bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between iron overload caused by abnormal hepcidin expression and liver disease: A review
Authors: Zheng Haoran , Yang Fan , Deng Kaige , Wei Jiaxin , Liu Zhenting , Zheng Yong-Chang , Xu Haifeng
Published: March 2023

Iron is essential to organisms, the liver plays a vital role in its storage. Under pathological conditions, iron uptake by the intestine or hepatocytes increases, allowing excess iron to accumulate in liver cells. When the expression of hepcidin is abnormal, iron homeostasis in humans cannot be regulated, and resulting in iron overload. Hepcidin also regulates the release of iron from siderophores, thereby regulating the concentration of iron in plasma. Important factors related to hepcidin and systemic iron homeostasis include plasma iron concentration, body iron storage, infection, inflammation, and erythropoietin. This review summarizes the mechanism and regulation of iron overload caused by hepcidin, as well as related liver diseases caused by iron overload and treatment.
Anesthesia during delivery in pregnant women with dilated cardiomyopathy
Authors: Sasaki Makoto , Ohnishi Yoshihiko
Published: March 2023

Emergency cesarean delivery in patients with heart failure increases maternal and fetal mortality. The present study aimed to identify the relationship between the use of anesthesia for delivery and progressive cardiac deterioration in women with dilated cardiomyopathy (DCM) and to examine its implications on maternal and fetal outcomes. Twenty-nine pregnancies in 25 women with DCM from the National Cerebral and Cardiovascular Center Hospital (Suita, Japan) were included in this retrospective longitudinal study. Fourteen of the patients (48.3%) delivered via cesarean section. Among these, 4 patients (13.8%) experienced heart failure within 42 days of delivery. The indication for cesarean delivery was heart failure in 3 patients and induction failure in 1 patient. The types of anesthesia used for these patients included general (n = 1), combined spinal-epidural (n = 2), and epidural (n = 1). Two of these cesarean deliveries were performed preterm. The left ventricular ejection fraction of patients with heart failure was ≤ 35% before 34 weeks gestation. Among the 25 patients without heart failure, 2 exhibited a left ventricular ejection fraction of ≤ 35% before 34 weeks gestation. Meanwhile, the types of anesthesia used for remaining 10 patients who did not experience heart failure included general (n = 1), combined spinal-epidural (n = 8), and epidural (n = 1). The rate of general anesthesia was 25% in patients who experienced heart failure and 4% in others. There was no incidence of maternal or fetal death. A preterm anesthetic evaluation may be warranted to optimize anesthetic management when the ejection fraction decreases to ≤ 35% before 34 weeks gestation in patients with DCM.
Neutrophil to lymphocyte ratio can predict overall survival in patients with stage II to III colorectal cancer
Authors: Cho Yerim , Park Su Bee , Yoon Jin Young , Kwak Min Seob , Cha Jae Myung
Published: March 2023

The neutrophil-to-lymphocyte ratio (NLR) is a prognostic inflammatory marker in colorectal cancer (CRC), however, little is known for its prognostic role in stage II to III CRC patients underwent curative resection. This study was aimed to investigate prognostic role of NLR in stage II to III CRC patients underwent surgery. Medical records of 1378 newly diagnosed CRC patients between June 2006 and March 2020 were reviewed. Data were collected by using electronic medical record software. Survival rate were analyzed using the Kaplan–Meier method. The cutoff values of NLR in stage II to III CRC patients were defined by maximally selected log-rank statistics. Multivariable cox proportional-hazard models were performed to find risk factors associated with overall survival (OS) in stage II to III CRC patients underwent surgery. Among 1378 CRC patients enrolled, 910 patients underwent surgery. In entire surgical cohort, age, body mass index (BMI), CEA, carbohydrate antigen 19-9 (CA 19-9), lymphatic invasion, NLR, and albumin-to-globulin ratio (AGR) were found to be risk factors associated with OS (all P < .05). In stage II to III CRC patients underwent curative resection (n = 623), age, BMI, lymphatic invasion, AGR, and NLR were found to be risk factors associated with OS (all P < .05). In the multivariable analysis, CA 19-9 and lymphatic invasion were independent risk factors for OS in entire surgical cohort. In the multivariable analysis for the stage II to III CRC patients, age, BMI, lymphatic invasion and NLR (Hazard ratio = 2.41, 95% confidential interval [CI]: 1.04–5.595, P = .041) were independent risk factors for OS. NLR can be used as a clinically simple and useful parameter for predicting OS in stage II to III CRC patients undergoing curative resection, however, its optimal cutoff value should be further evaluated.
Impending central retinal vein occlusion and granulomatous uveitis in a patient with Satoyoshi syndrome
Authors: Saima Yoshinari , Tanaka Yoshiaki , Kakehashi Akihiro , Kaburaki Toshikatsu
Published: March 2023

Rationale:

Satoyoshi syndrome is a rare systemic autoimmune disease that presents with painful muscle spasms. We report a case of impending central retinal vein occlusion (CRVO) secondary to granulomatous pan-uveitis in a 32-year-old woman with Satoyoshi syndrome.

Patient concerns:

At the age of 7 years, she developed generalized hair loss and painful spasms and was diagnosed with Satoyoshi syndrome. Her current symptoms included sudden metamorphopsia and decreased visual acuity in the left eye. She visited our hospital with extensive intraretinal hemorrhage (including the macula), meandering of the retinal veins, and swelling of the optic disc. Fluorescence fundus angiography demonstrated hyper fluorescence of the optic disc and leakage from the retinal veins, suggesting CRVO associated with optic papillitis and segmental periphlebitis.

Diagnoses:

In the left eye, there were 2 + cells in the anterior chamber and 1 + in the anterior vitreous.

Interventions:

We increased the existing dose of prednisolone for the treatment of uveitis and started her on oral aspirin and kallidinogenase for CRVO.

Outcomes:

The impending CRVO gradually subsided, and her visual acuity improved. However, during the subsequent treatment course, angle nodules were observed in the left eye, and the intraocular pressure (IOP) gradually increased. Although the angled nodules disappeared with topical corticosteroid treatment, the IOP did not reduce and became uncontrolled. Therefore, we performed trabeculotomy first, followed by trabeculectomy, after which the IOP decreased to approximately 10 mm Hg.

Lessons:

Unilateral granulomatous pan-uveitis and impending CRVO were observed in this patient. Several cases of Satoyoshi syndrome complicated by various autoimmune or immunological disorders have been reported. However, to the best of our knowledge, no reports of Satoyoshi syndrome presenting with uveitis or CRVO have been published. Physicians should consider uveitis as a complication of Satoyoshi syndrome.
The specific phagocytosis regulators could predict recurrence and therapeutic effect in thyroid cancer: A study based on bioinformatics analysis
Authors: Hou Changran , Wu Mengmeng , Zhang Haojie , Yang Zhenlin
Published: March 2023

Background:

Thyroid cancer (TC) is one of the growing cancers and is prone to recurrence. Meanwhile, in immunotherapy, antibody-dependent cellular phagocytosis (ADCP) phagocytosis related regulators (PRs) play an important role. This study aims to investigate the prognostic value of specific PRs in TC.

Methods:

The purpose of this study was to identify specific PRs in TC patients by retrieving RNA-seq and Clustered Regularly Interspaced Short Palindromic Repeats-cas9 data and an algorithm based on LASSO was used to construct the PRs-signature. Subsequently, prognosis value of PRs-signature for recurrence-free survival (RFS) was explored through various statistical analysis, including Cox regression analysis, Kaplan–Meier analysis, and receiver operating characteristic curve. Additionally, an analysis of immune cell content by risk group was conducted using CIBERSORT, single sample gene set enrichment analysis and MCP-counter algorithms, with a particular focus on the correlation between macrophages and specific PRs.

Results:

We identified 36 specific PRs, and a PRs-signature was constructed using 5-prognostic PRs (CAPN6, MUC21, PRDM1, SEL1L3, and CPQ). Receiver operating characteristic analysis showed that predictive power of PRs-signature was decent, and the PRs risk score as an independent prognostic factor was found to be correlated with RFS showed by multivariate cox regression analysis. Meanwhile, a lower RFS was observed in the high-risk group than in the low-risk group. The results of the 3 algorithms suggested that our PRs-signature may have certain significance for macrophage content and ADCP. Interestingly, the low-risk group had higher levels of mRNA expression than the high-risk group at PDCD1, CTLA4, and pro-inflammatory factors from macrophage.

Conclusion:

For the purpose of prognostic management, this study developed a prediction model. And the cross-talk between certain PRs and TC patients was revealed in this study. Besides, the PRs-signature can predict the immunotherapy response, macrophage content, and ADCP status. TC patients will benefit from these developments by gaining insight into novel therapeutic strategies.
The association between C509T, T869C, G915C gene polymorphisms of transforming growth factor-β1 and systemic lupus erythematosus risk: A meta-analysis
Authors: Chen Ning , Dai Yijun , He Juanjuan , Zhou Meng , Sun Hong , Lin Ling , Gao Fei , Lin He , Yan Qing
Published: March 2023

Background:

The relationship between transforming growth factor-β1 (TGF- β1) gene polymorphisms and systemic lupus erythematosus (SLE) has been reported in many studies, but there were still controversies with regard to their conclusions.

Methods:

Relevant documents were retrieved from 5 electronic databases such as PubMed, Embase, Cochrane Library, Wanfang, and China national knowledge infrastructure. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to assess the relationship between TGF-β1 genetic variation and SLE.

Results:

The present meta-analysis included 12 case-control studies with 1308 SLE patients and 1714 healthy controls. The results of the combined analyses showed that TGF-β1 C509T polymorphism showed no association with SLE risk (TC vs CC: OR = 1.16, 95% CI = 0.91–1.48, P
Heterogeneity (P
H) = 0.579; TT vs CC: OR = 1.15, 95% CI = 0.63–2.09, P
H = 0.003; T vs C: OR = 1.08, 95% CI = 0.8–1.45, P
H = 0.003; TC/TT vs CC: OR = 1.17, 95% CI = 0.93–1.46, P
H = 0.133; and TT vs TC/CC: OR = 1.06, 95% CI = 0.64–1.76, P
H = 0.004). TGF-β1 G915C and T869C polymorphisms were not linked with SLE risk. Moreover, subgroup analysis stratified by ethnicity and Hardy–Weinberg equilibrium revealed no significant correlation of TGF-β1 T869C, C509T, G915C polymorphisms with SLE risk.

Conclusion:

TGF-β1 T869C, C509T, G915C polymorphisms might not be associated with the development of SLE.
Can combined use of tumor markers in pancreatic cancer be a solution to short- and long-term consequences?: A retrospective study
Authors: Esen Ebru , Aslan Mehmet , Morkavuk Sevket Baris , Azili Cem , Ersoz Siyar , Bahcecioglu Ibrahim Burak , Unal Ali Ekrem
Published: March 2023

As in other types of cancer, tumor markers are used in pancreatic ductal adenocarcinoma (PDAC) for disease follow-up, especially after surgery. There has been shown to be a significant correlation between the tumor marker levels and poor prognosis in locally or systemic advanced stage PDAC patients. However, there is no significant correlation between prognosis and marker levels in patients with early stage PDAC patients. This study aimed to examine the effect of the carbohydrate antigen 19-9 (Ca19-9)/carcinoembryogenic antigen (CEA) ratio in ductal adenocarcinoma of the pancreatic head on disease prognosis and mean survival. This retrospective study was conducted with 129 pancreatic head adenocarcinoma patients who were treated with whipple procedure at the Ankara University Surgical Oncology Clinic between 2010 and 2020. All patients’ demographics, stage of the disease, CEA, CA 19-9 levels, and CEA/Ca 19-9 ratio were enrolled and compared statistically. A new cutoff value was calculated for the Ca19-9/CEA ratio. A Ca19-9/CEA ratio >29.77 showed 69.9% sensitivity and 70.9% specificity for the probability of the T3 and T4 stages. The cutoff value for the Ca19-9/CEA ratio was 27.18. This cutoff value had a sensitivity of 79.4% and a specificity of 80.3% for lymph node metastasis. Patients with a Ca19-9/CEA ratio below the cutoff value of 28.475 had a mean survival of 93.161 months and those with a value higher than the cutoff value had a mean survival of 28.541 months (P < .001). A simple combination of tumor markers was determined to have higher accuracy rates in predicting tumor prognosis and in determining mean survival, which are particularly needed in early stage cancers.
Fatty Acid Percentage Distribution in Complex Lipids of Breast Milk From Mothers on a Low Docosahexaenoic Acid Diet
Authors: González Horacio F. , Malpeli Agustina , Fasano Victoria , Pescio Lucila G. , Sterin-Speziale Norma B. , Visentin Silvana
Published: March 2023

The aim of this study was to assess the fatty acid (FA) percentage distribution in complex lipids of breast milk from mothers on a low docosahexaenoic acid (DHA) diet. We performed a descriptive, cross-sectional study of milk samples (n = 14) collected 90 days after delivery and analyzed them using gas chromatography, thin-layer chromatography, and the Fiske-Subbarow method. Complex lipid distribution was 40.70 ± 5.11% sphingomyelin (SM), 26.03 ± 5.98% phosphatidylethanolamine (PE), 21.12 ± 2.32% phosphatidylcholine, 7.94 ± 1.96% phosphatidylserine, and 4.22 ± 1.25% phosphatidylinositol. Median DHA and arachidonic acid values were 0.13% (0.12; 0.18) and 0.42% (0.33; 0.53), respectively. Mean FA percentage in SM and PE was as follows: palmitic acid, 34.45 ± 1.94% and 5.38 ± 0.94%; oleic acid, 16.50 ± 4.07% and 9.43 ± 4.05%; linoleic acid, 5.91 ± 4.69% and 9.05 ± 4.5%. DHA was not detectable in SM, but it was found in PE (55.33 ± 14.46). In conclusion, breast milk of mothers on a low DHA diet contained 55% DHA in PE, but no DHA in SM.
Epigenetic Regulation of Inflammatory Mechanisms and a Psychological Symptom Cluster in Patients Receiving Chemotherapy
Authors: Harris Carolyn S. , Miaskowski Christine A. , Conley Yvette P. , Hammer Marilyn J. , Dunn Laura B. , Dhruva Anand A. , Levine Jon D. , Olshen Adam B. , Kober Kord M.
Published: March 2023

Background

A psychological symptom cluster is the most common cluster identified in oncology patients. While inflammatory mechanisms are hypothesized to underlie this cluster, epigenetic contributions are unknown.

Objectives

This study’s purpose was to evaluate associations between the occurrence of a psychological symptom cluster and levels of DNA methylation for inflammatory genes in a heterogeneous sample of patients with cancer receiving chemotherapy.

Methods

Prior to their second or third cycle of chemotherapy, 1,071 patients reported the occurrence of 38 symptoms using the Memorial Symptom Assessment Scale. A psychological cluster was identified using exploratory factor analysis. Differential methylation analyses were performed in two independent samples using Illumina Infinium 450 K and EPIC microarrays. Expression-associated CpG (eCpG) loci in the promoter region of 114 inflammatory genes on the 450 K and 112 genes on the EPIC microarray were evaluated for associations with the psychological cluster. Robust Rank Aggregation was used to identify differentially methylated genes across both samples. Significance was assessed using a false discovery rate of .05 under the Benjamini-Hochberg procedure.

Results

Cluster of differentiation 40 (CD40) was differentially methylated across both samples. All six promoter eCpGs for CD40 that were identified across both samples were hypomethylated in the psychological cluster group.

Conclusions

This study is the first to suggest associations between a psychological symptom cluster and differential DNA methylation of a gene involved in tissue inflammation and cell-mediated immunity. Our findings suggest that increased CD40 expression through hypomethylation of promoter eCpG loci is involved in the occurrence of a psychological symptom cluster in patients receiving chemotherapy. These findings suggest a direction for mechanistic studies.
Self-Management and Glycemic Targets in Adult Haitian Immigrants With Type 2 Diabetes: Research Protocol
Authors: Magny-Normilus Cherlie , Whittemore Robin , Nunez-Smith Marcella , Lee Christopher S. , Schnipper Jeffrey L. , Wexler Deborah J. , Sanders Julie A. , Grey Margaret
Published: March 2023

Background

Type 2 diabetes (T2D) is a chronic condition affecting more than 34.2 million United States adults, and people of African descent have a disproportionate burden. Haitian immigrants’ unique cultural and biologic factors put them at elevated risk for T2D-related complications. Despite prior research highlighting the success of multimethod approaches to T2D self-management behaviors on glycemic targets, a dearth of studies have used these methods to improve diabetes self-management in this marginalized population.

Objectives

This paper describes a repeated measures design protocol of a going study about self-management behaviors among adult Haitian immigrants with T2D and characterizing their barriers to T2D-self-management.

Methods

We will enroll 100 Haitian immigrants aged 18–64 who have lived with T2D for ≥1 year. Using multiple recruitment methods and Research Electronic Data Capture, subjective and objective data on T2D self-management practices, glucose variability via continuous glucose monitor, and a comprehensive view of physical activity via actigraphy are collected.

Results

Data analysis will follow a two-part approach mirroring the two primary study objectives.

Discussion

Findings from the study will guide the development and testing of a culturally tailored diabetes self-management education program that will contribute essential information about best practices for this population and break barriers that may impede research on unique individuals and subsequent effective self-management.
The effect of antioxidants on increased oocyte competence in IVM: a review
Authors: Solati Arezoo , Taghvimi Sina , Jamali Zeinab , Vahedi Farzaneh , Moazamfard Mostafa , Bahmyari Sedigheh , Movahedpour Ahmad , Ghasemi Hassan
Published: March 2023

In vitro maturation (IVM) is considered a potential assisted reproductive technology that is a safer and simpler alternative to conventional in vitro fertilization. It is primarily used in patients with impaired oocyte maturation and for the treatment of infertile women who are at risk of fertility loss. In addition, IVM is currently used mainly in polycystic ovarian syndrome patients with a high ovarian response and is still considered an experimental option in fertility preservation. Producing highly competent oocytes during IVM is considered a key step in the success of in vitro production (IVP) of embryos. Some factors, such as culture medium conditions and other supplements, have a significant impact on oocyte IVM performance. One of the known disruptors of oocyte developmental competence in IVP is oxidative stress (OS), which is caused by an imbalance between the production and neutralization of reactive oxygen species (ROS). In vitro conditions induce supraphysiological ROS levels due to exposure to an oxidative environment and the isolation of the oocyte from the follicle protective antioxidant milieu. Given the importance of OS in oocyte competence, the establishment of standardized antioxidant IVM systems is critical for improving the overall success of IVP. This review focuses on the main antioxidants tested to protect oocytes against OS in IVM.
The Paediatric Vault Score (PVS)—A Novel Scoring Tool for Prioritisation of Surgical Management of Craniosynostosis Patients
Authors: Shathur Adam , Adeline Hennedige Anusha , Burnside Girvan , Sinha Ajay , Ellenbogen Jonathan , Dawes William , Richardson David , Duncan Christian , Parks Christopher
Published: March 2023

Craniosynostosis is the premature fusion of the skull sutures, resulting in abnormal skull shape and volume. Timely management is a priority in avoiding raised intracranial pressure which can result in blindness and neurodevelopmental delay. Due to the COVID-19 pandemic, theater access was reduced. A risk stratification scoring system was thus devised to score patients attending surgery and aid in prioritization according to surgical need. The authors present the Paediatric Vault Score (PVS), which can also be customized to each unit’s individual protocols. Ten patients on the waiting list were randomly selected and their clinical information was summarized in uniform anonymized reports. Six craniofacial consultants were selected as assessors and given 1 week to independently rank the patients from 1 to 10. Each scorer’s ranking was verified against the PVS template and concordance was analyzed using the Kendall tau correlation coefficient (KT). Three cycles of the scoring process were carried out. Improvements were made to the scoring tool following cycle 1. Cycle 1 revealed 2 clinicians to be concordant with the PVS system and 4 to be discordant. Cycle 2 revealed all 6 clinicians to be concordant, with a mean KT score of 0.61. The final cycle revealed all 6 clinicians to be concordant, with a mean KT score of 0.70. Four scorers increased their concordance once the scoring sheet was introduced. Kendall’s correlation of concordance calculated the interrater reliability to be 0.81. The PVS is the first known vault scoring system to aid in risk stratification and waiting list prioritization.
A Nationwide Analysis of Gunshot Wounds of the Head and Neck: Morbidity, Mortality, and Cost
Authors: Menezes John M. , Batra Kavita , Zhitny Vladislav Pavlovich
Published: March 2023

Background:

Gun violence in the United States rose continuously from 2010 to 2022, spiking during the pandemic, and peaking in 2021 at 48,830 deaths (14.8 per 100,000). Previous reports investigated health and financial burden associated with gunshot wounds (GSWs) during 2004 to 2013; however estimates related specifically to head and neck (H&N) injuries have been lacking. This population-based study aims to examine incidence, morbidity, mortality, and health resource utilization of H&N injuries utilizing the Nationwide Inpatient Sample database.

Methods:

A population-based study was undertaken using the National (Nationwide) Inpatient Sample (NIS) database (2015Q4–2017Q4). The International Classification of Diseases, Tenth Revision (ICD-10) codes were used to create a composite variable (inclusive of brain, eye, facial nerve, and facial fractures) resulting from GSW to the H&N. Incidence per 100,000 hospitalizations and case fatality rates were calculated to determine the health burden of H&N injuries. Length of hospital stay, and inflation- adjusted hospital charges were compared among H&N and non-H&N injuries. Χ2 (classical and bootstrapped) and Mann-Whitney tests were used to compare groups.

Results:

Of 101,300 injuries caused by firearms, 16,140 injuries (15.9%) involved H&N region. The average incidence of H&N injuries was 20.1 cases per 100,000 hospitalizations, with intentional injuries having the highest case fatality rates of 32.4%. Patients with H&N injuries had extreme loss of function (33.4% versus 18.3%, P<0.001) and extreme likelihood of mortality (27.0% versus 11.3%, P<0.001) than non-H&N injuries. Statistically significant differences in the median length of stay (4.8 d versus 3.7 d; P<0.001) and median inflation-adjusted hospital charges ($80,743 versus $58,946, P<0.001) were found among H&N and non-H&N injuries.

Conclusions:

Injuries due to GSW remain an inordinate health care and financial burden, with trauma to the H&N carrying an especially high cost in dollars, morbidity, and mortality.
A PILOT STUDY OF ANGIOTENSIN II AS PRIMARY VASOPRESSOR IN CRITICALLY ILL ADULTS WITH VASODILATORY HYPOTENSION: THE ARAMIS STUDY
Authors: See Emily J. , Clapham Caroline , Liu Jasmine , Khasin Monique , Liskaser Grace , Chan Jian Wen , Serpa Neto Ary , Costa Pinto Rahul , Bellomo Rinaldo
Published: March 2023

Objective: The aim of the study is to evaluate the efficacy and safety of using angiotensin II (Ang2) as primary vasopressor for vasodilatory hypotension. Methods: This was a prospective observational study of critically ill adults admitted to an academic intensive care unit (ICU) with vasodilatory hypotension. We treated 40 patients with Ang2 as primary vasopressor and compared them with 80 matched controls who received conventional vasopressors (norepinephrine, vasopressin, metaraminol, epinephrine, or combinations). Results: Mean age was 63 years and median Acute Physiology and Chronic Health Evaluation III score was 65. Ang2 patients had lower ICU mortality (10% vs 26%, P = 0.04); however, their 28- and 90-day mortality was not significantly different (18% vs 29%, P = 0.18; 22% vs 30%, P = 0.39). Peak serum creatinine levels were similar (128 vs 126 μmol/L, P = 0.81), as was the incidence and stage of acute kidney injury (70% vs 74%, P = 0.66), requirement for continuous renal replacement therapy (14% vs 13%, P = 0.84), and risk of major adverse kidney events at 7 days (20% vs 29%, P = 0.30). However, Ang2 patients with prior exposure to renin angiotensin aldosterone system inhibitors had a lower peak serum creatinine (P = 0.03 for interaction) than conventional vasopressors patients, and serum troponin elevations were less common with Ang2 (8% vs 22%, P = 0.04). The incidence of thromboembolic complications was similar. Conclusions: Primary Ang2 administration in vasodilatory hypotension did not seem harmful compared with conventional vasopressors. Although Ang2 did not decrease peak serum creatinine levels or major adverse kidney events, its effects on intensive care unit survival, serum troponin, and renal function in patients on renin angiotensin aldosterone system inhibitors warrant further exploration in randomized trials (ACTRN12621000281897).
THE PROTECTIVE EFFECT OF C23 IN A RAT MODEL OF CARDIAC ARREST AND RESUSCITATION
Authors: Gao Yu , Liu Haoxin , Zhou Jiejie , Guo Min , Sun Jie , Duan Manlin
Published: March 2023

Background: Systemic inflammation acts as a contributor to neurologic deficits after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Extracellular cold-inducible RNA-binding, protein (CIRP) has been demonstrated to be responsible in part for the inflammation through binding to toll-like receptor 4 (TLR4) after cerebral ischemia. The short peptide C23 derived from CIRP has a high affinity for TLR4, we hypothesize that C23 reduces systemic inflammation after CA/CPR by blocking the binding of CIRP to TLR4. Methods: Adult male SD rats in experimental groups were subjected to 5 min of CA followed by resuscitation. C23 peptide (8 mg/kg) or normal saline was injected intraperitoneally at the beginning of the return of spontaneous circulation (ROSC). Results: The expressions of CIRP, TNF-α, IL-6, and IL-1β in serum and brain tissues were significantly increased at 24 h after ROSC (P < 0.05). C23 treatment could markedly decrease the expressions of TNF-α, IL-6, and IL-1β in serum (P < 0.05). Besides, it can decrease the expressions of TLR4, TNF-α, IL-6, and IL-1β in the cortex and hippocampus and inhibit the colocalization of CIRP and TLR4 (P < 0.05). In addition, C23 treatment can reduce the apoptosis of hippocampus neurons (P < 0.05). Finally, the rats in the C23 group have improved survival rate and neurological prognosis (P < 0.05). Conclusions: These findings suggest that C23 can reduce systemic inflammation and it has the potential to be developed into a possible therapy for post-CA syndrome.
Racial and Ethnic Disparities in Operative Experience Among General Surgery Residents
Authors: Eruchalu Chukwuma N. , Etheridge James C. , Hammaker Austin C. , Kader Sarah , Abelson Jonathan S. , Harvey Jalen , Farr Deborah , Stopenski Stephen J. , Nahmias Jeffry T. , Elsaadi Ali , Campbell Samuel J. , Foote Darci C. , Ivascu Felicia A. , Montgomery Kelsey B. , Zmijewski Polina , Byrd Samuel E. , Kimbrough Mary K. , Smith Savannah , Postlewait Lauren M. , Dodwad Shah-Jahan M. , Adams Sasha D. , Markesbery Katherine C. , Meister Katherine M. , Woeste Matthew R. , Martin Robert C.G. , Callahan Zachary M. , Marks Joshua A. , Patel Purvi , Anstadt Michael J. , Nasim Bilal Waqar , Willis Ross E. , Patel Jitesh A. , Newcomb Melissa R. , Stahl Christopher C. , Yafi Motaz Al , Sutton Jeffrey M. , George Brian C. , Quillin Ralph C. , Cho Nancy L. , Cortez Alexander R.
Published: March 2023

Objective:

To determine the relationship between race/ethnicity and case volume among graduating surgical residents.

Background:

Racial/ethnic minority individuals face barriers to entry and advancement in surgery; however, no large-scale investigations of the operative experience of racial/ethnic minority residents have been performed.

Methods:

A multi-institutional retrospective analysis of the Accreditation Council for Graduate Medical Education case logs of categorical general surgery residents at 20 programs in the US Resident OPerative Experience Consortium database was performed. All residents graduating between 2010 and 2020 were included. The total, surgeon chief, surgeon junior, and teaching assistant case volumes were compared between racial/ethnic groups.

Results:

The cohort included 1343 residents. There were 211 (15.7%) Asian, 65 (4.8%) Black, 73 (5.4%) Hispanic, 71 (5.3%) “Other” (Native American or Multiple Race), and 923 (68.7%) White residents. On adjusted analysis, Black residents performed 76 fewer total cases (95% CI, −109 to −43, P<0.001) and 69 fewer surgeon junior cases (−98 to −40, P<0.001) than White residents. Comparing adjusted total case volume by graduation year, both Black residents and White residents performed more cases over time; however, there was no difference in the rates of annual increase (10 versus 12 cases per year increase, respectively, P=0.769). Thus, differences in total case volume persisted over the study period.

Conclusions:

In this multi-institutional study, Black residents graduated with lower case volume than non-minority residents throughout the previous decade. Reduced operative learning opportunities may negatively impact professional advancement. Systemic interventions are needed to promote equitable operative experience and positive culture change.
Sleep and Sport Performance
Authors: Fullagar Hugh H. K. , Vincent Grace E. , McCullough Michael , Halson Shona , Fowler Peter
Published: March 2023

Elite athletes and coaches believe sleep is the most important recovery strategy and widely consider it critical to optimal performance. Despite this perceived importance, there are numerous circumstances that can reduce sleep quantity and quality in athletic populations. Because of the effects of sleep loss on various physical, neurophysiological, and cognitive parameters, such perturbations can have consequences for performance and recovery outcomes. Although peer-reviewed literature examining the interaction between sleep, performance, and recovery in athletes is increasing, understanding of these issues remains equivocal. Perhaps most pertinently, the effect of sleep on sport performance does not align with a one-size-fits-all approach and rather depends on numerous factors such as type of sport, scheduling, time of the season, and the intraindividual requirements for sleep. The relationship between brain plasticity and memory, which in turn can influence learning processes and long-term memory consolidation, suggests that sleep may play an important role in learning new skills and tactics for both elite and developing athletes. The aim of this special issue review was to analyze the evidence of sleep loss on sport performance and recovery, with a specific focus on elite athletes. An assessment of these sleep-compromising situations that elite athletes may face during a typical season and practical considerations for alleviating these issues is also provided to further the understanding for medical professionals, scientists, and applied sporting practitioners alike.
Current and Emerging Techniques in Neuroimaging of Sport-Related Concussion
Authors: Esopenko Carrie , Sollmann Nico , Bonke Elena M. , Wiegand Tim L. T. , Heinen Felicitas , de Souza Nicola L. , Breedlove Katherine M. , Shenton Martha E. , Lin Alexander P. , Koerte Inga K.
Published: March 2023

Sport-related concussion (SRC) affects an estimated 1.6 to 3.8 million Americans each year. Sport-related concussion results from biomechanical forces to the head or neck that lead to a broad range of neurologic symptoms and impaired cognitive function. Although most individuals recover within weeks, some develop chronic symptoms. The heterogeneity of both the clinical presentation and the underlying brain injury profile make SRC a challenging condition. Adding to this challenge, there is also a lack of objective and reliable biomarkers to support diagnosis, to inform clinical decision making, and to monitor recovery after SRC. In this review, the authors provide an overview of advanced neuroimaging techniques that provide the sensitivity needed to capture subtle changes in brain structure, metabolism, function, and perfusion after SRC. This is followed by a discussion of emerging neuroimaging techniques, as well as current efforts of international research consortia committed to the study of SRC. Finally, the authors emphasize the need for advanced multimodal neuroimaging to develop objective biomarkers that will inform targeted treatment strategies after SRC.
Cingulate Cortex: Anatomy, Structural and Functional Connectivity
Authors: Oane Irina , Barborica Andrei , Mindruta Ioana R.
Published: March 2023

The cingulate cortex is a paired brain region located on the medial wall of each hemisphere. This review explores the anatomy as well as the structural and functional connectivity of the cingulate cortex underlying essential roles this region plays in emotion, autonomic, cognitive, motor control, visual–spatial processing, and memory.
Neurophysiological Markers to Guide Return to Sport After Sport-Related Concussion
Authors: Coenen Jessica , Reinsberger Claus
Published: March 2023

Sport-related concussion (SRC) has been defined as a subset of mild traumatic brain injury (mTBI), without structural abnormalities, reflecting a functional disturbance. Over the past decade, SRC has gained increasing awareness and attention, which coincides with an increase in incidence rates. Because this injury has been considered one of the most challenging encounters for clinicians, there is a need for objective biomarkers to aid in diagnosis (i.e., presence/severity) and management (i.e., return to sport) of SRC/mTBI.

The primary aim of this article was to present state-of-the-art neurophysiologic methods (e.g., electroencephalography, magnetoencephalography, transcranial magnetic stimulation, and autonomic nervous system) that are appropriate to investigate the complex pathophysiological process of a concussion. A secondary aim was to explore the potential for evidence-based markers to be used in clinical practice for SRC management. The article concludes with a discussion of future directions for SRC research with specific focus on clinical neurophysiology.
Stereo-electroencephalography (SEEG)-Guided Surgery in Epilepsy With Cingulate Gyrus Involvement: Electrode Implantation Strategies and Postoperative Seizure Outcome
Authors: d'Orio Piergiorgio , Revay Martina , Bevacqua Giuseppina , Battista Francesca , Castana Laura , Squarza Silvia , Chiarello Daniela , Lo Russo Giorgio , Sartori Ivana , Cardinale Francesco
Published: March 2023

Surgical treatment of cingulate gyrus epilepsy is associated with good results on seizures despite its rarity and challenging aspects. Invasive EEG monitoring is often mandatory to assess the epileptogenic zone in these patients. To date, only small surgical series have been published, and a consensus about management of these complex cases did not emerge. The authors retrospectively analyzed a large surgical series of patients in whom at least part of the cingulate gyrus was confirmed as included in the epileptogenic zone by means of stereo-electroencephalography and was thus resected. One hundred twenty-seven patients were selected. Stereo-electroencephalography-guided implantation of intracerebral electrodes was performed in the right hemisphere in 62 patients (48.8%) and in the left hemisphere in 44 patients (34.7%), whereas 21 patients (16.5%) underwent bilateral implantations. The median number of implanted electrodes per patient was 13 (interquartile range 12–15). The median number of electrodes targeting the cingulate gyrus was 4 (interquartile range 3–5). The cingulate gyrus was explored bilaterally in 19 patients (15%). Complication rate was 0.8%. A favorable outcome (Engel class I) was obtained in 54.3% of patients, with a median follow-up of 60 months. The chance to obtain seizure freedom increased in cases in whom histologic diagnosis was type-IIb focal cortical dysplasia or tumor (mostly ganglioglioma or dysembryoplastic neuroepithelial tumor) and with male gender. Higher seizure frequency predicted better outcome with a trend toward significance. Our findings suggest that stereo-electroencephalography is a safe and effective methodology in achieving seizure freedom in complex cases of epilepsy with cingulate gyrus involvement.
Delineation of two multi-invasion-induced rearrangement pathways that differently affect genome stability
Authors: Reitz Diedre , Djeghmoum Yasmina , Watson Ruth A. , Rajput Pallavi , Argueso Juan Lucas , Heyer Wolf-Dietrich , Piazza Aurèle
Published: March 2023

Punctuated bursts of structural genomic variations (SVs) have been described in various organisms, but their etiology remains incompletely understood. Homologous recombination (HR) is a template-guided mechanism of repair of DNA double-strand breaks and stalled or collapsed replication forks. We recently identified a DNA break amplification and genome rearrangement pathway originating from the endonucleolytic processing of a multi-invasion (MI) DNA joint molecule formed during HR. Genome-wide sequencing approaches confirmed that multi-invasion-induced rearrangement (MIR) frequently leads to several repeat-mediated SVs and aneuploidies. Using molecular and genetic analysis, and a novel, highly sensitive proximity ligation-based assay for chromosomal rearrangement quantification, we further delineate two MIR sub-pathways. MIR1 is a universal pathway occurring in any sequence context, which generates secondary breaks and frequently leads to additional SVs. MIR2 occurs only if recombining donors exhibit substantial homology, and results in sequence insertion without additional break or SV. The most detrimental MIR1 pathway occurs late on a subset of persisting DNA joint molecules in a PCNA/Polδ-independent manner, unlike recombinational DNA synthesis. This work provides a refined mechanistic understanding of these HR-based SV formation pathways and shows that complex repeat-mediated SVs can occur without displacement DNA synthesis. Sequence signatures for inferring MIR1 from long-read data are proposed.
HuR enhances SARS-CoV-2 non-structural protein translation through the genomic 5’-UTR, by promoting polypyrimidine tract-binding protein binding
Authors: Raheja Harsha , Sahu Risabh , Ghosh Trinath , Rani Priya , George Biju , Khatun Oyahida , Tripathi Shashank , Das Saumitra
Published: March 2023

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) viral RNA associates with different RNA-binding host proteins at each stage of its life cycle. We found sequence dependent binding of one such important protein, human antigen R (HuR) to SARS-CoV-2 5′UTR and studied its potential role in virus life cycle. The knockdown and knockout studies revealed importance of such binding in viral translation. We identified 5′-UTR mutations in SARS-CoV-2 variants of concern that altered the HuR-binding affinity. Interestingly, HuR enhanced non-structural protein translation through the genomic 5′-UTR, by promoting polypyrimidine tract-binding protein binding to the 5′-UTR. However, HuR suppressed the structural protein translation from sub genomic 5’UTR. HuR knockout increased the sensitivity to remdesivir treatment by decreasing its half-maximal inhibitory concentration. An antisense oligonucleotide (whose binding site overlapped the HuR-binding site) reduced viral RNA levels in wild-type cells but not HuR-knockout cells. Our results indicate that HuR regulates the balance between SARS-CoV-2 structural and non-structural proteins and guides the infection of viral variants, implying that HuR can potentially be targeted for therapeutic interventions.

Author Summary

Viruses interacts with various host proteins throughout their life cycle. One significant protein is HuR, an RNA-binding protein that regulates RNA stability and translation. HuR binds to viral RNAs at the 5’UTR or 3’UTR, impacting their translation and replication. We identified conserved HuR binding sites in the SARS-CoV-2 5’UTR across different beta coronaviruses. This binding enhanced the initiation of translation from the genomic 5’ UTR, increasing the production of non-structural proteins essential for viral replication. Additionally, we discovered that another host protein, PTB, promotes HuR binding to the viral 5’ UTR, facilitating its loading onto ribosomes. Conversely, HuR plays an antagonistic role concerning subgenomic RNAs (sgRNAs), which code for structural proteins, by regulating and limiting their levels. This dual regulation indicates that the virus exploits HuR for its benefit while the host employs it to control viral spread. Targeting HuR may help manipulate the SARS-CoV-2 life cycle. We found that HuR knockout increased sensitivity to the antiviral drug Remdesivir. Using an antisense oligonucleotide to block HuR binding effectively reduced viral RNA levels. Our findings highlight the critical role of HuR in regulating viral protein production and its potential as a therapeutic target.
A protein hydroxylase couples epithelial membrane biology to nucleolar ribosome biogenesis
Authors: Hendrix Eline , Andrijes Regina , Boora Uncaar , Kaur Arashpreet , Bundred James R , Officer-Jones Leah , Pennie Rachel , Powley Ian R , Zayer Adam , Heilig Raphael , Westrip Christian A E , Fletcher Sally C , Eaton Charlotte D , Kennedy Tristan J , Piasecka Sonia , Fischer Roman , Smerdon Stephen J , Le Quesne John , Coleman Mathew L
Published: March 2023

Jumonji-C (JmjC) ribosomal protein hydroxylases are an ancient class of oxygen- and Fe(II)-dependent oxygenases that spawned the wider JmjC family and Histone Lysine Demethylases (KDMs) in eukaryotes. Myc-induced Antigen (MINA) has been implicated in ribosome biogenesis and was assigned as a nucleolar-localized JmjC histidyl hydroxylase of the large ribosomal subunit protein RPL27A, consistent with reports that it supports cell growth and viability in a variety of tumor cell types. Reported roles in diverse aspects of disease biology may be consistent with additional MINA functions, although the molecular mechanisms involved remain unclear. Here, we describe an extra-nucleolar interaction of MINA with the Hinge domain of the membrane-associated guanylate kinase, MPP6. We show that MINA promotes the expression and membrane localization of MPP6 and that the MINA-MPP6 pathway is required for epithelial tight junction integrity and barrier function. The function of MINA in this novel pathway is suppressed by ribosomal RNA transcription and the nucleolar MINA interactome. In this way, MINA couples epithelial membrane biology to nucleolar ribosome biogenesis. Our work sheds light on how quiescent cells lose adhesion as they switch to proliferative states associated with increased ribosome biogenesis.
An alphacoronavirus polymerase structure reveals conserved co-factor functions
Authors: Anderson Thomas K. , Hoferle Peter J. , Lee Kenneth W. , Coon Joshua J. , Kirchdoerfer Robert N.
Published: March 2023

Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from the betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryoelectron microscopy to determine the structure of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. Our structure shows an unexpected nsp8 stoichiometry in comparison to other published coronavirus polymerase structures. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required forin vitroRNA synthesis for alpha and betacoronaviruses as previously hypothesized. Our work shows the importance of studying diverse coronaviruses to reveal aspects of coronavirus replication while also identifying areas of conservation to be targeted by antiviral drugs.

Significance Statement

Coronaviruses are important human and animal pathogens with a history of crossing over from animal reservoirs into humans leading to epidemics or pandemics. Betacoronaviruses, such as SARS-CoV and SARS-CoV-2, have been the focus of research efforts in the field of coronaviruses, leaving other genera (alpha, gamma, and delta) understudied. To broaden our understanding, we studied an alphacoronavirus polymerase complex. We solved the first structure of a non-betacoronavirus replication complex, and in doing so identified previously unknown, and conserved, aspects of polymerase cofactor interactions. Our work displays the importance of studying coronaviruses from all genera and provides important insight into coronavirus replication that can be used for antiviral drug development.