Miracle-dz/UniFAR-FTUs huggingface dataset:
Inherited Kidney Complement Diseases

In the past 20 years, we have witnessed tremendous advances in our ability to diagnose and treat genetic diseases of the kidney caused by complement dysregulation. Staggering progress was realized toward a better understanding of the genetic underpinnings and pathophysiology of many forms of atypical hemolytic uremic syndrome (aHUS) and C3-dominant glomerulopathies that are driven by complement system abnormalities. Many of these seminal discoveries paved the way for the design and characterization of several innovative therapies, some of which have already radically improved patients’ outcomes. This review offers a broad overview of the exciting developments that have occurred in the recent past, with a particular focus on single-gene (or Mendelian), complement-driven aHUS and C3-dominant glomerulopathies that should be of interest to both nephrologists and kidney researchers. The discussion is restricted to genes with robust associations with both aHUS and C3-dominant glomerulopathies (complement factor H, complement component 3, complement factor H–related proteins) or only aHUS (complement factor B, complement factor I, and membrane cofactor protein). Key questions and challenges are highlighted, along with potential avenues for future directions.
Individual, household and environmental factors associated with arboviruses in rural human populations, Brazil

Landscape change is one of the foremost drivers of the emergence of infectious diseases. Exploring demographic, household and environmental conditions under which infectious diseases occur may inform strategies to prevent disease emergence in human populations. We collected blood samples from 523 humans and explore factors for arbovirus emergence in Bahia, Brazil. The overall arbovirus seroprevalence was 65.2%, with the genus Flavivirus most prevalent (64.4%). Based on monotypic reactions, the population had contact with five arbovirus: Dengue 3, Ilheus, Oropouche, Caraparu and Eastern equine encephalitis virus. To our knowledge, this is the first study reporting exposure to Oropouche, Caraparu and Eastern equine encephalitis virus in human populations in Bahia, Northeast of Brazil. The best model fit demonstrated that household and environmental variables were more predictive of the risk of arbovirus exposure than demographic variables. The presence of forest and free‐living monkeys in the areas close to the communities had a protective effect for the human population (i.e. lower seroprevalence). The dilution effect is considered as one explanation for this finding. These results highlight the important ecological role of wildlife‐friendly agriculture.
Transient forebrain ischemia under hyperthermic condition accelerates memory impairment and neuronal death in the gerbil hippocampus by increasing NMDAR1 expression

Altered expression levels of N-methyl-D-aspartate receptor (NMDAR), a ligand-gated ion channel, have a harmful effect on cellular survival. Hyperthermia is a proven risk factor of transient forebrain ischemia (tFI) and can cause extensive and severe brain damage associated with mortality. The objective of the present study was to investigate whether hyperthermic preconditioning affected NMDAR1 immunoreactivity associated with deterioration of neuronal function in the gerbil hippocampal CA1 region following tFI via histological and western blot analyses. Hyperthermic preconditioning was performed for 1 h before tFI, which was developed by ligating common carotid arteries for 5 min. tFI-induced cognitive impairment under hyperthermia was worse compared with that under normothermia. Loss (death) of pyramidal neurons in the CA1 region occurred fast and was more severe under hyperthermia compared with that under normothermia. NMDAR1 immunoreactivity was not observed in the somata of pyramidal neurons of sham gerbils with normothermia. However, its immunoreactivity was strong in the somata and processes at 12 h post-tFI. Thereafter, NMDAR1 immunoreactivity decreased with time after tFI. On the other hand, NMDAR1 immunoreactivity under hyperthermia was significantly increased in the somata and processes at 6 h post-tFI. The change pattern of NMDAR1 immunoreactivity under hyperthermia was different from that under normothermia. Overall, accelerated tFI-induced neuronal death under hyperthermia may be closely associated with altered NMDAR1 expression compared with that under normothermia.
The experiences of Indian people living in New Zealand with stroke

Abstract Purpose Stroke can cause lifelong disability and participatory limitations. Stroke survivors thus manage their recovery long term. Health professionals can support self-management, tailoring this support to be culturally appropriate. This study explored the unique culture and ethnicity specific experiences of Indian people living in New Zealand with stroke, focussing on self-management and facilitators and challenges to recovery. Methods Eight individuals with stroke took part in semi-structured interviews. Data were analysed using the General Inductive Approach. Results Four themes were identified: (1) helping myself, in any way that I can, (2) family and support, (3) social connections, and (4) ethnicity was not a barrier. Conclusion All participants felt well looked after within the New Zealand healthcare context but highlighted the need for long term support. Self-management strategies participants considered important included changes to their diet, acceptance by oneself and society, returning to work, the role of family, and the use of technology and social media. Health professionals should consider these factors when providing self-management support to individuals of Indian ethnicity. IMPLICATIONS FOR REHABILITATION Advice and help around diet, lifestyle, and return to work were important priorities identified by our Indian stroke survivor participants. Our Indian stroke survivor participants requested more long-term specialist support and stroke information. Although the family willingly take increased responsibility for the wellbeing of the individual with stroke, it is not a substitute for professional input which needs to be tailored and offered proactively.
Images Are Data: A Breast Imaging Perspective on a Contemporary Paradigm

Abstract Background Considering radiological examinations not as mere images, but as a source of data, has become the key paradigm in the diagnostic imaging field. This change of perspective is particularly popular in breast imaging. It allows breast radiologists to apply algorithms derived from computer science, to realize innovative clinical applications, and to refine already established methods. In this context, the terminology “imaging biomarker”, “radiomics”, and “artificial intelligence” are of pivotal importance. These methods promise noninvasive, low-cost (e. g., in comparison to multigene arrays), and workflow-friendly (automated, only one examination, instantaneous results, etc.) delivery of clinically relevant information. Methods and Results This paper is designed as a narrative review on the previously mentioned paradigm. The focus is on key concepts in breast imaging and important buzzwords are explained. For all areas of breast imaging, exemplary studies and potential clinical use cases are discussed. Conclusion Considering radiological examination as a source of data may optimize patient management by guiding individualized breast cancer diagnosis and oncologic treatment in the age of precision medicine. Key Points: In conventional breast imaging, examinations are interpreted based on patterns perceivable by visual inspection. The radiomics paradigm treats breast images as a source of data, containing information beyond what is visible to our eyes. This results in radiomic signatures that may be considered as imaging biomarkers, as they provide diagnostic, predictive, and prognostic information. Radiomics derived imaging biomarkers may be used to individualize breast cancer treatment in the era of precision medicine. The concept and key research of radiomics in the field of breast imaging will be discussed in this narrative review. Citation Format Dietzel M, Clauser P, Kapetas P et al. Images Are Data: A Breast Imaging Perspective on a Contemporary Paradigm. Fortschr Röntgenstr 2021; 193: 898 – 908
Monogenic Causes in the Type 1 Diabetes Genetics Consortium Cohort: Low Genetic Risk for Autoimmunity in Case Selection

Abstract Hypothesis About 1% of patients clinically diagnosed as type 1 diabetes have non-autoimmune monogenic diabetes. The distinction has important therapeutic implications but, given the low prevalence and high cost of testing, selecting patients to test is important. We tested the hypothesis that low genetic risk for type 1 diabetes can substantially contribute to this selection. Methods As proof of principle, we examined by exome sequencing families with 2 or more children, recruited by the Type 1 Diabetes Genetics Consortium (T1DGC) and selected for negativity for 2 autoantibodies and absence of risk human leukocyte antigen haplotypes. Results We examined 46 families that met the criteria. Of the 17 with an affected parent, 7 (41.2%) had actionable monogenic variants. Of 29 families with no affected parent, 14 (48.3%) had such variants, including 5 with recessive pathogenic variants of WFS1 but no report of other features of Wolfram syndrome. Our approach diagnosed 55.8% of the estimated number of monogenic families in the entire T1DGC cohort, by sequencing only 11.1% of the autoantibody-negative ones. Conclusions Our findings justify proceeding to large-scale prospective screening studies using markers of autoimmunity, even in the absence of an affected parent. We also confirm that nonsyndromic WFS1 variants are common among cases of monogenic diabetes misdiagnosed as type 1 diabetes.
Exercise-Induced Release of Cardiac Troponins in Adolescent vs. Adult Swimmers

To examine the exercise-induced release of cardiac troponin T (cTnT) in adolescent and adult swimmers. Thirty-two trained male (18 adolescents, 14 adults) swam at maximal pace in a 45 min distance trial, and blood samples were drawn before, immediately and 3 h after exercise for subsequent cTnT analysis and comparison. Having comparable training experience and baseline values of cTnT (p = 0.78 and p = 0.13), adults exercised at lower absolute and relative intensity (p < 0.001 and p < 0.001, respectively), but presented higher immediate cTnT after exercise than adolescents (p < 0.001). Despite that, peak concentrations were observed at 3 h post exercise and peak elevations were comparable between groups (p = 0.074). Fourteen (44%) apparently healthy subjects exceeded the cutoff value for myocardial infarction (MI). Adolescents presented a delayed elevation of cTnT compared with adults, but achieved similar peak values.
Krüppel-Like Factor 14 Deletion In Myeloid Cells Accelerates Atherosclerotic Lesion Development.

AIMS Atherosclerosis is the dominant pathologic basis of many cardiovascular diseases. Large genome-wide association studies have identified that single nucleotide polymorphisms proximal to Krüppel-like factor 14 (KLF14), a member of the zinc finger family of transcription factors, are associated with higher cardiovascular risks. Macrophage dysfunction contributes to atherosclerosis development and has been recognized as a potential therapeutic target for treating many cardiovascular diseases. Herein, we address the biologic function of KLF14 in macrophages and its role during the development of atherosclerosis. METHODS AND RESULTS KLF14 expression was markedly decreased in cholesterol-loaded foam cells, and overexpression of KLF14 significantly increased cholesterol efflux and inhibited the inflammatory response in macrophages. We generated myeloid cell-selective Klf14 knockout (Klf14LysM) mice in the ApoE-/- background for the atherosclerosis study. Klf14LysMApoE-/- and litter-mate control mice (Klf14fl/flApoE-/-) were placed on the Western Diet for 12 weeks to induce atherosclerosis. Macrophage Klf14 deficiency resulted in increased atherosclerosis development without affecting the plasma lipid profiles. Klf14-deficient peritoneal macrophages showed significantly reduced cholesterol efflux resulting in increased lipid accumulation and exacerbated inflammatory response. Mechanistically, KLF14 upregulates the expression of a key cholesterol efflux transporter, ABCA1 (ATP-binding cassette transporter A1), while suppresses the expression of several critical components of the inflammatory cascade. In macrophages, activation of KLF14 by its activator, perhexiline, a drug clinically used to treat angina, significantly inhibited the inflammatory response and increased cholesterol efflux in a KLF14- dependent manner in macrophages without triggering hepatic lipogenesis. CONCLUSIONS This study provides insights into the anti-atherosclerotic effects of macrophage KLF14 through promoting cholesterol efflux and suppressing the inflammatory response. Activation of KLF14 may represent a potential new therapeutic approach to prevent or treat atherosclerosis. TRANSLATIONAL PERSPECTIVE Here, using both gain- and loss-of-function strategies, we show that KLF14 regulates cholesterol efflux by regulating the expression of ABCA1 and inhibits inflammatory response in macrophages. These findings, along with our previous data, put activation of KLF14 forward as a prospective therapeutic target for atherosclerotic cardiovascular disease.
Macrophages inhibit and enhance endometriosis depending on their origin

Significance Endometriosis is a chronic, incurable inflammatory disorder impacting 190 million women worldwide. Immune cells called macrophages are implicated in promoting endometriosis. Macrophages have different origins and their origin can dictate function. In this study we demonstrate that endometriotic lesion-resident macrophages are derived from the uterine lining (endometrium), the abdominal (peritoneal) cavity, and recruited bone-marrow precursors (monocytes). Endometriosis triggers continuous recruitment of monocytes that differentiate into macrophages that differ from those usually present within the peritoneal cavity. By depleting different populations, we demonstrate that endometrial macrophages are “proendometriosis” while monocyte-derived peritoneal macrophages are “antiendometriosis” acting to protect the cavity from lesion establishment. In the future, immune-based therapies may allow targeting of prodisease macrophages and/or harnessing of antiendometriosis macrophages in endometriosis. Macrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increases the number of lesions. Reprogramming the ontogeny of peritoneal macrophages such that embryo-derived LpM are replaced by monocyte-derived LpM decreases the number of lesions that develop. We propose a putative model whereby endometrial macrophages are “proendometriosis” while newly recruited monocyte-derived macrophages, possibly in LpM form, are “antiendometriosis. ” These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.
Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young children. The T cell response plays a critical role in facilitating clearance of an acute RSV infection, and memory T cell responses are vital for protection against secondary RSV exposures. Tissue-resident memory (TRM) T cells have been identified as a subset of memory T cells that reside in nonlymphoid tissues and are critical for providing long-term immunity. There is currently limited information regarding the establishment and longevity of TRM T cell responses elicited following an acute RSV infection as well as their role in protection against repeated RSV infections. In this study, we examined the magnitude, phenotype, and protective capacity of TRM CD4 and CD8 T cells in the lungs of BALB/c mice following an acute RSV infection. TRM CD4 and CD8 T cells were established within the lungs and waned by 149 d following RSV infection. To determine the protective capacity of TRMs, FTY720 administration was used to prevent trafficking of peripheral memory T cells into the lungs prior to challenge of RSV-immune mice, with a recombinant influenza virus expressing either an RSV-derived CD4 or CD8 T cell epitope. We observed enhanced viral clearance in RSV-immune mice, suggesting that TRM CD8 T cells can contribute to protection against a secondary RSV infection. Given the protective capacity of TRMs, future RSV vaccine candidates should focus on the generation of these cell populations within the lung to induce effective immunity against RSV infection.
Detecting High Frequency Oscillations for Stereoelectroencephalography in Epilepsy via Hypergraph Learning

Successful epilepsy surgeries depend highly on pre-operative localization of epileptogenic zones. Stereoelectroencephalography (SEEG) records interictal and ictal activities of the epilepsy in order to precisely find and localize epileptogenic zones in clinical practice. While it is difficult to find distinct ictal onset patterns generated the seizure onset zone from SEEG recordings in a confined region, high frequency oscillations are commonly considered as putative biomarkers for the identification of epileptogenic zones. Therefore, automatic and accurate detection of high frequency oscillations in SEEG signals is crucial for timely clinical evaluation. This work formulates the detection of high frequency oscillations as a signal segment classification problem and develops a hypergraph-based detector to automatically detect high frequency oscillations such that human experts can visually review SEEG signals. We evaluated our method on 4,000 signal segments from clinical SEEG recordings that contain both ictal and interictal data obtained from 19 patients who suffer from refractory focal epilepsy. The experimental results demonstrate the effectiveness of the proposed detector that can successfully localize interictal high frequency oscillations and outperforms multiple peer machine learning methods. In particular, the proposed detector achieved 90.7% in accuracy, 80.9% in sensitivity, and 96.9% in specificity.
Trauma and Maternal Caregivers as Risks for Executive Function Deficits Among Youth Who Have Sexually Harmed

Despite robust research linking trauma events to the commission of sexual harm by youth, the majority of victims do not become victimizers, imploring us to study potential interceding influences. Some research indicates that intermediary factors like attachment characteristics, trauma symptomatology, and executive functioning may be critical in understanding sexual harm committed by youth. This study explored relationships between trauma events, trauma symptoms, and attachment characteristics, and their relationship to executive functioning in a sample of 196 youth who committed sexual harm. Results revealed bivariate associations between trauma events, symptomatology, and maternal attachment characteristics. Structural equation modeling revealed numerous direct and indirect effects on the path to deficits in executive functioning, and that sexual abuse, above and beyond other forms of traumatic events, contributed to executive functioning deficits via trauma symptoms. The results are contextualized and implications are discussed.
Recent Trends in Creatinine Assays in Korea: Long-Term Accuracy-Based Proficiency Testing Survey Data by the Korean Association of External Quality Assessment Service (2011–2019)

Background Accurate serum creatinine (Cr) concentration measurement is essential for evaluating kidney function. In 2011, the Korean Association of External Quality Assessment Service (KEQAS) launched an accuracy-based Cr proficiency testing (ABCr PT) survey. We analyzed long-term data of the KEQAS ABCr PT survey collected between 2011 and 2019 to assess recent trends in Cr assays in Korea. Methods The ABCr PT survey including three commutable fresh-frozen serum samples was performed twice a year. The target Cr concentration was assigned using isotope-dilution mass spectrometry. We analyzed data obtained from the participating laboratories, calculated the yearly bias, and evaluated bias trends for the major reagents and instruments. Outliers were excluded from all analysis. Results The mean percentage bias based on the total data of all participating laboratories was 10.8% in the 2011-A survey and 0.2% in 2019-B survey. Bias for the major reagents and instruments differed depending on the manufacturer. Enzymatic assays generally showed desirable bias ranging from –3.9% to 3.2% at all Cr concentrations and lower interlaboratory variability than non-enzymatic assays (enzymatic vs. non-enzymatic, 3.3%–7.2% vs. 6.3%–9.1%). Conclusions Although the mean percentage bias of Cr assays tends to decrease over time, it is necessary to continuously strive to improve Cr assay accuracy, especially at low concentrations.
Intrathecal Baclofen Pump Infection With Meningitis: Effective Treatment by Radical Debridement and Intrareservoir Baclofen–Vancomycin Co‐Infusion

Intrathecal baclofen pump associated central nervous system (CNS) infection and meningitis is a rare but serious complication and may have dire consequences. Due to bacterial biofilm formation, the optimal treatment strategy is usually for removal of the pump, followed by systemic antibiotics for treatment of local and CNS infection. We describe this case of a patient with recurrent Staphylococcus aureus pump site empyema and meningitis leading to status dystonicus, who was successfully managed with radical debridement and intrareservoir baclofen–vancomycin co‐infusion.