Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytokine Levels in Critically Ill Children With Severe Sepsis and Their Relation With the Severity of Illness and Mortality

Objective: To study the baseline cytokine levels and their relation with the severity of illness and mortality in critically ill children with severe sepsis. Design: Subgroup analysis of a randomized, double-blind, placebo-controlled trial. Setting: Pediatric intensive care unit of a tertiary level teaching hospital in India. Patients: Fifty children with severe sepsis aged 3 months to 12 years. Material and Methods: Blood was collected at admission for estimation of pro-inflammatory (interleukin 6 [IL-6], IL-12p70, IL-17, and tumor necrotic factor α [TNF-α]) and anti-inflammatory (IL-10 and transforming growth factor β1 [TGF-β1]) cytokines. Primary Outcome: To find out correlation between cytokine levels and severity of illness scores (Pediatric Risk of Mortality [PRISM] III score, Sequential Organ Failure Assessment [SOFA], and Vasoactive-Inotropic Score [VIS]). Secondary Outcomes: To compare cytokine levels among survivors and nonsurvivors. Results: Baseline pro-inflammatory cytokine levels (median [interquartile range]) were IL-6: 189 (35-285) pg/mL, IL-12p: 48 (28-98) pg/mL, IL-17: 240 (133-345) pg/mL, and TNF-α: 296 (198-430) pg/mL; anti-inflammatory cytokine levels were IL-10: 185 (62-395) pg/mL and TGF-β1: 204 (92-290) ng/mL. Pro-inflammatory cytokines showed positive correlation with PRISM III score: IL-6 (Spearman correlation coefficient, ρ = 0.273, P = .06), IL-12 (ρ = 0.367, P = .01), IL-17 (ρ = 0.197, P = .17), and TNF-α (ρ = 0.284, P = .05), and anti-inflammatory cytokines showed negative correlation: IL-10 (ρ = −0.257, P = .09) and TGF-β (ρ = −0.238, P = .11). Both SOFA and VIS also showed weak positive correlation with IL-12 (ρ = 0.32, P = .03 and ρ = 0.31, P = .03, respectively). Among nonsurvivors (n = 5), the levels of all the measured pro-inflammatory cytokines were significantly higher as compared to survivors, IL-6: 359 (251-499) pg/mL versus 157 (97-223) pg/mL, P < . 0001, IL-12p70: 167 (133-196) pg/mL versus 66 (30-100) pg/mL, P < . 0001, IL-17: 400 (333-563) pg/mL versus 237 (122-318) pg/mL, P = . 009, and TNF-α: 409 (355-503) pg/mL versus 330 (198-415) pg/mL, P = . 002, respectively. Conclusion: In critically ill children with severe sepsis, pro-inflammatory cytokines (especially IL-12p70) showed a weak positive correlation with severity of illness and were significantly higher among nonsurvivors.
Comorbidity of HIV, hypertension, and diabetes and associated factors among people receiving antiretroviral therapy in Bahir Dar city, Ethiopia

Background: People living with human immunodeficiency virus (HIV) are facing an increased burden of noncommunicable diseases (NCDs) comorbidity. There is, however, paucity of information on the magnitude of HIV-NCDs comorbidity, its associated factors, and how the health system is responding to the double burden in Ethiopia. Objective: To determine the magnitude of comorbidity between HIV and hypertension or diabetes and associated factors among HIV-positive adults receiving antiretroviral therapy (ART) in Bahir Dar city, Ethiopia. Methods: A facility-based cross-sectional study was conducted among 560 randomly selected HIV-positive adults taking ART. Data were collected using a structured questionnaire and analyzed using SPSS version 23. Descriptive statistics were used to describe the data. A logistic regression model was fit to identify associated factors with comorbidity of HIV and NCDs. Results: The magnitude of comorbidity was 19.6% (95% confidence interval (CI): 16.0–23.0). Being older (55 and above years) adjusted odds ratio (AOR: 8.5; 95% CI: 3.2–15.1), taking second-line ART regimen containing tenofovir (AOR: 2.7; 95% CI: 1.3–5.6), and increased body mass index (BMI) ≥25 (AOR: 2.7; 95% CI: 1.2–6.5) were the factors associated with comorbidity. Participants reported that they were not managed in an integrated and coordinated manner. Conclusions: The magnitude of comorbidity among adults was high in the study area. Being older, second-line ART regimen and high BMI ≥25 increased the odds of having NCDs among HIV-positive adults. Targeted screening for the incidences of NCDs, addressing modifiable risk factors, and providing integrated care would help to improve the quality of life comorbid patients.
Putative Protein Biomarkers of Escherichia coli Antibiotic Multiresistance Identified by MALDI Mass Spectrometry

The commensal bacteria Escherichia coli causes several intestinal and extra-intestinal diseases, since it has virulence factors that interfere in important cellular processes. These bacteria also have a great capacity to spread the resistance genes, sometimes to phylogenetically distant bacteria, which poses an additional threat to public health worldwide. Here, we aimed to use the analytical potential of MALDI-TOF mass spectrometry (MS) to characterize E. coli isolates and identify proteins associated closely with antibiotic resistance. Thirty strains of extended-spectrum beta-lactamase producing E. coli were sampled from various animals. The phenotypes of antibiotic resistance were determined according to Clinical and Laboratory Standards Institute (CLSI) methods, and they showed that all bacterial isolates were multi-resistant to trimethoprim-sulfamethoxazole, tetracycline, and ampicillin. To identify peptides characteristic of resistance to particular antibiotics, each strain was grown in the presence or absence of the different antibiotics, and then proteins were extracted from the cells. The protein fingerprints of the samples were determined by MALDI-TOF MS in linear mode over a mass range of 2 to 20 kDa. The spectra obtained were compared by using the ClinProTools bioinformatics software, using three machine learning classification algorithms. A putative species biomarker was also detected at a peak m/z of 4528.00.
Stevens-Johnson Syndrome–Like Reaction After Exposure to Pembrolizumab and Recombinant Zoster Vaccine in a Patient With Metastatic Lung Cancer

Stevens-Johnson syndrome (SJS) is a life-threating mucocutaneous reaction predominantly induced by drugs. Targeted cancer therapies such as pembrolizumab, which has been approved for the treatment of metastatic malignancy, can cause severe skin toxicities, including SJS. They are rare and inconsistently reported. In this article, we report the case of a 80-year-old woman with metastatic non–small cell lung cancer who had a SJS-like eruption involving oral mucosa after 15 weeks of exposure of pembrolizumab (6 doses) and 7 days after 1 dose of recombinant zoster vaccine. SJS is a rare blistering disorder with high mortality rate and significant morbidity. Causes include drugs, herpes viruses, and immunization. The timing of the eruption soon after the receipt of recombinant zoster vaccine suggests a role of vaccination in our patient, yet patients receiving cancer immunotherapy may develop late-onset skin toxicity. Therefore, we recommend long-term monitoring for mucocutaneous reactions after initiation of pembrolizumab. Further research is needed to characterize the immunological pathogenesis and improve timely recognition and treatment strategies.
SUMOylation Stabilizes the Transcription Factor DREB2A to Improve Plant Thermotolerance1

SUMOylation increases the protein stability of DREB2A, a key transcription factor in the response to heat stress in plant cells. Heat stress (HS) has serious effects on plant development, resulting in heavy agricultural losses. A critical transcription factor network is involved in plant adaptation to high temperature. DEHYDRATION RESPONSIVE ELEMENT-BINDING PROTEIN2A (DREB2A) is a key transcription factor that functions in plant thermotolerance. The DREB2A protein is unstable under normal temperature and is degraded by the 26S proteasome; however, the mechanism by which DREB2A protein stability dramatically increases in response to HS remains poorly understood. In this study, we found that the DREB2A protein of Arabidopsis (Arabidopsis thaliana) is stabilized under high temperature by the posttranslational modification SUMOylation. Biochemical data indicated that DREB2A is SUMOylated at K163, a conserved residue adjacent to the negative regulatory domain during HS. SUMOylation of DREB2A suppresses its interaction with BPM2, a ubiquitin ligase component, consequently increasing DREB2A protein stability under high temperature. In addition, analysis of plant heat tolerance and marker gene expression indicated that DREB2A SUMOylation is essential for its function in the HS response. Collectively, our data reveal a role for SUMOylation in the maintenance of DREB2A stability under high temperature, thus improving our understanding of the regulatory mechanisms underlying HS response in plant cells.
Performance of the Modified Boston and Philadelphia Criteria for Invasive Bacterial Infections

In a multicenter study of infants 29 to 60 days old, the Boston and Philadelphia criteria misclassified a substantial number of infants with IBIs. BrightcoveDefaultPlayer10.1542/6129218681001PEDS-VA_2019-3538 Video Abstract BACKGROUND: The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated. METHODS: We assembled a multicenter cohort of infants 29 to 60 days of age who had cerebrospinal fluid (CSF) and blood cultures obtained. We report the performance of the modified Boston criteria (peripheral white blood cell count [WBC] ≥20 000 cells per mm3, CSF WBC ≥10 cells per mm3, and urinalysis with >10 WBC per high-power field or positive urine dip result) and modified Philadelphia criteria (peripheral WBC ≥15 000 cells per mm3, CSF WBC ≥8 cells per mm3, positive CSF Gram-stain result, and urinalysis with >10 WBC per high-power field or positive urine dip result) for the identification of invasive bacterial infections (IBIs). We defined IBI as bacterial meningitis (growth of pathogenic bacteria from CSF culture) or bacteremia (growth from blood culture). RESULTS: We applied the modified Boston criteria to 8344 infants and the modified Philadelphia criteria to 8131 infants. The modified Boston criteria identified 133 of the 212 infants with IBI (sensitivity 62.7% [95% confidence interval (CI) 55.9% to 69.3%] and specificity 59.2% [95% CI 58.1% to 60.2%]), and the modified Philadelphia criteria identified 157 of the 219 infants with IBI (sensitivity 71.7% [95% CI 65.2% to 77.6%] and specificity 46.1% [95% CI 45.0% to 47.2%]). The modified Boston and Philadelphia criteria misclassified 17 of 53 (32.1%) and 13 of 56 (23.3%) infants with bacterial meningitis, respectively. CONCLUSIONS: The modified Boston and Philadelphia criteria misclassified a substantial number of infants 29 to 60 days old with IBI, including those with bacterial meningitis.
Effect of HPV Status on Survival of Oropharynx Cancer with Distant Metastasis

Human papillomavirus (HPV)–positive oropharynx squamous cell carcinoma (OPSCC) is known to have improved survival over HPV-negative disease. However, it is largely unknown whether HPV status similarly affects survival in patients presenting with distant metastatic disease. We queried the National Cancer Database for OPSCC with distant metastasis. Kaplan-Meier curves and Cox proportional hazards regression models controlling for relevant demographics were used to evaluate overall survival. In total, 768 OPSCC cases were available for analysis with HPV and survival data: 50% of cases were HPV negative and 50% were HPV positive. The 1- and 2-year survival for HPV-negative disease was 49% and 27%, respectively, as compared with 67% and 42% in the HPV-positive cohort. HPV positivity was associated with improved median survival in treated and untreated patients. Age, comorbidities, and HPV status were predictive of improved survival on multivariate analysis. HPV-positive OPSCC has improved survival in the setting of distant metastatic presentation as compared with HPV-negative disease and shows greater responsiveness to treatment.
A “Step–Ramp–Step” Protocol to Identify the Maximal Metabolic Steady State

Supplemental digital content is available in the text. ABSTRACT The oxygen uptake (V̇O2) at the respiratory compensation point (RCP) closely identifies with the maximal metabolic steady state. However, the power output (PO) at RCP cannot be determined from contemporary ramp-incremental exercise protocols. Purpose This study aimed to test the efficacy of a “step–ramp–step” (SRS) cycling protocol for estimating the PO at RCP and the validity of RCP as a maximal metabolic steady-state surrogate. Methods Ten heathy volunteers (5 women; age: 30 ± 7 yr; V̇O2max: 54 ± 6 mL·kg−1·min−1) performed in the following series: a moderate step transition to 100 W (MOD), ramp (30 W·min−1), and after 30 min of recovery, step transition to ~50% POpeak (HVY). Ventilatory and gas exchange data from the ramp were used to identify the V̇O2 at lactate threshold (LT) and RCP. The PO at LT was determined by the linear regression of the V̇O2 versus PO relationship after adjusting ramp data by the difference between the ramp PO at the steady-state V̇O2 from MOD and 100 W. Linear regression between the V̇O2–PO values associated with LT and HVY provided, by extrapolation, the PO at RCP. Participants then performed 30-min constant-power tests at the SRS-estimated RCP and 5% above this PO. Results All participants completed 30 min of constant-power exercise at the SRS-estimated RCP achieving steady-state V̇O2 of 3176 ± 595 mL·min−1 that was not different (P = 0.80) from the ramp-identified RCP (3095 ± 570 mL·min−1) and highly consistent within participants (bias = −26 mL·min−1, r = 0.97, coefficient of variation = 2.3% ± 2.8%). At 5% above the SRS-estimated RCP, four participants could not complete 30 min and all, but two exhibited non–steady-state responses in blood lactate and V̇O2. Conclusions In healthy individuals cycling at their preferred cadence, the SRS protocol and the RCP are capable of accurately predicting the PO associated with maximal metabolic steady state.
Extracorporeal Cardiopulmonary Resuscitation for Out‐of‐Hospital Cardiac Arrest in Adult Patients

Abstract Extracorporeal cardiopulmonary resuscitation (ECPR) followed by targeted temperature management has been demonstrated to significantly improve the outcomes of out‐of‐hospital cardiac arrest (OHCA) in adult patients. Although recent narrative and systematic reviews on extracorporeal life support in the emergency department are available in the literature, they are focused on the efficacy of ECPR, and no comprehensively summarized review on ECPR for OHCA in adult patients is available. In this review, we aimed to clarify the prevalence, pathophysiology, predictors, management, and details of the complications of ECPR for OHCA, all of which have not been reviewed in previous literature, with the aim of facilitating understanding among acute care physicians. The leading countries in the field of ECPR are those in East Asia followed by those in Europe and the United States. ECPR may reduce the risks of reperfusion injury and deterioration to secondary brain injury. Unlike conventional cardiopulmonary resuscitation, however, no clear prognostic markers have been identified for ECPR for OHCA. Bleeding was identified as the most common complication of ECPR in patients with OHCA. Future studies should combine ECPR with intra‐aortic balloon pump, extracorporeal membrane oxygenation flow, target blood pressure, and seizure management in ECPR.
Augmentation of Tendon Graft–Bone Tunnel Interface Healing by Use of Bioactive Platelet-Rich Fibrin Scaffolds

Background: Platelet-rich fibrin (PRF) is a bioactive biomaterial wherein cytokines are enmeshed within the interconnecting fibrin network. PRF can be fabricated into a patch to augment healing of the interface between a tendon graft and bone tunnel. Hypothesis: The bioactivity of a PRF scaffold is preserved after PRF is mechanically compressed into a patch. A bioactive PRF patch could promote the incorporation of a tendon graft within the bone tunnel through the formation of a tendon-bone healing zone composed of both fibrocartilaginous tissue and new bone. Study Design: Controlled laboratory study. Methods: Bioactivity of PRF was evaluated through treatment of rabbit tenocytes with PRF-conditioned medium and cultivation of cells on a PRF patch. Cellular morphologic features, viability, and differentiation were analyzed accordingly. In an animal study, a rabbit tendon-bone healing model was established through use of New Zealand White rabbits. The implanted tendon graft was enveloped circumferentially with a bioactive PRF patch before being pulled through a bone tunnel in the proximal tibia. Micro–computed tomography (micro-CT) imaging and histological and biomechanical analyses of the tendon-bone interface were performed at 12 weeks postoperatively. Results: PRF improved the viability of the cultured tenocytes. The effects of PRF on in vitro mineralization of tenocytes were comparable with the effects of standard culture medium. The gene expressions of type I collagen and osteopontin were upregulated upon PRF treatment. For the in vivo study, micro-CT images revealed significant new bone synthesis at the tendon-bone interface in the PRF-enveloped group. The tendon-bone healing zone was characterized by abundant fibrocartilage tissue and new bone formation as demonstrated by histological analysis. Biomechanical testing showed significantly higher ultimate loads in the PRF-enveloped group. Conclusion: Bioactive PRF could effectively augment healing of tendon graft to bone by inducing the formation of a transitional tendon-bone healing zone composed of fibrocartilage and bone. Clinical Relevance: Complete healing of the tendon graft in the bone tunnel is a prerequisite for successful ligament reconstruction, which would allow early and aggressive rehabilitation and rapid return to preinjury activity level. From a translational standpoint, the PRF-augmented healing in this rabbit animal model showed a promising biological approach to enhance tendon graft to bone healing via promotion of the functional anchorage between the 2 different materials.
THE SUCCESS RATE OF ENDOFLAS POWDER MIXED WITH CURCUMIN GEL AS OBTURATING MATERIAL IN PRIMARY MOLARS: CASE- SERIES.

Introduction: Important requisites of an obturating material for primary teeth are that it should resorb at the same rate as the roots of a primary tooth, should be harmless to the periapical tissue and permanent tooth germ, resorb readily if pushed beyond the apex and must be easy to fill and remove as and when necessary. Nowadays herbal products are being recommended for use in dentistry because of their safety, efficacy, cultural acceptability and lesser side effects. Turmeric (Curcumin Longa), is a medicinal herb with bactericidal properties like anti-inflammatory and antimicrobial, thus it can be used as obturating material in primary teeth. Aims and objectives: To determine the efficacy of Endoflas powder mixed with Curcumin gel as obturating material in primary teeth. Materials and Methods: 4 primary molars indicated for pulpectomy in 4 children (4-9 year-old) were selected.After biomechanical preparation,the four primary molars were obturated with Endoflas powder mixed with Curcumin gel and its efficacy was evaluated both clinically and radiographically at 1 month and 3-month intervals. Conclusion: The Endoflas powder mixed with Curcumin gel showed faster resorption of the over pushed material within 1week, also showed a decrease in inter-radicular radiolucency after 1month and maintained until 3month follow-up. Keywords: Pulpectomy, Obturating materials, Curcumin, Endoflas, Antimicrobials, Turmeric.
An Algorithmic Immunohistochemical Approach to Define Tumor Type and Assign Site of Origin

Immunohistochemistry represents an indispensable complement to an epidemiology and morphology-driven approach to tumor diagnosis and site of origin assignment. This review reflects the state of my current practice, based on 15-years’ experience in Pathology and a deep-dive into the literature, always striving to be better equipped to answer the age old questions, “What is it, and where is it from? ” The tables and figures in this manuscript are the ones I “pull up on the computer” when I am teaching at the microscope and turn to myself when I am (frequently) stuck. This field is so exciting because I firmly believe that, through the application of next-generation immunohistochemistry, we can provide better answers than ever before. Specific topics covered in this review include (1) broad tumor classification and associated screening markers; (2) the role of cancer epidemiology in determining pretest probability; (3) broad-spectrum epithelial markers; (4) noncanonical expression of broad tumor class screening markers; (5) a morphologic pattern-based approach to poorly to undifferentiated malignant neoplasms; (6) a morphologic and immunohistochemical approach to define 4 main carcinoma types; (7) CK7/CK20 coordinate expression; (8) added value of semiquantitative immunohistochemical stain assessment; algorithmic immunohistochemical approaches to (9) “garden variety” adenocarcinomas presenting in the liver, (10) large polygonal cell adenocarcinomas, (11) the distinction of primary surface ovarian epithelial tumors with mucinous features from metastasis, (12) tumors presenting at alternative anatomic sites, (13) squamous cell carcinoma versus urothelial carcinoma, and neuroendocrine neoplasms, including (14) the distinction of pheochromocytoma/paraganglioma from well-differentiated neuroendocrine tumor, site of origin assignment in (15) well-differentiated neuroendocrine tumor and (16) poorly differentiated neuroendocrine carcinoma, and (17) the distinction of well-differentiated neuroendocrine tumor G3 from poorly differentiated neuroendocrine carcinoma; it concludes with (18) a discussion of diagnostic considerations in the broad-spectrum keratin/CD45/S-100-“triple-negative” neoplasm.
Bacteriological profile of urinary tract infections at a tertiary care hospital in Western Uttar Pradesh, India

Background: This prospective study was intended to identify the bacterial pathogens causing urinary tract infections and their antimicrobial resistance patterns in a tertiary care teaching hospital of Western Uttar Pradesh, India. Methods: Clean-catch mid-stream urine samples were collected from patients symptomatic for UTI. Samples were cultured aerobically on CLED agar and strains having significant growth (>10 5 cfu/ml) were further processed for identification using standard microbiological techniques and their antimicrobial susceptibility pattern evaluated by Kirby Bauer disk diffusion as per CLSI guidelines. Results: Out of the 2250 urine samples processed, 750 showed significant growth on aerobic culture. Thus, the prevalence of UTI in the population was 33.3%. E. coli was the commonest isolate (33.3%) followed by S. aureus (20 %), Klebsiella spp. (13.3%), Coagulase Negative Staphylococci (13.3%), Enterococcus spp . (6.7%), Pseudomonas spp . (6.7%) and Candida spp . (6.7%). Amongst these isolates, Gram negative bacilli have shown a high susceptibility to imipenem, levofloxacin, nitrofurantoin, linezolid and amoxyclav and Gram positive organisms towards levofloxacin, nitrofurantoin, linezolid, vancomycin and amikacin. Conclusions: This study has shown nitrofurantoin and fluoroquinolones to be the most effective drugs for the empirical therapy of UTI in our region. The study of antimicrobial susceptibility pattern of UTI in a particular area can guide the clinicians in the rational choice of antibiotic treatment so that misuse of antibiotics can be prevented.