bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of NECTIN1 as a novel restriction factor for flavivirus infection
Authors: Qi Shuhui , Sun Chao , Wang Jing , Wo Lijing , Li Yongfeng , Wang Chaonan , Zhang Ying , Bian Haiqiao , Guo Yongqi , Gao Ming , Wang Menghang , Tang Yandong , Zhu Yuanmao , Xue Fei , Pang Quanhai , Jiang Zhigang , Yin Xin
Published: November 2024

Nectin cell adhesion molecule 1 (NECTIN1) is a cell adhesion molecule that belongs to the immunoglobulin superfamily. It has been considered the most ubiquitous receptor for herpesviruses. However, in the context of flavivirus infection, its role was previously unknown. In this study, we described an arrayed siRNA screen mainly targeting Ig-like proteins that showed NECTIN1-restricted bovine viral diarrhea virus (BVDV) infection. We demonstrated that the depletion of NECTIN1 could significantly enhance the infection of both biotypes and multiple genotypes of BVDV, including BVDV-1a, -1b, -1c, -1p, -1m, -1v, and -2a. Notably, the IgV of NECTIN1 has emerged as the key domain restricting BVDV infection. Moreover, NECTIN1 inhibited BVDV attachment without exerting a significant influence on BVDV translation or transcription. Furthermore, we demonstrated that both NECTIN1 and CD46 could bind to BVDV E2, while the binding affinity of NECTIN1 for BVDV E2 was greater than that for CD46. We further identified that the BVDV E2 domain DD was a key domain of BVDV interacting with NECTIN1. In addition, we showed that NECTIN1 inhibited infections by classical swine fever virus (CSFV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV), which belong to the
Flaviviridae
family, but had limited effects on bluetongue virus (BTV), vesicular stomatitis virus (VSV), Akabane virus (AKAV), and Sindbis virus (SINV). Overall, our study has important implications for understanding the entry of BVDV and revealed a novel role for NECTIN1 as a restriction factor that inhibits flavivirus infection.

IMPORTANCE

NECTIN1, also known as CD111 or PVRL1, has been recognized as the primary receptor for several alpha herpesviruses, including herpes simplex virus (HSV), pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1). However, our study revealed a novel role for NECTIN1 in the virus life cycle by influencing BVDV infection. Contrary to its role as a receptor for alpha herpesviruses, NECTIN1 acts as a restriction factor for BVDV by inhibiting viral attachment via competition with CD46 for binding to the domain DD of BVDV E2. We further revealed that the replication of members of the
Flaviviridae
family was inhibited by NECTIN1, while the replication of other RNA viruses did not significantly differ. Our results demonstrate that NECTIN1 is a novel factor restricting
Flaviviridae
family virus replication and highlight the complexity of virus-host interactions and the multifaceted nature of host factors involved in viral infection.
New insights on an old friend: AroA linked to iron-dependent outer membrane stability
Authors: Chin Priscilla , Anderson Christopher J.
Published: November 2024

Salmonella
is a common causative agent of infectious intestinal and systemic disease and has been extensively studied for several decades. Yet, much of
Salmonella
pathogenicity remains a mystery due in part to the highly complex virulence and adaptation strategies at the pathogen’s disposal. One of the more influential tools within the field, an attenuated
aroA-
deficient
Salmonella
strain, has been used for many years to probe the host immune response that would otherwise be impossible with a fully virulent strain. Now, new work by Rooke et al. (J. L. Rooke, E. C. A. Goodall, K. Pullela, R. Da Costa, et al., mBio 15:e03319-23, 2024,
https://doi.org/10.1128/mbio.03319-23
) utilizes in-depth transposon-directed insertion-site sequencing to elucidate the contribution of genes to
Salmonella
fitness within isogenic wild-type and
aroA
-deficient strains. Specifically, Rooke et al. demonstrate that the deletion of the
aroA
gene leads to iron-dependent membrane instability, raising several exciting new ideas surrounding
Salmonella
biology and therapeutic strategies.
A rapid and simple clonality assay for bovine leukemia virus-infected cells by amplified fragment length polymorphism (AFLP) analysis
Authors: Kobayashi Tomoko , Makimoto Sakurako , Ohnuki Nagaki , Hossain Md Belal , Jahan M. Ishrat , Matsuo Misaki , Imakawa Kazuhiko , Satou Yorifumi
Published: November 2024

Enzootic bovine leukosis (EBL), although eradicated in some European countries, is still the most common neoplastic disease of cattle, caused by the bovine leukemia virus (BLV). During the progression of EBL, BLV-infected cells clonally expand, and some of which result in tumor onset. The clonality of BLV-infected cells is generally evaluated with NGS or Sanger sequencing. Although these methods clearly distinguish EBL from non-EBL cases, the procedures are complex and not practical for routine veterinary diagnosis. In this study, we developed an amplified fragment length polymorphism (AFLP) analysis for BLV clonality assay (BLV-AFLP). This analysis uses restriction enzyme digestion to amplify the chimeric regions of BLV 3’ linear transcribed region (LTR) and host genome through conventional polymerase chain reaction (PCR) and visualizes the results by gel-electrophoresis. The method was established using cattle samples representing different stages of the disease: BLV-uninfected, non-EBL, and EBL cattle. Non-EBL cattle showed smeared bands, indicating polyclonal proliferation, while EBL cattle showed distinct bands, indicating clonal expansion. The results of BLV-AFLP correlated well with those of previously reported methods, suggesting its efficacy in detecting clonal proliferation. The validation using blood samples of non-EBL cattle and tumor samples of EBL cattle confirmed that BLV-AFLP could effectively identify clonal proliferation in EBL samples. Moreover, the emergence of dominant clones in the tumor at later stages was successfully detected before EBL onset in some cattle, highlighting its sensitivity and potential for early detection. Overall, BLV-AFLP is suitable for practical use in the field, improving BLV management strategies and minimizing economic losses.

IMPORTANCE

Enzootic bovine leukosis (EBL) is routinely diagnosed based on external manifestations at the farm, such as the presence of tumors and/or general lymph node enlargement. However, due to the nonspecific clinical manifestations of EBL, over half of EBL cases are unrecognized at the farm, with most cases being diagnosed during postmortem inspection at the slaughterhouse. Early detection and monitoring of clonal expansion are necessary for managing EBL and reducing economic losses. In this study, we developed BLV-AFLP that represents a significant advancement in the diagnosis of EBL in cattle. This method can rapidly assess the clonal proliferation of BLV-infected cells, crucial for distinguishing between asymptomatic and EBL cattle. Additionally, tracking clonal dynamics offers insights into the disease’s progression, potentially providing strategies for avoiding economic losses. Overall, as BLV-AFLP is a simple and rapid test for detecting EBL, it is feasible and efficient for routine veterinary practice.
Efficacy of ceftazidime-avibactam with or without polymyxin for carbapenem-resistant
Klebsiella pneumoniae
infections after initial treatment with polymyxin
Authors: Lu Jingli , Ma Yani , Cao Zhe , Zhu Baoling , Fan Luna , Meng Haiyang
Published: November 2024

Although polymyxins are a suboptimal option for difficult-to-treat resistant infections, they are still preferred as the first-line treatment, especially in low- and middle-income countries. This study assesses the efficacy of ceftazidime-avibactam (CAZ-AVI) following polymyxin B failure in patients with carbapenem-resistant
Klebsiella pneumoniae
(CRKP) infections. We retrospectively reviewed cases of infections caused by CRKP in adults who received CAZ-AVI as salvage therapy. Clinical features and outcomes were described, and a logistic regression model was used to assess the risk factors associated with in-hospital crude mortality. One hundred and six patients were included in this study. The median age was 56 years. The most common infectious sites were lung. The patients received CAZ-AVI as salvage therapy for a median duration of 9 days following initial treatment with polymyxin B (median, 12.5 days). Also, 91 (85.8%) patients received CAZ-AVI combination therapy, and 34 (32.1%) patients received CAZ-AVI in combination with polymyxin B. The rate of in-hospital crude mortality was 25.5% (27/106), with the highest rate observed in patients treated with regimens containing polymyxin B (41.2%; 14/34). Therapeutic response was observed in 81 (76.4%) patients, with microbiological eradication achieved in 77.1% (74/96) of cases. Multivariable analysis identified that the length of intensive care unit stays, the sequential organ failure assessment (SOFA) score at CAZ-AVI withdrawal, and regimens containing polymyxin B were independently associated with in-hospital mortality, whereas the duration of CAZ-AVI treatment was independently associated with survival. CAZ-AVI salvage therapy demonstrated improved survival outcomes in patients who experienced failure with polymyxin B therapy.

IMPORTANCE

For patients with carbapenem-resistant
Klebsiella pneumoniae
(CRKP) infections, published experience with salvage therapy is limited after the failure of polymyxin-based initial therapy. Here, we found that ceftazidime-avibactam salvage therapy for patients with CRKP infections offers benefit in mortality.
Real-time, in situ viscosity mapping of active lava
Authors: Harris M. A. , Chevrel M. O. , Parsons J. T. , Latchimy T. , Thordarson T. , Höskuldsson A. , Moreland W. M. , Payet–Clerc M. , Kolzenburg S.
Published: November 2024

Viscosity is a fundamental physical property that controls lava flow dynamics, runout distance, and velocity, which are critical factors in assessing and mitigating risks associated with effusive eruptions. Natural lava viscosity is driven by a dynamic interplay among melt, crystals, and bubbles in response to the emplacement conditions. These conditions are challenging to replicate in laboratory experiments, yet this remains the most common method for quantifying lava rheology. Few in situ viscosity measurements exist, but none of those constrains the spatial evolution of viscosity along an entire active lava flow field. Here, we present the first real-time, in situ viscosity map of active lava as measured in the field at Litli-Hrútur, Iceland. We precisely measured a lava viscosity increase of over two orders of magnitude, associated with a temperature decrease, crystallinity increase, and vesicularity decrease from near-vent to distal locations, crossing the pāhoehoe–‘a‘ā transition. Our data expand the limited database of three-phase lava viscosity, which is crucial for improvements and validation of the current numerical, experimental, and petrological approaches used to estimate lava viscosity. Further, this study showcases that field viscometry provides a rapid, accurate, and precise assessment of lava viscosity that can be implemented in eruptive response modeling of lava transport.
Effect of Partial Knockout of the Plastid Starch Phosphorylase Gene NtPHO1-L1 on the Metabolism of Carbohydrates and Carotenoids in Nicotiana tabacum L. Leaves
Authors: Nezhdanova A. V. , Kulakova A. V. , Slugina M. A. , Kamionskaya A. M. , Kochieva E. Z. , Shchennikova A. V.
Published: November 2024

Starch metabolism is regulated by a complex catalytic network, one of the key enzymes of which is the plastid starch phosphorylase PHO1. In this study, using the CRISPR-Cas9 system, we obtained tobacco (Nicotiana tabacum L.) plants with a partial knockout of the NtPHO1-L1 gene due to deletion variants of the catalytic domain of the NtPHO1-L1 protein, leading to the formation of nonfunctional forms of the enzyme. The edited lines differed from wild-type plants by increased starch accumulation and decreased content of sugars, chlorophylls, and carotenoids in the leaves. It was shown that, compared to the control, the edited plants were characterized by differential expression of starch (NtPHO1-L1, NtGWD, NtBAM1, NtBAM9, NtAI) and carotenoid (NtPSY2, NtPDS, NtZDS, NtCRTISO, NtVDE) metabolism genes, as well as genes encoding MADS-domain transcription factors (NtFUL1, NtSEP1, NtSEP2, NtSEP3), which are presumably involved in the regulation of transcription of the studied metabolic genes. These data suggest that partial knockout of NtPHO1-L1 alters the functional activity of tobacco starch phosphorylase. This, in turn, may influence the coordinated activity of starch catabolism enzymes, as well as chlorophyll and carotenoid synthesis enzymes, possibly through differential expression of MADS-box genes. The results highlight the critical regulatory role of plastid starch phosphorylase in transient starch metabolism and in stimulating plant photosynthesis.
Data for whom?Experiences and perceptions of a perinatal eRegistry in two hospitals in Mtwara region, Tanzania
Authors: Molenaar Jil , Kikula Amani , Kionga Yusufu , Berenge Hassan Tearish , Benova Lenka , van Olmen Josefien , Hanson Claudia , Abeid Muzdalifat , Pembe Andrea Barnabas
Published: November 2024

Introduction

Digital data systems have the potential to improve data quality and provide individual-level information to understand gaps in the quality of care. This study explored experiences and perceptions of a perinatal eRegistry in two hospitals in Mtwara region, Tanzania. Drawing from realist evaluation and systems thinking, we go beyond a descriptive account of stakeholders’ experiences and provide insight into key structural drivers and underlying social paradigms.

Methods

We carried out 6 weeks of focused ethnographic observations at the labour wards of the two hospitals and 29 semi-structured qualitative interviews with labour ward staff, as well as with administrative and managerial stakeholders at hospital, district and regional levels. Multi-stage reflexive thematic data analysis was carried out.

Results

We provide an in-depth account of the day-to-day functioning of the eRegistry in the two hospitals, including both aspects of positive change and key challenges with its integration into routine documentation duties. Experiences with and perceptions of the eRegistry were inextricably linked to broader systemic constraints relating to staffing, workload and infrastructure. A key underlying theme shaping the way people engaged with the eRegistry was the notion of data ownership: the presence or absence of a feeling of being responsible, involved and in control of data.

Conclusion

Some of the key systemic challenges in recording accurate, timely information about women and their babies are not solved by digital tools. Our findings also underline that when healthcare workers feel that data are not primarily for them, they document only for reporting purposes. The eRegistry increased a sense of data ownership among the nurse-midwives directly involved with data entry, but the potential for promoting and supporting data use feedback loops for improvement in care provision remained largely untapped. Our findings highlight the importance of local relevance and ownership in digitisation of routine health information systems.
Effectiveness of different pharmacological or non-pharmacological interventions on preventing coughing during extubation: a protocol for a systematic review and network meta-analysis
Authors: Gong Zhichao , Wu Yixuan , Yang Di , Li Qian , Yang Longjun , Yang Lei
Published: November 2024

Introduction

Coughing during extubation can lead to several postoperative complications, including surgical site bleeding, intracranial hypertension and high intraocular pressure. Currently, various pharmacological and non-pharmacological interventions are employed in clinical practice to reduce coughing during extubation. However, it is unclear which of these interventions has the best preventive effect and the fewest adverse events. Therefore, we plan to conduct a systematic review and network meta-analysis to compare the effects of all interventions.

Methods and analysis

We will search MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, CNKI and Wanfang databases, as well as reference lists from previously published papers, from the date of their inception to April 2024. We will only include randomised controlled trials, regardless of publication in any language. The primary outcome is the incidence of cough during extubation, using the modified Minogue scales. The secondary outcomes are as follows: (1) the incidence of severe coughing (grade 4); (2) the incidence of other types of postoperative airway complications, such as laryngospasm, apnoea, hypoxaemia and sore throat, which will be evaluated within 24 hours after surgery; (3) the side effects related to the interventions, such as bradycardia (heart rate less than 60 beats per minute), hypotension or allergic reactions, which will be evaluated within 24 hours from the start of the drug to the postoperative period and (4) the time from the end of the surgery to the extubation of the endotracheal tube. The articles meeting the criteria will be independently evaluated by two researchers based on the established screening criteria. The data will then be extracted. Bias will be assessed for all included studies using the Cochrane Risk of Bias Risk Assessment Tool Version 2. We will use the Netmeta package of the R software with a random-effects model to make direct and indirect comparisons through the frequency framework. We will assess the quality of evidence using Confidence in Network Meta-Analysis.

Ethics and dissemination

Ethical approval is not required for this protocol, as we will only pool published data. We plan to submit our manuscript for publication in a peer-reviewed academic journal.

PROSPERO registration number

CRD42023401609.
Magnitude of late presentation for induced abortion care services and the associated factors among reproductive-age women at selected hospitals in the South Gondar district of Northwest Ethiopia in 2023: a multicentred, cross-sectional study
Authors: Dagnaw Eyaya Habtie , Berta Marta , Cherkos Endehsaw Admasu , Mequannent Endalamaw Wondie
Published: November 2024

Objective

The objective of the study was to determine the magnitude of and the factors associated with late presentation for induced abortion care services at hospitals in the South Gondar district of Ethiopia.

Design

This study employed an institution-based, cross-sectional design.

Setting

The study was conducted at five hospitals in the South Gondar district of Ethiopia.

Participants

A total of 381 women recruited through systematic random sampling techniques from October 2022 to February 2023 participated in the study. All women presenting for safe abortion care services at selected hospitals during the data collection period were included, whereas induced abortion care service due to the pregnancy being a high risk to maternal health or at high risk for fetal anomaly were excluded from the study. Data were collected at the abortion clinic at the time of presentation through face-to-face interviews using a pretested and structured questionnaire.

Outcome measures

The magnitude of and the factors associated with late presentation for induced abortion care service were assessed in the study.

Statistical analysis

The collected data were entered and coded using EpiData V.4.6, and SPSS V.25 was used for analysis. Binary logistic regression analyses were undertaken to identify the factors associated with the outcome variable. The level of significance was declared at a p value of <0.05.

Results

The magnitude of late presentation for induced abortion care service was 21.5% (95% CI 17.7, 25.7). Being a rural resident (adjusted OR (AOR) = 1.934; 95% CI 1.010, 3.703), history of use of contraceptives (AOR=0.462; 95% CI 0.227, 0.938), having irregular menstrual cycles (AOR=5.132; 95% CI 2.648, 9.944), delayed decision for termination (AOR=8.196; 95% CI 3.996, 16.808) and pregnancy resulting from incest (AOR=2.549; 95% CI 1.286, 5.052) were factors significantly associated with late presentation for induced abortion care.

Conclusion

Increased awareness and education in rural communities related to late presentations for induced abortion and the associated complications may facilitate timely decision-making in the context of induced abortion, resulting in reduced morbidity and mortality.
Allostatic load modelling, lifestyle and cardiological risk factor: evidence for integrating patient profiling in the optimisation of pharmacological therapies during follow-ups in hospital setting – PLAY-UP cohort study protocol
Authors: Di Giacomo Dina , Sciarra Luigi , Fusco Liuba , Robles Antonio Gianluca , Pernat Andrej , Romano Silvio
Published: November 2024

Introduction

The allostatic load (AL) is a framework for conceptualising the physiological multisystemic impact of prolonged exposure to stress and its related side effects on mental health.

Stress due to AL can influence the development and outcomes of cardiovascular diseases. AL increases the risk of coronary and peripherical artery diseases. AL emerges from the detection of emotional dimensions related to the disease, low psychosocial functioning and high rates of psychopathological signs in patients with hypertension or coronary heart disease.

Method and analysis

The primary endpoint of the PLAY-UP protocol is the implementation of a multidimensional model underlying the clinical treatment of patients with cardiovascular disease through the integration of medical and psychological clinical variables.

PLAY-UP is a cohort study that will last for 24 months. 200 participants will be recruited and divided into three groups: early disease, midterm disease and long disease. All patients will undergo a clinical evaluation based on the detection of biological, medical and psychological indicators and variables. The evaluation battery will comprise three types of measurements: medical, psychological and pharmacological treatments. Clinical and psychological measurements will be processed in an integrated manner through the combination of all variables examined, elaborating the Allostatic Load Index from a longitudinal time perspective. The Allostatic Load Index will be calculated by measuring the z-score.

Ethics and dissemination

Ethical Committee Approval was obtained from CEtRA Abruzzo Region (IT) (ID 0461499/23). The results of the present project will be published in peer-reviewed journals, disseminated electronically and in print, and presented as abstracts and/or personal communications during national and international conferences.
Impact of Ramadan fasting on kidney function and related outcomes in chronic kidney disease and kidney transplant recipients: a systematic review and meta-analysis
Authors: Bello Aminu Kasarawa , Lloyd Anita , Osman Mohamed Abdullahi , Kurzawa Julia , Chambers Thane , Habib Syed , Olah Michelle E , Habeeb Zahraa , Qarni Uwais , Shojai Soroush , Pauly Robert Peter
Published: November 2024

Objectives

Ramadan fasting is an Islamic religious practice involving abstinence from food and drink from dawn to sunset. Its consequences on kidney-relevant outcomes in patients with chronic kidney disease (CKD) and kidney transplant recipients remain unclear.

Design

Systematic review and meta-analysis.

Data sources

MEDLINE, Embase, Global Health, CINAHL (EBSCOhost), Scopus, Web of Science and Google Scholar were searched up to 18 September 2023.

Eligibility criteria

We included observational studies among non-dialysis CKD and kidney transplant recipients who fasted during Ramadan and examined changes in kidney function.

Data extraction and synthesis

Standardised methods were used by two independent reviewers to screen, select and extract data. Outcomes included changes in serum creatinine (SCr), estimated glomerular filtration rate (eGFR), proteinuria, blood pressure, electrolytes and adverse events—all pre- and post-Ramadan. Results were pooled using random effects modelling.

Results

We included 32 observational studies with a total of 2592 participants. 21 studies reported on participants with CKD and 11 studies reported on kidney transplant recipients (studies variably including non-fasting control arms). Meta-analysis of 25 studies revealed that Ramadan fasting was not associated with changes to SCr for the following groups according to study design: CKDwitha non-fasting arm (mean difference (MD)=0.82 µmol/L; 95% CI −7.22, 8.86; I2=38%); transplantwitha non-fasting arm (MD=−0.17 µmol/L; 95% CI −2.50, 2.15; I2=0%) and CKDwithouta non-fasting arm (post–pre MD=13.84 µmol/L; 95% CI −3.78, 31.47; I2=88%). For transplant studieswithouta non-fasting arm, lower SCr was associated with the post-Ramadan period (post–pre MD=−5.40 µmol/L; 95% CI –10.78, –0.02; I2=0%). In the 18 studies that reported on eGFR, fasting during Ramadan was not associated with an effect on eGFR for any of the groups.

Conclusion

We report inconsistent effects of Ramadan fasting on kidney function in CKD or kidney transplantation. Results should be interpreted with caution due to the significant limitations of the underlying studies.
Knowledge of stroke risk factors and prevention among hypertensive patients on follow-up at Addis Ababa University Tertiary Hospital, Addis Ababa, Ethiopia: a cross-sectional study
Authors: Tuli Wagari , Teshome Eyuel , Jiru Tlahun
Published: November 2024

Objective

This study was conducted to assess knowledge of stroke risk factors and prevention among hypertensive patients on follow-up at Addis Ababa University Tertiary Hospital, Addis Ababa, Ethiopia.

Design

Cross-sectional study design.

Setting

This study was conducted at Addis Ababa University Tertiary Hospital in Addis Ababa, Ethiopia.

Participants

The sample size was determined using the single population proportion calculation. A list of all patients with hypertension on follow-up was framed from the appointment book of the cardiovascular clinic. Then, 316 participants were recruited by simple random sampling procedure from 18 April 2022 to 19 May 2022. The study included all patients with hypertension >18 years of age who were on follow-up during the data-collecting period. In contrast, patients with memory loss or cognitive impairment and who are unable to communicate were excluded from the study.

Result

With a response rate of 96.8%, 306 respondents in total were questioned. The average age of the participants was 53.6 years (SD±13.4). More than half of participants (52.9%) were female. The average score for understanding stroke risk factors and prevention is 44.1% and 49.7%, respectively. Knowledge of stroke risk factors was substantially correlated with residency and educational level, while knowledge of stroke prevention was significantly associated with sex, income and educational level.

Conclusion

This study indicates that patients with hypertension who participated in the study had poor knowledge of stroke risk factors and prevention. The mean score of knowledge on risk factors and prevention strategies of stroke is 44.1% and 49.7%, respectively, and needs improvement.
Hearing impairment following surgically repaired congenital heart disease in children: a prospective study
Authors: Sakjirapapong Kanittha , Vijarnsorn Chodchanok , Thongyai Kanthong , Thirakulnanchai Yarlanphol , Chanthong Prakul , Chungsomprasong Paweena , Kanjanauthai Supaluck , Thammasate Ploy , Pacharapakornpong Thita , Boonchom Eakkarat , Durongpisitkul Kritvikrom , Soongswang Jarupim , Atipas Suvajana , Tocharoenchok Teerapong , Nitiyarom Ekarat , Tantiwongkosri Kriangkrai , Subtaweesin Thaworn
Published: November 2024

Objectives

To determine the prevalence of sensorineural hearing loss (SNHL) in children who underwent congenital cardiac surgery (CCS) by using a pre- and postoperative hearing test, a conventional audiometry, an extended high-frequency audiometry (HFA) or auditory steady-state response (ASSR), and distortion-product otoacoustic emissions (DPOAE).

Study design

This prospective study enrolled children with CCS in Siriraj Hospital, Thailand, between 2019 and 2023. Conventional audiometry including HFA or ASSR and DPOAE were performed pre- and postoperatively. The patients with bilateral abnormal hearing loss or an incomplete examination were excluded. Collected data included: demographics, cardiac surgery and ototoxic medication. Prevalence of SNHL by conventional audiometry and subclinical hearing impairment by HFA or DPOAE were ascertained, and risks were analysed.

Results

Ninety-eight patients were eligible for the study. The median age (IQR) was 5.3 (1.5–9.6) years. Fifteen patients (15.3%) had univentricular hearts. The preoperative audiologic test was performed 1 day prior to the CCS. The postoperative test was performed at a median of 4.4 (IQR: 2.7–8.0) months postoperatively. Preoperative unilateral hearing impairments were reported in 17 patients (17.3%). Postoperatively, four patients (4.1%) showed significantly abnormal audiogram (> 25 dB) or 15 dB shift at 250–8000 Hz consistent to a new SNHL. Subclinical hearing impairment by HFA was affected in 10 patients (10.2%). Thirty-three patients (33.6%) had abnormal DPOAE exclusively. Therefore, new SNHL, including subclinical hearing loss, revealed a prevalence of ototoxicity up to 47.9%. Age <1 year at surgery was the independent risk of postoperative SNHL (adjusted OR 18.5, 95% CI 1.2 to 293.8, p=0.04).

Conclusion

Routine post-CCS audiological surveillance especially CCS in infancy is recommended for early recognition and timely management based on the 43.8% subclinical and the 4.1% SNHL that was found in this study.

Trial registration number

TCTR20200421001.
Firefighters’ occupational exposure to air pollution: impact on COPD and asthma—study protocol
Authors: Barbosa Joana V , Branco Pedro T B S , Alvim-Ferraz Maria C M , Martins Fernando G , Sousa Sofia I V
Published: November 2024

Introduction

Firefighting continues to be among the most hazardous yet least studied occupations in terms of the impact of exposure to occupational disease. In particular, firefighters are at increased risk of adverse health effects due to exposure to significant levels of potentially harmful substances, namely carbon monoxide, particulate matter and formaldehyde, during their professional duties.

This paper reports an epidemiologic study aiming to reduce the gaps in assessing the long-term effects of air pollution exposure to forest fires’ combat on firefighters, namely regarding chronic obstructive pulmonary Disease (COPD) and asthma.

Methods and analysis

Based on the implementation in an area with high forest fires (in Portugal), the study will analyse firefighters’ exposure to fire emissions by measuring air pollutants with personal exposure monitors during forest fire combat through a retrospective cohort study (exposed vs non-exposed). Moreover, based on answers to validated questionnaires and medical examinations to be performed by medical doctors, the study will assess the prevalence, incidence and exacerbation of COPD and asthma in firefighters, thus considering both short-term and long-term effects. Based on the results above referred, the study aims to evaluate the impact of exposure and inhalation dose of air pollutants during forest fires’ combat on the development of the above-referred chronic diseases. The approximate number of participants in the study will never be less than 186, guaranteeing 80% of study power (significant at a 5% level).

Ethics and dissemination

The study has been approved by the Ethical Committee of Centro Hospitalar Universitário São João. The results will be published in international and national journals and conferences, allowing the results obtained to be communicated to the scientific community. Moreover, up-to-date data will be disseminated to stakeholders and decision-makers to help them decide on triggering official control measures.
Divergent lineage trajectories and genetic landscapes in human gastric intestinal metaplasia organoids associated with early neoplastic progression
Authors: Yue Sarah S K , Tong Yin , Siu Hoi Cheong , Ho Siu Lun , Law Simon Y K , Tsui Wai Yin , Chan Dessy , Huang Yuanhua , Chan Annie S Y , Yun Shui Wa , Hui Ho Sang , Choi Jee-Eun , Hsu Matthew S S , Lai Frank P L , Chan April S , Yuen Siu Tsan , Clevers Hans , Leung Suet Yi , Yan Helen H N
Published: November 2024

Background

Gastric intestinal metaplasia (IM) is a precancerous stage spanning a morphological spectrum that is poorly represented by human cell line models.

Objective

We aim to establish and characterise human IM cell models to better understand IM progression along the cancer spectrum.

Design

A large human gastric IM organoid (IMO) cohort (n=28), their clonal derivatives and normal gastric organoids (n=42) for comparison were established. Comprehensive multi-omics profiling and functional characterisation were performed.

Results

Single-cell transcriptomes revealed IMO cells spanning a spectrum from hybrid gastric/intestinal to advanced intestinal differentiation. Their lineage trajectories connected different cycling and quiescent stem and progenitors, highlighting differences in gastric to IM transition and the potential origin of IM fromSTMN1cycling isthmus stem cells. Hybrid IMOs showed impaired differentiation potential, high lineage plasticity beyond gastric or intestinal fates and reactivation of a fetal gene programme.

Cell populations in gastric IM and cancer tissues were highly similar to those derived from IMOs and exhibited a fetal signature. Genomically, IMOs showed elevated mutation burden, frequent chromosome 20 gain and epigenetic deregulation of many intestinal and gastric genes. Functionally, IMOs were FGF10 independent and showed downregulated FGFR2. Several IMOs exhibited a cell-matrix adhesion independent subpopulation that displayed chromosome 20 gain but lacked key cancer driver mutations, potentially representing the earliest neoplastic precursor of IM-induced gastric cancer.

Conclusions

Overall, our IMO biobank captured the heterogeneous nature of IM, revealing mechanistic insights on IM pathogenesis and progression, offering an ideal platform for studying early gastric neoplastic transformation and chemoprevention.
IL-18R supported CAR T cells targeting oncofetal tenascin C for the immunotherapy of pediatric sarcoma and brain tumors
Authors: Wickman Elizabeth , Lange Shannon , Wagner Jessica , Ibanez Jorge , Tian Liqing , Lu Meifen , Sheppard Heather , Chiang Jason , Koo Selene C , Vogel Peter , Langfitt Deanna , Perry S Scott , Shanmugam Raghuvaran , Bell Matthew , Shaw Timothy I , Krenciute Giedre , Zhang Jinghui , Gottschalk Stephen
Published: November 2024

Background

Oncofetal splice variants of extracellular matrix (ECM) proteins present a unique group of target antigens for the immunotherapy of pediatric cancers. However, limited data is available if these splice variants can be targeted with T cells expressing chimeric antigen receptors (CARs).

Methods

To determine the expression of the oncofetal version of tenascin C (TNC) encoding the C domain (C.TNC) in pediatric brain and solid tumors, we used quantitative reverse transcription PCR and immunohistochemistry. Genetically modified T cells were generated from human peripheral blood mononuclear cells and evaluated in vitro and in vivo.

Results

We demonstrate that C.TNC is expressed on a protein level in pediatric tumors, including diffuse intrinsic pontine glioma, osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma. We generate C.TNC-CAR T cells and establish that these recognize and kill C.TNC-positive tumor cells. However, their antitumor activity in vivo is limited. To improve the effector function of C.TNC-CAR T cells, we design a leucine zipper-based chimeric cytokine receptor that activates interleukin-18 signaling pathways (Zip18R). Expression of Zip18R in C.TNC-CAR T cells improves their ability to secrete cytokines and expand in repeat stimulation assays. C.TNC-CAR.Zip18R T cells also have significantly greater antitumor activity in vivo compared with unmodified C.TNC-CAR T cells.

Conclusions

Our study identifies the C domain of the ECM protein TNC as a promising CAR T-cell therapy for pediatric solid tumors and brain tumors. While we focus here on pediatric cancer, our work has relevance to a broad range of adult cancers that express C.TNC.
Risk of fall with device-based advanced treatments in Parkinson’s disease: a systematic review and network meta-analysis
Authors: Rajalingam Rajasumi , Sorrento Gianluca , Fasano Alfonso
Published: November 2024

Background

Deep brain stimulation (DBS) and infusion therapies are effective treatments for the motor complications of Parkinson’s disease (PD), but less established is their role in fall prevention. This systematic review and network meta-analysis (NMA) aimed to evaluate the risk of falls associated with advanced therapies in PD.

Methods

Following PRISMA-NMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses for Network Meta-analyses) guidelines, we searched PubMed, Medline, Embase and CINAHL up to 20 March 2024. Eligibility criteria based on PICOS (Population Intervention Control Outcome Study design) framework were used for DBS of the subthalamic nucleus (STN) or globus pallidus pars interna (GPi), or infusion therapies, compared with best medical treatment (BMT) or sham stimulation. Pairwise meta-analysis was conducted using RevMan V.5.4, and NMA using the netmeta package in R software.

Results

Fourteen studies were included. A higher number of falls were observed in the DBS group compared with BMT, although the difference was not significant. Sensitivity analysis excluding a heterogeneity-contributing study showed a significantly higher fall risk in the DBS group (Risk Ratio (RR)=2.74, 95% CI 1.60, 4.67, p=0.0002). Subgroup analyses indicated that levodopa-carbidopa intestinal gel tended towards increased fall risk, while continuous subcutaneous infusion of (fos)levodopa (CSCI) significantly decreased risk with high certainty of evidence. NMA showed CSCI as the most effective in reducing falls, while STN DBS was associated with the highest risk.

Conclusions

DBS, especially targeting the STN, may increase fall risk compared with other advanced non-DBS procedures. While LCIG might not alter fall risk, preliminary evidence suggests that CSCI positively affects fall prevention.

PROSPERO registration number

CRD42023420637.
Overspinning problem in Kerr black holes: second order corrections and self-energy
Authors: Vásquez Iván R.
Published: November 2024

We consider gedanken experiments to destroy Kerr black holes, by means of absorbing matter with sufficient energy and angular momentum. It is shown that extremal and near-extremal Kerr black holes cannot be destroyed in a process that includes a second order contribution to its final mass, and matter sources satisfy the null energy condition. Such contribution is calculated using hypersurface integration on the event horizon, and it traces similarities with terms related to matter-black hole interactions and a rotational self-energy lower bound suggested in previous works.
COMPLEX NETWORK CLASSIFICATION USING DENG ENTROPY AND BIDIRECTIONAL LONG SHORT-TERM MEMORY
Authors: SOTO-CAMACHO MARÍA-DEL-CARMEN , NAGY MARCELL , MOLONTAY ROLAND , RAMIREZ-ARELLANO ALDO
Published: November 2024

Network classification plays a crucial role in various domains like social network analysis and bioinformatics. While Graph Neural Networks (GNNs) have achieved significant success, they struggle with the problem of over-smoothing and capturing global information. Additionally, GNNs require a large amount of data, hindering performance on small datasets. To address these limitations, we propose a novel approach utilizing Deng’s entropy, capturing network topology and node/edge information. This entropy is calculated at multiple scales, resulting in an entropy sequence that incorporates both local and global features. We embed the networks by combining the entropy sequences for edges and nodes into a matrix, which then are fed into a bidirectional long short-term memory network to perform network classification. Our method outperforms GNNs in the bioinformatics, social, and molecule domains, achieving superior classification power on nine out of eleven benchmark datasets. Further experiments with both real-world and synthetic datasets highlight its exceptional performance, achieving an accuracy of 97.24% on real-world complex networks and 100% on synthetic complex networks. Additionally, our approach proves effective on datasets with a small number of networks and unbalanced classes and excels at distinguishing between synthetic and real-world networks.
Reconstructions of f(𝒫) and f(𝒬) gravity models from (m,n)-type Barrow Holographic Dark Energy: Analysis and Observational Constraints
Authors: Mukhopadhyay Tamal , Chakraborty Banadipa , Kotal Anamika , Debnath Ujjal
Published: November 2024

In this research, we have reconstructed the extended [Formula: see text] cubic gravity and symmetric [Formula: see text] teleparallel gravity from the [Formula: see text]-type Barrow Holographic Dark Energy (BHDE) model. We have derived the unknown functions [Formula: see text] and [Formula: see text] in terms of [Formula: see text] and [Formula: see text], assuming a flat, homogeneous, and isotropic universe. To constrain our model parameters, we employed cosmic chronometer datasets and Baryon Acoustic Oscillation (BAO) datasets, utilizing Markov Chain Monte Carlo (MCMC) method. We analyzed the behavior and stability of each model throughout the universe’s evolution by studying crucial parameters such as the deceleration parameter, equation of state (EoS) parameter [Formula: see text], density parameter [Formula: see text] and the square of the speed of sound [Formula: see text]. Additionally, we explored the cosmographic behavior by plotting the jerk parameter, snap parameter, and lerk parameter against the redshift. Furthermore, we examined the [Formula: see text] phase plane, the [Formula: see text], [Formula: see text] statefinder parameters, and the [Formula: see text] parameter offers profound revelations about the dynamics of the universe and the distinctive features of dark energy. Our analyses indicated that our model could produce a universe undergoing accelerated expansion with quintessence-type dark energy. These findings contribute to our understanding of the nature of dark energy and the evolution of the cosmos.
Exact solutions and their local structures of an inverse scattering integrable system with variable coefficients
Authors: Zhang Sheng , Qi Lin
Published: November 2024

An important manifestation of the integrability of nonlinear mathematical and physical models is their solvability through inverse scattering transform (IST). The problem to be investigated in this paper is a system of fifth-order nonlinear evolution equations (NLEEs) with variable coefficients related to time-varying spectral problems. The expected result is to derive the system of fifth-order NLEEs, obtain its exact solutions, verify its integrability in the sense IST solvability, and reveal some novel local structures of the obtained solutions. First, the system of fifth-order NLEEs is derived. Then, by combining the IST with a time-varying spectral parameter, the associated scattering data are determined for the reconstruction of potentials. Using the determined scattering data, exact solutions are ultimately obtained. Meanwhile, some local structures with new features are analyzed for two pairs of special solutions, including kink solitons, wide/narrow top bell solitons, and small-scale peaks in the time variable direction, as well as sine/cosine-like fluctuations in the spatial variable direction. This paper not only demonstrates that equipping the Ablowitz–Kaup–Newell–Segur (AKNS) problems with appropriate time-varying spectra can be used to derive some other inverse scattering integrable systems of NLEEs with variable coefficients, but also graphically illustrates the regulatory effect of time-varying spectral parameter on local solution structures.
Investigating dark energy and cosmic acceleration: A study using FRW and Tsallis entropy in Chern–Simons gravity
Authors: Ali Sarfraz , Sheikh Umber , Hasnain Muhammad , Awais Muhammad , Pincak Richard
Published: November 2024

This research delves into the study of the FRW spacetime within the framework of Chern–Simons modified gravity integrating the new Tsallis agegraphic dark energy model by examining the key cosmological parameters, including the density parameter, deceleration parameter, and equation of state. The Tsallis agegraphic dark energy model forecasts an Equation of State within the range of [Formula: see text] aligning well with the most recent observational data from Planck, WMAP, and BAO. The cosmic dynamics explored in this study reveal a transition from deceleration to acceleration, which is consistent with empirical observations. Density parameter graphs exhibit a shift from dark matter dominance to the prevalence of the Tsallis agegraphic model over specific redshift intervals. Furthermore, the interaction model predicts a density parameter within the range of [Formula: see text]. This comprehensive inquiry offers significant insights into the impact of the [Formula: see text] CDM model and quintessence on cosmic characteristics, underscoring the observed transition from a period of slowing expansion to accelerated expansion.
Design of Area-Efficient and Low-Power Magnetic Full Adder
Authors: Sreeja R. R. , Kamala J. , Sahaana K.
Published: November 2024

Complementary metal oxide semiconductor (CMOS) is an extensively used promising technology for developing integrated circuits, such as memory chips, microprocessors and microcontrollers with high noise immunity. However, deep scaling of CMOS technology ([Formula: see text] [Formula: see text]nm) suffers from various impediments at the device and architectural level, namely high leakage current, increased radiation sensitivity, more die area and dynamic power dissipation. To overcome these limitations of CMOS devices, logic-in-memory (LIM) structures have been developed with spin-based devices like Magnetic Tunnel Junctions (MTJs). MTJs are not affected by external particles and feature zero standby power. The MTJs in magnetic logic circuit and magnetic random-access memory (MRAM) applications are robust against radiation, high speed, low leakage power, nonvolatility and easily compatible with the back end. Existing magnetic full adder (MFA) techniques require augmented circuits for seamless operation. A major drawback in the existing MFA structure is the data loss due to single event upset (SEU) and poor sensitivity of pre-charge sense amplifiers (PCSAs) to input arrival timing. This paper proposes an MTJ-based nonvolatile magnetic full adder (NV-MFA) using 10T logic to address the above issues. The output buffer circuit is designed with a read-write parallel switching (RWPS) writing circuit based on spin orbit torque (SOT). The proposed circuit is more immune to the fault occurrence compared with the existing pass transistor and PCSA-based MFA logic. It leads to reduced power dissipation, die area and delay. Perpendicular anisotropy MTJ (CoFeB/MgO/CoFeB) model is chosen for the MTJ structure. It is suitable for efficient MRAM structure. The transient response is verified on Cadence virtuoso using 45[Formula: see text]nm gpdk CMOS technology. The simulation analysis shows the performance is enhanced with fault-free data output and improved reliability compared with previous MFAs.