bluuebunny/crossref_metadata_2025_split huggingface dataset:
The giants of education in geriatric medicine and gerontology
Authors: Romero-Ortuno Roman , Stuck Andreas E , Masud Tahir 
Published: January 2022

Abstract
In 2014, the European undergraduate curriculum in Geriatric Medicine was published to cover the minimum requirements that a medical student should achieve by the end of medical school. In 2019, the European postgraduate curriculum in Geriatric Medicine outlined the minimum recommended training requirements to become a geriatrician at specialist level in the EU. The postgraduate dimension of Geriatric Medicine education is a highly relevant topic for all, since most physicians—independently of their specialty—are inevitably involved in the care of older patients, but for most physicians, geriatrics is not part of their postgraduate generalist or specialty training. A key area for postgraduate education remains the provision of Geriatric Medicine competencies to all specialties outside geriatrics. There is also need for wider educational initiatives to improve the gerontological education of patients and the public. Bernard Isaacs famously coined the expression ‘geriatric giants’ or the four clinical I’s: Intellectual impairment, Incontinence, Immobility, and Instability. However, non-clinical giants exist. In education, we face challenges of Investment, Inspiration, Integration, and Interprofessionality; and in research, we need to attract Interest and Income, and generate Innovation and Impact. Without strengthening the links between all giants, we will not be able to achieve the ambition of age-attuned societies. A key goal for gerontological education is to enhance everyone’s understanding of the wide diversity underlying the ‘older people’ demographic label, which will ultimately promote services and societies that are more responsive and inclusive to the needs of all older adults, irrespective of their health status.
Endometriosis, Psoriasis, and Psoriatic Arthritis: A Prospective Cohort Study
Authors: Harris Holly R , Korkes Karen Moreno Nascimento , Li Tricia , Kvaskoff Marina , Cho Eunyoung , Carvalho Luiz Fernando , Qureshi Abrar A , Abrao Mauricio , Missmer Stacey A 
Published: January 2022

AbstractEndometriosis, psoriasis, and psoriatic arthritis (PsA) are chronic inflammatory disorders whose etiologies remain poorly understood but may be correlated, as endometriosis has been associated with other inflammatory disorders. We investigated the bidirectional associations between laparoscopically confirmed endometriosis and physician-diagnosed psoriasis and PsA in the Nurses’ Health Study II cohort (n = 116,429, United States, 1991–2013). We confirmed 4,112 incident cases of laparoscopically confirmed endometriosis (mean age at diagnosis = 40.3 years) and 697 validated physician-diagnosed cases of psoriasis (mean age at diagnosis = 43.6 years), 110 of which presented with concomitant PsA. A history of psoriasis with concomitant PsA was associated with a 2-fold higher risk of endometriosis (hazard ratio (HR) = 2.01, 95% CI: 1.23, 3.30); however, no association was observed between psoriasis without PsA and endometriosis risk (HR = 0.93, 95% CI: 0.68, 1.26). When endometriosis was the exposure, it was not associated with a risk of subsequent psoriasis (HR = 1.28, 95% CI: 0.95, 1.72). The risk of psoriasis with PsA was notably higher; however, the sample size was small and the confidence intervals wide (HR = 1.77, 95% CI: 0.89, 3.52). Our findings suggest that psoriasis with concomitant PsA is associated with greater risk of laparoscopically confirmed endometriosis. In addition, there was a suggestive association between endometriosis diagnosis and subsequent risk of psoriasis with PsA.
Tenecteplase use in the management of acute ischemic stroke: Literature review and clinical considerations
Authors: Hailu Kirubel , Cannon Chad , Hayes Sarah 
Published: January 2022

Abstract

Purpose
Several research articles have been published within the last decade comparing the use of tenecteplase to alteplase in ischemic stroke management. Prior reporting on the comparative therapeutic efficacy and safety profiles of tenecteplase and alteplase is reviewed.

Summary
Tenecteplase is a variant of native tissue-type plasminogen activator, which rapidly promotes thrombolysis by catalyzing formation of the serine protease plasmin. Tenecteplase has theoretical advantages over alteplase as it has greater fibrin specificity and has a longer half-life than alteplase. This allows the administration of a single bolus over 5 to 10 seconds, as opposed to a bolus followed by a 1-hour infusion with alteplase. While currently approved by the Food and Drug Administration for the treatment of ST-segment elevation myocardial infarction, tenecteplase has also been studied in the treatment of acute ischemic stroke and has extensive data for this off-label indication. The most comprehensive trials to date evaluating the use of tenecteplase in acute ischemic stroke include the TNK-S2B, Australian TNK, ATTEST, Nor-Test, and EXTEND-IA TNK trials. Findings from these randomized controlled studies suggest that tenecteplase is at least as efficacious as alteplase in terms of neurological outcomes. The majority of these studies also reported a trend toward improved safety profiles with the use of tenecteplase.

Conclusion
Current clinical evidence shows that tenecteplase is not inferior to alteplase for the treatment of ischemic stroke and suggests that tenecteplase may have a superior safety profile. Furthermore, tenecteplase also has practical advantages in terms of its administration. This can potentially lead to a decrease in medication errors and improvement in door to thrombolytic time.
Reversing the Lens on Public Engagement with Science: Positive Benefits for Participating Scientists
Authors: Nadkarni Nalini M , Horns Joshua , Chen Jacqueline M , Morris Jeremy S , Bush Kelli , Scalice Daniella , Trivett Joslyn R , Anholt Allison 
Published: January 2022

AbstractScientists increasingly seek to respond to urgent calls for equity in science but may be unsure how to engage with underserved public groups. Prisons, jails, and detention centers are venues in which scientists may use their educational privilege to serve and empower diverse populations that are underserved by science education and underrepresented in science disciplines. We reversed the lens that traditionally focuses on the benefits of public engagement to the audience by documenting the impacts of delivering science lectures on the scientists who offered seminars to incarcerated people. The scientists who engaged in carceral settings gained professional benefits, shifted their preconceptions of incarcerated people, raised their perceived value of community engagement, and increased their interest in social justice. Some took direct actions for social change. This program could model effective engagement for other underserved groups in our society. We provide guidance to initiate such a program in other institutions.
Nonparametric causal mediation analysis for stochastic interventional (in)direct effects
Authors: Hejazi Nima S , Rudolph Kara E , Van Der Laan Mark J , Díaz Iván 
Published: January 2022

Summary
Causal mediation analysis has historically been limited in two important ways: (i) a focus has traditionally been placed on binary exposures and static interventions and (ii) direct and indirect effect decompositions have been pursued that are only identifiable in the absence of intermediate confounders affected by exposure. We present a theoretical study of an (in)direct effect decomposition of the population intervention effect, defined by stochastic interventions jointly applied to the exposure and mediators. In contrast to existing proposals, our causal effects can be evaluated regardless of whether an exposure is categorical or continuous and remain well-defined even in the presence of intermediate confounders affected by exposure. Our (in)direct effects are identifiable without a restrictive assumption on cross-world counterfactual independencies, allowing for substantive conclusions drawn from them to be validated in randomized controlled trials. Beyond the novel effects introduced, we provide a careful study of nonparametric efficiency theory relevant for the construction of flexible, multiply robust estimators of our (in)direct effects, while avoiding undue restrictions induced by assuming parametric models of nuisance parameter functionals. To complement our nonparametric estimation strategy, we introduce inferential techniques for constructing confidence intervals and hypothesis tests, and discuss open-source software, the $\texttt{medshift}$$\texttt{R}$ package, implementing the proposed methodology. Application of our (in)direct effects and their nonparametric estimators is illustrated using data from a comparative effectiveness trial examining the direct and indirect effects of pharmacological therapeutics on relapse to opioid use disorder.
Leptin-reactive antibodies are distinctly correlated with body composition parameters and metabolic risk indexes in children and adolescents
Authors: Vázquez-Solórzano Rafael , Valdés-Miramontes Elia , Porchas-Quijada Mildren , Enciso-Ramírez Mayra , Contreras-Mata Guadalupe A , Martínez-Moreno Alma Gabriela , Barajas-García Lourdes , Espinoza-García Astrid Selene , Reyes-Castillo Zyanya 
Published: January 2022

Abstract
Studies have demonstrated the presence of low-affinity immunoglobulins (Igs) directed to leptin, a key hormone of the neuroendocrine axis that regulates appetite and metabolism, in adult healthy subjects, patients with obesity, and type 2 diabetes mellitus. In the present exploratory study, IgG leptin-reactive antibodies were analyzed for the first time in children and adolescents according to body mass index (BMI) and were correlated with biochemical profile (lipid profile, insulin, glucose, and leptin) and metabolic risk indexes [homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for β-cell function (HOMA-β), atherogenic index of plasma (AIP)]. One hundred and thirty-six participants were included (children n = 63, adolescents n = 73). An in-house enzyme-linked immunosorbent assay (ELISA) test was performed to measure IgG anti-leptin antibodies (free, total, and immune complexes). In adolescents, free and total IgG anti-leptin antibodies levels were higher in groups with overweight or obesity than in normal-weight group (P &lt; 0.01), while in children, the total fractions were lower in groups with overweight and obesity than in normal weight (P &lt; 0.02). Immune complexes percentage showed opposite correlations with BMI in children (r = 0.4004, P = 0.0473) and adolescents (r = −0.3983, P = 0.0133). IgG anti-leptin antibodies were also correlated with HOMA-IR in children (r = −0.4569, P = 0.0217) and adolescents (r = −0.3589, P = 0.0316), and with AIP (r = −0.3608, P = 0.0261) in adolescents. Our data suggest that the production and affinity of IgG anti-leptin antibodies can be affected by age, body composition, and metabolic conditions; additionally, in normal conditions, IgG anti-leptin antibodies may have a protective role in insulin resistance and cardiovascular events.
Interferon-gamma and perforin-positive T cells in acquired aplastic anemia: implication in therapeutic response
Authors: Sharma Vandana , Kumar Prabin , Kumar Rajiv , Chakraborty Sushmita , Namdeo Manju , Sazawal Sudha , Kanga Uma , Seth Tulika , Mitra Dipendra Kumar 
Published: January 2022

Abstract
Acquired aplastic anemia (aAA) is an autoimmune disease, characterized by infiltration of T lymphocytes in the bone marrow with destruction of hematopoietic stem cells by the effector cells. Interferon-gamma (IFN-γ) and perforin are important mediators of cell destruction. In this flow cytometry-based study, we have investigated the percentage of intracellular IFN-γ+ and perforin+ CD5+ T cells in peripheral blood of newly diagnosed aAA patients before and after immunosuppressive therapy (IST). Patients were categorized as per standard disease severity and response to IST. The median percentage of IFN-γ+ and perforin+ CD5+ T cells was higher in untreated patients compared to healthy controls. The percentage of these cells was also increased in untreated severe and very severe aplastic anemia when compared with non-severe aplastic anemia patients. In patients before and after IST the median percentage of T cells producing IFN-γ and perforin was elevated in non-responders as compared to partial plus complete responders. The higher percentage of IFN-γ+ and perforin+ CD5+ T cells may be useful as an early diagnostic marker for aberrant activation of immune system and predict poor response to IST in aAA patients, who will benefit from alternative therapy.
RORγt+Foxp3+ regulatory T cells in the regulation of autoimmune arthritis
Authors: Furuyama Kotona , Kondo Yuya , Shimizu Masaru , Yokosawa Masahiro , Segawa Seiji , Iizuka Akira , Tanimura Reona , Tsuboi Hiroto , Matsumoto Isao , Sumida Takayuki 
Published: January 2022

Abstract
RORγt+Foxp3+regulatory T (Treg) cells, known as T regulatory 17 cells (Tr17 cells), are a novel subset of Treg cells, which have the potential to regulate the development of experimental autoimmune encephalomyelitis (EAE) thorough a specific repression of T helper 17 (Th17) cell-mediated inflammation. However, the function of Tr17 cells the development of other autoimmune diseases such as autoimmune arthritis remains unclear. Collagen-induced arthritis (CIA) was found to be prolonged in Foxp3creRORγtfl/fl mice, in which Tr17 cells were deleted, compared with Foxp3wtRORγtfl/fl mice. Tr17 cells were significantly increased in ankle joints (AJ) compared with draining lymph nodes after the onset of arthritis. CC chemokine receptor 6 (CCR6) was up-regulated on Tr17 cells compared to RORγt negative Treg cells. CD25, cytotoxic T-lymphocyte antigen 4 (CTLA-4), glucocorticoid-induced TNF-receptor (GITR), and inducible T-cell co-stimulator (ICOS) expression was also up-regulated on Tr17 cells compared to RORγt negative Treg cells. IL-10-producing cells and Blimp-1+ and T-bet+ cells were increased in Tr17 cells compared to RORγt-negative Treg cells. Tr17-enriched Treg cells significantly suppressed proliferation of conventional T cells through IL-10 compared with CCR6-Treg cells. Tr17 cells increased during the clinical course of CIA and accumulated in inflamed joints. Taken together, it appears that Tr17 cells play a crucial role in the regulation of autoimmune arthritis.
Intestinal anti-tissue transglutaminase IgA deposits as a complementary method for the diagnostic evaluation of celiac disease in patients with low-grade histological lesions
Authors: Roca María , Donat Ester , Masip Etna , Ballester Verónica , Gómez Isabel , SanFelix Mercedes , Ramos David , Calvo-Lerma Joaquim , Giner-Pérez Lola , Bolonio Miguel , Polo Begoña , Ribes-Koninckx Carmen 
Published: January 2022

Abstract
Evaluating the usefulness of intestinal anti-transglutaminase IgA (anti-TG2 IgA) deposits detection as a complementary or decision-supporting tool in the diagnosis of celiac disease (CD) in patients with low degree of enteropathy. Small intestinal biopsies (SIB) were performed from 2008 to 2017 in patients on suspicion of CD (positive CD serology and/or symptoms) referred to our Pediatric Gastroenterology Unit. We determined anti-TG2 IgA deposits by using double immunofluorescence in all the patients in whom Marsh 0 or Marsh 1 was detected in the conventional histological study and in a random selection of patients with clearly positive serology and histological Marsh 2–3 lesion. Seventy-five pediatric patients were split into three groups according to the final diagnosis: (i) 13 children with a Marsh 0 or 1, negative CD serology and final non-CD diagnosis; none presented intestinal anti-TG2 IgA deposits; (ii) 15 potential CD cases (Marsh 0 or 1 and CD-associated antibodies), detecting anti-TG2 IgA deposits in 12; on follow-up, another biopsy performed in 11/15 showed villi atrophy in seven and a Marsh 2 lesion in two of them, patients being finally diagnosed as CD cases; and (iii) 47 children with Marsh 2–3 histological lesion and final CD diagnosis; all of them had intestinal anti-TG2 IgA deposits. Anti-TG2 deposits are a useful complementary tool for CD diagnosis in pediatric population with digestive pathologies suggestive of CD. It is especially helpful in those with low-grade lesion, in which anti-TG2 deposits are predictive of the development of more severe lesions on follow-up.
Characterization of allergic inflammation in chronic uterine cervicitis
Authors: Ma Fei , Liu Jun , Lv Xiaodan , Liu Hua-Zhen , Yang Ping-Chang , Ning Yan 
Published: January 2022

Abstract
Female genital tract chronic inflammation is common in clinics; the pathogenesis is not fully understood yet. House dust mite (HDM) involves the pathogenesis of many chronic diseases in human. This study aims to identify HDM-specific allergic response in the cervix of patients with cervical inflammation. Patients (n = 80) with chronic cervicitis (CC) and non-CC control (NC) subjects (n = 80) were recruited into this study. Vaginal lavage fluids (VLF) were collected from CC patients and NC subjects. Cellular components and fluid part of VLF were separated by centrifugation, and analyzed by flow cytometry and enzyme-linked immunosorbent assay. We found that a portion (52 out of 80) of CC patients responded to HDM, manifesting positive skin prick test, and HDM-specific IgE and IgG was detected in the VLF (designated CCp patients). VLF of CCp patients showed a Th2-dominant profile. HDM-specific Th2 cells were detected in VLF in CCp patients. Exposure to HDM in the culture induced proinflammatory cytokine release from CCp VLF CD4+ T cells. Exposure to CCp VLF CD4+ T cell-conditioned medium induced de novo Th2 response. Direct exposure to HDM induced allergic response in the cervix of CCp patients. In summary, a portion of CC patients respond to HDM challenge in the cervix. Exposure to HDM induces an allergy-like response in the cervix of CCp patients.
Impairment of antigen-presenting function of peripheral γδ T cells in patients with sepsis
Authors: Yang Xue-Wei , Li Hong , Feng Ting , Zhang Wei , Song Xiang-Rong , Ma Cheng-Yong , Nie Menzhen , Wang Lijie , Tan Xiaojiao , Kang Yan , Liao Xuelian 
Published: January 2022

Abstract
Impairment of antigen-presenting functions is a key mechanism contributing to sepsis-induced immunosuppression. Recently, γδ T cells have been demonstrated as professional antigen-presenting cells (APCs); however, their role in sepsis remains unknown. In this in vitro study, the APC function of human peripheral γδ T cells was assessed using samples collected from 42 patients with sepsis and 27 age-matched healthy controls. The APC-related markers HLA-DR, CD27, CD80, and CCR7 on fresh γδT cells were significantly higher in patients with sepsis compared with matched controls; however, they responded poorly to 4-hydroxy-3-methyl-2-butenyl pyrophosphate (HMBPP) stimulation, characterized by the deactivation of these APC markers and impaired proliferation. Furthermore, the adhesion function of γδ T cells, essential for antigen presentation, was greatly reduced in patients with sepsis; for instance, in co-cultures with green fluorescent protein-expressing Escherichia coli, HMBPP-activated γδT cells from healthy individuals adhered to E. coli efficiently, whereas no such phenomenon was observed with respect to γδT cells from patients with sepsis. In line with these results, in co-cultures with isolated CD4+ αβ T cells, HMBPP-activated γδT cells of healthy individuals promoted the efficient proliferation of CD4+ αβ T cells, whereas γδT cells from patients with sepsis did not do so. In conclusion, our findings show that the antigen-presenting function of γδT cells is severely impaired in patients with sepsis and the mechanisms behind need further study.
LncRNA MIR155HG functions as a ceRNA of miR-223-3p to promote cell pyroptosis in human degenerative NP cells
Authors: Yang Wei , Huang Xu-Dong , Zhang Tao , Zhou You-Bin , Zou Yong-Cheng , Zhang Jian 
Published: January 2022

Abstract
Nucleus pulposus (NP) cell pyroptosis plays a critical role in the pathogenesis of intervertebral disk degeneration (IDD). MIR155 host gene (MIR155HG) is a long non-coding RNA with pro-inflammatory activity. However, very little is known about its role in NP cell pyroptosis. This study aimed to observe the impact of MIR155HG on cell pyroptosis and to explore the underlying mechanism in human degenerative NP cells. Our results demonstrated that MIR155HG expression was significantly increased in human degenerative NP tissue samples and showed a positive correlation with Pfirrmann score. Overexpression of MIR155HG through a lentiviral vector decreased miR-223-3p levels, up-regulated NLRP3 expression and induced cell pyroptosis in human degenerative NP cells. A ceRNA action mode was identified among MIR155HG, miR-223-3p, and NLRP3. The stimulatory effect of MIR155HG on human degenerative NP cell pyroptosis was significantly reversed by pretreatment with miR-223-3p mimic or NLRP3 siRNA. In summary, these data suggest that MIR155HG sponges miR-223-3p to promote NLRP3 expression, leading to induction of cell pyroptosis in human degenerative NP cells. Targeting MIR155HG could be a novel and promising strategy to slow down the progression of IDD.
Droplet digital PCR for identifying copy number variations in patients with primary immunodeficiency disorders
Authors: Woon See-Tarn , Mayes Julia , Quach Alexander , Longhurst Hilary , Ferrante Antonio , Ameratunga Rohan 
Published: January 2022

Abstract
Primary immunodeficiency disorders comprise a rare group of mostly monogenic disorders caused by inborn errors of immunity. The majority can be identified by either Sanger sequencing or next generation sequencing. Some disorders result from large insertions or deletions leading to copy number variations (CNVs). Sanger sequencing may not identify these mutations. Here we present droplet digital PCR as an alternative cost-effective diagnostic method to identify CNV in these genes. The data from patients with large deletions of NFKB1, SERPING1, and SH2D1A are presented.
Common brain cortical abnormality in smoking behavior and bipolar disorder: discriminant analysis using cortical thickness and surface area
Authors: Ohi Kazutaka , Takai Kentaro , Kuramitsu Ayumi , Sugiyama Shunsuke , Shioiri Toshiki 
Published: January 2022

Abstract
Cigarette smoking is highly prevalent among patients with bipolar disorder (BD). Structural brain abnormalities related to smoking behavior and BD risk are indicated by magnetic resonance imaging (MRI) studies. However, cortical alterations common to smoking behavior and BD remain unclear. Our purpose was to identify common cortical alterations between smoking behavior and BD. 3T MRI-based indices of cortical thickness and surface area using FreeSurfer were acquired from 166 healthy control (HC) nonsmokers, 39 HC smokers, 33 BD nonsmokers, and 18 BD smokers. A stepwise discriminant-function analysis (DFA) with cortical structures as predictors was performed to classify BD patients into nonsmokers and smokers. Next, DFAs with the selected structures as predictors were performed to discriminate smoking status or diagnostic status. Differences in the selected features among the four groups were examined. The first DFA showed that six brain features discriminated between nonsmokers and smokers among BD patients. The six brain features related to BD smoking status also discriminated between HCs and BD patients and HC nonsmokers and BD smokers. Among the six features, left insular thickness showed a negative additive effect of smoking status and BD diagnosis. Our findings suggest the common neurobiological involvement of insular thickness in smoking behavior and BDrisk.