bluuebunny/crossref_metadata_2025 huggingface dataset:
Light-sensitive phosphorylation regulates enzyme activity and filament assembly of human IMPDH1 retinal splice variants
Authors: Calise S. John , O’Neill Audrey G. , Burrell Anika L. , Dickinson Miles S. , Molfino Josephine , Clarke Charlie , Quispe Joel , Sokolov David , Buey Rubén M. , Kollman Justin M.
Published: September 2023

Inosine monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme inde novoguanosine triphosphate (GTP) synthesis and is controlled by feedback inhibition and allosteric regulation. IMPDH assembles into micron-scale filaments in cells, which desensitizes the enzyme to feedback inhibition by GTP and boosts nucleotide production. The vertebrate retina expresses two tissue-specific splice variants IMPDH1(546) and IMPDH1(595). IMPDH1(546) filaments adopt high and low activity conformations, while IMPDH1(595) filaments maintain high activity. In bovine retinas, residue S477 is preferentially phosphorylated in the dark, but the effects on IMPDH1 activity and regulation are unclear. Here, we generated phosphomimetic mutants to investigate structural and functional consequences of phosphorylation in IMPDH1 variants. The S477D mutation re-sensitized both variants to GTP inhibition, but only blocked assembly of IMPDH1(595) filaments and not IMPDH1(546) filaments. Cryo-EM structures of both variants showed that S477D specifically blocks assembly of the high activity assembly interface, still allowing assembly of low activity IMPDH1(546) filaments. Finally, we discovered that S477D exerts a dominant-negative effect in cells, preventing endogenous IMPDH filament assembly. By modulating the structure and higher-order assembly of IMPDH, phosphorylation at S477 acts as a mechanism for downregulating retinal GTP synthesis in the dark, when nucleotide turnover is decreased. Like IMPDH1, many other metabolic enzymes dynamically assemble filamentous polymers that allosterically regulate activity. Our work suggests that posttranslational modifications may be yet another layer of regulatory control to finely tune activity by modulating filament assembly in response to changing metabolic demands.

SIGNIFICANCE STATEMENT

Over 20 different metabolic enzymes form micron-scale filaments in cells, suggesting that filament assembly is a conserved mechanism for regulating diverse metabolic pathways. Filament assembly regulates catalytic activity of many of these enzymes, including inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme inde novoGTP biosynthesis. The vertebrate retina expresses two IMPDH1 splice variants that are critical for maintaining nucleotide levels required for phototransduction. Here, we show that filament assembly by these variants is itself controlled by phosphorylation at a single residue, adding further complexity to the tight regulation of nucleotide metabolism in the retina. Phosphorylation and other posttranslational modifications are likely to be a general regulatory mechanism controlling filament assembly by enzymes in many different metabolic pathways.
Methionine Alkylation as an Approach to Quantify Methionine Oxidation Using Mass Spectrometry
Authors: Hoare Margaret , Tan Ruiyue , Welle Kevin A. , Swovick Kyle , Hryhorenko Jennifer R. , Ghaemmaghami Sina
Published: September 2023

Post-translational oxidation of methionine residues can destabilize proteins or modify their functions. Although levels of methionine oxidation can provide important information regarding the structural integrity and regulation of proteins, their quantitation is often challenging as analytical procedures in and of themselves can artifactually oxidize methionines. Here, we develop a mass spectrometry-based method called Methionine Oxidation by Blocking with Alkylation (MObBa) that quantifies methionine oxidation by selectively alkylating and blocking unoxidized methionines. Thus, alkylated methionines can be used as a stable proxy for unoxidized methionines. Using proof of concept experiments, we demonstrate that MObBa can be used to measure methionine oxidation levels within individual synthetic peptides and on proteome-wide scales. MObBa may provide a straightforward experimental strategy for mass spectrometric quantitation of methionine oxidation.

Significance Statement

Over time, cellular proteins can become oxidatively damaged by reactive oxygen species (ROS). A residue that is particularly prone to oxidative damage is methionine. Here, we develop and validate a methodology for detecting and quantifying levels of methionine oxidation by mass spectrometry. This approach has a number of practical advantages over methods currently available for analysis of methionine oxidation. The ability to accurately quantify methionine oxidation will provide important insights into factors that influence protein homeostasis within a cell.
The Inflammasome Pathway is Activated by Dengue Virus Non-structural Protein 1 and is Protective During Dengue Virus Infection
Authors: Wong Marcus P. , Juan Evan Y.W. , Chelluri Sai S. , Wang Phoebe , Pahmeier Felix , Castillo-Rojas Bryan , Blanc Sophie F. , Biering Scott B. , Vance Russell E. , Harris Eva
Published: September 2023

Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a major driver of dengue pathogenesis by inducing endothelial barrier dysfunction. However, less is known about how DENV NS1 interacts with immune cells and what role these interactions play. Here we report that DENV NS1 can trigger activation of inflammasomes, a family of cytosolic innate immune sensors that respond to infectious and noxious stimuli, in mouse and human macrophages. DENV NS1 induces the release of IL-1β in a caspase-1 dependent manner. Additionally, we find that DENV NS1-induced inflammasome activation is independent of the NLRP3, Pyrin, and AIM2 inflammasome pathways, but requires CD14. Intriguingly, DENV NS1-induced inflammasome activation does not induce pyroptosis and rapid cell death; instead, macrophages maintain cellular viability while releasing IL-1β. Lastly, we show that caspase-1/11-deficient, but not NLRP3-deficient, mice are more susceptible to lethal DENV infection. Together, these results indicate that the inflammasome pathway acts as a sensor of DENV NS1 and plays a protective role during infection.
PAI-1 Deficiency Drives Pulmonary Vascular Smooth Muscle Remodeling and Pulmonary Hypertension
Authors: Kudryashova Tatiana V. , Zaitsev Sergei , Jiang Lifeng , Buckley Benjamin J , McGuckin Joshua P. , Goncharov Dmitry , Zhyvylo Iryna , Lin Derek , Newcomb Geoffrey , Piper Bryce , Bogamuwa Srimathi , Saiyed Aisha , Teos Leyla , Ranson Marie , Wolters Paul J. , Kelso Michael J. , Poncz Mortimer , DeLisser Horace M. , Cines Douglas B. , Goncharova Elena A. , Farkas Laszlo , Stepanova Victoria
Published: September 2023

Pulmonary arterial hypertension (PAH) is a progressive and potentially a rapidly fatal disease characterized by vasoconstriction and remodeling of small pulmonary arteries (PA) leading to increased pulmonary vascular resistance and right heart failure. Central to the remodeling process is a switch of the smooth muscle cells in small PAs (PASMC) to a proliferative, apoptosis-resistant phenotype.

There is reason to suspect that the plasminogen activator system may play an important role in the remodeling program in PAH based on its roles in vascular post-injury restenosis, fibrosis, angiogenesis and tumorigenesis. Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological inhibitor of the plasminogen activators - urokinase-type and tissue-type (uPA and tPA, respectively). Immunohisto- chemical and immunoblot analyses revealed that PAI-1 was deficient in smooth muscle areas of small remodeled PAs and early-passage PASMC from subjects with PAH compared to non-PAH controls.PAI1-/-male and female mice developed spontaneous pulmonary vascular remodeling and pulmonary hypertension (PH) as evidenced by significant increase in PA medial thickness, systolic right ventricular pressure, and right ventricular hypertrophy. Lastly, the uPA inhibitors upamostat (WX-671) and amiloride analog BB2-30F down-regulated mTORC1 and SMAD3, restored PAI-1 levels, reduced proliferation, and induced apoptosis in human PAH PASMC. We examined the effect of inhibition of uPA catalytic activity by BB2-30F on the development of SU5416/Hypoxia (SuHx)-induced PH in mice. Vehicletreated SuHx-exposed mice had up-regulated mTORC1 in small PAs, developed pulmonary vascular remodeling and PH, as evidenced by significant increase of PA MT, sRVP, RV hypertrophy, and a significant decrease in the pulmonary artery acceleration time/pulmonary ejection time (PAAT/PET) ratio compared to age- and sex-matched normoxia controls, whereas BB2-30F-treated group was protected from all these pathological changes. Taken together, our data strongly suggest that PAI-1 down- regulation in PASMC from human PAH lungs promotes PASMC hyper-proliferation, remodeling, and spontaneous PH due to unopposed uPA activation. Further studies are needed to determine the potential benefits of targeting the PAI-1/uPA imbalance to attenuate the progression and/or reverse pulmonary vascular remodeling and PH.
MarrowDLD: a microfluidic method for label-free retrieval of fragile bone marrow cells
Authors: Porro Gloria , Sarkis Rita , Obergozo Clara , Godot Lucie , Amato Francesco , Humbert Magali , Naveiras Olaia , Guiducci Carlotta
Published: September 2023

Functional bone marrow studies have focused primarily on hematopoietic progenitors, leaving limited knowledge about other fragile populations, such as bone marrow adipocytes (BMAds) and megakaryocytes. The isolation of these cells is challenging due to rupture susceptibility and large size. We introduce here a label-free cytometry microsystem, MarrowDLD, based on deterministic lateral displacement. MarrowDLD enables the isolation of fragile cells based on intrinsic size properties while preserving their viability and functionality. Bone marrow adipocytes, obtained from mouse and human stromal line differentiation, as well as megakaryocytes, from primary human CD34+ hematopoietic stem and progenitor cells, were used for validation. Precise micrometer-range separation cutoffs were adapted for each cell type. Cells were sorted directly in culture media, without pre-labeling steps, and with real-time imaging for quality control. At least 106cells were retrieved intact per sorting round. Our method outperformed two FACS instruments in purity and yield, particularly for large cell size fractions. MarrowDLD represents a non-destructive sorting tool for fragile cells, facilitating the separation of phenotypically pure populations of BMAds and megakaryocytes to further investigate their physiological and pathological roles.
Spine apparatus modulates Ca2+in spines through spatial localization of sources and sinks
Authors: Mesa M. Herńandez , Garcia G. C. , Hoerndli F. J. , McCabe K. J. , Rangamani P.
Published: September 2023

Dendritic spines are small protrusions on dendrites in neurons and serve as sites of postsynaptic activity. Some of these spines contain smooth endoplasmic reticulum (SER), and sometimes an even further specialized SER known as the spine apparatus (SA). In this work, we developed a stochastic spatial model to investigate the role of the SER and the SA in modulating Ca2+dynamics. Using this model, we investigated how ryanodine receptor (RyR) localization, spine membrane geometry, and SER geometry can impact Ca2+transients in the spine and in the dendrite. Our simulations found that RyR opening is dependent on where it is localized in the SER and on the SER geometry. In order to maximize Ca2+in the dendrites (for activating clusters of spines and spine-spine communication), a laminar SA was favorable with RyRs localized in the neck region, closer to the dendrite. We also found that the presence of the SER without the laminar structure, coupled with RyR localization at the head, leads to higher Ca2+presence in the spine. These predictions serve as design principles for understanding how spines with an ER can regulate Ca2+dynamics differently from spines without ER through a combination of geometry and receptor localization.

1

Highlights

RyR opening in dendritic spine ER is location dependent and spine geometry dependent.

Ca2+buffers and SERCA can buffer against runaway potentiation of spines even when CICR is activated.

RyRs located towards the ER neck allow for more Ca2+to reach the dendrites.

RyRs located towards the spine head are favorable for increased Ca2+in spines.

Figure 1:

Graphical abstract.

Factors governing the dynamics of Ca2+in dendritic spines include plasma membrane geometry, RyR distribution and ER laminarity.
Sensitivity of the timing ofDrosophilapupal wing morphogenesis to external perturbations
Authors: Piscitello-Gómez Romina , Mahmoud Ali , Dye Natalie A , Eaton Suzanne
Published: September 2023

The morphogenesis of the pupal wing ofDrosophila melanogasteris a powerful model for understanding the physical mechanisms of tissue morphogenesis. During this process, the wing undergoes a dramatic reshaping where the hinge region contracts and pulls on the blade region, triggering a dynamic pattern of cell elongation changes, cell divisions, and cell neighborhood changes Etournay et al. (2015). Over our several year study of this process, we noticed that sometime after the year 2016, the onset of morphogenesis became consistently delayed by ∼6 h compared to previous years. Thus, the peak of cell elongation was now observed at 28 hours after puparium formation (hAPF) rather than at 20-22 hAPF. We show here that this delay is independent of genetic background and that the speed of the overall process is relatively unchanged, implying that an environmental factor causes a shift in the onset of the process relative to the start of pupariation. We then investigated how various environmental factors influence the timing of pupal wing morphogenesis, using the dynamics of cell elongation as a proxy. We find that imaging conditions, temperature, diet,Wolbachiainfection, and the light/dark cycle have relatively little effect. Preliminary data show that the spectra of light used to rear the flies affects cell elongation dynamics, although the delay was not completely reverted and more experiments are needed to know precisely how this variable affects morphogenesis. In sum, our work suggests the presence of a gate controlling the onset of pupal wing morphogenesis that is influenced by a specific, yet unclear, environmental factor. Once the gate is released, pupal wing morphogenesis occurs at a fairly constant rate, remarkably robust to many environmental variables.
Analyses of 600+ insect genomes reveal repetitive element dynamics and highlight biodiversity-scale repeat annotation challenges
Authors: Sproul John S. , Hotaling Scott , Heckenhauer Jacqueline , Powell Ashlyn , Marshall Dez , Larracuente Amanda M. , Kelley Joanna L. , Pauls Steffen U. , Frandsen Paul B.
Published: September 2023

Repetitive elements (REs) are integral to the composition, structure, and function of eukaryotic genomes, yet remain understudied in most taxonomic groups. We investigated REs across 601 insect species and report wide variation in RE dynamics across groups. Analysis of associations between REs and protein-coding genes revealed dynamic evolution at the interface between REs and coding regions across insects, including notably elevated RE–gene associations in lineages with abundant long interspersed nuclear elements (LINEs). We leveraged this large, empirical data set to quantify impacts of long-read technology on RE detection and investigate fundamental challenges to RE annotation in diverse groups. In long-read assemblies, we detected ∼36% more REs than short-read assemblies, with long terminal repeats (LTRs) showing 162% increased detection, whereas DNA transposons and LINEs showed less respective technology-related bias. In most insect lineages, 25%–85% of repetitive sequences were “unclassified” following automated annotation, compared with only ∼13% inDrosophilaspecies. Although the diversity of available insect genomes has rapidly expanded, we show the rate of community contributions to RE databases has not kept pace, preventing efficient annotation and high-resolution study of REs in most groups. We highlight the tremendous opportunity and need for the biodiversity genomics field to embrace REs and suggest collective steps for making progress toward this goal.
Hydrogen bonding patterns and C—H...π interactions in the structure of the antiparkinsonian drug (R)-rasagiline mesylate determined using laboratory and synchrotron X-ray powder diffraction data
Authors: Dugarte-Dugarte Analio J. , Toro Robert A. , van de Streek Jacco , Henao José Antonio , Fitch Andrew N. , Dejoie Catherine , Delgado José Miguel , Díaz de Delgado Graciela
Published: September 2023

The structure of (R)-rasagiline mesylate [(R)-RasH+·Mes−], an active pharmaceutical ingredient used to treat Parkinson's disease, is presented. The structure was determined from laboratory and synchrotron powder diffraction data, refined using the Rietveld method, and validated and optimized using dispersion-corrected DFT calculations. The unit-cell parameters obtained in both experiments are in good agreement and the refinement with both datasets converged to good agreement factors. The final parameters obtained from laboratory data were a = 5.4905 (8), b = 6.536 (2), c = 38.953 (3) Å, V = 1398.0 (4) Å3 and from synchrotron powder data were a = 5.487530 (10) Å, b = 6.528939 (12) Å, c = 38.94313 (9) Å, V = 1395.245 (5) Å3 with Z = 4 and space group P212121. Preferred orientation was properly accounted for using the synchrotron radiation data, leading to a March–Dollase parameter of 1.140 (1) instead of the 0.642 (1) value obtained from laboratory data. In the structure, (R)-RasH+ moieties form layers parallel to the ab plane connected by mesylate ions through N—H...O and C—H...O hydrogen bonds. These layers stack along the c axis and are further connected by C—H...π interactions. Hirshfeld surface analysis and fingerprint plot calculations indicate that the main interactions are: H...H (50.9%), H...C/C...H (27.1%) and H...O/O...H (21.1%).
Banking in the metaverse: a new frontier for financial institutions
Authors: Ooi Keng-Boon , Tan Garry Wei-Han , Aw Eugene Cheng-Xi , Cham Tat-Huei , Dwivedi Yogesh K. , Dwivedi Rohita , Hughes Laurie , Kar Arpan Kumar , Loh Xiu-Ming , Mogaji Emmanuel , Phau Ian , Sharma Anshuman
Published: September 2023

Purpose

Technological advancements have catalyzed disruption in the banking sector. The impact of the metaverse on the banking sector is no exception. In view of this, the current paper aims to provide valuable insights into four key areas (i.e. corporate banking, retail banking, banking employees and public policy) that the metaverse could significantly disrupt.

Design/methodology/approach

Insights into four key areas of the banking sector that the metaverse could significantly impact were gathered from various invited contributors.

Findings

The invited contributors first introduce the association between their respective key areas with the metaverse. Subsequently, the opportunities and challenges relevant to the key areas were identified. Finally, future research agendas were proposed for the attention of all relevant stakeholders.

Originality/value

The metaverse's impact on key areas of the banking sector is discussed in this paper. Following the metaverse's potentially wide application in the banking sector, insights from the invited contributions offer great value to the relevant stakeholders.
Privacy governance not included: analysis of third parties in learning management systems
Authors: Sanfilippo Madelyn Rose , Apthorpe Noah , Brehm Karoline , Shvartzshnaider Yan
Published: September 2023

Purpose

This paper aims to address research gaps around third party data flows in education by investigating governance practices in higher education with respect to learning management system (LMS) ecosystems. The authors answer the following research questions: how are LMS and plugins/learning tools interoperability (LTI) governed at higher education institutions? Who is responsible for data governance activities around LMS? What is the current state of governance over LMS? What is the current state of governance over LMS plugins, LTI, etc.? What governance issues are unresolved in this domain? How are issues of privacy and governance regarding LMS and plugins/LTIs documented or communicated to the public and/or community members?

Design/methodology/approach

This study involved three components: (1) An online questionnaire about LMS, plugin and LTI governance practices from information technology professionals at seven universities in the USA (n = 4) and Canada (n = 3). The responses from these individuals helped us frame and design the interview schedule. (2) A review of public data from 112 universities about LMS plugin and LTI governance. Eighteen of these universities provide additional documentation, which we analyze in further depth. (3) A series of extensive interviews with 25 university data governance officers with responsibilities for LMS, plugin and/or LTI governance, representing 14 different universities.

Findings

The results indicate a portrait of fragmented and unobtrusive, unnoticed student information flows to third parties. From coordination problems on individual college campuses to disparate distributions of authority across campuses, as well as from significant data collection via individual LTIs to a shared problem of scope across many LTIs, the authors see that increased and intentional governance is needed to improve the state of student privacy and provide transparency in the complex environment around LMSs. Yet, the authors also see that there are logical paths forward based on successful governance and leveraging existing collaborative networks among data governance professionals in higher education.

Originality/value

Substantial prior work has examined issues of privacy in the education context, although little research has directly examined higher education institutions’ governance practices of LMS, plugin and LTI ecosystems. The tight integration of first and third-party tools in this ecosystem raises concerns that student data may be accessed and shared without sufficient transparency or oversight and in violation of established education privacy norms. However, these technologies and the university governance practices that could check inappropriate data handling remain under-scrutinized. This paper addresses this gap by investigating the governance practices of higher education institutions with respect to LMS ecosystems.
Intensive and extensive margins of India's agricultural trade: implications for export diversification and development
Authors: Elumalai Kanan , Kumar Anjani
Published: September 2023

Purpose

This paper aims to analyze relative contribution of intensive margin (IM) and extensive margin (EM) to growth in India's agricultural exports for the period 2001 to 2020. It also analyses the determinants of IM and EMs through a standard gravity model.

Design/methodology/approach

The study uses export data from United Nations Comtrade, which is accessed through World Integrated Trade Solution (WITS) software. Data for the period 2001 to 2020 were compiled for analysis using the Harmonized System (HS) of commodity classification system at the six-digit level. This study decomposed the contribution of IM and EM in the growth of Indian agricultural trade by using Hummels and Klenow's approach. After performing the export decomposition analysis, the authors analyze the factors influencing IM and EM by using the Tobit regression model and Poisson pseudo-maximum-likelihood (PPML) method of estimation.

Findings

The EM grew at 1.24% per annum, while the intensive margin (IM) increased by 0.23%. The contribution of growth at the EM increased from 58.8% in 2001 to 70.2% in 2020. Export growth along the IM was relatively high for animal products and agricultural raw materials, while growth at the EM was an important contributor to the export growth of horticultural and processed agricultural products. There was a positive and significant effect of the free trade agreement (FTA) on export margins.

Research limitations/implications

More disaggregated commodity-specific studies on value chain analysis would provide valuable insights into the issues hindering exports and realizing the untapped export potential.

Originality/value

There is a scarcity of holistic and recent studies illustrating the role of IM and EMs in agricultural trade growth, covering a large number of commodities and geographies associated with Indian agricultural trade. The study would be helpful to the stakeholders in facilitating informed policy decisions.
An arts-based process to build Workforce agility
Authors: M Janani , V Vijayalakshmi
Published: September 2023

Purpose

The world of work is constantly evolving such that the Workforce in the previous era was driven by the need for stability and is now driven by the desire for creative disruption. While firms must respond to the challenges and dynamics continuously, employees must be ready for any upcoming change to progress despite the turbulence and attain a competitive position. This paper's focal theme is Workforce agility – the ability of employees to respond to and make the most out of changes. Studies on the personal factors affected by changes, in turn, influencing Workforce agility have been scarce. The authors propose a conceptual model with propositions to address this gap. Additionally, the authors propose an employee-centric experiential training practice to foster agility.

Design/methodology/approach

The authors have employed conceptual description methodology to build propositions about the personal factors influencing Workforce agility and an arts-based intervention to enhance it.

Findings

Intermodal arts-based intervention (IABI) can influence employees' epistemic curiosity, which aids with managing ruminative thoughts, thus enhancing Workforce agility, while dispositional joy moderates this relationship.

Practical implications

The proposed “Intermodal Arts-Based Intervention (IABI)” can help firms move from a traditional training-based approach to an experiential one to foster their Workforce's agile capacities. Considerations for its implementation are explained.

Originality/value

This study is one of the first attempts to integrate multiple art forms as a change management practice. The conceptualized model also brings out the adaptive and maladaptive aspects of epistemic curiosity and rumination and the role of joy in promoting agile behaviors.
Socioemotional wealth and family feuds: corporate social responsibility as insurance
Authors: Jung Young Hoon , Kim Dong Shin , Shin HoWook
Published: September 2023

Purpose

This study explores family firms' ex ante conflict management strategies to preserve their socioemotional wealth (SEW) under predictable conflict through the succession process. Specifically, the authors examine how family firms leverage the insurance-like benefits of corporate social responsibility (CSR) to mitigate the threat of foreseeable family feuds among the sons of firms' family heads.

Design/methodology/approach

The authors focus on the charitable donations pledged by Korean family business groups (chaebols). Using the data of 62 chaebols with generalized least squares (GLS) models, the authors analyze 711 observations from 2005 to 2017.

Findings

The authors find a positive relationship between the number of sons of a family firm's head and the firm's CSR activities such as spending on charitable donations. Furthermore, the number of daughters of heads in executive positions strengthens such a positive relationship, whereas the number of business and political marriage ties weakens this relationship.

Practical implications

Family heads of family businesses may leverage CSR activities and marriage ties to elite families interchangeably to ward off negative impacts from foreseeable family feuds and preserve their SEW. Thus, a policy-based incentive for CSR that encourages more family heads to use CSR as insurance would serve the public interest.

Originality/value

The authors contribute to the family business literature by suggesting that CSR activities can be used by family firms as an instrument to mitigate foreseeable damage to the SEW caused by family feuds. The authors also shed new light on CSR research by finding that marriage ties to elite families may reduce the strategic value of CSR activities.
The death of migrant workers in India during the first wave of COVID-19 pandemic
Authors: Kumar Sumant , Patel Avanish Bhai
Published: September 2023

Purpose

COVID-19 lockdown imposed by the government in India affected markets, factories, industries, construction sites, restaurants, transport services, etc. in which migrant workers were engaged. Migrant workers expected that after the imposition of the lockdown government will facilitate transportation facilities to their hometowns as they lost their jobs. But due to negligence from both the central and the state governments, neither transportation was arranged nor food, shelter or health facilities were arranged. This paper aims to investigate the causes of the death of migrant workers under the theoretical framework of negligence theory.

Design/methodology/approach

The authors have applied the content analysis method and collected 926 death cases of migrant workers from 28 Indian states. The researchers applied this technique as the newspapers in India are one of the largest and most useful sources to generate a report/record on migrant workers causes during the COVID-19 lockdown. During the lockdown period, due to lack of attention from the government, police atrocities, hunger and accidental cases increased which resulted in the death of migrant workers.

Findings

The finding of the study proves that during the first phase of COVID-19 lockdown the death cases of migrant workers increased due to negligence by the governments. The number of death cases of migrant workers has been analysed through applying negligence theory which included duty, breach, cause, in fact, proximate cause and harm which increased the death cases. It has been noticed that the central government without any prior notice-imposed lockdown all over India, in which all the states were not received any guidelines or communication which indicate what they have to do or how to handle the Covid-19 situation.

Originality/value

To the best of the authors’ knowledge, this is an original work of researchers which is basically based on negligence theory.
Reference ranges for third‐trimester maternal cardiovascular function parameters measured in normotensive pregnant women using a non‐invasive cardiac output monitor: A study based on data from the prospective PEACH cohort study
Authors: Lihme Frederikke , Basit Saima , Persson Lisa G. , Larsen Maria O. , Lauridsen Karin H. , Lykke Jacob A. , Andersen Anita S. , Halse Karen , Thorsen‐Meyer Annette , Melbye Mads , Wohlfahrt Jan , Boyd Heather A.
Published: September 2023

Objective

We defined reference ranges for maternal cardiac output, systemic vascular resistance, and stroke volume measured in the third trimester of pregnancy using the Ultrasound Cardiac Output Monitor 1A.

Design

Based on data from the prospective PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) cohort study.

Setting

Rigshospitalet and Hvidovre Hospital, Denmark.

Sample

Normotensive pregnant women aged 18–45 years with singleton pregnancies, enrolled in the PEACH study in 2016–2018.

Methods

We modelled cardiac output, systemic vascular resistance and stroke volume as a function of gestational age using multilevel linear models with fractional polynomials.

Main Outcome Measures

Unconditional and conditional reference ranges for cardiovascular parameters measured in gestational weeks 28–40.

Results

Our study cohort included 405 healthy pregnant women who contributed 1210 cardiovascular function measurements for analysis. Maximum cardiac output and stroke volume values were measured in gestational weeks 30–32 and decreased over the third trimester, whereas systemic vascular resistance increased during the same period. We created reference ranges for eight combinations of maternal height, age and parity. We also created a simple calculator to allow for implementation of the reference ranges in clinical practice.

Conclusions

Our reference ranges allow the use of a bedside ultrasound device to non‐invasively assess cardiac function in pregnancy and identify women at risk of complications. The unconditional ranges allow clinicians to evaluate isolated measurements and identify women needing follow‐up. The conditional ranges incorporate information from previous measurements and improve monitoring over time.
Population development ofRhyzopertha dominica(F.) (Coleoptera: Bostrichidae) on different stored products
Authors: Ren Yanling , Wang Tao , Wang Chun , D'Isita Ilaria , Hu Qiqi , Germinara Giacinto Salvatore , Cao Yu
Published: September 2023

The lesser grain borer,Rhyzopertha dominica, is an important pest of various stored products around the world. In this study, the development, survival, reproduction, and life table parameters ofR. dominicawere investigated on six stored products (angelica, jujube, maize, rice, soybean, and wheat). The developmental time of the immature stage ofR. dominicawas shortest on wheat (40.20 days) and longest on angelica (67.04 days). The survival rate of the immature stage was highest on wheat (76.33%) and lowest on angelica (41.00%). The fecundity level ofR. dominicawas highest on wheat (246.05 eggs/female) and lowest on angelica (69.38 eggs/female). The net reproductive rate (R0) and intrinsic rate of increase (rm) ofR. dominicadiffered significantly among the six stored products. The highestR0ofR. dominicawas on wheat (68.50), followed by rice (41.28), maize (32.32), soybean (27.17), jujube (23.16), and angelica (20.18); thermvalues showed a similar trend, with values of 0.059, 0.046, 0.042, 0.039, 0.036, and 0.033, respectively. Our results indicate that wheat was the most suitable stored product, whereas angelica was the least suitable, for the feeding, development, and population increase ofR. dominica. These findings provide basic information about the occurrence trends and characteristics ofR. dominicathat will be useful for the control of this pest on different stored products. The physicochemical properties of angelica should be further explored for potential application in the control or integrated management ofR. dominica.
Workload associated with manual assessment of vital signs as compared with continuous wireless monitoring
Authors: Sigvardt Emilie , Grønbæk Katja Kjær , Jepsen Mia Lind , Søgaard Marlene , Haahr Louise , Inácio Ana , Aasvang Eske Kvanner , Meyhoff Christian Sylvest
Published: September 2023

Background

Vital sign monitoring is considered an essential aspect of clinical care in hospitals. In general wards, this relies on intermittent manual assessments performed by clinical staff at intervals of up to 12 h. In recent years, continuous monitoring of vital signs has been introduced to the clinic, with improved patient outcomes being one of several potential benefits. The aim of this study was to determine the workload difference between continuous monitoring and manual monitoring of vital signs as part of the National Early Warning Score (NEWS).

Methods

Three wireless sensors continuously monitored blood pressure, heart rate, respiratory rate, and peripheral oxygen saturation in 20 patients admitted to the general hospital ward. The duration needed for equipment set‐up and maintenance for continuous monitoring in a 24‐h period was recorded and compared with the time spent on manual assessments and documentation of vital signs performed by clinical staff according to the NEWS.

Results

The time used for continuous monitoring was 6.0 (IQR 3.2; 7.2) min per patient per day vs. 14 (9.7; 32) min per patient per day for the NEWS. Median difference in duration for monitoring of vital signs was 9.9 (95% CI 5.6; 21) min per patient per day between NEWS and continuous monitoring (p < .001). Time used for continuous monitoring in isolated patients was 6.6 (4.6; 12) min per patient per day as compared with 22 (9.7; 94) min per patient per day for NEWS.

Conclusion

The use of continuous monitoring was associated with a significant reduction in workload in terms of time for monitoring as compared with manual assessment of vital signs.
SAEM GRACE: Anti‐craving medications for alcohol use disorder treatment in the emergency department: A systematic review of direct evidence
Authors: Punia Kiran , Scott William , Manuja Kriti , Sabbineni Monica , Campbell Kaitryn , Balodis Iris M. , MacKillop James
Published: September 2023

Objectives

Alcohol‐related concerns commonly present to the emergency department (ED), with a subset of individuals experiencing the symptoms of an alcohol use disorder (AUD). As such, examining the efficacy of pharmacological anti‐craving treatment for AUD in the ED is of increasing interest. The objective of this systematic review was to evaluate the direct evidence assessing the efficacy of providing anti‐craving medications for AUD treatment in the ED.

Methods

A systematic search was conducted according to the patient‐intervention‐control‐outcome question: (P) adults (≥18 years old) presenting to the ED with an AUD (including suspected AUD); (I) anti‐craving medications (i.e., naltrexone, acamprosate, gabapentin); (C) no prescription or placebo; (O) reduction of repeat ED visits, engagement in addiction services, reductions in heavy drinking days, reductions in any drinking and amount consumed (or abstinence), and in relapse. Two reviewers independently assessed articles for inclusion and conducted risk of bias assessments for included studies.

Results

From 143 potentially relevant articles, 6 met inclusion criteria: 3 clinical trials, and 3 case studies. The clinical trials identified evaluated oral versus extended‐release naltrexone, monthly extended‐release naltrexone injections, and disulfiram. Both oral and extended‐release naltrexone resulted in decreased alcohol consumption. Monthly extended‐release naltrexone injections resulted in significant improvements in drinking and quality of life. Although out of scope, the disulfiram studies identified did not result in an improvement in drinking in comparison to no medication.

Conclusions

Overall, there are few studies directly examining the efficacy of anti‐craving medications for AUD in the ED, although the limited evidence that exists is supportive of naltrexone pharmacotherapy, particularly extended‐release injection formulation. Additional randomized controlled trials are necessary for substantive direct evidence on anti‐craving medication initiation in the ED.
Increased AGE–RAGE axis stress in methamphetamine abuse and methamphetamine‐induced psychosis: Associations with oxidative stress and increased atherogenicity
Authors: Al‐Hakeim Hussein Kadhem , Altufaili Mazin Fadhil , Alhaideri Amer Fadhil , Almulla Abbas F. , Moustafa Shatha Rouf , Maes Michael
Published: September 2023

Methamphetamine (MA)‐induced psychosis (MIP) is associated with increased oxidative toxicity (especially lipid peroxidation) and lowered antioxidant defences. Advanced glycation end products (AGEs) cause oxidative stress upon ligand binding to AGE receptors (RAGEs). There is no data on whether MA use may cause AGE–RAGE stress or whether the latter is associated with MIP. This case–control study recruited 60 patients with MA use disorder and 30 normal controls and measured serum levels of oxidative stress toxicity (OSTOX, lipid peroxidation), antioxidant defences (ANTIOX), magnesium, copper, atherogenicity, AGE and soluble RAGE (sRAGE) and computed a composite reflecting AGE–RAGE axis activity. MA dependence and use were associated with elevated levels of AGE, sRAGE, OSTOX/ANTIOX, Castelli Risk Index 1 and atherogenic index of plasma. Increased sRAGE concentrations were strongly correlated with dependence severity and MA dose. Increased AGE–RAGE stress was correlated with OSTOX, OSTOX/ANTIOX and MA‐induced intoxication symptoms, psychosis, hostility, excitement and formal thought disorders. The regression on AGE–RAGE, the OSTOX/ANTIOX ratio, decreased magnesium and increased copper explained 54.8% of the variance in MIP symptoms, and these biomarkers mediated the effects of increasing MA concentrations on MIP symptoms. OSTOX/ANTIOX, AGE–RAGE and insufficient magnesium were found to explain 36.0% of the variance in the atherogenicity indices. MA causes intertwined increases in AGE–RAGE axis stress and oxidative damage, which together predict the severity of MIP symptoms and increased atherogenicity.
“to stop the earthquake”: Palestine and the Settler Colonial Logic of Fragmentation
Authors: Nabulsi Jamal
Published: September 2023

Fragmentation is a key colonial strategy to which Palestinians enact resistance, evident most prominently in the 2021 Unity Intifada. In this article, I take inspiration from such Palestinian resistance to theorise fragmentation as a central logic of Zionist/Israeli settler colonialism. I make three related points. First, I employ the metaphor of the earthquake to consider the fractality of settler colonial fragmentation across the dimensions of land, time, and bodies. Second, understanding the settler colonial logic of elimination as ultimately attempting to extinguish a Palestinian Indigenous sovereignty, I argue that the logic of fragmentation drives towards elimination. Finally, I demonstrate that, in fragmenting Palestine, Zionism seeks to render Israel a coherent entity. Ultimately then, the Zionist project works to fragment Palestine to eliminate Palestinian bodies from land and time, to render Israel a seamless nation across these dimensions. However, Palestinian Indigenous sovereignty is not something that can be broken or extinguished.
Clinical implications of endotoxin activity and Polymyxin‐B hemoperfusion in critically ill patients with septic cardiomyopathy: A single‐center, retrospective, observational study
Authors: Cutuli Salvatore Lucio , Carelli Simone , Cascarano Laura , Cicconi Sandra , Silvestri Davide , Cicetti Marta , Vallecoccia Maria Sole , Pintaudi Gabriele , Tanzarella Eloisa Sofia , Grieco Domenico Luca , Antonelli Massimo , De Pascale Gennaro
Published: September 2023

Background

To explore the association between endotoxin activity (EA) and septic cardiomyopathy (SCM), the relationship between endotoxin removal by Polymyxin‐B hemoperfusion (PMX‐HP) and recovery from SCM (R‐SCM), and the correlation between R‐SCM and the 28‐day mortality in septic patients admitted to the intensive care unit (ICU).

Methods

Observational study that included patients admitted to two ICUs of a tertiary university hospital between April 2011 and December 2019, who received PMX‐HP for sepsis/septic shock. The SCM and R‐SCM were assessed by transthoracic echocardiography.

Results

Among 148 patients, SCM was diagnosed in 60 (46%) of them and had no relationship with median EA (SCM group: 0.73; no‐SCM group: 0.66, p = 0.48). Recovery from SCM was observed in 24 patients (49%) and was independently associated with the PMX‐HP (OR 4.19, 95%CI [1.22, 14.3]; p = 0.02) and the SAPS2 II score (OR 0.94, 95%CI [0.9, 0.98]; p = 0.006). In the SCM group, the 28‐day mortality was 60% and was independently predicted by R‐SCM (OR 0.02, 95%CI [0.001, 0.3] p = 0.005) and SAPS II score (OR 1.11, 95%CI [1.01, 1.23] p = 0.037).

Conclusions

In septic patients, EA was not associated with SCM. However, endotoxin removal by Polymyxin‐B hemoperfusion was associated with recovery from cardiomyopathy, which was a predictor of lower 28‐day mortality.
Not realizing that you don't know: Fraction state anxiety is reduced by natural number bias
Authors: Halme Hilma , Van Hoof Jo , Hannula‐Sormunen Minna , McMullen Jake
Published: September 2023

Background

Research has shown that mathematics anxiety negatively correlates with primary school mathematics performance, including fraction knowledge. However, recently no significant correlation was found between fraction arithmetic performance and state anxiety measured after the fraction task. One possible explanation is the natural number bias (NNB), a tendency to apply natural number reasoning in fraction tasks, even when this is inappropriate. Students with the NNB may not realize they are answering incorrectly.

Aims

The aim is to examine whether a misconception, namely the NNB, can influence students' fraction state anxiety.

Sample

The participants were 119 fifth‐ and sixth‐grade students categorized as belonging to an NNB group (n = 60) or a No‐NNB group (n = 59), according to their NNB‐related answering profile on a fraction arithmetic task.

Methods

Group differences were examined for state anxiety and performance on a fraction and a whole number arithmetic task and self‐reported trait mathematics anxiety.

Results

The NNB group reported lower fraction state anxiety than the No‐NNB group, but there was no significant difference in trait mathematics anxiety. Furthermore, the NNB group reported lower fraction state anxiety than whole number state anxiety, while the opposite was true for the No‐NNB group.

Conclusion

The present study suggests that students' perceptions of their own performance influence their state anxiety responses, and students with a NNB may not be aware of their misconception and poor performance. Not taking into account qualitative differences in low performance, such as misconceptions, may lead to misinterpretations in state anxiety‐performance relations.
Is splenectomy a good strategy for refractory immune thrombocytopenia in adults?
Authors: Godeau Bertrand
Published: September 2023

Rituximab and thrombopoietin receptor agonists (TPO‐RAs) have profoundly changed the management of immune thrombocytopenia (ITP) over the last 20 years. Even if most current guidelines put splenectomy, rituximab and TPO‐RAs on the same treatment level, most clinicians and patients clearly prefer to postpone splenectomy and to multiply the lines of medical treatment before considering surgery. The management of ITP refractory to rituximab and TPO‐RAs is challenging. Splenectomy is currently performed much less frequently because of a better knowledge of its complications, particularly severe late infections and deep vein thrombosis, and the inability to reliably predict its effectiveness. Furthermore, there is a reluctance to propose splenectomy when other treatments have been ineffective, based on the not well‐documented risk that splenectomy could not be effective in such a case. The objective of this update was to review the most recent published data on the long‐term tolerability and side effects of splenectomy and the predictors of response and efficacy, especially for patients exposed to multiple medical lines. This update can help physicians and patients with failure of multiple lines of therapy make an informed decision on the indication for splenectomy with the help of up‐to‐date data.
The role of genetics in refractory immune thrombocytopenia
Authors: Zehnder James L. , Bussel James B. , Cooper Nichola
Published: September 2023

Patients with refractory immune thrombocytopenia (rITP) have increased morbidity and mortality. Currently, there is limited understanding of the cause of refractoriness and no markers to help direct novel treatment options. Understanding the reason(s) for refractoriness is crucial to determining novel treatment options. The pathogenesis underlying rITP has generally been thought to be an underlying genetic predisposition with an environmental trigger. Familial ITP remains rare, and there are few twin studies, suggesting that a simple genetic cause is unlikely. However, genetic mutations provide the background for several autoimmune diseases. In this review, we explore the evidence of either an inherited genetic cause of rITP or an acquired mutation, in particular one resulting in clonal expansion of cytotoxic T cells.