bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening of osmotic stress-tolerant bacteria for plant growth promotion in wheat (Triticum aestivum L.) and brinjal (Solanum melongena L.) under drought conditions
Authors: Patel P. , Patil T. , Maiti S. , Paul D. , Amaresan N.
Published: August 2022

Drought stress adversely affects plant growth and productivity. Therefore, the application of plant growth-promoting bacteria is a viable option for combating drought resistance in crops. In this study, 144 bacteria were isolated from the Kutch desert soil in Gujarat. Based on osmotic stress tolerance and PGP properties, two strains, Bacillus tequilensis (KS5B) and Pseudomonas stutzeri (KS5C) were tested for their effect on wheat (Triticum aestivum L.) and brinjal (Solanum melongena L.) under drought stress conditions. Inoculation with osmotic stress-tolerant bacteria showed 15·15–29·27% enhancement in root length of wheat and 15·27–32·59% in brinjal plants. Similarly, the enhancement of shoot length ranged from 14·72 to 37·70% for wheat and 59·39–95·94% for brinjal plants. Furthermore, the inoculated plants showed significant improvement in chlorophyll content and antioxidant properties such as proline, peroxidase and polyphenol oxidase activity compared to the control. Therefore, the bacterial strains identified in this study can be used to mitigate drought stress and enhance plant biomass.
Meta-analysis of the microbial biomarkers in the gut–lung crosstalk in COVID-19, community-acquired pneumonia and Clostridium difficile infections
Authors: Aishwarya S. , Gunasekaran K.
Published: August 2022

Respiratory infections are the leading causes of mortality and the current pandemic COVID-19 is one such trauma that imposed catastrophic devastation to the health and economy of the world. Unravelling the correlations and interplay of the human microbiota in the gut–lung axis would offer incredible solutions to the underlying mystery of the disease progression. The study compared the microbiota profiles of six samples namely healthy gut, healthy lung, COVID-19 infected gut, COVID-19 infected lungs, Clostridium difficile infected gut and community-acquired pneumonia infected lungs. The metagenome data sets were processed, normalized, classified and the rarefaction curves were plotted. The microbial biomarkers for COVID-19 infections were identified as the abundance of Candida and Escherichia in lungs with Ruminococcus in the gut. Candida and Staphylococcus could play a vital role as putative prognostic biomarkers of community-acquired pneumonia whereas abundance of Faecalibacterium and Clostridium is associated with the C. difficile infections in gut. A machine learning random forest classifier applied to the data sets efficiently classified the biomarkers. The study offers an extensive and incredible understanding of the existence of gut–lung axis during dysbiosis of two anatomically different organs.
CRISPR/Cas‐based tools for the targeted control of plant viruses
Authors: Robertson Gaëlle , Burger Johan , Campa Manuela
Published: August 2022

Plant viruses are known to infect most economically important crops and pose a major threat to global food security. Currently, few resistant host phenotypes have been delineated, and while chemicals are used for crop protection against insect pests and bacterial or fungal diseases, these are inefficient against viral diseases. Genetic engineering emerged as a way of modifying the plant genome by introducing functional genes in plants to improve crop productivity under adverse environmental conditions. Recently, new breeding technologies, and in particular the exciting CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR‐associated proteins) technology, was shown to be a powerful alternative to engineer resistance against plant viruses, thus has great potential for reducing crop losses and improving plant productivity to directly contribute to food security. Indeed, it could circumvent the “Genetic modification” issues because it allows for genome editing without the integration of foreign DNA or RNA into the genome of the host plant, and it is simpler and more versatile than other new breeding technologies. In this review, we describe the predominant features of the major CRISPR/Cas systems and outline strategies for the delivery of CRISPR/Cas reagents to plant cells. We also provide an overview of recent advances that have engineered CRISPR/Cas‐based resistance against DNA and RNA viruses in plants through the targeted manipulation of either the viral genome or susceptibility factors of the host plant genome. Finally, we provide insight into the limitations and challenges that CRISPR/Cas technology currently faces and discuss a few alternative applications of the technology in virus research.
The contribution of brain banks to knowledge discovery in amyotrophic lateral sclerosis: A systematic review
Authors: Mazumder Srestha , Kiernan Matthew C. , Halliday Glenda M. , Timmins Hannah C. , Mahoney Colin J.
Published: August 2022

Over the past decade, considerable efforts have been made to accelerate pathophysiological understanding of fatal neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) with brain banks at the forefront. In addition to exploratory disease mechanisms, brain banks have aided our understanding with regard to clinical diagnosis, genetics and cell biology. Across neurodegenerative disorders, the impact of brain tissue in ALS research has yet to be quantified. This review aims to outline (i) how postmortem tissues from brain banks have influenced our understanding of ALS over the last 15 years, (ii) correlate the location of dedicated brain banks with the geographical prevalence of ALS, (iii) identify the frequency of features reported from postmortem studies and (iv) propose common reporting standards for materials obtained from dedicated brain banks. A systematic review was conducted using PubMed and Web of Science databases using key words. From a total of 1439 articles, 73 articles were included in the final review, following PRISMA guidelines. Following a thematic analysis, articles were categorised into five themes; clinico‐pathological (13), genetic (20), transactive response DNA binding protein 43 (TDP‐43) pathology (12), non‐TDP‐43 neuronal pathology (nine) and extraneuronal pathology (19). Research primarily focused on the genetics of ALS, followed by protein pathology. About 63% of the brain banks were in the United States of America and United Kingdom. The location of brain banks overall aligned with the incidence of ALS worldwide with 88% of brain banks situated in Europe and North America. An overwhelming lack of consistency in reporting and replicability was observed, strengthening the need for a standardised reporting system. Overall, postmortem material from brain banks generated substantial new knowledge in areas of genetics and proteomics and supports their ongoing role as an important research tool.
Melodic Intonation Therapy for aphasia: A multi‐level meta‐analysis of randomized controlled trials and individual participant data
Authors: Popescu Tudor , Stahl Benjamin , Wiernik Brenton M. , Haiduk Felix , Zemanek Michaela , Helm Hannah , Matzinger Theresa , Beisteiner Roland , Fitch W. Tecumseh
Published: August 2022

Melodic Intonation Therapy (MIT) is a prominent rehabilitation program for individuals with post‐stroke aphasia. Our meta‐analysis investigated the efficacy of MIT while considering quality of outcomes, experimental design, influence of spontaneous recovery, MIT protocol variant, and level of generalization. Extensive literature search identified 606 studies in major databases and trial registers; of those, 22 studies—overall 129 participants—met all eligibility criteria. Multi‐level mixed‐ and random‐effects models served to separately meta‐analyze randomized controlled trial (RCT) and non‐RCT data. RCT evidence on validated outcomes revealed a small‐to‐moderate standardized effect in noncommunicative language expression for MIT—with substantial uncertainty. Unvalidated outcomes attenuated MIT's effect size compared to validated tests. MIT's effect size was 5.7 times larger for non‐RCT data compared to RCT data (g̅case report = 2.01 vs. g̅RCT = 0.35 for validated Non‐Communicative Language Expression measures). Effect size for non‐RCT data decreased with number of months post‐stroke, suggesting confound through spontaneous recovery. Deviation from the original MIT protocol did not systematically alter benefit from treatment. Progress on validated tests arose mainly from gains in repetition tasks rather than other domains of verbal expression, such as everyday communication ability. Our results confirm the promising role of MIT in improving trained and untrained performance on unvalidated outcomes, alongside validated repetition tasks, and highlight possible limitations in promoting everyday communication ability.
Productivity Slowdown in Japan's Lost Decades: How Much of It Can Be Attributed to Damaged Balance Sheets?*
Authors: Muto Ichiro , Sudo Nao , Yoneyama Shunichi
Published: August 2022

After the global financial crisis, slowdowns of total factor productivity (TFP), often measured as the Solow residual, have been observed across major countries. This study offers an explanation for this by focusing on Japan's financial crises during the 1990s. We first incorporate credit constraints, for financial intermediaries (FIs) and firms, and input–output structure into the standard New Keynesian model, and show that the model delivers multiple channels through which damaged balance sheets reduce measured TFP. We then estimate the model using Japanese data, and show that adverse shocks to FIs' balance sheets played a substantial role in lowering measured TFP.
Influence of PD‐1/PD‐L1 on immune microenvironment in oral leukoplakia and oral squamous cell carcinoma
Authors: Xu Shuang‐Bo , Wang Meng‐Yao , Shi Xin‐Zhan , Wang Qiong , Yu Miao , Zhang Wei , Xu Xiao‐Hui , Liu Lai‐Kui
Published: August 2022

Objective

To evaluate the relation between the expression of PD‐1, PD‐L1, CD3, CD8, Foxp3 and clinicopathological features in patients with oral leukoplakia (OLK) and oral squamous cell carcinomas (OSCC) as well as the malignant outcome in OLK patients, and to study the effect of PD‐1 and PD‐L1 on immune microenvironment in the progression of oral carcinogenesis.

Methods

We evaluated the expression of PD‐1/PD‐L1 and composition of CD3+, CD8+and Foxp3+ T lymphocytes in OLK and OSCC samples by immunohistochemical (IHC) staining and analyzed their relation with clinical information and malignant transformation in OLK patients.

Results

IHC staining demonstrated that the expression of PD‐1 was significantly increased in the high‐grade OLK group than in the low‐grade OLK group, while PD‐L1 was detected mainly in OSCC. The expression of CD3, CD8, and Foxp3 was found higher in the high‐grade OLK group than in the low‐grade OLK group, and the Foxp3+ cells were found more in the OSCC group than in the high‐grade OLK group. PD‐1 was significantly correlated with CD3 (p < 0.05, R = 0.52), CD8 (p < 0.05, R = 0.46), and Foxp3 (p < 0.05, R = 0.46), and the low PD‐1‐expression group showed a better malignant‐free survival than high PD‐1 expression group in the OLK (p < 0.05).

Conclusion

The PD‐1/PD‐L1 may induce immune suppression in OLK and accelerate the progress of malignant transformation.
Processes in international relationships: A critical review
Authors: Gaines Stanley O.
Published: August 2022

In the present review, the author draws upon Bell's (1987) critical race theory – especially as reflected in Crenshaw's (1989) construct of intersectionality – en route to examining the results of four studies of international relationship processes that have been published since 2002 (i.e., Holzapfel et al., 2018; Kaya et al., 2019; Kuramoto, 2018 and van Mol & de Valk, 2016). One common theme that emerged from the four studies was the importance of satisfaction‐related processes in international relationships – a theme that Thibaut and Kelley's (1959) interdependence theory would anticipate within intranational and international relationships alike. Although persons from African, Central American, and South American nations are conspicuously missing from the studies in question, the author does not attribute such omissions to structural racism. Implications for future research on inclusivity and the dynamics of international relationships are discussed.
Necessity of identity and Tarski's T‐schema
Authors: Blum Alex
Published: August 2022

It is argued that Tarski's T‐schema and the thesis of the necessity of identity cannot both be true.
Hooker's rule‐consequentialism and Scanlon's contractualism—A re‐evaluation
Authors: Suikkanen Jussi
Published: August 2022

Brad Hooker's rule‐consequentialism and T. M. Scanlon's contractualism have been some of the most debated ethical theories in normative ethics during the last twenty years or so. This article suggests that these theories can be compared at two levels. Firstly, what are the deep, structural differences between the rule‐consequentialist and contractualist frameworks in which Hooker and Scanlon formulate their views? Secondly, what are the more superficial differences between Hooker's and Scanlon's formulations of these theories? Based on exploring these questions and several purported differences between Hooker's and Scanlon's views, this article argues that, at the structural level, the two theories are more similar than previous recognised. It suggests that there is only one candidate for a deeper difference and even it may not be that significant. This insight sheds new light on both contractualism and rule‐consequentialism, and it will also help us to formulate better versions of the views.
Foreign market entry, upstream market power, and endogenous mode of downstream competition
Authors: Gilbert John , Koska Onur A. , Oladi Reza
Published: August 2022

In a differentiated duopoly model of trade and FDI featuring both horizontal and vertical product differentiation, we examine whether globalization and trade policy measures can generate welfare gains by leading firms to change their mode of competition. We show that when a high‐quality foreign variety is manufactured under large frictions due to upstream monopoly power, a foreign firm can become a Bertrand competitor against a Cournot local rival in equilibrium, especially when the relative product quality of the foreign variety is sufficiently high and trade costs are sufficiently low (implying higher input price distortions due to double marginalization). Our results suggest that such strategic asymmetry is welfare improving and that the availability of FDI as an alternative to trade can make welfare‐enhancing strategic asymmetry even more likely, especially when both input trade costs and fixed investment costs are sufficiently low and trade costs in final goods are sufficiently large.
General higher—order breathers and rogue waves in the two‐component long‐wave–short‐wave resonance interaction model
Authors: Rao Jiguang , Malomed Boris A. , Mihalache Dumitru , He Jingsong
Published: August 2022

General higher order breather and rogue wave (RW) solutions to the two‐component long wave–short wave resonance interaction (2‐LSRI) model are derived via the bilinear Kadomtsev–Petviashvili hierarchy reduction method and are given in terms of determinants. Under particular parametric conditions, the breather solutions can reduce to homoclinic orbits, or a mixture of breathers and homoclinic orbits. There are three families of RW solutions, which correspond to a simple root, two simple roots, and a double root of an algebraic equation related to the dimension reduction procedure. The first family of RW solutions consists of bounded fundamental RWs, the second family is composed of bounded fundamental RWs coexisting with another fundamental RWs of different a bounded state ( being positive integers), while the third one has fundamental bounded RWs ( being nonnegative integers). The second family can be regarded as the superpositions of the first family, while the third family can be the degenerate case of the first family under particular parameter choices. These diverse RW patterns are illustrated graphically.
Differential preferences for RBCs is key for Plasmodium species evolutionary diversity within human host
Authors: Djidjou‐Demasse Ramsès , Mann‐Manyombe Martin L. , Seydi Ousmane , Yatat‐Djeumen Valaire
Published: August 2022

Plasmodium species exhibit differential preferences for red blood cells (RBCs) of different ages. From a fundamental standpoint, we propose an age‐structured within‐host malaria model taking into account the variation in RBCs preference. We show that such a differential ecological characteristic of Plasmodium species within their human host is fundamental to capture species diversity within the same infected host individual. We show that with such difference in the RBCs preferences, the long‐term coexistence of different species is possible under a certain condition, basically based on a suitable order on the basic reproduction numbers of each species. In particular, we show that the dynamical behavior of the model is not trivial and can range from the extinction of all species, the persistence of a single species, to the coexistence of more than one species. We also describe how our general analysis can be applied in some coinfection configurations including three malaria species: Plasmodium falciparum, Plasmodium vivax, and/or Plasmodium malariae. This improved understanding of the within‐host parasite multiplication in a context of mixed Plasmodium species interactions.
Incidence of transfusion‐related acute lung injury temporally associated with solvent/detergent plasma use in the ICU: A retrospective before and after implementation study
Authors: Klanderman Robert B. , van Mourik Niels , Eggermont Dorus , Peters Anna‐Linda , Tuinman Pieter R. , Bosman Rob , Endeman Henrik , Cremer Olaf L. , Arbous Sesmu M. , Vlaar Alexander P. J.
Published: August 2022

Background

Transfusion‐related acute lung injury (TRALI) is a severe complication of plasma transfusion, though the use of solvent/detergent pooled plasma (SDP) has nearly eliminated reported TRALI cases. The goal of this study was to investigate the incidence of TRALI in intensive care units (ICU) following the replacement of quarantined fresh frozen plasma (qFFP) by SDP.

Study design and methods

A retrospective multicenter observational before–after cohort study was performed during two 6‐month periods, before (April–October 2014) and after the introduction of SDP (April–October 2015), accounting for a washout period. A full chart review was performed for patients who received ≥1 plasma units and developed hypoxemia within 24 h.

Results

During the study period, 8944 patients were admitted to the ICU. Exactly 1171 quarantine fresh frozen plasma (qFFP) units were transfused in 376 patients, and respectively, 2008 SDP units to 396 patients after implementation. Ten TRALI cases occurred during the qFFP and nine cases occurred during the SDP period, in which plasma was transfused. The incidence was 0.85% (CI95%: 0.33%–1.4%) per unit qFFP and 0.45% (CI95%: 0.21%–0.79%, p = 0.221) per SDP unit. One instance of TRALI occurred after a single SDP unit. Mortality was 70% for patients developing TRALI in the ICU compared with 22% in patients receiving at least one plasma transfusion.

Conclusion

Implementation of SDP lowered the incidence of TRALI in which plasma products were implicated, though not significantly. Clinically diagnosed TRALI can still occur following SDP transfusion. Developing TRALI in the ICU was associated with high mortality rates, therefore, clinicians should remain vigilant.
Blood donation behaviour and attitudes towards the 12‐month deferral policy among gay and bisexual men in New Zealand
Authors: Sriamporn Koson Tony , Saxton Peter , Consedine Nathan , Hammoud Mohamed , Prestage Garrett
Published: August 2022

Background and Objectives

Gay and bisexual men (GBM) are deferred from donating blood in many countries. Perceptions by GBM that blood donor deferral policies are unjustifiably discriminatory, especially due to advances in HIV prevention, could contribute to non‐compliance and need to be understood. We explore blood donation interest and history among GBM and attitudes towards donor deferral policies for the first time in New Zealand (NZ).

Materials and Methods

Data from a cross‐sectional online survey of GBM in NZ were examined. We constructed three groups: (1) never donated blood and not interested; (2) never donated but expressed interest; and (3) previously donated blood. We tested these for association with demographic and behavioural variables, as well as attitudes towards blood donation policy.

Results

A total of 607 GBM were eligible for the study, of whom 32.9% reported having donated blood previously, 44.3% had never donated blood but expressed interest and 22.7% expressed no interest in donating. Among previous donors, a third (8.6% of the total sample) reported non‐compliance with the deferral policy. Most participants found the 12‐month deferral policy to be too strict (81.8%), unfair (75.4%) and homophobic (68.8%).

Conclusion

We estimate that, for the first time in NZ, almost 10% of the sample did not report compliance with the 12‐month deferral policy for men who have sex with men (MSM). Negative attitudes towards the deferral policy were common and could potentially increase the risk to the blood supply if compliance reduces. Further work is needed to inform a deferral policy that is accepted by GBM while maintaining the safety of NZ's blood supply.
Zr-Al 16 wt. % and Na2CrO4 composite particles used for Na dispenser and its reaction kinetic
Authors: Song Wentao , Zhang Chao , Ma Ruibin , Zhong Ziyuan , Zhao Heng , Tian Wenhuai
Published: August 2022

An alkali metal dispenser is the core device for vacuum evaporation in producing multialkali photocathodes. However, the reaction kinetic of alkali metal chromate being reduced by a Zr-Al alloy, which is the most commonly used alkali metal dispenser, has not been reported. In this work, we made composite particles of Zr-Al 16 wt. % powders with Na2CrO4 by a method of liquid precipitation. Through thermal analysis of its reaction, we found that the difference of a Zr-Al particle size would affect the reaction starting temperature but would not make a significant difference on the apparent activation energy. Through the comparison method by Sharp, we found that the 3D Avrami–Erofeev equation fits for this reaction and established a reaction degree-temperature function, and the reaction kinetic was further verified by a vacuum evaporation experiment. Through an in situ XRD measurement, the chemical change during an Na dispenser’s working process is found to be Na2CrO4 → Na2CrO4, Na2CrO3, and Cr2O3 coexist → NaCrO2. This work may serve as a reference for the design of alkali metal dispensers and help to improve the control precision for an evaporation process.
Large amplitude oscillatory shear (LAOS) behavior of chocolates of different compositions
Authors: Sandoval Aleida J. , Fernández Mercedes , Sanz Oihane , Santamaría Antxon , Penott-Chang Evis , Müller Alejandro J.
Published: August 2022

The complex rheological response of chocolates of different compositions was analyzed in depth from stationary shear flow curves and large amplitude oscillatory shear tests. The samples have a wide range of cocoa content that controls the rheological behavior characterized by a yielding response. The strain amplitude at which the chocolates changed from elastic-dominated to viscous-dominated behavior ranged from 0.2 to 0.4%. In this region, the stress response to the applied sinusoidally oscillating shear strain showed transient overshoots whose values were similar to yield stress calculated using the Casson equation in continuous flow. The nonlinear response at the steady-state was analyzed. The Q0 nonlinearity parameter, obtained from Fourier Transform analysis, increases as the concentration of the solids conferring bimodality to the particle size distribution increases. In the study of intracycle nonlinearities, the analysis of the third-order Chebyshev elastic and viscous coefficients showed that the sample which contains the highest amount of solids different from cocoa exhibited the lowest strain-stiffening and the highest shear-thinning behaviors. Stress bifurcation analysis identified the beginning of the yielding transition and evidenced a nonlinear solid-like behavior before the solid-liquid transition. Analysis of Lissajous–Bowditch curves allowed the static and dynamic contributions of the yielding transition to be identified, and the full Sequence of Physical Process quantitative analysis captures the time-dependent nonlinear response of chocolates over the history of applied deformations.
Granulation and suspension rheology: A unified treatment
Authors: Hodgson Daniel J. M. , Hermes Michiel , Blanco Elena , Poon Wilson C. K.
Published: August 2022

Mixing a small amount of liquid into a powder can give rise to dry-looking granules; increasing the amount of liquid eventually produces a flowing suspension. We perform experiments on these phenomena using Spheriglass, an industrially realistic model powder. Drawing on recent advances in understanding friction-induced shear thickening and jamming in suspensions, we offer a unified description of granulation and suspension rheology. A “liquid incorporation phase diagram” explains the existence of permanent and transient granules and the increase of granule size with liquid content. Our results point to rheology-based design principles for industrial granulation.
Transcriptional variability accelerates preleukemia by cell diversification and perturbation of protein synthesis
Authors: Gupta Shikha , Dovey Oliver M. , Domingues Ana Filipa , Cyran Oliwia W. , Cash Caitlin M. , Giotopoulos George , Rak Justyna , Cooper Jonathan , Gozdecka Malgorzata , Dijkhuis Liza , Asby Ryan J. , Al-Jabery Noor , Hernandez-Hernandez Victor , Prabakaran Sudhakaran , Huntly Brian J. , Vassiliou George S. , Pina Cristina
Published: August 2022

Transcriptional variability facilitates stochastic cell diversification and can in turn underpin adaptation to stress or injury. We hypothesize that it may analogously facilitate progression of premalignancy to cancer. To investigate this, we initiated preleukemia in mouse cells with enhanced transcriptional variability due to conditional disruption of the histone lysine acetyltransferase gene
Kat2a
. By combining single-cell RNA sequencing of preleukemia with functional analysis of transformation, we show that
Kat2a
loss results in global variegation of cell identity and accumulation of preleukemic cells. Leukemia progression is subsequently facilitated by destabilization of ribosome biogenesis and protein synthesis, which confer a transient transformation advantage. The contribution of transcriptional variability to early cancer evolution reflects a generic role in promoting cell fate transitions, which, in the case of well-adapted malignancies, contrastingly differentiates and depletes cancer stem cells. That is, transcriptional variability confers forward momentum to cell fate systems, with differential multistage impact throughout cancer evolution.
A relatively dry mantle transition zone revealed by geomagnetic diurnal variations
Authors: Zhang Huiqian , Egbert Gary D. , Huang Qinghua
Published: August 2022

The distribution of water within the mantle transition zone (MTZ) has important implications for the material circulation and partial melting of the mantle. Although solubility of hydrogen is very high, leading to speculations that the MTZ plays a key role in the deep-Earth water cycle, the actual water content remains an open question. Electrical conductivity of mantle minerals is very sensitive to water content, so reliable estimates of this physical parameter in the MTZ would provide valuable constraints. Here, we use recently developed joint inversion of geomagnetic diurnal variation for realistic source structure and one-dimensional mantle conductivity profile. Synthetic tests show that the resulting profile is a reasonable proxy for the electrical conductivity distribution of continental mantle over depths where model resolution is best (200 to 600 kilometer), even in the presence of lateral heterogeneity. The inferred water concentration in the MTZ is 0.03 weight %, one to two orders of magnitude below the solubility of wadsleyite and ringwoodite.
Identification of the NRF2 transcriptional network as a therapeutic target for trigeminal neuropathic pain
Authors: Vasavda Chirag , Xu Risheng , Liew Jason , Kothari Ruchita , Dhindsa Ryan S. , Semenza Evan R. , Paul Bindu D. , Green Dustin P. , Sabbagh Mark F. , Shin Joseph Y. , Yang Wuyang , Snowman Adele M. , Albacarys Lauren K. , Moghekar Abhay , Pardo-Villamizar Carlos A. , Luciano Mark , Huang Judy , Bettegowda Chetan , Kwatra Shawn G. , Dong Xinzhong , Lim Michael , Snyder Solomon H.
Published: August 2022

Trigeminal neuralgia, historically dubbed the “suicide disease,” is an exceedingly painful neurologic condition characterized by sudden episodes of intense facial pain. Unfortunately, the only U.S. Food and Drug Administration (FDA)–approved medication for trigeminal neuralgia carries substantial side effects, with many patients requiring surgery. Here, we identify the NRF2 transcriptional network as a potential therapeutic target. We report that cerebrospinal fluid from patients with trigeminal neuralgia accumulates reactive oxygen species, several of which directly activate the pain-transducing channel TRPA1. Similar to our patient cohort, a mouse model of trigeminal neuropathic pain also exhibits notable oxidative stress. We discover that stimulating the NRF2 antioxidant transcriptional network is as analgesic as inhibiting TRPA1, in part by reversing the underlying oxidative stress. Using a transcriptome-guided drug discovery strategy, we identify two NRF2 network modulators as potential treatments. One of these candidates, exemestane, is already FDA-approved and may thus be a promising alternative treatment for trigeminal neuropathic pain.
Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity
Authors: López-Muñoz Alberto Domingo , Kosik Ivan , Holly Jaroslav , Yewdell Jonathan W.
Published: August 2022

SARS-CoV-2 nucleocapsid protein (N) induces strong antibody (Ab) and T cell responses. Although considered to be localized in the cytosol, we readily detect N on the surface of live cells. N released by SARS-CoV-2–infected cells or N-expressing transfected cells binds to neighboring cells by electrostatic high-affinity binding to heparan sulfate and heparin, but not other sulfated glycosaminoglycans. N binds with high affinity to 11 human chemokines, including CXCL12β, whose chemotaxis of leukocytes is inhibited by N from SARS-CoV-2, SARS-CoV-1, and MERS-CoV. Anti-N Abs bound to the surface of N-expressing cells activate Fc receptor–expressing cells. Our findings indicate that cell surface N manipulates innate immunity by sequestering chemokines and can be targeted by Fc-expressing innate immune cells. This, in combination with its conserved antigenicity among human CoVs, advances its candidacy for vaccines that induce cross-reactive B and T cell immunity to SARS-CoV-2 variants and other human CoVs, including novel zoonotic strains.
Triple-negative breast cancer metastasis involves complex epithelial-mesenchymal transition dynamics and requires vimentin
Authors: Grasset Eloïse M. , Dunworth Matthew , Sharma Gaurav , Loth Melanie , Tandurella Joseph , Cimino-Mathews Ashley , Gentz Melissa , Bracht Sydney , Haynes Meagan , Fertig Elana J. , Ewald Andrew J.
Published: August 2022

Triple-negative breast cancer (TNBC) is an aggressive subtype associated with early metastatic recurrence and worse patient outcomes. TNBC tumors express molecular markers of the epithelial-mesenchymal transition (EMT), but its requirement during spontaneous TNBC metastasis in vivo remains incompletely understood. We demonstrated that spontaneous TNBC tumors from a genetically engineered mouse model (GEMM), multiple patient-derived xenografts, and archival patient samples exhibited large populations in vivo of hybrid E/M cells that lead invasion ex vivo while expressing both epithelial and mesenchymal characteristics. The mesenchymal marker vimentin promoted invasion and repressed metastatic outgrowth. We next tested the requirement for five EMT transcription factors and observed distinct patterns of utilization during invasion and colony formation. These differences suggested a sequential activation of multiple EMT molecular programs during the metastatic cascade. Consistent with this model, our longitudinal single-cell RNA analysis detected three different EMT-related molecular patterns. We observed cancer cells progressing from epithelial to hybrid E/M and strongly mesenchymal patterns during invasion and from epithelial to a hybrid E/M pattern during colony formation. We next investigated the relative epithelial versus mesenchymal state of cancer cells in both GEMM and patient metastases. In both contexts, we observed heterogeneity between and within metastases in the same individual. We observed a complex spectrum of epithelial, hybrid E/M, and mesenchymal cell states within metastases, suggesting that there are multiple successful molecular strategies for distant organ colonization. Together, our results demonstrate an important and complex role for EMT programs during TNBC metastasis.
Whole-Genome Sequencing of Lysobacter capsici VKM B-2533
T
and Lysobacter gummosus 10.1.1, Promising Producers of Lytic Agents
Authors: Tarlachkov Sergey V. , Kudryakova Irina V. , Afoshin Alexey S. , Leontyevskaya Elena A. , Leontyevskaya (Vasilyeva) Natalia V.
Published: August 2022

Lysobacter capsici
VKM B-2533
T
and
Lysobacter gummosus
10.1.1 are promising strains for use in biomedicine as sources of new antimicrobial agents. Here, we report the whole-genome sequences of both strains (total lengths, 6,239,188 bp and 6,056,609 bp, respectively), obtained using the Illumina and Nanopore platforms.
Phage Resistance Accompanies Reduced Fitness of Uropathogenic Escherichia coli in the Urinary Environment
Authors: Zulk Jacob J. , Clark Justin R. , Ottinger Samantha , Ballard Mallory B. , Mejia Marlyd E. , Mercado-Evans Vicki , Heckmann Emmaline R. , Sanchez Belkys C. , Trautner Barbara W. , Maresso Anthony W. , Patras Kathryn A.
Published: August 2022

UTI is one of the most common causes of outpatient antibiotic use, and rising antibiotic resistance threatens the ability to control UTI unless alternative treatments are developed. Bacteriophage (phage) therapy is gaining renewed interest; however, much like with antibiotics, bacteria can readily become resistant to phages.
Supplemental Material: Mid–late Neoproterozoic tectonic evolution of the northern margin of the Yangtze lock, South China, as constrained from the detrital zircon record
Authors: Wang Ruirui , et al.
Published: August 2022

Table S1: Zircon U-Pb isotopic dating data. Table S2: Zircon Lu-Hf isotopic data. Table S3: Zircon trace (ppm) element compositions.
Supplemental Material: Timing and spatial variation of deformation along the Kanggur-Huangshan shear zone in the Chinese Tianshan: Implications for regional differential uplift and mineralization
Authors: Muhtar M.N. , Wu Chang-Zhi , al. et
Published: August 2022

Supplemental Text: Analytical methods. Supplemental Table S1: Zircon U-Pb age dating results. Supplemental Table S2: Argon step-heating data.
A Cell Model of an Ion-Exchange Membrane. Capillary-Osmosis and Reverse-Osmosis Coefficients
Authors: Filippov A. N.
Published: August 2022

The capillary-osmosis and reverse-osmosis coefficients of an ion-exchange membrane have been calculated as the kinetic coefficients of the Onsager matrix within the thermodynamics of nonequilibrium processes and on the basis of the cell model proposed previously by the author for charged porous layers. The membrane is assumed to consist of an ordered set of spherical completely porous charged particles placed into spherical shells filled with a binary electrolyte solution. Boundary value problems have been analytically solved to determine the capillary-osmosis and reverse-osmosis coefficients of such a membrane under the Kuwabara boundary condition imposed on the cell surface. The consideration has been implemented within the framework of small deviations of system parameters from their equilibrium values under the action of external fields. Different particular cases of the obtained exact analytical equations have been studied including the case of a binary symmetric electrolyte and an ideally selective membrane. It has been shown that, for the considered cell model of an ion-exchange membrane, the Onsager reciprocity theorem is violated; i.e., the found kinetic cross coefficients are unequal to each other. The violation is explained by the fact that the reciprocity theorem is valid only for systems implying the linear thermodynamics of irreversible processes, for which generalized flows are equal to zero at nonzero thermodynamic forces.
Intravitreal application of epidermal growth factor in non-exudative
age-related macular degeneration
Authors: Bikbov Mukharram M , Khalimov Timur A , Panda-Jonas Songhomitra , Jonas Jost B
Published: August 2022

Purpose

To assess the safety of intravitreally applied epidermal growth
factor (EGF).

Methods

The clinical interventional, prospective, single-centre, case series
study included patients with age-related macular degeneration-related
geographic atrophy (GA), in whom the eye with the worse best-corrected
visual acuity (BCVA) underwent a single, or repeated, intravitreal
injection of EGF (0.75 µg in 50 µL). At baseline and afterwards, the
eyes underwent ophthalmological examinations.

Results

The study included seven patients (mean age:70.0±12.2 years (range:
54–86 years), with five patients receiving a single injection and two
patients receiving two intravitreal injections in an interval of 4
weeks. Mean duration of follow-up was 97±97 days (median:35 days; range:
7–240 days). Mean BCVA was lower at baseline than at study end
(1.41±0.44 logMAR vs 0.97±0.12 logMAR; p=0.03). Mean size of the GA
lesions did not differ significantly between baseline and study end (29
212±22 887 pixels vs 29 300±22 905 pixels; p=0.59) nor did the mean
perimetric mean defect (−10.3±5.9 dB vs 12.0±8.8 dB; p=0.35) or the
electroretinographical b-wave amplitude (44.53±31.7 µV vs 64.5±25.5 µV;
p=0.12). After a second injection 4 weeks after the first injection, one
of two patients developed a cystoid macular oedema in association with
an induced incomplete posterior vitreous detachment. It persisted for 3
weeks. Visual acuity in this eye improved from 1.0 logMAR at baseline to
0.80 logMAR at study end.

Conclusions

Except for one eye with temporary, self-resolving cystoid macular
oedema, single and repeated intravitreal applications of EGF (0.75 µg)
in patients with GA did not lead to intraocular inflammations or any
observed intraocular side effect.

Trial registration number

NCT12733334.
Conceptual framework for systemic capacity strengthening for health policy and systems research
Authors: Mirzoev Tolib , Topp Stephanie M , Afifi Rima A , Fadlallah Racha , Obi Felix Abrahams , Gilson Lucy
Published: August 2022

Health policy and systems research (HPSR) is critical in developing health systems to better meet the health needs of their populations. The highly contextualised nature of health systems point to the value of local knowledge and the need for context-embedded HPSR. Despite such need, relatively few individuals, groups or organisations carry out HPSR, particularly in low-income and middle-income countries. Greater effort is required to strengthen capacity for, and build the field of, HPSR by capturing the multilevel and nuanced representation of HPSR across contexts. No comprehensive frameworks were found that inform systemic HPSR capacity strengthening. Existing literature on capacity strengthening for health research and development tends to focus on individual-level capacity with less attention to collective, organisational and network levels. This paper proposes a comprehensive framework for systemic capacity strengthening for HPSR, uniquely drawing attention to the blurred boundaries and amplification potential for synergistic capacity strengthening efforts across the individual, organisational and network levels. Further, it identifies guiding values and principles that consciously acknowledge and manage the power dynamics inherent to capacity strengthening work. The framework was developed drawing on available literature and was peer-reviewed by the Board and Thematic Working Groups of Health Systems Global. While the framework focuses on HPSR, it may provide a useful heuristic for systemic approaches to capacity strengthening more generally; facilitate its mainstreaming within organisations and networks and help maintain a focused approach to, and structure repositories of resources on, capacity strengthening.
Effect on bone anabolic markers of daily cheese intake with and without vitamin K2: a randomised clinical trial
Authors: Lundberg Helge Einar , Glasø Morten , Chhura Rahul , Shukla Arjun Andre , Austlid Torunn , Sarwar Zohaib , Hovland Kathrine , Iqbal Sapna , Fagertun Hans Erik , Holo Helge , Larsen Stig Einride
Published: August 2022

Background

Daily intake of 57 g Jarlsberg cheese has been shown to increase the total serum osteocalcin (tOC). Is this a general cheese effect or specific for Jarlsberg containing vitamin K2and 1,4-dihydroxy-2naphtoic acid (DHNA)?

Methods

66 healthy female volunteers (HV) were recruited. By skewed randomisation (3:2), 41 HV were allocated to daily intake of 57 g Jarlsberg (J-group) and 25–50 g Camembert (C-group) in 6 weeks. After 6 weeks the C-group was switched to Jarlsberg. The study duration was 12 weeks with clinical investigations every 6 weeks. The main variables were procollagen type 1 N-terminal propeptide (PINP), tOC, carboxylated osteocalcin (cOC) and the osteocalcin ratio (RO) defined as the ratio between cOC and undercarboxylated osteocalcin (ucOC). Serum cross-linked C-telopeptide type I collagen (CTX), vitamin K2, lipids and clinical chemistry were used as secondary variables.

Results

PINP, tOC, cOC, ROand vitamin K2increased significantly (p<0.01) after 6 weeks in the J-group. PINP remained unchanged in the C-group. The other variables decreased slightly in the C-group but increased significantly (p≤0.05) after switching to Jarlsberg. No CTX-changes detected in neither of the groups.

Serum lipids increased slightly in both groups. Switching to Jarlsberg, total cholesterol and low-density lipoprotein-cholesterol were significantly reduced (p≤0.05). Glycated haemoglobin (HbA1c), Ca++and Mg++were significantly reduced in the J-group, but unchanged in the C-group. Switching to Jarlsberg, HbA1c and Ca++decreased significantly.

Conclusion

The effect of daily Jarlsberg intake on increased s-osteocalcin level is not a general cheese effect. Jarlsberg contain vitamin K2and DHNA which increases PINP, tOC, cOC and ROand decreases Ca++, Mg++and HbA1c. These effects reflect increased bone anabolism and a possible reduced risk of adverse metabolic outcomes.

Trial registration number

NCT04189796.
Cooled and traditional thermal radiofrequency ablation of genicular nerves in patients with chronic knee pain: a comparative outcomes analysis
Authors: Wu Bernie P , Grits Daniel , Foorsov Victor , Xu Jijun , Tankha Pavan , Bolash Robert B
Published: August 2022

Introduction

Genicular nerve radiofrequency ablation (GNRFA) is a minimally invasive intervention for patients with chronic knee pain (CKP) not responding to conservative treatments. Few investigations have compared treatment outcomes of cooled-RFA (c-RFA) and thermal-RFA (t-RFA), two common approaches of GNRFA. This study aims to investigate and compare outcomes, including probability of treatment success, between c-RFA and t-RFA in patients with CKP.

Methods

This retrospective cohort study analyzed a total of 208 propensity score matched patients, including 104 patients who received c-RFA and 104 patients who received t-RFA. The primary outcome was probability of pain relief after the procedure, defined as reduction in Numeric Rating Scale (NRS) pain score of 2 or greater. The secondary outcomes were degree of NRS pain score reductions, duration of relief, and the probability of patients receiving TKA within 1 year of treatment.

Results

T-RFA was associated with a higher probability of pain relief within 1, 3, and 6 months after procedure when compared with c-RFA. Probabilities of pain relief from t-RFA and c-RFA were 62% (95% CI 51% to 71%) and 43% (95% CI 34% to 53%; p=0.01) within 1 month, 78% (95% CI 68% to 85%) and 55% (95% CI 45% to 64%; p<0.001) within 3 months, and 79% (95% CI 70% to 86%) and 59% (95% CI 49% to 68%; p<0.01) within 6 months, respectively. t-RFA was also associated with greater mean NRS pain score reduction at 1 month after procedure: −4.71 (95% CI −5.3 to −4.1) when compared with −3.59 (95% CI −4.3 to −2.9; p=0.02) from c-RFA. T-RFA and c-RFA were comparable in pain score reduction at 3, 6, 9 and 12 months after procedure. Both groups demonstrated comparable duration of relief and probability of patients receiving TKA within 1 year.

Discussion

Both t-RFA and c-RFA effectively reduced NRS pain scores in most patients with CKP within the 1 year follow-up period. Genicular nerve t-RFA was associated with a higher probability of treatment success and a greater degree of pain relief at 1 month after the procedure when compared with c-RFA in propensity score matched patients with CKP.
Antithrombotic drugs and the risk of bloody punctures in regional anesthesia - a retrospective registry analysis
Authors: Kubulus Christine , Gürtesch Christine A , Wagenpfeil Gudrun , Sessler Daniel I , Volk Thomas
Published: August 2022

Introduction

The risk of bleeding during regional anesthesia implementation in patients on antithrombotic therapy remains poorly characterized. We; therefore, analyzed bloody tap rates and adjusted ORs comparing patients who take antithrombotic medications with those who do not.

Methods

65,814 qualifying regional anesthetics (2007–2019) from the Network for Safety in Regional Anesthesia and Acute Pain Therapy registry were included in a retrospective cohort analysis. Procedures in patients who took antithrombotic drugs were compared with procedures in patients who did not. The primary outcome was bloody puncture, defined as any kind of blood aspiration during placement. Secondarily, we considered timely discontinuation of thromboprophylaxis and the impact of various drug classes. As a sensitivity analysis, we used propensity matched groups.

Results

Patients on antithrombotic therapy were more likely to have a bloody puncture during peripheral nerve block implementation (adjusted OR 1.60; 95% CI 1.33 to 1.93; p<0.001) irrespective of whether therapy was discontinued. In contrast, bloody neuraxial blocks were no more common in patients who took antithrombotic medications (adjusted OR 0.95; 95% CI 0.82 to 1.10; p=0.523) so long as they were paused per guideline. Across both peripheral and neuraxial blocks, concurrent use of more than one platelet and/or coagulation cascade inhibitor nearly doubled the odds (adjusted OR, 1.89; 95% CI 1.48 to 2.40; p<0.001).

Discussion

Patients on antithrombotic therapy receiving peripheral blocks are at increased risk for bloody punctures irrespective of discontinuation practice. Patients having neuraxial blocks are not at increased risk so long as antithrombotics are stopped per guidelines. Patients who take combined medications are at especially high risk. Guidelines for discontinuing antithrombotic treatments for neuraxial anesthesia appear to be effective and should possibly be extended to high-risk peripheral blocks.