bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiomyocyte βII spectrin plays a critical role in maintaining cardiac function by regulating mitochondrial respiratory function
Authors: Yang Rongjin , Ruan Banjun , Wang Rutao , Zhang Xiaomeng , Xing Pingping , Li Congye , Zhang Yunyun , Chang Xiaoqian , Song Haifeng , Zhang Shun , Zhao Huishou , Zhang Feiyu , Yin Tao , Qi Tingting , Yan Wenjun , Zhang Fuyang , Hu Guangyu , Wang Shan , Tao Ling 
Published: June 2024

Abstract

Aims
βII spectrin is a cytoskeletal protein known to be tightly linked to heart development and cardiovascular electrophysiology. However, the roles of βII spectrin in cardiac contractile function and pathological post-myocardial infarction remodelling remain unclear. Here, we investigated whether and how βII spectrin, the most common isoform of non-erythrocytic spectrin in cardiomyocytes, is involved in cardiac contractile function and ischaemia/reperfusion (I/R) injury.

Methods and results
We observed that the levels of serum βII spectrin breakdown products (βII SBDPs) were significantly increased in patients with acute myocardial infarction (AMI). Concordantly, βII spectrin was degraded into βII SBDPs by calpain in mouse hearts after I/R injury. Using tamoxifen-inducible cardiac-specific βII spectrin knockout mice, we found that deletion of βII spectrin in the adult heart resulted in spontaneous development of cardiac contractile dysfunction, cardiac hypertrophy, and fibrosis at 5 weeks after tamoxifen treatment. Moreover, at 1 week after tamoxifen treatment, although spontaneous cardiac dysfunction in cardiac-specific βII spectrin knockout mice had not developed, deletion of βII spectrin in the heart exacerbated I/R-induced cardiomyocyte death and heart failure. Furthermore, restoration of βII spectrin expression via adenoviral small activating RNA (saRNA) delivery into the heart reduced I/R injury. Immunoprecipitation coupled with mass spectrometry (IP–LC–MS/MS) analyses and functional studies revealed that βII spectrin is indispensable for mitochondrial complex I activity and respiratory function. Mechanistically, βII spectrin promotes translocation of NADH:ubiquinone oxidoreductase 75-kDa Fe-S protein 1 (NDUFS1) from the cytosol to mitochondria by crosslinking with actin filaments (F-actin) to maintain F-actin stability.

Conclusion
βII spectrin is an essential cytoskeletal element for preserving mitochondrial homeostasis and cardiac function. Defects in βII spectrin exacerbate cardiac I/R injury.
A suite of genome-engineered hepatic cells provides novel insights into the spatiotemporal metabolism of apolipoprotein B and apolipoprotein B–containing lipoprotein secretion
Authors: Meurs Amber , Ndoj Klevis , van den Berg Marlene , Marinković Goran , Tantucci Matteo , Veenendaal Tineke , Kuivenhoven Jan Albert , Klumperman Judith , Zelcer Noam 
Published: June 2024

AbstractAimsApolipoprotein B (APOB)-containing very LDL (VLDL) production, secretion, and clearance by hepatocytes is a central determinant of hepatic and circulating lipid levels. Impairment of any of the aforementioned processes is associated with the development of multiple diseases. Despite the discovery of genes and processes that govern hepatic VLDL metabolism, our understanding of the different mechanistic steps involved is far from complete. An impediment to these studies is the lack of tractable hepatocyte-based systems to interrogate and follow APOB in cells, which the current study addresses.Methods and resultsTo facilitate the cellular study of VLDL metabolism, we generated human hepatic HepG2 and Huh-7 cell lines in which CRISPR/Cas9-based genome engineering was used to introduce the fluorescent protein mNeonGreen into the APOB gene locus. This results in the production of APOB100-mNeon that localizes predominantly to the endoplasmic reticulum (ER) and Golgi by immunofluorescence and electron microscopy imaging. The production and secretion of APOB100-mNeon can be quantitatively followed in medium over time and results in the production of lipoproteins that are taken up via the LDL receptor pathway. Importantly, the production and secretion of APOB-mNeon is sensitive to established pharmacological and physiological treatments and to genetic modifiers known to influence VLDL production in humans. As a showcase, we used HepG2-APOBmNeon cells to interrogate ER-associated degradation of APOB. The use of a dedicated sgRNA library targeting all established membrane-associated ER-resident E3 ubiquitin ligases led to the identification of SYNV1 as the E3 responsible for the degradation of poorly lipidated APOB in HepG2 cells.ConclusionsIn summary, the engineered cells reported here allow the study of hepatic VLDL assembly and secretion and facilitate spatiotemporal interrogation induced by pharmacologic and genetic perturbations.
Gut Microbial Species and Endotypes Associate with Remission in Ulcerative Colitis Patients Treated with Anti-TNF or Anti-integrin Therapy
Authors: Tamburini Fiona B , Tripathi Anupriya , Gold Maxwell P , Yang Julianne C , Biancalani Tommaso , McBride Jacqueline M , Keir Mary E , GARDENIA Study Group  
Published: June 2024

Abstract

Background and Aims
The gut microbiota contributes to aberrant inflammation in inflammatory bowel disease, but the bacterial factors causing or exacerbating inflammation are not fully understood. Further, the predictive or prognostic value of gut microbial biomarkers for remission in response to biologic therapy is unclear.

Methods
We perform whole metagenomic sequencing of 550 stool samples from 287 ulcerative colitis patients from a large, phase 3, head-to-head study of infliximab and etrolizumab.

Results
We identify several bacterial species in baseline and/or post-treatment samples that associate with clinical remission. These include previously described associations [Faecalibacterium prausnitzii_F] as well as new associations with remission to biologic therapy [Flavonifractor plautii]. We build multivariate models and find that gut microbial species are better predictors for remission than clinical variables alone. Finally, we describe patient groups that differ in microbiome composition and remission rate after induction therapy, suggesting the potential utility of microbiome-based endotyping.

Conclusions
In this large study of ulcerative colitis patients, we show that few individual species associate strongly with clinical remission, but multivariate models including microbiome can predict clinical remission and have better predictive power compared with clinical data alone.
Rethinking weight loss treatments as cardiovascular medicine in obesity, a comprehensive review
Authors: Tuccinardi Dario , Watanabe Mikiko , Masi Davide , Monte Lavinia , Meffe Luigi Bonifazi , Cavallari Ilaria , Nusca Annunziata , Maddaloni Ernesto , Gnessi Lucio , Napoli Nicola , Manfrini Silvia , Grigioni Francesco 
Published: June 2024

Abstract
The global escalation of obesity has made it a worldwide health concern, notably as a leading risk factor for cardiovascular disease (CVD). Extensive evidence corroborates its association with a range of cardiac complications, including coronary artery disease, heart failure, and heightened vulnerability to sudden cardiac events. Additionally, obesity contributes to the emergence of other cardiovascular risk factors including dyslipidaemia, type 2 diabetes, hypertension, and sleep disorders, further amplifying the predisposition to CVD. To adequately address CVD in patients with obesity, it is crucial to first understand the pathophysiology underlying this link. We herein explore these intricate mechanisms, including adipose tissue dysfunction, chronic inflammation, immune system dysregulation, and alterations in the gut microbiome.Recent guidelines from the European Society of Cardiology underscore the pivotal role of diagnosing and treating obesity to prevent CVD. However, the intricate relationship between obesity and CVD poses significant challenges in clinical practice: the presence of obesity can impede accurate CVD diagnosis while optimizing the effectiveness of pharmacological treatments or cardiac procedures requires meticulous adjustment, and it is crucial that cardiologists acknowledge the implications of excessive weight while striving to enhance outcomes for the vulnerable population affected by obesity. We, therefore, sought to overcome controversial aspects in the clinical management of heart disease in patients with overweight/obesity and present evidence on cardiometabolic outcomes associated with currently available weight management interventions, with the objective of equipping clinicians with an evidence-based approach to recognize and address CVD risks associated with obesity.
Are Virtual Assistants Trustworthy for Medicare Information: An Examination of Accuracy and Reliability
Authors: Langston Emily , Charness Neil , Boot Walter 
Published: June 2024

Abstract

Background and Objectives
Advances in artificial intelligence (AI)-based virtual assistants provide a potential opportunity for older adults to use this technology in the context of health information-seeking. Meta-analysis on trust in AI shows that users are influenced by the accuracy and reliability of the AI trustee. We evaluated these dimensions for responses to Medicare queries.

Research Design and Methods
During the summer of 2023, we assessed the accuracy and reliability of Alexa, Google Assistant, Bard, and ChatGPT-4 on Medicare terminology and general content from a large, standardized question set. We compared the accuracy of these AI systems to that of a large representative sample of Medicare beneficiaries who were queried twenty years prior.

Results
Alexa and Google Assistant were found to be highly inaccurate when compared to beneficiaries’ mean accuracy of 68.4% on terminology queries and 53.0% on general Medicare content. Bard and ChatGPT-4 answered Medicare terminology queries perfectly and performed much better on general Medicare content queries (Bard = 96.3%, ChatGPT-4 = 92.6%) than the average Medicare beneficiary. About one month to a month-and-a-half later, we found that Bard and Alexa’s accuracy stayed the same, whereas ChatGPT-4’s performance nominally decreased, and Google Assistant’s performance nominally increased.

Discussion and Implications
LLM-based assistants generate trustworthy information in response to carefully phrased queries about Medicare, in contrast to Alexa and Google Assistant. Further studies will be needed to determine what factors beyond accuracy and reliability influence the adoption and use of such technology for Medicare decision-making.
Temporal dynamism and the persisting stable self
Authors: Latham Andrew J , Miller Kristie , Yechimovitz Shira 
Published: June 2024

AbstractEmpirical evidence suggests that a majority of people believe that time robustly passes and that many also report that it seems to them, in experience, as though time robustly passes. Non-dynamists deny that time robustly passes, and many contemporary non-dynamists—deflationists—even deny that it seems to us as though time robustly passes. Non-dynamists, then, face the dual challenge of explaining why people have such beliefs and make such reports about their experiences. Several philosophers have suggested the stable-self explanation, according to which what partly explains one or both of the explananda is that people believe themselves to have a stable persisting self that is imagined either as moving through time or as being stationary with time moving around it. This paper empirically investigates this explanation. We found, however, no evidential support for the stable-self explanation, leaving the non-dynamist but also, we will argue, the dynamist with an extant explanatory challenge.
How Effective are the Monin–Lundgren Hierarchy and the Karman–Howarth Equation for Low-Reynolds-Number Decaying Isotropic Turbulence?
Authors: Hosokawa Iwao 
Published: June 2024

Abstract
The study of decaying homogeneous isotropic turbulence (HIT) in a series of the author's recent works is extended here to present new aspects of its nearly final period of decay and the time-dependent Loitsyanskii integral. The works contain a Gaussian family of exact solutions for a velocity probability density function (PDF) of the first equation of the Monin–Lundgren hierarchy and time-dependence of many physical quantities for a wide range of Taylor-scale Reynolds numbers (${{{\mathop{{R}}\nolimits} }_\lambda } = 40 \sim 100000$ or more). In this Letter, the case with ${{{\mathop{{R}}\nolimits} }_\lambda } = 40$ is taken up in particular, and it is revealed to be almost the lower limit for the application of our method to treat decaying HIT.
Widespread Pressure Pain Hyperalgesia Is Not Associated With Morphological Changes of the Wrist Extensor Tendon in Unilateral Lateral Epicondylalgia: A Case–Control Study
Authors: Cancela-Cilleruelo Ignacio , Rodríguez-Jiménez Jorge , Fernández-de-las-Peñas César , Cleland Joshua A , Arias-Buría José L 
Published: June 2024

Abstract

Objective
The aims of the current study were to investigate the presence of widespread pressure hyperalgesia, the presence of structural changes in the wrist extensor tendon and muscle, and their association in people with lateral epicondylalgia (LE).

Methods
Thirty-seven patients with LE (43% women; mean age = 45.5 [SD = 9.5] years) and 37 controls matched for age and sex and free of pain participated in this study. Pressure pain thresholds (PPTs) were assessed bilaterally over the symptomatic area (elbow), 2 segment-related areas (C5–C6 joint, second intermetacarpal space), and 1 remote area (tibialis anterior) in a blinded design. Ultrasound measurements (eg, cross-sectional area, thickness, and width) of the common wrist extensor tendon and extensor carpi radialis brevis muscle as well as the thickness of the supinator muscle were assessed.

Results
Patients with LE exhibited lower PPTs bilaterally at all points and lower PPTs at the lateral epicondyle and second intermetacarpal space on the symptomatic side as compared to the nonsymptomatic side (η2 from 0.123–0.369; large effects). Patients exhibited higher cross-sectional area and width of the common wrist extensor tendon (η2 from 0.268–0.311; large effects) than controls bilaterally, whereas tendon thickness was also higher (η2 = 0.039; small effects) on the painful side than on the nonpainful side.

Conclusions
This study reported bilateral widespread pressure pain hyperalgesia and morphological changes in the tendon, but not the muscle, in LE. Pressure pain sensitivity and morphological changes were not associated in individuals with LE.

Impact
Management of LE should consider altered nociceptive pain processing and structural tendon changes as 2 different phenomena in patients with LE.
Piloting a Hospital-Based Rapid Methadone Initiation Protocol for Fentanyl
Authors: Liu Patricia , Chan Brian , Sokolski Eleasa , Patten Alisa , Englander Honora 
Published: June 2024

ObjectivesTreating acute opioid withdrawal and offering medications for opioid use disorder (OUD) is critical. Hospitalization offers a unique opportunity to rapidly initiate methadone for OUD; however, little clinical guidance exists. This report describes our experience during the first 9 months following introduction of a hospital-based rapid methadone initiation protocol.MethodsWe conducted a retrospective chart review of hospitalized patients with OUD seen by our interprofessional addiction medicine consult service at an urban academic center between December 2022 and August 2023. We identified patients who initiated methadone using the rapid methadone initiation protocol, which includes dose recommendations (maximum 60 mg day 1, 70 mg day 2, 80 mg day 3, 100 mg days 4–7) and strict inclusion and exclusion criteria (end organ failure, arrhythmia, concurrent benzodiazepine or alcohol use, age >65).ResultsThere were 171 patients that received methadone for OUD during the study period. Of those, 25 patients (15%) received rapid methadone initiation. The average total daily dose of methadone on days 1–7 was 53.0 mg, 69.2 mg, 75.4 mg, 79.5 mg, 87.1 mg, 92.2 mg, and 96.6 mg, respectively. There were no adverse events requiring holding a dose of scheduled methadone, naloxone administration, or transfer to higher level of care.ConclusionsA rapid methadone initiation protocol for OUD can be implemented in the inpatient setting. Patients up-titrated their methadone doses quicker than with traditional induction methods, and there were no serious adverse events. Appropriate patient selection may be important to avoid harms.
Guided Growth to Treat Anterolateral Tibial Bowing Associated with Congenital Pseudarthrosis of the Tibia
Authors: Todderud Julia E. , Carlson Samuel W. , Larson A. Noelle 
Published: June 2024

Background:
Anterolateral tibial bowing associated with congenital tibial pseudarthrosis occurs often in patients with neurofibromatosis type 1 and results from the inability of the fractured bone to unite, leading to persistent nonunion, abnormal bone growth, and further bowing of the tibia. Current surgical and nonsurgical approaches demonstrate persistent nonunion or refracture, often resulting in amputation.

Methods:
This report describes the management of 3 patients with anterolateral tibial bowing and NF1 who underwent distal tibia-guided growth.

Results:
The patients had an average age of 1.6 years at initial operation, with a total of 3 to 4 surgeries over an average of 2.1 years. The latest follow-up on all patients is included, at a mean of 5.1 years after the initial operation. All 3 patients experienced substantial functional improvement and improved alignment of the mechanical axis of the tibia. One patient has experienced refracture.

Conclusions:
Our study indicates that guided growth can serve as an additional surgical option to improve ALTB and potentially reduce the risk of fracture and pseudarthrosis by restoring normal mechanical alignment.

Level of Evidence:
Level—IV, Case Series.
The Evolution of Curve Patterns in Adolescent Idiopathic Scoliosis During Chêneau Brace Treatment
Authors: Hou Hao , Guo Dong , Liu Haonan , Luo Yanzhong , Yao Ziming , Feng Lei , Cao Jun , Gao Rongxuan , Zhang Xuejun 
Published: June 2024

Study Design/Setting.
This retrospective study analyzed bracing outcomes in patients with adolescent idiopathic scoliosis (AIS), focusing on curve pattern changes and brace efficacy.

Objective.
To analyze the effectiveness of the Chêneau brace across different curve patterns and to evaluate the tendencies in curve evolution during treatment.

Background.
AIS presents diverse curve patterns, each responding differently to bracing. Understanding these variations is crucial for optimizing treatment strategies.

Patients and Methods.
The study included 177 patients with AIS treated with Chêneau orthoses, categorized based on curve patterns as per the main curve and modified Lenke (mLenke) classifications. We compared patients according to curve patterns and assessed changes in curve magnitude and pattern before and after treatment.

Results.
Over an average follow-up of 28.1 ± 10.7 months, the primary curve magnitude decreased from 28.8 ± 6.6° to 25.9 ± 10.5°. Significant reductions were observed in mLenke V and VI patients (P < 0.05). Patients with main lumbar curves showed better initial in-brace correction and curve control compared with those with main thoracic curves (P < 0.05). In single-curve patterns, binary logistic regression indicated that mLenke V patients demonstrated higher rates of curve control compared with mLenke I patients (P < 0.05). No significant differences were found in double-curve patterns between mLenke III and VI (P > 0.05). At the final follow-up, thoracolumbar/lumbar curves improved significantly in mLenke III and VI patients (P < 0.05), whereas thoracic curves did not (P > 0.05). Furthermore, at the last follow-up, the proportions of mLenke I, II, and IV increased, whereas mLenke III, V, and VI decreased.

Conclusions.
Bracing outcomes were more favorable in patients with main lumbar curves than those with main thoracic curves. However, no significant differences were found in patients with double-curve patterns. Thoracic curves exhibited a higher progression risk compared with thoracolumbar/lumbar curves within the same curve pattern. During bracing, a tendency for primary curves to shift proximally was noted.

Level of Evidence.
Level III.
Quality Evaluation of Guidelines for the Diagnosis and Treatment of Liver Failure
Authors: Wang Xia , Zheng Meng-Yao , He Hai-Yu , Zhu Hui-Ling , Zhao Ya-Fang , Chen Yu-Hang , Xu Zhi-Yuan , Yang Jin-Hui , Sun Da-Li 
Published: June 2024

OBJECTIVES:
This study aimed to systematically assess the methodological quality and key recommendations of the guidelines for the diagnosis and treatment of liver failure (LF), furnishing constructive insights for guideline developers and equipping clinicians with evidence-based information to facilitate informed decision-making.

DATA SOURCES:
Electronic databases and manual searches from January 2011 to August 2023.

STUDY SELECTION:
Two reviewers independently screened titles and abstracts, then full texts for eligibility. Fourteen guidelines were included.

DATA EXTRACTION AND SYNTHESIS:
Two reviewers extracted data and checked by two others. Methodological quality of the guidelines was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Of the 14 guidelines, only the guidelines established by the Society of Critical Care Medicine and the American College of Gastroenterology (2023) achieved an aggregate quality score exceeding 60%, thereby meriting clinical recommendations. It emerged that there remains ample room for enhancement in the quality of the guidelines, particularly within the domains of stakeholder engagement, rigor, and applicability. Furthermore, an in-depth scrutiny of common recommendations and supporting evidence drawn from the 10 adult LF guidelines unveiled several key issues: controversy exists in the recommendation, the absence of supporting evidence and confusing use of evidence for recommendations, and a preference in evidence selection.

CONCLUSIONS:
There are high differences in methodological quality and recommendations among LF guidelines. Improving these existing problems and controversies will benefit existing clinical practice and will be an effective way for developers to upgrade the guidelines.
Impact of Cutaneous Squamous Cell Carcinoma Histologic Features on Percent Interrater Agreement Regarding Tumor Differentiation
Authors: Shahwan Kathryn T. , Varra Vamsi , Nash Jessica , Chung Catherine G. , Buckley Kaila A. , McIlwee Bridget E. , Carr David R. 
Published: June 2024

BACKGROUND
Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system.

OBJECTIVE
To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement.

MATERIALS AND METHODS
In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system.

RESULTS
The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study.

CONCLUSION
Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading.