bluuebunny/crossref_metadata_2025 huggingface dataset:
In the Christian Archives: Sacrifice, the Higher Criticism, and the History of Religion
Authors: Sheehan Jonathan
Published: August 2021

Much recent scholarship has shown just how indebted the secular sciences of religion were to the Protestant world from which they grew. Yet this “Protestant world” is typically described schematically, as if Protestantism offered a coherent worldview or even a consistent set of doctrines. A different picture emerges if we deepen our historical horizon, and explore the reflexes, aspirations, and norms that have found a home in the Christian (in this case, Protestant) theological imagination. This “Christian archive” was a heterogeneous place, with room for many things that we would now call secular or even profane. Protestant reform in fact began by condemning this heterogeneity, insisting that much of what the church had come to see was sacred was, at best, only and all too human. Yet centuries of conflict in Europe over the truth of Christianity only pluralized this archive further. The nineteenth-century history of religion grew less out of “Protestantism,” in other words, than out of the sedimented mixture of theological, historical, philological, and anthropological materials inherited from these earlier moments. It was, moreover, also an intellectual project that discovered new uses for these materials and thereby opened new horizons of humanistic inquiry. This article makes this argument with reference to sacrifice—a theological challenge for Christian thinkers from the outset of the tradition, but especially for Protestants; a magnet for diverse historical, anthropological, and theological reflections; and a productive zone of inquiry for the nineteenth-century German philosophers, philologians, and “higher critics” of the Hebrew Bible who together helped create the modern history of religion.
The Last Judgment before the Last
Authors: Wimmer Mario
Published: August 2021

Throughout the nineteenth century, most historians preferred not to ask philosophical questions. In their writings, however, they indirectly engaged with problems about the character of the world-historical process, thus confronting what might be called penultimate questions. This article analyzes both the notions and the practices of historical work in Leopold Ranke's writings to consider how his spontaneous philosophy of history came to shape an entire discipline. It argues that Ranke crafted what I call historical figures from archival materials and that these served as equivalents to concepts in G. W. F. Hegel's philosophical world history. The writing of history has not yet escaped the logic of these narrative figures of historical argumentation.
The Making of a Movement: An Intergenerational Mobilization Model of the Nonviolent Nashville Civil Rights Movement
Authors: Cornfield Daniel B. , Coley Jonathan S. , Isaac Larry W. , Dickerson Dennis C.
Published: August 2021

The 1960s-era, Nashville nonviolent civil rights movement—with its iconic lunch counter sit-ins—was not only an exemplary local movement that dismantled Jim Crow in downtown public accommodations. It was by design the chief vehicle for the intergenerational mentoring and training of activists that led to a dialogical diffusion of nonviolence praxis throughout the Southern civil rights movement of this period. In this article, we empirically derive from oral-history interviews with activists and archival sources a new “intergenerational model of movement mobilization” and assess its contextual and bridge-leading sustaining factors. After reviewing the literatures on dialogical diffusion and bridge building in social movements, we describe the model and its sustaining conditions—historical, demographic, and spatial conditions—and conclude by presenting a research agenda on the sustainability and generalizability of the Nashville model.
Eighteen years of Clearfield™ rice in Brazil: what have we learned?
Authors: Avila Luis Antonio de , Marchesan Enio , Camargo Edinalvo R. , Merotto Aldo , Ulguim André da Rosa , Noldin José Alberto , Andres André , Mariot Carlos H. P. , Agostinetto Dirceu , Dornelles Sylvio H. B. , Markus Catarine
Published: July 2021

Clearfield™ (CL) rice (Oryza sativa L.) is a weedy rice (Oryza spp.; synonym = red rice) control tool that has been used in Brazil since 2003. This system includes the use of an imidazolinone (IMI)-tolerant cultivar and the application of IMI herbicides. In this review article, Brazilian weed scientists evaluate the challenges and lessons learned over 18 yr of CL use. CL system benefits include selective weedy rice control, better crop establishment during the most advantageous period of the year, and more efficient fertilizer use. In Rio Grande do Sul state, the CL system, in conjunction with other improvements, has contributed to rice grain yield gains from 5,500 kg ha−1 before 2002 to around 8,400 kg ha−1 currently. In contrast, the main problem that has arisen over this period is the rapid evolution of IMI-resistant weedy rice, caused by gene flow from CL rice cultivars. The off-label use (rate and continuous use) of IMI herbicides has contributed to the evolution of resistance in Echinochloa spp. and other weeds. IMI herbicide carryover has also affected susceptible crops grown after CL rice. Crop rotation with soybean [Glycine max (L.) Merr.] is increasing, ensuring system sustainability. The importance of minimum tillage has also become apparent. Such cultivation includes applying nonselective herbicides before sowing or just before crop emergence (at the spiking stage to eliminate as much weedy rice as possible and other weeds at an early growth stage). It also includes the use of certified seeds free of weedy rice, following label instructions for IMI herbicides, applying the herbicide PRE followed by POST, and complementary weedy rice management practices, such as roguing of surviving weedy rice plants.
Rice farming components for biological weed control in transplanted rice: perspective on weedy rice management
Authors: Kathiresan Ramanathan , Vishnudevi Sangeeviraman
Published: August 2021

Farming elements other than the crop, when integrated into the system, are supplementary, with multifold uses that include weed and pest management. Elements such as fish and poultry birds are integrated with transplanted wetland rice (Oryza sativa L.) for ensuring farmers’ livelihoods and the nutritional security and sustainability of the system. Integrated animal components such as poultry birds and fish also supplement the system with weed control. The role and efficacy of these animal components as tools for managing weedy rice (Oryza sativa L.) were explored, as weedy rice infestation is increasing. This threat of weedy rice is due to scarcity of water resulting from poor water management and improper field leveling. Grass carp (Ctenopharyngodon idella val.) produced the highest reduction of weedy rice biomass, 28% within 24 h under laboratory conditions. Polyculture of C. idella, mrigal (Cirrhinus mrigala Ham.), and silver carp (Hypophthalmichthys molitrix val.) reduced the biomass of weedy rice by 21% within 24 h. In laboratory studies, poultry manure at the highest concentration of 5% reduced the weedy rice seed germination 100% compared with rice seed germination at 91%. This conformed with microplot experiments in which poultry manure at 15.6 g d−1 resulted in a weed control index (WCI) of 8% in both years. However, poultry manure at 15.6 g d−1 in combination with herbicide application resulted in the highest control indices of weedy rice: 52% in 2017 and 2018. Integrating fish and poultry with PRE application of oxyfluorfen (0.25 kg ha−1) resulted in the highest WCI and grain yield in field experiments.
Seed germination biology of sweet acacia (Vachellia farnesiana) and response of its seedlings to herbicides
Authors: Chauhan Bhagirath S. , Campbell Shane , Galea Victor J.
Published: August 2021

Sweet acacia [Vachellia farnesiana (L.) Willd.] is a problematic thorny weed species in several parts of Australia. Knowledge of its seed biology could help to formulate weed management decisions for this and similar species. Experiments were conducted to determine the effect of hot water (scarification), alternating temperatures, light, salt stress, and water stress on seed germination of two populations of V. farnesiana and to evaluate the response of its young seedlings (the most sensitive developmental stage) to commonly available postemergence herbicides in Australia. Both populations responded similarly to all the environmental factors and herbicides; therefore, data were pooled over the populations. Seeds immersed in hot water at 90 C for 10 min provided the highest germination (88%), demonstrating physical dormancy in this species. Seeds germinated at a wide range of alternating day/night temperatures from 20/10 C (35%) to 35/25 C (90%), but no seeds germinated at 15/5 C. Germination was not affected by light, suggesting that seeds are nonphotoblastic and can germinate under a plant canopy or when buried in soil. Germination was not affected by sodium chloride (NaCl) concentrations up to 20 mM, and about 50% of seeds could germinate at 160 mM NaCl, suggesting high salt tolerance ability. Germination was only 13% at −0.2 MPa osmotic potential, and no seeds germinated at −0.4 MPa, suggesting that V. farnesiana seeds may remain ungerminated until moisture conditions have become conducive for germination. A number of postemergence herbicides, including 2,4-D + picloram, glufosinate, paraquat, and saflufenacil, provided >85% control of biomass of young seedlings compared with the non-treated control treatment. Knowledge gained from this study will help to predict the potential spread of V. farnesiana in other areas and help to integrate herbicide use with other management strategies.
Scientists Uncover the Seasonality of COVID-19
Authors: Wheeling Kate
Published: July 2021

Researchers identify the environmental variables driving the seasonality of the novel coronavirus.
Integrating Process‐Based Reactive Transport Modeling and Machine Learning for Electrokinetic Remediation of Contaminated Groundwater
Authors: Sprocati R. , Rolle M.
Published: August 2021

Advanced reactive transport models of fluid flow and solute transport in subsurface porous media are instrumental for the assessment of contaminant environmental fate and for the design of in situ remediation interventions. However, the increasing complexity of process‐based reactive transport simulators often leads to long runtimes, which poses severe restrictions for tasks that require numerous model evaluations. To overcome this limitation, we demonstrate how machine learning surrogate models, trained on the outputs of a limited number of process‐based reactive transport simulations, can predict the evolution of complex subsurface systems. We focus on electrokinetic enhanced bioremediation of chlorinated solvents in low‐permeability porous media, which is an in situ remediation technology entailing a suite of complex and coupled physical, chemical, and biological processes. A process‐based, multicomponent reactive transport model, capable of describing the key mechanisms of electrokinetic flow and transport, is setup in a two‐dimensional domain. The model accounts for electromigration and electroosmosis, the electrostatic interactions between charged species, the chemistry of the pore water solution, the microbially mediated degradation of the organic compounds, and the dynamics of different degraders. We develop a response surface surrogate framework using an artificial neural network as approximation function and we show that the surrogate model has the capability and the flexibility to capture the complex dynamics of electrokinetic remediation in subsurface porous media and allows computationally efficient model exploration, sensitivity analysis, and uncertainty quantification.
Vocal features obtained through automated methods in verbal fluency tasks can aid the identification of mixed episodes in bipolar disorder
Authors: Weiner Luisa , Guidi Andrea , Doignon-Camus Nadège , Giersch Anne , Bertschy Gilles , Vanello Nicola
Published: August 2021

There is a lack of consensus on the diagnostic thresholds that could improve the detection accuracy of bipolar mixed episodes in clinical settings. Some studies have shown that voice features could be reliable biomarkers of manic and depressive episodes compared to euthymic states, but none thus far have investigated whether they could aid the distinction between mixed and non-mixed acute bipolar episodes. Here we investigated whether vocal features acquired via verbal fluency tasks could accurately classify mixed states in bipolar disorder using machine learning methods. Fifty-six patients with bipolar disorder were recruited during an acute episode (19 hypomanic, 8 mixed hypomanic, 17 with mixed depression, 12 with depression). Nine different trials belonging to four conditions of verbal fluency tasks—letter, semantic, free word generation, and associational fluency—were administered. Spectral and prosodic features in three conditions were selected for the classification algorithm. Using the leave-one-subject-out (LOSO) strategy to train the classifier, we calculated the accuracy rate, the F1 score, and the Matthews correlation coefficient (MCC). For depression versus mixed depression, the accuracy and F1 scores were high, i.e., respectively 0.83 and 0.86, and the MCC was of 0.64. For hypomania versus mixed hypomania, accuracy and F1 scores were also high, i.e., 0.86 and 0.75, respectively, and the MCC was of 0.57. Given the high rates of correctly classified subjects, vocal features quickly acquired via verbal fluency tasks seem to be reliable biomarkers that could be easily implemented in clinical settings to improve diagnostic accuracy.
Genome-wide DNA methylation and gene expression analyses in monozygotic twins identify potential biomarkers of depression
Authors: Wang Weijing , Li Weilong , Wu Yili , Tian Xiaocao , Duan Haiping , Li Shuxia , Tan Qihua , Zhang Dongfeng
Published: August 2021

Depression is currently the leading cause of disability around the world. We conducted an epigenome-wide association study (EWAS) in a sample of 58 depression score-discordant monozygotic twin pairs, aiming to detect specific epigenetic variants potentially related to depression and further integrate with gene expression profile data. Association between the methylation level of each CpG site and depression score was tested by applying a linear mixed effect model. Weighted gene co-expression network analysis (WGCNA) was performed for gene expression data. The association of DNA methylation levels of 66 CpG sites with depression score reached the level of P < 1 × 10−4. These top CpG sites were located at 34 genes, especially PTPRN2, HES5, GATA2, PRDM7, and KCNIP1. Many ontology enrichments were highlighted, including Notch signaling pathway, Huntington disease, p53 pathway by glucose deprivation, hedgehog signaling pathway, DNA binding, and nucleic acid metabolic process. We detected 19 differentially methylated regions (DMRs), some of which were located at GRIK2, DGKA, and NIPA2. While integrating with gene expression data, HELZ2, PTPRN2, GATA2, and ZNF624 were differentially expressed. In WGCNA, one specific module was positively correlated with depression score (r = 0.62, P = 0.002). Some common genes (including BMP2, PRDM7, KCNIP1, and GRIK2) and enrichment terms (including complement and coagulation cascades pathway, DNA binding, neuron fate specification, glial cell differentiation, and thyroid gland development) were both identified in methylation analysis and WGCNA. Our study identifies specific epigenetic variations which are significantly involved in regions, functional genes, biological function, and pathways that mediate depression disorder.
The neutralizing antibody response post COVID-19 vaccination in patients with myeloma is highly dependent on the type of anti-myeloma treatment
Authors: Terpos Evangelos , Gavriatopoulou Maria , Ntanasis-Stathopoulos Ioannis , Briasoulis Alexandros , Gumeni Sentiljana , Malandrakis Panagiotis , Fotiou Despina , Papanagnou Eleni-Dimitra , Migkou Magdalini , Theodorakakou Foteini , Roussou Maria , Eleutherakis-Papaiakovou Evangelos , Kanellias Nikolaos , Trougakos Ioannis P. , Kastritis Efstathios , Dimopoulos Meletios A.
Published: August 2021

Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies. Neutralizing antibodies (NAbs) against SARS-CoV-2 were evaluated in 276 patients with plasma cell neoplasms after vaccination with either the BNT162b2 or the AZD1222 vaccine, on days 1 (before the first vaccine shot), 22, and 50. Patients with MM (n = 213), SMM (n = 38), and MGUS (n = 25) and 226 healthy controls were enrolled in the study (NCT04743388). Vaccination with either two doses of the BNT162b2 or one dose of the AZD1222 vaccine leads to lower production of NAbs in patients with MM compared with controls both on day 22 and on day 50 (p < 0.001 for all comparisons). Furthermore, MM patients showed an inferior NAb response compared with MGUS on day 22 (p = 0.009) and on day 50 (p = 0.003). Importantly, active treatment with either anti-CD38 monoclonal antibodies (Mabs) or belantamab mafodotin and lymphopenia at the time of vaccination were independent prognostic factors for suboptimal antibody response following vaccination. In conclusion, MM patients have low humoral response following SARS-CoV-2 vaccination, especially under treatment with anti-CD38 or belamaf. This underlines the need for timely vaccination, possibly during a treatment-free period, and for continuous vigilance on infection control measures in non-responders.
Oncogene APOL1 promotes proliferation and inhibits apoptosis via activating NOTCH1 signaling pathway in pancreatic cancer
Authors: Lin Jiewei , Xu Zhiwei , Xie Junjie , Deng Xiaxing , Jiang Lingxi , Chen Hao , Peng Chenghong , Li Hongwei , Zhang Jiaqiang , Shen Baiyong
Published: August 2021

APOL1 encodes a secreted high-density lipoprotein, which has been considered as an aberrantly expressed gene in multiple cancers. Nevertheless, the role of APOL1 in the regulatory mechanisms of pancreatic cancer remains unknown and should be explored. We identified APOL1 was abnormally elevated in human pancreatic cancer tissues compared with that in adjacent tissues and was associated with poor prognosis. The effects of APOL1 in PC cell proliferation, cell cycle, and apoptosis was verified via functional in vitro and in vivo experiments. The results showed that knockdown of APOL1 significantly inhibited the proliferation and promoted apoptosis of pancreatic cancer. In addition, we identified APOL1 could be a regulator of NOTCH1 signaling pathway using bioinformatics tools, qRT-PCR, dual-luciferase reporter assay, and western blotting. In summary, APOL1 could function as an oncogene to promote proliferation and inhibit apoptosis through activating NOTCH1 signaling pathway expression in pancreatic cancer; therefore, it may act as a novel therapeutic target for pancreatic cancer.
Malignant cerebral infarction after ChAdOx1 nCov-19 vaccination: a catastrophic variant of vaccine-induced immune thrombotic thrombocytopenia
Authors: De Michele M. , Iacobucci M. , Chistolini A. , Nicolini E. , Pulcinelli F. , Cerbelli B. , Merenda E. , Schiavo O. G. , Sbardella E. , Berto I. , Petraglia L. , Caracciolo N. , Chiara M. , Truglia S. , Toni D.
Published: August 2021

Vaccine-induced thrombotic thrombocytopenia with cerebral venous thrombosis is a syndrome recently described in young adults within two weeks from the first dose of the ChAdOx1 nCoV-19 vaccine. Here we report two cases of malignant middle cerebral artery (MCA) infarct and thrombocytopenia 9-10 days following ChAdOx1 nCoV-19 vaccination. The two cases arrived in our facility around the same time but from different geographical areas, potentially excluding epidemiological links; meanwhile, no abnormality was found in the respective vaccine batches. Patient 1 was a 57-year-old woman who underwent decompressive craniectomy despite two prior, successful mechanical thrombectomies. Patient 2 was a 55-year-old woman who developed a fatal bilateral malignant MCA infarct. Both patients manifested pulmonary and portal vein thrombosis and high level of antibodies to platelet factor 4-polyanion complexes. None of the patients had ever received heparin in the past before stroke onset. Our observations of rare arterial thrombosis may contribute to assessment of possible adverse effects associated with COVID-19 vaccination.
White button mushroom interrupts tissue AR-mediated TMPRSS2 expression and attenuates pro-inflammatory cytokines in C57BL/6 mice
Authors: Wang Xiaoqiang , Ha Desiree , Yoshitake Ryohei , Chen Shiuan
Published: August 2021

White button mushroom (WBM) is a common edible mushroom consumed in the United States and many European and Asia-Pacific countries. We previously reported that dietary WBM antagonized dihydrotestosterone (DHT)-induced androgen receptor (AR) activation and reduced myeloid-derived suppressor cells (MDSCs) in prostate cancer animal models and patients. Transmembrane protease serine 2 (TMPRSS2), an androgen-induced protease in prostate cancer, has been implicated in influenza and coronavirus entry into the host cell, triggering host immune response. The present study on C57BL/6 mice revealed that WBM is a unique functional food that (A) interrupts AR-mediated TMPRSS2 expression in prostate, lungs, small intestine, and kidneys through its AR antagonistic activity and (B) attenuates serum pro-inflammatory cytokines and reduces MDSC counts through its immunoregulatory activity. These findings provide a scientific basis for translational studies toward clinical applications of WBM in diseases related to TMPRSS2 expression and immune dysregulation.
Transcriptomic response of Campylobacter jejuni following exposure to acidified sodium chlorite
Authors: Weerasooriya Gayani , McWhorter Andrea R. , Khan Samiullah , Chousalkar Kapil K.
Published: August 2021

Chemical decontamination during processing is used in many countries to mitigate the Campylobacter load on chicken meat. Chlorine is a commonly used sanitizer in poultry processing to limit foodborne bacterial pathogens but its efficacy is limited by high bacterial loads and organic material. Acidified sodium chlorite (ASC) is a potential alternative for poultry meat sanitization but little is known about its effects on the cellular response of Campylobacter. In this study, the sensitivity of C. jejuni isolates to ASC was established. RNAseq was performed to characterize the transcriptomic response of C. jejuni following exposure to either chlorine or ASC. Following chlorine exposure, C. jejuni induced an adaptive stress response mechanism. In contrast, exposure to ASC induced higher oxidative damage and cellular death by inhibiting all vital metabolic pathways and upregulating the genes involved in DNA damage and repair. The transcriptional changes in C. jejuni in response to ASC exposure suggest its potential as an effective sanitizer for use in the chicken meat industry.
Behavioural nudges increase COVID-19 vaccinations
Authors: Dai Hengchen , Saccardo Silvia , Han Maria A. , Roh Lily , Raja Naveen , Vangala Sitaram , Modi Hardikkumar , Pandya Shital , Sloyan Michael , Croymans Daniel M.
Published: August 2021

Enhancing vaccine uptake is a critical public health challenge1. Overcoming vaccine hesitancy2,3 and failure to follow through on vaccination intentions3 requires effective communication strategies3,4. Here we present two sequential randomized controlled trials to test the effect of behavioural interventions on the uptake of COVID-19 vaccines. We designed text-based reminders that make vaccination salient and easy, and delivered them to participants drawn from a healthcare system one day (first randomized controlled trial) (n = 93,354 participants; clinicaltrials number NCT04800965) and eight days (second randomized controlled trial) (n = 67,092 individuals; clinicaltrials number NCT04801524) after they received a notification of vaccine eligibility. The first reminder boosted appointment and vaccination rates within the healthcare system by 6.07 (84%) and 3.57 (26%) percentage points, respectively; the second reminder increased those outcomes by 1.65 and 1.06 percentage points, respectively. The first reminder had a greater effect when it was designed to make participants feel ownership of the vaccine dose. However, we found no evidence that combining the first reminder with a video-based information intervention designed to address vaccine hesitancy heightened its effect. We performed online studies (n = 3,181 participants) to examine vaccination intentions, which revealed patterns that diverged from those of the first randomized controlled trial; this underscores the importance of pilot-testing interventions in the field. Our findings inform the design of behavioural nudges for promoting health decisions5, and highlight the value of making vaccination easy and inducing feelings of ownership over vaccines.
Long-term outcomes of fully covered self-expandable metal stents versus plastic stents in chronic pancreatitis
Authors: Lee Sang Hoon , Kim Yeon Suk , Kim Eui Joo , Lee Hee Seung , Park Jeong Youp , Park Seung Woo , Song Si Young , Cho Jae Hee , Bang Seungmin
Published: August 2021

Chronic pancreatitis (CP) related main pancreatic duct (MPD) stricture has been a challenge for endoscopists. Fully covered self-expandable metal stents (FC-SEMS) has been tried in CP patients, but the efficacy and safety are still controversial. Thus, we aim to compare the long-term clinical efficacy of FC-SEMS vs. plastic stent placement in persistent MPD strictures secondary to CP. Between 2007 and 2018, 80 chronic pancreatitis patients (58 males, median age 49 years), who underwent endoscopic placement of FC-SEMS (n = 26) and plastic stent (n = 54) for persistent MPD strictures after at least 3 months of initial single plastic stenting, were retrospectively analyzed during a median follow-up duration of 33.7 months. As a result, MPD stricture resolution rate was statistically higher in FC-SEMS group (87.0% vs. 42.0%, p < 0.001). Although immediate complications occurred similarly (38.5% vs. 37.0%, p = 0.902), spontaneous migration (26.9%) and de novo strictures (23.1%) were pronounced delayed complications in FC-SEMS group. Pain relief during follow-up was significantly higher in FC-SEMS group (76.9% vs. 53.7%, p = 0.046). The total procedure cost was similar in both groups ($1,455.6 vs. $1,596.9, p = 0.486). In comparison with plastic stent, FC-SEMS placement for persistent MPD strictures had favorable long-term clinical efficacy, with its typical complications like spontaneous migration and de novo strictures.
Identification of non-classical hCA XII inhibitors using combination of computational approaches for drug design and discovery
Authors: Al-Sanea Mohammad M. , Chilingaryan Garri , Abelyan Narek , Arakelov Grigor , Sahakyan Harutyun , Arakelov Vahram G. , Nazaryan Karen , Hussein Shaimaa , Alazmi Gharam M. , Alsharari Haifa E. , Al-faraj Waad M. , Alruwaili Faten S. , Albilasi Nouf Q. , Alsharari Tahani S. , Alsaleh Abdulaziz A. S. , Alazmi Turki M. , Almalki Atiah H. , Alotaibi Nasser H. , Abdelgawad Mohamed A.
Published: July 2021

Human carbonic anhydrase XII (hCA XII) isozyme is of high therapeutic value as a pharmacological target and biomarker for different types of cancer. The hCA XII is one of the crucial effectors that regulates extracellular and intracellular pH and affects cancer cell proliferation, invasion, growth and metastasis. Despite the fact that interaction features of hCAs inhibitors with the catalytic site of the enzyme are well described, lack in the selectivity of the traditional hCA inhibitors based on the sulfonamide group or related motifs is an urgent issue. Moreover, drugs containing sulfanomides can cause sulfa allergies. Thus, identification of novel non-classical inhibitors of hCA XII is of high priority and is currently the subject of a vast field of study. This study was devoted to the identification of novel potential hCA XII inhibitors using comprehensive set of computational approaches for drug design discovery: generation and validation of structure- and ligand-based pharmacophore models, molecular docking, re-scoring of virtual screening results with MMGBSA, molecular dynamics simulations, etc. As the results of the study several compounds with alternative to classical inhibitors chemical scaffolds, in particular one of coumarins derivative, have been identified and are of high interest as potential non-classical hCA XII inhibitors.
Nurse-based secondary preventive follow-up by telephone reduced recurrence of cardiovascular events: a randomised controlled trial
Authors: Irewall Anna-Lotta , Ulvenstam Anders , Graipe Anna , Ögren Joachim , Mooe Thomas
Published: August 2021

Enhanced follow-up is needed to improve the results of secondary preventive care in patients with established cardiovascular disease. We examined the effect of long-term, nurse-based, secondary preventive follow-up by telephone on the recurrence of cardiovascular events. Open, randomised, controlled trial with two parallel groups. Between 1 January 2010 and 31 December 2014, consecutive patients (n = 1890) admitted to hospital due to stroke, transient ischaemic attack (TIA), or acute coronary syndrome (ACS) were included. Participants were randomised (1:1) to nurse-based telephone follow-up (intervention, n = 944) or usual care (control, n = 946) and followed until 31 December 2017. The primary endpoint was a composite of stroke, myocardial infarction, cardiac revascularisation, and cardiovascular death. The individual components of the primary endpoint, TIA, and all-cause mortality were analysed as secondary endpoints. The assessment of outcome events was blinded to study group assignment. After a mean follow-up of 4.5 years, 22.7% (n = 214) of patients in the intervention group and 27.1% (n = 256) in the control group reached the primary composite endpoint (HR 0.81, 95% CI 0.68–0.97; ARR 4.4%, 95% CI 0.5–8.3). Secondary endpoints did not differ significantly between groups. Nurse-based secondary preventive follow-up by telephone reduced the recurrence of cardiovascular events during long-term follow-up.
Confocal spectral microscopy, a non-destructive approach to follow contamination and biofilm formation of mCherry Staphylococcus aureus on solid surfaces
Authors: Munir Muhammad Tanveer , Maneewan Nattar , Pichon Julien , Gharbia Mohammed , Oumarou-Mahamane Ismael , Baude Jessica , Thorin Chantal , Lepelletier Didier , Le Pape Patrice , Eveillard Matthieu , Irle Mark , Pailhoriès Hélène , Aviat Florence , Belloncle Christophe , Federighi Michel , Dubreil Laurence
Published: August 2021

Methods to test the safety of wood material for hygienically sensitive places are indirect, destructive and limited to incomplete microbial recovery via swabbing, brushing and elution-based techniques. Therefore, we chose mCherry Staphylococcus aureus as a model bacterium for solid and porous surface contamination. Confocal spectral laser microscope (CSLM) was employed to characterize and use the autofluorescence of Sessile oak (Quercus petraea), Douglas fir (Pseudotsuga menziesii) and poplar (Populus euramericana alba L.) wood discs cut into transversal (RT) and tangential (LT) planes. The red fluorescent area occupied by bacteria was differentiated from that of wood, which represented the bacterial quantification, survival and bio-distribution on surfaces from one hour to one week after inoculation. More bacteria were present near the surface on LT face wood as compared to RT and they persisted throughout the study period. Furthermore, this innovative methodology identified that S. aureus formed a dense biofilm on melamine but not on oak wood in similar inoculation and growth conditions. Conclusively, the endogenous fluorescence of materials and the model bacterium permitted direct quantification of surface contamination by using CSLM and it is a promising tool for hygienic safety evaluation.
Magnitude integration in the Archerfish
Authors: Leibovich-Raveh Tali , Raveh Ashael , Vilker Dana , Gabay Shai
Published: August 2021

We make magnitude-related decisions every day, for example, to choose the shortest queue at the grocery store. When making such decisions, which magnitudes do we consider? The dominant theory suggests that our focus is on numerical quantity, i.e., the number of items in a set. This theory leads to quantity-focused research suggesting that discriminating quantities is automatic, innate, and is the basis for mathematical abilities in humans. Another theory suggests, instead, that non-numerical magnitudes, such as the total area of the compared items, are usually what humans rely on, and numerical quantity is used only when required. Since wild animals must make quick magnitude-related decisions to eat, seek shelter, survive, and procreate, studying which magnitudes animals spontaneously use in magnitude-related decisions is a good way to study the relative primacy of numerical quantity versus non-numerical magnitudes. We asked whether, in an animal model, the influence of non-numerical magnitudes on performance in a spontaneous magnitude comparison task is modulated by the number of non-numerical magnitudes that positively correlate with numerical quantity. Our animal model was the Archerfish, a fish that, in the wild, hunts insects by shooting a jet of water at them. These fish were trained to shoot water at artificial targets presented on a computer screen above the water tank. We tested the Archerfish's performance in spontaneous, untrained two-choice magnitude decisions. We found that the fish tended to select the group containing larger non-numerical magnitudes and smaller quantities of dots. The fish selected the group containing more dots mostly when the quantity of the dots was positively correlated with all five different non-numerical magnitudes. The current study adds to the body of studies providing direct evidence that in some cases animals’ magnitude-related decisions are more affected by non-numerical magnitudes than by numerical quantity, putting doubt on the claims that numerical quantity perception is the most basic building block of mathematical abilities.
Author Correction: Evaluation of usage-induced degradation of different endodontic file systems
Authors: Bhatia Shekhar , Nagendrababu Venkateshbabu , Peters Ove A. , Fawzy Amr , Daood Umer
Published: August 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes
Authors: Grabowicz Ilona E. , Wilczyński Bartek , Kamińska Bożena , Roura Adria-Jaume , Wojtaś Bartosz , Dąbrowski Michał J.
Published: August 2021

Genome-wide studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different glioma types. We have recently created a unique atlas encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA methylation and transcriptomes of 33 glioma samples of different grades. Here, we intersected genome-wide atlas data with topologically associating domains (TADs) and demonstrated that the chromatin organization and epigenetic landscape of enhancers have a strong impact on genes differentially expressed in WHO low grade versus high grade gliomas. We identified TADs enriched in glioma grade-specific genes and/or epigenetic marks. We found the set of transcription factors, including REST, E2F1 and NFKB1, that are most likely to regulate gene expression in multiple TADs, containing specific glioma-related genes. Moreover, many genes associated with the cell–matrix adhesion Gene Ontology group, in particular 14PROTOCADHERINs, were found to be regulated by long-range contacts with enhancers. Presented results demonstrate the existence of epigenetic differences associated with chromatin organization driving differential gene expression in gliomas of different malignancy.
Hidden pandemic: COVID-19-related stress, SLC6A4 methylation, and infants’ temperament at 3 months
Authors: Provenzi Livio , Mambretti Fabiana , Villa Marco , Grumi Serena , Citterio Andrea , Bertazzoli Emanuela , Biasucci Giacomo , Decembrino Lidia , Falcone Rossana , Gardella Barbara , Longo Maria Roberta , Nacinovich Renata , Pisoni Camilla , Prefumo Federico , Orcesi Simona , Scelsa Barbara , Giorda Roberto , Borgatti Renato
Published: August 2021

The COVID-19 pandemic represents a collective trauma that may have enduring stress effects during sensitive periods, such as pregnancy. Prenatal stress may result in epigenetic signatures of stress-related genes (e.g., the serotonin transporter gene, SLC6A4) that may in turn influence infants’ behavioral development. In April 2020, we launched a longitudinal cohort study to assess the behavioral and epigenetic vestiges of COVID-19-related prenatal stress exposure in mothers and infants. COVID-19-related prenatal stress was retrospectively assessed at birth. SLC6A4 methylation was assessed in thirteen CpG sites in mothers and infants’ buccal cells. Infants’ temperament was assessed at 3-month-age. Complete data were available from 108 mother-infant dyads. Greater COVID-19-related prenatal stress was significantly associated with higher infants’ SLC6A4 methylation in seven CpG sites. SLC6A4 methylation at these sites predicted infants’ temperament at 3 months.
Reduction in GLP-1 secretory capacity may be a novel independent risk factor of coronary artery stenosis
Authors: Nagase Chihiro , Tanno Masaya , Kouzu Hidemichi , Miki Takayuki , Nishida Junichi , Murakami Naoto , Kokubu Nobuaki , Nagano Nobutaka , Nishikawa Ryo , Yoshioka Nobuhiro , Hasegawa Tohru , Kita Hiroyuki , Tsuchida Akihito , Ohnishi Hirofumi , Miura Tetsuji
Published: August 2021

Multiple factors regulate glucagon-like peptide-1 (GLP-1) secretion, but a group of apparently healthy subjects showed blunted responses of GLP-1 secretion in our previous study. In this study, we examined whether the reduction in GLP-1 secretory capacity is associated with increased extent of coronary artery stenosis in non-diabetic patients. Non-diabetic patients who were admitted for coronary angiography without a history of coronary interventions were enrolled. Coronary artery stenosis was quantified by Gensini score (GS), and GS ≥ 10 was used as an outcome variable based on its predictive value for cardiovascular events. The patients (mean age, 66.5 ± 8.8 years; 71% males, n = 173) underwent oral 75 g-glucose tolerant tests for determination of glucose, insulin and active GLP-1 levels. The area under the curve of plasma active GLP-1 (AUC-GLP-1) was determined as an index of GLP-1 secretory capacity. AUC-GLP-1 was not correlated with fasting glucose, AUC-glucose, serum lipids or indices of insulin sensitivity. In multivariate logistic regression analysis for GS ≥ 10, AUC-GLP-1 < median, age and hypertension were selected as explanatory variables, though fasting GLP-1 level was not selected. The findings suggest that reduction in GLP-1 secretory capacity is a novel independent risk factor of coronary stenosis.
The effects of combined cognitive training on prospective memory in older adults with mild cognitive impairment
Authors: Chen Yifan , Zhou Wei , Hong Zijing , Hu Rongrong , Guo Zhibin , Liu Shen , Zhang Lin
Published: August 2021

This study aimed to assess the effects of combined cognitive training on prospective memory ability of older adults with mild cognitive impairment (MCI). A total of 113 participants were divided into a control group and three intervention groups. Over three months, the control group received only community education without any training, whereas for the first six weeks, an executive function training group received executive function training, a memory strategy training group received semantic encoding strategy training, and the combined cognitive training group received executive function training twice a week for the first six weeks, and semantic encoding strategy training twice a week for the next six weeks. The combined cognitive training group showed improvement on the objective neuropsychological testing (Montreal Cognitive Assessment scale). The memory strategy training group showed improvement on the self-evaluation scales (PRMQ-PM). Combined cognitive training improved the prospective memory and cognitive function of older adults with MCI.
Interpreting time-series COVID data: reasoning biases, risk perception, and support for public health measures
Authors: Harman Jason L. , Weinhardt Justin M. , Beck James W. , Mai Ivy
Published: August 2021

Effective risk communication during the COVID-19 pandemic is critical for encouraging appropriate public health behaviors. One way that the public is informed about COVID-19 numbers is through reports of daily new cases. However, presenting daily cases has the potential to lead to a dynamic reasoning bias that stems from intuitive misunderstandings of accumulation. Previous work in system dynamics shows that even highly educated individuals with training in science and math misunderstand basic concepts of accumulation. In the context of COVID-19, relying on the single cue of daily new cases can lead to relaxed attitudes about the risk of COVID-19 when daily new cases begin to decline. This situation is at the very point when risk is highest because even though daily new cases have declined, the active number of cases are highest because they have been accumulating over time. In an experiment with young adults from the USA and Canada (N = 551), we confirm that individuals fail to understand accumulation regarding COVID-19, have less concern regarding COVID-19, and decrease endorsement for public health measures as new cases decline but when active cases are at the highest point. Moreover, we experimentally manipulate different dynamic data visualizations and show that presenting data highlighting active cases and minimizing new cases led to increased concern and increased endorsement for COVID-19 health measures compared to a control condition highlighting daily cases. These results hold regardless of country, political affiliation, and individual differences in decision making. This study has implications for communicating the risks of contracting COVID-19 and future public health issues.
The genetic architecture of plasma kynurenine includes cardiometabolic disease mechanisms associated with the SH2B3 gene
Authors: Bagheri Minoo , Wang Chuan , Shi Mingjian , Manouchehri Ali , Murray Katherine T. , Murphy Matthew B. , Shaffer Christian M. , Singh Kritika , Davis Lea K. , Jarvik Gail P. , Stanaway Ian B. , Hebbring Scott , Reilly Muredach P. , Gerszten Robert E. , Wang Thomas J. , Mosley Jonathan D. , Ferguson Jane F.
Published: August 2021

Inflammation increases the risk of cardiometabolic disease. Delineating specific inflammatory pathways and biomarkers of their activity could identify the mechanistic underpinnings of the increased risk. Plasma levels of kynurenine, a metabolite involved in inflammation, associates with cardiometabolic disease risk. We used genetic approaches to identify inflammatory mechanisms associated with kynurenine variability and their relationship to cardiometabolic disease. We identified single-nucleotide polymorphisms (SNPs) previously associated with plasma kynurenine, including a missense-variant (rs3184504) in the inflammatory gene SH2B3/LNK. We examined the association between rs3184504 and plasma kynurenine in independent human samples, and measured kynurenine levels in SH2B3-knock-out mice and during human LPS-evoked endotoxemia. We conducted phenome scanning to identify clinical phenotypes associated with each kynurenine-related SNP and with a kynurenine polygenic score using the UK-Biobank (n = 456,422), BioVU (n = 62,303), and Electronic Medical Records and Genetics (n = 32,324) databases. The SH2B3 missense variant associated with plasma kynurenine levels and SH2B3−/− mice had significant tissue-specific differences in kynurenine levels.LPS, an acute inflammatory stimulus, increased plasma kynurenine in humans. Mendelian randomization showed increased waist-circumference, a marker of central obesity, associated with increased kynurenine, and increased kynurenine associated with C-reactive protein (CRP). We found 30 diagnoses associated (FDR q < 0.05) with the SH2B3 variant, but not with SNPs mapping to genes known to regulate tryptophan-kynurenine metabolism. Plasma kynurenine may be a biomarker of acute and chronic inflammation involving the SH2B3 pathways. Its regulation lies upstream of CRP, suggesting that kynurenine may be a biomarker of one inflammatory mechanism contributing to increased cardiometabolic disease risk.
Geomorphic effects of recurrent outburst superfloods in the Yigong River on the southeastern margin of Tibet
Authors: Hu Kaiheng , Wu Chaohua , Wei Li , Zhang Xiaopeng , Zhang Qiyuan , Liu Weiming , Yanites Brian J.
Published: August 2021

Landslide dam outburst floods have a significant impact on landform evolution in high mountainous areas. Historic landslide dams on the Yigong River, southeastern Tibet, generated two outburst superfloods > 105 m3/s in 1902 and 2000 AD. One of the slackwater deposits, which was newly found immediately downstream of the historic dams, has been dated to 7 ka BP. The one-dimensional backwater stepwise method gives an estimate of 225,000 m3/s for the peak flow related to the paleo-stage indicator of 7 ka BP. The recurrence of at least three large landslide dam impoundments and super-outburst floods at the exit of Yigong Lake during the Holocene greatly changed the morphology of the Yigong River. More than 0.26 billion m3 of sediment has been aggraded in the dammed lake while the landslide sediment doubles the channel slope behind the dam. Repeated landslide damming may be a persistent source of outburst floods and impede the upstream migration of river knickpoints in the southeastern margin of Tibet.
Salivary proteome of aphthous stomatitis reveals the participation of vitamin metabolism, nutrients, and bacteria
Authors: Hernández-Olivos Romina , Muñoz Mariagrazia , Núñez Esteban , Camargo-Ayala Paola Andrea , Garcia-Huidobro Jenaro , Pereira Alfredo , Nachtigall Fabiane M. , Santos Leonardo S. , Rivera César
Published: August 2021

There are currently no preventative options for recurrent aphthous stomatitis, and the only available treatments are palliative. This is partly due to a poor understanding of its etiopathogenesis. In this case–control study, we characterized the salivary proteome of patients with recurrent aphthous stomatitis in the presence and absence of lesions. Through mass spectrometry-based proteomics and bioinformatics tools, we identified that the presence of oral ulcers is associated with several specific biological processes, including the metabolic pathways of vitamin B9, B12, nitrogen, selenium, and the bacteriumNeisseria meningitidis. These changes occurred only in the presence of clinically visible lesions, and there were no relevant differences between patients in anatomical regions unaffected by ulcers. Additionally, using western blot and ELISA assays, we verified that carbonic anhydrase 1 (CA1) and hemoglobin subunit beta (HBB) proteins are highly expressed during the ulcerative and remission phases of recurrent aphthous stomatitis. Our results cumulatively support saliva as an indicator of the pathophysiological changes, which occur during the clinical course of lesions. From a clinical perspective, we suggest that recurrent aphthous stomatitis is a condition triggered by temporary biological changes in people with lesions.