bluuebunny/crossref_metadata_2025 huggingface dataset:
A Validated Assay to Quantify Osimertinib and Its Metabolites, AZ5104 and AZ7550, from Microsampled Dried Blood Spots and Plasma
Authors: Venkatesh Bharat , Yuile Alex , McKay Matthew J. , Narayanan Sathya , Wheeler Helen , Itchins Malinda , Pavlakis Nick , Clarke Stephen J. , Molloy Mark P.
Published: January 2024

Background:

Osimertinib is an oral small-molecule tyrosine kinase receptor inhibitor used to treat non–small cell lung cancer (NSCLC) with a sensitizing epidermal growth factor receptor mutation. Patients may experience drug toxicity and require dose deescalation. The study aimed to quantitate osimertinib and its 2 active metabolites, AZ5104 and AZ7550, in microsampled dried blood spots (DBS) collected from patients with NSCLC using a hemaPEN device and compare them with plasma drug levels.

Methods:

A 6-min ultrahigh-performance liquid chromatography–tandem mass spectrometry method was developed and validated using plasma and DBS. The accuracy, selectivity, matrix effect, recovery, and stability were assessed using bioanalytical validation criteria. The hematocrit effect was investigated in DBS. Drug levels were measured in 15 patients with NSCLC, and the Bland–Altman method was used to compare measurements between plasma and DBS.

Results:

The validated assay determined accurate and precise quantities, respectively, for osimertinib in both plasma (93.2%–99.3%; 0.2%–2.3%) and DBS (96.7%–99.6%; 0.5%–10.3%) over a concentration of 1–729 ng/mL. The osimertinib metabolites, AZ5104 and AZ7550, were similarly validated in accordance with bioanalytical guidelines. For 30%–60% patient hematocrit, no hematocrit bias was observed with DBS for all analytes. The Bland–Altman method showed high concordance between plasma and DBS analyte levels. Stability experiments revealed that osimertinib and its metabolites were poorly stable in plasma at room temperature, whereas all analytes were stable in DBS for 10 days at room temperature.

Conclusions:

The measurement of osimertinib, AZ5104, and AZ7550 from hemaPEN microsampled DBS is a convenient and reliable approach for therapeutic drug monitoring that produces measurements consistent with plasma drug levels.
Study on Correction Method of Counting Loss below the Threshold for Low Energy Radionuclides Based on Monte Carlo Simulation
Authors: Kong Shuying , Tuo Fei , Lu Tianxiang
Published: January 2024

In the absolute measurement method of nuclide radioactivity by the internal gas proportional counter, the reasonable correction of the small pulse counting loss is the key to obtaining the measurement results accurately. Considering the decay type and energy of radioactive gas nuclides, the influence of the low-energy beta particles and the wall effect counting loss on the activity measurement results is different also. To this end, two typical radioactive gas nuclides (37Ar and 3H) are used to study the cause of counting loss based on the Monte Carlo simulation. The results show that the counting loss of small pulse in the activity measurement of 37Ar comes mainly from the wall effect generated by x rays. Within the given gas pressure of 60-300 kPa, the simulated wall effect correction factors are 1.063-1.021. The decay energy of β particles generated by 3H is very low, and there is no obvious wall effect. The small pulse counting loss mainly comes from the low-energy beta particles’ contribution with the energy below the counting threshold, which can be corrected by extrapolating the beta energy spectrum at a lower counting threshold (below 1 keV).
Making Sense of Schizoposting
Authors: Johansson Jim A. , Holmes Dave
Published: January 2024

Online radicalization has gained considerable attention in the media and in academia. Much attention has shifted to so-called “homegrown terrorists.” Mental health concerns of those who display signs of online radicalization are identified as a potential contributing factor to this process. Although it seems both tempting to attribute mental health concerns, attempts to “make sense” of schizoposting (a bizarre and often violent form of online engagement) via conventional “clinical” analysis prove insufficient. This article offers a critical analysis of an extremely disturbing (online) phenomenon through the radical poststructuralist scholarship of late French philosophers, Deleuze and Guattari. Given that schizoposting and those individuals who engage in this behavior have yet to receive any attention in the nursing and health-related literature, it is critical that future research aims to better understand this population, such that appropriate interventions may be proposed.
Comparison of Quality of Life Outcomes for Percutaneous Versus Transcutaneous Implantable Hearing Devices: A Systematic Review and Meta-analysis
Authors: Gutierrez Jorge A. , Shannon Christian M. , Nguyen Shaun A. , Meyer Ted A. , Lambert Paul R.
Published: January 2024

Objective

To compare quality of life (QOL) outcomes of percutaneous and transcutaneous bone conduction devices (pBCD and tBCD, respectively).

Databases Reviewed

Pubmed, Scopus, CINAHL.

Methods

A systematic review was performed searching for English language articles from inception to March 15, 2023. Studies reporting QOL outcomes measured using a validated tool following implantation of either pBCDs or tBCDs were considered for inclusion. QOL outcomes included scores for Glasgow Benefit Inventory, Glasgow Children's Benefit Inventory, Abbreviated Profile of Hearing Aid Benefit, and the Speech, Spatial, and Qualities of Hearing Scale. A meta-analysis of continuous measures was performed.

Results

A total of 52 articles with 1,469 patients were included. Six hundred eighty-nine patients were implanted with pBCDs, and the remaining 780 were implanted with tBCDs. Average Glasgow Benefit Inventory scores for the tBCD group (33.0, 95% confidence interval [22.7–43.3]) were significantly higher than the pBCD group (30.9 [25.2–36.6]) (Δ2.1 [1.4–2.8],p< 0.0001). Mean Glasgow Children's Benefit Inventory scores (Δ3.9 [2.0–5.8],p= 0.0001) and mean gain in Abbreviated Profile of Hearing Aid Benefit scores (Δ5.6 [4.8–6.4],p< 0.0001) were significantly higher among patients implanted with tBCDs than those implanted with pBCDs. Patients implanted with tBCDs also had significantly higher gains on the Speech (Δ1.1 [0.9–1.3],p< 0.0001), Spatial (Δ0.8 [0.7–0.9],p< 0.0001), and Qualities of Hearing (Δ1.2 [1.1–1.3],p< 0.0001) portions of the Speech, Spatial, and Qualities of Hearing Scale than those implanted with pBCDs.

Conclusions

Patients implanted with transcutaneous devices had better QOL outcomes than those implanted with percutaneous devices.
A Clinical Prediction Model to Assess Risk for Pancreatic Cancer Among Patients With Acute Pancreatitis
Authors: Wang Louise , Rahimi Larki Navid , Dobkin Jane , Salgado Sanjay , Ahmad Nuzhat , Kaplan David E. , Yang Wei , Yang Yu-Xiao
Published: January 2024

Objectives

We aimed to develop and validate a prediction model as the first step in a sequential screening strategy to identify acute pancreatitis (AP) individuals at risk for pancreatic cancer (PC).

Materials and Methods

We performed a population-based retrospective cohort study among individuals 40 years or older with a hospitalization for AP in the US Veterans Health Administration. For variable selection, we used least absolute shrinkage and selection operator regression with 10-fold cross-validation to identify a parsimonious logistic regression model for predicting the outcome, PC diagnosed within 2 years after AP. We evaluated model discrimination and calibration.

Results

Among 51,613 eligible study patients with AP, 801 individuals were diagnosed with PC within 2 years. The final model (area under the receiver operating curve, 0.70; 95% confidence interval, 0.67–0.73) included histories of gallstones, pancreatic cyst, alcohol use, smoking, and levels of bilirubin, triglycerides, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and albumin. If the predicted risk threshold was set at 2% over 2 years, 20.3% of the AP population would undergo definitive screening, identifying nearly 50% of PC associated with AP.

Conclusions

We developed a prediction model using widely available clinical factors to identify high-risk patients with PC-associated AP, the first step in a sequential screening strategy.
Let’s Get LOUD
Authors: Farnsworth Nicole
Published: January 2024

Professional development specialists have been met with the challenge of engaging and retaining new graduate nurses in a postpandemic learning environment. Utilizing the idea of brain-based learning, one educator restructured their facility’s nurse residency program and created the “Let’s Get LOUD” talk series to increase learner satisfaction, engagement, and first-year retention among novice nurses.
Proximity of Percutaneous Tibial Nerve Stimulation Needle Insertion to Surrounding Anatomic Structures: A Cadaveric Study
Authors: Warehime Jenna M. , Gaskins Jeremy T. , Gupta Ankita S. , Hattab Eyas M. , Feroz Rehan T. , Rothenberger Rodger W. , Lenger Stacy M. , Francis Sean L. , Herring Nicole R.
Published: January 2024

(Abstracted from Am J Obstet Gynecol 2023;229:430.e1–430.e6)

Each year, spending on treatment of overactive bladder and urinary urgency sans incontinence uses at least $65.9 billion. Although many treatments for such conditions exist, the third line of medication is percutaneous tibial nerve stimulation (PTNS) for patients who wish to avoid onabotulinum toxin treatment and decline implanted devices.
Mesothelioma of Uncertain Malignant Potential (MUMP) of the Tunica Vaginalis
Authors: Ding Chien-Kuang C. , Van Roo Jason , Kryvenko Oleksandr N. , Ye Huihui , McKenney Jesse K. , Epstein Jonathan I.
Published: January 2024

A well-differentiated papillary mesothelial tumor (WDPMT) and malignant mesothelioma are 2 well-recognized entities arising from the testis tunica vaginalis. Another mesothelial lesion exclusively seen at this site is mesothelioma of uncertain malignant potential (MUMP)—a lesion reminiscent of WDPMT yet demonstrating variable proportions of more complex architectural patterns that could be confused with invasion. MUMP was first described in 2010 with a total of 11 cases reported to date. Herein, we describe 19 additional patients who underwent hydrocelectomy, excision, and/or orchiectomy. Novel morphologic patterns found in addition to the 2010 series include spindle cells, keloidal-type collagen, and multicystic architecture lined by bland mesothelial cells. Clinical follow-up in 9 patients for more than 1 year (1.5 to 22.5 y, median 4.5 y) revealed no evidence of disease recurrence or metastases. Despite greater architectural complexity, MUMP has (1) bland cytology; (2) merging in with WDPMT areas; (3) low mitotic rate and Ki-67 nuclear labeling index; (4) retention of MTAP and BAP1 expression; and (5) benign clinical follow-up. If these cases were malignant mesotheliomas, one would have expected at least some of the patients to demonstrate disease recurrence/progression without adjuvant therapy within the available follow-up time, particularly with limited resection in most patients. Thus, we propose that “mesothelioma of uncertain malignant potential” be renamed as “complex mesothelial tumor of the tunica vaginalis.” Using the term “complex” draws a contrast with the simple cuboidal lining and simple papillary architecture seen in WDPMT. Also, labeling the lesion as “tumor” removes the stigmata of “uncertain malignant potential” and “mesothelioma” that are alarming to patients and clinicians, and potentially could unduly lead to more extensive surgery in an attempt at “complete” resection. At the same time, not definitively labeling the lesion as benign allows recommendations for follow-up.
Rethinking Data Collection Methods During the Pandemic: Development and Implementation of CATI for the All of Us Research Program
Authors: Peterson Rachele , Hedden Sarra L. , Seo Isabell , Palacios Victoria Y. , Clark Emily C. , Begale Mark , Sutherland Scott , Givens Benjamin , McQueen Matthew , McClain James J.
Published: January 2024

The All of Us Research Program is a longitudinal cohort study aiming to build a diverse database to advance precision medicine. The COVID-19 pandemic hindered the ability of participants to receive in-person assistance at enrollment sites to complete digital surveys. Therefore, the program implemented Computer-Assisted Telephone Interviewing (CATI) to facilitate survey completion remotely to combat the disrupted data collection procedures. In January 2021, All of Us implemented a 1-year CATI Pilot supporting 9399 participants and resulting in 16 337 submitted surveys. The pilot showed that CATI was successful in increasing survey completion and retention activities for the All of Us Research Program, given the additional remote support offered to participants. Given the success of the CATI Pilot, multimodal survey administration will continue.
Telehealth and Outcomes in Patients With Cancer
Authors: Grant Michael J. , Chiang Ann C.
Published: January 2024

Despite that telehealth has been crucial to the delivery of oncology care during the COVID-19 pandemic, the impact of this care delivery mechanism on outcomes in cancer care has not been rigorously studied relative standard in-person care for patients with cancer. Patient-centered outcomes such as quality of life, patient satisfaction, and symptoms are important outcomes that have been the primary focus of many of the existing studies in this space, yet only a select few have evaluated overall survival and other objective efficacy endpoints. Studies have alluded to positive effects of telehealth on mitigating financial toxicity and enhancing cost-effective care delivery in oncology. Telehealth carries much potential for advancing care for patients with cancer, but future study should focus on additional efficacy endpoints, implementation, and ways to reduce disparities.
Evidence-Based Practices in Cleft Palate Surgery
Authors: Applebaum Sarah A. , Aronson Sofia , Termanini Kareem M. , Gosain Arun K.
Published: January 2024

Learning Objectives:

After studying this article, the participant should be able to: (1) Understand the embryologic origins, cause, and incidence of cleft palate. (2) Review the anatomy and common classifications of cleft palate and associated defects. (3) Describe surgical techniques for palatoplasty and understand their respective indications. (4) Gain an awareness of general perioperative care considerations, timing of repair, and risk factors for and operative mitigation of complications.

Cleft palate affects 0.1 to 1.1 per 1000 births, with a higher incidence in certain ethnic groups but affecting both sexes equally. Cleft palate may occur in isolation or in combination with cleft lip or in association with other congenital anomalies including various syndromes. The goals of cleft palate repair are to anatomically separate the oral and nasal cavities for normal feeding and improved speech and minimize the risk of oronasal fistulas, velopharyngeal dysfunction, and disruption of facial growth. This review discusses the incidence, causes, and classification of cleft palate; surgical techniques for palatoplasty and perioperative patient management; and complications of palatoplasty.
Comparison of Recombinant Human Thyroid-Stimulating Hormone and Thyroid Hormone Withdrawal for 131I Therapy in Patients With Intermediate- to High-Risk Thyroid Cancer
Authors: Park Sohyun , Bang Ji-In , Kim Keunyoung , Seo Youngduk , Chong Ari , Hong Chae Moon , Lee Dong-Eun , Choi Miyoung , Lee Sang-Woo , Oh So Won
Published: January 2024

Background

This meta-analysis and systematic review aimed to evaluate the therapeutic efficacy and advantages associated with the use of recombinant human thyroid-stimulating hormone (rhTSH) for radioactive iodine (RAI) therapy in patients with intermediate- to high-risk differentiated thyroid cancer.

Patients and Methods

MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles reporting clinical outcomes of rhTSH compared with thyroid hormone withdrawal (THW) in patients with intermediate- to high-risk differentiated thyroid cancer published between January 2012 and June 2023. Meta-analyses were performed (PROSPERO registration number: CRD42022340915) to assess the success rate of radioiodine remnant ablation (RRA) in patients with intermediate to high risk and determine the disease control rate among patients with distant metastases, evaluated using the RECIST criteria.

Results

Thirteen studies involving 1858 patients were included in the meta-analysis. Pooled analyses revealed significantly higher overall RRA success rate in the rhTSH group compared with the THW group, with a risk ratio (RR) of 1.12 (95% confidence interval [CI], 1.01–1.25). However, in the subgroup analysis of high-risk patients, pooled analyses showed no significant differences in RRA success rate between the rhTSH group compared with the THW group with a pooled RR of 1.05 (95% CI, 0.88–1.24). In patients with distant metastases, there were no significant differences in the disease control rate between groups, with a pooled RR of 1.06 (95% CI, 0.78–1.44).

Conclusions

rhTSH for RAI therapy is a practical option for RAI therapy in patients with intermediate- to high-risk thyroid cancer, including those with distant metastases.
Pulmonary Amyloidoma Imitating Lung Cancer on 18F-FDG PET/CT
Authors: Leike Tatjana , Svantesson Teodor , Minervini Fabrizio , Bhure Ujwal , Grünig Hannes
Published: January 2024

Localized pulmonary amyloidosis forming a solitary mass known as “amyloidoma of the lung” is rare. Differentiation from lung cancer can be difficult due to suspicious features on CT and high 18F-FDG uptake. We present a case of a 77-year-old woman with an incidental lung lesion on abdominal CT. Further evaluation with chest CT and 18F-FDG PET/CT maintained the suspicion of lung cancer. However, histology revealed amyloidoma without signs of malignancy. Knowledge of imaging similarities between pulmonary amyloidomas and malignancies is important for interpreting 18F-FDG PET/CT of lung tumors; however, only biopsy can confirm the rare differential diagnosis such as pulmonary amyloidoma.
Congenital Mesoblastic Nephroma Mimic Wilms Tumor on 18F-FDG PET/CT and PET/MR
Authors: Hu Wenzhu , Qin Chunxia , Shao Fuqiang , Li Mengting , Lan Xiaoli
Published: January 2024

Congenital mesoblastic nephroma is an extremely rare, low-grade malignant renal tumor in children. A 10-month-old boy and a 4-month-old girl were admitted to our hospital with a huge abdominal mass. For staging of the mass, 18F-FDG PET/CT and PET/MR were performed showing a huge heterogeneous abdominal mass accompanied by extensive heterogeneous aggregation. Both of them were highly suspected to be Wilms tumor, the most common renal malignant tumor in children. However, histopathological examination after surgery confirmed congenital mesodermal nephroma.
Modified Brain Injury Guidelines for preinjury anticoagulation in traumatic brain injury: An opportunity to reduce health care resource utilization
Authors: Gallagher Shea P. , Capacio Benedict A. , Rooney Alexandra S. , Schaffer Kathryn B. , Calvo Richard Y. , Sise C. Beth , Krzyzaniak Andrea , Sise Michael J. , Bansal Vishal , Biffl Walter L. , Martin Matthew J.
Published: January 2024

INTRODUCTION

The Brain Injury Guidelines (BIG) stratify patients by traumatic brain injury (TBI) severity to provide management recommendations to reduce health care resource burden but mandates that patients on anticoagulation (AC) are allocated to the most severe tertile (BIG 3). We sought to analyze TBI patients on AC therapy using a modified BIG model to determine if this population can offer further opportunity for safe reductions in health care resource utilization.

METHODS

Patients 55 years or older on AC with traumatic intracranial hemorrhage (ICH) from two centers were retrospectively stratified into BIG 1 to 3 risk groups using modified BIG criteria excluding AC as a criterion. Intracranial hemorrhage progression, neurosurgical intervention (NSI), death, and worsened discharge status were compared.

RESULTS

A total of 221 patients were included, with 23%, 29%, and 48% classified as BIG 1, BIG 2, and BIG 3, respectively. The BIG 3 cohort had a higher rate of AC reversal agents administered (66%) compared with the BIG 1 (40%) and BIG 2 (54%) cohorts (p < 0.01), as well as ICH progression discovered on repeat head computed tomography (56% vs. 38% vs. 26%, respectively; p < 0.001). No patients in the BIG 1 and 2 cohorts required NSI. No patients in BIG 1 and 3% of patients in BIG 2 died secondary to the ICH. In the BIG 3 cohort, 16% of patients required NSI and 26% died. Brain Injury Guidelines 3 patients had 15 times the odds of mortality compared with BIG 1 patients (p < 0.01).

CONCLUSION

The AC population had higher rates of ICH progression than the BIG literature, but this did not lead to more NSI or mortality in the lower tertiles of our modified BIG protocol. If the modified BIG used the original tertile management on our population, then NS consultation may have been reduced by up to 52%. These modified criteria may be a safe opportunity for further health care resource and cost savings in the TBI population.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Use of Transesophageal Echocardiography During Orthotopic Liver Transplantation: Simplifying the Procedure
Authors: Arcas-Bellas José J. , Siljeström Roberto , Sánchez Cristina , González Ana , García-Fernández Javier
Published: January 2024

The intraoperative management of patients undergoing orthotopic liver transplantation (OLT) is influenced by the cardiovascular manifestations typically found in the context of end-stage liver disease, by the presence of concomitant cardiovascular disease, and by the significant hemodynamic changes that occur during surgery.

Hypotension and intraoperative blood pressure fluctuations during OLT are associated with liver graft dysfunction, acute kidney failure, and increased risk of 30-d mortality. Patients also frequently present hemodynamic instability due to various causes, including cardiac arrest.

Recent evidence has shown transesophageal echocardiography (TEE) to be a useful minimally invasive monitoring tool in patients undergoing OLT that gives valuable real-time information on biventricular function and volume status and can help to detect OLT-specific complications or situations. TEE also facilitates rapid diagnosis of life-threatening conditions in each stage of OLT, which is difficult to identify with other types of monitoring commonly used.

Although there is no consensus on the best approach to intraoperative monitoring in these patients, intraoperative TEE is safe and useful and should be recommended during OLT, according to experts, for assessing hemodynamic changes, identifying possible complications, and guiding treatment with fluids and inotropes to achieve optimal patient care.
Optic Disc Edema Is an Under-Recognized Feature of Birdshot Chorioretinitis
Authors: Sabapathypillai Sharon , Miller Victoria J. , Shakoor Akbar , Palestine Alan G. , Thorne Jennifer E. , Goldstein Debra A. , Gaudio Paul A. , Goldberg Naomi , Vitale Albert , Schlaen Ariel , Thomas Akshay , Merrill Pauline T. , Raiji Veena , Lin Phoebe , Oliver Armando L. , Moorthy Ramana S. , Chandra Gaurav , Carreno Ester , Smith Wendy M. , Van Stavern Gregory , Hassman Lynn M.
Published: January 2024

Background:

Optic disc edema is a feature of many ophthalmic and neurologic conditions. It remains an underappreciated feature of birdshot chorioretinitis (BSCR), leading to delay in diagnosis and treatment. The purpose of our study was to identify clinical features that are concomitant with optic disc edema and suggest a diagnosis of BSCR.

Methods:

Retrospective multicenter case series of 29 patients who were referred to a neuro-ophthalmologist or uveitis specialist for evaluation of disc edema and were ultimately diagnosed with BSCR.

Results:

Fifty-four eyes of 30 patients, from the practices of 15 uveitis specialists, met the eligibility criteria. In addition to disc edema, concomitant features in all patients included vitritis, chorioretinal lesions, and retinal vasculitis. Visual recovery to 20/40 or better occurred in 26 of 29 patients. Visual acuity remained 20/100 or worse in 2 patients previously diagnosed with idiopathic intracranial hypertension, 1 patient previously diagnosed with optic neuritis, and 1 patient for whom treatment was delayed for years, leading to optic disc atrophy.

Conclusions:

Optic disc edema is a presenting feature in some cases of BSCR. A diagnosis of BSCR should be considered when disc edema occurs with vitritis, chorioretinal inflammation, and retinal vasculitis. Patients should be referred to a uveitis specialist for treatment.
Plant NLR immunity activation and execution: a biochemical perspective
Authors: Locci Federica , Parker Jane E.
Published: January 2024

Plants deploy cell-surface and intracellular receptors to detect pathogen attack and trigger innate immune responses. Inside host cells, families of nucleotide-binding/leucine-rich repeat (NLR) proteins serve as pathogen sensors or downstream mediators of immune defence outputs and cell death, which prevent disease. Established genetic underpinnings of NLR-mediated immunity revealed various strategies plants adopt to combat rapidly evolving microbial pathogens. The molecular mechanisms of NLR activation and signal transmission to components controlling immunity execution were less clear. Here, we review recent protein structural and biochemical insights to plant NLR sensor and signalling functions. When put together, the data show how different NLR families, whether sensors or signal transducers, converge on nucleotide-based second messengers and cellular calcium to confer immunity. Although pathogen-activated NLRs in plants engage plant-specific machineries to promote defence, comparisons with mammalian NLR immune receptor counterparts highlight some shared working principles for NLR immunity across kingdoms.
Multiple Sclerosis Stages and their Differentially Expressed Genes: A Bioinformatics Analysis
Authors: Alaya Faten , Baraket Ghada , Adediran Daniel A. , Cuttler Katelyn , Ajiboye Itunu , Kivumbi Mark T. , Sitharam Nikita , Awe Olaitan I.
Published: January 2024

Multiple Sclerosis (MS) is an inflammatory, chronic, autoimmune, and demyelinating disease of the central nervous system. MS is a heterogeneous disease with three main clinical forms, affecting the progression and therefore the treatment of the disease. Thus, finding key genes and microRNAs (miRNA) associated with MS stages and analyzing their interactions is important to better understand the molecular mechanism underlying the occurrence and the evolution of MS. Based on publicly available datasets of mRNA and miRNA expression profiles, differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between patients with different stages of MS and healthy controls and between relapsing and remitting phases of RRMS were determined using Deseq2 and GEO2R tools. We then analyzed miRNA-mRNA regulatory interactions and gene ontology for the DEGs.

Based on miRNA-mRNA regulatory interactions, we identified potential biomarkers of RRMS, 13 upregulated miRNA regulators of 30 downregulated genes and 17 downregulated miRNA regulators of 32 upregulated genes. We also identified 9 downregulated miRNA regulators of 12 upregulated genes as potential biomarkers of SPMS.

Our study findings highlight some key protein-coding genes and miRNAs that are involved in the occurrence and evolution of MS.
Analysis of B-cell receptor repertoire to evaluate immunogenicity of monovalent Omicron XBB.1.5 mRNA vaccines
Authors: Funakoshi Yohei , Yakushijin Kimikazu , Ohji Goh , Matsutani Takaji , Doi Kazuhiko , Sakai Hironori , Sasaki Tomoki , Kusakabe Takahiro , Matsumoto Sakuya , Saito Yasuyuki , Kawamoto Shinichiro , Yamamoto Katsuya , Koyama Taiji , Nagatani Yoshiaki , Kurata Keiji , Kimbara Shiro , Imamura Yoshinori , Kiyota Naomi , Ito Mitsuhiro , Minami Hironobu
Published: January 2024

Monovalent Omicron XBB.1.5 mRNA vaccines (BNT162b2 XBB.1.5 and mRNA- 1273.815) were newly developed and approved by the FDA in Autumn 2023 for preventing COVID-19. However, clinical efficacy for these vaccines is currently lacking. We previously established the Quantification of Antigen-specific Antibody Sequence (QASAS) method to assess the response to SARS-CoV-2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the Coronavirus Antibody Database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of monovalent XBB.1.5 vaccines in healthy volunteers. We analyzed repeated blood samples before and after vaccination for the BCR repertoire to assess BCR/antibody sequences that matched SARS-CoV-2-specific sequences in the database. The number of matched unique sequences and their total reads quickly increased 1 week after vaccination. Matched sequences included those bound to the Omicron strain and Omicron XBB sublineage. The antibody sequences that can bind to the Omicron strain and XBB sublineage revealed that the monovalent XBB.1.5 vaccines showed a stronger response than previous vaccines or SARS-CoV-2 infection before the emergence of XBB sublineage. The QASAS method was able to demonstrate the immunogenic effect of monovalent XBB.1.5 vaccines for the 2023-2024 COVID-19 vaccination campaign.
Changes in sensorimotor network dynamics in resting-state recordings in Parkinson’s Disease
Authors: Kohl Oliver , Gohil Chetan , Zokaeia Nahid , Hu Michele T. , Nobrea Anna C. , Woolrich Mark , Quinn Andrew
Published: January 2024

Non-invasive recordings of magnetoencephalography (MEG) have been used for developing biomarkers for neural changes associated with Parkinson’s Disease (PD) but have yielded inconsistent findings. Here, we investigated whether analysing motor cortical activity within the context of large-scale brain network activity provides a more sensitive marker of changes in PD using MEG.

We extracted motor cortical beta power and beta bursts from resting-state MEG scans of individuals with PD (N=28) and well-matched healthy controls (N=36). To situate beta bursts in their brain network contexts, we used a time-delay embedded Hidden Markov Model (TDE-HMM) to extract brain network activity and investigated co-occurrence patterns between brain networks and beta bursts.

PD was associated with decreased beta power in motor cortex and decreased occurrences of the sensorimotor network, while motor cortical beta-burst dynamics were not changed. By comparing conventional burst and large-scale network occurrences, we observed that motor beta bursts occurred during both sensorimotor network and non-sensorimotor network activations. When using the large-scale network information provided by the TDE-HMM to focus on bursts that were active during sensorimotor network activations, significant decreases in burst dynamics could be observed in individuals with PD.

In conclusion, our findings suggest that decreased motor cortical beta power in PD is prominently associated with changes in sensorimotor network dynamics using MEG. Thus, investigating large-scale networks or considering the large-scale network context of motor cortical activations may be crucial for identifying alterations in the sensorimotor network that are prevalent in PD, and might help resolve contradicting findings in the literature.

Highlights

Sensorimotor network occurrences are decreased in Parkinson’s Disease.

Motor cortical beta bursts occur during both sensorimotor network and non-sensorimotor network activations.

Focusing on motor beta bursts occurring during sensorimotor network activations enables for better discrimination between controls and individuals with PD.

The spatiotemporal details provided by large-scale network analysis may help to overcome discrepancies found in the PD literature.
Inference of alveolar capillary network connectivity from blood flow dynamics
Authors: Schmid Kerstin , Olivares Andy L. , Camara Oscar , Kuebler Wolfgang M. , Ochs Matthias , Hocke Andreas C. , Fischer Sabine C.
Published: January 2024

The intricate structure of the lungs is essential for the gas exchange within the alveolar region. Despite extensive research on the pulmonary vasculature, there are still unresolved questions regarding the connection between capillaries and the vascular tree. A major challenge is obtaining comprehensive experimental data that integrates morphological and physiological aspects.

We propose a computational approach that combines data-driven 3D morphological modeling with computational fluid dynamics simulations. This method enables investigating the connectivity of the alveolar capillary network with the vascular tree based on the dynamics of blood flow. We developed 3D sheet-flow models to accurately represent the morphology of the alveolar capillary network and conducted computational fluid dynamics simulations to predict flow velocities and pressure distributions.

Our approach focuses on leveraging functional features to identify the most plausible architecture of the system. For given capillary flow velocities and arteriole-to-venule pressure drops, we deduce details about arteriole connectivity. Preliminary connectivity analyses for non-human species indicate that their alveolar capillary network of a single alveolus is linked to at least two arterioles with diameters of 20 µm or a single arteriole with a minimum diameter of 30 µm.

Our study provides insights into the structure of the pulmonary microvasculature by evaluating blood flow dynamics. This inverse approach represents a new strategy to exploit the intricate relationship between morphology and physiology, applicable to other tissues and organs. In the future, the availability of experimental data will play a pivotal role in validating and refining the hypotheses analyzed with our computational models.

New and noteworthy

The alveolus is pivotal for gas exchange. Due to its complex morphology and dynamic nature, structural experimental studies are challenging. Computational modeling offers an alternative. We developed a databased 3D model of the alveolar capillary network and performed blood flow simulations within it. Choosing a novel perspective, we inferred structure from function. We systematically varied properties of vessels connected to our capillary network and compared simulation results with experimental data to obtain plausible vessel configurations.
Morphine-induced side effects can be differentially modulated by cannabidiol in male and female rats
Authors: Jesus Carlos Henrique Alves , Volpe Jaqueline , Sotomaior Bruna Bittencourt , Barbosa Maria Augusta Ruy , Ferreira Matheus Vinicius , Fiatcoski Fernanda , Genaro Karina , Crippa José Alexandre de Souza , Souto Dênio Emanuel Pires , da Cunha Joice Maria
Published: January 2024

Opioid use disorder (OUD) is a public health problem that includes symptoms such as withdrawal syndrome and opioid-induced hyperalgesia (OIH). Currently, drugs to treat side effects of opioids also have undesirable effects, which lead to limitations. This study investigated the effect of a treatment with cannabidiol (CBD) in morphine-induced hyperalgesia and withdrawal signs in morphine-dependent rats. Male and female rats were submitted to morphine-induced physical dependence protocol consisting of a twice daily treatment with morphine (7.89 mg/kg, 1ml/kg, s.c.) for 10 days. Nociception was measured using the hot plate test and morphine-induced thermal hyperalgesia was equally achieved following 7-10 days of morphine administration in male and female rats. Repeated treatment with CBD (30 mg/kg) was sufficient to prevent thermal hyperalgesia in male and female rats. Subsequently, rats received an acute administration of naloxone (2 mg/kg. s.c.), 90 minutes after the morphine treatment on day 11, the number of withdrawal signs was scored. Rats that received treatment exclusively with morphine presented significant withdrawal signs compared to control (Water). Morphine-dependent female rats showed a prevalent stereotyped behavior of rearing, whereas male rats had the sign of teeth chattering as the most preeminent. Treatment with CBD on day 11 partially attenuated the withdrawal signs in morphine-dependent male rats, but not female rats. Altogether, our data provide evidence of an anti-hyperalgesic effect of CBD in rats. Male and female rats treated chronically with morphine exhibited withdrawal signs in different ratios, indicating sex-differences in withdrawal behavior and CBD attenuated withdrawal signs in a sex-dependent manner.
A Non-targeted Proteomics Newborn Screening Platform for Genetic Disorders
Authors: Shibata Hirofumi , Nakajima Daisuke , Konno Ryo , Hijikata Atsuhi , Higashiguchi Motoko , Nihira Hiroshi , Shimodera Saeko , Miyamoto Takayuki , Nishitani-Isa Masahiko , Hiejima Eitaro , Izawa Kazushi , Takita Junko , Heike Toshio , Okamura Ken , Ohnishi Hidenori , Ishimura Masataka , Okada Satoshi , Yamashita Motoi , Morio Tomohiro , Kanegane Hirokazu , Imai Kohsuke , Nakamura Yasuko , Nonoyama Shigeaki , Uchiyama Toru , Onodera Masafumi , Nishikomori Ryuta , Ohara Osamu , Kawashima Yusuke , Yasumi Takahiro
Published: January 2024

Newborn screening using dried blood spot (DBS) samples has made a substantial contribution to public healthcare by detecting patients with genetic disorders as neonates. Targeted measurements of nucleic acids and metabolites have played major roles in newborn screening to date, while the feasibility of new non-targeted approaches, including genome-wide DNA sequencing, has been explored. Here, we investigated the applicability of non-targeted quantitative proteomics analysis to newborn screening for genetic diseases. DBS protein profiling allowed monitoring of levels of proteins encoded by 2912 genes, including 1106 listed in the Online Mendelian Inheritance in Man database, in healthy newborn samples, and was useful in identifying patients with inborn errors of immunity by detecting reduced levels of disease causative proteins and cell-phenotypical alterations. Our results indicate that application of non-targeted quantitative protein profiling of DBS samples can forge a new path in screening for genetic disorders.
General and Anxiety-Linked Influence of Acute Serotonin Reuptake Inhibition on Neural Responses Associated with Attended Visceral Sensation
Authors: Livermore James J A , Skora Lina I , Adamatzky Kristian , Garfinkel Sarah N , Critchley Hugo D , Campbell-Meiklejohn Daniel
Published: January 2024

Serotonin is known to have state-dependent modulatory influences on exteroceptive sensory processes and the processing of pain, but much less is known about its role in ordinary interoceptive processes and their relationships to affective states. This experiment compared the impact of a selective serotonin reuptake inhibitor (SSRI) (20mg CITALOPRAM), acutely increasing extracellular serotonin, to that of a PLACEBO on the neural processing of ordinary interoceptive sensations and the relationship of these influences to anxious states. Twenty-one healthy young volunteers completed the visceral interoceptive attention (VIA) task with each treatment, focusing attention on heart, stomach, or visual sensation control while scanned with functional magnetic resonance imaging (fMRI). The relative neural interoceptive response (IR) to heart sensation [heartminusvisual] and stomach sensation [stomachminusvisual] were compared between treatment conditions, controlling for general effects on sensory processing. CITALOPRAM reduced interoceptive processing in viscerosensory (bilateral posterior insular cortex, stomach-IR) and integrative/affective components (bilateral amygdala, stomach-IR and heart-IR) of known interoceptive pathways. We then searched for state-dependent modulatory effects of CITALOPRAM that varied with current levels of anxiety. The anterior insular cortex response to heart sensation increased with anxiety, replicating prior findings. This relationship disappeared on CITALOPRAM. Preliminarypost hocexploration found that CITALOPRAM’S effects on amygdalae response to stomach sensation predicted acute increases and decreases in anxiety. Overall, this evidence of general and state-dependent serotonergic influence advances our understanding of interoception, its regulation, and its relationship to anxious states.
Identifying the components of theShewanellaphage LambdaSo lysis system
Authors: Thöneböhn Svenja , Fischer Dorian , Kreiling Vanessa , Kemmler Alina , Oberheim Isabella , Hager Fabian , Schmid Nicole E , Thormann Kai M
Published: January 2024

Phage-induced lysis of Gram-negative bacterial hosts usually requires a set of phage lysis proteins, a holin, an endopeptidase and a spanin system, to disrupt each of the three cell envelope layers. Genome annotations and previous studies identified a gene region in theShewanella oneidensisprophage LambdaSo, which comprises potential holin- and endolysin-encoding genes but lacks an obvious spanin system. By a combination of candidate approaches, mutant screening, characterization and microscopy we found that LambdaSo uses a pinholin/signal-anchor-release (SAR) endolysin system to induce proton-leakage and degradation of the cell wall. Between the corresponding genes we found that two extensively nested open reading frames encode a two-component spanin module Rz/Rz1. Unexpectedly, we identified another factor strictly required for LambdaSo-induced cell lysis, the phage protein Lcc6. Lcc6 is a transmembrane protein of 65 amino acid residues with hitherto unknown function, which acts at the level of holin in the cytoplasmic membrane to allow endolysin release. Thus, LambdaSo-mediated cell lysis requires at least four protein factors (pinholin, SAR-endolysin, spanin, Lcc6). The findings further extend the known repertoire of phage proteins involved in host lysis and phage egress.

Significance

For the release of the assembled virions, phages have to breach the cell envelope. For Gram-negatives, this requires the disruption of three layers, the outer and inner membrane and the cell wall. In most cases, the lysis systems of phages infecting Gram-negatives comprises holins to disrupt or depolarize the membrane, thereby releasing or activating endolysins, which then degrade the cell wall. This, in turn, allows the spanins to become active and fuse outer and inner membrane, completing cell envelope disruption and allowing phage egress. Here we show that the presence of these three components may not be sufficient to allow cell lysis, implicating that also in known phages further factors may be required.
Antenatal care utilisation in Nigeria: assessing disparities between rural and urban areas—analysis of the 2018 Nigeria demographic and health survey
Authors: Adewuyi Emmanuel O , Auta Asa , Adewuyi Mary I , Phili Aaron Akpu , Olutuase Victory , Zhao Yun , Khanal Vishnu
Published: January 2024

Objectives

This study presents a comprehensive assessment of antenatal care (ANC) utilisation in Nigeria, focusing on the disparities between rural and urban areas.

Methods

We used the data disaggregation approach to analyse the 2018 Nigeria Demographic and Health Survey. We estimated ANC utilisation, assessed the receipt of ANC components, and identified factors associated with eight or more (≥ 8) ANC contacts nationally and across rural and urban residences.

Results

The overall ≥ 8 ANC utilisation was 20.3% in Nigeria—35.5% in urban and 10.4% in rural areas. Nationally and in urban areas, the North-East region had the lowest ANC use at 3.7% and 3.0%, respectively, while the North-West had the lowest in rural areas (2.7%). Nationally, 69% of mothers received iron supplements, 70% had tetanus injections, and 16% received drugs for intestinal parasites, with urban residents having higher percentages across all ANC components. Maternal and husband education, health insurance, and maternal autonomy were common factors associated with increased ANC odds at the national, rural, and urban residences. All ethnic groups had higher ANC odds than the Hausa/Fulanis in urban areas, while only the Yorubas had greater odds in rural areas. Internet use was significant only in the national context, watching television only in urban settings, while maternal working status, wealth, birth type, religion, and listening to the radio were significant only in rural areas.

Conclusion

Our study highlights considerable disparities in ANC utilisation and quality with a greater vulnerability for rural residents, rural northern regions, and socioeconomically disadvantaged mothers. Targeted interventions are imperative to address the disparities and improve ANC use in Nigeria, with priority for the most vulnerable sub-populations.
Longitudinal pathways between maternal depression, parenting behaviors, and early childhood development: a mediation analysis
Authors: Frost Allison , Scherer Elissa , Chung Esther O. , Gallis John A. , Sanborn Kate , Zhou Yunji , Hagaman Ashley , LeMasters Katherine , Sikander Siham , Turner Elizabeth , Maselko Joanna
Published: January 2024

Maternal depression is a global public health concern with far-reaching impacts on child development, yet our understanding of mechanisms remains incomplete. This study examined whether parenting mediates the association between maternal depression and child outcomes. Participants included 841 rural Pakistani mother-child dyads (50% female). Maternal depression was measured at 12 months postpartum, parenting behaviors (warmth, stimulation, and harsh parenting) were measured at 24 months, and child outcomes (mental health, socioemotional development, and cognitive skills) were measured at 36 months. Maternal depression predicted increased harsh parenting, child mental health difficulties, and child socioemotional concerns; however, there was little evidence for parenting as a mediator between maternal depression and child outcomes. Sex-stratified results are discussed, and findings are situated in context.
Occupational differences in COVID-19 hospital admission and mortality risks between women and men in Scotland: a population-based study using linked administrative data
Authors: Pattaro Serena , Bailey Nick , Dibben Chris
Published: January 2024

Introduction

Occupations vary with respect to workplace factors that influence exposure to COVID-19, such as ventilation, social contacts and protective equipment. Variations between women and men may arise because they have different occupational roles or behavioural responses. We estimate occupational differences in COVID-19 hospital admission and mortality risks by sex.

Methods

We combined individual-level data from 2011 Census with (i) health records and (ii) household-level information from residential identifiers. We used data for a cohort of 1.7 million Scottish adults aged 40-64 years between 1 March 2020 and 31 January 2021. We estimated age-standardised COVID-19 hospital admission and mortality rates, stratified by sex and occupation. Using Cox proportional hazards models, we estimated COVID-19 hospital admission and death risks, adjusting for relevant factors.

Results

Generally, women had lower age-standardised COVID-19 hospital admission and mortality rates compared to men. Among women, adjusted death risks were lower for health professionals, and those in associate professional and technical occupations (paramedics and medical technicians). Among men, elevated adjusted admission and death risks were observed for large vehicle and taxi drivers. Additionally, admission risks remained high among men working in caring personal services, including home and care workers, while elevated risks were observed among women working in customer service occupations (call centre operators) and as process, plant and machine operatives (assemblers/sorters).

Conclusion

Occupational differences in COVID-19 hospital admission and mortality risks between women and men highlight the need to account for sex differences when developing interventions to reduce infections among vulnerable occupational groups.