Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammatory Cells in Nephrectomy Tissue from Patients without and with a History of Urinary Stone Disease

Visual Abstract Background and objectives Urinary stone disease has been associated with inflammation, but the specific cell interactions that mediate events remain poorly defined. This study compared calcification and inflammatory cell patterns in kidney tissue from radical nephrectomy specimens of patients without and with a history of urinary stone disease. Design, setting, participants, & measurements Nontumor parenchyma of biobanked radical nephrectomy specimens from age- and sex-matched stone formers (n=44) and nonstone formers (n=82) were compared. Calcification was detected by Yasue staining and inflammatory cell populations by immunohistochemistry for CD68 (proinflammatory M1 macrophages), CD163 and CD206 (anti-inflammatory M2 macrophages), CD3 (T lymphocytes), and tryptase (mast cells). Calcifications and inflammatory cells were quantified in cortex and medulla using Image-Pro analysis software. Results Calcification in the medulla of stone formers was higher than in nonstone formers (P<0.001). M1 macrophages in the cortex and medulla of stone formers were greater than in nonstone formers (P<0.001), and greater in stone former medulla than stone former cortex (P=0.02). There were no differences in age, sex, body mass index, tumor characteristics (size, stage, or thrombus), vascular disease status, or eGFR between the groups. M2 macrophages, T lymphocytes, and mast cells did not differ by stone former status. There was a correlation between M1 macrophages and calcification in the medulla of stone formers (rho=0.48; P=0.001) and between M2 macrophages and calcification in the medulla of nonstone formers (rho=0.35; P=0.001). T lymphocytes were correlated with calcification in the cortex of both nonstone formers (rho=0.27; P=0.01) and stone formers (rho=0.42; P=0.004), whereas mast cells and calcification were correlated only in the cortex of stone formers (rho=0.35; P=0.02). Conclusions Higher medullary calcification stimulated accumulation of proinflammatory rather than anti-inflammatory macrophages in stone formers.
Brain functional network abnormalities in parkinson’s disease with mild cognitive impairment

Abstract Mild cognitive impairment in Parkinson’s disease (PD-M) is related to a high risk of dementia. This study explored the whole-brain functional networks in early-stage PD-M. Forty-one patients with PD classified as cognitively normal (PD-N, n = 17) and PD-M (n = 24) and 24 demographically matched healthy controls (HC) underwent clinical and neuropsychological evaluations and resting-state functional magnetic resonance imaging. The global, regional, and modular topological characteristics were assessed in the brain functional networks, and their relationships to cognitive scores were tested. At the global level, PD-M and PD-N exhibited higher characteristic path length and lower clustering coefficient, local and global efficiency relative to HC. At the regional level, PD-M and PD-N showed lower nodal centrality in sensorimotor regions relative to HC. At the modular level, PD-M showed lower intramodular connectivity in default mode and cerebellum modules, and lower intermodular connectivity between default mode and frontoparietal modules than PD-N, correlated with Montreal Cognitive Assessment scores. Early-stage PD patients showed weaker small-worldization of brain networks. Modular connectivity alterations were mainly observed in patients with PD-M. These findings highlight the shared and distinct brain functional network dysfunctions in PD-M and PD-N, and yield insight into the neurobiology of cognitive decline in PD.
Pridopidine modifies disease phenotype in a SOD1 mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a lethal and incurable neurodegenerative disease due to the loss of upper and lower motor neurons, which leads to muscle weakness, atrophy, and paralysis. Sigma‐1 receptor (σ‐1R) is a ligand‐operated protein that exhibits pro‐survival and anti‐apoptotic properties. In addition, mutations in its codifying gene are linked to development of juvenile ALS pointing to an important role in ALS. Here, we investigated the disease‐modifying effects of pridopidine, a σ‐1R agonist, using a delayed onset SOD1 G93A mouse model of ALS. Mice were administered a continuous release of pridopidine (3.0 mg/kg/day) for 4 weeks starting before the appearance of any sign of muscle weakness. Mice were monitored weekly and several behavioural tests were used to evaluate muscle strength, motor coordination and gait patterns. Pridopidine‐treated SOD1 G93A mice showed genotype‐specific effects with the prevention of cachexia. In addition, these effects exhibited significant improvement of motor behaviour 5 weeks after treatment ended. However, the survival of the animals was not extended. In summary, these results show that pridopidine can modify the disease phenotype of ALS‐associated cachexia and motor deficits in a SOD1 G93A mouse model.
A Quantification of Scalp Thickness before and after Posterior Vault Distraction Osteogenesis

Summary: Previous literature has documented craniometric changes of the bony calvaria, increases in intracranial volume, and resolution of Chiari malformations following posterior vault distraction osteogenesis. No studies have analyzed changes to the soft-tissue envelope after posterior vault distraction osteogenesis. In this study, the authors aimed to provide objective measurements of scalp thickness in patients undergoing posterior vault distraction osteogenesis, utilizing facial soft-tissue thickness as a proxy to control for growth. The authors hypothesized that the soft tissues of the scalp are not made thinner by the distraction process, either in the region of distraction or in neighboring areas. Subjects who underwent posterior vault distraction osteogenesis for a craniosynostosis diagnosis who had high-resolution predistraction and post–distractor removal computed tomographic scans within 100 days of each operation were included. The scans were analyzed on Materialise Mimics version 21 software (Materialise, Ghent, Belgium). Six key craniometric landmarks (glabella, pogonion, zygion, vertex, euryon, and opisthocranium) were identified on the three-dimensional bone masks in the Frankfort horizontal plane. The points were overlaid onto soft-tissue thickness masks and thicknesses were recorded. Percent change in postoperative facial soft-tissue thickness was used to control for growth of the craniofacial soft-tissue envelope during the study interval. The preoperative and postoperative posterior vault distraction osteogenesis cohorts did not differ significantly at the glabella, pogonion, opisthocranium, vertex, and zygion. The corrected median thickness at the euryon was significantly increased in the post–posterior vault distraction osteogenesis cohort [2.67 mm (IQR, 2.49 mm to 4.02 mm) versus 5.26 mm (IQR, 3.83 mm to 7.82 mm), p = 0.002]. This is the first study to quantify changes in soft-tissue thicknesses preoperatively and postoperatively in patients undergoing posterior vault distraction osteogenesis, demonstrating maintenance of scalp thickness. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
Acute ischaemic stroke associated with SARS-CoV-2 infection in North America

Background To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. Methods Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. Results A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age >60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p<0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. Conclusion There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality.
Percutaneous Lumbar Interbody Fusion With an Expandable Titanium Cage Through Kambin’s Triangle: A Case Series With Initial Clinical and Radiographic Results

Background There has been an increased interest in lumbar interbody fusions through Kambin’s triangle. In this study, we describe percutaneous access to the lumbar disc and insertion of an expandable titanium cage through Kambin’s triangle without facetectomy. The objective of this study is to determine the feasibility as well as clinical and radiographical outcomes of completely percutaneous lumbar interbody fusion (percLIF) using an expandable titanium cage through Kambin’s triangle. Methods A retrospective review of patients undergoing single-level percLIF for grade 1 lumbar spondylolisthesis via Kambin’s triangle using an expandable titanium cage was performed. Demographic information, Oswestry Disability Index (ODI), preoperative and postoperative radiographic factors, perioperative data, and complications were recorded. Fusion was assessed with 1-year postoperative computed tomography scan or lumbar spine x-ray and defined as bridging disc or posterolateral fusion without evidence of hardware fracture or perihardware lucency. Results A total of 16 patients (3 males) were included in this study. Spondylolisthesis, anterior disc height, and posterior disc height were significantly improved at 6 weeks, 6 months, and 12 months, postoperatively (P < 0.05). ODI was significantly improved by 24.4% at 12 months postoperatively (P = 0.0036). One patient was readmitted within 30 days for pain control but otherwise there were no complications including permanent neurological injury, infection, deep vein thrombosis, pulmonary embolism, or cardiac events. Fifteen (93.8%) patients had radiographic fusion at their 1-year postoperative imaging. Conclusion Our initial experiences have shown that percLIF can be performed using an expandable titanium cage through Kambin’s triangle with excellent radiographic and clinical results. In this series, percLIF is a safe and clinically efficacious procedure for reducing grade 1 lumbar spondylolisthesis and improving radiculopathy. This procedure is completed percutaneously without the use of an endoscope. Clinical Relevance This study highlights improvements in outcomes of minimally invasive surgery. Level of Evidence IV.
Psychobiotic Therapy: Method to Reinforce the Immune System

Psychobiotics are probiotic microorganisms that beneficially affect the central nervous system functions mediated by the gut-brain axis, improving the host’s immune system. Psychobiotic microorganisms can regulate brain pathways and serotonin production (mood controller). The main microbial genera with psychobiotic characteristics are Lactobacillus, Lactococcus and Bifidobacterium. The daily consumption of psychobiotics is called “Psychobiotic Therapy”. Psychobio-tic therapy has proven antidepressant/anxiolytic properties. Psychobiotic therapy can be used to boost the host’s immune balance against pathogens, for example: virus, bacteria and fungus. Thus, psychobiotic therapy can be a promising strategy to improve and/or maintain the quality of life of people who are healthy or who suffer from anxiety/stress disorders, intestinal dysbiosis and even immunosuppressed people. This is such a hot theme it can surely only be a matter of time for psychobiotic therapy offers an “alternative treatment”, but scientific, for people diagnosed with a variety of mental/immunological disorders. Instead of targeting the mind (brain), we could go for the gut. “This new way of looking at mental health linked to gut health is literally looking at health upside down”.
Preclinical Immunopharmacologic Assessment of KPL-404, a Novel, Humanized, Non-Depleting Antagonistic Anti-CD40 Monoclonal Antibody

The CD40/CD40L pathway plays a major role in multiple inflammatory processes involving different immune and stromal cells. Abnormal activation of this pathway has been implicated in pathogenesis of complex autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, Graves’ disease, and Sjogren’s Syndrome. We completed in vitro and in vivo preclinical characterization of KPL-404, a novel humanized anti-CD40 IgG4 monoclonal antibody, to demonstrate its potency, efficacy, and pharmacokinetic profile; safety was also assessed. In vitro, KPL-404 bound recombinant human and cynomolgus monkey CD40 with comparable affinity in the nanomolar range. KPL-404 binding to cell surface CD40 did not induce antibody- or complement-mediated cytotoxicity of CD40-expressing cells. Pharmacological antagonistic activity of KPL-404 was demonstrated in vitro by inhibition of CD40-mediated downstream NF-kB activation. In the in vivo study with cynomolgus monkeys, KPL-404, administered intravenously as a single dose (10 mg/kg) or two monthly doses of 1 or 5 mg/kg, did not elicit observable safety findings, including thrombocytopenia over 8 weeks. KPL-404 engaged CD40 expressed on peripheral B cells for 2 and 4 weeks after a single administration of 5 or 10 mg/kg IV, respectively, without depletion of peripheral B cells. At 5 mg/kg IV, KPL-404 blocked both primary and secondary responses to T-cell dependent antibody responses to test antigens, KLH, and tetanus toxoid. These data illustrated the relationship between KPL-404 serum concentration and pharmacodynamic effects of CD40-targeting in circulation and in lymphoid tissues. These data support clinical development of KPL-404 in autoimmune diseases. SIGNIFICANCE STATEMENT We aimed to develop a potent and efficacious CD40 antagonist. In vitro and in vivo findings show that KPL-404 blocks the anti-CD40 antibody that potently inhibits primary and secondary antibody responses at pharmacologically relevant concentrations, has a favorable pharmacokinetic profile, and does not deplete B cells by antibody-dependent cellular cytotoxicity or apoptosis (“nondepleting”). These findings support clinical development of KPL-404 as a potential therapeutic in autoimmune diseases.
Metabolic Dysfunction–Associated Fatty Liver Disease Increases Colon Cancer Risk: A Nationwide Cohort Study

INTRODUCTION: The association between nonalcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC) has been controversial. Using the new consensus-driven definition, we evaluated the association of metabolic dysfunction–associated fatty liver disease (MAFLD) with the risk of developing CRC. METHODS: From a nationwide health screening database, we included 8,933,017 participants (48.6% male) aged 40–64 years between 2009 and 2010. Participants were categorized by the presence of fatty liver disease (FLD)—NAFLD and MAFLD, separately—and by the combination of the 2 definitions: neither FLD, NAFLD only, MAFLD only, or both FLD. The primary outcome was the development of CRC. RESULTS: Among the participants, 2,517,330 (28.2%) had NAFLD, and 3,337,122 (37.4%) had MAFLD, whereas 2,465,151 (27.6%) met both NAFLD and MAFLD definitions. Over a median follow-up period of 10.1 years, 60,888 new CRC cases developed. NAFLD and MAFLD were each associated with a significantly higher risk of developing CRC. When the neither FLD group was the reference, multivariable-adjusted hazard ratios (95% confidence interval) for CRC were 1.16 (1.06–1.28) in the NAFLD only group, 1.18 (1.16–1.20) in the both FLD group, and 1.32 (1.28–1.35) in the MAFLD only group. The presence of advanced liver fibrosis further increased CRC risk in each FLD group. DISCUSSION: FLD was associated with a higher risk of CRC development. CRC risk was higher in the presence of MAFLD, especially when accompanied by liver fibrosis.
Neural correlates of successful costly punishment in the Ultimatum game on a trial-by-trial basis

Abstract Costly punishment describes decisions of an interaction partner to punish an opponent for violating rules of fairness at the expense of personal costs. Here, we extend the interaction process by investigating the impact of a socio-emotional reaction of the opponent in response to the punishment that indicates whether punishment was successful or not. In a modified Ultimatum game, emotional facial expressions of the proposer in response to the decision of the responder served as feedback stimuli. We found that both honored reward following acceptance of an offer (smiling compared to neutral facial expression) and successful punishment (sad compared to neutral facial expression) elicited a reward positivity, indicating that punishment was the intended outcome. By comparing the pattern of results with a probabilistic learning task, we show that the reward positivity on sad facial expressions was specific for the context of costly punishment. Additionally, acceptance rates on a trial-by-trial basis were altered according to P3 amplitudes in response to the emotional facial reaction of the proposer. Our results are in line with the concept of costly punishment as an intentional act following norm-violating behavior. Socio-emotional stimuli have an important influence on the perception and behavior in economic bargaining.
High‐density lipoprotein lipid peroxidation as a diagnostics biomarker in coronary artery disease

This study aimed at evaluating the serum High‐density lipoprotein lipid peroxidation (HDLox) levels and their association with coronary artery disease (CAD). This case–control study comprised 572 patients with stable CAD and 281 healthy subjects with no history of cardiovascular disease (control group). Based on the results of coronary angiography, the patient group was divided into two groups: CAD− and CAD+. HDLox was measured using a fluorimetric method. The ability of HDLox and serum high‐density lipoprotein cholesterol (HDL‐C) to detect CAD and coronary artery stenosis ≥50% was also compared using the receiver operating characteristic (ROC) curve analysis. The CAD patients showed significantly higher serum HDLox levels, compared to the control group [1.15 (1.01–1.31) vs. 0.85 (0.62–1.06), no units, p < 0.001]. Moreover, serum HDLox levels were significantly lower in CAD− patients, compared to the CAD+ patients [1.05 (0.92–1.22) vs. 1.24 (1.12–1.35), no units, p < 0.001]. According to the results of univariate and multivariate logistic regression, the HDLox showed association with the presence of CAD (odds ratio [OR]: 1.754; 95% confidence interval [CI]: 1.564–1.968; p < 0.001) and coronary artery stenosis ≥50% (OR: 1.729; 95% CI: 1.534–1.949; p < 0.001). The results obtained from the area under the ROC curve revealed that the HDLox could better detect the risk of CAD and coronary artery stenosis ≥50% compared to serum HDL‐C level. The oxidation of HDL leads to a reduction in its antioxidant function and it has a crucial role in the development of atherosclerosis. HDLox is suggested as a diagnostics biomarker for CAD.
The dentine‐sealer interface: Modulation of antimicrobial effects by irrigation

Abstract Aim Assess whether sodium hypochlorite (NaOCl) or chlorhexidine (CHX) and two irrigation protocols may alter the antibacterial properties of dentine and three endodontic sealers using a novel ex vivo tooth model. Methodology Prior to antibacterial testing, the tooth model was validated by means of scanning electron microscopy (SEM) to evaluate the separation between dentine and sealer surfaces. Root blocks prepared from extracted human roots were pre‐treated with 17% EDTA + 0.9% saline and subsequently treated with 1% NaOCl (G1), 2% CHX (G2) or no irrigant (G3). Two irrigation protocols were further investigated, “1% NaOCl + 17% EDTA” (P1) and “1% NaOCl + 17% EDTA + 2% CHX” (P2). Following irrigation, the root blocks were either filled with AH Plus, BioRoot RCS and Pulp Canal Sealer (PCS), or left empty. All groups were incubated for 1, 7 and 28 days. Direct contact tests for planktonic E. faecalis and 48 h E. faecalis biofilms were performed at the level of dentine and sealer surfaces. Statistical analysis was performed on the bacterial survival between irrigants (G1, G2 and G3) and between irrigation protocols (P1 and P2); p < . 05. Results The model was considered reproducible as SEM examination of dentine samples indicated consistent separation between dentine and sealer surfaces. Irrigation with CHX (G2) and irrigation protocol P2 enhanced the antibacterial properties of dentine without sealer application as well as dentine in contact with all three sealers tested, especially against planktonic E. faecalis. G2 and P2 also improved the antibacterial effect of AH Plus surfaces for all three incubation times. No irrigation groups (G1, G2) or irrigation protocols (P1, P2) altered the antibacterial properties of BioRoot RCS surfaces against planktonic bacteria or biofilms. Only BioRoot RCS surfaces eliminated the planktonic E. faecalis in all irrigation groups (G1, G2, G3) and protocols (P1, P2) investigated whilst PCS surfaces eliminate E. faecalis in biofilms in all groups up to 7 days. Conclusions The tooth model was reproducible. CHX improved the antibacterial activity upon both sealer and dentine surfaces. Amongst sealers, BioRoot RCS was less affected by NaOCl and CHX, and exhibited high antibacterial properties regardless the irrigation applied.
Maternal and paternal involvement in complementary feeding in Kaduna State, Nigeria: The continuum of gender roles in urban and rural settings

Abstract Household gender roles influence infant and young child feeding behaviours and may contribute to suboptimal complementary feeding practices through inequitable household decision‐making, intra‐household food allocation and limited paternal support for resources and caregiving. In Igabi local government area of Kaduna State, Nigeria, the Alive & Thrive (A&T) initiative implemented an intervention to improve complementary feeding practices through father engagement. This study describes household gender roles among A&T participants and how they influence maternal and paternal involvement in complementary feeding. We conducted 16 focus group discussions with mothers and fathers of children aged 6–23 months in urban and rural administrative wards and analysed them using qualitative thematic analysis methods. Most mothers and fathers have traditional roles with fathers as ‘providers’ and ‘supervisors’ and mothers as ‘caregivers’. Traditional normative roles of fathers limit their involvement in ‘hands‐on’ activities, which support feeding and caring for children. Less traditional normative roles, whereby some mothers contributed to the provision of resources and some fathers contributed to caregiving, were also described by some participants and were more salient in the urban wards. In the rural wards, more fathers expressed resistance to fathers playing less traditional roles. Fathers who participated in caregiving tasks reported respect from their children, strong family relationships and had healthy home environments. Our research findings point to the need for more context‐specific approaches that address prevalent gender normative roles in complementary feeding in a variety of settings.