bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxoplasma gondii modulates the host cell cycle, chromosome segregation, and cytokinesis irrespective of cell type or species origin
Authors: Rojas-Baron Lisbeth , Senk Kira , Hermosilla Carlos , Taubert Anja , Velásquez Zahady D.
Published: April 2024

Abstract﻿

Background

Toxoplasma gondii is an apicomplexan intracellular obligate parasite and the etiological agent of toxoplasmosis in humans, domestic animals and wildlife, causing miscarriages and negatively impacting offspring. During its intracellular development, it relies on nutrients from the host cell, controlling several pathways and the cytoskeleton. T. gondii has been proven to control the host cell cycle, mitosis and cytokinesis, depending on the time of infection and the origin of the host cell. However, no data from parallel infection studies have been collected. Given that T. gondii can infect virtually any nucleated cell, including those of humans and animals, understanding the mechanism by which it infects or develops inside the host cell is essential for disease prevention. Therefore, we aimed here to reveal whether this modulation is dependent on a specific cell type or host cell species.

Methods

We used only primary cells from humans and bovines at a maximum of four passages to ensure that all cells were counted with appropriate cell cycle checkpoint control. The cell cycle progression was analysed using fluorescence-activated cell sorting (FACS)-based DNA quantification, and its regulation was followed by the quantification of cyclin B1 (mitosis checkpoint protein). The results demonstrated that all studied host cells except bovine colonic epithelial cells (BCEC) were arrested in the S-phase, and none of them were affected in cyclin B1 expression. Additionally, we used an immunofluorescence assay to track mitosis and cytokinesis in uninfected and T. gondii-infected cells.

Results

The results demonstrated that all studied host cell except bovine colonic epithelial cells (BCEC) were arrested in the S-phase, and none of them were affected in cyclin B1 expression. Our findings showed that the analysed cells developed chromosome segregation problems and failed to complete cytokinesis. Also, the number of centrosomes per mitotic pole was increased after infection in all cell types. Therefore, our data suggest that T. gondii modulates the host cell cycle, chromosome segregation and cytokinesis during infection or development regardless of the host cell origin or type.

Graphical Abstract
Epigenetics in diabetic cardiomyopathy
Authors: Ma Xiaozhu , Mei Shuai , Wuyun Qidamugai , Zhou Li , Sun Dating , Yan Jiangtao
Published: April 2024

Diabetic cardiomyopathy (DCM) is a critical complication that poses a significant threat to the health of patients with diabetes. The intricate pathological mechanisms of DCM cause diastolic dysfunction, followed by impaired systolic function in the late stages. Accumulating researches have revealed the association between DCM and various epigenetic regulatory mechanisms, including DNA methylation, histone modifications, non-coding RNAs, and other epigenetic molecules. Recently, a profound understanding of epigenetics in the pathophysiology of DCM has been broadened owing to advanced high-throughput technologies, which assist in developing potential therapeutic strategies. In this review, we briefly introduce the epigenetics regulation and update the relevant progress in DCM. We propose the role of epigenetic factors and non-coding RNAs (ncRNAs) as potential biomarkers and drugs in DCM diagnosis and treatment, providing a new perspective and understanding of epigenomics in DCM.
Glymphatic inhibition exacerbates tau propagation in an Alzheimer’s disease model
Authors: Lopes Douglas M. , Wells Jack A. , Ma Da , Wallis Lauren , Park Daniel , Llewellyn Sophie K. , Ahmed Zeshan , Lythgoe Mark F. , Harrison Ian F.
Published: April 2024

Background

The aggregation and spread of misfolded amyloid structured proteins, such as tau and α-synuclein, are key pathological features associated with neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. These proteins possess a prion-like property, enabling their transmission from cell to cell leading to propagation throughout the central and peripheral nervous systems. While the mechanisms underlying their intracellular spread are still being elucidated, targeting the extracellular space has emerged as a potential therapeutic approach. The glymphatic system, a brain-wide pathway responsible for clearing extracellular metabolic waste from the central nervous system, has gained attention as a promising target for removing these toxic proteins.

Methods

In this study, we investigated the impact of long-term modulation of glymphatic function on tau aggregation and spread by chronically treating a mouse model of tau propagation with a pharmacological inhibitor of AQP4, TGN-020. Thy1-hTau.P301S mice were intracerebrally inoculated with tau into the hippocampus and overlying cortex, and subsequently treated with TGN-020 (3 doses/week, 50 mg/kg TGN-020, i.p.) for 10-weeks. During this time, animal memory was studied using cognitive behavioural tasks, and structural MR images were acquired of the brain in vivo prior to brain extraction for immunohistochemical characterisation.

Results

Our findings demonstrate increased tau aggregation in the brain and transhemispheric propagation in the hippocampus following the inhibition of glymphatic clearance. Moreover, disruption of the glymphatic system aggravated recognition memory in tau inoculated mice and exacerbated regional changes in brain volume detected in the model. When initiation of drug treatment was delayed for several weeks post-inoculation, the alterations were attenuated.

Conclusions

These results indicate that by modulating AQP4 function and, consequently, glymphatic clearance, it is possible to modify the propagation and pathological impact of tau in the brain, particularly during the initial stages of the disease. These findings highlight the critical role of the glymphatic system in preserving healthy brain homeostasis and offer valuable insights into the therapeutic implications of targeting this system for managing neurodegenerative diseases characterized by protein aggregation and spread.
Pyrroloquinoline quinone promotes human mesenchymal stem cell-derived mitochondria to improve premature ovarian insufficiency in mice through the SIRT1/ATM/p53 pathway
Authors: Liu Shengjie , Wang Yuanmei , Yang Hanlin , Tan Jun , Zhang Jingkaiwen , Zi Dan
Published: April 2024

Background

DNA damage and oxidative stress induced by chemotherapy are important factors in the onset of premature ovarian insufficiency (POI). Studies have shown that mitochondria derived from mesenchymal stem cells (MSC-Mito) are beneficial for age-related diseases, but their efficacy alone is limited. Pyrroloquinoline quinone (PQQ) is a potent antioxidant with significant antiaging and fertility enhancement effects. This study aimed to investigate the therapeutic effect of MSC-Mito in combination with PQQ on POI and the underlying mechanisms involved.

Methods

A POI animal model was established in C57BL/6J mice by cyclophosphamide and busulfan. The effects of MSC-Mito and PQQ administration on the estrous cycle, ovarian pathological damage, sex hormone secretion, and oxidative stress in mice were evaluated using methods such as vaginal smears and ELISAs. Western blotting and immunohistochemistry were used to assess the expression of SIRT1, PGC-1α, and ATM/p53 pathway proteins in ovarian tissues. A cell model was constructed using KGN cells treated with phosphoramide mustard to investigate DNA damage and apoptosis through comet assays and flow cytometry. SIRT1 siRNA was transfected into KGN cells to further explore the role of the SIRT1/ATM/p53 pathway in combination therapy with MSC-Mito and PQQ for POI.

Results

The combined treatment of MSC-Mito and PQQ significantly restored ovarian function and antioxidant capacity in mice with POI. This treatment also reduced the loss of follicles at various stages, improving the disrupted estrous cycle. In vitro experiments demonstrated that PQQ facilitated the proliferation of MitoTracker-labelled MSC-Mito, synergistically restoring mitochondrial function and inhibiting oxidative stress in combination with MSC-Mito. Both in vivo and in vitro, the combination of MSC-Mito and PQQ increased mitochondrial biogenesis mediated by SIRT1 and PGC-1α while inhibiting the activation of ATM and p53, consequently reducing DNA damage-mediated cell apoptosis. Furthermore, pretreatment of KGN cells with SIRT1 siRNA reversed nearly all the aforementioned changes induced by the combined treatment.

Conclusions

Our research findings indicate that PQQ facilitates MSC-Mito proliferation and, in combination with MSC-Mito, ameliorates chemotherapy-induced POI through the SIRT1/ATM/p53 signaling pathway.
circRNA_8521 promotes Senecavirus A infection by sponging miRNA-324 to regulate LC3A
Authors: Yang Xiwang , Liu Rui , Du Yunsha , Mei Caiqiu , Zhang Guangneng , Wang Chen , Yang Yijun , Xu Zhiwen , Li Wenting , Liu Xiao
Published: April 2024

Senecavirus A (SVA) causes outbreaks of vesicular disease in pigs, which imposes a considerable economic burden on the pork industry. As current SVA prevention measures are ineffective, new strategies for controlling SVA are urgently needed. Circular (circ)RNA is a newly characterized class of widely expressed, endogenous regulatory RNAs, which have been implicated in viral infection; however, whether circRNAs regulate SVA infection remains unknown. To investigate the influence of circRNAs on SVA infection in porcine kidney 15 (PK-15) cells, RNA sequencing technology was used to analyze the circRNA expression profiles of SVA-infected and uninfected PK-15 cells, the interactions between circRNAs, miRNAs, and mRNAs potentially implicated in SVA infection were predicted using bioinformatics tools. The prediction accuracy was verified using quantitative real-time (qRT)-PCR, Western blotting, as well as dual-luciferase reporter and RNA pull-down assays. The results showed that 67 circRNAs were differentially expressed as a result of SVA infection. We found that circ_8521 was significantly upregulated in SVA-infected PK-15 cells and promoted SVA infection. circ_8521 interacted with miR-324. miR-324 bound to LC3A mRNA which inhibited the expression of LC3A. Knockdown of LC3A inhibited SVA infection. However, circ_8521 promoted the expression of LC3A by binding to miR-324, thereby promoting SVA infection. We demonstrated that circ_8521 functioned as an endogenous miR-324 sponge to sequester miR-324, which promoted LC3A expression and ultimately SVA infection.
MIR145 Core Promoter Methylation in Pretreatment Cell-Free DNA: A Liquid Biopsy Tool for Muscle-Invasive Bladder Cancer Treatment Outcome
Authors: Pilala Katerina-Marina , Kotronopoulos Georgios , Levis Panagiotis , Giagkos Georgios-Christos , Stravodimos Konstantinos , Vassilacopoulou Dido , Scorilas Andreas , Avgeris Margaritis
Published: April 2024

PURPOSE

The lack of personalized management of bladder cancer (BlCa) results in patients' lifelong post-treatment monitoring with invasive interventions, underlying the urgent need for tailored and minimally invasive health care services. On the basis of our previous findings on miR-143/145 cluster methylation in bladder tumors, we evaluated its clinical significance in pretreatment cell-free DNA (cfDNA) of patients with BlCa.

MATERIALS AND METHODS

Methylation analysis was performed in our screening cohort (120 patients with BlCa; 20 age-matched healthy donors) by bisulfite-based pyrosequencing. Tumor recurrence/progression for patients with non–muscle-invasive bladder cancer, and progression and mortality for patients with muscle-invasive bladder cancer (MIBC) were used as clinical end point events in survival analysis. Bootstrap analysis was applied for internal validation of Cox regression models and decision curve analysis for assessment of clinical benefit on disease prognosis.

RESULTS

Decreased methylation of MIR145 core promoter in pretreatment cfDNA was associated with short-term disease progression (multivariate Cox: hazard ratio [HR], 2.027 [95% CI, 1.157 to 3.551]; P = .010) and poor overall survival (multivariate Cox: HR, 2.098 [95% CI, 1.154 to 3.817]; P = .009) of patients with MIBC after radical cystectomy (RC). Multivariate models incorporating MIR145 promoter methylation in cfDNA with tumor stage clearly ameliorated patients' risk stratification, highlighting superior clinical benefit in MIBC prognostication.

CONCLUSION

Reduced pretreatment cfDNA methylation of MIR145 core promoter was markedly correlated with increased risk for short-term progression and worse survival of patients with MIBC after RC and adjuvant therapy, supporting modern personalized and minimally invasive prognosis. Methylation profiling of MIR145 core promoter in pretreatment cfDNA could serve as a minimally invasive and independent predictor of MIBC treatment outcome and emerge as a promising marker for blood-based test in BlCa.
Repeat Next-Generation Sequencing Testing on Progression in Men With Metastatic Prostate Cancer Can Identify New Actionable Alterations
Authors: Park Joseph J. , Chu Alec , Li Jinju , Ali Alicia , McKay Rana R. , Hwang Clara , Labriola Matthew K. , Jang Albert , Kilari Deepak , Mo George , Ravindranathan Deepak , Graham Laura S. , Sokolova Alexandra , Tripathi Abhishek , Pilling Amanda , Jindal Tanya , Ravindra Aditya , Cackowski Frank C. , Sweeney Patrick L. , Thapa Bicky , Amery Taylor S. , Heath Elisabeth I. , Garje Rohan , Zakharia Yousef , Koshkin Vadim S. , Bilen Mehmet A. , Schweizer Michael T. , Barata Pedro C. , Dorff Tanya B. , Cieslik Marcin , Alva Ajjai S. , Armstrong Andrew J.
Published: April 2024

PURPOSE

There are limited data available on the real-world patterns of molecular testing in men with advanced prostate cancer. We thus sought to evaluate next-generation sequencing (NGS) testing in the United States, focused on single versus serial NGS testing, the different disease states of testing (hormone-sensitive v castration-resistant, metastatic vs nonmetastatic), tissue versus plasma circulating tumor DNA (ctDNA) assays, and how often actionable data were found on each NGS test.

METHODS

The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort clinical-genomic database was used for this retrospective analysis, including 1,597 patients across 15 institutions. Actionable NGS data were defined as including somatic alterations in homologous recombination repair genes, mismatch repair deficiency, microsatellite instability (MSI-high), or a high tumor mutational burden ≥10 mut/MB.

RESULTS

Serial NGS testing (two or more NGS tests with specimens collected more than 60 days apart) was performed in 9% (n = 144) of patients with a median of 182 days in between test results. For the second NGS test and beyond, 82.1% (225 of 274) of tests were from ctDNA assays and 76.1% (217 of 285) were collected in the metastatic castration-resistant setting. New actionable data were found on 11.1% (16 of 144) of second NGS tests, with 3.5% (5 of 144) of tests detecting a new BRCA2 alteration or MSI-high. A targeted therapy (poly (ADP-ribose) polymerase inhibitor or immunotherapy) was given after an actionable result on the second NGS test in 31.3% (5 of 16) of patients.

CONCLUSION

Repeat somatic NGS testing in men with prostate cancer is infrequently performed in practice and can identify new actionable alterations not present with initial testing, suggesting the utility of repeat molecular profiling with tissue or blood of men with metastatic castration-resistant prostate cancer to guide therapy choices.
First Use of AXL Targeting in Metastatic, Refractory, Adenoid Cystic Carcinoma: A Case Report
Authors: Hoff Camilla O. , Dal Lago Eduardo Andreazza , Siqueira Juliana Mota , de Sousa Luana G. , El-Naggar Adel K. , Ahnert Jordi Rodon , Ferrarotto Renata
Published: April 2024

First use of AXL-targeting in adenoid cystic carcinoma (ACC); with positive results, ACC now included in AXL studies.
TERT Promoter Mutations Increase Tumor Aggressiveness by Altering TERT mRNA Splicing in Papillary Thyroid Carcinoma
Authors: Sako Ayaka , Matsuse Michiko , Saenko Vladimir , Tanaka Aya , Otsubo Ryota , Morita Michi , Kuba Sayaka , Nishihara Eijun , Suzuki Keiji , Ogi Tomoo , Kawakami Atsushi , Mitsutake Norisato
Published: April 2024

Context

Telomerase reverse transcriptase promoter (TERT-p) mutations, which upregulate TERT expression, are strongly associated with tumor aggressiveness and worse prognosis in papillary thyroid carcinomas (PTCs). TERT expression is also observed in a proportion of PTCs without TERT-p mutations, but such tumors show less aggressiveness and better prognosis than TERT-p mutation–positive tumors.

Objective

TERT has multiple splicing variants whose relationships with the TERT-p status and clinicopathological characteristics remain poorly understood. We examined the relationship between the TERT-p mutational status, the TERT splicing pattern, and clinicopathological features.

Methods

We investigated the expression of 2 major variants, α deletion (dA) and β deletion (dB), in a series of 207 PTCs operated on between November 2001 and March 2020 in Nagasaki University Hospital and Kuma Hospital.

Results

The TERT-p mutations were found in 33 cases, and among 174 mutation-negative cases, 24 showed TERT expression. All cases were classified into 3 groups: the TERT-p mutation–negative/expression–negative group (mut−/exp−), the TERT-p mutation–negative/expression–positive group (mut−/exp+), and the TERT-p mutation–positive group (mut+/exp+). The +A+B/dB ratio in mut+/exp+ was significantly higher than that in mut−/exp+ PTCs. Analysis with clinicopathological data revealed that +A+B expression was associated with higher PTC aggressiveness, whereas dB expression counteracted this effect. Functional in vitro study demonstrated that dB strongly inhibited cell growth, migration, and clonogenicity, suggesting its tumor-suppressive role.

Conclusion

These results provide evidence that the TERT-p mutations alter the expression of different TERT splice variants, which, in turn, associates with different tumor aggressiveness.
Local Anesthetic Systemic Toxicity in Cardiac Surgery Patient with Erector Spinae Plane Catheter: A Case Report
Authors: Smith Derek , Tsui Ban C.H. , Khoo Cynthia
Published: April 2024

Regional anesthesia nerve blocks are increasingly used for patients undergoing cardiac surgery as part of multimodal pain management. Though rare, local anesthetic systemic toxicity (LAST) is a severe complication that requires vigilant monitoring. We present a case of a postcardiac surgery patient who developed LAST multiple days after surgery from lidocaine via an erector spinae plane catheter. This episode was determined to be a result of impaired lidocaine metabolism from liver shock caused by worsening pulmonary hypertension. Even under continuous monitoring, patients with cardiac or liver dysfunction are at increased risk of complications from local anesthetics.
Ανάπτυξη και υλοποίηση αλγορίθμων βελτιστοποίησης σε προβλήματα ναυτιλιακής εφοδιαστικής αλυσίδας
Authors: Τσακιράκης Ελευθέριος
Published: April 2024

Η παρούσα διδακτορική διατριβή εξετάζει τα προβλήματα των θαλάσσιων μεταφορών και των λιμενικών λειτουργιών στο πλαίσιο της διαχείρισης της θαλάσσιας αλυσίδας εφοδιασμού. Κύριος στόχος αποτελεί η ανάπτυξη καινοτόμων αλγορίθμων βελτιστοποίησης για την επίλυση αυτών των προβλημάτων σε πραγματικό χρόνο, υλοποιώντας μεθοδολογίες προερχόμενες από τον κλάδο της τεχνητής νοημοσύνης. Πιο συγκεκριμένα, η διατριβή επικεντρώνεται σε δύο κύρια προβλήματα αυτά της δρομολόγησης των πλοίων και τον ελλιμενισμό των πλοίων στους λιμένες. Η δρομολόγηση των πλοίων ορίζεται ως η διαδικασία καθορισμού των βέλτιστων διαδρομών για ένα στόλο πλοίων, ο οποίος εξυπηρετεί ένα σύνολο λιμένων και πελατών, λαμβάνοντας υπόψη διάφορους παράγοντες, όπως η ζήτηση φορτίου, η κατανάλωση καυσίμου, η συμφόρηση λιμένων, κ.ά. Για το δεύτερο πρόβλημα, ο ελλιμενισμός των πλοίων θεωρείται η διαδικασία της βέλτιστης εκχώρησης των εισερχόμενων πλοίων στους λιμενικούς τερματικούς σταθμούς λαμβάνοντας υπόψη διάφορους περιορισμούς, όπως τις ώρες άφιξης πλοίων, τους χρόνους εξυπηρέτησης τους, την διάρκεια παραμονής σε αυτά, τα χαρακτηριστικά των πλοίων, κ.ά. Η ανάλυση των δύο προαναφερθέν προβλημάτων πραγματοποιείται με την παρουσιάση των μαθηματικών μοντέλων βασισμένα από την επιστημονική βιβλιογραφία. Η επίλυση αυτών των προβλημάτων βελτιστοποίησης της ναυτιλιακής εφοδιαστικής αλυσίδας επιτυγχάνεται με την ανάπτυξη μεθόδων τεχνητής νοημοσύνης και ειδικότερα από την κατηγορία των αλγορίθμων εμπνευσμένων από φυσικές διαδικασίες. Σε κάθε ένα από τα δύο προβλήματα ακολουθούνται διαφορετικές στρατηγικές αντιμετώπισης τους και υλοποιούνται διάφορες τεχνικές βελτιστοποιήσης με στόχο την επίτευξη ποιοτικών λύσεων σε ρεαλιστικό πραγματικό χρόνο. Τα αποτελέσματα των προτεινόμενων αλγοριθμικών μεθόδων συγκρίνονται με τα αντίστοιχα από την επιστημονική βιβλιογραφία παρουσίαζοντας σημαντικές βελτιώσεις από αυτά τόσο στην ποιότητα των λύσεων, όσο και στον απαιτούμενο υπολογιστικό χρόνο παραγωγής τους. Η ανάλυση των αποτελεσμάτων αποδεικνύει την δυναμική των προτεινόμενων μεθόδων της διδακτορικής διατριβής στην επίλυση πολύπλοκων προβλημάτων βελτιστοποίησης και προτείνει την περεταίρω εφαρμογή τους σε περισσότερα πραγματικά προβλήματα. Τέλος, η διδακτορική διατριβή ολοκληρώνεται με τις κύριες συνεισφορές για την βελτίωση της διαχείρισης της θαλάσσιας αλυσίδας εφοδιασμού και τις κατευθύνσεις για μελλοντική έρευνα.
Lawfare as a decolonial tool: The Chagos Archipelago case as an example of libertarian possibilities promoted by the proliferation of cases before different courts
Authors: Cardoso Squef Tatiana , Borges Murilo
Published: April 2024

Historically, war has resignified the international political process, transforming the interaction promoted by lawsuits and arbitration into a process through which law and politics evolve. At this point, the term lawfare appears, which refers to a type of warfare in which the rule of law is used as a weapon. Although there are some negative connotations to the term, this study seeks to demonstrate that it can also be an emancipatory tool, assisting nations of the Global South in advancing their arguments and points of view against the old colonial empires that have dictated International Law since the 15th century. Following this syllogism and employing the hypothetical-deductive approach method, this paper attempts to confirm the thesis regarding the feasibility of advancing discourses that seek to “free” international law through descriptive and explanatory methodology. The cases involving the Chagos Archipelago before various international courts that directly or indirectly address the United Kingdom’s inadequate/incomplete decolonization are examined.
Los actos unilaterales del Estado chileno como fuente de la obligación de negociar con Bolivia un acceso al océano Pacífico: observaciones a la sentencia de la Corte Internacional de Justicia proferida el 1 de octubre de 2018
Authors: Mora Ramírez Danna Carolina
Published: April 2024

Este capítulo propone un análisis de la sentencia de fondo proferida por la Corte Internacional de Justicia (CIJ) para el caso sobre la obligación de negociar el acceso al océano Pacífico (Bolivia c. Chile) [excepción preliminar], fallo de 24 de septiembre de 2015, con énfasis en los actos unilaterales como fuente de obligaciones internacionales. Para ello, se presenta un breve resumen del caso, luego se expone el concepto de actos unilaterales del Estado y su desarrollo a lo largo de la historia, aunado al enfoque que el Estado Plurinacional de Bolivia le dio a este tema en su demanda. Finalmente, se presentan las observaciones a la sentencia en mención a partir del análisis que realizó.
The More You Know: The Impact of Personal Knowledge on Interpersonal Treatment at Work
Authors: Hardin Ashley E.
Published: April 2024

Employees often receive conflicting advice about sharing personal information in the workplace. They are told to “bring your whole self to work” but also to keep it professional and not share too much personal information with colleagues. Research has been equivocal in its overall guidance about sharing personal information at work: it may be either beneficial or harmful for work relationships. These inconsistencies are likely driven by the types of questions posed. Specifically, existing research has studied the impact of a particular piece of personal information and the specific details of what is learned, not what all of these pieces of personal information amount to. Instead, this paper takes a new vantage point to understand how the amount of personal knowledge (the quantity of information that one person knows across many aspects of a colleague’s personal life) influences positive interpersonal dynamics at work by humanizing the known colleague. Through a full-cycle research approach, I establish causal support experimentally and then replicate support for my hypotheses in the field, demonstrating a positive, persistent effect: having more personal knowledge—regardless of whether that knowledge conveys value incongruence or life-to-work interference—leads to a more humanized perception of the known colleague, resulting in increased responsiveness toward that colleague. These findings resolve an existing puzzle in the literature and also contribute to a more nuanced understanding of work relationships and interpersonal learning at work.

Funding: This work was supported by Washington University in St. Louis (faculty research funds) and the University of Michigan (doctoral research funds).

Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2021.15606 .
National Lymphoedema Conference 2024: session summaries
Authors: Hashimi Samina , Rajagopalan Upasana
Published: April 2024

The 11th annual National Lymphoedema Conference, organised by the British Journal of Community Nursing in association with the British Lymphology Society and Lipoedema UK, was hosted at the America Square Conference Centre, London, on 22 February 2024. The conference, which aims to provide new insights into the latests developments in lymphoedema care and management through talks by leading experts in the field, was attended by an impressive number of delegates and exhibitors. The sessions were Chaired by BLS Trustee Rebecca Elwell, and are summarised below.
Analysis of the Design and Curricular Practices in an Educational Re-Engagement Program
Authors: Barea Eva María González , Rodríguez-Entrena María Jesús , Bernárdez-Gómez Abraham
Published: April 2024

In this article, which is part of a broader investigation based on the study of the educational and socio-occupational re-engagement processes of young people in vulnerable situations, the curricular design of the vocational training programs (VTP) is described. Further, the curricular practices developed in the classrooms of these programs are analyzed, based, above all, on how the contents are selected, as well as the methodological approaches for their development. The research methodology that was followed responds to the conduct of multiple case studies with the integration of quantitative and qualitative processes. The data collection instruments used for this purpose were questionnaires, interviews, and discussion groups. The conclusions reveal the selection of contents that are relevant, interesting, and close to the reality of the students. The development of these contents is displayed through varied methodological strategies and diverse activities that enhance the students’ involvement and the practical sense of their learning.
Rasselas : The Enigma and the “Agile Music”
Authors: Loveridge Mark
Published: April 2024

Abstract: This essay reads Samuel Johnson’s Rasselas (1759) against the background of negative or apophatic theology and argues that it is unique among Johnson’s works in expressing a sense of life as an enigma . The silent or hidden symbol of the story is the Giza Sphinx, one of the foundational symbols of such theology: the second-century Church Father Clement of Alexandria, whose works Johnson owned, associated the enigmas of the Hebrew Bible with the mystery of the Egyptian sphinxes. More widely, Rasselas contains absent objects and symbols, enigmatic silences and responses, hidden images and paradoxes, self-defeating dualisms and habits of style, apophatic philosophy (“philosophy can tell no more”), and an enigmatic conclusion (“ nothing ”). The apophatic quality is embodied in the text through what Jorge Luis Borges refers to as Rasselas ’s “agile music,” the subtle, flexible management of narrative voices, which generates a distinctive kind of attention in the reader.
Viscoelasticity quantification of cancerous tongue using intraoral optical coherence elastography: a preliminary study
Authors: Zhang Yubao , Han Xiao , Luo Jiahui , Zhang Qin , He Xingdao
Published: April 2024

Quantifying the biomechanical properties of the tongue is significant for early diagnosis of tongue carcinoma. Therefore, an intraoral optical coherence elastography system based on a miniature probe was proposed here to evaluate the viscoelasticity of in vivo tongue for the first time. Results of experiments with Sprague-Dawley rats indicate that considerable elasticity diversity occurred between cancerous and normal tongues, and the corresponding ratio of their Young’s modulus was evaluated to be 3.74. It is also found that, viscosity in diseased tissue is smaller than that in normal tissue. Additionally, healthy, transitional and cancerous regions in the cancerous tongue can be distinguished easily by calculating viscoelasticity characteristics. Based on this preliminary attempt, our method with advantages of noninvasive, high-resolution, high-sensitivity and real-time detection and convenient operation may have good potential to become a useful tool for tongue carcinoma assessment after further optimization.
Constant Field of View Display Size Effects on First-Person Aiming Time
Authors: Spjut Josef , Boudaoud Ben , Kim Joohwan
Published: April 2024

Under constant display field of view, FPS game aiming performance improves with display size, resulting in 3% faster aiming time comparing 13 and 26 inches diagonal.
Performance enhancement of multiple-mode FBMC-IM VLC systems with group-interleaved precoding
Authors: Wen Hong , Chen Hao , Chen Qinghui , Liu Kexiong , Chen Chen , Mo Dalong
Published: April 2024

In this paper, we introduce the application of multiple-mode index modulation (MMIM) to filter bank multi-carrier (FBMC) for the first time in visible light communication (VLC) systems. Additionally, we propose a group-interleaved precoding (GIP) technique to enhance the performance of MM-FBMC-IM-based VLC systems. The GIP technique reduces complexity in precoding by grouping and achieves equalization of the signal-to-noise ratio (SNR) through subcarrier interleaving. Furthermore, we develop a robust low-complexity maximum likelihood (LCML) detector, which can maintain the same computational complexity as a conventional LCML detector and achieve similar performance as an ML detector. The effectiveness and superiority of the proposed MM-FBMC-IM-based VLC system with GIP are demonstrated through comprehensive validation by both simulation and experimental results.
Observing perineuronal nets like structures via coaxial scattering quantitative interference imaging at multiple wavelengths
Authors: Sun Chaofu , Wang Yuhang , Jin Xiao , Ni Bin , Xu Bin , Hou Jamie Jiangmin , Zhong Chuyu , Liu Juan , Wu Yijia , Song Liang , Hou Lianping , Yi Muhua , Liu Xuefeng , Xiong Jichuan
Published: April 2024

Perineuronal nets (PNNs) are important functional structures on the surface of nerve cells. Observation of PNNs usually requires dyeing or fluorescent labeling. As a network structure with a micron grid and sub-wavelength thickness but no special optical properties, quantitative phase imaging (QPI) is the only purely optical method for high-resolution imaging of PNNs. We proposed a Scattering Quantitative Interference Imaging (SQII) method which measures the geometric rather than transmission or reflection phase during the scattering process to visualize PNNs. Different from QIP methods, SQII method is sensitive to scattering and not affected by wavelength changes. Via geometric phase shifting method, we simplify the phase shift operation. The SQII method not only focuses on interference phase, but also on the interference contrast. The singularity points and phase lines of the scattering geometric phase depict the edges of the network structure and can be found at the valley area of the interference contrast parameter SIND
R
under different wavelengths. Our SQII method has its unique imaging properties, is very simple and easy to implement and has more worth for promotion.
A probabilistic knowledge graph for target identification
Authors: Liu Chang , Xiao Kaimin , Yu Cuinan , Lei Yipin , Lyu Kangbo , Tian Tingzhong , Zhao Dan , Zhou Fengfeng , Tang Haidong , Zeng Jianyang
Published: April 2024

Early identification of safe and efficacious disease targets is crucial to alleviating the tremendous cost of drug discovery projects. However, existing experimental methods for identifying new targets are generally labor-intensive and failure-prone. On the other hand, computational approaches, especially machine learning-based frameworks, have shown remarkable application potential in drug discovery. In this work, we propose Progeni, a novel machine learning-based framework for target identification. In addition to fully exploiting the known heterogeneous biological networks from various sources, Progeni integrates literature evidence about the relations between biological entities to construct a probabilistic knowledge graph. Graph neural networks are then employed in Progeni to learn the feature embeddings of biological entities to facilitate the identification of biologically relevant target candidates. A comprehensive evaluation of Progeni demonstrated its superior predictive power over the baseline methods on the target identification task. In addition, our extensive tests showed that Progeni exhibited high robustness to the negative effect of exposure bias, a common phenomenon in recommendation systems, and effectively identified new targets that can be strongly supported by the literature. Moreover, our wet lab experiments successfully validated the biological significance of the top target candidates predicted by Progeni for melanoma and colorectal cancer. All these results suggested that Progeni can identify biologically effective targets and thus provide a powerful and useful tool for advancing the drug discovery process.
Belt and braces: Two escape ways to maintain the cassette reservoir of large chromosomal integrons
Authors: Richard Egill , Darracq Baptiste , Littner Eloi , Millot Gael A. , Conte Valentin , Cokelaer Thomas , Engelstädter Jan , Rocha Eduardo P. C. , Mazel Didier , Loot Céline
Published: April 2024

Integrons are adaptive devices that capture, stockpile, shuffle and express gene cassettes thereby sampling combinatorial phenotypic diversity. Some integrons called sedentary chromosomal integrons (SCIs) can be massive structures containing hundreds of cassettes. Since most of these cassettes are non-expressed, it is not clear how they remain stable over long evolutionary timescales. Recently, it was found that the experimental inversion of the SCI of Vibrio cholerae led to a dramatic increase of the cassette excision rate associated with a fitness defect. Here, we question the evolutionary sustainability of this apparently counter selected genetic context. Through experimental evolution, we find that the integrase is rapidly inactivated and that the inverted SCI can recover its original orientation by homologous recombination between two insertion sequences (ISs) present in the array. These two outcomes of SCI inversion restore the normal growth and prevent the loss of cassettes, enabling SCIs to retain their roles as reservoirs of functions. These results illustrate a nice interplay between gene orientation, genome rearrangement, bacterial fitness and demonstrate how integrons can benefit from their embedded ISs.
Determinants of coexistence of undernutrition and anemia among under-five children in Rwanda; evidence from 2019/20 demographic health survey: Application of bivariate binary logistic regression model
Authors: Asmare Abebew Aklog , Agmas Yitateku Adugna
Published: April 2024

Background

Undernutrition and anemia are significant public health issues among under-5 children, with potential long-term consequences for growth, development, and overall health. Thus, this study aims to conduct a bivariate binary logistic regression model by accounting for the possible dependency of childhood undernutrition and anemia.

Methods

The data came from the DHS program’s measurement. A total of 3,206 under-five children were involved in this study. A single composite index measure was calculated for stunting, wasting, and underweight using principal component analysis. A bivariate binary logistic regression model is used to assess the association between undernutrition and anemia given the effect of other predictors.

Results

Among 3,206 under-five children considered in this study, 1482 (46.2%) and 658 (20.5%) children were agonized by anemia and undernutrition, respectively. In bivariate binary logistic regression model; Urban children [AOR = 0.751, 96% CI: 0.573–0.984; AOR = 0.663, 95% CI: 0.456–0.995] and anemic mothers [AOR = 1.160, 95% CI: 1.104–1.218; AOR = 1.663, 95% CI: 1.242–2.225] were significantly associated with both childhood anemia and undernutrition, respectively. Improved water sources [AOR = 0.681, 95% CI: 0.446–0.996], average-sized children [AOR = 0.567, 95% CI: 0.462–0.696], and diarrhea [AOR = 1.134, 95% CI: 1.120–2.792] were significantly associated with childhood anemia. Large-sized children [AOR = 0.882, 95% CI: 0.791–0.853] and those with fever [AOR = 1.152, 95% CI: 1.312–2.981] were significantly associated with under-five children’s undernutrition.

Conclusion

The prevalence of both undernutrition and anemia among under-five-year-old children was high in Rwanda. The following determinants are statistically associated with both childhood undernutrition and anemia: place of residence; source of drinking water; maternal anemia; being a twin; birth size of children; diarrhea; fever; and child age. Anemia and nutritional deficiencies must be treated concurrently under one program, with evidence-based policies aimed at vulnerable populations.
County medical community, medical insurance package payment, and hierarchical diagnosis and treatment—Empirical analysis of the impact of the pilot project of compact county medical communities in Sichuan Province
Authors: Ding Shaoqun , Zhou Yuxuan
Published: April 2024

Hierarchical diagnosis and treatment (HDT) is an important exploration direction to alleviate the rising pressure of health expenses and medical insurance fund expenditure in China, and to maintain and protect the public health in this country. In recent years, the construction of compact county medical communities (CCMC) has become the primary approach for implementing the HDT. Utilizing the quasi-natural experiment of the pilot project of CCMC in Sichuan Province in 2019, coupled with county-level data extracted from the ’ Sichuan Provincial Health Statistics Yearbook ’ spanning the years 2008 to 2021, this research evaluates the effect of the pilot project of CCMC on promoting HDT under the medical insurance package payment model. The results show that the pilot project of CCMC has significantly increased the number of consultations per capita of medical and health institutions in pilot counties by 0.434 times, of which the number of consultations per capita of primary medical institutions has increased by 0.340 times; the number of hospitalizations per capita in public hospitals and primary medical institutions in pilot counties increased significantly, and the surgery rate of inpatients in public hospitals increased by 5% compared to before the pilot. There was no significant impact on the allocation of medical facilities and human resources in the pilot counties. Therefore, the construction of CCMC under the medical insurance package payment mode has promoted the realization of the county-level HDT. These findings provide valuable insights for healthcare policy, especially in developing and implementing effective strategies for HDT in county-level medical institutions.
Factors influencing household and women’s dietary diversity in migrant households in central Nepal
Authors: Gartaula Hom Nath , Atreya Kishor , Kattel Kanchan , Rahut Dil Bahadur
Published: April 2024

Food security and dietary diversity, defined as providing either physical (availability) or economic (accessibility) access to food, are linked with access to and control over productive resources and is a highly-gendered phenomenon. In Nepal, labor out-migration has increased household income and may have increased people’s ability to access diverse food either by increasing investment in agriculture or purchasing various food items from the market. However, the relationship between household dietary improvement and labor out-migration is complex. Drawing on a survey of 1,053 migrant households in three agroecological regions of Nepal, this paper disentangles this complex phenomenon by showing how household dietary diversity and women’s dietary diversity are influenced by biophysical, social, economic, and cultural factors. The influence of the amount of remittances, land abandonment, and women confined to the house by household chores are some factors that policy makers should consider seriously in designing gender-sensitive nutrition policies. The expansion of women’s agency contributes to enhancing dietary diversity and specifically women’s dietary diversity at the household level; however, how these factors determine an individual’s dietary diversity depends on intrahousehold dynamics and relations.
Uncovering the causes and socio-demographic constructs of stillbirths and neonatal deaths in an urban slum of Karachi
Authors: Muhammad Ameer , Rizvee Muhammad Salman Haider , Khan Uzma , Khan Hina , Bachlany Alishan , Baloch Benazir , Shafiq Yasir
Published: April 2024

Introduction

Neonatal deaths and stillbirths are significant public health concerns in Pakistan, with an estimated stillbirth rate of 43 per 1,000 births and a neonatal mortality rate of 46 deaths per 1,000 live births. Limited access to obstetric care, poor health seeking behaviors and lack of quality healthcare are the leading root causes for stillbirths and neonatal deaths. Rehri Goth, a coastal slum in Karachi, faces even greater challenges due to extreme poverty, and inadequate infrastructure. This study aims to investigate the causes and pathways leading to stillbirths and neonatal deaths in Rehri Goth to develop effective maternal and child health interventions.

Methods

A mixed-method cohort study was nested with the implementation of large maternal, neonatal and child health program, captured all stillbirths and neonatal death during the period of May 2014 till June 2018. The Verbal and Social Autopsy (VASA) tool (WHO 2016) was used to collect primary data from all death events to determine the causes as well as the pathways. Interviews were conducted both retrospectively and prospectively with mothers and caregivers. Two trained physicians reviewed the VASA form and the medical records (if available) and coded the cause of death blinded to each other. Descriptive analysis was used to categorize stillbirth and neonatal mortality data into high- and low-mortality clusters, followed by chi-square tests to explore associations between categories, and concluded with a qualitative analysis.

Results

Out of 421 events captured, complete VASA interviews were conducted for 317 cases. The leading causes of antepartum stillbirths were pregnancy-induced hypertension (22.4%) and maternal infections (13.4%), while obstructed labor was the primary cause of intrapartum stillbirths (38.3%). Neonatal deaths were primarily caused by perinatal asphyxia (36.1%) and preterm birth complications (27.8%). The qualitative analysis on a subset of 40 death events showed that health system (62.5%) and community factors (37.5%) contributing to adverse outcomes, such as delayed referrals, poor triage systems, suboptimal quality of care, and delayed care-seeking behaviors.

Conclusion

The study provides an opportunity to understand the causes of stillbirths and neonatal deaths in one of the impoverished slums of Karachi. The data segregation by clusters as well as triangulation with qualitative analysis highlight the needs of evidence-based strategies for maternal and child health interventions in disadvantaged communities.
Beneficial impacts of physical activity on heart rate variability: A systematic review and meta-analysis
Authors: El-Malahi Ouahiba , Mohajeri Darya , Mincu Raluca , Bäuerle Alexander , Rothenaicher Korbinian , Knuschke Ramtin , Rammos Christos , Rassaf Tienush , Lortz Julia
Published: April 2024

Background

Cardiovascular diseases (CVD) are the leading causes of morbidity and mortality. Heart rate variability (HRV) represents the modulatory capacity of the autonomous nervous system and influences mortality. By surveying this meta-analysis, we investigated the impact of physical activity on HRV.

Methods

Databases, online journal libraries and clinical trial registries were searched for publications of randomized controlled and non-randomized controlled trials concerning adults with coronary artery disease (CAD)/ischemic heart disease (IHD), congestive heart failure (CHF), peripheral arterial disease (PAD) or after acute coronary syndrome (ACS) joining an intervention group with physical activity or a control group with usual care or no intervention. Extracted time-domain and frequency-domain parameter of HRV were analyzed in a meta-analysis using a random effect model. Subgroup analyses concerning intervention type, study design and type of heart disease and sensitivity analysis were performed.

Results

Significant results were obtained for RR-Interval (p = 0.05) and standard deviation of Normal-to-Normal intervals (SDNN) (p = 0.01) for short-term assessment and for the ratio of low-frequency power (LF) to high-frequency power (HF) (p = 0.05) for 24-hour assessment. Subgroup analyses also resulted significant: root-mean-square difference of successive normal R-R intervals (RMSSD) (p = 0.01), SDNN (p = 0.02) and HF (p < 0.01) concerning CHF.

Conclusion

We were able to demonstrate the positive impact of physical activity on HRV, especially in patients with CHF. Cardiac rehabilitation exercise programs need to be individualized to identify the most beneficial method of training for improving the prognosis of patients with CVD.
Research and application of bag filter system for railway ballast bed coal suction vehicles: An optimization and application study
Authors: Lu Ke , Guo Shengjun , Zhao Zhongtai
Published: April 2024

The current bag filter system used by railway ballast bed coal suction vehicles for cleaning coal dust from railway tunnels has low operational efficiency and generates significant volumes of dust. This paper describes a simulation test unit designed to enhance the dust removal performance in railway tunnels. The flow field inside the simulation test unit is investigated under different operating conditions through numerical simulations, and the variations in air volume and working resistance, total dust collection efficiency, and optimal operating parameters of a pulse cleaning system are identified through a series of experiments. The numerical results show that the pulse cleaning system does not significantly affect the uniformity of the flow field distribution at the bottom of the filter cartridge during the process of operation. The experimental research indicates that the simulation test unit satisfies the design requirements, achieving an average total dust removal efficiency of 99.93%. A field application shows that the total dust mass concentration at the operator position can be reduced from 335.8 mg∙m−3 to 4.2 mg∙m−3, effectively improving the operating environment within the tunnel.