bluuebunny/crossref_metadata_2025 huggingface dataset:
Fitness and transcriptomic analysis of pathogenicVibrio parahaemolyticusin seawater at different shellfish harvesting temperatures
Authors: Liu Zhuosheng , Liao Chao , Wang Luxin
Published: May 2023

To better characterize the population dynamics ofVibrio parahaemolyticus(Vp) containing different virulence genes, twoVpstrains were inoculated into seawater separately and incubated at temperatures (30 and 10 °C) mimicking summer and winter pre-harvest shellfish rearing seasons. The cellular responses of these two strains, one containing the thermostable direct hemolysin (tdh+) gene and the other one containingtdh-related hemolysin (trh+) gene, were studied at the transcriptomic level. Results showed that, at 30 °C,tdh+ andtrh+ strains reached 6.77 ± 0.20 and 6.14 ± 0.07 Log CFU/ml respectively after 5 days. During this time, higher growth rate was observed in thetdh+ strain than thetrh+ strain. When being kept at 10 °C, bothVpstrains persisted at ca. 3.0 Log CFU/ml in seawater with no difference observed between them. Growth and persistence predictive models were then established based on the Baranyi equation. The goodness of fit scores ranged from 0.674 to 0.950. RNA sequencing results showed that downregulated central energy metabolism and weakened degradation of branched chain amino acid were observed only intrh+ strain not intdh+ strain at 30 °C. This might be one reason for the lower growth rates of thetrh+ strain at 30 °C. Histidine metabolism and biofilm formation pathways were significantly downregulated in both strains at 10 °C. No significant difference was observed for virulence-associated gene expression between 10 and 30 °C, regardless of the strains.

SIGINIFICANCE

Given the involvement ofVpin a wide range of seafood outbreaks, a systematical characterization ofVpfitness and transcriptomic changes at temperatures of critical importance for seafood production and storage is needed. In this study, predictive models describing the behavior ofVpstrains containing different virulence factors are established. While no difference was observed at the lower temperature (10 C),tdh+ strain had faster growth rate than thetrh+ strain. Transcriptomic analysis showed that significantly higher number of genes were upregulated at 30 °C than 10 °C. Majority of differentially expressed genes ofVpat 30 °C were annotated to functional categories supporting cellular growth. At the lower temperature, the down regulation of the biofilm formation pathway and histidine metabolism indicates that the current practice of storing seafood at lower temperatures not only protect the seafood quality but also ensure the seafood safety.
The lncRNANeat1is associated with astrocyte reactivity and memory deficits in a mouse model of Alzheimer’s disease
Authors: Irwin Ashleigh B , Martina Verdion , Sint Jago Silvienne C , Bahabry Rudhab , Schreiber Anna Maria , Lubin Farah D.
Published: May 2023

Dysregulation of long non-coding RNAs (lncRNAs) have been associated with Alzheimer’s disease (AD). However, the functional role of lncRNAs in AD remains unclear. Here, we report a crucial role for the lncRNANeat1in astrocyte dysfunction and memory deficits associated with AD. Transcriptomics analysis show abnormally high expression levels ofNEAT1in the brains of AD patients relative to aged-matched healthy controls, with the most significantly elevated levels in glial cells. In a human transgenic APP-J20 (J20) mouse model of AD, RNA-fluorescentin situhybridization characterization ofNeat1expression in hippocampal astrocyte versus non-astrocyte cell populations revealed a significant increase inNeat1expression in astrocytes of male, but not female, mice. This corresponded with increased seizure susceptibility in J20 male mice. Interestingly,Neat1deficiency in the dCA1 in J20 male mice did not alter seizure threshold. Mechanistically,Neat1deficiency in the dorsal area CA1 of the hippocampus (dCA1) J20 male mice significantly improved hippocampus-dependent memory.Neat1deficiency also remarkably reduced astrocyte reactivity markers suggesting thatNeat1overexpression is associated with astrocyte dysfunction induced by hAPP/Aβ in the J20 mice. Together, these findings indicate that abnormalNeat1overexpression may contribute to memory deficits in the J20 AD model not through altered neuronal activity, but through astrocyte dysfunction.
Identifying candidatede novogenes expressed in the somatic female reproductive tract ofDrosophila melanogaster
Authors: Lombardo Kaelina D. , Sheehy Hayley K. , Cridland Julie M. , Begun David J.
Published: May 2023

Most eukaryotic genes have been vertically transmitted to the present from distant ancestors. However, variable gene number across species indicates that gene gain and loss also occurs. While new genes typically originate as products of duplications and rearrangements of pre-existing genes, putativede novogenes - genes born out of previously non-genic sequence - have been identified. Previous studies ofde novogenes inDrosophilahave provided evidence that expression in male reproductive tissues is common. However, no studies have focused on female reproductive tissues. Here we begin addressing this gap in the literature by analyzing the transcriptomes of three female reproductive tract organs (spermatheca, seminal receptacle, and parovaria) in three species - our focal species,D. melanogaster- and two closely related species,D. simulansandD. yakuba, with the goal of identifying putativeD. melanogaster-specificde novogenes expressed in these tissues. We discovered several candidate genes, which, consistent with the literature, tend to be short, simple, and lowly expressed. We also find evidence that some of these genes are expressed in otherD. melanogastertissues and both sexes. The relatively small number of candidate genes discovered here is similar to that observed in the accessory gland, but substantially fewer than that observed in the testis.
Structure of the N-terminal didomain d1_d2 of the Thrombospondin type-1 domain-containing 7A
Authors: Bochel Alice , Mortensen Simon A. , Seifert Larissa , Hengel Felicitas E. , Jeffries Cy M. , Chojnowski Grzegorz , Kretz Oliver , Huber Tobias B. , Tomas Nicola M. , Wilmanns Matthias
Published: May 2023

Thrombospondin type-1 domain-containing 7A (THSD7A) is a large extracellular protein that is found in podocyte foot processes of the kidney glomerulus. It has been established as a causative autoantigen in membranous nephropathy. Amongst the predicted 21 thrombospondin repeat domains of its extracellular segment, the highest frequency of autoimmune response has been associated with the two N-terminal domains. Here, we show that antibodies against this THSD7A segment in mice induce typical clinical and morphological signs of membranous nephropathy. The high-resolution structure of these two domains reveals a non-canonical thrombospondin repeat fold that is distinct from the established type 1 thrombospondin repeat. As it shares a conserved disulfide pattern with the canonical fold, we refer to these domains d1 and d2 as type 1A thrombospondin repeats. Both domains comprise a seven layered CC-W-PP-R-W-QQ-CC pattern, which is only partly shared by other THSD7A thrombospondin repeat domains. The two domains form a well-defined V-shaped tandem arrangement. Our findings provide crucial insight into specific structural features of these two domains that are distinct from other regions of THSD7A and hence could cause the high level of antigenicity found for these two domains.
In silicoevolution of protein binders with deep learning models for structure prediction and sequence design
Authors: Goudy Odessa J , Nallathambi Amrita , Kinjo Tomoaki , Randolph Nicholas , Kuhlman Brian
Published: May 2023

There has been considerable progress in the development of computational methods for designing protein-protein interactions, but engineering high-affinity binders without extensive screening and maturation remains challenging. Here, we test a protein design pipeline that uses iterative rounds of deep learning (DL)-based structure prediction (AlphaFold2) and sequence optimization (ProteinMPNN) to design autoinhibitory domains (AiDs) for a PD-L1 antagonist. Inspired by recent advances in therapeutic design, we sought to create autoinhibited (or masked) forms of the antagonist that can be conditionally activated by proteases. Twenty-threede novodesigned AiDs, varying in length and topology, were fused to the antagonist with a protease sensitive linker, and binding to PD-L1 was tested with and without protease treatment. Nine of the fusion proteins demonstrated conditional binding to PD-L1 and the top performing AiDs were selected for further characterization as single domain proteins. Without any experimental affinity maturation, four of the AiDs bind to the PD-L1 antagonist with equilibrium dissociation constants (KDs) below 150 nM, with the lowest KDequal to 0.9 nM. Our study demonstrates that DL-based protein modeling can be used to rapidly generate high affinity protein binders.

Significance statement

Protein-protein interactions are critical to most processes in biology, and improved methods for designing protein binders will enable the creation of new research reagents, diagnostics, and therapeutics. In this study, we show that a deep learning-based method for protein design can create high-affinity protein binders without the need for extensive screening or affinity maturation.
The D84G mutation in STIM1 causes nuclear envelope dysfunction and myopathy in mice
Authors: Bryson Victoria , Wang Chaojian , Zhou Zirui , Singh Kavisha , Volin Noah , Yildirim Eda , Rosenberg Paul
Published: May 2023

Stromal interaction molecule 1 (STIM1) is a Ca2+sensor located in the sarcoplasmic reticulum (SR) of skeletal muscle where it is best known for its role in store operated Ca2+entry (SOCE). Genetic syndromes resulting from STIM1 mutations are recognized as a cause of muscle weakness and atrophy. Here, we focus on a gain of function mutation that occurs in humans and mice (STIM1+/D84Gmice) where muscles exhibit constitutive SOCE. Unexpectedly, this constitutive SOCE did not affect global Ca2+transients, SR Ca2+content or excitation contraction coupling (ECC) and was therefore unlikely to underlie the reduced muscle mass and weakness observed in these mice. Instead, we demonstrate that the presence of D84G STIM1 in the nuclear envelope of STIM1+/D84Gmuscle disrupts nuclear-cytosolic coupling causing severe derangement in nuclear architecture, DNA damage, and altered lamina A associated gene expression. Functionally, we found D84G STIM1 reduced the transfer of Ca2+from the cytosol to the nucleus in myoblasts resulting in a reduction of [Ca2+]N. Taken together, we propose a novel role for STIM1 in the nuclear envelope that links Ca2+signaling to nuclear stability in skeletal muscle.
STIM1 interacts with HCN4 channels to coordinate diastolic depolarization in the mouse Sinoatrial node
Authors: Zhang Hengtao , Graham Victoria , Nepliouev Igor , Stiber Jonathan A. , Rosenberg Paul
Published: May 2023

Cardiomyocytes in the sinoatrial node (SAN) are specialized to undergo spontaneous diastolic depolarization (DD) to create action potentials (AP) that serve as the origin of the heartbeat. Two cellular clocks govern DD: the membrane clock where ion channels contribute ionic conductance to create DD and the Ca2+clock where rhythmic Ca2+release from sarcoplasmic reticulum (SR) during diastole contributes pacemaking. How the membrane and Ca2+clocks interact to synchronize and drive DD is not well understood. Here, we identified stromal interaction molecule 1 (STIM1), the activator of store operated Ca2+entry (SOCE), in the P-cell cardiomyocytes of the SAN. Functional studies from STIM1 KO mice reveal dramatic changes in properties of AP and DD. Mechanistically, we show that STIM1 regulates the funny currents and HCN4 channels that are required to initiate DD and maintain sinus rhythm in mice. Taken together, our studies suggest that STIM1 acts as a sensor for both the Ca2+and membrane clocks for mouse SAN for cardiac pacemaking.
Common Analysis of Direct RNA SequencinG CUrrently Leads to Misidentification of 5-Methylcytosine Modifications at GCU Motifs
Authors: Watson Kaylee J. , Bromley Robin E. , Sparklin Benjamin C. , Gasser Mark T. , Bhattacharya Tamanash , Lebov Jarrett F. , Tyson Tyonna , Teigen Laura E. , Graf Karen T. , Michalski Michelle , Bruno Vincent M. , Lindsey Amelia R. I. , Hardy Richard W. , Newton Irene L. G. , Dunning Hotopp Julie C.
Published: May 2023

RNA modifications, such as methylation, can be detected with Oxford Nanopore Technologies direct RNA sequencing. One commonly used tool for detecting 5-methylcytosine (m5C) modifications is Tombo, which uses an “Alternative Model” to detect putative modifications from a single sample. We examined direct RNA sequencing data from diverse taxa including virus, bacteria, fungi, and animals. The algorithm consistently identified a 5-methylcytosine at the central position of a GCU motif. However, it also identified a 5-methylcytosine in the same motif in fully unmodifiedin vitrotranscribed RNA, suggesting that this a frequent false prediction. In the absence of further validation, several published predictions of 5-methylcytosine in human coronavirus and human cerebral organoid RNA in a GCU context should be reconsidered.

IMPORTANCE

The detection of chemical modifications to RNA is a rapidly expanding field within epigenetics. Nanopore sequencing technology provides an attractive means of detecting these modifications directly on the RNA, but accurate modification predictions are dependent upon the software developed to interpret the sequencing results. One of these tools, Tombo, allows users to detect modifications using sequencing results from a single RNA sample. However, we find that this method falsely predicts modifications in a specific sequence context across a variety of RNA samples, including RNA that lacks modifications. Results from previous publications include predictions in human coronaviruses with this sequence context and should be reconsidered. Our results highlight the importance of using RNA modification detection tools with caution in the absence of a control RNA sample for comparison.
Soil viral communities differed by management and over time in organic and conventional tomato fields
Authors: Sorensen Jess W. , ter Horst Anneliek M. , Zinke Laura A. , Emerson Joanne B.
Published: May 2023

Viruses are known contributors to biogeochemical cycling in diverse habitats, but viral community studies in soil are relatively rare. Although prior work has suggested spatial structuring as a primary driver of local soil viral community ecological patterns, here we show that agricultural management can significantly impact soil viral community composition. We generated 18 soil viromes and 24 total metagenomes from six plots, three under organic and three under conventional management in Davis, CA, USA. Despite the significant impact of management on viral community structure and soil physicochemistry, approximately 44% of the detected viral ‘species’ (vOTUs) were present in soils from both management practices. These common vOTUs regularly comprised >65% of the viral community by relative abundance. Many (56%) of the vOTUs were detected both during the tomato growing season and post-harvest, indicating persistence through time. Together, these results indicate habitat-specific differences in viral community composition, yet relative stability and persistence of viral communities within agricultural soils, in contrast to their recently observed dynamics in natural soils.
Establishment of a CPER Reverse Genetics System for Powassan Virus Defines Attenuating NS1 Glycosylation Sites and an Infectious NS1-GFP11 Reporter Virus
Authors: Conde Jonas N. , Himmler Grace E. , Mladinich Megan C. , Setoh Yin Xiang , Amarilla Alberto A. , Schutt William R. , Saladino Nicolas , Gorbunova Elena E. , Salamango Daniel J. , Wimmer Eckard , Kim Hwan Keun , Mackow Erich R.
Published: May 2023

Powassan virus (POWV) is an emerging tick-borne Flavivirus that causes lethal encephalitis and long term neurologic damage. Currently there are no POWV therapeutics, licensed vaccines or reverse genetics systems for producing infectious POWVs from recombinant DNA. Here we used a circular polymerase extension reaction (CPER) approach to generate recombinant LI9 (recLI9) POWVs with attenuating NS1 protein mutations and a recLI9-split-eGFP reporter virus. Flavivirus NS1 proteins are highly conserved glycoproteins that regulate replication, spread and neurovirulence. POWV NS1 proteins contain three putative N-linked glycosylation sites that we modified individually in infectious recLI9 mutants (N85Q, N208Q, N224Q). NS1 glycosylation site mutations reduced replication kinetics and were attenuated with a 1-2 log decrease in infectious titers. The severely attenuated recLI9-N224Q mutant exhibited a 2-3 day delay in focal cell-to-cell spread and reduced NS1 secretion. Like WT LI9, the recLI9-N224Q mutant was lethal when intracranially inoculated into suckling mice. However, footpad inoculation of recLI9-N224Q resulted in the survival of 80% of mice and demonstrated that NS1-N224Q mutations attenuate POWV neuroinvasionin vivo. To monitor NS1 trafficking, we CPER fused a split GFP11-tag to the NS1 C-terminus and generated an infectious reporter virus, recLI9-NS1-GFP11. Cells infected with recLI9-NS1-GFP11 revealed NS1 trafficking in live cells and the novel formation of large NS1 lined intracellular vesicles. An infectious recLI9-NS1-GFP11 reporter virus permits real-time analysis of NS1 functions in POWV replication, assembly and secretion, and provides a platform for evaluating antiviral compounds. Collectively, our robust POWV reverse genetics system permits analysis of viral spread and neurovirulence determinantsin vitroandin vivo, and enables the rational genetic design of live attenuated POWV vaccines.
The CCP4 suite: integrative software for macromolecular crystallography
Authors: Agirre Jon , Atanasova Mihaela , Bagdonas Haroldas , Ballard Charles B. , Baslé Arnaud , Beilsten-Edmands James , Borges Rafael J. , Brown David G. , Burgos-Mármol J. Javier , Berrisford John M. , Bond Paul S. , Caballero Iracema , Catapano Lucrezia , Chojnowski Grzegorz , Cook Atlanta G. , Cowtan Kevin D. , Croll Tristan I. , Debreczeni Judit É. , Devenish Nicholas E. , Dodson Eleanor J. , Drevon Tarik R. , Emsley Paul , Evans Gwyndaf , Evans Phil R. , Fando Maria , Foadi James , Fuentes-Montero Luis , Garman Elspeth F. , Gerstel Markus , Gildea Richard J. , Hatti Kaushik , Hekkelman Maarten L. , Heuser Philipp , Hoh Soon Wen , Hough Michael A. , Jenkins Huw T. , Jiménez Elisabet , Joosten Robbie P. , Keegan Ronan M. , Keep Nicholas , Krissinel Eugene B. , Kolenko Petr , Kovalevskiy Oleg , Lamzin Victor S. , Lawson David M. , Lebedev Andrey A. , Leslie Andrew G. W. , Lohkamp Bernhard , Long Fei , Malý Martin , McCoy Airlie J. , McNicholas Stuart J. , Medina Ana , Millán Claudia , Murray James W. , Murshudov Garib N. , Nicholls Robert A. , Noble Martin E. M. , Oeffner Robert , Pannu Navraj S. , Parkhurst James M. , Pearce Nicholas , Pereira Joana , Perrakis Anastassis , Powell Harold R. , Read Randy J. , Rigden Daniel J. , Rochira William , Sammito Massimo , Sánchez Rodríguez Filomeno , Sheldrick George M. , Shelley Kathryn L. , Simkovic Felix , Simpkin Adam J. , Skubak Pavol , Sobolev Egor , Steiner Roberto A. , Stevenson Kyle , Tews Ivo , Thomas Jens M. H. , Thorn Andrea , Valls Josep Triviño , Uski Ville , Usón Isabel , Vagin Alexei , Velankar Sameer , Vollmar Melanie , Walden Helen , Waterman David , Wilson Keith S. , Winn Martyn D. , Winter Graeme , Wojdyr Marcin , Yamashita Keitaro
Published: May 2023

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.
Finance – growth nexus: evidence from systemically important Islamic finance countries
Authors: Smolo Edib , Nagayev Ruslan
Published: May 2023

Purpose

The purpose of this study is to examine the effects of financial development on the economic growth of jurisdictions with systemically important Islamic finance.

Design/methodology/approach

The authors use several estimation methods. The primary analysis is based on the LSDVC method using a sample of 23 countries covering the period of 2000–2019.

Findings

The findings suggest that the financial sector may not be a significant factor in determining economic growth, or that it may decrease it depending on the proxy used. These results are in line with recent studies and robust across different estimation specifications and methods used.

Practical implications

Finance practitioners may reconsider the way they conduct their daily activities as their impact on economic growth is fading away. Similarly, policymakers should consider the role that financial development plays in economic growth alongside other factors that may influence its impact. It may be necessary to examine the moderating effects of institutional development on the relationship between finance and growth and consider the channels through which financial development can contribute to economic growth. Additionally, it would be useful to study the impact of Islamic finance on economic growth using different data sources.

Originality/value

Although the topic has been explored using different data sets and focusing on different samples, it has not been explored considering the impact of Islamic finance development on economic growth. Given the global appeal of the Islamic finance industry, it is worth investigating its significance for economic growth.
Revolutionizing language processing in libraries with SheetGPT: an integration of Google Sheet and ChatGPT plugin
Authors: Panda Subhajit , Kaur Navkiran
Published: May 2023

Purpose

The purpose of this research paper is to explore the significance of language processing in library systems and evaluate the effectiveness of integrating artificial intelligence and generative pre-trained transformer (GPT) technology in modern libraries. Specifically, the paper focuses on SheetGPT, a Google Sheet and GPT Plugin and its impact on language processing in library systems.

Design/methodology/approach

This paper adopts a comprehensive analysis approach to evaluate the integration of SheetGPT in library systems. The authors outlined a user-friendly approach for installation and use of SheetGPT using its “beginner plan”, appropriate for personal/student use or extended experimentation. The study includes a quantitative analysis to provide a thorough understanding of the benefits and limitations of SheetGPT in library systems.

Findings

The findings of this research paper suggest that SheetGPT is a highly effective language-processing tool for library systems. Additionally, ChatGPT’s integration with Google Sheets and easy accessibility over Google Marketplace makes it an efficient and user-friendly tool for library professionals. Overall, this study highlights the potential of SheetGPT to enhance language processing in library systems

Originality/value

This research paper contributes to the existing literature by providing a comprehensive analysis of the effectiveness of SheetGPT in library systems. The study’s approach is unique in that it evaluates SheetGPT’s impact on language processing and provides insights into its benefits and limitations. The study’s findings are original and provide a valuable resource for library professionals and researchers interested in exploring the potential of SheetGPT to enhance language processing in library systems.
Mothers' participation in family gatherings and social events with their children with autism spectrum disorder: A scoping review
Authors: Moorthy Shobana Devi , Carlstedt Anita Björklund , Fischl Caroline
Published: May 2023

Introduction

Participating in family gatherings can provide enjoyment and quality time together as a family. However, being the primary carers, mothers of children with autism spectrum disorder may experience this phenomenon differently. The purpose of this study is to explore how available literature describes mothers' experiences of participation in family gatherings and social events with their children with autism spectrum disorder.

Methods

A scoping review was used to explore available literature and identify studies describing mothers' experiences of family gatherings and social events with their children. A thematic synthesis was performed to analyse and synthesise the findings.

Results

A total of 8 articles were included for review. The analysis of the included studies resulted in one central theme—Negative experiences despite strategies—and four analytical themes: Feeling fear, stress, and anxiety; Avoiding family gatherings; Enjoying less and becoming less confident; and Using strategies.

Conclusion

These findings indicate that mothers of children with autism spectrum disorder experience difficulties during gatherings even when using strategies, hence limiting their participation.
Optimizing peritoneal dialysis initiation: A comparative cohort study of catheter placement methods for shortening break‐in periods
Authors: Chávez‐Chávez Hugo E. , Hernández‐Paredes Elisa Naomi , Cojuc‐Konigsberg Gabriel , Vargas‐Rodríguez Cecilia , Díaz‐Canchola Laura Margarita , Vergara‐Zavala Octavio , Fernández‐Venegas Alonso , Acevedo‐Juárez Nadia Stephani , Correa‐Rotter Ricardo , Ramirez‐Sandoval Juan C.
Published: May 2023

Introduction

Peritoneal dialysis (PD) guidelines recommend a 14‐day break‐in period after catheter placement, yet this period could be shortened with new insertion techniques.

Methods

We conducted a prospective cohort study to compare percutaneous vs. surgical catheter insertion in a newly established PD program. The break‐in period was intentionally shortened to <24 h to start PD almost immediately.

Results

We included 223 subjects who underwent percutaneous (34%) or surgical (66%) catheter placement. Compared to the surgical group, the percutaneous group had a higher proportion of early dialysis initiation within 24 h (97% vs. 8%,p < 0.001), similar successful initiation rates (87% vs. 92%,p = 0.34), and shorter lengths of stay (12 [9–18] vs. 18 [14–22] days,p < 0.001). Percutaneous insertion increased the likelihood of successful PD initiation within 24 h (OR 74, 95% CI 31–182), without increasing major complications.

Conclusion

Percutaneous placement could represent a cost‐effective and efficient technique to shorten break‐in periods.
Research culture in Australian and New Zealand radiation oncology: Fact or fantasy?
Authors: Roos Daniel
Published: May 2023

Introduction

Fostering a research culture is a key goal of the Royal Australian and New Zealand College of Radiologists, yet there has never been an organization‐wide enquiry into the extent to which this is being realized. The purpose of this work was to address that deficit for the Radiation Oncology (RO) Faculty to serve as a baseline for future comparison. The hypothesis was that such a culture is closer to fact than fantasy.

Methods

With College approval, three de‐identified Excel spreadsheets detailing 25 research‐related sub‐categories of the Faculty's Continuing Professional Development (CPD) database were interrogated for the 2019–21 triennium, accepting that research activity in 2020–21 would be COVID‐19 suppressed. The numbers obligated to self‐report CPD were 482, 496 and 511, respectively. Primary endpoints were the percentages of ROs claiming at least one research‐related activity overall, and in each of the sub‐categories individually, by year. Secondary endpoints were the “breadth” (number of sub‐categories claimed/individual) and “depth” (percentages solely claiming in one of four lower‐level sub‐categories), by year.

Results

ROs claimed in 23/25 sub‐categories. The percentages of ROs claiming at least one research‐related activity were 71%, 44%, and 62% in 2019–21, respectively. The median number of sub‐categories claimed by these ROs was 2 (range 1–10) in each year. The commonest activity was journal article co‐author (25%, 16% and 27%, respectively). For 2019, the most representative year, other common activities were inhouse/local meeting presentation (17%), invited lecture at state level or above (15%), manuscript peer review and research project principal investigator (14% each). The percentages of ROs solely claiming in one lower‐level activity ranged between 4.4% and 5.9% per year.

Conclusion

A culture of research is arguably more fact than fantasy in ANZ. It is likely that Faculty curriculum requirements, research funding and other promotional initiatives have contributed substantively to this.
Immunosuppression for the treatment of pulmonary hypertension in patients with systemic lupus erythematosus: A systematic review
Authors: Bruera Sebastian , Sreedhar Arsha , Agarwal Sandeep K. , Muthukumar Varsha , Geng Yimin , Lopez‐Olivo Maria A.
Published: May 2023

Purpose

To conduct a systematic review with meta‐analysis to determine the effects of immunosuppression on Group 1 Pulmonary Arterial Hypertension in patients with systemic lupus erythematosus (SLE).

Methods

We searched Medline, Embase, Web of Science, Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) with a search strategy developed by a medical librarian. We included retrospective, cross‐sectional, case‐control, prospective studies, and randomized controlled trials (RCTs) in our analysis and only included studies that contained data for patients with SLE. We included any immunosuppressive agents (including but not limited to cyclophosphamide, glucocorticoids, mycophenolate mofetil, azathioprine, and rituximab) We assessed for risk of bias and certainty of evidence. Outcomes included hemodynamics (as measured by pulmonary arterial hypertension), functional status, 6 minute walk test (6MWT), quality of life, mortality, and serious adverse events.

Results

We included three studies. One RCT and two single‐arm interventional observational studies. The RCT had a high risk of bias whereas the two single‐arm interventional studies were graded as fair quality. Meta‐analysis could not be conducted because of insufficient data. The RCT showed significant improvements in hemodynamics (as measured by pulmonary arterial pressures) and functional status. One observational study showed improvements in hemodynamics, functional status, and 6MWT. There were insufficient data for serious adverse events, mortality, and quality of life.

Conclusions

Despite a high prevalence and with a poor prognosis, there is a paucity of data for the role of immunosuppression in the treatment of Group 1 Pulmonary Arterial Hypertension in SLE. More high‐quality studies are needed, especially to investigate serious adverse events and quality of life.
Predicting fluid responsiveness using esophagus Doppler monitoring and pulse oximetry derived pleth variability index; retrospective analysis of a hemodynamic study
Authors: Hahn Robert G. , Nilsson Lena , Bahlmann Hans
Published: May 2023

Background

Fluid therapy during major surgery can be managed by providing repeated bolus infusions until stroke volume no longer increases by ≥ 10%. However, the final bolus in an optimization round increases stroke volume by < 10% and is not necessary. We studied how different cut‐off values for the hemodynamic indications given by esophagus Doppler monitoring, as well as augmentation by pulse oximetry, are associated with a higher or smaller chance that stroke volume increases by ≥ 10% (fluid responsiveness) before fluid is infused.

Methods

An esophagus Doppler and a pulse oximeter that displayed the pleth variability index were used to monitor the effects of a bolus infusion in 108 patients undergoing goal‐directed fluid therapy during major open abdominal surgery.

Results

The analyzed data set comprised 266 bolus infusions. The overall incidence of fluid responsiveness was 44%, but this varied greatly depending on pre‐infusion hemodynamics. The likelihood of being fluid‐responsive was 30%–38% in the presence of stroke volume > 80 mL, corrected flow time > 360 ms, or pleth variability index < 10%. The likelihood was 21% if stroke volume had decreased by <8% since the previous optimization, which decreased to 0% if combined with stroke volume > 100 mL. By contrast, the likelihood of fluid responsiveness increased to 50%–55% when stroke volume ≤ 50 mL, corrected flow time ≤ 360 ms, or pleth variability index ≥ 10. A decrease in stroke volume by > 8% since the previous optimization was followed by a 58% likelihood of fluid responsiveness that, in combination with any of the other hemodynamic variables, increased to 66%–76%.

Conclusions

Single or combined hemodynamic variables provided by esophagus Doppler monitoring and pulse oximetry derived pleth variability index could help clinicians avoid unnecessary fluid bolus infusions.
Systemic antibiotic treatment for meibomian gland dysfunction—A systematic review and meta‐analysis
Authors: Ben Ephraim Noyman Dror , Chan Clara C. , Mimouni Michael , Safir Margarita
Published: May 2023

Purpose

To review the efficacy and safety of oral doxycycline antibiotics versus macrolides in the treatment of meibomian gland dysfunction (MGD).

Design

Systematic review and meta‐analysis.

Methods

We performed a systematic search of electronic databases for all peer‐reviewed published studies which included clinical outcomes of oral antibiotic MGD treatment. Individual study data were extracted and evaluated in a weighted pooled analysis, including total sign and symptom scores, meibomian gland secretion score, tear break‐up time (TBUT), fluorescein staining score and rate of complications.

Results

Two thousand nine hundred and thirty‐three studies were found, of which 54 were eligible for the systematic review, and six prospective studies were ultimately included for analysis, reporting on 563 cases from three countries. Age of affected patients ranged between 12 and 90 years. Overall, both treatment methods induced improvement in MGD signs and symptoms. In pooled analysis, macrolides were significantly superior in the total signs score (pooled standardized mean difference (SMD) −0.51, 95% confidence interval (CI): −0.99 to −0.03), meibomian gland secretion score (pooled SMD −0.25, 95%CI: [−0.48, −0.03]), TBUT (SMD −0.31, 95%CI: [−0.50, −0.13]) and fluorescein staining score (SMD −1.01, 95%CI: [−1.72, −0.29]). Moreover, while no severe complications were reported for both treatments, the macrolide group exhibited significantly less adverse events (pooled odds ratio 0.24 with a 95% CI of 0.16 to 0.34).

Conclusions

Both macrolides and tetracyclines are effective treatments for MGD. In this study, macrolides exhibited better efficacy and safety profile compared to tetracyclines.
Review: Improving access to mental health interventions for children from birth to five years: A Scoping Review
Authors: Hickey Lyndal , Harms Louise , Evans Jackson , Noakes Tahnee , Lee Henrietta , McSwan Amity , Bean Helena , Hope Judith , Allison Lynne , Price Sophie , Harris Nicole
Published: May 2023

Background

In spite of infants and children aged 0–5 years experiencing mental health difficulties being estimated to be in the range of 6%–18% globally, the mental health care needs for this age group are often overlooked in the design of specialist mental health services. Although there is increasing recognition of the importance of infant mental health services and treatments for younger children, access remains a barrier. Mental health services specifically designed for children 0–5 years are vital; however, little is known about how these services ensure access for infants at risk of mental health difficulties and their families. This scoping review seeks to address this knowledge gap.

Methods

A scoping review methodology framework was used to search for relevant articles published between January 2000 and July 2021, identified using five databases: MEDLINE, CINAHL, PsycINFO, SocIndex and Web of Science. The selection of studies was based on empirical research about access to infant mental health services and models of care. A total of 28 relevant articles met the eligibility criteria for inclusion in this review.

Results

Findings can be summarised under five broad themes: (1) accessibility for at‐risk populations (2) the importance of early detection of infants in need of mental health services and interventions; (3) the promotion of culturally responsive services and interventions; (4) ensuring the sustainability of IMH services and programs and (5) the integration of innovative interventions to improve existing practice models.

Conclusions

The findings from this scoping review highlight barriers to access and provision of infant mental health services. Future infant mental health service design, informed by research, is needed to improve access for infants and young children with mental health difficulties and their families.
ANP32B suppresses B‐cell acute lymphoblastic leukemia through activation of PU.1 in mice
Authors: Yang Qian , Liu Hao‐Ran , Yang Shuo , Wei Yu‐Sheng , Zhu Xiao‐Na , Zhi Zhe , Zhu Di , Chen Guo‐Qiang , Yu Yun
Published: May 2023

ANP32B, a member of the acidic leucine‐rich nuclear phosphoprotein 32 kDa (ANP32) family of proteins, is critical for normal development because its constitutive knockout mice are perinatal lethal. It is also shown that ANP32B acts as a tumor‐promoting gene in some kinds of cancer such as breast cancer and chronic myelogenous leukemia. Herein, we observe that ANP32B is lowly expressed in B‐cell acute lymphoblastic leukemia (B‐ALL) patients, which correlates with poor prognosis. Furthermore, we utilized the N‐myc or BCR‐ABLp190‐induced B‐ALL mouse model to investigate the role of ANP32B in B‐ALL development. Intriguingly, conditional deletion of Anp32b in hematopoietic cells significantly promotes leukemogenesis in two B‐ALL mouse models. Mechanistically, ANP32B interacts with purine rich box‐1 (PU.1) and enhances the transcriptional activity of PU.1 in B‐ALL cells. Overexpression of PU.1 dramatically suppresses B‐ALL progression, and highly expressed PU.1 significantly reverses the accelerated leukemogenesis in Anp32b‐deficient mice. Collectively, our findings identify ANP32B as a suppressor gene and provide novel insight into B‐ALL pathogenesis.
Pitfalls of mitral regurgitation assessment in the presence of mitral valve prolapse
Authors: Zach Veronika , Morris Daniel Armando , Pieske Burkert , Schneider‐Reigbert Matthias
Published: May 2023

Adequate grading of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) in the presence of mid‐late systolic jets can represent a major challenge. In this entity, jets are commonly overestimated by echocardiography. Correct quantification is crucial and highly relevant for the further management and prognosis of these oftentimes young patients. This case points out potential pitfalls and underlines the importance to systematically include qualitative, quantitative, and semi‐quantitative parameters into the echocardiographic assessment.
Day‐to‐day individual alpha frequency variability measured by a mobile EEG device relates to anxiety
Authors: Sidelinger Lauren , Zhang Mengsen , Frohlich Flavio , Daughters Stacey B.
Published: May 2023

The individual alpha frequency (IAF) has previously been identified as a unique neural signature within the 8–12 Hz alpha frequency band. However, the day‐to‐day variability of this feature is unknown. To investigate this, healthy participants recorded their own brain activity daily at home using the Muse 2 headband, a low‐cost consumer‐grade mobile electroencephalography (EEG) device. Resting‐state recordings of all participants using a high‐density (HD) EEG were also collected in lab before and after the at‐home data collection period. We found that the IAF extracted from the Muse 2 was comparable to that of location‐matched HD‐EEG electrodes. No significant difference was found between these IAF values before and after the at‐home recording period for the HD‐EEG device. Similarly, there was also no statistically significant difference between the beginning and end of the at‐home recording period for the Muse 2 headband over 1 month. Despite the group‐level stability of IAF, the individual‐level day‐to‐day IAF variability carried mental health‐relevant information: Exploratory analyses revealed a relationship between IAF day‐to‐day variability and trait anxiety. We also noted that the IAF systematically varied across the scalp and although the Muse 2 electrodes do not cover the occipital lobe where alpha oscillations were the strongest, IAFs measured in the temporal lobe and occipital lobe were strongly correlated. Altogether, these results show that mobile EEG devices are useful for studying IAF variability. The relationship between day‐to‐day variability of region‐specific IAF and the dynamics of psychiatric symptoms, particularly anxiety, should be further investigated.
Hybrid computer aided diagnostic system designs for screen film mammograms using DL‐based feature extraction and ML‐based classifiers
Authors: Rani Jyoti , Singh Jaswinder , Virmani Jitendra
Published: May 2023

Mammography is most popular imaging method used often in predicting breast cancer within women above age of 38 years. Various computer‐assisted algorithms have been employed for classifying breast masses as normal or malignant using screen film mammographic (SFM) images. In present research work, exhaustive experimentations have been carried out with nine deep learning‐based convolutional neural networks (CNNs) belonging to the three different categories of CNN architectures including (a) simple convolution‐based series models, that is VGG16 and VGG19 (b) simple convolution‐based directed acyclic graph (DAG) model, that is GoogleNet and (c) dilated convolution‐based DAG models, that is ResNet18, ResNet50, Inceptionv3, XceptionNet, ShuffleNet and MobileNet‐V2, for binary classification of the mammographic masses with SFM images. The experimental work has been carried out using 518 mammographic images taken from DDSM dataset with 208 images ϵ benign class and 310 images ϵ malignant class, respectively. The encoder‐decoder based semantic segmentation network model, that is ResNet50 has been used for the segmentation of mammographic masses from SFM images. The segmented masses images obtained from the ResNet50 model are subjected to classification experiments. To design a robust hybrid classifier design, that is, deep learning (DL)‐based feature extraction and machine learning (ML)‐based classification, the first step is to obtain an optimal DL‐based feature extractor for classification task. The optimal feature set obtained by the best performing CNN Model, that is, VGG 19 has been subjected to correlation‐based feature extraction and ML‐based classifiers including (i) adaptive neuro fuzzy classifier‐linguistic hedges (ii) principal component analysis‐ support vector machine classifier and (iii) GA‐SVM classifier to yield an optimal hybrid computer aided diagnostic (CAD) system design. It is found that hybrid CAD system using VGG19 as feature extractor and ANFC‐LH as classifier yields 96% the highest classification accuracy. The other performance parameters yield values, that is 96% sensitivity, 96% specificity, 96% F‐score, 96% precision and 92% MCC, which indicates a best prediction of binary classification. The test images which were misclassified by these hybrid CAD system designs were analysed subjectively by experienced participating radiologist. The results obtained by present work suggests that proposed hybrid CAD system with VGG19 Network model acting as feature extractor and ANFC‐LH classifier can be employed for the differential diagnosis of benign as well as malignant mammographic masses using SFM images in a routine clinical setting.
Validity of self‐reported migraine in adolescents and children
Authors: Kellier Danielle J. , de Prado Blanca Marquez , Haagen Dana , Grabner Philip , Raj Nichelle , Lechtenberg Lara , Velasquez Gerardo , Hsu Jesse Y. , Farrar John T. , Hershey Andrew D. , Szperka Christina L.
Published: May 2023

Objective

To assess agreement for migraine day between self‐report and diagnostic guidelines for children and adolescents using a headache diary.

Background

Trial guidelines recommend prospective collection of headache features and adoption of migraine day as an outcome measure, but there is no clear consensus on the definition of migraine day.

Methods

This is a secondary analysis of data from two projects—a prospective cohort study validating a pediatric scale of treatment expectancy and a clinical trial of occipital nerve blocks to treat status migrainosus. Participants completed a text message‐based diary for 4 or 12 weeks (depending on treatment), and a detailed headache assessment on a random 20% of headache days. Using this assessment, we determined whether a headache day qualified for migraine or probable migraine, based on the International Classification of Headache Disorders, 3rd edition (ICHD‐3).

Results

Of 122 enrolled children and adolescents, 106 (86.9%) completed ≥1 detailed headache assessment (438 entries). We found moderate agreement between self‐reported and ICHD‐derived migraine day, with a Cohen's Kappa of 0.50 (positive predictive value [PPV]: 0.66; negative predictive value [NPV]: 0.85; correlation: 0.51). Allowing for ICHD‐derived probable migraine significantly increased PPV (0.66 vs. 0.94; 95% CI: 0.57–0.74 vs. 0.90–0.97), but decreased NPV (0.85 vs. 0.293; CI: 0.77–0.90 vs. 0.199–0.40), Cohen's Kappa (0.50 vs. 0.237; CI: 0. 389–0.60 vs. 0.139–0.352), and correlation (r = 0.51 vs. 0.302; CI: 0.41–0.61 vs. 0.192–0.41). Pain severity (OR: 5.7; CI: 2.39–13.8), photophobia (OR: 4.1; CI: 1.02–16.6), and phonophobia (OR: 7.5; CI: 1.95–29.3) were significantly associated with participants' perception of migraine.

Conclusion

We found only moderate agreement between self‐reported and ICHD‐derived migraine day, suggesting both measures are not equal but may represent overlapping aspects of migraine as a disease. This highlights the difficulty of applying ICHD criteria to individual attacks. We recommend greater methodological transparency in future research to avoid readers conflating both measures.