bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage mediators and mechanisms in cardiovascular disease
Authors: Schelemei Patrik , Wagner Elena , Picard Felix Simon Ruben , Winkels Holger 
Published: January 2024

AbstractMacrophages are major players in myocardial infarction (MI) and atherosclerosis, two major cardiovascular diseases (CVD). Atherosclerosis is caused by the buildup of cholesterol‐rich lipoproteins in blood vessels, causing inflammation, vascular injury, and plaque formation. Plaque rupture or erosion can cause thrombus formation resulting in inadequate blood flow to the heart muscle and MI. Inflammation, particularly driven by macrophages, plays a central role in both atherosclerosis and MI. Recent integrative approaches of single‐cell analysis‐based classifications in both murine and human atherosclerosis as well as experimental MI showed overlap in origin, diversity, and function of macrophages in the aorta and the heart. We here discuss differences and communalities between macrophages in the heart and aorta at steady state and in atherosclerosis or upon MI. We focus on markers, mediators, and functional states of macrophage subpopulations. Recent trials testing anti‐inflammatory agents show a major benefit in reducing the inflammatory burden of CVD patients, but highlight a necessity for a broader understanding of immune cell ontogeny and heterogeneity in CVD. The novel insights into macrophage biology in CVD represent exciting opportunities for the development of novel treatment strategies against CVD.
Cleavage efficiency of the intramembrane protease γ‐secretase is reduced by the palmitoylation of a substrate's transmembrane domain
Authors: Aßfalg Marlene , Güner Gökhan , Müller Stephan A. , Breimann Stephan , Langosch Dieter , Muhle‐Goll Claudia , Frishman Dmitrij , Steiner Harald , Lichtenthaler Stefan F. 
Published: January 2024

AbstractThe intramembrane protease γ‐secretase has broad physiological functions, but also contributes to Notch‐dependent tumors and Alzheimer's disease. While γ‐secretase cleaves numerous membrane proteins, only few nonsubstrates are known. Thus, a fundamental open question is how γ‐secretase distinguishes substrates from nonsubstrates and whether sequence‐based features or post‐translational modifications of membrane proteins contribute to substrate recognition. Using mass spectrometry‐based proteomics, we identified several type I membrane proteins with short ectodomains that were inefficiently or not cleaved by γ‐secretase, including ‘pituitary tumor‐transforming gene 1‐interacting protein’ (PTTG1IP). To analyze the mechanism preventing cleavage of these putative nonsubstrates, we used the validated substrate FN14 as a backbone and replaced its transmembrane domain (TMD), where γ‐cleavage occurs, with the one of nonsubstrates. Surprisingly, some nonsubstrate TMDs were efficiently cleaved in the FN14 backbone, demonstrating that a cleavable TMD is necessary, but not sufficient for cleavage by γ‐secretase. Cleavage efficiencies varied by up to 200‐fold. Other TMDs, including that of PTTG1IP, were still barely cleaved within the FN14 backbone. Pharmacological and mutational experiments revealed that the PTTG1IP TMD is palmitoylated, which prevented cleavage by γ‐secretase. We conclude that the TMD sequence of a membrane protein and its palmitoylation can be key factors determining substrate recognition and cleavage efficiency by γ‐secretase.
Feasibility of Saphenous Nerve Somatosensory-Evoked Potential Intraoperative Monitoring During Lumbar Spine Surgery
Authors: Rucker Sydney , Singh Nishtha , Mai Eric , Asada Tomoyuki , Shahi Pratyush , Mercado Kristin , Leung Dora , Iyer Sravisht , Emerson Ronald , Qureshi Sheeraz A. 
Published: January 2024

Study Design.
Retrospective review.

Objective.
Assess the feasibility of saphenous nerve somatosensory evoked potentials (SN-SSEP) monitoring in lumbar spine surgeries.

Background Context.
SN-SSEPs have been proposed for detecting lumbar plexus and femoral nerve injury during lateral lumbar surgery where tibial nerve (TN) SSEPs alone are insufficient. SN-SSEPs may also be useful in other types of lumbar surgery, as stimulation of SN below the knee derives solely from the L4 root and provides a means of L4 monitoring, whereas TN-SSEPs often do not detect single nerve root injury. The feasibility of routine SN-SSEP monitoring has not been established.

Methods.
A total of 563 consecutive cases using both TN-SSEP and SN-SSEP monitoring were included. Anesthesia was at the discretion of the anesthesiologist, using an inhalant in 97.7% of procedures. SN stimulation was performed using 13 mm needle electrodes placed below the knee using 200-400 μsec pulses at 15 to 100 mA. Adjustments to stimulation parameters were made by the neurophysiology technician while obtaining baselines. Data were graded retrospectively for monitorability and cortical response amplitudes were measured by two independent reviewers.

Results.
Ninety-eight percent of TN-SSEPs and 92.5% of SN-SSEPs were monitorable at baseline, with a mean response amplitude of 1.35 μV for TN-SSEPs and 0.71 μV for SN-SSEPs. A significant difference between the stimulation parameters used to obtain reproducible TN and SN-SSEPs at baseline was observed, with SN-SSEPs requiring greater stimulation intensities. Body mass index is not associated with baseline monitorability. Out of 20 signal changes observed, 11 involved SN, while TN-SSEPs were unaffected.

Conclusion.
With adjustments to stimulation parameters, SN-SSEP monitoring is feasible within a large clinical cohort without modifications to the anesthetic plan. Incorporating SN into standard intraoperative neurophysiological monitoring protocols for lumbar spine procedures may expand the role of SSEP monitoring to include detecting injury to the lumbar plexus.

Level of Evidence.
3.
Effects of Vibration Therapy on the Physical Function of Critically Ill Adults Trial: A Randomized Controlled Trial
Authors: Doi Satoshi , Nakanishi Nobuto , Kawahara Yoshimi , Nomura Keiko , Shima Mamiko , Shiraishi Mie , Oto Jun 
Published: January 2024

Objectives:
Vibration therapy uses vibration to rehabilitate physical functions. Recently, it has been demonstrated to be safe for critically ill patients. However, its effects on physical functions are unclear.

Design:
Randomized controlled trial.

Setting:
A single-center, ICU.

Patients:
Patients were randomly assigned to either vibration therapy coupled with protocolized mobilization or protocolized mobilization alone. We included patients who could sit at the edge of the bed or in a wheelchair during their ICU stay. The exclusion criteria were based on the early mobilization inhibition criteria.

Interventions:
The primary outcome was the Functional Status Score for the ICU (FSS-ICU) at ICU discharge. Secondary outcomes were the Medical Research Council score, ICU-acquired weakness, delirium, ICU Mobility Scale (IMS), and ventilator- and ICU-free days. For safety assessment, vital signs were monitored during the intervention.

Measurements and Main Results:
Among 180 patients, 86 and 90 patients remained in the vibration therapy and control groups, respectively. The mean age was 69 ± 13 vs. 67 ± 16 years in the vibration therapy and control groups, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score was 19 (14–25) vs. 18 (13–23). The total FSS-ICU at ICU discharge was 24 (18–27) and 21 (17–26) in the intervention and control groups, respectively (p = 0.09), and the supine-to-sit ability significantly improved in the intervention group (p < 0.01). The secondary outcomes were not significantly different. Vital signs remained stable during vibration therapy. In the predefined subgroup analysis, FSS-ICU improved in the population with a higher body mass index (≥ 23 kg/m2), lower APACHE II scores (< 19), and higher IMS scores (≥ 6).

Conclusions:
Vibration therapy did not improve the total FSS-ICU. However, the supine-to-sit ability in the FSS-ICU improved without any adverse event.
Factors Associated With Performing Ileal Pouch-Anal Anastomosis After Total Colectomy for Ulcerative Colitis
Authors: Chen Kevin A. , Pak Joyce , Agala Chris B , Stem Jonathan M. , Guillem Jose G. , Barnes Edward L , Herfarth Hans H. , Kapadia Muneera R. 
Published: January 2024

BACKGROUND:
Ileal pouch-anal anastomosis is considered the procedure of choice for restorative surgery after total colectomy for ulcerative colitis. Previous studies have examined the rate of ileal pouch-anal anastomosis within individual states, but not at the national level in the United States.

OBJECTIVE:
Assess the rate of ileal pouch-anal anastomosis after total colectomy for ulcerative colitis in a national population and identify factors associated with ileal pouch-anal anastomosis.

DESIGN:
This was a retrospective cohort study.

SETTINGS:
This study was performed in the United States.

PATIENTS:
Patients who were ≥18 years old who underwent total colectomy between 2009 and 2019 for a diagnosis of ulcerative colitis were identified within a commercial database. This database excluded patients with public insurance, including all patients >65 years old with Medicare.

MAIN OUTCOME MEASURES:
The primary outcome was ileal pouch-anal anastomosis. Multivariable logistic regression was used to assess the association between covariates and likelihood of undergoing ileal pouch-anal anastomosis.

RESULTS:
In total, 2,816 patients were included of whom 1414 (50.2%) underwent ileal pouch-anal anastomosis, 928 (33.0%) underwent no further surgery, and 474 (16.8%) underwent proctectomy with end ileostomy. Younger age, lower comorbidities, elective case, and laparoscopic approach in the initial colectomy were significantly associated with ileal pouch-anal anastomosis, but not socioeconomic status.

LIMITATIONS:
This retrospective study included only patients with commercial insurance.

CONCLUSIONS:
A total of 50.2% of patients undergo ileal pouch-anal anastomosis and younger age, lower co-morbidities, and elective cases are associated with a higher rate of ileal pouch-anal anastomosis placement. This emphasizes the importance of ensuring follow-up with colorectal surgeons to provide the option of restorative surgery, especially for patients undergoing urgent or emergent colectomies. See Video Abstract.
Endoscopic Evaluation of the Ileal Pouch
Authors: Shen Bo 
Published: January 2024

BACKGROUND:
Structural and inflammatory adverse sequelae are common after restorative proctocolectomy and ileal pouch-anal anastomosis. On rare occasions, neoplasia can occur in patients with ileal pouches. Pouchoscopy plays a key role in the diagnosis, differential diagnosis, disease monitoring, assessment of treatment response, surveillance, and delivery of therapy.

OBJECTIVE:
A systemic review of the literature was performed and principles and techniques of pouchoscopy were described.

DATA SOURCES:
PubMed, Google Scholar, and Cochrane database.

STUDY SELECTION:
Relevant articles on endoscopy in ileal pouches published between Jan 2000 and May 2023 were including based on PRISMA guidelines.

INTERVENTION:
Diagnostic, surveillance, and therapeutic endoscopy in ileal pouch disorders were included.

MAIN OUTCOME MEASURES:
Accurate characterization of the ileal pouch at the healthy or diseased states.

RESULTS:
The main anatomic structures of a J or S pouch are the stoma closure site, prepouch ileum, inlet, tip of the “J,” pouch body, anastomosis, cuff, and anal transition zone. Each anatomic location can be prone to the development of structural, inflammatory, or neoplastic disorders. For example, ulcers and strictures are common at the stoma closure site, inlet, and anastomosis. Leaks are commonly detected at the tip of the “J” and anastomosis. Characterization of the anastomotic distribution of inflammation is critical for the differential diagnosis of subtypes of pouchitis and other inflammatory disorders of the pouch. Neoplastic lesions, albeit rare, mainly occur at the cuff, anal transition zone, or anastomosis.

LIMITATIONS:
This is a qualitative, not quantitative review of mainly case series.

CONCLUSIONS:
Most structural, inflammatory, and neoplastic disorders can be reliably diagnosed with a careful pouchoscopy. The endoscopist and other clinicians taking care of pouch patients should be familiar with the anatomy of the ileal pouch, and recognize common abnormalities. See video from symposium. See Video.
Exosomes miRNA-499a-5p targeted CD38 to alleviate anthraquinone induced cardiotoxicity: experimental research
Authors: Ma Chunhua , Yang Zhaocong , Wang Jing , She Han , Tan Lei , Ye Qing , Wang Fei , Feng Xiaochun , Mo Xuming , Liu Kun , Liu Liangming 
Published: January 2024

Background:
The purpose of this study was to investigate the effects of cardiac homing peptide (CHP) engineered bone marrow mesenchymal stem cells (BMMSc) derived exosomes (B-exo) loaded miRNA-499a-5p on doxorubicin (DOX) induced cardiotoxicity.

Methods:
miRNA chip analysis was used to analyze the differences between DOX induced H9c2 cells and control group. CHP engineering was performed on BMMSc derived exosomes to obtain C-B-exo. miRNA-499a-5p mimic was introduced into C-B-exo by electroporation technology to obtain C-B-exo-miRNA-499a-5p. DOX was used to establish a model of cardiotoxicity to evaluate the effects of C-B-exo- miRNA-499a-5p in vivo and in vitro. Western blot, immunohistochemistry, immunofluorescence, and other molecular biology methods were used to evaluate the role and mechanism of C-B-exo-miRNA-499a-5p on DOX induced cardiotoxicity.

Results:
miRNA chip analysis revealed that miRNA-499a-5p was one of the most differentially expressed miRNAs and significantly decreased in DOX induced H9c2 cells as compared to the control group. Exo-and B-exo have a double-layer membrane structure in the shape of a saucer. After engineering the CHP of B-exo, the results showed that the delivery of miRNA-499a-5p significantly increased and significantly reached the target organ (heart). The experimental results showed that C-B-exo-miRNA-499a-5p significantly improved electrocardiogram, decreased myocardial enzyme, serum and cardiac cytokines, improved cardiac pathological changes, inhibited CD38/MAPK/NF-κB signal pathway.

Conclusions:
In this study, C-B-exo-miRNA-499a-5p significantly improved DOX-induced cardiotoxicity via CD38/MAPK/NF-κB signal pathway, providing a new idea and method for the treatment of DOX induced cardiotoxicity.
C-reactive protein, pharmacological treatments and diet: how to target your inflammatory burden
Authors: Bay Benjamin , Arnold Natalie , Waldeyer Christoph 
Published: January 2024

Purpose of review
This article focuses on pharmacological agents as well as dietary changes aimed at the reduction of the inflammatory burden measured by circulating C-reactive protein concentrations.

Recent findings
Over the last years, repurposed as well as new anti-inflammatory agents have been investigated in outcome trials in the cardiovascular field. Currently, a specific inhibition of the inflammatory cascade via the interleukin-6 ligand antibody ziltivekimab is being explored in large-scale outcome trials, after the efficacy of this agent with regard to the reduction of inflammatory biomarkers was proven recently. Next to the investigated pharmacological agents, specific dietary patterns possess the ability to improve the inflammatory burden. This enables patients themselves to unlock a potential health benefit ahead of the initiation of a specific medication targeting the inflammatory pathway.

Summary
Both pharmacological agents as well as diet provide the opportunity to improve the inflammatory profile and thereby lower C-reactive protein concentrations. Whilst advances in the field of specific anti-inflammatory treatments have been made over the last years, their broad implementation is currently limited. Therefore, optimization of diet (and other lifestyle factors) could provide a cost effective and side-effect free intervention to target low-grade vascular inflammation.
Wilson’s disease causing acute-onset of optic neuropathy in a child: a case report and literature review
Authors: Albostani Ammar , Warda Hamza , Alhashemi Fares , Rajabieh Manar , Abdulrazzak Mohammed , Kanjo Muhamad 
Published: January 2024

Introduction and importance:
Wilson disease (WD) is a rare genetic disorder with a wide range of clinical manifestations, including hepatic, neurologic, and psychiatric symptoms. To date, there have been five cases (including our case) representing optic neuropathy caused by WD.

Case presentation:
A 15-year-old female presented to the emergency department with neurological symptoms. The patient exhibited confusion but maintained stable vital signs, and physical examinations were all normal. Abdominal ultrasound and axial brain computed tomography (CT) scan were both normal. The patient’s neurological condition and laboratory test results suggested diagnoses of WD. After 2 days, the patient experienced sudden bilateral blindness. The patient’s condition deteriorated rapidly, and was subsequently referred to the ICU.

Clinical discussion:
The incidence of the disease varies by ethnicity, with a higher prevalence in Eastern Asian populations. Diagnosis can be challenging due to the diverse presentation of symptoms, but it is important to consider WD as a differential diagnosis in patients presenting with acute hepatitis and/or neurologic abnormalities.

Conclusion:
Healthcare professionals should be educated about the diverse clinical manifestations of WD to help in early recognition and diagnosis of the disease.
The Role of Guar Fiber in Improving the Management of Irritable Bowel Syndrome, Functional Constipation, and Functional Diarrhea
Authors: Tupper Lara , Terol Monique , Utter Jennifer , Morley Shannon 
Published: January 2024

Background and Aims
Guar fiber is a soluble fiber that has been used for symptom management of irritable bowel syndrome (IBS), functional constipation (FC), and functional diarrhea (FD). However, the effect of guar fiber supplementation on symptom management is currently unclear. The aim of this review is to determine the effect of guar fiber supplementation compared with any other nutrition intervention on gastrointestinal (GI) symptoms with individuals diagnosed with IBS, FC, and FD. A secondary aim is to determine the dosage of guar fiber supplementation required to elicit an improvement in associated symptoms.

Methods
A systematic review (CRD42022374730) was performed with literature from inception. PubMed, EMBASE, CINAHL, and Web of Science were searched on October 28, 2022, to identify eligible studies which reported guar fiber supplementation in patients diagnosed with IBS, FC, and/or FD using the Rome criterion. Findings were synthesized narratively. Study quality was assessed using the Johanna Briggs Institute quality assessment tools.

Results
Nine articles reported on stool consistency, defecation frequency, laxative use, bloating, abdominal pain, flatulence, and quality of life (QOL). All pre-post studies (n = 5) reported statistically significant improvements for GI symptoms and QOL. Two of 4 randomized controlled trial studies reported improvements in GI symptoms when supplemented daily with 5 to 6 g of guar fiber for 4 to 12 weeks.

Conclusions
Our study shows that guar fiber supplementation appears effective in improving symptom management of IBS and FC with a 5-g/d dosage most used. Future studies are required to more clearly understand the benefits of guar fiber supplementation and elucidate dosing strategies. This review provides the grounds for further well-designed studies to investigate the impact of guar fiber supplementation in populations with IBS, FC, and FD.
Virtual geriatric and frailty assessment for older adults with cancer
Authors: Tejero Isabel , Amor Eva , Vázquez-Ibar Olga 
Published: January 2024

Purpose of review
Since SARS-CoV2 pandemic, many specialties have introduced virtual assessments within clinical practice. Conducting an online geriatric assessment, or relying on self-reported questionnaires, may be more challenging than a conventional medical appointment. This review aims to discuss the state of research on virtual assessment and self-reported questionnaires in the general geriatric population and specifically in Oncology.

Recent findings
Virtual assessment of older adults has been the focus of two separate position papers. Aside from videoconferences or phone appointments, self-reported questionnaires have emerged in recent years as reliable tools to screen for frailty and triage patients who would benefit from a comprehensive in-person assessment, with adequate correlation with in-person tests, good acceptance by the respondents and being well received by healthcare providers. Although some have been tried in geriatric oncology, many still lack validation, and their widespread use may be limited by digital literacy, cognitive impairment, and social supports.

Summary
The development, validation and adoption of self-reported questionnaires and virtual assessment in the care of older adults with cancer may overcome the staffing limitations and time constrains that frequently hampers the widespread evaluation of this population to improve their care.
The Relationship between microbial population adenosine triphosphate and quantitative polymerase chain reaction bioburdens in diesel fuel microcosms
Authors: Passman Frederick Jay , Schmidt Jordan , Nicoletti Danika 
Published: January 2024

Fluid samples drawn from the fuel, interface, and water phases of fuel over water microcosms were tested for cellular adenosine triphosphate concentration ([cATP]), and quantitative polymerase chain reaction (qPCR) bioburdens. Additionally, surface swab samples from steel corrosion coupon surfaces exposed to each of these three phases were collected and tested for total ATP concentration ([tATP]) and qPCR bioburdens. Statistical relationships between ATP and qPCR bioburdens were examined. Correlation coefficients between the two variables were matrix dependent and ranged from negligible (|r| = 0.2) to strong (|r| = 0.7). When results were categorized into negligible, moderate, and heavy bioburdens, parameter agreement was again matrix dependent. Percent agreement between [ATP] and qPCR gene copies ranged from 11 % to 89 % – with qPCR-bioburden ratings typically being greater than ATP-bioburden ratings.
Functional impairment of “helpless” CD8+memory T cells is transient and driven by prolonged but finite cognate antigen presentation
Authors: van der Heide Verena , Davenport Bennett , Cubitt Beatrice , Roudko Vladimir , Choo Daniel , Humblin Etienne , Jhun Kevin , Angeliadis Krista , Dawson Travis , Furtado Glaucia , Kamphorst Alice , Ahmed Rafi , de la Torre Juan Carlos , Homann Dirk 
Published: January 2024

SUMMARYGeneration of functional CD8+T cell memory typically requires engagement of CD4+T cells. However, in certain scenarios, such as acutely-resolving viral infections, effector (TE) and subsequent memory (TM) CD8+T cell formation appear impervious to a lack of CD4+T cell help during priming. Nonetheless, such “helpless” CD8+TMrespond poorly to pathogen rechallenge. At present, the origin and long-term evolution of helpless CD8+T cell memory remain incompletely understood. Here, we demonstrate that helpless CD8+TEdifferentiation is largely normal but a multiplicity of helpless CD8 TMdefects, consistent with impaired memory maturation, emerge as a consequence of prolonged yet finite exposure to cognate antigen. Importantly, these defects resolve over time leading to full restoration of CD8+TMpotential and recall capacity. Our findings provide a unified explanation for helpless CD8+T cell memory and emphasize an unexpected CD8+TMplasticity with implications for vaccination strategies and beyond.