Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and verification of vascular cell adhesion protein 1 as an immune-related hub gene associated with the tubulointerstitial injury in diabetic kidney disease

ABSTRACT Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), but the pathogenesis is not completely understood. Tubulointerstitial injury plays critical roles in the development and progression of DKD. The present study aimed to investigate the profile of tubulointerstitial immune cell infiltration and reveal the underlying mechanisms between tubular cell injury and interstitial inflammation in DKD using bioinformatics strategies. First, xCell analysis identified immune cells displaying significant changes in the DKD tubulointerstitium, including upregulated CD4+ T cells, Th2 cells, CD8+ T cells, M1 macrophages, activated dendritic cells (DCs) and conventional DCs, as well as downregulated Tregs. Second, pyroptosis was identified as the main form of cell death compared with other forms of programmed cell death. Vascular cell adhesion protein 1 (VCAM1) was identified as the top ranked hub gene. The correlation analysis showed that VCAM1 was significantly positively correlated with pyroptosis and infiltrated immune cells in the tubulointerstitium. Upregulation of VCAM1 in the DKD tubulointerstitium was further verified in European Renal cDNA Bank cohort and was observed to negatively correlate with the glomerular filtration rate (GFR). Our in vitro study validated increased VCAM1 expression in HK-2 cells under diabetic conditions, and pyroptosis inhibition by disulfiram decreased VCAM1 expression, inflammatory cytokine release and fibrosis. In conclusion, our study identified upregulated VCAM1 expression in renal tubular cells, which might interact with infiltrated immune cells, thus promoting fibrosis. The FDA-approved drug disulfiram might improve fibrosis in DKD by targeting tubular pyroptosis and VCAM1 expression.
Ferricyanide Confined in a Protonated Amine-Functionalized Silica Film on Gold: Application to Electrocatalytic Sensing of Nitrite Ions

ABSTRACT An amine-functionalized porous sol–gel silica film was shown to be an effective platform to immobilize small anionic redox mediators of high solubility on solid electrodes by electrostatic interaction. The highly soluble mediator hexacyanoferrate was used as a model. The film was grown and firmly anchored on a gold electrode surface via thiol groups of a self-assembled monolayer of (3-mercaptopropyl)trimethoxysilane. Film growth and thickness were controlled by electrochemical modulation of pH at the electrode/solution interface in a sol of a hydrolyzed solution of tetraethoxysilane and 3-[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane by the application of a negative potential to the electrode. Protonation of the amine groups made the amine-functionalized surface useful to immobilize hexacyanoferrate on gold. Thus, the immobilization is pH dependent, being highly effective in strongly acidic medium. Cyclic voltammetry and scanning electron microscopy were used to characterize the film and to optimize the experimental conditions. The stability of the film was demonstrated by applying the catalytic properties of the hexacyanoferrate containing surface for nitrite sensing using a flow injection analysis (FIA) system. Under the optimized conditions, the sensor exhibited high sensitivity, low detection limit, easy handling, and stability with a linear range from 1.0 to 40.0 µmol L−1 and a detection limit of 0.53 µmol L−1 based on a signal-to-noise ratio of 3. The sensor was successfully applied to nitrite determination in water samples using FIA with excellent recoveries.
Psychobiological Mechanisms in Somatic Symptom Disorder and Depressive Disorders: An Ecological Momentary Assessment Approach

Supplemental digital content is available in the text. ABSTRACT Objective Persistent somatic symptoms cause strong impairment in persons with somatic symptom disorder (SSD) and depressive disorders (DDs). Specific negative psychological factors (NPFs), such as catastrophizing, negative affectivity, and behavioral avoidance, are assumed to contribute to this impairment and may maintain symptoms via dysregulations of biological stress systems. We examined the associations between NPF and somatic symptoms in the daily life of women with SSD or DD and investigated the mediating role of psychobiological stress responses. Methods Twenty-nine women with SSD and 29 women with DD participated in an ecological momentary assessment study. For 14 days, intensity of and impairment by somatic symptoms, NPF, and stress-related biological measures (cortisol, alpha-amylase) were assessed five times per day using an electronic device and saliva samples. Multilevel models were conducted. Results The greater the number of NPF, the higher the concurrent and time-lagged intensity of and impairment by somatic symptoms in both groups (12.0%–38.6% of variance explained; χ2(12) p < . 001 for all models). NPFs were associated with higher cortisol levels in women with DD and with lower levels in women with SSD (interaction NPF by group: B = −0.04, p = .042 for concurrent; B = −0.06, p = .019 for time-lagged). In women with SSD, lower cortisol levels were associated with higher intensity at the next measurement time point (group by cortisol: B = −1.71, p = .020). No mediation effects were found. Conclusions NPFs may be considered as transdiagnostic factors in the development and treatment of impairing somatic symptoms. Our findings will allow the development of new treatment strategies that use ecological momentary intervention approaches focusing on NPF.
Secure human attachment can promote support for climate change mitigation

Significance Attachment theory focuses on the primal form of emotional bonding between humans. Attachment is conceptualized as an innate behavioral system aimed at safeguarding against potential threats by assuring proximity to caring and supportive others. When individuals feel securely attached (thus feeling less threatened in most situations), the activation of the caregiving behavioral system (concern for others) is facilitated. With this research, we show that priming attachment security influences how much people care about and accept climate change via an increased empathy for humanity. Furthermore, we demonstrate that this activation bypasses the resistance of politically conservative individuals to mitigate climate change. Overall, we show that attachment security–based stimuli can inform intervention and policymaking strategies to help fight climate change. Attachment theory is an ethological approach to the development of durable, affective ties between humans. We propose that secure attachment is crucial for understanding climate change mitigation, because the latter is inherently a communal phenomenon resulting from joint action and requiring collective behavioral change. Here, we show that priming attachment security increases acceptance (Study 1: n = 173) and perceived responsibility toward anthropogenic climate change (Study 2: n = 209) via increased empathy for others. Next, we demonstrate that priming attachment security, compared to a standard National Geographic video about climate change, increases monetary donations to a proenvironmental group in politically moderate and conservative individuals (Study 3: n = 196). Finally, through a preregistered field study conducted in the United Arab Emirates (Study 4: n = 143,558 food transactions), we show that, compared to a message related to carbon emissions, an attachment security–based message is associated with a reduction in food waste. Taken together, our work suggests that an avenue to promote climate change mitigation could be grounded in core ethological mechanisms associated with secure attachment.
Self-mediated positive selection of T cells sets an obstacle to the recognition of nonself

Significance It is well established that peptides that are dissimilar to human proteins are more immunogenic. However, the immune system is still unable to recognize a large fraction of highly dissimilar peptides found in a wide variety of pathogens. We propose that this phenomenon could be explained by the mechanism of T cell positive selection. During this process, only those cells survive that recognize human peptides on the surface of thymic epithelial cells. As self-peptides mediate positive selection, the immune system is unable to recognize many nonself peptides, most of which are highly dissimilar to human peptides. Adaptive immune recognition is mediated by the binding of peptide–human leukocyte antigen complexes by T cells. Positive selection of T cells in the thymus is a fundamental step in the generation of a responding T cell repertoire: only those T cells survive that recognize human peptides presented on the surface of cortical thymic epithelial cells. We propose that while this step is essential for optimal immune function, the process results in a defective T cell repertoire because it is mediated by self-peptides. To test our hypothesis, we focused on amino acid motifs of peptides in contact with T cell receptors. We found that motifs rarely or not found in the human proteome are unlikely to be recognized by the immune system just like the ones that are not expressed in cortical thymic epithelial cells or not presented on their surface. Peptides carrying such motifs were especially dissimilar to human proteins. Importantly, we present our main findings on two independent T cell activation datasets and directly demonstrate the absence of naïve T cells in the repertoire of healthy individuals. We also show that T cell cross-reactivity is unable to compensate for the absence of positively selected T cells. Additionally, we show that the proposed mechanism could influence the risk for different infectious diseases. In sum, our results suggest a side effect of T cell positive selection, which could explain the nonresponsiveness to many nonself peptides and could improve the understanding of adaptive immune recognition.
Predictability effects and parafoveal processing of compound words in natural Chinese reading

We report a boundary paradigm eye movement experiment to investigate whether the predictability of the second character of a two-character compound word affects how it is processed prior to direct fixation during reading. The boundary was positioned immediately prior to the second character of the target word, which itself was either predictable or unpredictable. The preview was either a pseudocharacter (nonsense preview) or an identity preview. We obtained clear preview effects in all conditions, but more importantly, skipping probability for the second character of the target word and the whole target word from pretarget was greater when it was predictable than when it was not predictable from the preceding context. Interactive effects for later measures on the whole target word (gaze duration and go-past time) were also obtained. These results demonstrate that predictability information from preceding sentential context and information regarding the likely identity of upcoming characters are used concurrently to constrain the nature of lexical processing during natural Chinese reading.
Impact of Blinding on Patient-Reported Outcome Differences between Treatment Arms in Cancer Randomized Controlled Trials.

Some concerns have been raised about potential bias in patient-reported outcome (PRO) results from open-label cancer randomized controlled trials (RCTs). We investigated if open-label trials favor the experimental treatment over the standard treatment more frequently than blinded trials. We also examined if the effect of treatment concealment differs for distal vs more proximal PROs. We assessed 538 RCTs with a PRO endpoint conducted in the most prevalent cancers, of which 366 (68.0%) were open-label, 148 (27.5%) were blinded, and 24 (4.5%) were categorized as unclear. In our multivariable logistic regression model, we did not observe a statistically significant association of the independent variable treatment concealment (open-label vs blinded) on the dependent variable measuring the proportion of trials favoring the experimental treatment (adjusted odds ratio = 1.19, 95% confidence interval = 0.79 to 1.79, 2-sided P = . 40. This was also the case when comparing distal and proximal PROs. Our findings provide novel evidence-based data that support the validity of PRO results from open label cancer RCTs.
Value Analysis of Methods of Inguinal Hernia Repair

Objective: Value is defined as health outcomes important to patients relative to cost of achieving those outcomes: Value = Quality/Cost. For inguinal hernia repair, Level 1 evidence shows no differences in long-term functional status or recurrence rates when comparing surgical approaches. Differences in value reside within differences in cost. The aim of this study is to compare the value of different surgical approaches to inguinal hernia repair: Open (Open-IH), Laparoscopic (Lap-IH), and Robotic (R-TAPP). Methods: Variable and fixed hospital costs were compared among consecutive Open-IH, Lap-IH, and R-TAPP repairs (100 each) performed in a university hospital. Variable costs (VC) including direct materials, labor, and variable overhead ($/min operating room [OR] time) were evaluated using Value Driven Outcomes, an internal activity-based costing methodology. Variable and fixed costs were allocated using full absorption costing to evaluate the impact of surgical approach on value. As cost data is proprietary, differences in cost were normalized to Open-IH cost. Results: Compared to Open-IH, VC for Lap-IH were 1.02X higher (including a 0.81X reduction in cost for operating room [OR] time). For R-TAPP, VC were 2.11X higher (including 1.36X increased costs for OR time). With allocation of fixed cost, a Lap-IH was 1.03X more costly, whereas R-TAPP was 3.18X more costly than Open-IH. Using equivalent recurrence as the quality metric in the value equation, Lap-IH decreases value by 3% and R-TAPP by 69% compared to Open-IH. Conclusions: Use of higher cost technology to repair inguinal hernias reduces value. Incremental health benefits must be realized to justify increased costs. We expect payors and patients will incorporate value into payment decisions.
The Myeloid-Kidney Interface in Health and Disease

Kidney homeostasis is highly dependent upon the correct functioning of myeloid cells. These cells form a distributed surveillance network throughout the kidney, where they play an integral role in the response to organ threat. Dysregulation of resident proinflammatory and profibrotic macrophages leads to kidney structural damage and scarring after kidney injury. Fibrosis throughout the kidney parenchyma contributes to the progressive functional decline observed in CKD, independent of the etiology. Circulating myeloid cells bearing intrinsic defects also affect the kidney substructures, such as neutrophils activated by autoantibodies that cause GN in ANCA-associated vasculitis. The kidney can also be affected by disorders of myelopoiesis, including myeloid leukemias (acute and chronic myeloid leukemias) and myelodysplastic syndromes. Clonal hematopoiesis of indeterminate potential is a common, newly recognized premalignant clinical entity characterized by clonal expansion of hyperinflammatory myeloid lineage cells that may have significant kidney sequelae. A number of existing therapies in CKD target myeloid cells and inflammation, including glucocorticoid receptor agonists and mineralocorticoid receptor antagonists. The therapeutic indications for these and other myeloid cell-targeted treatments is poised to expand as our understanding of the myeloid-kidney interface evolves.
Prognostic value of the triglyceride-glucose index among non-diabetic patients with acute myocardial infarction in one year follow-up.

BACKGROUND The triglyceride-glucose index (TyG index) is a novel metabolic marker initially used as an indicator of insulin resistance. Recently, its use as a cardiovascular risk factor has been taken into consideration; however, there is a shortage of evidence for its clinical importance. AIM The aim of the study was to assess the relationship between the TyG index = ln (fasting triglyceride [mg/dl] × fasting glucose [mg/dl]/2) and the incidence of major adverse cardiovascular events (MACE) in one year follow-up among non- diabetic patients with acute myocardial infarction (MI). In addition, the predictive value of the TyG index concerning all-cause mortality in the study group was evaluated. METHODS For the study, 1340 non-diabetic patients with acute MI (median age 67 years, 70.4% male) were consecutively enrolled between 2013 and 2019. Fasting lipid profile and fasting glucose level were assessed within 24 hours of admission. RESULTS MACE occurred in 8.13 % (n = 109) of the study group, whereas one year mortality rate was 14.5% (n = 195). There was no difference in the median TyG index value among patients with and without incidence of MACE in one year follow-up (8.73 [8.36-9.08] vs 8.81 [8.5-9.17], P = 0.09). Moreover, the TyG index was not a predictor of these events (P = 0.06). In multivariable regression analysis, only previously diagnosed coronary artery disease (CAD) was an independent predictor of MACE (OR, 1.54; 95% CI, 1.02-2.32; P = 0.03). Finally, the TyG index was not an indicator of all-cause mortality (P = 0.25). CONCLUSIONS The TyG index should not be used as a predictor of MACE and all-cause mortality among non-diabetic patients with MI in one year follow-up.
Hemodynamic Response to Laryngoscopy and Intubation Using McCoy Laryngoscope: A Descriptive Cross-sectional Study

ABSTRACT Introduction: Laryngoscopy and intubation are stressful as they lead to a rise in heart rate and blood pressure. Though transient, it may be detrimental to the cardiac and neurosurgical patients. There is a need to explore the possibility of obtunding the pressor response to laryngoscopy and intubation with the use of McCoy blade laryngoscope. We aimed to find out the hemodynamic response to laryngoscopy and intubation using McCoy laryngoscope in adult patients undergoing general anesthesia. Methods: The descriptive cross-sectional study was conducted in 37 American Society of Anesthesiologists' Physical Status I/IIpatients, with normal airway from December 2019-May 2020 in a tertiary care hospital. Ethical approval was obtained from Institutional Research Committee (reference number.: MEMG/IRC/290/GA). Convenience sampling method was used. The mean systolic and diastolic blood pressures were measured at baseline, one, three and five minutes after laryngoscopy and intubation. Data were analyzed using the Statistical Package for the Social Sciences Version 21.0. Results: In the first minute after laryngoscopy and intubation, the rise in mean blood pressure was noted in 14 (37.83%) cases. The peak rise in mean blood pressure was 3%, note done minute after laryngoscopy and intubation. Conclusions: We noted better attenuation of pressor response to laryngoscopy and intubation using McCoy blade laryngoscope in adult patients undergoing general anesthesia.
Microbial transformation of icariin and its derivatives

Abstract Microbial transformation is an important tool to perform selective conversion of compounds to derivatives which are difficult to produce synthetically. In order to obtain icariside II and icaritin, the active components in Herba Epimedii in vivo, biotransformation studies using microbes as biocatalysts were carried out. Icariside II (2) and icaritin (3) were produced through biotransformation of icariin (1) using the fungi Hormoconis resinae and Mortierella ramanniana var. angulispora in 98% and 92% yields, respectively. In the subsequent transformation studies, 2 was deglycosylated to form 3 by Gliocladium deliquescens, whereas 3 was further converted to a novel compound icaritin-3-O-β-d-glucopyranoside (4) and previously known icaritin-3,7-O-β-d-diglucopyranoside (5) by Mucor hiemalis. Biological evaluation of these compounds using MTT assay exhibited potent cytotoxic activities against human cancer cell lines A549, A375P, and MCF-7, with icariin being the most active, indicating that glycosylation plays a role in the cytotoxic activity. Graphical Abstract
JNSBU Enhancing Managerial Skills for Intern-Nurses by Using Problem-Based Learning Strategy 1

Background: Problem-based learning (PBL) has been implemented throughout the world as an innovative learning method in nursing education and some Egyptian universities have adopted PBL as a learning method to enhance intern-nurses application of knowledge, promotes self-learning, and develops managerial skills. The study aimed to enhance managerial skills for intern-nurses by using problem-based learning strategy. Study Design: A quasi-experimental design was utilized. The study sample: A convenient sample of 124 intern-nurses divided into two groups; Traditional based learning (TBL) group (70 intern-nurses) and PBL group (54 intern-nurses). Study Setting: The study was conducted in the intern-nurses' clinical training areas at Benha University Hospital. Tools: Five tools were used for data collection; (1) Intern-nurses' opinionnaire sheet, (2) Managerial skills knowledge questionnaire, (3) Managerial skills' practice questionnaire, (4) Attitude toward PBL questionnaire and (5) Evaluation questionnaire. Results: The majority of intern-nurses (92.6% & 72.2%) preferred PBL at immediate post and follow up phases respectively than TBL as a strategy of learning. Also, the majority of intern-nurses (96.3% & 87.1%) had satisfactory level of managerial skills knowledge at PBL and TBL group respectively during immediate post program phase. The majority of intern-nurses (87.0%) had positive attitude toward PBL at follow up phase compared to pre-program. Conclusion: There was highly statistically significant difference improvement found in the immediate post program between both groups with higher total mean scores in PBL group than TBL group during immediate post program. Also, there was highly statistically significant positive correlation between total managerial skills' knowledge and total managerial skills' practice at both groups. Recommendations: The study recommended that PBL strategy should be adopted by Faculty of Nursing Benha University for better skills and learning outcome, to allow students' interactions and encourage higher thinking level.
Cervical Spine Navigation and Enabled Robotics: A New Frontier in Minimally Invasive Surgery

Background: Robotic-assisted and computer-assisted navigation (CAN) systems utilization has been rapidly increasing in recent years. Most existing data using these systems are performed in the thoracic, lumbar, and sacral spine. The unique anatomy of the cervical spine maybe where these technologies have the greatest potential. To date, the role of navigation-enabled robotics in the cervical spine remains in its early stages of development and study. Purpose: This review article describes the early experience, case descriptions and technical considerations with cervical spine screw fixation and decompression using CAN and robotic-assisted surgery. Methods: Representative cervical cases with early surgical experience with cervical and robotic assisted surgery with CAN. Surgical set up, technique considerations, instrumentation, screw accuracy and screw placement were elevated and recorded for each representative cervical case. Results: Existing robotic assisted spine surgical systems are reviewed as they pertain to the cervical spine. Method for cervical reference and positioning on radiolucent Mayfield tongs are presented. C1 lateral mass, odontoid fracture fixation, C2 pedicle, translaminar, subaxial lateral mass, mid cervical pedicle, navigated decompression and ACDF cases and techniques are presented. Conclusion: In conclusion, within the last several years, the use of CANs in spinal surgery has grown and the cervical spine shows the greatest potential. Several robotic systems have had FDA clearance for use in the spine, but such use requires simultaneous intraoperative fluoroscopic confirmation. In the coming years, this recommendation will likely be dropped as accuracy improves.