bluuebunny/crossref_metadata_2025 huggingface dataset:
How firms realign to tackle the grand challenge of climate change: An innovation ecosystems perspective
Authors: Falcke Lukas , Zobel Ann‐Kristin , Comello Stephen D.
Published: June 2023

This study investigates how, why, and under which conditions incumbents and new entrants realign in innovation ecosystems to collectively tackle the grand challenge (GC) of climate change. The discussion on innovation and GCs is still lacking sufficient theoretical underpinnings and empirical insights to make sense of the role of for‐profit firms and their collaborative innovation efforts to address the GCs of our times. We introduce innovation ecosystems as a theoretical lens for understanding the combinations of technological interfaces and strategic relations that firms can employ to craft value propositions with high potential for tackling GCs. Empirically, this study focuses on the GC of climate change that requires a transformation of the electricity sector. We investigate collaborative pilot projects between 10 international electric utilities and 57 clean‐tech startups. In these pilots, incumbents and new entrants explore low‐carbon value propositions through novel technological interfaces and strategic relations. Via qualitative comparative analysis, we identify three configurations of ecosystem realignment with high climate impact: an incumbent‐led digital platform realignment, a device complementor and customer‐enabling realignment, and a new orchestrator realignment. Based on a multiple case analysis, we uncover three innovation mechanisms that explain why these specific configurations unlock climate impact: they enhance resource efficiency, the flexibility and resilience of infrastructure, and the trading and leveraging of information and resources. On this basis, we contribute to the literature at the intersection of innovation management and GCs by developing theory that explicates (1) how the realignment of incumbents and startups in innovation ecosystems changes existing industry structures; (2) why specific configurations of such ecosystems are associated with high climate impact and are thus effective in addressing GCs; and (3) the boundary conditions under which collective innovation efforts in ecosystems can translate into climate impact.
Reducing diarrhoea in an adult surgical intensive care unit: A quality improvement study
Authors: Occhiali Emilie , Rodrigues Bastien , Prieur Wendy , Tiarci Safia , Carmon Nicolas , Veber Benoit , Achamrah Najate
Published: June 2023

Background

Although diarrhoea is a real source of morbidity for critically ill patients, this issue has been little studied, making it difficult to understand its mechanisms and management.

Aims

We conducted a quality improvement study in an adult surgical intensive care unit before/after the implementation of a specific protocol to firstly improve diarrhoea management for patient benefit and secondly to understand the impact on caregivers.

Study design

The first part of this before/after study consisted in assessing the proportion of patients receiving an anti‐diarrheal treatment before (phase I)/after (phase II) the implementation of the protocol. The second part of the study was to survey the caregivers on this topic.

Results

Sixty four adults were included (33 in phase I; 31 in phase II) with 280 diarrheal episodes (129 in phase I; 151 in phase II). The proportion of patients who received at least one anti‐diarrheal treatment was similar between the two phases (79% (26/33) vs. 68% (21/31), p = .40). Diarrhoea incidence was also similar (9% (33 patients/368 admissions) vs. 11% (31 patients/275 admissions), p = .35). The delay to initiate at least one treatment was significantly shorter in phase II (2 days [1–7] vs. 0 day [0–2]; p < .001). The patients' rehabilitation was no longer impacted by the occurrence of a diarrheal episode in phase II (39% (13/33) vs. 0% (0/31), p < .001). Eighty team members completed the surveys in phase I and 70 in phase II. Caregivers perceived diarrhoea like a burden and its economic impact remained high.

Conclusions

The implementation of a protocol for the management of ICU diarrhoea did not increase the proportion of patients treated, but it did significantly improve the delay to initiate a treatment. The patients' rehabilitation was no longer affected by diarrhoea.

Relevance to clinical practice

The use of specific anti‐diarrhoea guidelines may help to reduce the burden of diarrhoea in an ICU.
The physiological role of thiol‐based redox sensors in plant defense signaling
Authors: Chae Ho Byoung , Bae Su Bin , Paeng Seol Ki , Wi Seong Dong , Phan Kieu Anh Thi , Kim Min Gab , Kim Woe‐Yeon , Yun Dae‐Jin , Lee Sang Yeol
Published: June 2023

Plants have developed multilayered defense strategies to adapt and acclimate to the kaleidoscopic environmental changes that rapidly produce reactive oxygen species (ROS) and induce redox changes. Thiol‐based redox sensors containing the redox‐sensitive cysteine residues act as the central machinery in plant defense signaling. Here, we review recent research on thiol‐based redox sensors in plants, which perceive the changes in intracellular H2O2 levels and activate specific downstream defense signaling. The review mainly focuses on the molecular mechanism of how the thiol sensors recognize internal/external stresses and respond to them by demonstrating several instances, such as cold‐, drought‐, salinity‐, and pathogen‐resistant signaling pathways. Also, we introduce another novel complex system of thiol‐based redox sensors operating through the liquid–liquid phase separation.
A shorter R wave peak time in left bundle branch pacing may not be a marker of more physiological ventricular activation: A case report
Authors: Zhang Yuelin , Jiang Longfu , Shen Jiabo , Zhang Lu
Published: June 2023

Left bundle branch pacing (LBBp) is a promising alternative to conventional biventricular pacing cardiac resynchronization therapy. The left anterior fascicle (LAF) is adjacent to the left ventricular outflow tract, while the left posterior fascicle (LPF) dominates a broader area of the left ventricle. Whether LAF or LPF dominates ventricular activation has not been determined. We present the case of a 76‐year‐old man who underwent LBBp implantation and propose the left ventricular activation domination in LPF pacing, an alternative when LBBp is unavailable.
Detection of atrial fibrillation in real world setting in patients with cryptogenic stroke and an implantable loop recorder
Authors: Kim Seulgi Erica , Khawaja Muzamil , Kim Jitae Alex , Safavi‐Naeini Payam , Pickett June , Molina‐Razavi Joanna , Saeed Mohammad , Razavi Mehdi , Rasekh Abdi , Chelu Mihail
Published: June 2023

Introduction

Implantable loop recorders (ILR) are used to screen for atrial fibrillation (AF) in patients with cryptogenic stroke (CS). However, there is limited real‐world data regarding the long‐term rate of AF detection using ILR and management consequences in patients with CS. The objective is to assess the rate of AF detection in patients with CS in a real‐world study over 36 months of follow‐up and its consequences on stroke prevention.

Methods

This retrospective study included patients with an ILR placed for CS at Baylor College of Medicine and Baylor St. Luke's Medical Center between January 2014 and July 2021. The primary outcome was AF detection in patients with ILR. The secondary outcome was the rate of subsequent strokes after ILR placement in patients with or without diagnosed AF. The AF detection rate in our cohort was compared to the rate in CRYSTAL‐AF Trial at 36‐month follow‐up. The impact of AF detection on clinical management was examined.

Results

We identified 225 patients. 51.1% were women and 38.2% African American. Among 85 patients with ILR labeled AF, 43 patients had true AF, and 42 had incorrectly labeled AF (48.3% false positive). The estimated AF detection rate at 36 months follow‐up was 28.6% (95% CI, 26.6%–30.6%). 58.1% of patients with AF were initiated on oral anticoagulation, 80.0% of whom were started on a direct oral anticoagulant. 13.8% of patients had recurrent strokes after ILR implantation; 4 of whom were diagnosed with AF.

Conclusion

Compared to CRYSTAL‐AF, the AF detection rate in our cohort is similar, but this cohort includes a higher proportion of female and African American patients. Most patients with recurrent strokes after ILR implant did not have AF during 36 months of monitoring.
Intraoperative fluid administration volumes during pediatric liver transplantation and postoperative outcomes: A multicenter analysis
Authors: Efune Proshad N. , Hoyt Matthew J. , Saynhalath Rita , Ahn Chul , Pearsall Matthew F. , Khan Umar H. , Feehan Thomas , Desai Dev M. , Szmuk Peter
Published: June 2023

Introduction

Fluid administration is an important aspect of the management of children undergoing liver transplantation and may impact postoperative outcomes. Our aim was to evaluate the association between volume of intraoperative fluid administration and our primary outcome, the duration of postoperative mechanical ventilation following pediatric liver transplantation. Secondary outcomes included intensive care unit length of stay and hospital length of stay.

Methods

We conducted a multicenter, retrospective cohort study using electronic data from three major pediatric liver transplant centers. Intraoperative fluid administration was indexed to weight and duration of anesthesia. Univariate and stepwise linear regression analyses were conducted.

Results

Among 286 successful pediatric liver transplants, the median duration of postoperative mechanical ventilation was 10.8 h (IQR 0.0, 35.4), the median intensive care unit length of stay was 4.3 days (IQR 2.7, 6.8), and the median hospital length of stay was 13.6 days (9.8, 21.1). Univariate linear regression showed a weak correlation between intraoperative fluids and duration of ventilation (r2 = .037, p = .001). Following stepwise linear regression, intraoperative fluid administration remained weakly correlated (r2 = .161, p = .04) with duration of postoperative ventilation. The following variables were also independently correlated with duration of ventilation: center (Riley Children's Health versus Children's Health Dallas, p = .001), and open abdominal incision after transplant (p = .001).

Discussion

The amount of intraoperative fluid administration is correlated with duration of postoperative mechanical ventilation in children undergoing liver transplantation, however, it does not seem to be a strong factor.

Conclusions

Other modifiable factors should be sought which may lead to improved postoperative outcomes in this highly vulnerable patient population.
CRISPR/Cas9‐mediated simultaneous mutation of three salicylic acid 5‐hydroxylase (OsS5H) genes confers broad‐spectrum disease resistance in rice
Authors: Liu Xiong , Yu Yan , Yao Wei , Yin Zhongliang , Wang Yubo , Huang Zijian , Zhou Jie‐Qiang , Liu Jinling , Lu Xuedan , Wang Feng , Zhang Guilian , Chen Guihua , Xiao Yunhua , Deng Huabing , Tang Wenbang
Published: June 2023

Salicylic acid (SA) is an essential plant hormone that plays critical roles in basal defence and amplification of local immune responses and establishes resistance against various pathogens. However, the comprehensive knowledge of the salicylic acid 5‐hydroxylase (S5H) in rice‐pathogen interaction is still elusive. Here, we reported that three OsS5H homologues displayed salicylic acid 5‐hydroxylase activity, converting SA into 2,5‐dihydroxybenzoic acid (2,5‐DHBA). OsS5H1, OsS5H2, and OsS5H3 were preferentially expressed in rice leaves at heading stage and responded quickly to exogenous SA treatment. We found that bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) strongly induced the expression of OsS5H1, OsS5H2, and OsS5H3. Rice plants overexpressing OsS5H1, OsS5H2, and OsS5H3 showed significantly decreased SA contents and increased 2,5‐DHBA levels, and were more susceptible to bacterial blight and rice blast. A simple single guide RNA (sgRNA) was designed to create oss5h1oss5h2oss5h3 triple mutants through CRISPR/Cas9‐mediated gene mutagenesis. The oss5h1oss5h2oss5h3 exhibited stronger resistance to Xoo than single oss5h mutants. And oss5h1oss5h2oss5h3 plants displayed enhanced rice blast resistance. The conferred pathogen resistance in oss5h1oss5h2oss5h3 was attributed to the significantly upregulation of OsWRKY45 and pathogenesis‐related (PR) genes. Besides, flg22‐induced reactive oxygen species (ROS) burst was enhanced in oss5h1oss5h2oss5h3. Collectively, our study provides a fast and effective approach to generate rice varieties with broad‐spectrum disease resistance through OsS5H gene editing.
Accelerating gene discovery in climate‐resilient and nutrient‐rich major and minor millets through genome‐wide association studies: Progress and prospects
Authors: Vellaichamy Gandhimeyyan Renganathan , Chockalingam Vanniarajan , Muthurajan Raveendran , Raman Renuka
Published: June 2023

Millets are known for their resilience and nutritional benefits and hence believed to have a promising role in ensuring food and nutritional security under changing climatic conditions. Research on millets has intensified in recent years, especially in dissecting the genetic components of yield, stress tolerance and nutritional quality traits. Recent advances in next‐generation sequencing, bioinformatics and associated statistical procedures for genome‐wide association studies (GWAS) have provided wide opportunities to resolve the genetic complexity of polygenic traits by measuring historical and evolutionary recombination events in the natural population(s). During the past decade, GWAS has been successfully employed to identify key genes controlling growth, development, stress tolerance, nutrient use efficiency and nutritional quality traits in sorghum, pearl millet, foxtail millet and finger millet. However, progress in other minor millets is still in its infancy. Genetic dissection of these complex traits in millets may pave the way for genetic alteration of climate resilience, photosynthesis and nutrient accumulation in rice and wheat. In this review, progress in GWAS analysis in detecting QTLs underlying complex traits in sorghum and other millets is highlighted.
Vaccines and use of immunosuppressive and immunomodulatory therapy in a pediatric dermatology clinic—A single institution experience
Authors: Tran Jacqueline , Trinh Dylan L. , Pan Amy Y. , Humphrey Stephen R.
Published: June 2023

Vaccine type and timing are critical issues to prevent unintended infections in those on immunosuppressive therapies. We retrospectively chart reviewed patients at Children's Wisconsin Pediatric Dermatology Clinic on immunosuppressives and immunomodulators between 11/1/2012 and 6/1/2020 and found that approximately 76% of patient encounters do not have documented vaccine counseling in the medical chart before initiation of immunosuppressives and immunomodulators. As age increased, vaccine counseling was less likely to be documented (odds ratio: 0.89; 95% confidence interval: 0.84–0.95, p = .001). In addition, 13 patient encounters (4%) were not up to date with live vaccines before immunosuppressive or immunomodulating therapy. There is an opportunity to improve clinical processes to ensure documentation of vaccination status and vaccine counseling before starting immunosuppressive and immunomodulator medications in a pediatric dermatology clinic.
Decoding neural patterns for the processing of fearful faces under different visual awareness conditions: A multivariate pattern analysis
Authors: Qiu Zeguo , Li Xuqian , Pegna Alan J.
Published: June 2023

Previous studies have provided mixed findings regarding the nonconscious processing of fearful faces. Here, we used multivariate pattern analysis on electroencephalography data from three backward masking experiments to examine the processing of fearful faces under different visual awareness conditions. Three groups of participants were shown pairs of face images presented very briefly (for 16 ms) or for sufficiently long (for 266 ms), and completed tasks where the faces were either relevant to the experimental task (Experiment 1) or not (Experiments 2 and 3). Three main decoding analyses were performed. First, in the visual awareness decoding, the visibility of the faces, and hence participants' awareness of them, was maximally decodable in three time windows: 158–168 ms, 235–260 ms and 400–600 ms where the earlier neural patterns were generalized to the later stage activity. Second, we found that the spatial location of a fearful face in the face pairs was decodable, however only when the faces were consciously seen and task‐relevant. Finally, we successfully decoded distinct neural patterns associated with the fearful‐face‐present conditions, compared to the fearful‐face‐absent conditions, and these patterns were decodable during both short and long presentations of the faces. Together, our results suggest that, while the processing of the spatial location of fearful faces requires awareness and task‐relevancy, the mere presence of fearful faces can be processed even when visual awareness is highly restricted.
The MADS‐box protein SlTAGL1 regulates a ripening‐associated SlDQD/SDH2 involved in flavonoid biosynthesis and resistance against Botrytis cinerea in post‐harvest tomato fruit
Authors: Wang Ruochen , Liu Kaidong , Tang Bei , Su Dan , He Xiaoqing , Deng Heng , Wu Mengbo , Bouzayen Mondher , Grierson Don , Liu Mingchun
Published: June 2023

3‐Dehydroquinate dehydratase/shikimate dehydrogenase (DQD/SDH) is a key rate‐limiting enzyme that catalyzes the synthesis of the shikimate, which is an important metabolic intermediate in plants and animals. However, the function of SlDQD/SDH family genes in tomato (Solanum lycopersicum) fruit metabolites is still unknown. In the present study, we identified a ripening‐associated SlDQD/SDH member, SlDQD/SDH2, that plays a key role in shikimate and flavonoid metabolism. Overexpression of this gene resulted in an increased content of shikimate and flavonoids, while knockout of this gene by CRISPR/Cas9 mediated gene editing led to a significantly lower content of shikimate and flavonoids by downregulation of flavonoid biosynthesis‐related genes. Moreover, we showed that SlDQD/SDH2 confers resistance against Botrytis cinerea attack in post‐harvest tomato fruit. Dual‐luciferase reporter and EMSA assays indicated that SlDQD/SDH2 is a direct target of the key ripening regulator SlTAGL1. In general, this study provided a new insight into the biosynthesis of flavonoid and B. cinerea resistance in fruit tomatoes.
A Proteção de Dados Pessoais sob o Regulamento de Proteção de Dados da União Europeia
Authors: Spiecker genannt Döhmann Indra
Published: June 2023

O presente artigo tem como objetivo apresentar o direito sobre proteção de dados na Europa, expondo os seus conceitos, princípios e traços fundamentais. Como a efetivação foi tema de grande importância para a motivação do RGPD-UE, introduzem-se as estruturas da implementação, particularmente a importância das autoridades independentes de fiscalização, bem como o novo mecanismo de coerência mediante o qual atua o novo Comitê Europeu para a Proteção de Dados (European Data Protection Board – EDPB) (4). Conclui-se a contribuição com uma perspectiva referente a novos desafios e novas abordagens de regulação (5).
New Solutions of the Fractional Differential Equations With Modified Mittag-Leffler Kernel
Authors: Odibat Zaid , Baleanu Dumitru
Published: June 2023

This paper is concerned with some features of the modified Caputo-type Mittag-Leffler fractional derivative operator and its associated fractional integral operator. Mainly, new types of solutions for fractional differential equations with Mittag-Leffler kernel are generated based on a numerical algorithm developed in this paper. The suggested algorithm is used to describe the solution behavior of models involving modified Caputo-type Mittag-Leffler fractional derivatives. The results described in this paper are expected to be effectively employed in the area of simulating related fractional models.
Development of Analysis Tools for Heat Pipes Used in the Core Cooling of Small Modular Reactors: Potassium Property Correlations
Authors: Beuthe Thomas , Jazebizadeh Hooman , Vasić Aleksandar , Pegarkov Alex , Kaya Tarik , Zahlan Hussam
Published: June 2023

Alkali metal heat pipes can be used for core cooling in advanced micro- and small modular reactors. This article provides a detailed review of currently available saturation property correlations for potassium that can be utilized in heat pipe simulation models. Using these properties, numerical models will be developed and employed to simulate and compare the performance of heat pipe models to experimental results. A comprehensive comparative overview of the best available potassium saturation property correlations developed over the past century has been assembled. The results show most of the potassium property correlations needed to model a heat pipe are relatively well defined and recommendations for their use can be provided, but the findings also suggest a significant disparity in some cases.
Molecular beam epitaxy and crystal structure of majority a-plane-oriented and substrate-strained Mn3Sn thin films grown directly on sapphire (0001)
Authors: Upadhyay Sneha , Erickson Tyler , Hall Hannah , Shrestha Ashok , Ingram David C. , Sun Kai , Moreno Hernandez Juan Carlos , Hernandez Cocoletzi Gregorio , Takeuchi Noboru , Smith Arthur R.
Published: June 2023

The Kagome antiferromagnet Mn3Sn has garnered much attention due to the presence of exciting properties such as anomalous Hall and Nernst effects. This paper discusses the synthesis of crystalline Mn3Sn thin films, prepared on Al2O3 (0001) substrates at 453±5°C using molecular beam epitaxy. The growth is monitored in situ using reflection high energy electron diffraction and measured ex situ using x-ray diffraction, Rutherford back-scattering, and cross-sectional scanning transmission electron microscopy. Our analysis shows the in-plane lattice constants of a1,M=4.117±0.027 Å and a2,M=4.943±0.033 Å, which is a very unexpected result when compared to the bulk a-plane Mn3Sn. This indicates a strain in the film and makes it challenging to provide a straightforward explanation. In an effort to explain our results, we discuss two possible orientation relationships between the Mn3Sn films and the sapphire substrates. Samples prepared under these conditions appear to have smooth surfaces locally, but overall the film has a 3D island morphology. First-principles calculations provide atomic models of the Mn3Sn (112¯0) lattice on Al2O3 (0001) high symmetry sites, indicating that the L3-R90° is the most stable configuration. A detailed discussion of the experimental data and theoretical results, as well as strain effects, is provided.
Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response
Authors: Doloff Joshua C. , Ma Minglin , Sadraei Atieh , Tam Hok Hei , Farah Shady , Hollister-Lock Jennifer , Vegas Arturo J. , Veiseh Omid , Quiroz Victor M. , Rakoski Amanda , Aresta-DaSilva Stephanie , Bader Andrew R. , Griffin Marissa , Weir Gordon C. , Brehm Michael A. , Shultz Leonard D. , Langer Robert , Greiner Dale L. , Anderson Daniel G.
Published: June 2023

Biomedical devices comprise a major component of modern medicine, however immune-mediated fibrosis and rejection can limit their function over time. Here, we describe a humanized mouse model that recapitulates fibrosis following biomaterial implantation. Cellular and cytokine responses to multiple biomaterials were evaluated across different implant sites. Human innate immune macrophages were verified as essential to biomaterial rejection in this model and were capable of cross-talk with mouse fibroblasts for collagen matrix deposition. Cytokine and cytokine receptor array analysis confirmed core signaling in the fibrotic cascade. Foreign body giant cell formation, often unobserved in mice, was also prominent. Last, high-resolution microscopy coupled with multiplexed antibody capture digital profiling analysis supplied spatial resolution of rejection responses. This model enables the study of human immune cell–mediated fibrosis and interactions with implanted biomaterials and devices.
Single-cell and spatial transcriptome analysis reveals the cellular heterogeneity of liver metastatic colorectal cancer
Authors: Wang Fei , Long Jie , Li Liang , Wu Zi-Xin , Da Tian-Tian , Wang Xiao-Qing , Huang Chuan , Jiang Yi-Hua , Yao Xue-Qing , Ma Hai-Qing , Lian Zhe-Xiong , Zhao Zhi-Bin , Cao Jie
Published: June 2023

In this study, we comprehensively charted the cellular landscape of colorectal cancer (CRC) and well-matched liver metastatic CRC using single-cell and spatial transcriptome RNA sequencing. We generated 41,892 CD45
−
nonimmune cells and 196,473 CD45
+
immune cells from 27 samples of six CRC patients, and found that CD8_CXCL13 and CD4_CXCL13 subsets increased significantly in liver metastatic samples that exhibited high proliferation ability and tumor-activating characterization, contributing to better prognosis of patients. Distinct fibroblast profiles were observed in primary and liver metastatic tumors.
F3
+
fibroblasts enriched in primary tumors contributed to worse overall survival by expressing protumor factors. However,
MCAM
+
fibroblasts enriched in liver metastatic tumors might promote generation of CD8_CXCL13 cells through Notch signaling. In summary, we extensively analyzed the transcriptional differences of cell atlas between primary and liver metastatic tumors of CRC by single-cell and spatial transcriptome RNA sequencing, providing different dimensions of the development of liver metastasis in CRC.
Nerve-independent formation of membrane infoldings at topologically complex postsynaptic apparatus by caveolin-3
Authors: Kwan Hui-Lam Rachel , Chan Zora Chui-Kuen , Bi Xinyi , Kutkowska Justyna , Prószyński Tomasz J. , Chan Chi Bun , Lee Chi Wai
Published: June 2023

Junctional folds are unique membrane specializations developed progressively during the postnatal maturation of vertebrate neuromuscular junctions (NMJs), but how they are formed remains elusive. Previous studies suggested that topologically complex acetylcholine receptor (AChR) clusters in muscle cultures undergo a series of transformations, resembling the postnatal maturation of NMJs in vivo. We first demonstrated the presence of membrane infoldings at AChR clusters in cultured muscles. Live-cell super-resolution imaging further revealed that AChRs are gradually redistributed to the crest regions and spatially segregated from acetylcholinesterase along the elongating membrane infoldings over time. Mechanistically, lipid raft disruption or caveolin-3 knockdown not only inhibits membrane infolding formation at aneural AChR clusters and delays agrin-induced AChR clustering in vitro but also affects junctional fold development at NMJs in vivo. Collectively, this study demonstrated the progressive development of membrane infoldings via nerve-independent, caveolin-3–dependent mechanisms and identified their roles in AChR trafficking and redistribution during the structural maturation of NMJs.
A symmetry mismatch unraveled: How phage HK97 scaffold flexibly accommodates a 12-fold pore at a 5-fold viral capsid vertex
Authors: Huet Alexis , Oh Bonnie , Maurer Josh , Duda Robert L. , Conway James F.
Published: June 2023

Tailed bacteriophages and herpesviruses use a transient scaffold to assemble icosahedral capsids with hexameric capsomers on the faces and pentameric capsomers at all but one vertex where a 12-fold portal is thought to nucleate the assembly. How does the scaffold orchestrate this step? We have determined the portal vertex structure of the bacteriophage HK97 procapsid, where the scaffold is a domain of the major capsid protein. The scaffold forms rigid helix-turn-strand structures on the interior surfaces of all capsomers and is further stabilized around the portal, forming trimeric coiled-coil towers, two per surrounding capsomer. These 10 towers bind identically to 10 of 12 portal subunits, adopting a pseudo-12-fold organization that explains how the symmetry mismatch is managed at this early step.
Composition and sequence-controlled conductance of crystalline unimolecular monolayers
Authors: Wang Jinxin , Zhao Yongjie , Li Shumu , Shen Lingyun , Zhang Hao , Ding Caijun , Wei Chang , Wang Yanfang , Li Yongfang , Hong Wenjing , Li Mao
Published: June 2023

Understanding how the charge travels through sequence-controlled molecules has been a formidable challenge because of simultaneous requirements in well-controlled synthesis and well-manipulated orientation. Here, we report electrically driven simultaneous synthesis and crystallization as a general strategy to study the conductance of composition and sequence-controlled unioligomer and unipolymer monolayers. The structural disorder of molecules and conductance variations on random positions can be extremely minimized, by uniform synthesis of monolayers unidirectionally sandwiched between electrodes, as an important prerequisite for the reproducible measurement on the micrometer scale. These monolayers show tunable current density and on/off ratios in four orders of magnitude with controlled multistate and massive negative differential resistance (NDR) effects. The conductance of monolayer mainly depends on the metal species in homo-metal monolayers, while the sequence becomes a matter in hetero-metal monolayers. Our work demonstrates a promising way to release an ultra-rich variety of electrical parameters and optimize the functions and performances of multilevel resistive devices.
Cambrian radiation speciation events driven by sea level and redoxcline changes on the Siberian Craton
Authors: Zhuravlev Andrey Yu. , Wood Rachel A. , Bowyer Fred T.
Published: June 2023

The evolutionary processes of speciation during the Cambrian radiation and their potential extrinsic drivers, such as episodic oceanic oxygenation events, remain unconfirmed. High-resolution temporal and spatial distribution of reef-associated archaeocyath sponge species on the Siberian Craton during the early Cambrian [ca. 528 to 510 million years ago] shows that speciation was driven by increased endemism particularly ca. 521 million years (59.7% endemic species) and 514.5 million years (65.25% endemic species) ago. These mark rapid speciation events after dispersal of ancestors from the Aldan-Lena center of origin to other regions. These speciation events coincided with major sea-level lowstands, which we hypothesize were intervals when relative deepening of the shallow redoxcline permitted extensive oxygenation of shallow waters over the entire craton. This provided oxic corridors for dispersal and allowed the formation of new founder communities. Thus, shallow marine oxygen expansion driven by sea-level oscillations provides an evolutionary driver for sucessive speciation events during the Cambrian radiation.
Hexokinase dissociation from mitochondria promotes oligomerization of VDAC that facilitates NLRP3 inflammasome assembly and activation
Authors: Baik Sung Hoon , Ramanujan V. Krishnan , Becker Courtney , Fett Sarah , Underhill David M. , Wolf Andrea J.
Published: June 2023

NLRP3 inflammasome activation is a highly regulated process for controlling secretion of the potent inflammatory cytokines IL-1β and IL-18 that are essential during bacterial infection, sterile inflammation, and disease, including colitis, diabetes, Alzheimer’s disease, and atherosclerosis. Diverse stimuli activate the NLRP3 inflammasome, and unifying upstream signals has been challenging to identify. Here, we report that a common upstream step in NLRP3 inflammasome activation is the dissociation of the glycolytic enzyme hexokinase 2 from the voltage-dependent anion channel (VDAC) in the outer membrane of mitochondria. Hexokinase 2 dissociation from VDAC triggers activation of inositol triphosphate receptors, leading to release of calcium from the ER, which is taken up by mitochondria. This influx of calcium into mitochondria leads to oligomerization of VDAC, which is known to form a macromolecule-sized pore in the outer membranes of mitochondria that allows proteins and mitochondrial DNA (mtDNA), often associated with apoptosis and inflammation, respectively, to exit the mitochondria. We observe that VDAC oligomers aggregate with NLRP3 during initial assembly of the multiprotein oligomeric NLRP3 inflammasome complex. We also find that mtDNA is necessary for NLRP3 association with VDAC oligomers. These data, together with other recent work, help to paint a more complete picture of the pathway leading to NLRP3 inflammasome activation.
Efficacy and safety of luseogliflozin in Caucasian patients with type 2 diabetes: results from a phase III, randomized, placebo-controlled, clinical trial
Authors: Shestakova Marina , Kvasnikov Boris , Erina Ekaterina , Isachenko Elena , Andreev Alexander
Published: June 2023

Introduction

Most data demonstrating the efficacy and safety of luseogliflozin (luseo) in people with type 2 diabetes mellitus (T2DM) originate from the Japanese population. This study evaluated luseo versus placebo (PCB) as add-on to metformin in a Caucasian population with inadequately controlled T2DM.

Research design and methods

This was a multicenter, randomized, double-blind, PCB-controlled, parallel-group study. Patients aged 18–75 years with inadequately controlled T2DM (glycated hemoglobin (HbA1c) ≥7% to ≤10% (≥53 to ≤86 mmol/mol)) despite a diet and exercise program and on a stable metformin regimen were eligible. Patients were randomized to one of three luseo groups (2.5, 5.0 and 10.0 mg) or PCB for 12 weeks (W12). The primary endpoint was change in HbA1c expressed as least-square means from baseline (W0) to W12.

Results

A total of 328 patients were randomized: PCB (n=83) and luseo 2.5 mg (n=80), 5.0 mg (n=86), and 10.0 mg (n=79). Mean age (±SD) was 58.5±8.8 years; 64.6% were women; body mass index was 31.5±3.4 kg/m2; and HbA1c was 8.54±0.70. At W12, mean reductions in HbA1c from W0 were −0.98%, −1.09%, −1.18%, and −0.73% in the luseo 2.5, 5.0 and 10.0 mg, and PCB groups, respectively, all of which were statistically significant. Compared with PCB, HbA1c levels were significantly decreased by 0.25% (p=0.045), 0.36% (p=0.006), and 0.45% (p=0.001) in the luseo 2.5, 5.0, and 10.0 mg groups, respectively. In all luseo dose groups, reductions in body weight were statistically significant compared with PCB. Data from the safety analysis were consistent with the known luseo safety profile.

Conclusions

All doses of luseo as add-on to metformin in Caucasian patients with uncontrolled T2DM demonstrated significant efficacy in decreasing HbA1c after W12 of treatment.

Trial registration number

ISRCTN39549850.
Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials
Authors: Hong Hwanhee , Friedland Anne , Hu Mengyi , Anstrom Kevin J , Halabi Susan , McKinnon John E , Amaravadi Ravi , Rojas-Serrano Jorge , Abella Benjamin S , Portillo-Vázquez Angélica Margarita , Woods Christopher W , Hernandez Adrian F , Boulware David R , Naggie Susanna , Rajasingham Radha
Published: June 2023

Objective

We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs).

Data sources

PubMed and EMBASE databases were searched to identify randomised trials studying HCQ.

Study selection

Ten RCTs were identified (n=5079 participants).

Data extraction and synthesis

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and meta-analysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written.

Main outcomes

The primary efficacy outcome was PCR-confirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection.

Results

Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95% CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95% CI: 1.03, 1.73).

Conclusions and relevance

Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as pre-exposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events.

PROSPERO registration number

CRD42021285093.
Suicide postvention for staff and students on university campuses: a scoping review
Authors: Allie Sophia-Lorraine Noxolo , Bantjes Jason , Andriessen Karl
Published: June 2023

Objective

To examine current knowledge about suicide bereavement and postvention interventions for university staff and students.

Design

Scoping review.

Data sources and eligibility

We conducted systematic searches in 12 electronic databases (PubMed, PsycINFO, MEDLINE, CINAHL, Africa-Wide Information, PsycARTICLES, Health Source: Nursing/Academic Edition, Academic Search Premier, SocINDEX through the EBSCOHOST platform; Cochrane Library, Web of Science, SCOPUS), hand searched lists of references of included articles and consulted with library experts during September 2021 and June 2022. Eligible studies were screened against the inclusion criteria independently by two reviewers. Only studies published in English were included.

Data extraction and synthesis

Screening was conducted by two independent reviewers following a three-step article screening process. Biographical data and study characteristics were extracted using a data extraction form and synthesised.

Results

Our search strategy identified 7691 records from which 3170 abstracts were screened. We assessed 29 full texts and included 17 articles for the scoping review. All studies were from high-income countries (USA, Canada, UK). The review identified no postvention intervention studies on university campuses. Study designs were mostly descriptive quantitative or mixed methods. Data collection and sampling were heterogeneous.

Conclusion

Staff and students require support measures due to the impact of suicide bereavement and the unique nature of the university context. There is a need for further research to move from descriptive studies to focus on intervention studies, particularly at universities in low-income and middle-income countries.
What does high value care for musculoskeletal conditions mean and how do you apply it in practice? A consensus statement from a research network of physiotherapists in New South Wales, Australia
Authors: Gleadhill Connor , Dooley Katherine , Kamper Steven J , Manvell Nicole , Corrigan Michael , Cashin Aidan , Birchill Noah , Donald Bruce , Leyland Murray , Delbridge Andrew , Barnett Chris , Renfrew David , Lamond Steven , Boettcher Craig Edward , Chambers Lucia , Maude Travis , Davis Jon , Hodgson Stephanie , Makaroff Andrew , Wallace James B , Kotrick Kelly , Mullen Nicholas , Gallagher Ryan , Zelinski Samuel , Watson Toby , Davidson Simon , Viana Da Silva Priscilla , Mahon Benjamin , Delore Caitlin , Manvell Joshua , Gibbs Benedicta , Hook Chris , Stoddard Chris , Meers Elliot , Byrne Michael , Schneider Tim , Bolsewicz Katarzyna , Williams Christopher Michael
Published: June 2023

Objectives

To develop a physiotherapist-led consensus statement on the definition and provision of high-value care for people with musculoskeletal conditions.

Design

We performed a three-stage study using Research And Development/University of California Los Angeles Appropriateness Method methodology. We reviewed evidence about current definitions through a rapid literature review and then performed a survey and interviews with network members to gather consensus. Consensus was finalised in a face-to-face meeting.

Setting

Australian primary care.

Participants

Registered physiotherapists who are members of a practice-based research network (n=31).

Results

The rapid review revealed two definitions, four domains of high value care and seven themes of high-quality care. Online survey responses (n=26) and interviews (n=9) generated two additional high-quality care themes, a definition of low-value care, and 21 statements on the application of high value care. Consensus was reached for three working definitions (high value, high-quality and low value care), a final model of four high value care domains (high-quality care, patient values, cost-effectiveness, reducing waste), nine high-quality care themes and 15 statements on application.

Conclusion

High value care for musculoskeletal conditions delivers most value for the patient, and the clinical benefits outweigh the costs to the individual or system providing the care. High-quality care is evidence based, effective and safe care that is patient-centred, consistent, accountable, timely, equitable and allows easy interaction with healthcare providers and healthcare systems.
Burden of maternal high-risk fertility behaviour on under-five children’s health status in Hadiya zone, Southern Ethiopia: a facility-based cross-sectional study
Authors: Kusheta Samuel , Demelash Robel , Kenea Elias , Kasa Genet , Ermako Woineshet , Daniel Dinku
Published: June 2023

Background

Maternal high-risk fertility behaviours (HRFBs) are common in African countries and can potentially affect child survival. Evidence of the burden of maternal HRFB on under-five children is scant in Ethiopia.

Objective

To determine the burden of maternal HRFB on under-five children’s health status in Hadiya zone, Southern Ethiopia.

Design

A facility-based cross-sectional study was conducted.

Setting

All secondary and tertiary public healthcare centres; that are, one referral and three district hospitals providing comprehensive emergency obstetric care services in the Hadiya zone, Southern Ethiopia.

Participants

Three hundred women of reproductive age (15–49 years) who had undergone childbirth in the 5 years preceding this study and living with at least one child younger than 5 years admitted to public hospitals in Hadiya zone were included.

Main outcome measure

Under-five children’s health status.

Results

The overall proportion of maternal HRFB among currently married women was 60.3%, with 35.0% falling into a single high-risk category and 25.3% falling into multiple high-risk categories. Children younger than 5 years born to mothers having HRFB had an increased chance of acute respiratory infections five times, diarrhoea six times, fever eight times, low birth weight six times and a chance of dying before the fifth birthday two times than children born to mothers with no risk. The risks of morbidity and mortality further increased when children were born to mothers falling into multiple high-risk categories.

Conclusions

The overall proportion of maternal HRFB among currently married women was high in the study area. A statistically significant association was seen between maternal HRFB and health outcomes of children younger than 5 years old. Intervening to avert maternal HRFBs through family planning may help to reduce childhood morbidity and mortality.
A hypothesis - generating Swedish extended national cross-sectional family study of multimorbidity severity and venous thromboembolism
Authors: Ahrén Jonatan , Pirouzifard MirNabi , Holmquist Björn , Sundquist Jan , Halling Anders , Sundquist Kristina , Zöller Bengt
Published: June 2023

Objectives

Venous thromboembolism (VTE) is a common worldwide disease. The burden of multimorbidity, that is, two or more chronic diseases, has increased. Whether multimorbidity is associated with VTE risk remains to be studied. Our aim was to determine any association between multimorbidity and VTE and any possible shared familial susceptibility.

Design

A nationwide extended cross-sectional hypothesis - generating family study between 1997 and 2015.

Setting

The Swedish Multigeneration Register, the National Patient Register, the Total Population Register and the Swedish cause of death register were linked.

Participants

2 694 442 unique individuals were analysed for VTE and multimorbidity.

Main outcomes and measures

Multimorbidity was determined by a counting method using 45 non-communicable diseases. Multimorbidity was defined by the occurrence of ≥2 diseases. A multimorbidity score was constructed defined by 0, 1, 2, 3, 4 or 5 or more diseases.

Results

Sixteen percent (n=440 742) of the study population was multimorbid. Of the multimorbid patients, 58% were females. There was an association between multimorbidity and VTE. The adjusted odds ratio (OR) for VTE in individuals with multimorbidity (2 ≥ diagnoses) was 3.16 (95% CI: 3.06 to 3.27) compared with individuals without multimorbidity. There was an association between number of diseases and VTE. The adjusted OR was 1.94 (95% CI: 1.86 to 2.02) for one disease, 2.93 (95% CI: 2.80 to 3.08) for two diseases, 4.07 (95% CI: 3.85 to 4.31) for three diseases, 5.46 (95% CI: 5.10 to 5.85) for four diseases and 9.08 (95% CI: 8.56 to 9.64) for 5 ≥ diseases. The association between multimorbidity and VTE was stronger in males OR 3.45 (3.29 to 3.62) than in females OR 2.91 (2.77 to 3.04). There were significant but mostly weak familial associations between multimorbidity in relatives and VTE.

Conclusions

Increasing multimorbidity exhibits a strong and increasing association with VTE. Familial associations suggest a weak shared familial susceptibility. The association between multimorbidity and VTE suggests that future cohort studies where multimorbidity is used to predict VTE might be worthwhile.
Examination of the demographic representativeness of a cross-sectional mobile phone survey in collecting health data in Colombia using random digit dialling
Authors: Guzman-Tordecilla Deivis Nicolas , Vecino-Ortiz Andres I , Torres-Quintero Angélica , Solorzano-Barrera Camila , Ali Joseph , Peñaloza-Quintero Rolando Enrique , Ahmed Saifuddin , Pariyo George W , Maniar Vidhi , Gibson Dustin G
Published: June 2023

Objectives

As mobile phone ownership becomes more widespread in low-income and middle-income countries, mobile phone surveys (MPSs) present an opportunity to collect data on health more cost-effectively. However, selectivity and coverage biases in MPS are concerns, and there is limited information about the population-level representativeness of these surveys compared with household surveys. This study aims at comparing the sociodemographic characteristics of the respondents of an MPS on non-communicable disease risk factors to a household survey in Colombia.

Design

Cross-sectional study. We used a random digit dialling method to select the samples for calling mobile phone numbers. The survey was conducted using two modalities: computer-assisted telephone interviews (CATIs) and interactive voice response (IVR). The participants were assigned randomly to one of the survey modalities based on a targeted sampling quota stratified by age and sex. The Quality-of-Life Survey (ECV), a nationally representative survey conducted in the same year of the MPS, was used as a reference to compare the sample distributions by sociodemographic characteristics of the MPS data. Univariate and bivariate analyses were performed to evaluate the population representativeness between the ECV and the MPSs.

Setting

The study was conducted in Colombia in 2021.

Participants

Population at least 18 years old with a mobile phone.

Results

We completed 1926 and 2983 interviews for CATI and IVR, respectively. We found that the MPS data have a similar (within 10% points) age–sex data distribution compared with the ECV dataset for some subpopulations, mainly for young populations, people with none/primary and secondary education levels, and people who live in urban and rural areas.

Conclusions

This study shows that MPS could collect similar data to household surveys in terms of age, sex, high school education level and geographical area for some population categories. Strategies are needed to improve representativeness of the under-represented groups.