bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical validation of an innovative dried whole-blood spot method to quantify simultaneously vancomycin and creatinine in adult patients
Authors: Hassanzai M , Bahmany S , van Onzenoort H A W , van Oldenrijk J , Koch B C P , de Winter B C M
Published: January 2025

Background

A drawback of vancomycin use is the need for therapeutic drug monitoring and renal function monitoring. Traditional blood sampling involves drawing blood through a venepuncture. An alternative method, dried blood spot (DBS) sampling allows for self-sampling at home.

Objectives

To clinically validate a DBS method for simultaneous monitoring of vancomycin and creatinine.

Methods

Hospitalized adults treated with intravenous vancomycin were included (trial registration NCT05257070). Blood sampling consisted of one venepuncture and one finger prick. Whole-blood DBS samples from patients were obtained by applying one drop of whole blood onto Whatman 903 filtrate paper. Bland–Altman analyses were used to assess the agreement and bias between the two measurements. Patients were asked to state their preferences for one of the two sampling methods.

Results

The study involved a final analysis of 39 patient samples for the clinical validation of vancomycin and 46 patient samples for the clinical validation of creatinine. The difference between plasma and DBS concentrations was ≤20% for 77% of the vancomycin samples, the mean bias was −0.1379% (95% limit of agreement −5.899–5.623). The difference between plasma and DBS concentrations was ≤20% for 89% of the creatinine samples, the mean bias was 2.656% (95% limit of agreement −26.16–31.47). Most patients (18 out of 31) preferred a finger prick over a venepuncture and 12 patients indicated no preference.

Conclusions

This is the first study that successfully clinically validated a DBS sampling method for simultaneous measurement of vancomycin and creatinine, allowing for direct use in (outpatient) practice.
“Svá daufr orðinn, at hann mátti eigi heyra”: a critical exploration of depictions of deaf and non-speaking characters in medieval Icelandic literature
Authors: Hardonk Stefan C , Tirosh Yoav
Published: January 2025

This article revisits the polarities of oralist and cultural-linguistic approaches to deaf identities through the perspective of the medieval Icelandic sagas, a product of mainly the thirteenth to fifteenth centuries. Through a historically informed close reading of the Sagas of Early Icelanders corpus, 5 saga episodes were selected for further analysis with regard to the meaning of being deaf and/or non-speaking and intersections with other social categories like gender and class. This study suggests diverse ways in which being deaf and/or non-speaking was given meaning before the advent of oralism and the establishment of Deaf communities in Iceland, that is, as traits that lead to social exclusion as well as a part of the identities of individuals with considerable social status. An intersectional perspective shows male deaf characters exerting control over their lives and yielding political power, while deaf and non-speaking women are more portrayed as disenfranchised, regardless of their social class.
The neurorepellent SLIT2 inhibits LPS-induced proinflammatory signaling in macrophages
Authors: Skrtic Marko , Yusuf Bushra , Patel Sajedabanu , Reddy Emily C , Ting Kenneth K Y , Cybulsky Myron I , Freeman Spencer A , Robinson Lisa A
Published: January 2025

Macrophages are important mediators of immune responses with critical roles in the recognition and clearance of pathogens, as well as in the resolution of inflammation and wound healing. The neuronal guidance cue SLIT2 has been widely studied for its effects on immune cell functions, most notably directional cell migration. Recently, SLIT2 has been shown to directly enhance bacterial killing by macrophages, but the effects of SLIT2 on inflammatory activation of macrophages are less known. Using RNA sequencing analysis, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, we determined that in murine bone marrow–derived macrophages challenged with the potent proinflammatory mediator lipopolysaccharide (LPS), exposure to the bioactive N-terminal fragment of SLIT2 (NSLIT2) suppressed production of proinflammatory cytokines interleukin (IL)-6 and IL-12 and concurrently increased the anti-inflammatory cytokine IL-10. We found that NSLIT2 inhibited LPS-induced MyD88- and TRIF-mediated signaling cascades and did not inhibit LPS-induced internalization of Toll-like receptor 4 (TLR4), but instead inhibited LPS-induced upregulation of macropinocytosis. Inhibition of macropinocytosis in macrophages attenuated LPS-induced production of proinflammatory IL-6 and IL-12 and concurrently enhanced anti-inflammatory IL-10. Taken together, our results indicate that SLIT2 can selectively modulate macrophage response to potent proinflammatory stimuli, such as LPS, by attenuating proinflammatory activation and simultaneously enhancing anti-inflammatory activity. Our results highlight the role of macropinocytosis in proinflammatory activation of macrophages exposed to LPS. Given that LPS-producing bacteria cause host illness through synergistic direct bacterial infection and excessive LPS-induced systemic inflammation, our work suggests a novel therapeutic role for SLIT2 in combatting the significant morbidity and mortality of patients with Gram-negative bacterial sepsis.
Novel technique for repair of symmastia using external negative pressure therapy for continuous pre-sternal compression
Authors: Lawrence Zachary , Stroman Joel C , Karu Heather
Published: January 2025

Symmastia, a term used to describe the medial intermammary confluence that may appear as a complication following breast augmentation or reconstruction, is a cosmetic issue breast surgeons occasionally encounter and must be prepared to correct. Over-dissection of medial structures, oversized implants, and forces applied to implants in the sub-pectoral space have all been proposed as potential causes of the development of symmastia. Numerous techniques to correct symmastia have been described in previous literature, including capsulorrhaphy, dermo-sternal adhesion, neo-pocket creation, and techniques based on muscle repair. However, these methods are susceptible to recurrence. In this case report series, we present three cases in which symmastia was successfully corrected following surgical repair with post-operative external negative pressure therapy over the intermammary sulcus.
Prohibiting commercial surrogacy in Ireland
Authors: Bracken Lydia
Published: January 2025

The Health (Assisted Human Reproduction) Act 2024 regulates surrogacy for the first time in Ireland. The Act is based on a model of altruistic surrogacy, which applies to both domestic and international arrangements undertaken by Irish intending parents. The definition and prohibition on ‘commercial’ surrogacy in the legislation are broad, covering virtually all payments connected with surrogacy. Certain exceptions to the prohibition on commercial surrogacy apply in respect of international surrogacy, but not domestic surrogacy. Most notably, intending parents are permitted to make payments to surrogacy intermediaries in international surrogacy, but no such payments can be made domestically. In fact, the prohibition on commercial surrogacy appears to prohibit all payments other than the payment of legal fees and the surrogate’s reasonable expenses in the domestic context. As a result, this article argues that the definition and prohibition on commercial surrogacy under the 2024 Act will stymie domestic surrogacy in practice and create a two-tier approach to the prohibition on commercial surrogacy. At the same time, notwithstanding the exceptions that apply in respect of payments in international surrogacy, it is suggested that the 2024 Act will also restrict attempts by Irish intending parents to engage in surrogacy outside of the State due to the unworkable nature of the relevant provisions.
Applied Anatomy of the Heart and Great Vessels
Authors: Murphy Joseph G.
Published: January 2025

This chapter summarizes cardiac anatomy and its important clinical functional significance.
Evidence-Based Medicine and Statistics in Cardiology
Authors: Rihal Charanjit S.
Published: January 2025

Evidence-based medicine is the conscientious and explicit use of the current best evidence from systematic research to guide medical decision making in the care of individual patients. Its practice takes into consideration 3 elements: clinical setting, scientific evidence, and physician-patient factors.
Transesophageal Echocardiography
Authors: Mahowald Madeline , Sinak Lawrence J. , Chandrasekaran Krishnaswamy
Published: January 2025

Multiplane transesophageal echocardiography provides excellent visualization of cardiac structures and the great vessels. The common clinical indications for transesophageal echocardiography are a need to visualize fine cardiac structures with higher spatial resolution than transthoracic echocardiography offers, evaluation of the posterior structures of the heart and vasculature, and real-time guidance during surgical and transcatheter procedures.
Cardiac Imaging: CT and MRI
Authors: Ryan Samantha M. , Bois John P. , Anavekar Nandan S.
Published: January 2025

Cardiac computed tomography and magnetic resonance imaging are rapidly evolving fields of cardiac imaging. These individual modalities will be reviewed in detail in this chapter. A summary of the strengths and weaknesses of cardiac computed tomography and magnetic resonance imaging compared to other cardiac imaging modalities such as transthoracic echocardiography, transesophageal echocardiography, and nuclear imaging are discussed.
Atlas of Congenital Heart Defects
Authors: Phillips Sabrina D.
Published: January 2025

Detailed descriptions of images of congenital heart defects are covered.
Antiarrhythmic Agents and Mechanistic  Effects,
Authors: DeSimone Christopher V. , Noseworthy Peter A.
Published: January 2025

Reentrant arrhythmias are sustained by a propagating wavefront that can excite a region of myocardial tissue. After the propagating wavefront has depolarized the myocardium, the tissue is refractory to further stimulation and requires time to recover before reexcitation from the encircling wavefront. The amount of tissue in the reentrant circuit that is repolarized at any given time (and is, thus, subsequently able to be depolarized) is known as the excitable gap. In broad mechanistic terms, antiarrhythmic drugs work by either 1) slowing conduction velocity or 2) increasing refractoriness. Through these 2 actions, these antiarrhythmic agents alter the myocardial-electrical substrate to change the reentrant circuits. However, in some circumstances, these drugs may exert a proarrhythmic effect. For instance, they may slow conduction such that they actually increase, rather than decrease, the stability of the reentrant circuit.
Prosthetic Heart Valves
Authors: Lane Colleen E , Grogan Martha A. , Miller Fletcher A.
Published: January 2025

Prosthetic valves approximate normal human valve hemodynamics, and carry the risk of unique complications, such as structural failure, thrombosis, hemolysis, and infections.
Atrial Disease and Stroke
Authors: Murphy Joseph G.
Published: January 2025

The source of stroke due to thromboembolism is frequently the left atrium, particularly the left atrial appendage and, less commonly, the right atrium as a result of paradoxical embolism in patients with an interatrial shunt.
Renal Artery Disease
Authors: Sabbah Michael , Mathew Verghese , Barsness Gregory W.
Published: January 2025

Obstructive disease of the renal arteries can be broadly categorized as resulting from either atherosclerosis or fibromuscular dysplasia and may lead to hypertension and/or ischemic nephropathy. Atherosclerotic renal artery stenosis affecting the proximal, juxta-aortic renal arterial segment is one of the most commonly identified causes of secondary hypertension in persons aged 65 years and older. The true prevalence of renal artery stenosis in the general population is unknown, although the prevalence in select patient populations with atherosclerosis in other vascular beds has been reported to be 10% to 30%, and conversely, obstructive renal artery stenosis is often accompanied by abnormalities in other vascular beds.
Coronary Artery Disease Epidemiology
Authors: Mankad Rekha , Allison Thomas G.
Published: January 2025

Coronary heart disease refers to the development of atherosclerosis within the coronary tree and may or may not be obstructive. Atherosclerosis is a progressive condition if risk factors are not modulated or controlled. Fatty streaks and some raised lesions have been identified in various autopsy studies of men as young as their late teens and early 20s and women in their late 20s and early 30s. The development of atherosclerosis appears to follow a complex pathway. Ischemic cardiomyopathy also can be a manifestation of coronary heart disease. Congestive heart failure is a frequent problem for patients with ischemic cardiomyopathy. Heart failure is essentially an end-stage process characterized by exercise intolerance; pulmonary or peripheral edema, or both; and a high mortality rate.
Chronic Stable Angina
Authors: Waterbury Thomas M. , Brozovich Frank V.
Published: January 2025

An estimated 20 million Americans over 20 years of age have coronary artery disease. The lifetime risk of coronary artery disease after the age of 40 years is 49% for men and 32% for women. Half of the patients with coronary artery disease present with chronic stable angina. William Heberden gave one of the earliest descriptions of angina pectoris: “They who are afflicted with it are seized while they are walking with a painful and most disagreeable sensation in the breast.”
Adjunctive Therapy in Acute Myocardial Infarction
Authors: Al-Hijji Mohammed A. , Anavekar Nandan S.
Published: January 2025

Adjunctive medical therapies for patients with acute myocardial infarction are essential for decreasing postinfarction complications, subsequent cardiovascular events, and death. Various therapies are used to stabilize plaque and electrical rhythm and to prevent further myocardial injury and remodeling. The primary therapies used are antiplatelet and anticoagulant agents; anti-ischemic and analgesic drugs; and heart failure treatment.
Hemodynamic Classification and Complications of Acute Myocardial Infarction
Authors: Prasad Megha , Anavekar Nandan S. , Murphy Joseph G.
Published: January 2025

Mechanical complications of acute myocardial infarction leading to cardiogenic shock are less common in the current era of aggressive coronary revascularization strategies than in earlier years, but they remain a leading cause of in-hospital morbidity and mortality in acute myocardial infarction. Cardiogenic shock and heart failure are the most common causes of death among patients hospitalized with acute myocardial infarction. Cardiogenic shock reflects the most severe hemodynamic compromise of several hemodynamic classifications of myocardial infarction. Hemodynamic classification of acute myocardial infarction is based on findings of cardiac examination, specifically Killip class, and invasive monitoring, specifically Forrester classification.
Pregnancy and the Heart
Authors: Connolly Heidi M.
Published: January 2025

Approximately 2% of pregnancies occur in women who have heart disease. Congenital heart disease is the predominant form of heart disease among pregnant women in developed countries. Heart disease does not preclude successful pregnancy, but it does increase the risk of complications for both mother and baby and therefore requires special management. This chapter discusses the normal hemodynamic changes that occur during pregnancy and the resultant effect on common cardiovascular diseases.
Infective Endocarditis
Authors: Saric Petar , Hubers Scott A. , DeSimone Daniel C. , Sohail M. Rizwan , Anavekar Nandan S.
Published: January 2025

Infective endocarditis is an infection on the endocardial surface of the heart, usually affecting the heart valves, a congenital heart shunt, or an intravascular device. Acute endocarditis has a fulminant course with high fever, systemic toxicity, and death within days to weeks if left untreated; subacute and chronic endocarditis have an indolent course with low-grade fever, night sweats, weight loss, embolic and immunologic phenomena, and death within weeks to months if left untreated. Acute endocarditis is caused by Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, or Neisseria gonorrhoeae, and the subacute and chronic forms are usually due to viridans streptococci.
Acute Brain Injury and the Heart
Authors: El Sabbagh Abdallah , Anavekar Nandan S. , Chandrasekaran Krishnaswamy
Published: January 2025

Cerebral perfusion is dependent on cardiac performance, and much of cardiac function is regulated by higher brain centers. Dysfunction in either organ system can precipitate dysfunction in the other.
Heart Failure With Preserved  Ejection Fraction
Authors: Borlaug Barry A. , Boilson Barry A.
Published: January 2025

Heart failure affects nearly 6 million Americans and represents the leading cause of hospitalization among patients aged 65 years and older. Of the total heart failure population, approximately 50% have heart failure with preserved ejection fraction. The prevalence of heart failure with preserved ejection fraction relative to heart failure with reduced ejection fraction, or “systolic” heart failure, is increasing at an alarming rate of 1% per year. With the population of developed countries aging overall, heart failure with preserved ejection fraction will become the most common form of heart failure in the next 2 decades. In contrast to heart failure with reduced ejection fraction, in which abundant trial evidence is available to guide diagnosis and treatment, evidence-based data to guide optimal management of heart failure with preserved ejection fraction are more limited.
Mechanical Ventricular Assist Devices,
Authors: Boilson Barry A.
Published: January 2025

Cardiogenic shock is defined as persistent hypotension; severely decreased cardiac index; and increased filling pressures. Cardiogenic shock is associated with an almost 50% mortality rate at 30 days. The standard treatment of cardiogenic shock is temporary mechanical support. The goal of temporary mechanical support is LV offloading, which decreases energy consumption. Inotropic support increases energy consumption, and although effective in the short term, with prolonged use it worsens outcomes.
Dilated Cardiomyopathy
Authors: Boilson Barry A. , Chen Horng H. , Dandamudi Sanjay
Published: January 2025

Dilated cardiomyopathy is a descriptive term for a myocardial disease phenotype characterized by dilatation and impaired contraction of one or both ventricles. Dilated cardiomyopathy is actually a collective term for many different disease processes that result in this phenotype. Dilated cardiomyopathy presents clinically with heart failure with reduced ejection fraction, although some asymptomatic patients may be diagnosed through screening and in some it may be detected incidentally. Dilated cardiomyopathy is an important topic to review for cardiovascular board examinations, and special attention should be paid to the general features, causes, and evaluation of this disease process.
The World Is Too Complex To Perceive Directly
Authors: Friedland Robert P.
Published: January 2025

Our world is too complex to perceive directly or completely. Perceptual capacities have evolved to enhance our survival, which means that our image of the world is not complete and not entirely reliable. Awareness of this situation is important in our understanding of patients and scientific problems. Similarly, our brain evolved the capacity for appreciation of stories because they are valuable for our survival. Therefore, the construction of stories enhances learning for all of us. Making stories out of our learning is a valuable method for enhancing the power of our memory. It is also critical to appreciate the importance of the unique story presented by every patient and every scientific problem. Being fierce in the pursuit of your education is necessary because it enhances the power of our memory of what happens to us. Doctors should also be fierce in the pursuit of their patient’s benefit and scientists must be fierce in the pursuit of the scientific questions they are addressing.
“Listen to Your Patient, He Is Telling You the Diagnosis”
Authors: Friedland Robert P.
Published: January 2025

It is necessary to listen to what the patient has to say both verbally and nonverbally
Consider the Patient’s Experience
Authors: Friedland Robert P.
Published: January 2025

Be aware of what the patient is experiencing.
A Mnemonic for Etiologies, VITAMINS ABCD
Authors: Friedland Robert P.
Published: January 2025

The VITAMINNS ABCD mnemonic is valuable to comprehensively evaluate possible etiologies.
Do Not Confuse Etiology with Pathophysiology
Authors: Friedland Robert P.
Published: January 2025

Etiology describes the origin of disease and pathophysiology describes its mechanisms—they must not be confused.
Much of What We Know Is Wrong (So Don’t Believe Everything You Read)
Authors: Friedland Robert P.
Published: January 2025

Many things that we know today will be discovered to be wrong in the future.
Smart People Make Mistakes
Authors: Friedland Robert P.
Published: January 2025

There are no humans that are incapable of error. There is no error which is so tragic and obvious that it will not occur.
Manifestations of Bias
Authors: Friedland Robert P.
Published: January 2025

Although it is not possible to be free of all forms of bias it is important to be aware of how bias may influence your actions.
Don’t Be Afraid of Your Imagination
Authors: Friedland Robert P.
Published: January 2025

Allow your imagination and your creativity to be active and respected.
Search for Your Passion and Follow It (Gnaw Your Own Bone)
Authors: Friedland Robert P.
Published: January 2025

Explore your sources of meaning and pursue them avidly.
Be Grateful
Authors: Friedland Robert P.
Published: January 2025

Gratitude is a key toward happiness.
Be Persistent and Tenacious
Authors: Friedland Robert P.
Published: January 2025

Persistent tenacious actions are the key to success in research.
Never Whisper in the Presence of Wrong
Authors: Friedland Robert P.
Published: January 2025

History shows us that we must be responsible for our own actions at all times. We cannot allow institutions or governments to take over our own accountability. We need to consider the consequences of our actions for society, as well as for our patients. These considerations include social factors, which are highly related to health outcomes. We must not allow our understanding of how patients contribute to their disease to lead to the conclusions that they are not deserving of compassionate care. Compassion is part of our fundamental nature and a key part of healthcare. Excessive stress in providing care can lead to empathy fatigue, with effects on care delivery as well as on the health of the provider. Bias against older persons is widespread in our societies and needs to be rejected.
GEMCAT—a new algorithm for gene expression-based prediction of metabolic alterations
Authors: Sharma Suraj , Sauter Roland , Hotze Madlen , Prowatke Aaron Marcellus Paul , Niere Marc , Kipura Tobias , Egger Anna-Sophia , Thedieck Kathrin , Kwiatkowski Marcel , Ziegler Mathias , Heiland Ines
Published: January 2025

The interpretation of multi-omics datasets obtained from high-throughput approaches is important to understand disease-related physiological changes and to predict biomarkers in body fluids. We present a new metabolite-centred genome-scale metabolic modelling algorithm, the Gene Expression-based Metabolite Centrality Analysis Tool (GEMCAT). GEMCAT enables integration of transcriptomics or proteomics data to predict changes in metabolite concentrations, which can be verified by targeted metabolomics. In addition, GEMCAT allows to trace measured and predicted metabolic changes back to the underlying alterations in gene expression or proteomics and thus enables functional interpretation and integration of multi-omics data. We demonstrate the predictive capacity of GEMCAT on three datasets and genome-scale metabolic networks from two different organisms: (i) we integrated transcriptomics and metabolomics data from an engineered human cell line with a functional deletion of the mitochondrial NAD transporter; (ii) we used a large multi-tissue multi-omics dataset from rats for transcriptome- and proteome-based prediction and verification of training-induced metabolic changes and achieved an average prediction accuracy of 70%; and (iii) we used proteomics measurements from patients with inflammatory bowel disease and verified the predicted changes using metabolomics data from the same patients. For this dataset, the prediction accuracy achieved by GEMCAT was 79%.
Detection of plasma circulating GD2 ganglioside in patients with neuroblastoma and age-matched healthy children. Diagnostic and prognostic evaluation
Authors: Morini Martina , Barco Sebastiano , Ardito Martina , Cafaro Alessia , Pigliasco Federica , Rossi Lucilla , Fragola Martina , Segalerba Daniela , Conte Massimo , Garaventa Alberto , Ponzoni Mirco , Cangemi Giuliana , Corrias Maria Valeria
Published: January 2025

Background

GD2 ganglioside, a known specific marker for neuroblastoma (NB), exists in different lipoforms, including C18 and C20, which are distinguished by the length of their fatty acid chains. C18 and C20 GD2 lipoforms can be simultaneously measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We evaluated the diagnostic and prognostic performance of circulating GD2 levels in children with NB.

Methods

Thirty microliters of peripheral blood (PB) plasma samples from 83 children with NB at diagnosis and 83 age-matched healthy controls were analyzed by LC-MS/MS. From stage M patients, 29 additional PB plasma samples were collected after induction therapy, 7 before and after immunotherapy, and 6 at relapse. For 22 stage M patients, bone marrow (BM) plasma samples were also collected at diagnosis.

Results

C18 and C20 GD2 concentrations were significantly higher in children with NB than in controls. Receiver operating characteristic (ROC) analysis showed a cut-point of 44.1 and 0.47 nM for C18 and C20, respectively, able to discriminate with high specificity and sensitivity in patients with NB from controls. Circulating C18 and C20 levels in PB strongly correlated with those in BM. At diagnosis, C18 and C20 GD2 concentrations were significantly higher in stage M, deceased patients, and in those bearing tumors with MYCN amplification. ROC analysis identified prognostic cut points for the whole population, whereas only C20 concentrations above the cut points were significantly associated with a worse event-free survival of patients with stage M disease or with MYCN-amplified tumors. C18 and C20 plasma concentrations strongly decreased during treatment but increased at relapse.

Conclusions

Measurement of circulating GD2 seems to have prognostic power in the subsets of patients with stage M disease and with MYCN-amplified tumors, and be able to early detect relapse, thus its ability to monitor disease should be prospectively evaluated in future studies.
Anti-citrullinated procollagen C-endopeptidase enhancer antibody (anti-PCOLCE): a potential biomarker for seronegative rheumatoid arthritis
Authors: Lin Hongying , Xie Yang , Wei Xihua , Wei Chaonan , Li Zhanguo , Hu Fanlei
Published: January 2025

Objectives

Although with great advances, the biomarkers used in the diagnosis of rheumatoid arthritis (RA) are still challenging, especially in seronegative RA. Recently, procollagen C-endopeptidase enhancer (PCOLCE) was revealed as a potential autoantigen of seronegative RA by our group. This study aimed to further analyse the B-cell autoantigenic epitopses of PCOLCE and the diagnostic value of its antibody in seronegative RA.

Methods

The B-cell epitopes of PCOLCE were elucidated by the Immune Epitope Database and molecular mimicry analyses. The anti-citrullinated PCOLCE271-284 antibody (anti-PCOLCE) was tested in a total of 612 serum samples including RA patients, healthy controls and patients with other rheumatic diseases. The diagnostic value of anti-PCOLCE in RA, especially for seronegative RA, was evaluated by ROC curve, sensitivity and specificity. Anti-PCOLCE in combination with anti-CCP for RA diagnosis was also demonstrated. The correlations of anti-PCOLCE with RA patient features were further analysed.

Results

Anti-PCOLCE was significantly elevated in RA serums with a sensitivity of 51.53% and specificity of 93.60%. More importantly, anti-PCOLCE had a favorable diagnostic value in seronegative RA, revealing a positive rate of 40.00% in anti-CCP negative RA, 38.76% in RF negative RA and 36.46% in anti-CCP and RF negative RA. The combination of anti-PCOLCE with anti-CCP demonstrated a high sensitivity of 82.14% and specificity of 90.21%. Anti-PCOLCE also has good diagnostic value in RA patients with normal inflammatory factors and early RA. Moreover, anti-PCOLCE was positively correlated with CRP, anti-CCP and RF.

Conclusion

Anti-PCOLCE could serve as a novel biomarker for RA, especially for seronegative RA.
The Status of the Surveilled: Hyper Surveillance and Status Attainment among Gangs
Authors: Leverso John , Lee Sou
Published: January 2025

Using a case study of Latino gangs in Chicago over a 15-year period and original data compiled from gang cassette mixtapes, CDs, and DVDs, this research analyzes highly ritualized interactions in public media to investigate how status rituals change over time. Specifically, we focus on how factors external to the gang space, such as hyper-surveillance and enhanced policing techniques, influence status attainment in gangs. To date, research on hyper-surveillance focuses on justice system avoidance and crime rates in hot spots, but largely unaddressed are the consequences on the culture of urban gangs. We find that gangs have normalized and incorporated hyper-surveillance into their interaction rituals. Rather than avoidance, increased surveillance is associated with elevated status both at the individual and gang levels. In addition, due to intensified policing practices, even simple loitering on street corners is now associated with elevated status because of the threat of discovery and sanction. These new status attainment methods are encompassed in what we term the “status of the surveilled.” These results shed light on unique, unintended consequences of hyper-surveillance and enhanced policing in urban areas, as well as how they are incorporated into group processes related to status attainment within the urban street gang.
Examining risk assessment implications of genetic and dose-dependent dynamics of lead exposure in breastfeeding using the collaborative cross mouse population
Authors: Cuomo Danila , Song Zhuolin , Nitcher Megan , Lynch Rachel , Barba Estefania , Feinberg Andrew P , Rusyn Ivan , Wright Fred A , Chiu Weihsueh A , Threadgill David W
Published: January 2025

Breastfeeding offers well-documented advantages but may inadvertently introduce lead (Pb) exposure to infants. Scarce data exist on the risks of Pb exposure for breastfed infants, and strategies for risk mitigation are needed, particularly considering the heightened susceptibility of children to adverse effects from Pb exposure. To investigate the potential influence of breastfeeding on blood Pb levels (BLL) in offspring, population variation in BLL between nonparous and parous mouse dams was quantified, as well as in dams exposed to low and high dose while breastfeeding, and their offspring. Female mice from 14 distinct collaborative cross (CC) mouse strains were mated with sires from different CC strains to produce 14 F1 hybrids. Subsequently, dams were administered either low- (100 ppm) or high- (1,000 ppm) dose Pb through ad libitum access drinking water starting the day of delivery for a duration of 4 wk, leading to the subsequent exposure of the offspring via lactation. Genetic background emerged as a predominant factor contributing to variation, with substantial interstrain variability observed in both CC dams and F1 hybrids exposed to low and high doses of Pb. Crucially, the degree of variation in BLL among CC dams exceeded the default variability estimate (geometric SD = 1.6) utilized in regulatory standard settings. These findings underscore the importance of integrating population variability in risk assessment. Ultimately, this study provides critical insights to guide public health decision-making processes concerning Pb exposure through breastfeeding and its potential implications for infants’ health.
Comparative analysis of Caco-2 cells and human jejunal and duodenal enteroid-derived cells in gel- and membrane-based barrier models of intestinal permeability
Authors: Moyer Haley L , Vergara Leoncio , Stephan Clifford , Sakolish Courtney , Ford Lucie C , Tsai Han-Hsuan D , Lin Hsing-Chieh , Chiu Weihsueh A , Villenave Remi , Hewitt Philip , Ferguson Stephen S , Rusyn Ivan
Published: January 2025

Intestinal absorption is a key toxicokinetics parameter. Although the colon carcinoma cell line Caco-2 is the most used in vitro model to estimate human drug absorption, models representing other intestinal segments are available. We characterized the morphology, tissue-specific markers, and functionality of 3 human intestinal cell types: Caco-2, primary human enteroid-derived cells from jejunum (J2), and duodenum (D109) when cultured in the OrganoPlate 3-lane 40 microphysiological system (MPS) or static 24-well Transwells. In both conditions, J2 and D109 formed dome-like structures; Caco-2 formed uniform monolayers. In MPS, only Caco-2 formed tubules. Cells grown on Transwells formed a thicker monolayer. All cells and conditions exhibited expression of ZO-1 (tight junctions). Polarization markers Ezrin and Villin were highest in J2 and D109 in MPS, highest expression of Mucin was observed with J2. However, J2 and D109 exhibited poor barrier (70 kDa TRITC-dextran) in MPS, whereas robust barrier was recorded in Transwells. Barrier function and drug transport were evaluated using caffeine, indomethacin, and propranolol. The gel lane in MPS acted as a blockade; only a small fraction crossed, even without cells. The permeability ratios were used to parameterize the probabilistic compartmental absorption model to determine whether in vitro data could reduce uncertainty. The most accurate prediction of the fraction absorbed was achieved with Transwell-derived data from Caco-2, combined with the experimentally derived segment-specific absorption ratios. The impact of this study includes demonstration that enteroid-derived cells cultured in MPS show most physiological morphology, but that studies of drug permeability in this MPS are challenging.
METTL3 promotes renal ischemia‐reperfusion injury by modulating miR‐374b‐5p/SRSF7 axis
Authors: Zhu Kun , Sun Shirui , Li Zepeng , Deng Ge , Guo Yingcong , Zheng Bingxuan , He Qi , Zhao Zhenting , Ding Chenguang
Published: January 2025

Renal ischemia–reperfusion injury (IRI) is a prevalent cause of acute kidney injury, however, the regulatory mechanisms of miR‐374b‐5p in renal IRI remain poorly understood. We established hypoxia/reoxidation (H/R)‐induced renal injury models using HK‐2 and TCMK‐1 cells, as well as an ischemia–reperfusion (I/R)‐induced mouse model. Renal tubular epithelial cells (RTECs) viability and apoptosis were assessed using CCK‐8, flow cytometry, and TUNEL assays. The targeting relationship between miR‐374b‐5p and SRSF7 was analyzed using dual luciferase reporter assays. The interaction between METTL3 and miR‐374b‐5p was confirmed through methylated RNA immunoprecipitation (MeRIP) and co‐immunoprecipitation (Co‐IP) assays. We found that miR‐374b‐5p levels were significantly upregulated in H/R‐induced HK‐2 and TCMK‐1 cells. Furthermore, miR‐374b‐5p promoted H/R‐induced RTEC injury by suppressing cell viability and exacerbating apoptosis. SRSF7 was identified as a downstream target of miR‐374b‐5p, inhibition of SRSF7 reversed the inhibitory effects of miR‐374b‐5p inhibitors on RTEC injury. Additionally, METTL3 interacted with the microprocessor protein DGCR8 and modulated the processing of pri‐miR‐374b‐5p in an m6A‐dependent manner. In the renal IRI model, METTL3 and miR‐374b‐5p levels were upregulated, and knockdown of METTL3 inhibited apoptosis in H/R‐induced HK‐2 and TCMK‐1 cells. Conversely, miR‐374b‐5p reversed the protective effects of METTL3 knockdown on renal IRI. Our findings provide novel insights into the role of m6A methylation in the development of renal IRI, demonstrating that METTL3 promotes renal IRI by modulating the miR‐374b‐5p/SRSF7 axis.
Trends and Disparities in Acute Lymphoblastic Leukemia–Related Mortality in the United States from 1999 to 2020
Authors: Ahmed Shahzaib , Ahmad Eeman , Ashraf Hamza , Ashfaq Haider , Akram Umar , Ahmad Shoaib
Published: January 2025

Objectives:

The incidence of acute lymphoblastic leukemia (ALL) shows a bimodal distribution, with the first peak in children under 10 years old and the second in adults. It is imperative to understand disparities in ALL-related mortality.

Methods:

ALL-related mortality trends in the United States from 1999 to 2020 were studied by extracting age-adjusted mortality rates (AAMRs) from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. Changes in AAMR were evaluated by calculating annual percentage change (APC) and average APC using Joinpoint regression.

Results:

A total of 35,056 ALL-related deaths were reported. The AAMR declined from 1999 to 2020 (APC: −0.65). Men exhibited a higher AAMR (0.59) than women (0.43). Hispanic or Latinos exhibited the highest AAMR (0.75), followed by non-Hispanic (NH) whites (0.47), NH black or African Americans (0.37), and NH Asian or Pacific Islanders (0.35). Among census regions, the West was observed to have the highest AAMR (0.59), followed by the South (0.49), the Midwest (0.47), and the Northeast (0.45). California had the highest AAMR (0.64), while the District of Columbia had the lowest (0.40). Stratification by urbanization revealed a higher overall AAMR in rural areas (0.52) than in urban areas (0.48). A majority of the deaths occurred in medical facilities (63.52%).

Conclusions:

Even though a decrease was observed in ALL-related mortality in the United States from 1999 to 2020, disparities were identified in trends stratified by sex, race, census regions, and urbanization. It is essential to direct efforts towards high-risk populations to ensure a decrease in ALL-related mortality across the board.
Clinical Evaluation of Nd:YAG Capsulotomy on the Light-Adjustable Intraocular Lens
Authors: Abing Ashley A. , Lee Jimmy K. , Tran Dan B. , Marvasti Amir H.
Published: January 2025

Purpose:

To investigate the safety and refractive outcomes of neodymium-doped yttrium-aluminum-garnet (Nd:YAG) capsulotomy in pseudophakic eyes with the Light Adjustable Lens (LAL) both before and after completing the light delivery device (LDD) lock-in treatments.

Setting:

Private practice in Orange, California, USA.

Design:

Retrospective, comparative study.

Methods:

Patients were divided into two groups according to the timing of their YAG capsulotomy (Group I underwent YAG capsulotomy before lock-in treatments and Group II underwent YAG capsulotomy upon completion of lock-in treatments). Sphere, cylinder, axis, spherical equivalent, uncorrected visual acuity, and best-corrected visual acuity were compared pre- and postoperatively using two-tailed paired t-tests. Postoperative data were measured one month after Nd:YAG capsulotomy. The alpha level (type I error) was set at 0.05.

Results:

The LAL was successfully implanted in 485 eyes from January 2020 to March 2023. Ten eyes (0.02%) needed YAG capsulotomy prior to the completion of lock-in treatments (Group I) and 28 eyes (5.77%) needed YAG capsulotomy after the lock-in was completed (Group II). Postoperative BCVA significantly improved compared to preoperative values in both groups. Changes in sphere, cylinder, axis, SE, and UCVA pre- and postoperative measurements were not statistically significant (p > 0.05) in both groups.

Conclusions:

YAG capsulotomy can be safe and effective for patients with the LAL who develop PCO during the adjustment period. There were no significant changes in sphere, cylinder, axis, or spherical equivalence after YAG capsulotomy in both groups.
Optimal Management of the Inpatient With Decompensated Cirrhosis
Authors: Sikerwar Sandeep , Yao Leah , Elfarra Yasmine , Jesudian Arun
Published: January 2025

Over the past several years, there has been a wealth of new data pertaining to the management of complications of cirrhosis, resulting in several important updates to best practices and consensus guidelines. Despite these advancements and numerous recent targeted quality initiatives, hospitalizations resulting from complications of cirrhosis remain frequent, costly and associated with poor patient outcomes. An emphasis on evidence-based management of hospitalized patients with decompensated cirrhosis has the potential to decrease readmission rates and length of stay while improving overall patient outcomes. Herein, we provide an updated, evidence-based overview of the optimal inpatient management of the most frequently encountered complications associated with cirrhosis.
ECPR combined with CRRT successfully rescues a patient who experienced sudden cardiac arrest for 152 minutes: A case report
Authors: Wang Ya-Dong , Lin Jin-Feng , Cao Zhi-Long , Zhang Su-Yan , Han Xu-Dong
Published: January 2025

Rationale:

Cardiac arrest (CA) is a life-threatening event with a high mortality rate, and neurological injury following cardiopulmonary resuscitation (CPR) is a leading cause of death and disability in survivors. While prolonged CPR is often associated with poor neurological outcomes, there is limited evidence of successful recovery following extended resuscitation efforts. This study aims to highlight the potential for recovery after prolonged CPR by reporting a case of a patient who underwent 152 minutes of CPR, regained consciousness, and made a full recovery. The purpose is to explore whether advanced life-support techniques, such as extracorporeal CPR (ECPR), can improve survival and neurological outcomes even after prolonged CA.

Patient concerns:

A 53-year-old man with no prior health issues experienced sudden CA while exercising and underwent prolonged CPR.

Diagnoses:

Restoration of spontaneous circulation following CA and ventricular fibrillation.

Interventions:

ECPR, target temperature management, continuous renal replacement therapy, and intracranial pressure management.

Outcomes:

Immediate recovery: following the restoration of spontaneous circulation, the patient was immediately transferred to the intensive care unit for further treatment. Despite the prolonged CPR duration, the patient remained hemodynamically stable and was able to tolerate the intensive interventions. Neurological recovery: after 1 week of intensive therapy, the patient regained consciousness. Initially, there was some confusion and disorientation, but he gradually became fully alert, oriented, and communicative. Neurological assessments indicated no significant long-term deficits, and brain imaging showed no signs of irreversible damage. Cardiological and renal recovery: cardiac function was closely monitored, with no evidence of significant ischemic damage to the myocardium. The patient’s renal function improved with continuous renal replacement therapy, and kidney function returned to normal following the discontinuation of dialysis. Discharge: after 2 weeks of treatment in the intensive care unit and a transfer to the cardiology department for rehabilitation, the patient was discharged from the hospital. He had fully recovered both neurologically and physiologically, with no residual deficits.

Lessons:

This case demonstrates that prolonged CPR, when combined with advanced interventions such as ECPR, can result in favorable outcomes, including survival and neurological recovery. The findings suggest that with timely and appropriate treatment, even patients with extended resuscitation efforts may achieve full recovery, thus underscoring the potential of ECPR as a critical life-saving intervention in cases of prolonged CA.
Mendelian randomization analysis of female reproductive factors on osteoarthritis
Authors: Pang Liang , Wu Kai , Su Pingping , Liao Zhicheng , Lv Cunxian
Published: January 2025

Epidemiology shows women have a higher incidence of osteoarthritis (OA) than men. However, there is not enough evidence to suggest a direct correlation between female reproductive factors and OA. Therefore, this study will employ Mendelian randomization (MR) analysis to investigate whether there is a causal relationship between the 2. This study used a 2-sample MR analysis with single nucleotide polymorphisms significantly associated with female reproductive factors as instrumental variables (IV). We used inverse variance weighted (IVW), MR-Egger regression, weighted median method to infer a causal relationship between female reproductive factors and OA, Cochran Q heterogeneity test by IVW and MR-Egger method, MR PRESSO method and IVW-radial method to detect outliers, MR_pleiotropy_test function and MR PRESSO method for multivariate validity test, and calculation of F-value was used to assess the presence of weak IVs. Finally, the stability of the findings was assessed using the leave-one-out method. Our research shows that there is no reliable causal relationship between an increase in Age at menarche (years) (AAM) and Age at menopause (years) (AM) and OA, that an increase in Age first had sexual intercourse (years) (AFS) is associated with a decreased risk of knee OA and/or hip OA and hand OA, that an increase in Age at first live birth (years) (AFB) is associated with a decreased risk of knee OA and/or hip OA and knee OA, and that an increase in Number of live births (NOB) is associated with an increased risk of knee OA and/or hip OA. This study provides genetic support for an increase in AFS as a reduced knee OA and/or hip OA and hand OA risk factor, an increase in AFB as a reduced knee OA and/or hip OA and knee OA risk factor, and an increase in NOB as an increased knee OA and/or hip OA risk factor. Further studies are needed to elucidate the potential mechanisms underlying the causal associations between AFS, AFB, and NOB and site-specific OA.