Miracle-dz/UniFAR-FTUs huggingface dataset:
CT Lung Abnormalities after COVID-19 at 3 Months and 1 Year after Hospital Discharge

Background Data on the long-term pulmonary sequelae in COVID-19 are lacking. Purpose To assess symptoms, functional impairment, and residual pulmonary abnormalities on serial chest CT scans in COVID-19 survivors discharged from hospital at up to 1-year follow-up. Materials and Methods Adult patients with COVID-19 discharged between March 2020 and June 2020 were prospectively evaluated at 3 months and 1 year through systematic assessment of symptoms, functional impairment, and thoracic CT scans as part of the PHENOTYPE study, an observational cohort study in COVID-19 survivors. Lung function testing was limited to participants with CT abnormalities and/or persistent breathlessness. Bonferroni correction was used. Results Eighty participants (mean age, 59 years ± 13 [SD]; 53 men) were assessed. At outpatient review, persistent breathlessness was reported in 37 of the 80 participants (46%) and cough was reported in 17 (21%). CT scans in 73 participants after discharge (median, 105 days; IQR, 95–141 days) revealed persistent abnormalities in 41 participants (56%), with ground-glass opacification (35 of 73 participants [48%]) and bands (27 of 73 participants [37%]) predominating. Unequivocal signs indicative of established fibrosis (ie, volume loss and/or traction bronchiectasis) were present in nine of 73 participants (12%). Higher admission serum C-reactive protein (in milligrams per liter), fibrinogen (in grams per deciliter), urea (millimoles per liter), and creatinine (micromoles per liter) levels; longer hospital stay (in days); older age (in years); and requirement for invasive ventilation were associated with CT abnormalities at 3-month follow-up. Thirty-two of 41 participants (78%) with abnormal findings at 3-month follow-up CT underwent repeat imaging at a median of 364 days (range, 360–366 days), with 26 (81%) showing further radiologic improvement (median, 18%; IQR, 10%–40%). Conclusion CT abnormalities were common at 3 months after COVID-19 but with signs of fibrosis in a minority. More severe acute disease was linked with CT abnormalities at 3 months. However, radiologic improvement was seen in the majority at 1-year follow-up. ClinicalTrials.gov identifier: NCT04459351. © RSNA, 2022 Online supplemental material is available for this article.
Association of CT-Based Hypoperfusion Index With Ischemic Core Enlargement in Patients With Medium and Large Vessel Stroke

Background and Objectives The rate of infarct core progression in patients with acute ischemic stroke is variable and affects outcome of reperfusion therapy. We evaluated the hypoperfusion index (HI) to estimate the initial rate of core progression in patients with medium vessel occlusion (MeVO) compared to large vessel occlusion (LVO) stroke and within a larger time frame since stroke onset. Methods Core progression was assessed in 106 patients with acute stroke and CT perfusion. Using reperfusion trial core time criteria, fast progressors had core >70 mL within 6 hours of stroke onset and slow progressors had core ≤70 mL, mismatch ≥15 mL, and mismatch to core ratio ≥1.8 within 6 to 24 hours. The relationship between HI and infarct core progression (core/time) was examined using receiver operating characteristics to determine optimal HI cutoff. The HI cutoff was then tested in the overall cohort, compared between MeVO and LVO, and evaluated in patients up to 24 hours from stroke onset to differentiate fast from slow rate of core progression. HI threshold was assessed in a second independent cohort of 110 patients with acute ischemic stroke. Results In 106 patients with acute stroke, 6.6% were fast progressors, 27.4% were slow progressors, and 66% were not classified as fast or slow progressor by reperfusion trial core time criteria. HI >0.5 was associated with fast progression and able to distinguish fast from slow progressors (area under the curve [AUC] 0.94; 95% confidence interval [CI] 0.80–0.99). In MeVO (n = 26) HI >0.5 had a core progression of 0.30 mL/min compared to 0.03 mL/min for HI ≤0.5 (p < 0.001). In LVO (n = 80), HI >0.5 had a core progression of 0.26 mL/min compared to 0.02 mL/min for HI ≤0.5 (p < 0.001). In patients not classified as fast or slow progressor by reperfusion trial criteria, those with HI >0.5 had progression rate of 0.21 mL/min compared to 0.03 mL/min for those with HI ≤0.5 (p < 0.001). Validation in a second cohort of patients with acute ischemic stroke (n = 110; MeVO = 42, LVO = 68) yielded similar results for HI >0.5 to distinguish fast and slow core progression with an AUC of 0.84 (95% CI 0.72–0.97). Discussion HI can differentiate fast from slow core progression in MeVO and LVO within the first 24 hours of acute ischemic stroke. Consideration of core progression rate at time of stroke evaluation may have implications in the selection of patients with MeVO and LVO stroke for reperfusion therapy that warrant further study.
Genome-Wide Meta-analysis Identifies Genetic Variants Associated With Glycemic Response to Sulfonylureas

OBJECTIVE Sulfonylureas, the first available drugs for the management of type 2 diabetes, remain widely prescribed today. However, there exists significant variability in glycemic response to treatment. We aimed to establish heritability of sulfonylurea response and identify genetic variants and interacting treatments associated with HbA1c reduction. RESEARCH DESIGN AND METHODS As an initiative of the Metformin Genetics Plus Consortium (MetGen Plus) and the DIabetes REsearCh on patient straTification (DIRECT) consortium, 5,485 White Europeans with type 2 diabetes treated with sulfonylureas were recruited from six referral centers in Europe and North America. We first estimated heritability using the generalized restricted maximum likelihood approach and then undertook genome-wide association studies of glycemic response to sulfonylureas measured as HbA1c reduction after 12 months of therapy followed by meta-analysis. These results were supported by acute glipizide challenge in humans who were naïve to type 2 diabetes medications, cis expression quantitative trait loci (eQTL), and functional validation in cellular models. Finally, we examined for possible drug-drug-gene interactions. RESULTS After establishing that sulfonylurea response is heritable (mean ± SEM 37 ± 11%), we identified two independent loci near the GXYLT1 and SLCO1B1 genes associated with HbA1c reduction at a genome-wide scale (P < 5 × 10−8). The C allele at rs1234032, near GXYLT1, was associated with 0.14% (1.5 mmol/mol), P = 2.39 × 10−8), lower reduction in HbA1c. Similarly, the C allele was associated with higher glucose trough levels (β = 1.61, P = 0.005) in healthy volunteers in the SUGAR-MGH given glipizide (N = 857). In 3,029 human whole blood samples, the C allele is a cis eQTL for increased expression of GXYLT1 (β = 0.21, P = 2.04 × 10−58). The C allele of rs10770791, in an intronic region of SLCO1B1, was associated with 0.11% (1.2 mmol/mol) greater reduction in HbA1c (P = 4.80 × 10−8). In 1,183 human liver samples, the C allele at rs10770791 is a cis eQTL for reduced SLCO1B1 expression (P = 1.61 × 10−7), which, together with functional studies in cells expressing SLCO1B1, supports a key role for hepatic SLCO1B1 (encoding OATP1B1) in regulation of sulfonylurea transport. Further, a significant interaction between statin use and SLCO1B1 genotype was observed (P = 0.001). In statin nonusers, C allele homozygotes at rs10770791 had a large absolute reduction in HbA1c (0.48 ± 0.12% [5.2 ± 1.26 mmol/mol]), equivalent to that associated with initiation of a dipeptidyl peptidase 4 inhibitor. CONCLUSIONS We have identified clinically important genetic effects at genome-wide levels of significance, and important drug-drug-gene interactions, which include commonly prescribed statins. With increasing availability of genetic data embedded in clinical records these findings will be important in prescribing glucose-lowering drugs.
Striatal networks for tinnitus treatment targeting

Neuromodulation treatment effect size for bothersome tinnitus may be larger and more predictable by adopting a target selection approach guided by personalized striatal networks or functional connectivity maps. Several corticostriatal mechanisms are likely to play a role in tinnitus, including the dorsal/ventral striatum and the putamen. We examined whether significant tinnitus treatment response by deep brain stimulation (DBS) of the caudate nucleus may be related to striatal network increased functional connectivity with tinnitus networks that involve the auditory cortex or ventral cerebellum. The first study was a cross‐sectional 2‐by‐2 factorial design (tinnitus, no tinnitus; hearing loss, normal hearing, n = 68) to define cohort level abnormal functional connectivity maps using high‐field 7.0 T resting‐state fMRI. The second study was a pilot case–control series (n = 2) to examine whether tinnitus modulation response to caudate tail subdivision stimulation would be contingent on individual level striatal connectivity map relationships with tinnitus networks. Resting‐state fMRI identified five caudate subdivisions with abnormal cohort level functional connectivity maps. Of those, two connectivity maps exhibited increased connectivity with tinnitus networks—dorsal caudate head with Heschl's gyrus and caudate tail with the ventral cerebellum. DBS of the caudate tail in the case‐series responder resulted in dramatic reductions in tinnitus severity and loudness, in contrast to the nonresponder who showed no tinnitus modulation. The individual level connectivity map of the responder was in alignment with the cohort expectation connectivity map, where the caudate tail exhibited increased connectivity with tinnitus networks, whereas the nonresponder individual level connectivity map did not.
Recombinant activated factor VII for hemostasis in patients undergoing complex ascending aortic surgery: A single‐center, single‐surgeon retrospective analysis

Use of recombinant activated factor VII (rFVIIa) to achieve hemostasis during cardiac surgery continues to be debated, as support for its efficacy and safety has not been consistent. We examined our experience with rFVIIa for achieving hemostasis in high‐risk patients undergoing complex ascending aortic surgery.
Who tugs at our heart strings? The effect of avatar images on player generosity in the dictator game

The present research was motivated by a prior study, where several wallets, each containing a photo of either a baby, a puppy, a family, or an elderly couple, were scattered across a city in the United Kingdom. Most of the wallets containing a photo of a baby were returned compared with less than one-third of the wallets containing a photo of an elderly couple. To investigate further, in a series of three studies we examined, using a pseudo online version of the dictator game, possible subtle cues supporting prosocial behaviour by manipulating the type of avatar used by the recipient of the donation made by the “dictator. ” Overall, it emerged that participants showed significantly higher levels of generosity towards babies and older people, supporting the notion that perceptions of vulnerability and need drive prosocial behaviour.
Vibrational Spectroscopic Study of 6-Aminouracil Tetracyanonickelate Complexes

Iki boyutlu kordinasyon polimer kompleksleri M(6AU)2Ni(CN)4 (burada M = Mn, Co, Ni ve Cd; 6AU = 6-aminouracil = 4-amino-2,6-dihydroxypyrimidine) ilk kez elde edilmis ve FT-IR, FT-Raman ve far-IR ile incelenmistir. 6-aminouracil molekulleri pirimidin halkasinin azot atomlarinin biri ile kordinasyon yaptigi bulunmustur. Ni(CN) 4 2iyonlari ile M(6AU) 2 2+ katyonlarinin kordinasyonu sonucu, Hofmann tipi iki boyutlu kordinasyon polimer bilesikleri olusturdugu spektral ozellikler ile desteklenmistir. 6AU ve Ni(CN) 4 grubunun her ikisinden kaynaklanan titresim bandlari tanimlanmistir.
Immunomodulation induced by central nervous system‐related peptides as a therapeutic strategy for neurodegenerative disorders

Neurodegenerative diseases (NDD) are disorders characterized by the progressive loss of neurons affecting motor, sensory, and/or cognitive functions. The incidence of these diseases is increasing and has a great impact due to their high morbidity and mortality. Unfortunately, current therapeutic strategies only temporarily improve the patients’ quality of life but are insufficient for completely alleviating the symptoms. An interaction between the immune system and the central nervous system (CNS) is widely associated with neuronal damage in NDD. Usually, immune cell infiltration has been identified with inflammation and is considered harmful to the injured CNS. However, the immune system has a crucial role in the protection and regeneration of the injured CNS. Nowadays, there is a consensus that deregulation of immune homeostasis may represent one of the key initial steps in NDD. Dr. Michal Schwartz originally conceived the concept of “protective autoimmunity” (PA) as a well‐controlled peripheral inflammatory reaction after injury, essential for neuroprotection and regeneration. Several studies suggested that immunizing with a weaker version of the neural self‐antigen would generate PA without degenerative autoimmunity. The development of CNS‐related peptides with immunomodulatory neuroprotective effect led to important research to evaluate their use in chronic and acute NDD. In this review, we refer to the role of PA and the potential applications of active immunization as a therapeutic option for NDD treatment. In particular, we focus on the experimental and clinical promissory findings for CNS‐related peptides with beneficial immunomodulatory effects.
Not all patients with AML over 60 years of age should be offered early allogeneic stem cell transplantation

The median age at diagnosis of acute myeloid leukemia (AML) is 68 years, and the prognosis worsens with increasing age. For many patients, allogeneic hematopoietic cell transplantation (HCT) is the only chance for cure, and HCT has been used with increasing frequency. For patients age 60 to 69 years and those age 70 years or older, data from the Center for International Blood and Marrow Transplant Research show 150 and 13 transplantations, respectively, for 1995 to 2000, and 3927 and 773 transplantations for 2011 to 2015. There has been considerable progress in reducing toxicity and preventing graft-versus-host disease (GVHD), but relapse after HCT has remained a major challenge.
Association of Age at Onset With Gray Matter Volume and White Matter Microstructural Abnormalities in People With Multiple Sclerosis

Background and Objectives To investigate whether age at onset influences brain gray matter volume (GMV) and white matter (WM) microstructural abnormalities in adult patients with multiple sclerosis (MS), given its influence on clinical phenotype and disease course. Methods In this hypothesis-driven cross-sectional study, we enrolled 67 patients with pediatric-onset MS (POMS) and 143 sex- and disease duration (DD)–matched randomly selected patients with adult-onset MS (AOMS), together with 208 healthy controls. All participants underwent neurologic evaluation and 3T MRI acquisition. MRI variables were standardized based on healthy controls, to remove effects of age and sex. Associations with DD in patients with POMS and patients with AOMS were studied with linear models. Time to reach clinical and MRI milestones was assessed with product-limit approach. Results At DD 1 year, GMV and WM fractional anisotropy (FA) were abnormal in AOMS but not in POMS. Significant interaction of age at onset (POMS vs AOMS) into the association with DD was found for GMV and WM FA. The crossing point of regression lines in POMS and AOMS was at 20 years of DD for GMV and 14 for WM FA. For POMS and AOMS, median DD was 29 and 19 years to reach Expanded Disability Status Scale score 3 (p < 0.001), 31 and 26 years to reach abnormal Paced Auditory Serial Addition Task, 3-second version (p = 0.01), 24 and 18 years to reach abnormal GMV (p = 0.04), and 19 and 17 years to reach abnormal WM FA (p = 0.36). Discussion Younger patients are initially resilient to MS-related damage. Then, compensatory mechanisms start failing with loss of WM integrity, followed by GM atrophy and finally disability.
Focusing on the self in context as an emotion regulatory strategy: an evaluation of the “self-as-context” component of ACT compared to cognitive reappraisal in managing stress

ABSTRACT Background Self-as-Context (SAC) is one of the six core components of the Acceptance and Commitment Therapy model (ACT). Objective The aim of the current study was to investigate whether SAC is effective in reducing negative affect and maintaining positive affect in response to a personally relevant stressor relative to cognitive reappraisal (CR) and spontaneous coping strategies. Method An undergraduate sample (N = 105) completed baseline measures and were asked to discuss a recent personally relevant stressor which was audiotaped, before being randomized to one of three conditions. Participants randomized to the SAC and CR conditions received 5-minutes of training, whilst participants allocated to the control condition were asked to read a brochure for 5-minutes. All participants then listened to their recorded stressful experience before completed follow-up measures. Results The SAC group reported significantly less negative affect than participants in the control group post-training induction; although the CR group did not differ from the SAC or control participants in reductions in negative affect post-induction. There were no significant group differences for positive affect. Conclusions The findings provide preliminary evidence that SAC is an effective emotion regulatory strategy in reducing acute distress in a stress-exposed young adult sample.
Gene expression for biodosimetry and effect prediction purposes: promises, pitfalls and future directions – key session ConRad 2021

Abstract Purpose In a nuclear or radiological event, an early diagnostic or prognostic tool is needed to distinguish unexposed from low- and highly exposed individuals with the latter requiring early and intensive medical care. Radiation-induced gene expression (GE) changes observed within hours and days after irradiation have shown potential to serve as biomarkers for either dose reconstruction (retrospective dosimetry) or the prediction of consecutively occurring acute or chronic health effects. The advantage of GE markers lies in their capability for early (1–3 days after irradiation), high-throughput, and point-of-care (POC) diagnosis required for the prediction of the acute radiation syndrome (ARS). Conclusions As a key session of the ConRad conference in 2021, experts from different institutions were invited to provide state-of-the-art information on a range of topics including: (1) Biodosimetry: What are the current efforts to enhance the applicability of this method to perform retrospective biodosimetry? (2) Effect prediction: Can we apply radiation-induced GE changes for prediction of acute health effects as an approach, complementary to and integrating retrospective dose estimation? (3) High-throughput and point-of-care diagnostics: What are the current developments to make the GE approach applicable as a high-throughput as well as a POC diagnostic platform? (4) Low level radiation: What is the lowest dose range where GE can be used for biodosimetry purposes? (5) Methodological considerations: Different aspects of radiation-induced GE related to more detailed analysis of exons, transcripts and next-generation sequencing (NGS) were reported.
Kidney Transplantation After Rescue Allocation—the Eurotransplant Experience: A Retrospective Multicenter Outcome Analysis

Background. At Eurotransplant (ET), kidneys are transferred to “rescue allocation” (RA), whenever the standard allocation (SA) algorithms Eurotransplant Kidney Allocation System (ETKAS) and Eurotransplant Senior Program (ESP) fail. We analyzed the outcome of RA. Methods. Retrospective patient clinical and demographic characteristics association analyses were performed with graft outcomes for 2422 recipients of a deceased donor renal transplantation (DDRT) after RA versus 25 481 after SA from 71 centers across all ET countries from 2006 to 2018. Results. Numbers of DDRTs after RA increased over the time, especially in Germany. RA played a minor role in ESP versus ETKAS (2.7% versus 10.4%). RA recipients and donors were older compared with SA recipients and donors, cold ischemia times were longer, waiting times were shorter, and the incidence of primary nonfunction was comparable. Among ETKAS recipients, HLA matching was more favorable in SA (mean 3.7 versus 2.5). In multivariate modeling, the incidence of graft loss in ETKAS recipients was reduced in RA compared with SA (subdistribution hazard ratio, 0.80; 95% confidence interval [0.70-0.91], P < 0.001), whereas other outcomes (mortality, death with functioning graft (DwFG)) were not significantly different. None of the 3 outcomes were significantly different when comparing RA with SA within the ESP program. Conclusions. Facing increased waiting times and mortality on dialysis due to donor shortage, this study reveals encouragingly positive DDRT outcomes following RA. This supports the extension of RA to more patients and as an alternative tool to enable transplantation in patients in countries with prohibitively long waiting times or at risk of deterioration.
Is Open Reduction Internal Fixation Using Titanium Plates in the Mandible as Successful as We Think?

Abstract Titanium plats are the gold-standard for fracture fixation. Titanium is considered biocompatible, corrosion resistant with an elasticity-modulus closest to bone. Nonetheless, titanium plates are not always as inherent as hoped. The authors investigated morbidity associated with titanium plates in mandibular fractures. A retrospective study of mandibular fractures treated between 2000 and 2018 using internal-fixation was conducted. Data included age, gender, complications, and location. Predictor-variable was location. Outcome-variable was plate removal. A total of 571 patients were included, 107 resulted in plate removal (18.7%). Body was the most prevalent location of fracture (29.3%). Symphysis/para-sym-physis showed the highest removal rate (24.1%), followed by body and angle (21.3/19.8%). A total of 23.4% of double-plating cases resulted in plate removal, upper-border in 15% and lower-border in 8.8%, all reconstruction-plates. Exposure was the most frequent complication leading to removal. Although titanium plates are the gold standard, almost every fifth patient returns for plate removal. Age-distribution emphasizing 41 to 50 with decrease towards extremities may imply better healing in the young and soft-tissue elasticity and less complaints in the elderly. Significantly more complications in double-plating compared to lower border suggests proximity to the oral-cavity as a risk-factor for removal. Complication rates and patterns are not negligible and perhaps should encourage clinicians to consider using biodegradable-systems for upper-border plates.