bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a nutrition-related genetic–clinical–radiological nomogram associated with behavioral and psychological symptoms in Alzheimer’s disease
Authors: Jiang Jiwei , Liu Yaou , Wang Anxin , Zhuo Zhizheng , Shi Hanping , Zhang Xiaoli , Li Wenyi , Sun Mengfan , Jiang Shirui , Wang Yanli , Zou Xinying , Zhang Yuan , Jia Ziyan , Xu Jun
Published: November 2023

Background:

Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic–clinical–radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.

Methods:

This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demoimagedatas, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.

Results:

Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276–13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086–0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830–21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001–0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884–0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686–0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations.

Conclusion:

A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.

Registration:

Chictr.org.cn, ChiCTR2100049131.
Cardiac Rehabilitation Program Effect on Health-Related Quality of Life Among Patients With Coronary Artery Bypass Grafts
Authors: Alrahahleh Mohammad , Subih Maha , Megdadi Raya , Altarabsheh Salah Eldien , Alfawaeer Zyad , Saad Alaa , Khalil Tahani
Published: November 2023

Coronary artery bypass graft (CABG) necessitates modification in patients' lifestyle after discharge, which leads to a decrease in their health-related quality of life (HRQOL). Hence, cardiac rehabilitation programs (CRPs) are needed. This study aimed to explore the effect of a CRP on HRQOL and physiological factors on CABG patients after discharge. The study used a quasiexperimental pre-/posttest design. Two experimental and control groups tested with 30 patients with CABG surgery participated in a rehabilitation center after discharge. The Arabic version of the Nottingham Health Profile for measuring HRQOL was used. In addition to several sociodemographic and physiological variables, findings indicated a significant improvement in HRQOL and its domains for the experimental group after CRP (mean = 2.06, SD = 1.7) when compared with the control group (mean = 19.9, SD = 3.1; P = .01), as well as some physiological variables 3 months after surgery. The CRP is an important intervention that administrators and cardiologists should take into consideration for CABG patients. It improves not just their HRQOL but also many physiological indicators.
Health Literacy Among Patients With Acute Coronary Artery Diseases
Authors: Aburadwan Maha K. , Hayajneh Ferial A.
Published: November 2023

The purpose of this study is to integrate evidence on predictors, consequences, in addition to the strategies for enhancing health literacy (HL) for patients with acute coronary artery diseases. An integrative review was conducted by searching four main electronic databases: the Web of Science, PubMed, ScienceDirect, and MEDLINE. Twenty-three studies met the inclusion criteria and were included in the final review process. The review identified the most common predictors, consequences, and relationship of HL with health outcomes in patients with acute coronary artery disease. In addition to the main strategies that enhance HL, patients with or at risk for acute coronary artery disease need a good level of HL to cope with the disease's consequences. It is recommended to include routine assessment and management of HL levels in acute coronary artery disease treatment protocols to improve clinical outcomes.
Factors of Missed Nursing Care in Intensive Care Units
Authors: Daraghmeh Hameed , Ayed Ahmad , Salameh Basma , Fashafsheh Imad
Published: November 2023

Maintaining a high standard of nursing care is imperative for ensuring patient safety. Several factors significantly impact the provision of nursing care, including work environment resources, personnel coordination, work systems, and head nurse leadership. In addition, each nurse's clinical and academic career also plays a role in shaping the quality of care provided to patients.

This article reports results of a cross-sectional study aimed to identify the different types of missed nursing care and the factors that contribute to them, as perceived by nurses, and second, to investigate how nurses' characteristics may relate to the occurrence of missed nursing care. Data for this study were obtained through a self-administered questionnaire that was distributed to participants working in an intensive care unit. The study included a final sample size of 176 participants, all of whom worked in intensive care unit hospitals located in the north region of Palestine.

The study found that handwashing, setting up meals for patients who feed themselves, discharge planning, and response to a call light were the most frequently missed nursing care activities. The primary factors identified as reasons for missed nursing care were inadequate availability of labor and material resources, along with communication issues. Efforts to address these identified issues can potentially lead to improved quality of nursing care in intensive care units.
Antiplatelet Agents Inhibit Platelet Adhesion and Aggregation on Glass Surface Under Physiological Flow Conditions: Toward a Microfluidic Platelet Functional Assay Without Additional Adhesion Protein Modification
Authors: Liu Zhanshu , Huang Xiaojing , Gao Xuemei , Zhang Tiancong , He Cui , Ding Ling , Li Yuan
Published: November 2023

As the pathogenesis of arterial thrombosis often includes platelet adhesion and aggregation, antiplatelet agents are commonly used to prevent thromboembolic events. Here, a new microfluidic method without additional adhesion protein modification was developed to quantify the inhibitory effect of antiplatelet drugs on the adhesion and aggregation behavior of platelets on glass surfaces under physiological flow conditions. Polydimethylsiloxane-glass microfluidic chips were fabricated by soft photolithography. Blood samples from healthy volunteers or patients before and after taking antiplatelet drugs flowed through the microchannels at wall shear rates of 300 and 1500 second−1, respectively. The time to reach 2.5% platelet aggregation surface coverage (Ti), surface coverage (A150s), and mean fluorescence intensity (F150s) were used as quantitative indicators. Aspirin (80 μM) prolonged Ti and reduced F150s. Alprostadil, ticagrelor, eptifibatide, and tirofiban prolonged Ti and reduced A150s and F150s in a concentration-dependent manner, whereas high concentrations of alprostadil did not completely inhibit platelet aggregation. Aspirin combined with ticagrelor synergistically inhibited platelet adhesion and aggregation; GPIb-IX-von Willebrand factor inhibitors partially inhibited platelet aggregation, and the inhibition was more pronounced at 1500 than at 300 second−1. Patient administration of aspirin or (and) clopidogrel inhibited platelet adhesion and aggregation on the glass surface under flow conditions. This technology is capable of distinguishing the pharmacological effects of various antiplatelet drugs on inhibition of platelet adhesion aggregation on glass surface under physiological flow conditions, which providing a new way to develop microfluidic platelet function detection method without additional adhesive protein modification for determining the inhibitory effects of antiplatelet drugs in the clinical setting.
A Systematic Review and Meta-analysis of Renin–angiotensin System Inhibitors and Angiotensin Receptor Neprilysin Inhibitors in Preventing Recurrence After Atrial Fibrillation Ablation
Authors: Sun Qian , Cui Wenyan , Zhang Xinhui , Tian Yunfei , Huang Guangliang , He Wenjuan , Zhao Yonghong , Zhao Xiaojuan , Li Dan , Liu Xiuju
Published: November 2023

To systematically evaluate the efficacy and safety of renin–angiotensin system inhibitors (RASIs) and angiotensin receptor neprilysin inhibitors in preventing the recurrence of atrial fibrillation after atrial fibrillation ablation, we have written this meta-analysis. We systematically searched randomized controlled trials or cohort studies on RASIs and angiotensin receptor neprilysin inhibitor-sacubitril/valsartan (SV) in preventing the recurrence of atrial fibrillation. Two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Afterward, the meta-analysis was performed using RevMan 5.3 software. This meta-analysis results showed that the recurrence rate of atrial fibrillation after ablation in subjects using RASIs was lower than that in subjects not using them [relative risk = 0.85, 95% confidence interval (CI) (0.72–0.99), P = 0.03]; the recurrence rate in subjects using SV was lower than that in subjects using RASIs [RR= 0.50, 95% CI (0.37–0.68), P < 0.00001]. These results show that both the use of RASIs and SV can prevent the recurrence of after atrial fibrillation ablation, among which the use of SV is more effective.
CAR-T Cell Therapy Shows Similar Efficacy and Toxicity in Patients With DLBCL Regardless of CNS Involvement
Authors: Shumilov Evgenii , Boyadzhiev Hristo , Mazzeo Paolo , Akhoundova Dilara , Daskalakis Michael , Novak Urban , Lenz Georg , Bacher Ulrike , Pabst Thomas
Published: November 2023

Efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) involvement remain understudied. Here we analyzed the outcomes of CAR-T cell therapy in r/r DLBCL patients with CNS involvement and compared them with patients without CNS disease. Retrospective and monocentric comparative analysis of patient cohort with r/r DLBCL treated with CAR-T cell therapy: 15 patients with CNS versus 65 patients without CNS involvement. Overall response rates (80% versus 80%; P = 1.0), progression-free survival (P = 0.157), and overall survival (P = 0.393) were comparable for both cohorts. The frequency of cytokine release syndrome was comparable in the CNS and non-CNS cohorts; 93% versus 80%; P = 1.0. Numerically, immune effector-cell–associated neurotoxicity syndrome (all grades) was more frequent in patients with CNS manifestation (53% versus 29%; P = 0.063), although no grade 4 events were documented. Our study suggests that CAR-T cell therapy is effective and feasible in patients with r/r DLBCL and CNS manifestation.
Aligning Professional Development With Service Coordinator Knowledge and Skills
Authors: Childress Dana C. , Prohn Seb M. , Hill Corinne F. , Terry Lisa M.
Published: November 2023

Service coordinators under Part C of the Individuals With Disabilities Education Act (IDEA, 2004) help families navigate the early intervention (EI) system and ensure regular communication among team members so services are aligned with family priorities and recommended EI practices. To meet the demands of service coordination, personnel entering the EI field who will serve as service coordinators must receive high-quality professional development to orient them to their unique roles and responsibilities. The purpose of this program evaluation was to examine the effectiveness of one state's service coordination training program and its alignment with the Knowledge and Skills for Service Coordinators (KSSC), a resource document in the Division for Early Childhood and IDEA Infant Toddler Coordinators Association (DEC & ITCA) Joint Position Statement: Service Coordination in Early Intervention (2020). Survey results suggested that the training program was associated with increased knowledge and skills for service coordinator participants in many of the KSSC areas. Participants also reported using what they learned in their work with families. The rubric used to evaluate this training program could be a resource for state-level professional development providers to evaluate alignment of current and future training for service coordinators with the KSSC.
Risk factors associated with haptic malposition in eyes implanted with implantable collamer lenses
Authors: Chang Weiteng , Niu Lingling , Zhou Xingtao , Wang Xiaoying , Yu Zhiqiang , Qian Yishan
Published: November 2023

Purpose:

To examine the risk factors for haptic malposition in eyes with implantable collamer lens (ICL).

Setting:

Eye and ENT Hospital, Fudan University, Shanghai, China.

Design:

Prospective nonrandomized observational study.

Methods:

This study included 134 (77.9%) of 172 initially enrolled patients who underwent ICL implantation and completed a 1-year follow-up. The extent of haptics present in the ciliary sulcus (ICS) was measured. Patients were categorized based on ICS count (0 to 4). The position of the haptics was quantified as the distance between the iris root and the terminal tip of ICL haptics (iris root to haptic tip, IRH). The related factors to the ICS count and its correlation with the central vault were analyzed.

Results:

ICS distribution was 0 ICS in 19 eyes (14.2%), 1 in 22 eyes (16.4%), 2 in 32 eyes (23.9%), 3 in 29 eyes (21.6%), and 4 in 32 eyes (23.9%). Parameters like maximum ciliary body thickness (CBTmax,P= .008), iris–ciliary process distance (ICPD,P< .001), and ciliary process length (P= .034) varied significantly across ICS groups. A multiple linear regression analysis revealed that the iris–ciliary angle (P= .006), CBTmax (P= .007), the distance between the sulcus-to-sulcus plane and the anterior crystalline lens surface (STSL,P= .035), and ICL size (P= .015) were significantly associated with IRH. Spherical equivalents (P= .042), STSL (P= .001), and ICS count (P= .020) significantly correlated with the central vault.

Conclusions:

Shortened ciliary process is a primary risk for haptic malposition. The ICS count significantly relates to the central vault.
Hemodynamic monitoring in liver transplantation ‘the hemodynamic system’
Authors: Kandil Sherif , Sedra Ashraf
Published: November 2023

Purpose of review

The purpose of this article is to provide a comprehensive review of hemodynamic monitoring in liver transplantation.

Recent findings

Radial arterial blood pressure monitoring underestimates the aortic root arterial blood pressure and causes excessive vasopressor and worse outcomes. Brachial and femoral artery monitoring is well tolerated and should be considered in critically ill patients expected to be on high dose pressors. The pulmonary artery catheter is the gold standard of hemodynamic monitoring and is still widely used in liver transplantation; however, it is a highly invasive monitor with potential for serious complications and most of its data can be obtained by other less invasive monitors. Rescue transesophageal echocardiography relies on few simple views and should be available as a standby to manage sudden hemodynamic instability. Risk of esophageal bleeding from transesophageal echocardiography in liver transplantation is the same as in other patient populations. The arterial pulse waveform analysis based cardiac output devices are minimally invasive and have the advantage of real-time beat to beat monitoring of cardiac output. No hemodynamic monitor can improve clinical outcomes unless integrated into a goal-directed hemodynamic therapy. The hemodynamic monitoring technique should be tailored to the patient's medical status, surgical technique, and the anesthesiologist's level of expertise.

The current article provides a review of the current hemodynamic monitoring systems and their integration in goal-directed hemodynamic therapy.
Bevacizumab in the Treatment of Refractory Brain Edema in High-grade Glioma
Authors: Alsahlawi Aysha K. , Michaud-Couture Claudie , Lachance Alexandre , Bergeron-Gravel Samuel , Létourneau Mélanie , Bourget Catherine , Gould Peter V. , Giannakouros Panagiota , Nakada Emily M. , Faury Damien , Crevier Louis , Bouffet Éric , Jabado Nada , Larouche Valérie , Renzi Samuele
Published: November 2023

We report the case of a 14-year-old boy with a steroid-dependent refractory tumor whose longstanding dexamethasone treatment was successfully discontinued after a course of bevacizumab. The use of bevacizumab despite the absence of clear evidence of radionecrosis allowed a significant decrease in the amount of the brain edema.
The Mediating Effects of Perceived Family Support in the Relationship Between Anxiety and Problematic Smartphone Use
Authors: Long Jiang , Liu Yueheng , Wang Yingying , Pottié Aurore , Cornil Aurélien , Deleuze Jory , Wu Qiuxia , Chen Shubao , Ma Yuejiao , Wang Qianjin , Hao Yuzhu , Lu Jing , Radu Ilinca-Gabriela , Liu Tieqiao , Billieux Joël
Published: November 2023

Problematic smartphone use (PSU) is frequently considered a public health issue, especially in East Asia and Europe. Yet, there is a paucity of research focusing on cultural and familial determinants of PSU. This cross-cultural study aimed to investigate smartphone usage patterns and possible mediating effects of perceived family support (PFS) from a stress-coping perspective. Convenience samples of 790 Chinese and 439 Belgian undergraduates completed an online survey that focused on sociodemographics and psychological variables (i.e., anxiety, depression, PFS, and PSU). In both samples, PSU was positively associated with anxiety and depression, and negatively associated with PFS. However, after controlling for sex and age in structural equation models, the consistent mediating effects of PFS were only found between anxiety and PSU in both cultural settings. These findings suggest that psychological interventions that take into account familial factors could be helpful for young people presenting with anxiety and PSU.
The Relationship Between Elbow Flexion Postures and Overhead Reaching in Birth Brachial Plexus Injuries
Authors: Goins T. R. , Fox John , Saul Katherine , Servello Cindy , Sullivan Jane E.
Published: November 2023

Purpose:

The aim of this study was to investigate the effect of alterations in muscle length of the biceps in various elbow postures during shoulder elevation and muscle activation.

Methods:

Participants aged 5 years and older with a birth brachial plexus injury were asked to perform elevation shoulder (abduction and flexion) in 7 elbow conditions. Surface electromyography was applied to bilateral biceps and triceps.

Results:

Peak shoulder elevation was present in the immobilized 20° elbow posture. Muscle activity of the triceps and biceps was impacted by the elbow posture via immobilization.

Conclusions:

Elbow postures in elongated postures, via immobilization, may result in higher shoulder elevation due to increased passive forces when there is an altered muscle state of the biceps in this population. Clinicians should consider the optimal elbow joint posture (<30°) to improve overhead reaching in this population.
Examining Characteristics of Local Public Health Systems With Exceptional Tribal Organization Participation
Authors: Bauer Kyla L. , Mitchell Amelia L. , Mays Glen P.
Published: November 2023

Objective:

To learn feasible ways to increase multisector community partnership with tribal organizations, meaning tribal health authorities or American Indian and Alaska Native (AI/AN)–serving organizations, by examining characteristics of local public health systems with exceptional tribal organization participation.

Design, Setting, and Participants:

In total, 728 local public health departments were surveyed in 2018 to generate a nationally representative sample of local public health systems in the United States. A positive deviance approach using logistic regression helped identify local public health systems that had tribal organization participation despite characteristics that make such participation statistically unlikely. Local public health systems with exceptional tribal organization participation were compared with systems with conventional participation, examining measures known to impact the formation of public health partnerships.

Main Outcome Measure:

This study used an exploratory logistic regression approach to identify unique characteristics of local public health systems with exceptional tribal organization participation.

Results:

Of 728 health systems surveyed, 21 were identified as having exceptional tribal organization participation. Across varying thresholds to identify exceptional participation, having a higher network density and prioritizing equity in public health activities were found to consistently distinguish exceptional tribal organization participation in both nonrural and rural areas.

Conclusions:

Public health partnerships with tribal organizations are possible even in circumstances that make them unlikely. Efforts to build denser networks of collaborating organizations and prioritize equity may help public health systems achieve success with tribal organization partnerships.
Do the Ultrasonographic Measures of Midurethral Sling Location Relate With Surgical Outcomes?
Authors: Seval Mehmet Murat , Cetinkaya Serife Esra , Baydemir Kaan , Varli Bulut , Dokmeci Fulya
Published: November 2023

Importance

The proper placement of a midurethral sling (MUS) is the key factor for a successful surgical outcome.

Objective

This study aimed to evaluate the relationship of perineal ultrasonographic measures of the tape location with subjective and objective outcomes after MUS surgery at midterm follow-up of women.

Methods

The tape percentile (TP; total urethral length/bladder neck tape distance×100) and urethra tape distance (UTD; the shortest distance from the longitudinal smooth muscle complex of the urethra to the midpoint of the tape) were correlated with midterm surgical success. Patient satisfaction measured with the visual analog scale (VAS) was considered as the primary outcome. The presence of stress urinary incontinence on direct questioning, the Urinary Distress Inventory 6 (UDI-6) scores, findings of the cough stress test, free uroflowmetry, postvoid residual volume, and single-cycle voiding ambulatory urodynamic monitoring (AUM) were the other outcomes.

Results

Seventy-eight women were evaluated at a mean follow-up of 4.4 ±3.3 years. Women who were highly satisfied (VAS ≥ 8) had a significantly higher TP (64.7% vs 50.8%, P < 0.001) and lower UTD (3.6 vs 4.5 mm, P = 0.018). Irritative, stress, and obstructive scores at UDI-6 increased as the tape was located closer to the bladder neck (P < 0.001, P < 0.001 and P = 0.044, respectively), and stress symptoms decreased with a tape closer to the urethra (P < 0.001). Women with detrusor overactivity at AUM were found to have a lower TP (P < 0.001).

Conclusion

The perineal ultrasonographic evaluation of tape location with UTD and TP seems to be well correlated with the women's midterm MUS surgical outcomes.
Central vestibular networking for sensorimotor control, cognition, and emotion
Authors: Dieterich Marianne , Brandt Thomas
Published: November 2023

Purpose of review

The aim of this study was to illuminate the extent of the bilateral central vestibular network from brainstem and cerebellum to subcortical and cortical areas and its interrelation to higher cortical functions such as spatial cognition and anxiety.

Recent findings

The conventional view that the main function of the vestibular system is the perception of self-motion and body orientation in space and the sensorimotor control of gaze and posture had to be developed further by a hierarchical organisation with bottom-up and top-down interconnections. Even the vestibulo-ocular and vestibulo-spinal reflexes are modified by perceptual cortical processes, assigned to higher vestibulo-cortical functions. A first comparative fMRI meta-analysis of vestibular stimulation and fear-conditioning studies in healthy participants disclosed widely distributed clusters of concordance, including the prefrontal cortex, anterior insula, temporal and inferior parietal lobe, thalamus, brainstem and cerebellum. In contrast, the cortical vestibular core region around the posterior insula was activated during vestibular stimulation but deactivated during fear conditioning. In recent years, there has been increasing evidence from studies in animals and humans that the central vestibular system has numerous connections related to spatial sensorimotor performance, memory, and emotion. The clinical implication of the complex interaction within various networks makes it difficult to assign some higher multisensory disorders to one particular modality, for example in spatial hemineglect or room-tilt illusion.

Our understanding of higher cortical vestibular functions is still in its infancy. Different brain imaging techniques in animals and humans are one of the most promising methodological approaches for further structural and functional decoding of the vestibular and other intimately interconnected networks. The multisensory networking including cognition and emotion determines human behaviour in space.
Antimicrobial resistance research in Singapore – mapping current trends and future perspectives
Authors: Poon Selina , Goh Dai Mei , Khoo Astrid , Lin Yueh Nuo , Leo Yee Sin , Lee Tau Hong
Published: November 2023

Antimicrobial resistance (AMR) research is increasing globally, but its extent in Singapore is unclear. The aim of this study was to review the current research trends on AMR in Singapore and identify the types of research conducted. Scientific literature on AMR from Singapore published between 2009 and 2019 were retrieved from databases using a search string that included search terms that would encompass the range of terminologies related to “antimicrobial resistance” and “Singapore”. A total of 741 AMR research and review articles published between 2009 and 2019 were identified, which described research led by researchers from Singapore, that involved researchers from Singapore in overseas collaborations, or involved samples or data from Singapore. Articles were assigned to the most appropriate research domain and relevant sector(s) (animal, environment, food or human). Although an upward trend in the number of AMR research articles published was observed, articles that described research on AMR knowledge, awareness, socioeconomic impacts and transmission remained scarce. Furthermore, the higher proportion of research articles from the human sector highlighted that more research from the non-human sectors was needed, which coincidentally began to gradually increase in the last five years. By reviewing the types of studies that were conducted in each domain, broad areas where research gaps exist could be identified, as well as currently unexplored topics. With increasing complexity of the AMR problem and its impacts on multiple sectors, having a comprehensive overview of the evidence gaps is paramount to the development of a relevant One Health research agenda in AMR.

Highlights

A review of the trend and scope of AMR research including all sectors was conducted

AMR research in Singapore is on the upward trend

AMR research in the non-human sectors remained low

Research on socio-behavioural factors and transmission of AMR to be prioritised
Cell-mediated cholesterol crystal processing and clearance observed by 3D cryo-imaging in human atherosclerotic plaques
Authors: Capua-Shenkar Jenny , Kaestner Antonia , Rechav Katya , Brumfeld Vlad , Kaplan-Ashiri Ifat , Avinoam Ori , Speter Chen , Halak Moshe , Kruth Howard , Addadi Lia
Published: November 2023

Atherosclerosis is a pathology affecting the arteries, characterized by the buildup of plaques in the blood vessel walls. Atherosclerosis is the main cause of cardiovascular diseases, which constitute the leading cause of death in the world. Cholesterol crystals are the main components of the plaques, which actively participate in plaque growth and rupture and do not dissolve in aqueous environments. Employing novel cryo-scanning electron microscopy techniques, we examined human atherosclerotic plaques at high resolution, in 3D, and in close to native conditions. We show that cholesterol crystal clearance occurs in advanced human plaques through the activity of cells. We suggest that this occurs by enzymatic esterification of cholesterol to cholesteryl ester, which aggregates into intra- and extra-cellular pools. This discovery provides further understanding of the disease process in atherosclerosis, and may inspire new therapeutic approaches.
Engraftment and injury repair in regionally conditioned rat lungin vivoby lung progenitors derived from human pluripotent stem cells
Authors: Liu Hsiao-Yun , Predella Camilla , Chen Ya-Wen , Wang Jing , Pezet Mikael , Liang Songjingyi , Farè Silvia , Murray John W. , Saqi Anjali , Vunjak-Novakovic Gordana , Snoeck Hans-Willem , Dorrello N. Valerio
Published: November 2023

Although lung disease is a major cause of mortality, the mechanisms involved in human lung regeneration are unclear because of the lack of experimental models. Here we report a novel model where human pluripotent stem cell-derived expandable cell lines sharing features of airway secretory and basal cells engraft in the distal rat lung after conditioning by locoregional de-epithelialization followed by irradiation and immunosuppression. The engrafting cells, which we named distal lung epithelial progenitors (DLEPs), contributed to alveolar epithelial cells and generated ‘KRT5-pods’, structures involved in distal lung repair after severe injury, but only rarely to distal airways. Most strikingly, however, injury induced by the conditioning regimen was largely prevented by the engrafting DLEPs. The approach described here provides a model to study mechanisms involved in human lung regeneration, and potentially lays the foundation for the preclinical development of cell therapy to treat lung injury and disease.
pyaging: a Python-based compendium of GPU-optimized aging clocks
Authors: de Lima Camillo Lucas Paulo
Published: November 2023

Motivation

Aging is intricately linked to diseases and mortality and is reflected in molecular changes across various tissues. The development and refinement of biomarkers of aging, healthspan, and lifespan using machine learning models, known as aging clocks, leverage epigenetic and other molecular signatures. Despite advancements, as noted by the Biomarkers of Aging Consortium, the field grapples with challenges, notably the lack of robust software tools for integrating and comparing these diverse models.

Results

I introducepyaging, a comprehensive Python package, designed to bridge the gap in aging research software tools.pyagingintegrates over 30 aging clocks, with plans to expand to more than 100, covering a range of molecular data types including DNA methylation, transcriptomics, histone mark ChIP-Seq, and ATAC-Seq. The package features a variety of model types, from linear and principal component models to neural networks and automatic relevance determination models. Utilizing a PyTorch-based backend for GPU acceleration,pyagingensures rapid inference even with large datasets and complex models. The package supports multi-species analysis, currently including humans, various mammals, and C. elegans.

Availability and Implementation

pyagingis accessible athttps://github.com/rsinghlab/pyaging. The package is structured to facilitate ease of use and integration into existing research workflows, supporting the flexible anndata data format.

Supplementary Information

Supplementary materials, including detailed documentation and usage examples, are available online at thepyagingdocumentation site (https://pyaging.readthedocs.io/en/latest/index.html).
Impact of the Excitatory-Inhibitory Neurons Ratio on Scale-Free Dynamics in a Leaky Integrate-and-Fire Model
Authors: Dehghani-Habibabadi Mohammad , Safari Nahid , Shahbazi Farhad , Zare Marzieh
Published: November 2023

The relationship between ratios of excitatory to inhibitory neurons and the brain’s dynamic range of cortical activity is crucial. However, its full understanding within the context of cortical scale-free dynamics remains an ongoing investigation. To provide insightful observations that can improve the current understanding of this impact, and based on studies indicating that a fully excitatory neural network can induce critical behavior under the influence of noise, it is essential to investigate the effects of varying inhibition within this network. Here, the impact of varying ratios on neural avalanches and phase transition diagrams, considering a range of control parameters in a leaky integrate-and-fire model network, is examined. Our computational results show that the network exhibits critical, sub-critical, and super-critical behavior across different control parameters. In particular, a certain ratio leads to a significantly extended dynamic range compared to others and increases the probability of the system being in the critical regime. To address differences between various ratios, we utilized the Kuramoto order parameter and conducted a finite-size scaling analysis to determine the critical exponents associated with phase transitions. In order to characterize the criticality, we examined the distribution of neuronal avalanches at the critical point and the scaling behavior characterized by specific exponents.
Artificial environment impact: O2 concentration changes between IVM and IVF alter embryo production, metabolism, and epigenetic marks
Authors: Cruz Jessica B , Nogueira Carolina M , Sangalli Juliano R , Nociti Ricardo P , Ambrizi Dewison R , Bridi Alessandra , Pinzon Jorge , Alves Maira BR , de Lima Vera FMH , Watanabe Yeda F , Bressan Fabiana F , Meirelles Flavio V , Sampaio Rafael V
Published: November 2023

Creating an optimal in vitro cell culture environment requires careful simulation of all critical components, especially the gaseous atmosphere. Although it is well-documented that embryonic culture under low oxygen tension promotes embryonic development, little is known about the effect of changes in in vitro maturation (IVM) and fertilization (IVF) on the epigenome. This study explores the role of oxygen tension variation in the early stages of in vitro production of bovine embryos and its impact on oxidative stress and epigenetic remodeling. We initially validated our system by scrutinizing the epigenetic effects on bovine fibroblasts. We observed that cell cultures under 20% O2 exhibited reduced H3K9me2 levels in early passages, which stabilized with prolonged cultivation and elevated gene expression of HIF2a and KDM5C. Our results reveal that oocytes maturing in 20% O2 environments have heightened levels of reactive oxygen species (ROS) and glutathione (GSH), whereas blastocyst embryos maturing under reduced oxygen tension exhibit increased oxidative stress markers (NRF2,SOD1,SOD2), with upregulated transcripts observed in epigenetic remodelers (KDM5A,TET1). Elevated O2 levels in both IVM and IVF processes showcase improved embryo production. Maintaining consistent O2 levels at either 5% or 20% between IVM and IVF results in heightened GSH, reduced ROS, and increased levels of H3K9me2/3 in embryos. Finally, distinct DNA methylation patterns emerge, indicating higher levels in groups matured under low O2 tension and increased DNA hydroxymethylation in groups fertilized under low O2 tension. In conclusion, our comprehensive investigation underscores the critical role of oxygen concentration in shaping the epigenetic landscape during the early stages of in vitro culture. These findings provide valuable insights for optimizing conditions in assisted reproductive technologies.
Multivariate analysis of metabolic state vulnerabilities across diverse cancer contexts reveals synthetically lethal associations
Authors: Abecunas Cara , Kidd Audrey D. , Jiang Ying , Zong Hui , Fallahi-Sichani Mohammad
Published: November 2023

Targeting the distinct metabolic needs of tumor cells has recently emerged as a promising strategy for cancer therapy. The heterogeneous, context-dependent nature of cancer cell metabolism, however, poses challenges in identifying effective therapeutic interventions. Here, we utilize various unsupervised and supervised multivariate modeling approaches to systematically pinpoint recurrent metabolic states within hundreds of cancer cell lines, elucidate their association with tumor lineage and growth environments, and uncover vulnerabilities linked to their metabolic states across diverse genetic and tissue contexts. We validate key findings via analysis of data from patient-derived tumors and pharmacological screens, and by performing new genetic and pharmacological experiments. Our analysis uncovers new synthetically lethal associations between the tumor metabolic state (e.g., oxidative phosphorylation), driver mutations (e.g., loss of tumor suppressor PTEN), and actionable biological targets (e.g., mitochondrial electron transport chain). Investigating the mechanisms underlying these relationships can inform the development of more precise and context-specific, metabolism-targeted cancer therapies.
A reappraisal of the default mode and frontoparietal networks in the common marmoset brain
Authors: Okuno Takuto , Ichinohe Noritaka , Woodward Alexander
Published: November 2023

In recent years the common marmoset homologue of the human default mode network (DMN) has been a hot topic of discussion in the marmoset research field. Previously, the posterior cingulate cortex regions (PGM, A19M) and posterior parietal cortex regions (LIP, MIP) were defined as the DMN, but some studies claim that these form the frontoparietal network (FPN). We restarted from a neuroanatomical point of view and identified two DMN candidates: Comp-A (which has been called both the DMN and FPN) and Comp-B. We performed GLM analysis on auditory task-fMRI and found Comp-B to be more appropriate as the DMN, and Comp-A as the FPN. Additionally, through fingerprint analysis, a DMN and FPN in the tasking human was closer to the resting common marmoset. The human DMN appears to have an advanced function that may be underdeveloped in the common marmoset brain.
Robust diagnosis of infectious disease, autoimmunity and cancer from the paratope networks of adaptive immune receptors
Authors: Xu Zichang , Ismanto Hendra S , Saputri Dianita S , Haruna Soichiro , Sun Guanqun , Wilamowski Jan , Teraguchi Shunsuke , Sengupta Ayan , Li Songling , Standley Daron M
Published: November 2023

Liquid biopsies based on peripheral blood offer a minimally invasive alternative to solid tissue biopsies for the detection of diseases, primarily cancers. However, such tests currently consider only the serum component of blood, overlooking a potentially rich source of biomarkers: adaptive immune receptors (AIRs) expressed on circulating B and T cells. Machine learning-based classifiers trained on AIRs have been reported to accurately identify not only cancers, but also autoimmune and infectious diseases as well. However, when using the conventional “clonotype cluster” representation of AIRs, donors within a disease or healthy cohort exhibit vastly different features, limiting the generalizability of these classifiers. This paper addresses the challenge of classifying specific diseases from circulating B or T cells by developing a novel representation of AIRs based on similarity networks constructed from their antigen-binding regions (paratopes). Features based on this novel representation, paratope cluster occupancies (PCOs), significantly improved disease classification performance for infectious disease, autoimmunity and cancer. Under identical methodological conditions, classifiers trained on PCOs achieved a mean ROC AUC of 0.893 when applied to new donors, compared to clonotype cluster-based classifiers (0.714) or the best-performing published classifier (0.777). Surprisingly, for cancer patients, we observed that some of the AIRs that were important for classification were significantly more abundant in healthy controls than in individuals with disease. These “healthy-biased” AIRs were predicted to target known cancer-associated antigens at dramatically higher rates than healthy AIRs as a whole (Z scores > 75), suggesting the existence of an overlooked reservoir of cancer-targeting immune cells that are diagnostic and identifiable from a routine blood test. Consequently, PCOs not only enhance classification of a broad range of diseases but also identify immune cells with therapeutic potential.
Sensory uncertainty influences motor learning differently in blocked versus interleaved trial contexts when both feedforward and feedback processes are engaged
Authors: Crossley Matthew J. , Hewitson Christopher L. , Kaplan David M.
Published: November 2023

Theories of human motor learning commonly assume that the degree to which movement plans are adjusted in response to movement errors scales with the precision of sensory feedback received regarding their success. However, support for such error-scaling models has mainly come from experiments that limit the amount of correction that can occur within an ongoing movement. In contrast, we have recently shown that when this restriction is relaxed, and both within-movement and between-movement corrections co-occur, movement plans undergo large and abrupt changes that are strongly correlated with the degree of sensory uncertainty present on the previous trial and are insensitive to the magnitude and direction of the experienced movement error. Here, we show that the presence of these abrupt and error-insensitive changes can only be reliably detected when different levels of sensory precision are interleaved pseudo randomly on a trial-by-trial basis. These results augment our earlier findings and suggest that the co-occurrence of within-movement and between-movement corrections is not the only important aspect of our earlier study that challenged the error-scaling models of motor learning under uncertainty.

Author summary

A large body of literature shows that sensory uncertainty inversely scales the degree of error-driven corrections made to motor plans from one trial to the next. However, by limiting sensory feedback to the endpoint of movements, these studies prevent corrections from taking place during the movement. We have recently shown that when such corrections are promoted, sensory uncertainty punctuates between-trial movement corrections with abrupt changes that closely track the degree of sensory uncertainty but are insensitive to the magnitude and direction of movement error. Here, we show that this result requires different levels of sensory uncertainty to be mixed on a trial-by-trial basis. This carries important implications for how previous studies of motor learning under uncertainty are interpreted, and what future studies will likely constitute progress for the field.
Erythrovirus B19 (B19V) in patients with acute febrile illness suspected of arboviruses in Mato Grosso do Sul, Brazil
Authors: Lichs Gislene Garcia C. , Fernandez Grillo Zoraida del Carmen , Alves do Nascimento Valdinete , Alcantara Daniel Maximo Corrêa , Lemos Everton Ferreira , Espínola Carvalho Cristiano M. , Ferraz Demarchi Luiz Henrique , Maymone Gonçalves Crhistinne Carvalho , Naveca Felipe Gomes , Rodrigues de Mendonça Favacho Alexsandra
Published: November 2023

Human Erythrovirus (parvovirus) B19 infection can produce symptoms similar to those produced by Dengue, Chikungunya, and Zika viruses, making clinical diagnosis difficult. The importance of erythrovirus B19 in human pathology has been increased and reported in numerous studies published globally. The B19V infection was investigated by real-time PCR in samples from patients with signs and symptoms related to classic arboviral symptoms. This study was conducted to provide information on the genetic diversity of Human Erythrovirus B19 (B19V) circulating in the state of Mato Grosso do Sul, Midwest region of Brazil, from 2017 to 2022. A total of 773 sera samples of patients with negative diagnostic results for Dengue, Chikungunya, and Zika, during the study period were analyzed. Erythrovirus DNA was found in 10.6% (82/773) of patients, among them 10 were pregnant women. Four samples were completely sequenced, and the other five partially, to genotype by phylogenetic reconstruction. All samples belong to worldwide dispersed genotype 1, subgenotype 1a. These results demonstrate the importance of including B19V in differential laboratory diagnosis for epidemiological purposes and appropriate patient management. The diagnosis for B19V should be performed, particularly among pregnant women, immunocompromised patients, and individuals with hemolytic diseases, as the infection is more severe in these cases.
Land use density, land use mix, and walking: insight from a simple theoretical model
Authors: Yang Yong
Published: November 2023

Background

Land use density and land use mix are the two most studied characteristics of the built environment and generally, it is believed that higher land use density and higher level of land use mix are associated with more walking, especially for utilitarian purposes. However, although a large number of studies including population density and land use mix have been conducted over the last two decades, overall, the result is still not very clear.

Methods

I developed a simple computer model to simulate the influence of land use density and land use mix on walking. It includes a hypothetical city with a grid space and a number of households and non-residential places located across the city. Eventually, we varied the contexts to explore the corresponding results of the walking trips and walking distance across the population.

Results

Only at a very low level, increased land use density may increase walking trips. At the same time, increased land use density may decrease the total distance of walking trips. A higher level of land use mix is associated with higher walking trips. However, a higher level of land use mix level may be not associated with a higher total distance of walking trips. The relationship between land use and walking is significantly modified by other factors.

Conclusion

The relationship between land use and walking is complicated because multiple factors at multiple levels could contribute to this relationship and the conclusions from the most existing practical studies may apply only to a specific population in a specific context. Computer models will be supplemental because they provide a method to disentangle the complex relationship by separating and removing confounding factors and focusing on the interested factors.