bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous clavicular hook plate fixation in bilateral distal clavicle fractures (Neer type II): A case report
Authors: Akar Bedrettin , Ugur Fatih
Published: November 2024

Rationale:

Bilateral distal clavicle fractures (BDCF) are exceedingly rare types of fractures. This study aimed to evaluate the surgical treatment under a single anesthesia for trauma-induced BDCF (Neer type II) through a case report.

Patient concerns:

The patient brought to the emergency department due to a motor vehicle accident exhibited severe pain, tenderness, swelling, and deformity in both shoulder regions upon physical examination. No significant pain or tenderness was detected in other areas of the body. There were also no signs of additional neurological deficits or vascular pathology in the extremities.

Diagnoses:

Radiographic examinations led to a diagnosis of BDCF (Neer type II).

Interventions:

Surgical intervention involved the simultaneous application of a neutral-angled hook plate to both clavicles via open reduction.

Outcomes:

Postoperative radiographs taken at the 12th week demonstrated complete healing in both fractures and no functional limitations in shoulder movements.

Lessons:

BDCF can compromise the stability of the shoulder girdle, necessitating surgical intervention with anatomical reduction and rigid fixation.
The prevalence and associated factors of intraoperative hypotension following thoracic surgery in resources limited area, 2023: multicentre approach
Authors: Wolde Yisehak , Argawi Adugna , Alemayehu Yabtsega , Desalegn Mitiku , Samuel Sintayehu
Published: November 2024

Background:

Hypotension is an independent predictor of long-term patient morbidity and duration of hospital stay. Multiple factors contribute to the development of intraoperative hypotension. Prevention and treatment of these factors may reduce patients’ hypotension and its associated morbidity and mortality. This study aimed to assess the prevalence and associated factors of intraoperative hypotension in patients undergoing elective thoracic surgery.

Methods:

This institution-based cross-sectional study was conducted among 174 adult patients who underwent elective thoracic surgery. A systematic random sampling technique was used, and quantitative data were collected through interviews and data retrieval from charts via a pretested questionnaire. Both bivariable and multivariable logistic regression analyses were performed to evaluate the associations between independent and dependent variables. The level of statistical significance was defined as a P-value less than 0.05. The data were entered into Info 7.2.1 and analyzed via SPSS version 26 software, which was used to calculate descriptive statistics, and bivariate and multivariate logistic regression were performed.

Results:

In general, information was collected from 174 patients during the study period. The results of the present study revealed that 65 (41%) patients developed intraoperative hypotension (95% CI: 36.43–48%). Intraoperative blood loss was significantly associated with intraoperative hypotension [AOR=9.58, 95% CI (2.57–35.8)] (P=0.001).

Conclusion and Recommendation:

The findings of this study revealed high rates of intraoperative hypotension episodes, which were 41%, in patients who underwent elective thoracic surgery. Age, ASA class, type of intraoperative blood loss, type of procedure pre-existence comorbidity, and duration of surgery were predictors of intraoperative hypotension in patients who underwent elective thoracic surgery. The anaesthetist’s, surgeon, and PACU staff’s understanding of these factors is very crucial for close follow-up of this group of patients.
The Association between Home Health Nursing and 30-Day Hospital Readmission after Tracheostomy in Children
Authors: Lodge Madison , Bashiri Sowgand , Durazo-Arvizu Ramon , Russell Christopher J.
Published: November 2024

To identify the association between home health nursing (HHN) and hospital readmissions for patients discharged after tracheostomy placement, we conducted a single-center prospective cohort study of children ages 0 to 21 years who underwent tracheostomy placement at Children's Hospital Los Angeles between 12/2016 and 2/2023 and were discharged to home. We collected demographic, clinical, and discharge variables for the index hospitalization to test the association between our primary exposure, HHN after discharge, and 30-day same-hospital all-cause, adjusting for potential confounders. Our population of 130 children was primarily male, of Hispanic/Latino ethnicity, and on public insurance. The majority of patients (57%) received HHN on discharge and the 30-day readmission rate was 14.6%. On multivariable analysis, HHN was not associated with readmission for children discharged on home mechanical ventilation [HMV; adjusted OR (aOR = 1.11; 95% CI: 0.30-4.02)] but was associated with lower odds of all-cause 30-day readmission in children discharged without HMV (aOR = 0.12; 95% CI: 0.02-0.81). Our findings support consideration for HHN as a hospital-to-home bridge for children after tracheostomy placement to decrease hospital readmissions and support parents and caregivers during this transition period.
Out of the Hospital, Out of the Box
Authors: Manning Jennifer , Meyer Jeannette , Girasol Nerina
Published: November 2024

The United States has poorer population health outcomes compared to similar developed nations despite higher healthcare spending. Multiple factors contribute to this problem, including high healthcare costs, insurance coverage limitations, and a lack of focus on preventive care and wellness. Clinical Nurse Specialists (CNSs), primarily known for their impact in acute care settings, increasingly demonstrate their value in outpatient settings like home healthcare. CNSs possess graduate-level training, equipping them with the skills and expertise to develop and implement strategies that improve population health outcomes in home health settings. CNSs provide clinical leadership and support to staff while remaining at the forefront of ensuring the organization delivers high-quality patient care. Understanding the specific skills and competencies of the CNS to support the patient, family, staff, and organization is necessary to improve outcomes for patients in outpatient settings. The CNS delivers care through direct patient care, supporting nurses and nursing practice, and improving organizational systems. This unique skill set allows CNSs to influence home healthcare outcomes across various levels of care positively. This article sheds light on how CNSs enhance patient outcomes in outpatient settings like home healthcare.
Reducing Violence Risk
Authors: Lambert Paula
Published: November 2024

An expanding body of literature suggests that informal caregiver burden is a growing issue that negatively impacts care recipients, informal caregivers, and formal care providers. Costs associated with informal caregiver burden include risk to the informal caregiver's physical, emotional, and psychological well-being and increased potential to perpetrate violence. By identifying interventions to support informal caregivers, home healthcare nurses can help decrease the risk of negative outcomes and reduce the burden on informal caregivers. This paper examines home healthcare nurses' role in helping reduce the impact of informal caregiver burden, thereby reducing the risk for violence. By prioritizing caregiver burden as a critical area of focus in reducing violence risk, home healthcare organizations and the nurses who work for them can help address gaps in care while also recognizing the informal caregivers' critical role in caring for their loved ones.
Hospital-Level Care at Home Patients Remain at Home Longer Following Acute Illness
Authors: Lally Julianne M.
Published: November 2024

Hospital-level care at home (HCaH) is a modern alternative to traditional inpatient hospitalization (TIH) for acutely ill adults which is cost-effective without impacting patient mortality. Additional outcomes comparing HCaH and TIH have been studied including hospital readmission and post-acute care admission. There is convincing evidence that suggests a trend in the reduction of readmissions following acute hospitalization in the home. Additionally, post-acute care admissions have been significantly reduced following HCaH compared to TIH. The concept of a home hospital allows patients to remain home during acute illness and stay at home longer following discharge, thereby avoiding the need for hospital readmission and post-acute care placement. This research is increasingly important to the aging population in the United States that seeks a safe and beneficial alternative to overwhelmed medical facilities.
The Effects of Teach-Back and Blended Training on Self-Care and Care Burden Among Caregivers of Patients with Heart Failure Caregivers
Authors: Najafi Elham , Rafiei Hossein , Rashvand Farnoosh , Pazoki Ali
Published: November 2024

A quasi-experimental study aimed to investigate the effects of both teach-back and blended training methods on the contribution to self-care and perceived care burden among family caregivers of patients with heart failure. Seventy family caregivers of patients with heart failure were randomly allocated to two groups: one receiving the teach-back method and the other receiving the blended training method. Data were collected before, 1 month, and 3 months after the intervention. Data collection included demographic data and two tools: the Caregiver Contribution to Self-Care of Heart Failure Index and the Caregiver Burden Questionnaire for Heart Failure. Both teach-back and blended training methods were effective in educating family caregivers of patients with heart failure requiring home care. However, the teach-back method demonstrated better outcomes for the two concepts examined in this study.
Existential aspects of breathlessness in serious disease
Authors: Baglow David , Johnston Kylie , Williams Marie
Published: November 2024

Purpose of the review

Breathlessness may evoke existential threat but may also affect the person with serious illness or their caregiver/s in other important ways which can be considered ‘existential’. This review explores existential aspects of breathlessness in people with serious illness and presents recent studies of assessment and management of associated distress and suffering.

Recent findings

Both existential distress and breathlessness are multidimensional and include a range of constructs, many of which have behavioural consequences. Existential distress tracks closely with distressing breathing potentially due to shared underlying neurobiological processing. Paradoxically ‘contagious’ and isolating effects of breathlessness and related distress have been recently highlighted. Approaches to screening and assessment vary. Preliminary studies have investigated novel approaches to breathing-related anxiety and existential distress.

Studies with existential constructs as outcome measures in people with breathlessness are scarce. Interventions for existential distress developed for those with malignant disease may be beneficial for those with non-malignant conditions, but adaptations may be required. Recently proposed taxonomies of existential distress/concerns may guide assessment and direct novel therapeutic interventions in people living with serious illness and breathlessness-related distress. Neglecting existential aspects of breathlessness represents a missed opportunity to support holistic well-being in people with serious illness.
Topological organization of the brain network in thyroid-associated ophthalmopathy using graph theoretical analysis
Authors: Fang Jian-Wen , Liu Hao , Huang Xin
Published: November 2024

Mounting neuroimaging evidence indicates that patients with thyroid-associated ophthalmopathy (TAO) demonstrate altered brain function and structure. Nonetheless, the alterations in the topological properties of the functional brain connectome in TAO patients are not yet fully understood. This study aimed to investigate the topological organization of the functional brain connectome in TAO patients using graph-theoretic methods. Twenty-five TAO patients (10 males and 15 females) and 25 age-, sex-, and education-matched healthy controls (HCs) (10 males and 15 females) (the TAO and HC data are from the same dataset in previous studies) underwent resting-state MRI scans. Graph-theoretic analysis was used to study the global, nodal, and edge topological properties of the brain’s functional connectome. Both the TAO and HC groups exhibited high-efficiency small-world networks in their brain functional networks. However, there were no significant differences in small-world properties (Cp, γ, λ, Lp, and σ) and network efficiency [global and local efficiencies (Eloc)] between the two groups. In addition, the TAO group demonstrated reduced betweenness centrality in the right fusiform and increased nodal Eloc in the right intraparietal sulcus (P < 0.05, Bonferroni-corrected). Furthermore, the TAO group displayed altered functional connections among the default-mode network (DMN), visual network (VN), sensorimotor network (SMN), and cingulo-opercular network (CON). Patients with TAO exhibited abnormal topological organization of the human brain connectome, including decreased betweenness centrality and increased nodal Eloc. Moreover, the TAO group displayed altered functional connections primarily within the DMN, VN, SMN, and CON. These findings provide crucial insights into the neural mechanisms underlying visual loss, abnormal emotion regulation, and cognitive deficits in TAO patients.
Significant gaps in practise present despite higher level of public awareness in Antibiotic Use and Antimicrobial Resistance in the western province of Sri Lanka
Authors: Gunatilake Gayan Danushka , Anthony Conganige Hiranya Hansali , Hettiarachchige Done Anne Sithuvili , Hettige Sandani Kaveesha Dinudhya , Tennakoon Dinushi
Published: November 2024

Background:
Antibiotic misuse, influenced by urbanization and limited healthcare access, has accelerated antibiotic resistance, impacting global health. Surveillance in Sri Lanka's National Strategic Plan for Combating Antimicrobial Resistance (2017-2022) shows significant multi-drug resistance in hospitals, with 12.7% of the health budget (3.3 billion) spent on antimicrobials. This resistance complicates treatment and increases patient management costs, particularly in the Western Province, a focal area for analyzing antibiotic misuse.
 
Objectives:
To assess public awareness of antibiotic misuse and antimicrobial resistance in the Western Province of Sri Lanka.
Methodology:
A cross-sectional study was conducted on 200 adults in the Western Province from December 23, 2023, to January 16, 2024, using in-person interviews and a Google form questionnaire. Descriptive statistics were applied to analyze the data.
 
Results:
Of the respondents, 83% knew antibiotics combat bacterial infections, while 71.5% adhered to completing antibiotic courses. However, 28.5% opposed doing so, with 65.5% stopping antibiotics once they felt better. Regarding antimicrobial resistance, 60.5% recognized the term, and 61% acknowledged that unnecessary antibiotic use could increase bacterial resistance.
Conclusion:
Most participants understood antibiotics' role, though gaps in correct use and awareness of misuse consequences persisted. While there was a positive attitude toward antimicrobial resistance, further educational efforts are essential to address knowledge gaps, as recent studies show high resistance levels and limited progress in awareness.
Keywords:
AMR; Antibiotic resistance; antimicrobial resistance; Knowledge; Awareness; Sri Lanka
Deep generative model for protein subcellular localization prediction
Authors: Yuan Guo-Hua , Li Jinzhe , Yang Zejun , Chen Yao-Qi , Yuan Zhonghang , Chen Tao , Ouyang Wanli , Dong Nanqing , Yang Li
Published: November 2024

Protein sequence determines not only its structure but also its subcellular localization. Although a series of artificial intelligence models have been reported to predict protein subcellular localization, most of them provide only textual outputs. Here, we present deepGPS, adeepgenerative model forproteinsubcellular localization prediction. After trained with both protein primary sequences and protein subcellular localization fluorescence images, deepGPS shows the ability to predict cytoplasmic and nuclear localizations by reporting both textual labels and generative images as outputs. In addition, deepGPS shows potential to be further extended for other types of subcellular localization prediction, even with limited input data volumes for training. Finally, an openGPS website (https://bits.fudan.edu.cn/opengps) is constructed to provide a public and convenient platform for protein subcellular localization prediction with the scientific community.
Investigating a possible role ofR3HCC1Lin embryonic development and ocular disease
Authors: Fischer Megan C. , Reis Linda M. , Muheisen Sanaa , Seese Sarah E. , Semina Elena V.
Published: November 2024

Peters anomaly (PA) is an anterior segment ocular disorder with wide phenotypic variability and genetic heterogeneity. Here we report a family consisting of a male with a diagnosis of syndromic PA and his unaffected parents, with no causative variants identified in known developmental ocular genes. Exome sequencing analysis identified compound heterozygous missense variants, c. 1022A>T p.(Asp341Val) and c.1457T>A p.(Phe486Tyr), inR3HCC1L. Both variants are ultra-rare in control populations and have CADD scores of 21.9 and 23.3, respectively, suggesting possible deleterious effects. TheR3HCC1Ltranscript variants encode three different protein isoforms all sharing two conserved C-terminal domains, an RNA recognition motif (RRM) and a coiled-coil domain (CCD), and likely represent an RNA-binding protein involved in post-transcriptional gene regulation; the identified patient variants are located within the N-terminal part of the protein shared by two of the three protein isoforms, upstream of the RRM and CCD domains. To investigate the possible role ofR3HCC1Lin embryonic development, the single zebrafish ortholog ofR3HCC1L, r3hcc1l, was examined for its expression and function.In situexpression studies showed that zebrafishr3hcc1lis expressed in the developing lens, cornea, retina and hyaloid vasculature, supporting its possible role in ocular development in vertebrates. CRISPR-Cas9 gene editing was used to generate a zebrafish line with a 4-bp deletion inr3hcc1l, c.623-626del, that is predicted to result in a nonsense-mediated decay and, if expressed, a nonfunctional truncated protein (p.Thr208fs*39) lacking 80% of the RRM and the entire CCD. The resultantr3hcc1lc.623-626delheterozygous and homozygous animals did not show any visible structural abnormalities in the eye or any other systems, with normal survival of all genotypes to adulthood, providing no support for its possible role in the congenital phenotype of interest. However, the function ofr3hcc1lmay not be completely conserved with humanR3HCC1L, and/or zebrafish may have compensatory mechanisms that are not present in humans. In addition, the engineered zebrafish variant disrupts the most conserved C-terminal region of R3HCC1L/r3hcc1l shared by all protein isoforms and likely leads to a complete loss-of-function of this gene, which may be different from the disease mechanism associated with the specific missense alleles identified in the patient. Finally, while it is important to consider the possible limitations of animal models, it is also necessary to highlight that the identifiedR3HCC1Lvariants may not have any role in the phenotype observed in this single patient. Identification of newR3HCC1Lvariants of interest in families affected with PA or other congenital phenotypes, if successful, will provide further support for the possible developmental function of this gene.
Spiders bring new insight into the eco-evolutionary drivers of body size variation and sexual size dimorphism in arthropods
Authors: Ameline Camille , Lafage Denis , Vernon Philippe , Hedde Mickaël , Pétillon Julien
Published: November 2024

Body size has been used thoroughly in arthropod ecology as a reliable trait to assess fitness responses to changes in environmental factors. Among these, spiders represent a large and diverse group, colonizing almost all terrestrial habitats. Here, we propose a review on intraspecific body size variation in arthropods over two main macroecological spatial gradients—latitude and elevation—both of high interest in a global warming context. We found that more species with a direct than with an indirect development present a converse Bergmann cline along both gradients. Focusing on spiders, we propose that life history traits such as voltinism, mobility, and brood care influence intraspecific body size patterns—potentially hiding large-scale patterns. Further, we assessed interspecific sexual size dimorphism (SSD) in spider species. We found that extreme SSD—the most original feature in spider biometry—is influenced by hunting guild rather than phylogeny of spider families, suggesting that ecological factors prevail over evolutionary drivers in shaping SSD.
A simple, cost-effective microfluidic device using a 3D cross-flow T-junction for producing decellularized extracellular matrix-derived microcarriers
Authors: Kamar Farah , Gillis Connor J. , Bischoff Grace , Ali Anorin , de Bruyn John R. , Flynn Lauren E. , Poepping Tamie L.
Published: November 2024

Cell therapies using human mesenchymal stromal cells (MSCs) are promising for a wide variety of clinical applications. However, broad-scale clinical translation is limited by conventional culture methods for MSC expansion within 2D tissue-culture flasks. MSC expansion on ECM-derived microcarriers within stirred bioreactor systems offers a promising approach to support MSC growth. Previously, our team established methods for fabricating ECM-derived microcarriers from a variety of decellularized tissue sources using electrospraying techniques. However, these microcarriers are relatively large and have a broad size distribution, which may limit their utility. Smaller and more uniform microcarriers may be favorable for MSC growth within bioreactors and have greater potential to serve as a minimally invasive injectable cell delivery platform. To address these limitations, the current project focused on the development of a new microfluidic-based approach enabling both uniform and small microcarrier production. Using a novel, modified 3D T-junction design, we successfully generated microcarriers using human decellularized adipose tissue (DAT) as the ECM source. Our new cost-effective device produced microbeads that were small and monodisperse, at a range of flow rate combinations and with high production rates. Photo-crosslinking using rose bengal allowed for the generation of microcarriers that were stable following rehydration, with a mean diameter of 196 ± 47 µm. Following methods optimization and microcarrier characterization,in vitrostudies confirmed that the new microcarriers supported human adipose-derived stromal cell (hASC) attachment and growth, as well as ECM production, across 14 days within spinner flask bioreactors. Overall, this study demonstrates the feasibility of using our novel, cost-effective, and reusable microfluidics device to generate cell-supportive microcarriers comprised exclusively of ECM in a size range that could be injected via a small gauge needle and were stable in long-term culture.
CIWARS: a web server for waterborne antibiotic resistance surveillance using longitudinal metagenomic data
Authors: Emon Muhit Islam , Cheung Yat Fei , Stoll James , Rumi Monjura Afrin , Brown Connor , Choi Joung Min , Moumi Nazifa Ahmed , Ahmed Shafayat , Song Haoqiu , Sein Justin , Yao Shunyu , Khan Ahmad , Gupta Suraj , Kulkarni Rutwik , Butt Ali , Vikesland Peter , Pruden Amy , Zhang Liqing
Published: November 2024

The rise of antibiotic resistance (AR) is a major global health crisis, exacerbated by the overuse and misuse of antibiotics, leading to the rapid spread of antibiotic resistance genes (ARGs) in bacterial pathogens. This phenomenon poses significant threats to human and animal health, food security, and economic stability. Water bodies, particularly wastewater treatment plants (WWTPs), serve as critical reservoirs for ARGs, creating environments that favor the proliferation of resistant bacteria. Wastewater-based surveillance (WBS) has emerged as a cost-effective strategy for monitoring AR at the population level, providing real-time data to guide public health and policy decisions. Despite advancements in WBS, there are no comprehensive online analytical platforms for continuous environmental AR surveillance. This paper introduces CIWARS, a web server designed for AR analyses of longitudinal metagenomic data. CIWARS offers comprehensive ARG profiling, taxonomic annotation, and anomalous AR risk points detection. We demonstrate its capabilities through an interactive temporal data visualization, showcasing its potential for enhancing AR risk monitoring and guiding effective mitigation strategies. CIWARS is broadly applicable to longitudinal metagenomic data generated from any environment and aims to support global efforts in addressing the AR crisis by providing cyberinfrastructure for continuous AR surveillance. The web server is freely available athttps://ciwars.cs.vt.edu/.
Neuroprotection by chronic administration of Fluoroethylnormemantine (FENM) in mouse models of Alzheimer’s disease
Authors: Carles Allison , Freyssin Aline , Guehairia Sarra , Reguero Thomas , Vignes Michel , Hirbec Hélène , Rubinstenn Gilles , Maurice Tangui
Published: November 2024

Background

Fluoroethylnormemantine (FENM), a new Memantine (MEM) derivative, prevented amyloid-β[25–35] peptide (Aβ25–35)-induced neurotoxicity in mice, a pharmacological model of Alzheimer’s disease (AD) with high predictive value for drug discovery. Here, as drug infusion is likely to better reflect drug bioavailability due to the interspecies pharmacokinetics variation, we analyzed the efficacy of FENM after chronic subcutaneous (SC) infusion, in comparison with IP injections in two AD mouse models, Aβ25–35–injected mice and the transgenic APP /PSEN1∂E9(APP/PS1) line.

Methods

In Aβ25–35-treated mice, FENM was infused at 0.03-0.3 mg/kg/day during one week after Aβ25–35injection. For comparison, FENM and MEM were administered IP daily at 0.03-0.3 mg/kg. In 10-month-old APP/PS1 mice, FENM was administered during four weeks by daily IP injections at 0.3 mg/kg or chronic SC infusion at 0.1 mg/kg/day. Memory deficits, spatial working memory and recognition memory, were analysed. Markers of neuroinflammation, apoptosis, oxidative stress, and amyloid burden in APP/PS1 mice, were quantified. Markers of synaptic plasticity such as PSD-95 and GluN2A/B/D subunits expression in hippocampus homogenates or synaptosomes were quantified in Aβ25–35-treated mice and synaptic long-term potentiation (LTP) in hippocampal slices was analysed in APP/PS1 mice.

Results

Deficits in spontaneous alternation and object recognition in Aβ25–35mice were prevented by infused FENM at all doses tested. Similar effects were observed with the daily FENM or MEM treatments. Animals infused with 0.1 mg/kg/day FENM showed prevention of Aβ25–35-induced neuroinflammation, oxidative stress and apoptosis. FENM infusion restored Aβ25–35-induced alterations in synaptosomal PSD-95, GluN2A and P-GluN2B levels. GluN2D levels were unchanged whatever the treatment. In APP/PS1 mice, FENM infused or administered IP alleviated spontaneous alternation deficits, neuroinflammation, increases in Aβ1-40/Aβ1-42and hippocampal LTP alteration.

Conclusion

These data confirmed the neuroprotective potential of FENM in the pharmacological Aβ25–35and transgenic APP/PS1 mouse models of AD, with a superiority to MEM, and showed that the drug can be efficiently infused chronically.
Rapamycin Enhances CAR-T Control of HIV Replication and Reservoir Eliminationin vivo
Authors: Mu Wenli , Tomer Shallu , Harding Jeffrey , Kedia Nandita , Rezek Valerie , Cook Ethan , Patankar Vaibahavi , Carrillo Mayra , Martin Heather , Ng Hwee , Wang Li , Marsden Matthew D. , Kitchen Scott G. , Zhen Anjie
Published: November 2024

Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a powerful immune therapy for various diseases. Our studies in humanized mice and non-human primates (NHPs) demonstrate that hematopoietic stem cell (HSCs) modified with anti-HIV CAR leads to lifelong engraftment and supply of functional anti-viral CAR-T cells, leading to significantly reduced viral rebound after ART withdrawal. However, T cell exhaustion, driven by chronic immune activation, remains a major challenge for the continuous efficacy of CAR-T therapy, necessitating additional measures to achieve functional cure. We recently showed thatin vivotreatment with low dose rapamycin reduced chronic inflammation and improved anti-HIV T cell function in HIV-infected humanized mice. Here, we report that rapamycin significantly improved CAR-T cell function bothin vitroandin vivo.In vitrotreatment with rapamycin improved CAR-T cell mitochondria respiration and cytotoxicity.In vivotreatment with low-dose rapamycin in HIV-infected, CAR-HSC treated mice reduced chronic inflammation, prevented exhaustion of CAR-T cells and improved CAR-T control of viral replication compared to CAR-HSCs treatment alone. RNAseq analysis of sorted CAR-T cells from humanized mice showed that rapamycin significantly modified the CAR-T cell transcriptome, including the downregulation of multiple check point inhibitors and the upregulation of key genes related to cell survival. We also observed significantly delayed viral rebound after ART withdrawal and diminished HIV reservoir in mice that were treated with rapamycin and CAR-HSCs as compared to CAR-HSCs treatment alone. Taken together, our data indicate that HSCs-based anti-HIV CAR-T combined with rapamycin treatment is a promising approach for treating persistent inflammation and improving immune control of HIV replication.
Deep learning-based detection and segmentation of osseous metastatic prostate cancer lesions on computed tomography
Authors: Pawan S J , Rich Joseph , Malewar Shreyas , Patel Daksh , Muellner Matt , Hwang Darryl H , Lei Xiaomeng , Cen Steven Y , Triche Timothy , Goldkorn Amir , Mohammed Passant , Oberai Assad , Duddalwar Vinay
Published: November 2024

Purpose

Prostate adenocarcinoma frequently metastasizes to bone and is detected via computed tomography (CT) scans. Accurate detection and segmentation of these lesions are critical for diagnosis, prognosis, and monitoring. This study aims to automate lesion detection and segmentation using deep learning models.

Methods and Materials

We evaluated several deep learning models for lesion detection (EfficientNet, ResNet34, DenseNet) and segmentation (nnUNetv2, UNet, ResUNet, ResAttUNet). Performance metrics included F1 score, precision, recall, Area Under the Curve (AUC), and Dice Similarity Coefficient (DSC). Pairwise t-tests compared segmentation accuracy. Additionally, we conducted radiomic analyses to compare lesions segmented by deep learning to manual segmentations

Results

EfficientNet achieved the highest detection performance, with an F1 score of 0.82, precision of 0.88, recall of 0.79, and AUC of 0.71. Among segmentation models, nnUNetv2 performed best, achieving a DSC of 0.74, with precision and recall values of 0.73 and 0.83, respectively. Pairwise t-tests showed that nnUNetv2 outperformed ResAttUNet, ResUNet, and UNet in segmentation accuracy (p < 0.01). Clinically, nnUNetv2 also demonstrated superior specificity for lesion detection (0.9) compared to the other models. All models performed similarly in distinguishing diffuse and focal lesions, predicting weight-bearing lesions, and identifying lesion locations, although nnUNetv2 had higher specificity for these tasks. Sensitivity was highest for rib lesions and lowest for spine lesions across all models.

Conclusions

EfficientNet and nnUNetv2 were the top-performing models for detection and segmentation, respectively. The radiomic features derived from deep learning-based segmentations were comparable to those from manual segmentations, supporting the clinical applicability of these methods. Further analysis of lesion detection and spatial distribution, as well as lesion quality differentiation, underscores the models’ potential for improving diagnostic workflows and patient outcomes in clinical settings.
Low-pressure Isochoric Freezing as a scalable technique for fresh food preservation
Authors: Maida Alan L. , Consiglio Anthony N. , Bilbao-Sainz Cristina , Karman Andrew , Takeoka Gary , Powell-Palm Matthew J. , Rubinsky Boris
Published: November 2024

Efficient means of reducing food waste are critically needed to meet the demands of a growing global population, while mounting consumer interest in minimally-processed food products has simultaneously driven renewed interest in non-chemical preservation modalities. Here, we investigate the potential of low-pressure isochoric freezing (LPIF) at –1.5°C / 15 MPa to simultaneously inhibit microbial growth and preserve fresh-like physiochemical and bioactive properties during storage. Using raw cow’s milk as a model product, we demonstrate synergistic effects of mild low temperature and mild enhanced pressure that significantly improve preservation for storage periods up to 5 weeks. Given the passive nature of the technique and the compatibility of the employed pressures with standard industrial compressed gas containers, these results suggest a route towards a scalable new cold storage modality.
Modulating adipose-derived stromal cells’ secretomes by culture conditions: effects on angiogenesis, collagen deposition, and immunomodulation
Authors: Pinheiro-Machado Erika , Koster Claudia C. , Smink Alexandra M.
Published: November 2024

The secretome of adipose-derived stromal cells (ASC) presents a promising avenue for cell-free therapies due to their rich mixture of bioactive molecules. Different culture conditions can modulate the composition of this mixture, but how this affects the functional properties of the secretome remains to be investigated. This study investigated thein vitroeffects of normoxia, cytokines, high glucose, hypoxia, and hypoxia + high glucose-derived ASC secretomes on angiogenesis (tube formation assay), collagen deposition (Picrosirius-Red staining), and immunomodulation (One-way Mixed Lymphocyte Reaction in combination with an antibody-mediated cell-dependent cytotoxicity assay). The data showed that normoxia and hypoxia-derived secretomes consistently exhibited potent proangiogenic effects in both human and rat models. These secretomes also demonstrated positive influences on collagen deposition and immunomodulation. Interestingly, the human ASC hypoxia + high glucose-derived secretome emerged as a stimulator of collagen deposition and modulator of the immune system. Conversely, cytokines and high glucose-derived secretomes have shown less strong effects in almost all functional parameters. In conclusion, our findings indicate that modulating culturing conditions results in secretomes with different functional properties and emphasizes the multifaceted role of ASC secretomes in regenerative processes.
AURKA controls oocyte spindle assembly checkpoint and chromosome alignment by HEC1 phosphorylation
Authors: Blengini Cecilia S. , Mendola Robert J. , Garrisi G. John , Swain Jason E. , Schindler Karen
Published: November 2024

In human oocytes, meiosis I is error-prone, causing early miscarriages and developmental disorders. The Aurora protein kinases are key regulators of chromosome segregation in mitosis and meiosis and their dysfunction is associated with aneuploidy. Oocytes contain three Aurora kinase (AURK) proteins, but only AURKA is necessary and sufficient to support oocyte meiosis in mice. However, the unique molecular contributions of AURKA remain unclear. Here, using a combination of genetic and pharmacological approaches, we evaluated how AURKA phosphorylation regulates outer kinetochore function during oocyte meiosis. We found that the outer kinetochore protein Ndc80/HEC1 is constitutively phosphorylated at multiple residues by Aurora kinases during meiosis I, but that Serine 69 is specifically phosphorylated by AURKA in mouse and human oocytes. We further show that Serine 69 phosphorylation regulates spindle assembly checkpoint (SAC) activation and chromosome alignment during meiosis I. These results provide a fundamental mechanistic understanding of how AURKA regulates meiosis and kinetochore function to ensure meiosis I fidelity.
Interplay between material properties and cellular effects drives distinct pattern of interaction of graphene oxide with cancer and non-cancer cells
Authors: Chen Yingxian , Rosano Vinicio , Lozano Neus , Shin YuYoung , Mironov Aleksandr , Spiller David , Casiraghi Cinzia , Kostarelos Kostas , Vranic Sandra
Published: November 2024

Understanding how graphene oxide (GO) interacts with cells is crucial for its safe and efficient biomedical applications. Despite extensive research, a systematic investigation using a panel of cell lines, thoroughly characterized label-free nanomaterials, and complementary analytical techniques is lacking. Here, we examined the uptake of thin GO sheets with distinct lateral dimensions in 13 cell lines: 8 cancer (HeLa, A549, PC3, DU-145, LNCaP, SW-480, SH-SY5Y, U87-MG) and 5 non-cancer (BEAS-2B, NIH/3T3, PNT-2, HaCaT, 293T), using confocal microscopy, transmission electron microscopy, and flow cytometry. Our results reveal a striking difference in GO uptake: non-cancer cells internalized GO efficiently, while in cancer cells, GO predominantly interacted with the plasma membrane, showing minimal to no internalization. Comparison to other nanomaterials (polystyrene beads and graphene flakes) confirmed that cancer cells internalize materials similarly to non-cancer cells, indicating GO-specific interactions. We identified that GO thickness plays a pivotal role in this differential uptake. Additionally, GO disrupted the actin cytoskeleton, impairing migration in cancer but not in non-cancer cells. We propose that thin GO sheets act as a cue upon interaction with the plasma membrane of cancer cell lines, subsequently inducing actin filaments disruption leading to impaired endocytosis, migration activity, and reduced capacity of cancer cells towards GO uptake.
Relationship between calculated total blood count inflammatory readings and the degree of coronary atherosclerosis (Pilot study)
Authors: Agnė Liuizė , Aušra Mongirdienė , Jolanta Laukaitienė
Published: November 2024

Background

Some calculated total blood count readings are investigated as additional readings to help with evaluation of CAD patients’ clinical management and prognosis.

Aim

We aimed to investigate the association between readings such as NLR, MLR, PLR, NMR, LMR, MHR, SII, SIRI and the severity of CAD in patients with SAP.

Methods

This retrospective pilot study included 166 patients. All these patients underwent CA or CCTA, or both, to assess severity of CAD. Patients were divided into three ways: 1) according to presence (n=146) or absence (n=20) of CAD; 2) according to Gensini score; 3) according to the CAD-RADS score.

Results

Patients with CAD had lower LMR, higher NLR, SIRI, MLR and SII compared to patients without CAD(p<0.001 and p=0.018,respectively for SII). According to the CAD severity by Gensini score, the NLR, MLR, SII and SIRI values increases and LMR decreases gradually with severity of CAD (p<0.001). It was found moderate correlation between SII (r=0.511, p<0.001), NLR (r=0.567, p<0.001)and SIRI (r=0.474, p<0.001)and severity of CAD according to Gensini score. MLR and LMR low correlated with severity of CAD according to Gensini score (r=0.356, p<0.001; r=-0.355, p<0.001,respectively). The CAD-RADS score weakly correlated with NLR and MHR(r=0.365, p<0.001; r=0.346, p<0.001, respectively), and moderately – with LMR, MLR and SIRI (r=-0.454, p<0.001; r=0.455, p<0.001; r=0.522, p<0.001,respectively).

Conclusions

NLR, LMR and SIRI appear to be potential predictors of chronic inflammation, and SIRI is the best predictor of the degree of atherosclerosis of all the other assessed blood parameters.
In vivosingle-cell ribosome profiling reveals cell-type-specific translational programs during aging
Authors: Duré Clara , Ghoshdastider Umesh , Weber Ramona , Valdivia-Francia Fabiola , Renz Peter F. , Khandekar Ameya , Sella Federica , Hyams Katie , Taborsky David , Yigit Merve , Ormiston Mark , Yamahachi Homare , Levesque Mitchell , Ellis Stephanie , Sendoel Ataman
Published: November 2024

Somatic stem cells are characterized by their low overall protein synthesis rates, a feature implicated in driving their stemness. However, how aging reshapes the translational landscape of stem cells and how these changes impact their regenerative capacity remains poorly understood. Here, we present anin vivosingle-cell ribosome profiling strategy to monitor tissue-wide translational landscapes of the young and aged mouse epidermis. By implementing ribosomal elongation-inhibited cell isolation and switching to RNase I ribonuclease for generating ribosomal footprints, we expand the applicability of single-cell ribosome profiling toin vivosystems and facilitate the evaluation of triplet periodicity, a hallmark of high-quality ribosome profiling data. Leveraging this strategy and integrating ribosome profiling with single-cell RNA sequencing, we document thein vivotranslational landscapes of the major epidermal cell types, outline cell-type-specific translational efficiencies and capture heterogeneity in differentiation commitment within stem cell populations. Notably, we identify a pronounced translational reprogramming of AP-1 subunits specifically in aged epidermal stem cells, with functional consequences for keratinocyte behavior. Our study illustrates the power ofin vivosingle-cell ribosome profiling to map cell-type-specific translational programs and offers a scalable strategy for tissue-wide interrogation of translational landscapes at single-cell resolution.
Gene expression differences in differentially methylated sites associated with HIV status and cocaine use
Authors: Earley Eric J. , Quach Bryan C. , Fang Fang , Bierut Laura J. , Milloy M-J S. , Hayashi Kanna , DeBeck Kora , Hancock Dana B. , Aouizerat Bradley E. , Xu Ke , Johnson Eric Otto
Published: November 2024

Background

Epigenome studies of human HIV-1 (HIV) in whole blood have uncovered a growing list of differentially methylated genes associated with either HIV acquisition, disease progression, or both. Cocaine use is associated with increased disease severity, and methylation changes in some of the HIV-associated genes mediate this effect. Many of these genes are critical players in innate immune response, including both regulators and targets of interferon-alpha and NF-kB activation. However, no study to date has evaluated the gene expression dynamics for these genes in the context of HIV.

Methods

Targeted gene expression analyses were performed on 588 people who used illicit drugs within a harmonized cohort comprised of the Vancouver People Who Inject Drugs Study (VPWIDS) using RNAseq in whole blood, including 227 people living with HIV (PLWH). Eighteen genes were selected from six recent epigenome-wide association studies to test for differential expression by HIV status. Both gene-level and transcript-level expression changes were estimated using negative binomial regression models.

Results

Nine of the 18 target genes exhibited significant upregulation in PLWH after multiple hypothesis testing correction:EPSTI1, IFI44L, IFIT3, MX1, NLRC5, PARP9, PLSCR1, RIN2, andRSAD2. Transcript-level analysis detected additional upregulation of isoforms for genesCD44, RASSF3, andTAP1. Stratified analysis by cocaine use revealedMX1andRSAD2to be exclusively upregulated among PLWH who recently used cocaine. Pathway analysis identified significant dysregulation in the interferon alpha/beta signaling pathway.

Conclusions

We confirm the dysregulation of genes previously reported to have differential methylation among PLWH. Results from this study support the model of epigenetic changes altering gene expression for key immune genes such asNLRC5andMX1, and demonstrate systemic dysregulation of genes involved in innate immune function.
Comparative Analysis of MS/MS Search Algorithms in Label-Free Shotgun Proteomics for Monitoring Host-Cell Proteins Using Trapped Ion Mobility and ddaPASEF
Authors: Khalil Somar , Plisnier Michel
Published: November 2024

Host cell proteins (HCPs) are critical quality attributes that can impact the safety, efficacy, and quality of biotherapeutics. Label-free shotgun proteomics is a vital approach for HCP monitoring, yet the choice of tandem mass spectrometry (MS/MS) search algorithms directly influences identification depth and quantification reliability. In this study, six prominent MS/MS search tools—Mascot, MaxQuant, SpectroMine, FragPipe, Byos, and PEAKS—were systematically benchmarked for their performance on complex samples spiked with isotopically labeled proteins from Chinese hamster ovary cells, using trapped ion mobility spectrometry and parallel accumulation-serial fragmentation in data-dependent acquisition mode. Key performance metrics, including peptide and protein identifications, data extraction precision, fold-change (FC) accuracy, linearity, and measurement trueness, were evaluated. A Bayesian modeling framework with Hamiltonian Monte Carlo sampling was employed to robustly estimate FC means and variances, alongside local false discovery rates through posterior probability calibration. Bayesian decision theory, implemented via expected utility maximization, was used to balance accuracy against posterior uncertainty, providing a probabilistic assessment of each tool’s performance. Through this cumulative analysis, variability across tools was observed: some excelled in identification sensitivity and protein coverage, others in quantitative accuracy with minimal bias, and a few offered balanced performance across metrics. This study establishes a rigorous, data-driven framework for tool benchmarking, delivering insights for selecting MS/MS tools suited to HCP monitoring in biopharmaceutical development.

Graphical abstract
RCANE: A Deep Learning Algorithm for Whole-genome Pan-Cancer Somatic Copy Number Aberration Prediction using RNA-seq Data
Authors: Ge Changhao , Hu Xiaowen , Zhang Lin , Li Hongzhe
Published: November 2024

Transcriptome sequencing (RNA-seq) is widely used in cancer research to study the transcriptome and its role in disease progression. Somatic copy number aberrations (SCNAs) are key drivers of cancer development, and inferring SCNAs from RNA-seq data can provide critical insights for disease classification and treatment prediction. We introduce RCANE, a deep learning-based method designed to predict genome-wide SCNAs across various cancer types using RNA-seq data. RCANE is trained on data from The Cancer Genome Atlas (TCGA) and DepMap cancer cell lines, demonstrating superior performance compared to existing methods. This scalable approach offers a robust solution for improving SCNA prediction in cancer diagnostics and treatment.