bluuebunny/crossref_metadata_2025 huggingface dataset:
Research progress of natural products targeting tumor-associated macrophages in antitumor immunity: A review
Authors: Chengzhi Wang , Yifan Liu , Xiaoqing Zhang , Peimin Liu , Dongdong Li
Published: November 2024

As an important innate immune cell in the body, macrophages have a strong ability to phagocytic tumor cells and maintain the innate immune response. Tumor-associated macrophages play a more prominent role in regulating tumor immunity and are currently an important target of antitumor immunity. As a new type of antitumor therapy, tumor immunotherapy has great potential, combined chemotherapy, targeting and other therapeutic means can significantly enhance the antitumor therapy effect. At present, a number of natural products have been proved to have significant immunomodulatory and antitumor effects, and have become a hot field of antitumor immunity research. Studies have found that a variety of natural products, such as polysaccharides, flavonoids, saponins, lactones, and alkaloids, can induce the polarization of M1 macrophages, inhibit the polarization of M2 macrophages, and regulate the expression of immune-related cytokines by targeting specific signaling pathways to enhance the killing effect of macrophages on tumor cells and improve the tumor immune microenvironment, and finally better play the antitumor immune function. In this paper, by summarizing the research results of the specific mechanism of natural products targeting tumor-associated macrophages to exert antitumor immunity in recent years, we discussed the aspects of natural products targeting tumor-associated macrophages to enhance antitumor immunity, in order to provide a new research idea for tumor immunotherapy and further improve the effectiveness of clinical antitumor therapy.
Bronchoscopy in children with diffuse alveolar hemorrhage under general anesthesia with spontaneous respiration by face mask ventilation
Authors: Yang Ruimin , Wei Qing , Chen Xun , Liu Jing , Li Yan , Liu Jingchen
Published: November 2024

To improve the management level of general anesthesia during bronchoscopy in the children with diffuse alveolar hemorrhage (DAH). A retrospective study was conducted in the children with DAH who had performed bronchoscopy under general anesthesia with spontaneous respiration by face mask ventilation initially from June 2021 to June 2022 in our hospital. (1) Thirty-four children who had underwent 38 bronchoscopy procedures were included. (2) General anesthesia induction was performed by bolus of propofol intravenous in all the procedures. For maintaining anesthesia, combination use of propofol and remifentanil intravenously infusion were given in 31 procedures (81.6%) and propofol intravenously infusion alone was given in the rest 7 procedures (18.4%). An intravenous bolus of ketamine or propofol was given as an anesthetic adjuvant in 21 procedures (55.3%). Thirty-five procedures (92.1%) were successfully completed under non-tracheal intubation ventilation, whereas the rest 3 procedures (7.9%) needed change to tracheal intubation ventilation. (3) Respiratory depression was found in 7 procedures (18.4%), laryngospasm was found in 2 procedure (2.6%), and bronchospasm was found in 17 procedures (44.7%). Intraoperative hypoxemia occurred in 16 procedures (42.1%). The incidence of intraoperative hypoxemia in the procedures at the active phage of disease was significantly higher compared to those at the remission phage of the disease (P < .05). Intraoperative hypercapnia also occurred in 16 procedures (42.1%). Two procedures (5.3%) were complicated by severe pulmonary hemorrhage. General anesthesia with spontaneous respiration by face mask ventilation is feasible and relatively safe for the children with DAH undergoing bronchoscopy, whereas the anesthetic protocol still needs to be improved.
Sequential treatment from bisphosphonate to denosumab improves lumbar spine bone mineral density in postmenopausal osteoporosis patients: A meta-analysis of randomized controlled trials
Authors: Jiang Xu , Hou Siyi , Deng Xiaolei , Hu Liyou , Wang Jian , Hou Decai
Published: November 2024

Background:

Bisphosphonates are effective in the treatment of postmenopausal osteoporosis. However, their prolonged use induces adverse events and may lead to a rapid decline in bone mineral density (BMD) after discontinuation. Denosumab, a human monoclonal antibody, is a widely used antiresorptive agent that is more effective than bisphosphonates in improving bone density. Whether sequential treatment with denosumab after bisphosphonate therapy can maintain or further increase BMD at all sites has not been conclusively demonstrated. Thus, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the effects of this sequential therapy on BMD.

Methods:

We searched the PubMed, Embase, and Cochrane Library databases from December 1, 1986, to May 2, 2024, for all RCTs that assessed the efficacy of sequential therapy of bisphosphonate transition to denosumab in postmenopausal women with osteoporosis. BMD changes at the lumbar spine, femoral neck, and total hip were used as outcomes. We assessed methodological quality, extracted relevant data according to the Cochrane Handbook for Systematic Reviews of Interventions, applied random-effects models for meta-analyses, performed heterogeneity analyses, and assessed publication bias.

Results:

A total of 3290 patients from 4 RCTs were included in the meta-analysis. Forest plot analysis showed that sequential treatment with bisphosphonate–denosumab was associated with higher lumbar spine BMD gain than continuous bisphosphonate treatment [mean difference (MD) = 5.50, 95% confidence interval (CI) = 5.26–5.75, I
2 = 32.88%). No risk of bias was observed for the 4 trials, but there was an increase in femoral neck and total hip BMD. Moreover, analyses could not be performed because of high heterogeneity (femoral neck BMD: MD = 3.85, 95% CI = 2.84–4.85, I
2 = 97.88%; total hip BMD: MD = 5.65, 95% CI = 4.28–7.02, I
2 = 97.91%).

Conclusion:

Sequential therapy that involves a transition from bisphosphonates to denosumab had a positive effect on lumbar spine bone density, and this type of therapy may be a potential treatment option for increasing lumbar spine bone density in postmenopausal women.
Patterns of orthopedic injuries associated with increasing e-scooter-related trauma: A retrospective observational study with a 4-year evaluation from a tertiary center in Istanbul, Turkey
Authors: Senel Ahmet , Sert Selman , Aktas Mehmet Akif , Tekin Saltuk Bugra , Carkci Engin , Erdogan Sinan
Published: November 2024

The increasing use of electric scooters (e-scooters) has been accompanied by an increase in the number of traumas. Noncompliance with regulations and the effectiveness of legal measures remain subjects of ongoing debate. This study aimed to investigate the demographic characteristics of patients with e-scooter-related orthopedic injuries, temporal distribution of trauma, and patterns of these injuries. We retrospectively evaluated 534 patients with e-scooter-related injuries who were referred to the Department of Orthopedics and Traumatology between January 2020 and October 2023. Variables such as patient sex, age, time of trauma, type of hospital transfer, mechanism of trauma, injury location and type, accompanying head trauma in extremity injuries, and treatment approach were recorded. Temporal analysis was performed by hour, day, month, season, and weekday versus weekend. The majority of patients were male (80.0%), with injuries most common in the 25 to 39 age group (33.7%). Trauma was frequent in the summer (45.7%), especially in July (16.5%), with most hospital visits occurring on Fridays (18.2%) and weekends (32.2%). Blunt soft tissue injuries (47.3%) and fractures (42.4%) were prevalent, particularly in the elbow (18.4%), wrist (16.9%), and knees (14.3%). A total of 247 fractures were identified, with the radial head (17.0%) and distal radius (10.9%) being the most common fractures. Fracture rates have increased in 2022 and 2023 compared to those in previous years. While 86.0% of patients received nonsurgical treatment, 14.0% underwent surgery, with a rise in surgical cases in 2022 and 2023. Elbow (19.0%), knee (16.7%), and wrist (16.7%) were the most frequent surgical sites. The increasing use of e-scooters among young people has increased trauma cases, with a growing proportion of fractures over time. The higher incidence of injuries, particularly in the elbow and knee joints, underscores the importance of protective equipment. Therefore, additional legal regulations can help to prevent such injuries.
Construction and validation of a nomogram prediction model for postoperative recurrence of lumbar disc herniation treated with percutaneous laminectomy
Authors: Zhou Lin-feng , Jiang Tao , Zhang Xiao-qin , Li Zhi-rong
Published: November 2024

The aim was to investigate the independent risk factors for postoperative recurrence of lumbar disc herniation treated by percutaneous intervertebral laminectomy, and to establish a nomogram prediction model accordingly. Data on patients with lumbar disc herniation were collected from January 2018 to December 2023 in our hospital, and single-factor and multifactorial logistic regression analyses were used to determine the independent risk factors for postoperative recurrence of lumbar disc herniation and establish the corresponding nomogram. The receiver operating characteristic curves were plotted the area under the curve was calculated, and the calibration curves and decision curves were plotted to evaluate the model performance. A total of 644 patients with lumbar disc herniation were included in the study, and 61 patients had a postoperative recurrence, with a recurrence rate of 9.5%. After univariate and multivariate logistic regression model analysis, a total of 7 variables were identified as independent risk factors for postoperative recurrence of lumbar disc herniation: age > 60 years (OR, 3.709; 95% CI, 1.284–10.714), type of nucleus pulposus protrusion as herniation (OR, 7.342; 95% CI, 1.500–35.929), nucleus pulposus degeneration grade III-V (OR, 4.068; 95% CI, 1.214–13.627), operative segment L4–L5 (OR, 5.060; 95% CI, 1.659–15.431), incomplete intraoperative medullary removal (OR, 5.355; 95% CI, 2.017–14.220), and broken fibrous ring (OR, 5.229; 95% CI, 1.235–22.142), and postoperative high-intensity activity (OR, 5.096; 95% CI, 1.420–17.669). The nomogram constructed in this study for postoperative recurrence of lumbar disc herniation treated by percutaneous intervertebral foramenoscopy has good predictive accuracy, which helps orthopedic surgeons to intervene in advance in patients at high risk of postoperative recurrence of lumbar disc herniation treated by percutaneous intervertebral foramenoscopy.
Understanding the Concept of Patient Safety Culture
Authors: Fontenele Lima de Carvalho Rhanna Emanuela , Bates David W.
Published: November 2024

Background:

Patient safety culture is crucial for improving health care quality, however, there is no consensus on its definition.

Purpose:

This study aimed to clarify and update the concept of patient safety culture.

Methods:

We employed Norris’ 6-step concept clarification method. The content was organized through a scoping review of 4 databases. Twelve health professionals participated in focus groups and 10 experts participated in content validation. The content validity coefficient (CVC) was calculated for agreement between experts.

Results:

Three patient safety culture domains were identified: organizational, professional, and patient and family participation. The experts rated the definitions favorably, with high CVC scores (>0.87), indicating good agreement. The operational definitions were reduced from 76 to 54 items after expert evaluation.

Conclusion:

An updated definition of patient safety culture is provided, which can inform development of assessment instruments by managers and health care professionals.
Quantity of Caloric Support After Pediatric Severe Traumatic Brain Injury: Description of Associated Outcomes in a Single Retrospective Center Cohort, 2010–2022
Authors: Elliott Elizabeth C. , Trujillo-Rivera Eduardo A. , Dughly Omar , Dean Terry , Harrar Dana , Bell Michael J. , Wai Kitman
Published: November 2024

OBJECTIVES:

To examine the relationship between adequacy of caloric nutritional support during the first week after severe traumatic brain injury (TBI) and outcome.

DESIGN:

Single-center retrospective cohort, 2010–2022.

SETTING:

Tertiary care children’s hospital with a level 1 trauma center.

PATIENTS:

Children younger than 18 years with PICU stay greater than 7 days for management of TBI, who had severe TBI, defined as Glasgow Coma Scale (GCS) score less than or equal to 8 at initial presentation and/or placement of an intracranial pressure monitor or external ventricular drain, and/or decompressive hemicraniectomy.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 93 patients were identified (median age 46 mo; 53% male; median GCS 5; hospital mortality 4%). Caloric goal was assigned by a dietician and the proportion of prescribed calories delivered to each patient over the first 7 days of PICU admission were analyzed. At the end of the first 7 days post-injury, overall median (interquartile range [IQR]) caloric and protein adequacies were 42% (IQR, 28–62%) and 48% (IQR, 29–61%), respectively. We failed to identify an association between adequacy of caloric support and greater odds of higher Functional Status Scale (FSS) score or higher Glasgow Outcome Scale Extended for Pediatrics score at discharge. However, at outpatient follow-up, prior adequacy of PICU caloric support was associated with greater odds of worse FSS (multiplicative increase per 10% increase in calories [MI], 1.10; 95% CI, 1.03–1.18; p = 0.002) and worse GOS E-Peds (MI, 1.16; 95% CI, 1.08–1.27; p < 0.001) at outpatient follow-up.

CONCLUSIONS:

In pediatric patients with severe TBI, there is an association between delivery of a greater proportion of their goal calories during the first 7 days after injury and greater odds of worse outcome at outpatient follow-up.
Using Machine Learning Techniques to Predict Viral Suppression Among People With HIV
Authors: Yang Xueying , Cai Ruilie , Ma Yunqing , Zhang Hao H. , Sun XiaoWen , Olatosi Bankole , Weissman Sharon , Li Xiaoming , Zhang Jiajia
Published: November 2024

Background:

This study aims to develop and examine the performance of machine learning (ML) algorithms in predicting viral suppression among statewide people living with HIV (PWH) in South Carolina.

Methods:

Extracted through the electronic reporting system in South Carolina, the study population was adult PWH who were diagnosed between 2005 and 2021. Viral suppression was defined as viral load <200 copies/mL. The predictors, including sociodemographics, a historical information of viral load indicators (eg, viral rebound), comorbidities, health care utilization, and annual county-level factors (eg, social vulnerability), were measured in each 4-month windows. Using historic information in different lag time windows (1-, 3- or 5-lagged time windows with each 4-month window as a unit), both traditional and ML approaches (eg, Long Short-Term Memory Network) were applied to predict viral suppression. Comparisons of prediction performance between different models were assessed by area under curve (AUC), recall, precision, F1 score, and Youden index.

Results:

ML approaches outperformed the generalized linear mixed model. In all the 3 lagged analysis of a total of 15,580 PWH, the Long Short-Term Memory Network (Lag 1: AUC = 0.858; Lag 3: AUC = 0.877; Lag 5: AUC = 0.881) algorithm outperformed all the other methods in terms of AUC performance for predicting viral suppression. The top-ranking predictors that were common in different models included historical information of viral suppression, viral rebound, and viral blips in the Lag-1 time window. Inclusion of county-level variables did not improve the model prediction accuracy.

Conclusions:

Supervised ML algorithms may offer better performance for risk prediction of viral suppression than traditional statistical methods.
Leveraging Phase Information of 3D Isotropic Ultrashort Echo Time Pulmonary MRI for the Detection of Thoracic Lymphadenopathy
Authors: Ziegelmayer Sebastian , Van Anh Tu , Weiss Kilian , Marka Alexander W. , Lemke Tristan , Scheuerer Florian , Huber Thomas , Sauter Andreas , Robison Ryan , Gawlitza Joshua , Makowski Marcus R. , Karampinos Dimitrios C. , Graf Markus
Published: November 2024

Background

Ultrashort echo time (UTE) allows imaging of tissues with short relaxation times, but it comes with the expense of long scan times. Magnitude images of UTE magnetic resonance imaging (MRI) are widely used in pulmonary imaging due to excellent parenchymal signal, but have insufficient contrast for other anatomical regions of the thorax. Our work investigates the value of UTE phase images (UTE-Ps)—generated simultaneously from the acquired UTE signal used for the magnitude images—for the detection of thoracic lymph nodes based on water-fat contrast. It employs an advanced imaging sequence and reconstruction allowing isotropic 3D UTE MRI in clinically acceptable scan times.

Methods

In our prospective study, 42 patients with 136 lymph nodes had undergone venous computed tomography and pulmonary MRI scans with UTE within a 14-day interval. 3D isotropic UTE images were acquired using FLORET (fermat looped, orthogonally encoded trajectories). Background-corrected phase images (UTE-P) and magnitude images were reconstructed simultaneously from the UTE-Signal. Three radiologists performed a blinded reading in which all lymph nodes with a short-axis diameter (SAD) of at least 0.5 cm were detected. Detection rates and performance metrics of UTE-P for all lymph node regions and for pathologic (SAD ≥10 mm) and nonpathologic lymph nodes (SAD <10 mm) were calculated using computed tomography as a reference. The interreader agreement defined as the presence or absence of lymph nodes based on patient and region was calculated using Fleiss kappa (κ).

Findings

In the phase images, pathologic lymph nodes in the mediastinal and hilar region were detected with a high diagnostic confidence due to the achieved water-fat contrast (average sensitivity, specificity, positive predictive value, and negative predictive value of 95.83% [confidence interval (CI), 92.76%–98.91%], 100%, 100%, and 99.32% [CI, 98.08%–100%]). Stepwise inclusion of all lymph node regions and nonpathologic lymph nodes was associated with a moderate decrease resulting in an average sensitivity, specificity, positive predictive value, and negative predictive value of 77.9% (CI, 70.9%–84.7%), 99.4% (CI, 98.7%–99.9%), 97.0% (CI, 93.4%–99.7%), and 94.7% (CI, 92.8%–96.4%) for the inclusion of all lymph nodes sizes and regions. Interreader agreement was almost perfect (κ = 0.92).

Conclusions

Pathological lymph nodes in the mediastinal and hilar region can be detected in phase-images with high diagnostic confidence, thanks to the ability of the phase images to depict water-fat contrast in combination with high spatial 3D resolution, extending the clinical applicability of UTE into the simultaneous assessment of lung parenchyma and lymph nodes.
Genomics and pharmacogenomics of cluster headache: implications for personalized management? A systematic review
Authors: Isayeva Ulker , Paribello Pasquale , Ginelli Enrico , Pisanu Claudia , Comai Stefano , Carpiniello Bernardo , Squassina Alessio , Manchia Mirko
Published: November 2024

The role of genetic factors in cluster headache etiology, suggested by familial and twin studies, remains ill-defined, with the exact pathophysiological mechanisms still largely elusive. This systematic review aims to synthesize current knowledge on cluster headache genetics and explore its implications for personalized treatment and prediction of treatment response. Thus, we searched PubMed, Scopus, and the Cochrane Library databases and reference lists of identified research articles, meta-analyses, and reviews to identify relevant studies up to 10 July 2024. The quality of the evidence was assessed using Newcastle-Ottawa Scale for case control studies and NIH Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. The protocol of this study was registered via the Open Science Framework (https://osf.io/cd4s3). Fifty-one studies were selected for the qualitative synthesis: 34 candidate gene studies, 5 GWAS, 7 gene expression studies, 4 pharmacogenetic association studies, and 1 whole genome sequencing study. The bulk of genetic evidence in cluster headache underscores the involvement of genes associated with chronobiological regulation. The most studied gene in cluster headache is the HCRTR2, which is expressed in the hypothalamus; however, findings across studies continue to be inconclusive. Recent GWAS have uncovered novel risk loci for cluster headache, marking a significant advancement for the field. Nevertheless, there remains a need to investigate various genes involved in specific mechanisms and pathways.
Roseicyclus sediminis sp. nov. and Roseicyclus salinarum sp. nov., isolated from marine environment, and reclassification of two species of the genus Roseibacterium as species of the genus Roseicyclus
Authors: Zhou Ziyang , Yang Xunian , Yue Yuyan , Liu Xinjiang , Xu Zhenxing , Du Zongjun
Published: November 2024

Two Gram-stain-negative, facultatively anaerobic, rod-shaped bacteria were isolated from coastal sediments and salt marshes in Weihai, China, and designated as SDUM158017T and SDUM158016T, respectively. Both grew at temperatures ranging from 20 to 43°C and within a pH range of 6.0 to 9.0. However, strain SDUM158016T grew in the presence of 1.0–7.0% (w/v) NaCl, whereas strain SDUM158017T was able to grow in the presence of 1.0–10.0% (w/v) NaCl. Strains SDUM158016T and SDUM158017T contain major fatty acids of C18 : 1
ω7ϲ and C16 : 0 and contain Q10 as the sole quinone. Based on 16S rRNA gene sequence analysis, the closest relatives of strains SDUM158016T and SDUM158017T are ‘Roseibacterium beibuensis’ MCCC 1F00103T, followed by Roseibacterium elongatum JCM 11220T, with the highest similarities 97.1 and 97.3 %, respectively. The average nucleotide identity values between strain SDUM158016T and species of the genera Roseibacterium and Roseicyclus ranged from 76.0 to 78.9 %, while they ranged from 75.9 to 78.6% for strain SDUM158017T. These values are below the species delineation threshold of 98.6%, suggesting that both strains represent novel species. Phylogenetic analysis of the 16S rRNA genes and genome sequences further indicates that Roseibacterium species within the genus Roseicyclus and these isolates represent two potentially novel species within the genus Roseicyclus. Taken together, strains SDUM158017T and SDUM158016T represent two novel species of the genus Roseicyclus, for which the names Roseicyclus sediminis and Roseicyclus salinarum are proposed with the type strains SDUM158016T (=KCTC 92632T =MCCC 1H01367T) and SDUM158017T (=KCTC 92633T =MCCC 1H01363T), respectively. Based on phylogenetic and genomic analyses, we also propose the reclassification of Roseibacterium elongatum as Roseicyclus elongatus comb. nov. and Roseibacterium persicicum as Roseicyclus persicicus comb. nov.
Restoration ofPKM1improves functional maturation of human stem-cell derived-β cell by regulating PEP metabolism
Authors: Lin Haopeng , Chen Deqi , Zhang Feng , Liu Xin , Xie Xiaoxiao , Dong Qifei , Yan Jiawei , Yin Jiaxiang , Bi Zirong , Jiang Kuo , Zhang Tongran , Xue Peng , Peng Wei , Chen Lihua , Xu Tao , Guo Yanying , Li Zonghong , Liu Huisheng
Published: November 2024

Human stem cell-derived β (SC-β) cells still exhibit limited glucose response required for insulin secretion due to glycolytic bottlenecks, yet how these metabolic abnormalities impact glucose response and functional maturation of SC-β cells remains unclear. In this study, we identified a metabolic checkpoint located at PEP accumulation that impeded the functional maturation, which was rescued by restoration of pyruvate kinase 1 (PKM1). Glucose-tracing metabolomics in human stem cell-derived islets revealed abnormal glycolytic PEP accumulation at resting condition, resulting in impaired calcium response and insulin secretion upon high glucose or glycolytic metabolite stimulation. Mechanistically, elevated PEP significantly raised intracellular basal calcium levels, leading to downregulated expression of genes involved in TCA cycle elucidated by single cell transcriptomics. Furthermore, the activity of pyruvate kinase, which metabolizes PEP, was notably reduced due to low PKM1 expression. By overexpressing PKM1, the impairment of TCA-related genes caused by PEP accumulation was reversed via modulating PEP metabolism, resulting in enhanced calcium responses and insulin secretion upon high glucose stimulation. Together, we discovered a novel role of PKM1-regulated PEP metabolism in mediating the functional maturation of human SC-β cells. This study highlights the importance of metabolic reprogramming in human SC-β cell maturation, advancing cell therapy approaches for diabetes treatment.
“Biomarkers of recovery: characterizing trophic flow following ecological restoration”
Authors: Spindel Nathan B. , Galloway Aaron W. E. , Schram Julie B. , Mcneill Gwiisihlgaa Daniel , Bellis Sgiids Kung Vanessa , Guujaaw Niisii , Yakgujanaas Jaasaljuus , Thompson Markus , Lee Lynn C. , Okamoto Daniel K.
Published: November 2024

Coastal kelp forests are important sources of primary productivity and provide essential habitat and ecosystem services. In many areas around the world, the formation and persistence of urchin barrens threatens kelp forest ecosystems. Over the past several decades, restoration efforts have emerged aiming to increase the abundance of foundation species like kelp in such systems. However, we lack a comprehensive understanding of how successful kelp restoration affects the nutritional landscape and the fitness of kelp forest herbivores. We bridge this knowledge gap with a Before-After-Control-Impact Paired Series (BACIPS) focused on kelp forest restoration where reductions of herbivorous sea urchins in Haida Gwaii resulted in substantial increases in kelp abundance in habitat previously characterized as barrens. Specifically, we document body size specific shifts in the fatty acid (FA) profiles of red sea urchins (Mesocentrotus franciscanus) and northern abalone (Haliotis kamtschatkana). FAs associated with bacteria and diatoms were elevated in tissues of urchins and abalone in barrens habitat while kelp biomarkers were elevated in restored kelp forest habitat. For urchins, these shifts tracked the increase in gonad mass following kelp forest recovery. For abalone, these results varied depending on animal body size. Specifically, abalone exhibited a continuous size-specific shift from biofilm-associated markers at small sizes to kelp-associated markers as animals increased in size. For both species, a marked increase in essential fatty acids was observed following kelp restoration. Our results demonstrate kelp restoration via sea urchin reduction enhances not only the quantity but also the quality and diversity of food in previously degraded habitats, and subsequently enhances the amount and nutritional quality of roe (i.e., gonads) in sea urchins therein.
GOBoost: Leveraging Long-Tail Gene Ontology Terms for Accurate Protein Function Prediction
Authors: Zhang Lei , Wang Yang , Chen Xiao , Hou Jie , Si Dong , Ding Rui , Jiang Bo , Ledenko Hailey , Cao Renzhi
Published: November 2024

Motivation

With the advancement of deep learning, researchers have increasingly proposed computational methods based on deep learning techniques to predict protein function. However, many of these methods treat protein function prediction as a multi-label classification problem, often overlooking the long-tail distribution of functional labels (i.e., Gene Ontology Terms) in datasets. To address this issue, we propose the GOBoost method, which incorporates the proposed long-tail optimization ensemble strategy. Besides, GOBoost introduces the proposed global-local label graph module and multi-granularity focal loss function to enhance long-tail functional information, mitigate the long-tail phenomenon, and improve overall prediction accuracy.

Results

We evaluate GOBoost and other state-of-the-art (SOTA) protein function prediction methods on the PDB and AF2 datasets. The GOBoost outperformed SOTA methods across all evaluation metrics on both datasets. Notably, in the AUPR evaluation on the PDB test set, GOBoost improved by 10.71%, 35.91%, and 22.71% compared to the SOTA HEAL method in the MF, BP, and CC functions. The experimental results demonstrate the necessity and superiority of designing models from the label long-tail distribution perspective.

Availability

https://github.com/Cao-Labs/GOBoost

Contact

caora@plu.edu
Isolated Mouse Adult Cardiomyocytes Display Minimal Mitochondrial ATP Demand and Maximal Reliance on Glycolysis
Authors: Mattam Ushodaya , Talari Noble Kumar , Sathyanarayana Ashish Rao , Mia Sobuj , Frazier James , Slone Sam , Drosatos Konstantinos , Chella Krishnan Karthickeyan
Published: November 2024

Mitochondrial maladaptation is a hallmark of heart failure, contributing to impaired energy production and contractile dysfunction. Understanding the bioenergetics of cardiomyocytes under healthy and pathological conditions is critical for characterizing mitochondrial maladaptation. While adult cardiomyocytes from rodents are a widely used model, recent studies have reported oligomycin insensitivity in these cells, a phenomenon often overlooked. This has led to incomplete assessments of key bioenergetic parameters, such as ATP-linked respiration and glycolytic capacity, focusing primarily on basal and maximal respiration. In this study, we performed a comprehensive characterization of bioenergetic and glycolytic profiles in three cardiomyocyte models: neonatal rat ventricular myocytes (NRVMs), human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and mouse adult cardiomyocytes (mouse ACMs). Our findings demonstrate distinct metabolic adaptations in mouse ACMs, revealing critical insights into mitochondrial function, ATP demand, and glycolytic reliance. These results underscore the importance of selecting appropriate cellular models for studying mitochondrial bioenergetics in cardiac physiology and pathology.
Replication of DNA containing trinucleotide repeats by the bacteriophage T7 replisome
Authors: Lee Seung-Joo , Mitsunobu Hitoshi , Hernandez Alfredo J.
Published: November 2024

Trinucleotide repeats in the human genome are implicated in various neurodegenerative diseases. The tendency of these repetitive DNA sequences to form non-B DNA structures can cause abnormal replication, leading to genomic instability. This instability contributes to disease progression, though the underlying mechanisms are not fully understood. We investigated the replication of DNA containing CAG and CTG trinucleotide repeats using individual components of the T7 bacteriophage replication machinery, as well as the complete replisome. Our results show that repeats in linear single-stranded DNA (ssDNA) inhibit the activity of T7 DNA polymerase and ssDNA-binding proteins, with a more pronounced effect observed in CTG repeats compared to CAG repeats. Minicircle templates containing CTG repeats exhibited robust DNA synthesis on both the leading and lagging strands, though synthesis was not enhanced by the T7 gene 2.5 ssDNA-binding protein. The lagging strand products generated from the CTG repeat minicircle were significantly longer than those from random sequence templates, and their lengths were not extended by the presence of T7 gene 2.5 protein. When the repeated sequences were incorporated into the T7 phage genome, heterogeneity was observed downstream of the repeats, depending on their length. We propose that aberrant extension occurs predominantly in the lagging strand, driven by dynamic interactions between the repeated sequences and the DNA replisome. This study may provide a foundation for understanding the mechanisms underlying the extension or deletion of repetitive genomic regions.
Enzyme-constrained Metabolic Model ofTreponema pallidumIdentified Glycerol-3-phosphate Dehydrogenase as an Alternate Electron Sink
Authors: Shahreen Nabia , Chowdhury Niaz Bahar , Stone Edward , Knobbe Elle , Saha Rajib
Published: November 2024

Treponema pallidum, the causative agent of syphilis, poses a significant global health threat. Its strict intracellular lifestyle and challenges inin vitrocultivation have impeded detailed metabolic characterization. In this study, we present iTP251, the first genome-scale metabolic model ofT. pallidum, reconstructed and extensively curated to capture its unique metabolic features. These refinements included the curation of key reactions such as pyrophosphate-dependent phosphorylation and pathways for nucleotide synthesis, amino acid synthesis, and cofactor metabolism. The model demonstrated high predictive accuracy, validated by a MEMOTE score of 92%. To further enhance its predictive capabilities, we developed ec-iTP251, an enzyme-constrained version of iTP251, incorporating enzyme turnover rate and molecular weight information for all reactions having gene-protein-reaction associations. Ec-iTP251 provides detailed insights into protein allocation across carbon sources, showing strong agreement with proteomics data (Pearson’s correlation of 0.88) in the central carbon pathway. Moreover, the thermodynamic analysis revealed that lactate uptake serves as an additional ATP-generating strategy to utilize unused proteomes, albeit at the cost of reducing the driving force of the central carbon pathway by 27%. Subsequent analysis identified glycerol-3-phosphate dehydrogenase as an alternative electron sink, compensating for the absence of a conventional electron transport chain while maintaining cellular redox balance. These findings highlightT. pallidum’s metabolic adaptations for survival and redox balance in intracellular environments, providing a foundation for future research into its unique bioenergetics.

IMPORTANCE

This study advances our understanding ofTreponema pallidum, the syphilis-causing pathogen, through the reconstruction of iTP251, the first genome-scale metabolic model for this organism, and its enzyme-constrained version, ec-iTP251. The work addresses challenges of studyingT. pallidumdue to its strict intracellular nature and difficulties inin vitrocultivation. Validated with strong agreement to proteomics data, the model demonstrates high predictive reliability. Key insights include unique metabolic adaptations such as lactate uptake for ATP production and alternative redox-balancing mechanisms. These findings provide a robust framework for future studies aimed at unraveling the pathogen’s survival strategies and identifying potential metabolic vulnerabilities.
A Review on Calibration Methods of Cancer Simulation Models
Authors: Zhang Yichi , Alagoz Oguzhan
Published: November 2024

Calibration, a critical step in the development of simulation models, involves adjusting unobservable parameters to ensure that the outcomes of the model closely align with observed target data. This process is particularly vital in cancer simulation models with a natural history component where direct data to inform natural history parameters are rarely available. This work reviews the literature of cancer simulation models with a natural history component and identifies the calibration approaches used in these models with respect to the following attributes: calibration target, goodness-of-fit (GOF) measure, parameter search algorithm, acceptance criteria, and stopping rules. After a comprehensive search of the PubMed database from 1981 to June 2023, 68 studies were included in the review. Nearly all (n=66) articles specified the calibration targets, and most articles (n=56) specified the parameter search algorithms they used, whereas goodness-of-fit metric (n=51) and acceptance criteria/stopping rule (n=45) were reported for fewer times. The most frequently used calibration targets were incidence, mortality, and prevalence, whose data sources primarily come from cancer registries and observational studies. The most used goodness-of-fit measure was weighted mean squared error. Random search has been the predominant method for parameter search, followed by grid search and Nelder-mead method. Machine learning-based algorithms, despite their fast advancement in the recent decade, has been underutilized in the cancer simulation models. More research is needed to compare different parameter search algorithms used for calibration.

Key points

This work reviewed the literature of cancer simulation models with a natural history component and identified the calibration approaches used in these models with respect to the following attributes: calibration target, goodness-of-fit (GOF) measure, parameter search algorithm, acceptance criteria, and stopping rules.

Random search has been the predominant method for parameter search, followed by grid search and Nelder-mead method.

Machine learning-based algorithms, despite their fast advancement in the recent decade, has been underutilized in the cancer simulation models. Furthermore, more research is needed to compare different parameter search algorithms used for calibration.
Identifying resilience factors for adolescent mental health with cyberbullying victimisation as a risk factor
Authors: Kandola Aaron , Mansfield Rosie , Kelly Yvonne , Rahman Yasmin , Choi Karmel , Hollis Chris , Townsend Ellen , Patalay Praveetha
Published: November 2024

Promoting resilience can reduce the mental health risks of cyberbullying victimisation in adolescents.

We conducted a longitudinal cohort study with 9,969 adolescents (Millennium Cohort Study (MCS)) at ages 14-15 (baseline) and 17 (follow-up). We replicated our analyses in 4,240 adolescents (Longitudinal Study of Australian Children). The outcome was psychological distress at follow-up. Cyberbullying victimisation was a single-item question. Aim one identified modifiable resilience factors (exposures) associated with psychological distress. Aim two examined whether these resilience factors (moderators) interacted with the cyberbullying-distress association.

478/1,466 baseline variables were associated with distress after confounder adjustment (aim one). 31/478 potential resilience factors moderated the cyberbullying-distress association. 15 models replicated in the individual (n=8, e.g., happiness with friends), family and friends (n=3, e.g., sexual activities), structural (n=2, e.g., income sources), and learning environment (n=2, e.g., misbehaviour) domains.

We identified several factors for further research on developing interventions to reduce adolescent cyberbullying mental health risks.
Respiratory acclimatization and psychomotor performance after rapid ascent and during 3 weeks at 3100 m. A prospective cohort study in healthy
Authors: Muralt Lara , Lichtblau Mona , Aeschbacher Sayaka S , Bisang Maya , von Gruenigen Kay , Sooronbaev Talant M. , Ulrich Silvia , Bloch Konrad E , Furian Michael
Published: November 2024

Background

The acclimatization to high altitudes over several weeks is not extensively studied. Repeated physiological assessments were performed in healthy lowlanders staying at 3100m for 3 weeks. We hypothesized that over the course of 3 weeks, the arterial oxygen saturation (SpO2) improves and has favorable effects on psychomotor vigilance, postural control, and sleep.

Methods

16 healthy volunteers (23-33y) underwent sleep studies during 1 night in Bishkek (760m), and during nights 1, 8 and 22 at Too-Ashu (3100m), Kyrgyzstan. The day after, reaction time (psychomotor vigilance test reaction time test, PVT) and postural control (center of gravity path length on balance board [COPL]) were assessed.

Results

Compared to 760m, mean nocturnal SpO2dropped in the first night at 3100m from mean±SD 94.8±1.9% to 86.3±2.9% and recovered partially to 89.8±1.5% after 3 weeks (P<0.05 both comparisons to 760m). Corresponding median (quartiles) oxygen desaturation indices were 1.0/h(0.3;2.2), 6.5/h(4.5;12.1) and 6.4/h(4.2;11.1) time in bed (P<0.05 both comparisons to 760m). Median (quartiles) reaction times were 226ms(212;231), 236ms(210;259) and 228ms(212;246), P=NS, all comparisons. COPL worsened from 25.1±4.1cm to 27.1±4.1cm (P<0.05) and 26.4±3.7cm (P=NS compared to 760m).

Conclusion

In healthy lowlanders staying at 3100m, nocturnal SpO2increased over 3 weeks after an initial drop but did not reach 760m baseline values. Postural control was impaired in the first week of acute exposure to high altitude despite improvements in hypoxemia. Altitude exposure had no effect on reaction time. Thus, acute and prolonged exposure to hypobaric hypoxia has differential effects on oxygenation, control of breathing, postural control and reaction time.
The role of natural language processing in cancer care: a systematic scoping review with narrative synthesis
Authors: Sun Mengxuan , Reiter Ehud , Duncan Lisa , Adam Rosalind
Published: November 2024

Objectives

To review studies of Natural Language Processing (NLP) systems that assist in cancer care, explore use cases and summarize current research progress.

Methods

A systematic scoping review, searching six databases (1) MEDLINE, (2) Embase, (3) IEEE Xplore, (4) ACM Digital Library, (5) Web of Science, and (6) ACL Anthology. Studies were included that reported NLP systems that had been used to improve cancer management by patients or clinicians. Studies were synthesized descriptively and using content analysis.

Results

Twenty-nine studies were included. Studies mainly applied NLP in mixed cancer types (n=10, 34.48%) and breast cancer (n=8, 27.59%). NLP was used in four main ways: (1) to support patient education and self-management; (2) to improve efficiency in clinical care by summarizing, extracting, and categorizing data, and supporting record-keeping; (3) to support prevention and early detection of patient problems or cancer recurrence; and (4) to improve cancer treatment by supporting clinicians to make evidence-based treatment decisions. Studies highlighted a wide variety of use cases for NLP technologies in cancer care. However, few technologies had been evaluated within clinical settings, none were evaluated against clinical outcomes, and none had been implemented into clinical care.

Conclusion

NLP has the potential to improve cancer care via several mechanisms, including information extraction and classification, which could enable automation and personalization of care processes. Additionally, NLP tools such as chatbots show promise in improving patient communication and support. However, there are deficiencies in the evaluation and clinical integration challenges. Interdisciplinary collaboration between computer scientists and clinicians will be essential if NLP technologies are to fulfil their potential to improve patient experience and outcomes. Registered Protocol:https://doi.org/10.17605/OSF.IO/G9DSR
In utero exposure to per – and polyfluoroalkyl substances (PFAS) associates with altered human infant T helper cell development
Authors: Meléndez Darline Castro , Laniewski Nathan , Jusko Todd A. , Qiu Xing , Paige Lawrence B. , Rivera-Núñez Zorimar , Brunner Jessica , Best Meghan , Macomber Allison , Leger Alena , Kannan Kurunthachalam , Miller Richard Kermit , Barrett Emily S. , O’Connor Thomas G. , Scheible Kristin
Published: November 2024

Background

Environmental exposures to chemical toxicants during gestation and infancy can dysregulate multiple developmental processes, causing lifelong effects. There is compelling evidence of PFAS-associated immunotoxicity in adults and children. However, the effect of developmental PFAS exposure on infant T-cell immunity is unreported, and, if present, could be implicated in immune-related health outcomes.

Objectives

We seek to model longitudinal changes in CD4+ T-cell subpopulations from birth through 12 months and their association with in-utero PFAS exposure and postnatal CD4+ T-cell frequencies and functions.

Methods

Maternal-infant dyads were recruited as part of the UPSIDE-ECHO cohort during the first trimester between 2015 and 2019 in Rochester, New York; dyads were followed through the infant’s first birthday. Maternal PFAS concentrations (PFOS, PFOA, PFNA, and PFHXS) were quantified in serum during the second trimester using high-performance liquid chromatography and tandem mass spectrometry. Infant lymphocyte frequencies were assessed at birth, 6- and 12-months using mass cytometry and high-dimensional clustering methods. Linear mixed-effects models were employed to analyze the relationship between maternal PFAS concentrations and CD4+ T-cell subpopulations (n=200). All models included a PFAS and age interaction and were adjusted for parity, infant sex, and pre-pregnancy body mass index.

Results

In-utero PFAS exposure correlated with multiple CD4+ T-cell subpopulations in infants. The greatest effect sizes were seen in T-follicular helper (Tfh) and T-helper 2 (Th2) cells at 12 months. A log2-unit increase in PFOS was associated with lower Tfh [0.17% (95%CI: −0.30, −0.40)] and greater Th2 [0.27% (95%CI: 0.18, 0.35)] cell percentages at 12 months. Similar trends were observed for PFOA, PFNA, and PFHXS.

Discussion

Maternal PFAS exposures correlate with cell-specific changes in the infant T-cell compartment, including key CD4+ T-cell subpopulations that play central roles in coordinating well-regulated, protective immunity. Future studies into the role of PFAS-associated T-cell distribution and risk of adverse immune-related health outcomes in children are warranted.
Sex and hormonal effects on drug cue-reactivity and its regulation in human addiction
Authors: Huang Yuefeng , Butelman Eduardo R. , Ceceli Ahmet O. , Kronberg Greg , King Sarah G. , McClain Natalie E. , Wong Yui Ying , Boros Maggie , Drury K Rachel , Sinha Rajita , Alia-Klein Nelly , Goldstein Rita Z.
Published: November 2024

Objective

To study the sex and hormonal effects on cortico-striatal engagement during drug cue-reactivity and its regulation focusing on drug reappraisal.

Methods

Forty-nine men (age=41.96±9.71) with heroin use disorder (HUD) and 32 age-matched women (age=38.85±9.84) with HUD (n=16) or cocaine use disorder (CUD; n=16) were scanned using functional MRI, with a subgroup of women scanned twice, during the late-follicular and mid-luteal phases, to examine sex and menstrual phase differences in cortico-striatal drug cue-reactivity and its cognitive reappraisal and their correlations with ovarian hormones and drug craving.

Results

Women showed higher medial prefrontal cortex (PFC) drug cue-reactivity while men showed higher frontal eye field (FEF)/dorsolateral PFC (dlPFC) drug reappraisal as associated with lower cue-induced drug craving. In the women, drug cue-reactivity was higher during the follicular phase in the FEF/dlPFC, whereas drug reappraisal was higher during the luteal phase in the anterior PFC/orbitofrontal cortex. The more the estradiol during the follicular vs. luteal phase (Δ), the higher the Δdrug cue-reactivity in the vmPFC, which also correlated with higher Δdrug craving (observed also in the inferior frontal gyrus). The more this Δestradiol, the lower the Δdrug reappraisal in the vmPFC, anterior PFC and striatum. Conversely, Δprogesterone/estradiol ratio was positively associated with Δdrug reappraisal in the dlPFC.

Conclusions

Compared to men, women with addiction show more cortico-striatal reactivity to drug cue exposure and less PFC activity during drug reappraisal, driven by the follicular compared to luteal phase and directly related to craving and fluctuations in estrogen and progesterone with the former constituting a vulnerability and the latter a protective factor. This study provides insights for developing precisely timed and hormonally informed treatments for women with addiction.