusions point to a high risk of postcrisis symptoms in older adults. The article recommends methods for maintaining mental health, highlighting the role of social interaction.
Crustal Velocity Variations and Constraints on Material Properties in the Charlevoix Seismic Zone, Eastern Canada
Authors: Onwuemeka J. , Liu Y. , Harrington R. M.
Published: July 2021

Crustal velocity variation within impact‐related seismic zones is commonly attributed to factors such as the presence of dense fracture networks, fluid pressure change, and compositional variations. In this study, we combine seismic tomography, rock physics analysis, and gravity anomaly modeling to quantitatively investigate the mechanisms that influence crustal velocity heterogeneities in the Charlevoix Seismic Zone (CSZ), the most active seismic zone in eastern Canada. Earthquakes in the CSZ align in two broad NE‐SW trending clusters, possibly due to the reactivation of St. Lawrence paleorift faults. Within the meteorite impact structure, earthquakes are diffusely distributed, and ubiquitous lower velocity volumes have been attributed to crustal damage from tectonic inheritance exacerbated by the meteorite impact. The Bouguer gravity anomaly contrast across the St. Lawrence River is due to density disparities between the Grenville Province on the north shore and the Appalachians on the south shore. We find a higher velocity region northeast of the impact structure that does not exhibit an observable gravity anomaly, which suggests the co‐existence of rock types of comparable densities but different elastic moduli (e.g., anorthosite and charnockite). Outside the impact structure, compositional variations control velocity changes, whereas inside the impact structure, velocity variations can be explained by porosity enhancement of up to 10% by low (0.1) aspect‐ratio cracks. Our results suggest that intense fracturing and compositional alteration, rather than pore pressure change, have the primary control on seismic velocity variations, and consequently, earthquake processes in the CSZ.
Reply to Comment by Poli et al. on “Fragmentation of the Adriatic Promontory: New Chronological Constraints From Neogene Shortening Rates Across the Southern Alps (NE Italy)”
Authors: Moulin Adrien , Benedetti Lucilla
Published: July 2021

In a comment on our manuscript published three years ago (Moulin & Benedetti [2018] https://doi.org/10.1029/2018TC004958), the authors raise concern about so‐called “mis‐interpreted alluvial and tectonic structures,” and conclude that these issues “invalidate all the consequent interpretations on the deformation rates.” Two points raised by the comment are acknowledged, and affect our results only by slightly reducing (by at most 15%) the Late Pleistocene shortening‐rate across the Eastern Southern Alps. The others issues raised by the comment are mainly dealing with the literature review, and alternative interpretations. Herein, we provide additional information to support our interpretations, and to relate our observations to existing data. Most importantly, our results do not call into question the existing consensus on both the crustal architecture of the Eastern Southern Alps, and the rate of recent shortening.
Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan
Authors: Li Cesheng , Yu Ding , Wu Xiao , Liang Hong , Zhou Zhijun , Xie Yong , Li Taojing , Wu Junzheng , Lu Fengping , Feng Lu , Mao Min , Lin Lianzhen , Guo Huanhuan , Yue Shenglan , Wang Feifei , Peng Yan , Hu Yong , Wang Zejun , Yu Jianhong , Zhang Yong , Lu Jia , Ning Haoran , Yang Huichuan , Fu Daoxing , He Yanlin , Zhou Dongbo , Du Tao , Duan Kai , Dong Demei , Deng Kun , Zou Xia , Zhang Ya , Zhou Rong , Gao Yang , Zhang Xinxin , Yang Xiaoming
Published: July 2021

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 35.7% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.
Lack of consideration of sex and gender in COVID-19 clinical studies
Authors: Brady Emer , Nielsen Mathias Wullum , Andersen Jens Peter , Oertelt-Prigione Sabine
Published: July 2021

Sex and gender differences impact the incidence of SARS-CoV-2 infection and COVID-19 mortality. Furthermore, sex differences influence the frequency and severity of pharmacological side effects. A large number of clinical trials to develop new therapeutic approaches and vaccines for COVID-19 are ongoing. We investigated the inclusion of sex and/or gender in COVID-19 studies on ClinicalTrials.gov, collecting data for the period January 1, 2020 to January 26, 2021. Here, we show that of the 4,420 registered SARS-CoV-2/COVID-19 studies, 935 (21.2%) address sex/gender solely in the context of recruitment, 237 (5.4%) plan sex-matched or representative samples or emphasized sex/gender reporting, and only 178 (4%) explicitly report a plan to include sex/gender as an analytical variable. Just eight (17.8%) of the 45 COVID-19 related clinical trials published in scientific journals until December 15, 2020 report sex-disaggregated results or subgroup analyses.
Neofunctionalisation of the Sli gene leads to self-compatibility and facilitates precision breeding in potato
Authors: Eggers Ernst-Jan , van der Burgt Ate , van Heusden Sjaak A. W. , de Vries Michiel E. , Visser Richard G. F. , Bachem Christian W. B. , Lindhout Pim
Published: July 2021

Genetic gain in potato is hampered by the heterozygous tetraploid genome of cultivated potato. Converting potato into a diploid inbred-line based F1-hybrid crop provides a promising route towards increased genetic gain. The introduction of a dominant S-locus inhibitor (Sli) gene into diploid potato germplasm allows efficient generation of self-fertilized seeds and thus the development of potato inbred lines. Little is known about the structure and function of theSlilocus. Here we describe the mapping ofSlito a 12.6 kb interval on chromosome 12 using a recombinant screen approach. One of two candidate genes present in this interval shows a unique sequence that is exclusively present in self-compatible lines. We describe an expression vector that converts self-incompatible genotypes into self-compatible and a CRISPR-Cas9 vector that converts SC genotypes into SI. TheSligene encodes an F-box protein that is specifically expressed in pollen from self-compatible plants. A 533 bp insertion in the promotor of that gene leads to a gain of function mutation, which overcomes self-pollen rejection.
Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins
Authors: Liu Zhiwen , Zhao Fanglong , Zhao Boyang , Yang Jie , Ferrara Joseph , Sankaran Banumathi , Venkataram Prasad B. V. , Kundu Biki Bapi , Phillips George N. , Gao Yang , Hu Liya , Zhu Tong , Gao Xue
Published: July 2021

Prenylated indole alkaloids featuring spirooxindole rings possess a 3R or 3S carbon stereocenter, which determines the bioactivities of these compounds. Despite the stereoselective advantages of spirooxindole biosynthesis compared with those of organic synthesis, the biocatalytic mechanism for controlling the 3R or 3S-spirooxindole formation has been elusive. Here, we report an oxygenase/semipinacolase CtdE that specifies the 3S-spirooxindole construction in the biosynthesis of 21R-citrinadin A. High-resolution X-ray crystal structures of CtdE with the substrate and cofactor, together with site-directed mutagenesis and computational studies, illustrate the catalytic mechanisms for the possible β-face epoxidation followed by a regioselective collapse of the epoxide intermediate, which triggers semipinacol rearrangement to form the 3S-spirooxindole. Comparing CtdE with PhqK, which catalyzes the formation of the 3R-spirooxindole, we reveal an evolutionary branch of CtdE in specific 3S spirocyclization. Our study provides deeper insights into the stereoselective catalytic machinery, which is important for the biocatalysis design to synthesize spirooxindole pharmaceuticals.
Encapsulate α-MnO2 nanofiber within graphene layer to tune surface electronic structure for efficient ozone decomposition
Authors: Zhu Guoxiang , Zhu Wei , Lou Yang , Ma Jun , Yao Wenqing , Zong Ruilong , Zhu Yongfa
Published: July 2021

Major challenges encountered when developing manganese-based materials for ozone decomposition are related to the low stability and water inactivation. To solve these problems, a hierarchical structure consisted of graphene encapsulating α-MnO2 nanofiber was developed. The optimized catalyst exhibited a stable ozone conversion efficiency of 80% and excellent stability over 100 h under a relative humidity (RH) of 20%. Even though the RH increased to 50%, the ozone conversion also reached 70%, well beyond the performance of α-MnO2 nanofiber. Here, surface graphite carbon was activated by capturing the electron from inner unsaturated Mn atoms. The excellent stability originated from the moderate local work function, which compromised the reaction barriers in the adsorption of ozone molecule and the desorption of the intermediate oxygen species. The hydrophobic graphene shells hindered the chemisorption of water vapour, consequently enhanced its water resistance. This work offered insights for catalyst design and would promote the practical application of manganese-based catalysts in ozone decomposition.
Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5
Authors: Zhang Hui , Chen Kun , Tan Qiuxiang , Shao Qiang , Han Shuo , Zhang Chenhui , Yi Cuiying , Chu Xiaojing , Zhu Ya , Xu Yechun , Zhao Qiang , Wu Beili
Published: July 2021

The chemokine receptor CCR5 plays a vital role in immune surveillance and inflammation. However, molecular details that govern its endogenous chemokine recognition and receptor activation remain elusive. Here we report three cryo-electron microscopy structures of Gi1 protein-coupled CCR5 in a ligand-free state and in complex with the chemokine MIP-1α or RANTES, as well as the crystal structure of MIP-1α-bound CCR5. These structures reveal distinct binding modes of the two chemokines and a specific accommodate pattern of the chemokine for the distal N terminus of CCR5. Together with functional data, the structures demonstrate that chemokine-induced rearrangement of toggle switch and plasticity of the receptor extracellular region are critical for receptor activation, while a conserved tryptophan residue in helix II acts as a trigger of receptor constitutive activation.
Lure-and-kill macrophage nanoparticles alleviate the severity of experimental acute pancreatitis
Authors: Zhang Qiangzhe , Zhou Julia , Zhou Jiarong , Fang Ronnie H. , Gao Weiwei , Zhang Liangfang
Published: July 2021

Acute pancreatitis is a disease associated with suffering and high lethality. Although the disease mechanism is unclear, phospholipase A2 (PLA2) produced by pancreatic acinar cells is a known pathogenic trigger. Here, we show macrophage membrane-coated nanoparticles with a built-in ‘lure and kill’ mechanism (denoted ‘MΦ-NP(L&K)’) for the treatment of acute pancreatitis. MΦ-NP(L&K) are made with polymeric cores wrapped with natural macrophage membrane doped with melittin and MJ-33. The membrane incorporated melittin and MJ-33 function as a PLA2 attractant and a PLA2 inhibitor, respectively. These molecules, together with membrane lipids, work synergistically to lure and kill PLA2 enzymes. These nanoparticles can neutralize PLA2 activity in the sera of mice and human patients with acute pancreatitis in a dose-dependent manner and suppress PLA2-induced inflammatory response accordingly. In mouse models of both mild and severe acute pancreatitis, MΦ-NP(L&K) confer effective protection against disease-associated inflammation, tissue damage and lethality. Overall, this biomimetic nanotherapeutic strategy offers an anti-PLA2 treatment option that might be applicable to a wide range of PLA2-mediated inflammatory disorders.
Both microRNA-455-5p and -3p repress hypoxia-inducible factor-2α expression and coordinately regulate cartilage homeostasis
Authors: Ito Yoshiaki , Matsuzaki Tokio , Ayabe Fumiaki , Mokuda Sho , Kurimoto Ryota , Matsushima Takahide , Tabata Yusuke , Inotsume Maiko , Tsutsumi Hiroki , Liu Lin , Shinohara Masahiro , Tanaka Yoko , Nakamichi Ryo , Nishida Keiichiro , Lotz Martin K. , Asahara Hiroshi
Published: July 2021

Osteoarthritis (OA), the most common aging-related joint disease, is caused by an imbalance between extracellular matrix synthesis and degradation. Here, we discover that both strands of microRNA-455 (miR-455), -5p and -3p, are up-regulated by Sox9, an essential transcription factor for cartilage differentiation and function. Both miR-455-5p and -3p are highly expressed in human chondrocytes from normal articular cartilage and in mouse primary chondrocytes. We generate miR-455 knockout mice, and find that cartilage degeneration mimicking OA and elevated expression of cartilage degeneration-related genes are observed at 6-months-old. Using a cell-based miRNA target screening system, we identify hypoxia-inducible factor-2α (HIF-2α), a catabolic factor for cartilage homeostasis, as a direct target of both miR-455-5p and -3p. In addition, overexpression of both miR-455-5p and -3p protect cartilage degeneration in a mouse OA model, demonstrating their potential therapeutic value. Furthermore, knockdown of HIF-2α in 6-month-old miR-455 knockout cartilage rescues the elevated expression of cartilage degeneration-related genes. These data demonstrate that both strands of a miRNA target the same gene to regulate articular cartilage homeostasis.
Children’s role in the COVID-19 pandemic: a systematic review of early surveillance data on susceptibility, severity, and transmissibility
Authors: Gaythorpe Katy A. M. , Bhatia Sangeeta , Mangal Tara , Unwin H. Juliette T. , Imai Natsuko , Cuomo-Dannenburg Gina , Walters Caroline E. , Jauneikaite Elita , Bayley Helena , Kont Mara D. , Mousa Andria , Whittles Lilith K. , Riley Steven , Ferguson Neil M.
Published: July 2021

SARS-CoV-2 infections have been reported in all age groups including infants, children, and adolescents. However, the role of children in the COVID-19 pandemic is still uncertain. This systematic review of early studies synthesises evidence on the susceptibility of children to SARS-CoV-2 infection, the severity and clinical outcomes in children with SARS-CoV-2 infection, and the transmissibility of SARS-CoV-2 by children in the initial phases of the COVID-19 pandemic. A systematic literature review was conducted in PubMed. Reviewers extracted data from relevant, peer-reviewed studies published up to July 4th 2020 during the first wave of the SARS-CoV-2 outbreak using a standardised form and assessed quality using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. For studies included in the meta-analysis, we used a random effects model to calculate pooled estimates of the proportion of children considered asymptomatic or in a severe or critical state. We identified 2775 potential studies of which 128 studies met our inclusion criteria; data were extracted from 99, which were then quality assessed. Finally, 29 studies were considered for the meta-analysis that included information of symptoms and/or severity, these were further assessed based on patient recruitment. Our pooled estimate of the proportion of test positive children who were asymptomatic was 21.1% (95% CI: 14.0–28.1%), based on 13 included studies, and the proportion of children with severe or critical symptoms was 3.8% (95% CI: 1.5–6.0%), based on 14 included studies. We did not identify any studies designed to assess transmissibility in children and found that susceptibility to infection in children was highly variable across studies. Children’s susceptibility to infection and onward transmissibility relative to adults is still unclear and varied widely between studies. However, it is evident that most children experience clinically mild disease or remain asymptomatically infected. More comprehensive contact-tracing studies combined with serosurveys are needed to quantify children’s transmissibility relative to adults. With children back in schools, testing regimes and study protocols that will allow us to better understand the role of children in this pandemic are critical.