bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shiga Toxin–Induced Complement-Mediated Hemolysis and Release of Complement-Coated Red Blood Cell–Derived Microvesicles in Hemolytic Uremic Syndrome
Authors: Arvidsson Ida , Ståhl Anne-lie , Manea Hedström Minola , Kristoffersson Ann-Charlotte , Rylander Christian , Westman Julia S. , Storry Jill R. , Olsson Martin L. , Karpman Diana 
Published: January 2015

Abstract
Shiga toxin (Stx)-producing Escherichia coli (STEC) cause hemolytic uremic syndrome (HUS). This study investigated whether Stx2 induces hemolysis and whether complement is involved in the hemolytic process. RBCs and/or RBC-derived microvesicles from patients with STEC-HUS (n = 25) were investigated for the presence of C3 and C9 by flow cytometry. Patients exhibited increased C3 deposition on RBCs compared with controls (p &lt; 0.001), as well as high levels of C3- and C9-bearing RBC-derived microvesicles during the acute phase, which decreased after recovery. Stx2 bound to P1k and P2k phenotype RBCs, expressing high levels of the Pk Ag (globotriaosylceramide), the known Stx receptor. Stx2 induced the release of hemoglobin and lactate dehydrogenase in whole blood, indicating hemolysis. Stx2-induced hemolysis was not demonstrated in the absence of plasma and was inhibited by heat inactivation, as well as by the terminal complement pathway Ab eculizumab, the purinergic P2 receptor antagonist suramin, and EDTA. In the presence of whole blood or plasma/serum, Stx2 induced the release of RBC-derived microvesicles coated with C5b-9, a process that was inhibited by EDTA, in the absence of factor B, and by purinergic P2 receptor antagonists. Thus, complement-coated RBC-derived microvesicles are elevated in HUS patients and induced in vitro by incubation of RBCs with Stx2, which also induced hemolysis. The role of complement in Stx2-mediated hemolysis was demonstrated by its occurrence only in the presence of plasma and its abrogation by heat inactivation, EDTA, and eculizumab. Complement activation on RBCs could play a role in the hemolytic process occurring during STEC-HUS.
Protective Immunity against Chlamydia trachomatis Can Engage Both CD4+ and CD8+ T Cells and Bridge the Respiratory and Genital Mucosae
Authors: Nogueira Catarina V. , Zhang Xuqing , Giovannone Nicholas , Sennott Erica L. , Starnbach Michael N. 
Published: January 2015

Abstract
Understanding the cellular populations and mechanisms responsible for overcoming immune compartmentalization is valuable for designing vaccination strategies targeting distal mucosae. In this study, we show that the human pathogen Chlamydia trachomatis infects the murine respiratory and genital mucosae and that T cells, but not Abs, elicited through intranasal immunization can protect against a subsequent transcervical challenge. Unlike the genital infection where CD8+ T cells are primed, yet fail to confer protection, we found that intranasal priming engages both CD4+ and CD8+ T cells, allowing for protection against genital infection with C. trachomatis. The protection is largely dependent on IFN-γ secretion by T cells. Moreover, different chemokine receptors are critical for C. trachomatis–specific CD4+ T cells to home to the lung, rather than the CXCR3- and CCR5-dependent migration observed during genital infection. Overall, this study demonstrates that the cross-mucosa protective immunity against genital C. trachomatis infection following intranasal immunization is not dependent on Ab response but is mediated by not only CD4+ T cells but also by CD8+ T cells. This study provides insights for the development of vaccines against mucosal pathogens that threaten reproductive health worldwide.
Cutting Edge: SHARPIN Is Required for Optimal NLRP3 Inflammasome Activation
Authors: Gurung Prajwal , Lamkanfi Mohamed , Kanneganti Thirumala-Devi 
Published: January 2015

Abstract
The NLRP3 inflammasome is a multimeric protein complex that is assembled in response to a wide array of pathogens and danger-associated molecular patterns. Despite the ability of NLRP3 to respond to diverse cues, the mechanisms controlling the assembly of this complex are contested. Recently published studies showed that HOIL-1, a member of the linear ubiquitin chain assembly complex, contributes to activation of the NLRP3 inflammasome. SHARPIN, along with HOIP and HOIL-1, constitute the linear ubiquitin chain assembly complex. In this study, we examined whether SHARPIN is required for the activation of the NLRP3 inflammasome. Using Sharpincpdm macrophages (deficient in SHARPIN expression), we demonstrate that SHARPIN is required for optimal activation of the NLRP3 inflammasome by both canonical and noncanonical stimuli. Furthermore, Sharpincpdm macrophages had dramatic defects on both the NF-κB and MAPK pathways, suggesting a role in transcriptional priming of the NLRP3 inflammasome. In conclusion, our study identified SHARPIN as a novel regulator of the NLRP3 inflammasome.
Cryoablation of lung malignancies recurring close to surgical clips following surgery: Report of three cases
Authors: Grasso Rosario R , Luppi Giacomo , Cazzato Roberto L , Vescovo Riccardo Del , Giurazza Francesco , Mercurio Simona , Faiella Eliodoro , Zobel Bruno Beomonte 
Published: January 2015

Abstract
Background: Minimally ablative therapies are now available for the treatment of lung malignancies. However, selection of the appropriate technique is not always easy and requires accurate preoperative planning. Aims: To describe the treatment of lung tumors with cryoablation. Settings and Design: We report three cases of lung malignancies that recurred close to surgical clips after surgical treatment, successfully treated by cryoablation. Materials and Methods: An initial freezing cycle was performed for 10 min, followed by a 5-min thawing cycle, and an additional 10-min freezing cycle. A final 5-min thaw was necessary to remove the needle from the iceball formed during the freezing cycle. Results: The procedures were completed successfully with no signs of surgical-clip misplacement, and excellent ablation of the lesions. Conclusion: Cryoablation is a relatively new procedure that potentially permits the local treatment of lung tumors with minimal loss of lung parenchyma.
Trans-orbital orbitocranial penetrating injury by pointed iron rod
Authors: Tewari Vinod Kumar , Dubey Ram Shringar , Dubey Gyan Chand 
Published: January 2015

ABSTRACTTrans-orbital orbitocranial penetrating injury (TOPI) by a foreign body is an extremely rare compound head injury having a potential to cause major morbidity and mortality. Preoperative radiological imaging by CT scan is very important for operative guidance, but in remote area where CT scan is not available, the patient is generally referred to tertiary level. Here we present a case which was dealt successfully without CT scan, only on the basis of stable clinical status and X-rays. We present a case of a 35-year-old man who had an accidental injury (fall from height) by rod. Immediate X-ray (anteroposterior and lateral views) revealed that the pointed end of the foreign body (rod) was inside the ipsilateral anterior fossa via basifrontal bone up to frontal vertex, not crossing the midline. CT scan was not available and his vitals with GCS were normal (15/15). He was operated with the help of an ophthalmic surgeon by right frontotemporal craniotomy. The patient was discharged on 10th day without any neurological deficit except restricted right eyeball movement to superolateral and ptosis. The restricted eyeball movements recovered after third month of follow up with remnant ptosis for 2 years. This case highlights an unusual case, direct visualization and repair of brain structures with higher antibiotics can save the life even in remote areas where CT scan is still not available only on the basis of stable GCS and X-rays.
Subependymal hemorrhage following drainage of chronic subdural hematoma: Probable causative mechanisms and prevention strategies
Authors: Savardekar Amey R. , Salunke Pravin 
Published: January 2015

ABSTRACTChronic subdural hematoma (cSDH) is a common clinical entity treated by neurosurgeons with good cure rates. Recurrence of the hematoma and failure of the brain to re-expand are commonly observed complications following surgery for cSDH. An intracerebral or intraventricular hemorrhage following evacuation of cSDH is very rarely observed, albeit with devastating consequences. We report the finding of a subependymal hemorrhage after evacuation of a cSDH and discuss the probable causative mechanisms underlying this rare occurrence and the prevention strategies to avoid it.
Aspectos éticos y deontológicos de la actividad periodística online. Su percepción por los profesionales
Authors: Suárez Villegas Juan Carlos 
Published: January 2015

Los periodistas digitalesde tres países de la UE (Bélgica, España e Italia) mantienen que el ejercicio ético del periodismo depende tanto de los valores personales y profesionales del periodista como de factoresexternos: empresariales, económicos, políticos y tecnológico. La ética, por tanto, se ve afectada por las condiciones de trabajos, así como con la tecnología con los que se desarrolla la actividad profesional. No obstante, el grado de independencia del medio en el que se trabaja y los valores del profesional de la información son percibidos como los más influyentes, mientras que la interacción con los públicos y la respuesta, u opinión de éstos se sitúa en un segundo plano.
Enforcement Matters: Reframing the Philosophical Debate over Immigration
Authors: Mendoza José Jorge 
Published: January 2015

ABSTRACT
In debating the ethics of immigration, philosophers have focused much of their attention on determining whether a political community ought to have the discretionary right to control immigration. They have not, however, given the same amount of consideration to determining whether there are any ethical limits on how a political community enforces its immigration policy. This article, therefore, offers a different approach to immigration justice. It presents a case against legitimate states having discretionary control over immigration by showing both how ethical limits on enforcement circumscribe the options legitimate states have in determining their immigration policy and how all immigrants (including undocumented immigrants) are entitled to certain protections against a state's enforcement apparatus.
Lessons from America's Public Philosopher
Authors: Weber Eric Thomas 
Published: January 2015

ABSTRACT
This article argues for a definition of public philosophy inspired by John Dewey's understanding of the “supreme intellectual obligation.” The first section examines five strong reasons why more public philosophy is needed and why the growing movement in public philosophy should be encouraged. The second section begins with a review of common understandings of public philosophy as well as some initial challenges that call for widening our conception of the practice. Then, it applies Dewey's argument in “The Supreme Intellectual Obligation” to public philosophy, which must not be seen simply as a one-way street from intellectuals to the masses but, rather, as the task of fostering the scientific attitude and intellectual habits of mind in all citizens.
Rescue of an In Vitro Neuron Phenotype Identified in Niemann-Pick Disease, Type C1 Induced Pluripotent Stem Cell-Derived Neurons by Modulating the WNT Pathway and Calcium Signaling
Authors: Efthymiou Anastasia G. , Steiner Joe , Pavan William J. , Wincovitch Stephen , Larson Denise M. , Porter Forbes D. , Rao Mahendra S. , Malik Nasir 
Published: January 2015

Abstract

Niemann-Pick disease, type C1 (NPC1) is a familial disorder that has devastating consequences on postnatal development with multisystem effects, including neurodegeneration. There is no Food and Drug Administration-approved treatment option for NPC1; however, several potentially therapeutic compounds have been identified in assays using yeast, rodent models, and NPC1 human fibroblasts. Although these discoveries were made in fibroblasts from NPC1 subjects and were in some instances validated in animal models of the disease, testing these drugs on a cell type more relevant for NPC1 neurological disease would greatly facilitate both study of the disease and identification of more relevant therapeutic compounds. Toward this goal, we have generated an induced pluripotent stem cell line from a subject homozygous for the most frequent NPC1 mutation (p.I1061T) and subsequently created a stable line of neural stem cells (NSCs). These NSCs were then used to create neurons as an appropriate disease model. NPC1 neurons display a premature cell death phenotype, and gene expression analysis of these cells suggests dysfunction of important signaling pathways, including calcium and WNT. The clear readout from these cells makes them ideal candidates for high-throughput screening and will be a valuable tool to better understand the development of NPC1 in neural cells, as well as to develop better therapeutic options for NPC1.
Continued Homelessness and Depressive Symptoms in Older Adults
Authors: Dobbins Sarah K. , Garcia Cheyenne M. , Evans Jennifer L. , Valle Karen , Guzman David , Kushel Margot B. 
Published: August 2024

ImportanceDepression is common in adults experiencing homelessness. It is unclear whether continued homelessness is associated with more depressive symptoms.ObjectiveTo examine the association between residential status and depressive symptoms in adults aged 50 years or older experiencing homelessness at study entry.Design, Setting, and ParticipantsThis cohort study analyzed results from the Health Outcomes of People Experiencing Homelessness in Older Middle Age (HOPE HOME) project, which in 2013 began enrolling adults aged 50 years or older experiencing homelessness in Oakland, California, and conducted structured interviews every 6 months for a mean duration of 5.5 years through 2023 (for this cohort study). Eligible participants included those aged 50 years or older, able to speak English, and experiencing homelessness at enrollment. We analyzed data collected from 2013 to 2023.ExposuresThe exposure of interest was residential status. At follow-up visits, residential status was categorized as (1) homelessness (meeting the HEARTH [Homeless Emergency Assistance and Rapid Transition to Housing] Act definition) or (2) housed (living in a noninstitutional environment and not meeting the HEARTH Act definition).Main Outcomes and MeasuresThe primary outcome was moderate to severe depressive symptoms (with Center for Epidemiologic Studies–Depression [CES-D] scale score ≥22). The augmented inverse probability of treatment weighting (AIPTW) approach was used to examine the association between continued homelessness and depressive symptoms. The AIPTW adjusted for the following variables: number of chronic health conditions, age, sex, visiting a health care practitioner, receiving outpatient mental health treatment, receiving mental health medication, exposure to abuse, substance use disorder, and binge drinking.ResultsThe cohort was composed of 450 participants, of whom 343 (76.2%) were males, and the mean (SD) age was 58.5 (5.2) years. Participants completed a median (IQR) of 8.9 (8-11) follow-up visits. With 1640 person-years of observation time, participants continued homelessness for 880 person-years (57.1%) and experienced being housed for 715 person-years (44.3%). Many participants (304 [78.0%]) were housed during at least 1 follow-up visit. The odds of a CES-D scale score of 22 or higher was significantly higher among participants who continued experiencing homelessness than among housed participants (marginal causal odds ratio, 1.08; 95% CI, 1.04-1.11; P &amp;lt; .001).Conclusions and RelevanceThis cohort study found that continued homelessness was associated independently with increased odds of depressive symptoms. Obtaining housing may have a favorable role in depression and overall well-being of older adults experiencing homelessness and may be considered as a mental health intervention.
Suicide Attempt and Suicide Death Among Spouses of Patients With Cancer
Authors: Liu Qianwei , Yang Fen , László Krisztina D. , Hu Kejia , Feychting Maria , Wei Dang , Fall Katja , Valdimarsdóttir Unnur , Li Jiong , Fang Fang 
Published: August 2024

ImportanceLittle is known about the risk of suicidal behavior in relation to having a spouse with a cancer diagnosis.ObjectiveTo estimate the risk of suicide attempt and suicide death among spouses of patients with cancer.Design, Setting, and ParticipantsThis nationwide cohort study in Denmark collected registry-based data from 1986 through 2016. Analyses were performed from August 8, 2022, to October 30, 2023. Individuals who had a spouse with a cancer diagnosed during 1986 to 2015 were compared with individuals whose spouse did not have a cancer diagnosis during the same period, randomly selected from the general population and matched by birth year and sex.ExposureHaving a spouse with a cancer diagnosis.Main Outcomes and MeasuresSuicide attempt was identified through the Danish National Patient Register and the Danish Psychiatric Central Research Register, whereas suicide death was identified through the Danish Causes of Death Register, through 2016. Flexible parametric and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for suicide attempt and suicide death among spouses of patients with a cancer diagnosis.ResultsThe study included 409 338 exposed individuals and 2 046 682 unexposed individuals (median [IQR] age at cohort entry for both groups, 63 [54-70] years; 55.4% women). During the follow-up, 2714 incident cases of suicide attempt among exposed individuals (incidence rate [IR], 62.6 per 100 000 person-years) and 9994 among unexposed individuals (IR, 50.5 per 100 000 person-years) were identified, as well as 711 cases of suicide death among the exposed individuals (IR, 16.3 per 100 000 person-years) and 2270 among the unexposed individuals (IR, 11.4 per 100 000 person-years). An increased risk of suicide attempt (HR, 1.28; 95% CI, 1.23-1.34) and suicide death (HR, 1.47; 95% CI, 1.35-1.60) was observed among spouses of patients with cancer throughout the follow-up. The increased risk was particularly notable during the first year after the cancer diagnosis, with an HR of 1.45 (95% CI, 1.27-1.66) for suicide attempt and 2.56 (95% CI, 2.03-3.22) for suicide death. There was a greater risk increase for both suicide attempt and suicide death when the cancer was diagnosed at an advanced stage or when the spouse died after the cancer diagnosis.Conclusions and RelevanceThese findings suggest a need for clinical and societal awareness to prevent suicidal behaviors among spouses of patients with cancer, particularly during the first year following the cancer diagnosis.
Vitreoretinopathy in Asymptomatic Children With CTNNB1 Syndrome
Authors: Bedoukian Emma C. , Forbes Grace , Scoles Drew 
Published: August 2024

ImportancePrevious studies have identified familial exudative vitreoretinonpathy (FEVR) in patients with CTNNB1 syndrome based on severe congenital ocular phenotypes. However, ophthalmoscopy may not be sufficient to detect vision-threatening vitreoretinopathy in all patients.ObjectiveTo report a consecutive retrospective case series of 11 patients with CTNNB1 variants who had previously unremarkable ophthalmoscopic examination results and to describe their detailed ophthalmic phenotypes.Design, Setting, and ParticipantsThis retrospective case series was conducted at the Children’s Hospital of Philadelphia from October 2022 to November 2023 among patients with identified variants in CTNNB1 and previously documented normal results in office retinal examinations. These consecutive patients subsequently underwent an examination under anesthesia with fluorescein angiography. Detailed genotype information was analyzed for all patients, and each variant was mapped on the CTNNB1 gene to observe any associations with severity of vitreoretinopathy.Main Outcomes and MeasuresNumber of patients with vitreoretinopathy and number requiring treatment for vitreoretinopathy.ResultsThe mean (SD) age at the time of CTNNB1 syndrome diagnosis was 2 (1) years, and the mean (SD) age at examination was 6 (3) years for the 11 total patients. A total of 9 patients had a diagnosis of strabismus, and 5 patients had undergone strabismus surgery. FEVR was present in 5 of 11 patients and in 9 eyes. The presence of disease requiring treatment was identified in 6 eyes, including 1 retinal detachment. Detailed genotype analysis of the patients found no clearly delineated high-risk loci in CTNNB1 in association with high severity of FEVR.Conclusions and RelevanceIn this case series study, nearly all patients with CTNNB1 syndrome required ophthalmic care for refractive error and strabismus, and a subset also required treatment for FEVR. These findings support consideration of ultra-widefield fluorescein angiography among individuals with CTNNB1 syndrome when feasible, including the use of sedation if such an assessment is not possible in the office setting.
Cell‐Specific Transposable Element and Gene Expression Analysis Across Systemic Lupus Erythematosus Phenotypes
Authors: Cutts Zachary , Patterson Sarah , Maliskova Lenka , Taylor Kimberly E. , Ye Chun Jimmie , Dall'Era Maria , Yazdany Jinoos , Criswell Lindsey A. , Fragiadakis Gabriela K. , Langelier Charles , Capra John A. , Sirota Marina , Lanata Cristina M. 
Published: August 2024

ObjectiveThere is an established yet unexplained link between interferon (IFN) and systemic lupus erythematosus (SLE). The expression of sequences derived from transposable elements (TEs) may contribute to SLE phenotypes, specifically production of type I IFNs and generation of autoantibodies.MethodsWe profiled cell‐sorted RNA‐sequencing data (CD4+ T cells, CD14+ monocytes, CD19+ B cells, and natural killer cells) from peripheral blood mononuclear cells of 120 patients with SLE and quantified TE expression identifying 27,135 TEs. We tested for differential TE expression across 10 SLE phenotypes, including autoantibody production and disease activity.ResultsWe found 731 differentially expressed (DE) TEs across all SLE phenotypes that were mostly cell specific and phenotype specific. DE TEs were enriched for specific families and open reading frames of viral genes encoded in TE sequences. Increased expression of DE TEs was associated with genes involved in antiviral activity, such as LY6E, ISG15, and TRIM22, and pathways such as IFN signaling.ConclusionThese findings suggest that expression of TEs contributes to activation of SLE‐related mechanisms in a cell‐specific manner, which can impact disease diagnostics and therapeutics.
Robust fixed‐point Kalman smoother for bilinear state‐space systems with non‐Gaussian noise and parametric uncertainties
Authors: Wang Xuehai , Liu Yage , Zhao Sirui 
Published: August 2024

SummaryKalman smoother is an effective algorithm to estimate the state of the dynamic systems with Gaussian noise. However, when the system is affected by non‐Gaussian noise, the traditional Kalman smoother may suffer severe performance degradation, since it is derived from the minimum mean square error criterion. By introducing the maximum correntropy criterion, which accounts for all higher order moments and has the ability to resist non‐Gaussian noise, this article studies the state estimation problem of the bilinear state‐space system with non‐Gaussian noises and parametric uncertainties. The bilinear system with parametric uncertainties is transformed into a linear time‐varying system, and a robust fixed‐point Kalman filter algorithm is derived based on the Cauchy kernel‐based correntropy criterion. To improve the state estimation accuracy, a Cauchy kernel‐based fixed‐point Kalman smoother (CK‐FPKS) algorithm is presented by introducing the backward smoothing. Simulation results show the effectiveness of the proposed algorithm.