bluuebunny/crossref_metadata_2025_split huggingface dataset:
The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease
Authors: Avolio Elisa , Carrabba Michele , Milligan Rachel , Kavanagh Williamson Maia , Beltrami Antonio P. , Gupta Kapil , Elvers Karen T. , Gamez Monica , Foster Rebecca R. , Gillespie Kathleen , Hamilton Fergus , Arnold David , Berger Imre , Davidson Andrew D. , Hill Darryl , Caputo Massimo , Madeddu Paolo 
Published: November 2021

Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a broad range of clinical responses including prominent microvascular damage. The capacity of SARS-CoV-2 to infect vascular cells is still debated. Additionally, the SARS-CoV-2 Spike (S) protein may act as a ligand to induce non-infective cellular stress. We tested this hypothesis in pericytes (PCs), which are reportedly reduced in the heart of patients with severe coronavirus disease-2019 (COVID-19). Here we newly show that the in vitro exposure of primary human cardiac PCs to the SARS-CoV-2 wildtype strain or the α and δ variants caused rare infection events. Exposure to the recombinant S protein alone elicited signalling and functional alterations, including: (1) increased migration, (2) reduced ability to support endothelial cell (EC) network formation on Matrigel, (3) secretion of pro-inflammatory molecules typically involved in the cytokine storm, and (4) production of pro-apoptotic factors causing EC death. Next, adopting a blocking strategy against the S protein receptors angiotensin-converting enzyme 2 (ACE2) and CD147, we discovered that the S protein stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) through the CD147 receptor, but not ACE2, in PCs. The neutralisation of CD147, either using a blocking antibody or mRNA silencing, reduced ERK1/2 activation, and rescued PC function in the presence of the S protein. Immunoreactive S protein was detected in the peripheral blood of infected patients. In conclusion, our findings suggest that the S protein may prompt PC dysfunction, potentially contributing to microvascular injury. This mechanism may have clinical and therapeutic implications.
Randomisierte Studien zum Einsatz von Rekonvaleszentenplasma bei COVID-19: eine Standortbestimmung
Authors: Körper Sixten , Appl Thomas , Jahrsdörfer Bernd , Lotfi Ramin , Rojewski Markus , Wuchter Patrick , Tonn Torsten , Bakchoul Tamam , Karatas Mesut , Schmidt Michael , Klüter Harald , Seifried Erhard , Schrezenmeier Hubert 
Published: November 2021

ZusammenfassungPlasma von genesenen Spendern mit COVID-19 (COVID-19 Convalescent Plasma, CCP) wurde als Behandlungsoption für Patienten mit COVID-19 in Betracht gezogen. In der ersten Phase der Pandemie wurden mehrere Fallberichte und Fallkontrollstudien mit Hinweisen auf eine therapeutische Wirkung veröffentlicht. Inzwischen liegen die Ergebnisse zahlreicher randomisierter Studien vor. Die Studien unterscheiden sich in vielen Aspekten, u. a. in den Patientenpopulationen, die von ambulanten Patienten mit mildem COVID-19 bis zu kritisch Kranken reichten, wie auch den Endpunkten. Ebenso war der Behandlungsstandard innerhalb der klinischen Studien sehr unterschiedlich. Vor allem aber unterschied sich das Prüfpräparat CCP erheblich in Bezug auf das Behandlungsschema, das Volumen und den Gehalt an Antikörpern. Im Folgenden werden wir die Ergebnisse der bisher publizierten randomisierten Studien diskutieren. Aus den bisher veröffentlichten Ergebnissen lässt sich eine Wirksamkeit von CCP ableiten, sofern es sehr hohe Titer neutralisierender Antikörper enthält und früh im Krankheitsverlauf verabreicht wird. COVID-19-Rekonvaleszenten-Plasma ist noch keine Routinebehandlung und sollte möglichst weiter in klinischen Studien untersucht werden. Neu konzipierte Studien sollten sich auf die frühe Anwendung von CCP mit einem hohen Gehalt an neutralisierenden Antikörpern bei Patienten mit hohem Risiko für eine Progression zu einer schweren COVID-19-Erkrankung konzentrieren und wichtige Begleitmedikationen kontrollieren.
Recyclable Pd2dba3/XPhos/PEG-2000 System for Efficient Boryl­ation of Aryl Chlorides: Practical Access to Aryl Boronates
Authors: Cai Mingzhong , Huang Bin , Luo Chengkai , Xu Caifeng 
Published: November 2021

AbstractPd2dba3/XPhos in poly(ethylene glycol) (PEG-2000) is shown to be a highly stable and efficient catalyst for the borylation of aryl chlorides with bis(pinacolato)diboron. The borylation reaction proceeds smoothly at 110 °C, delivering a wide variety of aryl boronates in good to excellent yields with high functional group tolerance. The crude products were easily isolated via simple extraction of the reaction mixture with cyclohexane. Moreover, both expensive Pd2dba3 and XPhos in PEG-2000 system could be readily recycled and reused more than six times without loss of catalytic efficiency.
Total Synthesis of (–)-Aristoquinoline via an Intramolecular Nitrilium Ion Cyclization
Authors: Reber Keith P. , Gujarati Priyansh D. 
Published: November 2021

AbstractThe enantioselective total synthesis of the alkaloid aristoquinoline has been achieved in seven steps and 26% overall yield. A new preparation of the useful synthetic building block (–)-α-terpinyl amine was also developed in order to avoid stoichiometric mercury reagents or azide-containing intermediates. Key steps in the optimized synthetic route include an intramolecular nitrilium ion cyclization to form the characteristic azabicyclo[3.3.1]nonane ring system and a dia­stereoselective reduction of the resulting imine mixture to afford the natural product. An isomer of aristoquinoline containing an exocyclic alkene was also obtained and found to exhibit unusual chromatographic and spectroscopic properties.
Left-Handedness in Obstetrics and Gynecology: A Nationwide Survey of U.S. Trainees and Educators
Authors: Moutos Christopher P. , Arena Goncharov Daphne D. , Saad Antonio F. , Richardson Gwyn , Jain Sangeeta 
Published: November 2021

Objective This study aimed to evaluate the views and influence of left-handedness among obstetrics and gynecology (OBGYN) trainees and educators and to identify perceived obstacles in training by left-handed (LH) trainees.
Study Design An online survey was sent to the U.S. Obstetrics and Gynecology training programs. All participants were asked questions on hand preference for various medical and nonmedical activities, as well as on demographics. Participant responses to handedness and their role as a learner or educator directed them toward further questions. Trainees were surveyed on their experience and outlook as a LH physician in OBGYN. Educators were surveyed on their experience and attitudes in working with LH trainees. LH educators were also surveyed on their experience as a LH physician, similar to the LH trainees. Chi-square or Fisher's exact analysis was used as appropriate, with p-value <0.05 considered statistically significant.
Results Responses were received from 21 training programs, totaling 304 individuals. Participants included 205 learners (156 right handed and 49 left handed), and 99 faculty (82 right handed and 17 left handed). A lack of LH surgical instrument availability (93.6%) and difficulty using right-handed (RH) instruments (83%) were notable obstacles reported by LH learners. The majority of LH learners (57.4%) did not consider their handedness to be disadvantageous but did note added difficulty when training under RH mentors when compared with training under LH mentors (66%). In contrast to LH educators, RH educators endorsed added difficulty in instructing operative procedures to LH learners (32.1 vs. 13.3%, p = 0.012).
Conclusion LH trainees face unique challenges during their OBGYN training. Educators would benefit from guidance on how best to manage these trainees. Educators should work to adapt surgical and procedural techniques to accommodate LH trainees.
Key Points
Serum Lactate Level as a Predictor for Blood Transfusion in Postpartum Hemorrhage
Authors: Agrawal Surbhi , Smith Maria , Berg Robert , Hoskins Iffath A. 
Published: November 2021

Objective Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality. At present, there are no reliable clinical or laboratory indicators to identify which patients might require blood transfusions during a PPH. Serum lactate has long been used as an early biomarker of tissue hypoperfusion in trauma settings. The aim of this study is to understand serum lactate's role in the management of obstetric hemorrhage.
Study Design A retrospective chart review was performed of women who delivered between 2016 and 2019 at our institution and experienced a PPH. The patients were divided into two groups: those with a normal serum lactate level, defined as ≤2 mmol/L, and those with an abnormal serum lactate level, defined as >2 mmol/L. Need for packed red blood cell transfusion, as part of the resuscitation, was assessed for both groups.
Results During the study period, 938 women experienced PPH. Of these, 108 (11.5%) had a normal serum lactate, ≤2 mmol/L, and 830 (88.5%) had an abnormal lactate, >2 mmol/L. Women with elevated lactate levels were more likely to receive a blood transfusion versus those with a normal lactate level (57.0 vs. 46.3%, p = 0.035, respectively). Additionally, the average number of blood transfusions administered was significantly higher in the abnormal lactate group versus in the normal lactate group (1.34 vs. 0.97, respectively, p = 0.004). In a multivariable linear regression model, increasing serum lactate levels were found to be predictive of requiring more than 1 unit of blood (p < 0.001).
Conclusion Women with elevated serum lactate levels were more likely to require blood transfusions during a PPH versus those with a normal serum lactate level. Thus, serum lactate levels are useful as an early indicator of requirement for blood transfusion in the management of obstetric hemorrhage.
Key Points
The impact of specialization, ownership, competition and regulation on efficiency: a case study of Indian seaports
Authors: Adler Nicole , Hirte Georg , Kumar Shravana , Niemeier Hans-Martin 
Published: November 2021

AbstractWe develop a two-stage formulation to estimate seaport performance and to understand the drivers of efficiency, which could potentially include specialization, ownership, competition and tariff regulation. The first-stage non-parametric, slacks-based measure estimates the technical efficiency of each port. For the second-stage analysis, we develop a set of contextual variables including an absolute measure of specialization and a berth-level measure of ownership structure. To measure competition, we develop spatial measures that quantify the level of competition as a function of distance. We subsequently apply this formulation to major Indian seaports, covering a period of 21 years, from 1995 to 2015. The first-stage results suggest that average seaport efficiency has increased gradually over time. The second-stage fixed effects regressions show that specialization and external stakeholder participation have significant positive impacts on seaport performance. Perhaps surprisingly, we find that, in a tiered governance framework, competition between major seaports and local seaports has a significant negative impact on performance, potentially due to excessive infrastructure. Finally, changes in the regulatory mechanism over time are shown to be efficiency improving.
Mobility and phone call behavior explain patterns in poverty at high-resolution across multiple settings
Authors: Steele Jessica E. , Pezzulo Carla , Albert Maximilian , Brooks Christopher J. , zu Erbach-Schoenberg Elisabeth , O’Connor Siobhán B. , Sundsøy Pål R. , Engø-Monsen Kenth , Nilsen Kristine , Graupe Bonita , Nyachhyon Rajesh Lal , Silpakar Pradeep , Tatem Andrew J. 
Published: November 2021

AbstractCall detail records (CDRs) from mobile phone metadata are a promising data source for mapping poverty indicators in low- and middle-income countries. These data provide information on social networks, call behavior, and mobility patterns in a population, which are correlated with measures of socioeconomic status. CDRs are passively collected and provide information with high spatial and temporal resolution. Identifying features from these data that are generalizable and able to predict poverty and wealth beyond a single context could promote broader usage of mobile data, contribute to a reduction in the cost of socioeconomic data collection and processing, as well as complement existing census and survey-based methods of poverty estimation with improved temporal resolution. This is especially important within the context of the sustainable development goals (SDGs), where poverty and related health indicators are to be reduced significantly across subnational geographies by 2030. Here we utilize measures of cell phone user behavior derived from three CDR datasets within a Bayesian modeling framework to map poverty and wealth patterns across Namibia, Nepal, and Bangladesh. We demonstrate five metrics of user mobility and call behavior that are able to explain between 50% and 65% of the variance in socioeconomic status nationally for these three countries. These key metrics prove useful in very different contexts and can be readily provided as part of an existing CDR platform or software package. This paper provides a key contribution in this regard by identifying such metrics relevant to estimating poverty. We highlight the inclusion of ancillary data and local context as an important factor in understanding model outputs when targeting poverty alleviation strategies.
Scientific Value Relativism
Authors: Ruiz-Gallardón Isabel 
Published: November 2021

AbstractRelativism stresses that value judgements are statements about meaning and not about facts, about “ought” and not about “is”. Professor Arnold Brecht explained and substantiated the existence of a link between “is” and “ought”, which does not have a logical character, but does indeed have a “factual” one; a link that, being so evident and intersubjectively transmissible, makes doctrine based on logical separation less important. Suffice it to observe this factual link in a sufficient number of individual cases to arrive inductively at the conclusion of its universal presence with the same certainty or uncertainty as any other inductive conclusion. This paper studies the considerations made by Brecht in the first half of the twentieth century on universal elements that do not derive from arbitrary decisions on justice, but can stem from the necessary feelings inherent to human beings. Confirming this is within the bounds of scientific research. And if these elements are considered as a whole and combined with the two methods proposed by the relativists—clarifying the meaning of the proposed interpretations and analysing their implications—the demonstrable elements obtained are of considerable worth.
Generalized Kohn–Sham equations with accurate total energy and single-particle eigenvalue spectrum
Authors: Pitts Thomas C. , Lathiotakis Nektarios N. , Gidopoulos Nikitas 
Published: November 2021

We propose a new generalized Kohn–Sham or constrained hybrid method, where the exchange potential is the (equally weighted) average of the nonlocal Fock–exchange term and the self-interaction-corrected exchange potential, as obtained from our constrained minimization method of semi-local approximations. The new method gives an accurate single-particle eigenvalue spectrum with an average deviation between (the negative of) the valence orbital eigenvalues and the experimental ionization potentials of about 0.5 eV, while the deviation of core orbitals is within 2 eV. The improvement in the eigenvalue spectrum is achieved with a minimal increase in the total energy.
Chemical bonding theories as guides for self-interaction corrected solutions: Multiple local minima and symmetry breaking
Authors: Trepte Kai , Schwalbe Sebastian , Liebing Simon , Schulze Wanja T. , Kortus Jens , Myneni Hemanadhan , Ivanov Aleksei V. , Lehtola Susi 
Published: November 2021

Fermi–Löwdin orbitals (FLOs) are a special set of localized orbitals, which have become commonly used in combination with the Perdew–Zunger self-interaction correction (SIC) in the FLO-SIC method. The FLOs are obtained for a set of occupied orbitals by specifying a classical position for each electron. These positions are known as Fermi-orbital descriptors (FODs), and they have a clear relation to chemical bonding. In this study, we show how FLOs and FODs can be used to initialize, interpret, and justify SIC solutions in a common chemical picture, both within FLO-SIC and in traditional variational SIC, and to locate distinct local minima in either of these approaches. We demonstrate that FLOs based on Lewis theory lead to symmetry breaking for benzene—the electron density is found to break symmetry already at the symmetric molecular structure—while ones from Linnett’s double-quartet theory reproduce symmetric electron densities and molecular geometries. Introducing a benchmark set of 16 planar cyclic molecules, we show that using Lewis theory as the starting point can lead to artifactual dipole moments of up to 1 D, while Linnett SIC dipole moments are in better agreement with experimental values. We suggest using the dipole moment as a diagnostic of symmetry breaking in SIC and monitoring it in all SIC calculations. We show that Linnett structures can often be seen as superpositions of Lewis structures and propose Linnett structures as a simple way to describe aromatic systems in SIC with reduced symmetry breaking. The role of hovering FODs is also briefly discussed.
Click chemistry–enabled CRISPR screening reveals GSK3 as a regulator of PLD signaling
Authors: Bumpus Timothy W. , Huang Shiying , Tei Reika , Baskin Jeremy M. 
Published: November 2021

Significance
The application of CRISPR-Cas9 to genome-wide screening has revolutionized our ability to discover new functions for genes and regulators of physiological processes. However, a major constraint placed on such screens is the choice of phenotypic selection step, typically limited to live/dead or conventional fluorescent reporter/labeling. Here, we develop a CRISPR interference–based screening platform harnessing click chemistry tagging to reveal regulators of a specific signaling pathway. Using this tool, we discovered a regulatory circuit involving glycogen synthase kinase 3 and protein kinase C in the control of phospholipase D signaling. More broadly, this work illustrates how emergent chemical biology approaches can expand the power of genome-wide CRISPR screening to elucidate mechanisms regulating specific enzyme-driven signaling pathways.
Lymph node formation and B cell homeostasis require IKK-α in distinct endothelial cell–derived compartments
Authors: McCorkell Kelly A. , Jayachandran Nipun , Cully Michelle D. , Freund-Brown Jacquelyn , Weinkopff Tiffany , Monslow James , Hu Yinling , Puré Ellen , Freedman Bruce D. , Alvarez Jorge I. , Cancro Michael P. , May Michael J. 
Published: November 2021

Significance
Noncanonical NF-κB controls lymph node (LN) formation and B cell homeostasis. We previously demonstrated that IKK-α–dependent noncanonical NF-κB signaling is activated in vascular endothelial cells (ECs). Here, we find that ablation of IKK-α in ECs leads to complete loss of LNs and markedly reduced B cell numbers, recapitulating the phenotype of global IKK-α inactivation. Using cell type–specific conditional knockout models, we find that loss of IKK-α in hematopoietic cells underlies the B cell defect, whereas deletion in lymphatic ECs (LECs) results in the absence of LNs. Thus, our findings reveal that IKK-α in distinct EC-derived compartments is uniquely required to promote B cell homeostasis and LN development and demonstrate that LEC-intrinsic IKK-α is essential for LN formation.
The physical basis of mollusk shell chiral coiling
Authors: Chirat Régis , Goriely Alain , Moulton Derek E. 
Published: November 2021

Significance
A theoretical model suggests that a mechanically induced twist of the soft body underlies the formation of helicospiral shells in snails and ammonites and also accounts for the startling and unique meandering shells observed in certain species. This theory addresses fundamental developmental issues of chirality and symmetry breaking: in the case of ammonites, how a bilaterally symmetric body can sometimes secrete a nonsymmetric shell; for gastropods, how an intrinsic twist possibly due to the asymmetric development of musculature can provide a mechanical motor for generating a chiral shell. Our model highlights the importance of physical forces in biological development and sheds light on shell coiling in snails, which have been used for a century as model organisms in genetic research.
Claudin-2 and claudin-12 form independent, complementary pores required to maintain calcium homeostasis
Authors: Beggs Megan R. , Young Kennedi , Pan Wanling , O’Neill Debbie D. , Saurette Matthew , Plain Allein , Rievaj Juraj , Doschak Michael R. , Cordat Emmanuelle , Dimke Henrik , Alexander R. Todd 
Published: November 2021

Significance

Significant calcium absorption across renal and intestinal epithelia occurs via the paracellular pathway. However, the identity of the paracellular pore involved is unknown. Claudin-2 and claudin-12 contribute paracellular calcium permeability in cell models, but single knockout animals don’t have altered serum calcium or bone mineralization. To investigate this,
Cldn2/12
double knockout mice were generated. They display decreased intestinal calcium absorption and renal calcium wasting, resulting in hypocalcemia and markedly reduced bone mineralization. Claudin-2 and claudin-12 don’t physically interact in vitro, and coexpression has an additive effect on calcium permeability. Our work identifies claudin-2 and claudin-12 as important constituents of the paracellular Ca
2+
pathway in intestine and kidney enabling calcium transport and highlights their important complementary roles in maintaining calcium homeostasis.
Scaling concepts in ‘omics: Nuclear lamin-B scales with tumor growth and often predicts poor prognosis, unlike fibrosis
Authors: Vashisth Manasvita , Cho Sangkyun , Irianto Jerome , Xia Yuntao , Wang Mai , Hayes Brandon , Wieland Daniel , Wells Rebecca , Jafarpour Farshid , Liu Andrea , Discher Dennis E. 
Published: November 2021

Significance
Nonlinear scaling analyses pervade polymer physics and chemistry, yielding characteristic exponents that conceivably apply to expressed genes and their assemblies. Stoichiometric scaling and fractal scaling indeed emerge as gene-gene power laws in human cancer data for key structural polymers in nuclei or extracellular matrix. Only one nuclear envelope factor, lamin-B1, scales with tumor proliferation genes, predicting poor survival for multiple cancers, including liver cancer. These genes include one transcription factor that directly regulates lamin-B1 and broadly categorizes prognosis. In contrast, collagen-1 scales with fibrosis genes, increases in tumors relative to adjacent tissue, and predicts “wound that heals”–type survival only for liver cancer—albeit intertumor comparisons show no correlation without adjacent referencing. Scaling thus identifies and characterizes fundamental gene-gene interrelationships.