bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer factors peptides (Imuno TF®) modulate the lung inflammation and airway remodeling in allergic asthma
Authors: Oliveira Carlos Rocha , Carvalho Jessica , Olímpio Fabiana , Vieira Rodolfo , Aimbire Flavio , Polonini Hudson 
Published: January 2023

BackgroundAllergic asthma is a chronic lung disease in which the lung inflammation and airway remodeling are orchestrated by both the inflammatory and the immune cells that creates a lung millieu that favors the perpetuation of clinical symptoms. The cell signaling in asthma involves the mast cells activation during initial contact with the allergen and, principally, the participation of eosinophils as well as Th2 cells which determine increased levels of IgE, exaggerated secretion of mucus and collagen, and bronchial hyperreactivity. Moreover, allergic asthma presents lower level of cytokines associated to the both Th1 and Treg cells response, and it implies in deficiency of anti-inflammatory response to counterregulate the exaggerated inflammation against allergen. Therefore, the equilibrium between cytokines as well as transcription factors associated to Th2, Th1, and Treg cells is compromised in allergic asthma. Imuno TF® is a food supplement with ability to interfere in immune system pathways. It has been previously demonstrated that Imuno TF® upregulated Th1 cell response whilst downregulated Th2 cell response in human lymphocytes.ObjectiveFor this reason, we hypothesized that the Imuno TF effect could be restore the balance between Th1/Th2 CD4 T cells response in murine allergic asthma.MethodsInitially, animals were sensitized with OVA via i.p. and challenged with OVA i.n. on days 14, 15 and 16. Treatment with Imuno TF once a day was performed via orogastric from day 17 to day 20. Mice were euthanized on day 21.ResultsThe Imuno TF reduced eosinophilia, mucus production, and airway remodeling (collagen deposition) in asthma mice. Imuno TF influenced cellular signaling associated to allergic asthma once downregulated STAT6 expression as well as decreased IL-4, IL-5, and IL-13 in lung and serum. In addition, Imuno TF restored T-bet and Foxp3 expression as well as increased IL-12, IFN-ɣ, and IL-10.ConclusionUltimately, Imuno TF mitigated the allergic asthma due to the restoration of balance between the responses of Th1/Th2 as well as Treg cells, and their respective transcription factors the T-bet/STAT6 and Foxp3.
Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis
Authors: Höppner Jakob , Tabeling Christoph , Casteleyn Vincent , Kedor Claudia , Windisch Wolfram , Burmester Gerd Rüdiger , Huscher Dörte , Siegert Elise 
Published: January 2023

BackgroundSystemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of these specific antibodies and their possible pathophysiological properties. Interestingly, they are associated with specific clinical manifestations, but for some rarer antibodies this association is not fully clarified. The aim of this study is a comprehensive analysis of the serum autoantibody status in patients with SSc followed by correlation analyses of autoantibodies with the clinical course of the disease.MethodsSerum from SSc patients was analyzed using a line blot (EUROLINE, EUROIMMUN AG) for SSc-related autoantibodies. Autoantibodies to centromere, Topo-1, antimitochondrial antibodies (AMA) M2 subunit, angiotensin II type 1 receptors (AT1R) and endothelin-1 type-A-receptors (ETAR) were also determined by ELISA. We formed immunological clusters and used principal components analysis (PCA) to assign specific clinical characteristics to these clusters.ResultsA total of 372 SSc patients were included. 95.3% of the patients were antinuclear antibody positive and in 333 patients at least one SSc specific antibody could be detected. Four immunological clusters could be found by PCA. Centromere, Topo-1 and RP3 all formed own clusters, which are associated with distinct clinical phenotypes. We found that patients with an inverted phenotype, such as limited cutaneous SSc patients within the Topo-1 cluster show an increased risk for interstital lung disease compared to ACA positive patients. Anti-AT1R and anti-ETAR autoantibodies were measured in 176 SSc patients; no association with SSc disease manifestation was found. SSc patients with AMA-M2 antibodies showed an increased risk of cardiovascular events.ConclusionIn our in large cluster analysis, which included an extended autoantibody profile, we were able to show that serologic status of SSc patients provides important clues to disease manifestation, co-morbidities and complications. Line blot was a reliable technique to detect autoantibodies in SSc and detected rarer autoantibodies in 42% of our patients.
Viral load and its relationship with the inflammatory response and clinical outcomes in hospitalization of patients with COVID-19
Authors: Kuri-Ayache Mauricio , Rivera-Cavazos Andrea , Pérez-Castillo María Fátima , Santos-Macías Juan Enrique , González-Cantú Arnulfo , Luviano-García José Antonio , Jaime-Villalón Diego , Gutierrez-González Dalia , Romero-Ibarguengoitia Maria Elena 
Published: January 2023

BackgroundThe values of viral load in COVID-19 disease have gained relevance, seeking to understand its prognostic value and its behavior in the course of the disease, although there have been no conclusive results. In this study we sought to analyze serum viral load as a predictor of clinical outcome of the disease, as well as its association with inflammatory markers.MethodsAn observational and retrospective study in a private hospital in North Mexico, patients with SARS-COV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) were followed through clinical outcome, viral load measurement, quantification of inflammatory markers and lymphocyte subpopulations. For the analysis, multiple regression models were performed. Results: We studied 105 patients [47 (SD 1.46) years old, 68.6% men]. After analysis with multiple regression models, there was an association between viral load at admission and vaccination schedule (β-value=-0.279, p= 0.007), age (β-value= 0.010, p = 0.050), mechanical ventilation (β-value= 0.872, p = 0.007), lactate dehydrogenase (β-value= 1.712, p= 0.004), D-dimer values at admission (β-value= 0.847, p= 0.013) and subpopulation of B lymphocytes at admission (β-value= -0.527, p= 0.042). There was no association with days of hospitalization, use of nasal prongs or high flux mask. Peak viral load (10 days after symptoms onset) was associated with peak IL-6 (β-value= 0.470, p= 0.011). Peak viral load matched with peak procalcitonin and minimal lymphocyte values. C-reactive protein peak was before the peak of viral load. The minimum value viral load was documented on day 12 after symptom onset; it matched with the minimum values of IL-6 and ferritin, and the peak of D-dimer.ConclusionsSARS-COV-2 admission viral load is associated with vaccination status, mechanical ventilation, and different inflammatory markers.
Spatial genomics reveals a high number and specific location of B cells in the pancreatic ductal adenocarcinoma microenvironment of long-term survivors
Authors: Aziz Hosein M. , Saida Lawlaw , de Koning Willem , Stubbs Andrew P. , Li Yunlei , Sideras Kostandinos , Palacios Elena , Feliu Jaime , Mendiola Marta , van Eijck Casper H. J. , Mustafa Dana A. M. 
Published: January 2023

Background and aimOnly 10% of pancreatic ductal adenocarcinoma (PDAC) patients survive longer than five years. Factors underlining long-term survivorship in PDAC are not well understood. Therefore, we aimed to identify the key players in the tumor immune microenvironment (TIME) associated with long-term survivorship in PDAC patients.MethodsThe immune-related gene expression profiles of resected PDAC tumors of patients who survived and remained recurrence-free of disease for ≥36 months (long-term survivors, n=10) were compared to patients who had survived ≤6 months (short-term survivors, n=10) due to tumor recurrence. Validation was performed by the spatial protein expression profile of immune cells using the GeoMx™ Digital Spatial Profiler. An independent cohort of samples consisting of 12 long-term survivors and 10 short-term survivors, was used for additional validation. The independent validation was performed by combining qualitative immunohistochemistry and quantitative protein expression profiling.ResultsB cells were found to be significantly increased in the TIME of long-term survivors by gene expression profiling (p=0.018). The high tumor infiltration of B cells was confirmed by spatial protein profiling in the discovery and the validation cohorts (p=0.002 and p=0.01, respectively). The higher number of infiltrated B cells was found mainly in the stromal compartments of PDAC samples and was exclusively found within tumor cells in long-term survivors.ConclusionThis is the first comprehensive study that connects the immune landscape of gene expression profiles and protein spatial infiltration with the survivorship of PDAC patients. We found a higher number and a specific location of B cells in TIME of long-term survivors which emphasizes the importance of B cells and B cell-based therapy for future personalized immunotherapy in PDAC patients.
Serum organic acid metabolites can be used as potential biomarkers to identify prostatitis, benign prostatic hyperplasia, and prostate cancer
Authors: He Jinhua , Han Zeping , Luo Wenfeng , Shen Jian , Xie Fangmei , Liao Liyin , Zou Ge , Luo Xin , Guo Zhonghui , Li Yuguang , Li Jianhao , Chen Hanwei 
Published: January 2023

BackgroundNoninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) are current clinical challenges.MethodsThe serum metabolites of 20 healthy individuals and patients with prostatitis, BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS). In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort.ResultsOrganic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. Three diagnostic models identified patients with PROSTATITIS: phenyllactic acid (area under the curve [AUC]=0.773), pyroglutamic acid (AUC=0.725), and pantothenic acid (AUC=0.721). Three diagnostic models identified BPH: citric acid (AUC=0.859), malic acid (AUC=0.820), and D-glucuronic acid (AUC=0.810). Four diagnostic models identified PCa: 3-hydroxy-3-methylglutaric acid (AUC=0.804), citric acid (AUC=0.918), malic acid (AUC=0.862), and phenyllactic acid (AUC=0.713). Two diagnostic models distinguished BPH from PCa: phenyllactic acid (AUC=0.769) and pyroglutamic acid (AUC=0.761). Three diagnostic models distinguished benign BPH from PROSTATITIS: citric acid (AUC=0.842), ethylmalonic acid (AUC=0.814), and hippuric acid (AUC=0.733). Six diagnostic models distinguished BPH from prostatitis: citric acid (AUC=0.926), pyroglutamic acid (AUC=0.864), phenyllactic acid (AUC=0.850), ethylmalonic acid (AUC=0.843), 3-hydroxy-3-methylglutaric acid (AUC=0.817), and hippuric acid (AUC=0.791). Three diagnostic models distinguished PCa patients with PROSTATITISA &lt; 4.0 ng/mL from those with PSA &gt; 4.0 ng/mL: 5-hydromethyl-2-furoic acid (AUC=0.749), ethylmalonic acid (AUC=0.750), and pyroglutamic acid (AUC=0.929). Conclusions: These results suggest that serum organic acid metabolites can be used as biomarkers to differentiate prostatitis, BPH, and PCa.
Towards the development of reliable and economical mHealth solutions: A methodology for accurate detection of Buruli ulcer for hard-to-reach communities
Authors: Queen Courtney M. , Hu Rui , Zouridakis George 
Published: January 2023

mHealth interventions have the potential to increase access to healthcare for the most hard-to-reach communities. For rural communities suffering disproportionately from skin-related NTDs, and Buruli ulcer, there is a need for low-cost, non-invasive and mobile tools for the early detection and management of disease. Dermoscopy is a noninvasive in-vivo technique that has been useful in improving the diagnostic accuracy of pigmented skin lesions based on anatomical features and morphological structures of lesions.ObjectivesUsing dermoscopy, this study develops the automated tools necessary for developing an effective mHealth intervention towards identifying BU lesions in the early stages. Methods: This imaging methodology relies on an external attachment, a dermoscope, which uses polarized light to cancel out skin surface reflections. In our initial studies we used a dermoscope with only crosspolarized white-light (DL100, 3Gen) but later we adopted a more advanced multispectral dermoscope (DLIIm, 3Gen). The latter employed additional monochromatic light at different wavelengths of the visible spectral range, specifically blue (470 nm), yellow (580 nm), and red (660 nm) color, to visualize pigmented structures of skin layers at different depths.ResultsResults obtained using a subset of 58 white-light images with confirmed diagnosis (16 lesions BU and 42 lesions non-BU) resulting in sensitivity of 100 and specificity of 88.10, with an overall accuracy of 94.05 at 95% CI. Performance obtained using a second dataset of 197 dermoscopic multispectral images (16 lesions BU and 181 lesions non-BU) resulted in sensitivity of 90.00% and specificity of 93.39% with a balanced accuracy of 91.69% (86.95% to 95.12% at 95% CI).ConclusionsThis system will continue to perform even as the technology evolves and newer dermoscopes are available. Subsequent studies involve the DL4 which provides more uniform and brighter illumination, higher lesion magnification, and wider field of view which, combined with the superb resolution of modern smartphones, can result in faster and more accurate lesion assessment. This is an important step for the development of mHealth tools for use by non-specialists in community settings for the early detection of Buruli ulcer, skin-NTDs, and other dermatologic conditions associated with disease, including wound healing and management of disease progression.
Interfacial intermetallic compound modification to extend the electromigration lifetime of copper pillar joints
Authors: Yang Dongsheng , Huang Yilong 
Published: January 2023

Electromigration is the massive metal atom transport due to electron flow, which could induce a disconnect in electronics. Due to the size of copper pillar bump reduction, the portion of interfacial intermetallic compound in solder joints is increasing obviously. However, there is lack of systematical research on the effects of intermetallic compound on the EM lifetime of solder joints. In this paper, the interfacial intermetallic compound of copper pillar joints is modified to extend the electromigration lifetime. The growth rate of intermetallic compound in solder joints sample is calculated firstly. From 230°C to 250°C, the growth rate of intermetallic compound increases from 0.09 μm/min to 0.19 μm/min. With a longer reaction time, the intermetallic compound layers continuously grow. Then electromigration tests were conducted under thermo-electric coupling loading of 100°C and 1.0 × 104 A/cm2. Compared with lifetime of thin and thick intermetallic compound samples, the lifetime of all intermetallic compound sample improved significantly. The lifetime of thin, thick, and all intermetallic compound samples is 400 min, 300 min, and 1,200 min, respectively. The failure mechanism for the thin intermetallic compound sample is massive voids generation and aggregation at the interface between solder joints and pads. For the thick intermetallic compound sample, the intermetallic compound distance is short between cathode and anode in solder joints, leading to lots of crack create in the middle of solder joints. As the all intermetallic compound sample can greatly reduce the number of voids generated by crystal structure transforming, the lifetime extend obviously.
Peripheral vascular catheter use in Latin America (the vascular study): A multinational cross-sectional study
Authors: Walker Rachel M. , Pires Maria Paula Oliveira , Ray-Barruel Gillian , Cooke Marie , Mihala Gabor , Azevedo Silvia Schoenau , Peterlini Maria Angelica Sorgini , Felipe Marcelle Di Angelis Ambar , Álvarez Cirlia Petrona , Quintanilla Marcela , Corzo Martha Claudia , Villareal Gabriela Cortez , Cigarroa Eliazib Nataren , Pedreira Mavilde L. G. , Rickard Claire M. 
Published: January 2023

BackgroundPeripheral intravenous catheter (PIVC) insertion is one of the most common clinical procedures worldwide, yet little data are available from Latin America. Our aim was to describe processes and practices regarding PIVC use in hospitalized patients related to hospital guidelines, characteristics of PIVC inserters, prevalence of PIVC complications, and idle PIVCs.MethodsIn 2019 we conducted a multinational, cross-sectional study of adult and pediatric patients with a PIVC in hospitals from five Latin American countries: Argentina, Brazil, Chile, Colombia, and Mexico. We used two data collection tools to collect hospital guidelines and patient-specific data on the day of the study. The vessel health and preservation (VHP) model guided synthesis of the study aims/questions and suggested opportunities for improvement.ResultsA total of 9,620 PIVCs in adult (86%) and pediatric inpatients in 132 hospitals were assessed. Routine replacement 8–72 hourly was recommended for adults in 22% of hospitals, rather than evidence-based clinical assessment-based durations, and 69% of hospitals allowed the use of non-sterile tape rather than the international standard of a sterile dressing. The majority (52%) of PIVCs were inserted by registered nurses (RNs), followed by nursing assistants/technicians (41%). Eight percent of PIVCs had pain, hyperemia, or edema, 6% had blood in the extension tubing/connector, and 3% had dried blood around the device. Most PIVCs had been inserted for intravenous medications (81%) or fluids (59%) in the previous 24 h, but 9% were redundant.ConclusionGiven the variation in policies, processes and practices across countries and participating hospitals, clinical guidelines should be available in languages other than English to support clinician skills and knowledge to improve PIVC safety and quality. Existing and successful vascular access societies should be encouraged to expand their reach and encourage other countries to join in multinational communities of practice.
Modified tarsorrhaphy versus gold weight implant technique for paralytic lagophthalmos treatment in patients with leprosy: One-year observation of a randomized controlled trial study
Authors: Irawati Yunia , Natalia Michelle Eva Rebeca , Gondhowiardjo Tjahjono D. , Dachlan Ishandono , Soebono Hardyanto 
Published: January 2023

Trial designThis study was a multicenter, Prospective Randomized Open-label Blinded-Endpoint (PROBE) clinical trial, parallel-group study conducted in Indonesia (three sites).MethodsThe aim of this study was to compare the effectivity and efficiency of modified tarsorrhaphy (MT) and gold weight implant (GWI) techniques in the surgical treatment of paralytic lagophthalmos in patients with leprosy. The study sample consisted of 23 eyes, with 11 eyes in the MT group and the remaining 12 eyes in the GWI group—the control group.ResultsThe central eyelid margin distance (lagophthalmos distance) decreased when gentle pressure was applied in the MT (3.09 mm to 0.43 mm) and GWI groups (3.21 mm to 0.83 mm) at postoperative year 1. The Ocular Surface Disease Index score, the tear break-up time, and the Schirmer test without and with anesthesia in the MT and GWI groups showed a p-value of &gt; 0.05. Epitheliopathy improvement occurred in 54.55% of the MT group and 58.33% of the GWI group. Corneal sensitivity change in the inferior quadrant of the MT group (50.00 to 51.30 mm) and in the GWI group (49.61 to 52.93 mm) resulted in a p &gt; 0.05. Postoperative complications occurred in 15% of patients in the GWI group. In addition, the surgery duration of both techniques was similar. Furthermore, the surgery cost in the MT and GWI groups yielded a p &lt; 0.05.ConclusionThe MT technique is as effective as the GWI technique but more efficient than the GWI technique as a surgical treatment for paralytic lagophthalmos in patients with leprosy.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT0494 4498].
AI-RADS: Successes and challenges of a novel artificial intelligence curriculum for radiologists across different delivery formats
Authors: Lindqwister Alexander L. , Hassanpour Saeed , Levy Joshua , Sin Jessica M. 
Published: January 2023

IntroductionArtificial intelligence and data-driven predictive modeling have become increasingly common tools integrated in clinical practice, heralding a new chapter of medicine in the digital era. While these techniques are poised to affect nearly all aspects of medicine, medical education as an institution has languished behind; this has raised concerns that the current training infrastructure is not adequately preparing future physicians for this changing clinical landscape. Our institution attempted to ameliorate this by implementing a novel artificial intelligence in radiology curriculum, “AI-RADS,” in two different educational formats: a 7-month lecture series and a one-day workshop intensive.MethodsThe curriculum was structured around foundational algorithms within artificial intelligence. As most residents have little computer science training, algorithms were initially presented as a series of simple observations around a relatable problem (e.g., fraud detection, movie recommendations, etc.). These observations were later re-framed to illustrate how a machine could apply the underlying concepts to perform clinically relevant tasks in the practice of radiology. Secondary lessons in basic computing, such as data representation/abstraction, were integrated as well. The lessons were ordered such that these algorithms were logical extensions of each other. The 7-month curriculum consisted of seven lectures paired with seven journal clubs, resulting in an AI-focused session every two weeks. The workshop consisted of six hours of content modified for the condensed format, with a final integrative activity.ResultsBoth formats of the AI-RADS curriculum were well received by learners, with the 7-month version and workshop garnering 9.8/10 and 4.3/5 ratings, respectively, for overall satisfaction. In both, there were increases in perceived understanding of artificial intelligence. In the 7-lecture course, 6/7 lectures achieved statistically significant (P &lt; 0.02) differences, with the final lecture approaching significance (P = 0.07). In the one-day workshop, there was a significant increase in perceived understanding (P = 0.03).ConclusionAs artificial intelligence becomes further enmeshed in clinical practice, it will become critical for physicians to have a basic understanding of how these tools work. Our AI-RADS curriculum demonstrates that it is successful in increasing learner perceived understanding in both an extended and condensed format.