Miracle-dz/UniFAR-FTUs huggingface dataset:
Perforating and Nonperforating Crohn's Disease An Unpredictable Guide to Recurrence After Surgery

Four hundred eighty-six patients who have had resections for Crohn's disease at the Cleveland Clinic were reviewed. The patients were categorized by indication for surgery into three groups: perforating (P) (135 patients), nonperforating (NP) (278 patients), and miscellaneous (M) (77 ) patients. One hundred ninety-four patients had two or more resections and 56 underwent a third resection. Patients were no more likely to have the same indication for surgery at the time of the second resection (P = 25 percent; NP : 44 percent; M = 57 percent) or the third resection (P = 11 percent; NP = 65 percent; M = 55 percent). There was also no difference in the interval between resections for the P and NP groups. The lack of agreement between resections suggests that the categorization of patients into P and NP groups does not facilitate prediction of the nature of recurrent disease. The concept of aggressive perforating and indolent nonperforating Crohn's is not substantiated by this study. [
Automated lipid droplet quantification system for phenotypic analysis of adipocytes using CellProfiler

Abstract Adipogenic differentiation is the process by which preadipocytes become mature adipocytes, cells that store energy and regulate metabolic homeostasis. During differentiation, neutral lipids that accumulate in adipocytes can be detected using stains and used as an index of cell differentiation. However, imaging tools for evaluating intracellular lipid droplets remain at their infancy. Nutrition, stress, or chemical exposure can dysregulate adipogenic differentiation and lipid metabolism. Therefore, the aims of this study were to develop an accurate, standardized approach to quantify lipid droplet size of mature adipocytes and a clustering approach to analyze the total lipid content per adipocyte. For the lipid droplet analysis, we used two approaches, the free online computer software of reference, ImageJ, and another free online computer software, CellProfiler. For ImageJ, we used an already developed macro designed to identify particles and quantify their area, and for CellProfiler, we developed a new analysis pipeline. Our results show that CellProfiler is able to accurately identify a greater number of lipid droplets compared to ImageJ. A clustering analysis is also possible using CellProfiler which allows for the quantification of total lipid content per individual adipocyte to provide insight into single-cell responsiveness to adipogenic stimuli. CellProfiler streamlines the lipid droplet phenotypic analysis of adipocytes compared to more traditional analysis methods. In conclusion, this novel image analysis tool can provide a more precise evaluation of lipid droplet and adipogenesis dysregulation, a critical need in the understanding of metabolic disorders.
New Strategies in Clinical Guideline Delivery: Randomized trial of online, interactive decision-support versus guidelines for HIV treatment selection by trainees.

BACKGROUND Support for clinicians in HIV medicine is critical given national HIV-provider shortages. Department of Health and Human Services (DHHS) guidelines are comprehensive but complex to apply for antiretroviral therapy (ART) selection. HIV-ASSIST (www.hivassist.com) is a free tool providing ART decision-support that could augment implementation of clinical practice guidelines. METHODS We conducted a randomized study of medical students and residents at Johns Hopkins University, in which participants were asked to select an ART regimen for 10 HIV case-scenarios through an electronic survey. Participants were randomized to receive either DHHS guidelines alone (with video tutorial), or DHHS guidelines and HIV-ASSIST (with video tutorial) to support their decision-making. ART selections were graded 'appropriate' if consistent with DHHS guidelines, or concordant with regimens selected by HIV experts at four academic institutions. RESULTS Among 118 trainees, participants randomized to receive HIV-ASSIST had significantly higher percentage of appropriate ART selections compared to those receiving DHHS guidelines alone (% appropriate responses in DHHS vs HIV-ASSIST arms: median 40% [Q1, Q3: 30%, 50%] vs 90% [80%, 100%], p<0.001). This difference was consistent among both medical students (median 40% vs 90%, p<0.001) and residents (median 40% vs 90%, p<0.001). The effect was seen for all case-types, but most pronounced for complex cases involving ART-experienced patients with ongoing viremia (DHHS vs HIV-ASSIST: median 0% [0%, 33%] vs 100% [66%, 100%]). CONCLUSION Trainees using HIV-ASSIST were significantly more likely to choose appropriate ART regimens compared to those using guidelines alone. Interactive decision-support tools may be important to ensure appropriate implementation of HIV guidelines.
Correlation of Cardiac and Liver Iron Level with T2*MRI and Vitamin D3 Serum Level in Patients with Thalassemia Major

Introduction Thalassemia is a hypochromic microcytic anemia, which is characterized by congenital disorders. In thalassemia patients, bone diseases are one of the causes of mortality. Our goal was to investigate the association between vitamin D deficiency and increased iron uptake by cardiac myocytes and hepatocytes. Materials and Methods Forty patients with thalassemia major were studied in Amir Kabir Hospital, Arak, Iran. The information obtained through clinical examination. Serum ferritin level was determined by ELISA and T2*MRI performed for measuring iron content in the heart and the liver. Results The average age of the patients was 23.8 ± 10.7 years. The mean T2*MRI values were 23.7 ± 7. The vitamin D3 level in 33 patients (82.5% cases) was less than 20 ng/dl, 2 patients (5%) in the range of 20–30 ng/dl, and the others had above 30 ng/dl. Correlation between vitamin D and age was 0.611. Correlation coefficient between heart and liver T2*MRI with ferritin level in patients was 0.437 and 0.335, respectively. Conclusion Due to significant associations, the periodic measurement of vitamin D, as well as PTH, is recommended for patients with thalassemia major.
Hyperthermic intraperitoneal chemotherapy enhances blood coagulation perioperatively evaluated by thromboelastography: a pilot study

Abstract Background and Objectives Postoperative thromboembolism is a significant cause of prolonged recovery in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Thromboelastography (TEG) can detect hypercoagulable states and predict thromboembolic complications after surgery. This study assessed the impact of CRS and HIPEC on TEG values. Methods TEG parameters reaction time (R), kinetics time (K), angle (α), maximum amplitude (MA), and lysis percent at 60 min (LY60) were determined preoperatively, and at the end of CRS, during HIPEC, and at the end of the operation using blood samples from 15 HIPEC patients. Platelets, P-TT, and aPTT were also determined before and after CRS. Results A total of 75 samples were analyzed. During CRS, there was a significant reduction in the mean MA (3.06 mm, p = 0.001). The mean P-TT declined by 32% (p < 0.001) and mean platelets by 55 × 109/L (p < 0.001). During HIPEC, the mean R and K shortened by 1.04 min (p = 0.015) and 0.18 min (p = 0.018), respectively, whereas α increased by 2.48° (p = 0.005). Conclusions During CRS, both TEG and conventional laboratory tests indicated hypocoagulation. During HIPEC, however, the initiation of coagulation and the kinetics of thrombin formation were accelerated.
Development and evaluation of a food frequency questionnaire for use among young children

Background/Objectives This study described the development of a parent food frequency questionnaire (FFQ) for measuring diets of young children over the past month and the validation of this FFQ against three non-consecutive 24 hour recalls. Subjects/Methods Food and nutrient intakes from a 68-item FFQ were compared with three non-consecutive 24 hour recalls in a follow-up cohort of children aged 1.5, 3.5 and 5.0 years old. Data from both methods were available for 231, 172 and 187 participants at ages 1.5, 3.5 and 5.0 years, respectively. Results Out of 11 nutrients, four (protein, fat, fibre, iron), two (Vitamin C, folate) and three (protein, vitamin C and folate) nutrients showed good-acceptable outcome for 2 out of 3 group-level validation tests at ages 1.5, 3.5 and 5.0 years, respectively. Of 26 food groups, good-acceptable outcome for 2 out of 3 group-level validation tests was revealed for two, four and six food groups at ages 1.5, 3.5 and 5.0 years, respectively. For individual-level validation tests, all nutrients showed good-acceptable outcome for 2 out of 3 individual level tests across three time points, except for folate at age 1.5 years and energy intake at age 3.5 years. Most food groups (22 out of 26) at age 1.5 years and all food groups at both ages 3.5 and 5.0 years showed good-acceptable outcome for 2 out of 3 individual-level validation tests. Conclusions At all three time points, the FFQ demonstrated good-acceptable validity for some nutrients and food groups at group-level, and good-acceptable validity for most nutrients and food groups at individual-level. This quantitative FFQ is a valid and robust tool for assessing total diet of young children and ranking individuals according to nutrient and food intakes.
Updates and new perspectives in nonmelanoma skin cancer therapy: highlights from 'Immunotherapy Bridge'.

Over the last few years, extensive research has improved our understanding of tumor immunology and has enabled the development of novel treatments. The state of the art of immunotherapy in various types of malignancies was exhaustively discussed in the 'Immunotherapy bridge' meeting, which was held in Naples on 4-5 December 2019. Highlights related to the immunological treatment of nonmelanoma skin cancer are the content of this article.
Salmonella expresses foreign genes during infection by degrading their silencer

Significance Foreign genes confer new properties upon organisms. However, their expression often requires overcoming the silencing effects of the heat-stable nucleoid structuring (H-NS, also referred to as histone-like nucleoid structuring) protein, which binds to AT-rich foreign DNA in enteric bacteria. We establish that Salmonella enterica degrades H-NS when inside macrophages and that the resulting decrease in H-NS abundance de-represses foreign genes, even those not bound by antisilencing DNA-binding proteins. Conservation in the amino acid sequences of both the protease degrading H-NS and H-NS itself suggests that enteric bacteria share the uncovered strategy to express foreign genes silenced by H-NS. The heat-stable nucleoid structuring (H-NS, also referred to as histone-like nucleoid structuring) protein silences transcription of foreign genes in a variety of Gram-negative bacterial species. To take advantage of the products encoded in foreign genes, bacteria must overcome the silencing effects of H-NS. Because H-NS amounts are believed to remain constant, overcoming gene silencing has largely been ascribed to proteins that outcompete H-NS for binding to AT-rich foreign DNA. However, we report here that the facultative intracellular pathogen Salmonella enterica serovar Typhimurium decreases H-NS amounts 16-fold when inside macrophages. This decrease requires both the protease Lon and the DNA-binding virulence regulator PhoP. The decrease in H-NS abundance reduces H-NS binding to foreign DNA, allowing transcription of foreign genes, including those required for intramacrophage survival. The purified Lon protease degraded free H-NS but not DNA-bound H-NS. By displacing H-NS from DNA, the PhoP protein promoted H-NS proteolysis, thereby de-repressing foreign genes—even those whose regulatory sequences are not bound by PhoP. The uncovered mechanism enables a pathogen to express foreign virulence genes during infection without the need to evolve binding sites for antisilencing proteins at each foreign gene.
Meditation Practice Improves Short-Term Changes in Heart Rate Variability

Background: It is well known that meditation improves the physical and psychological condition of its practitioners. This study investigated the heart rate variability response of meditation practitioners in two Chan master teaching environments, namely face-to-face and video classes. Methods: Experimental sessions were conducted, one featuring face-to-face classes and the other featuring video classes. The difference in participants’ physiological parameters (blood pressure and heart rate variability) between the two experimental sessions was determined. In the first session, physiological parameters were recorded twice, before and after one teaching course, and the second session took place one month after the first. The first and second sessions had 45 and 27 participants, respectively. Those involved in the first experiment had no experience with meditation, whereas participants in the second experiment had practiced meditation for an average of 9 years (range = 1 to 27 years). Both experiments were conducted once a week, with each session lasting 1.5 h. Results: For both experiments, both heart rate and heart rate variability by age significantly decreased after one teaching course. Conclusions: Chan meditation practitioners benefit from receiving both face-to-face and video class teaching from a Chan master.
Current Understanding of the Mechanism of Water Oxidation in Photosystem II and Its Relation to XFEL Data.

The investigation of water oxidation in photosynthesis has remained a central topic in biochemical research for the last few decades due to the importance of this catalytic process for technological applications. Significant progress has been made following the 2011 report of a high-resolution X-ray crystallographic structure resolving the site of catalysis, a protein-bound Mn4CaOx complex, which passes through ≥5 intermediate states in the water-splitting cycle. Spectroscopic techniques complemented by quantum chemical calculations aided in understanding the electronic structure of the cofactor in all (detectable) states of the enzymatic process. Together with isotope labeling, these techniques also revealed the binding of the two substrate water molecules to the cluster. These results are described in the context of recent progress using X-ray crystallography with free-electron lasers on these intermediates. The data are instrumental for developing a model for the biological water oxidation cycle. Expected final online publication date for the Annual Review of Biochemistry, Volume 89 is June 22, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Influence of chronic cocaine, methamphetamine, or heroin exposure on brain dopamine D1 receptor levels: Human and experimental animal studies

bjective and Hvpothesis: Supersensitivity of dopamine D l receptor-mediated intracellular signalling in the nucleus accumbens has been hypothesized as a mechanisrn underlying drug craving. In this regard, Schering-Plough Corp. (Madison, N.J.) is currently developing a D l dopamine antagonist in an effort to diminish the use of cocaine in chronic users of the drug, and prevent drug relapse. The objective of this study was to measure levels of the D l receptor protein in post mortem human brain of chronic users of methamphetamine. cocaine. heroin, and matched controls. Based on the evidence of D l receptor supersensitivity in animal studies, my tentative working hypothesis was that an increase in the nurnber of striatal (caudate, putamen, and nucleus accumbens) dopamine D l receptors would be observed. In order to rneasure the D l receptor with increased specificity and potentially measure homoligomen, a quantitative immunoblot technique was developed. For cornparison, I examined the effects of chronic methamphetamine administration on D l receptor protein levels in rat brain under controlled conditions. Methods: Dopamine D l receptor protein levels were deterrnined in brain membrane hornogenates of chronic users of cocaine, methamphetamine, heroin, and age-matched controls, by quantitative blot immunolabelling with a monoclonal antibody directed against the carboxy terminus of the humanlrat D l receptor. ResuIb: The native, human, striatal D l receptor protein migrated with an apparent molecular weight of 70-80 kDa. Following incubation with the endoglycosidase, peptide N-glycosidase F, the D l migrated at the predicted molecular weight of approxirnately 50 kDa, consistent with N-glycosylation of the D l receptor in human brain. The human brain regional distribution of the D l receptor protein was similar to that observed in previous radioligand binding and mRNA studies. Comparison of D l levels in subjects with Huntington's disease (a disorder in which D l receptor levels are known to be decreased) and matched controls revealed the predicted loss (-54%) of Dl receptor protein. No alterations in dopamine D l levels were observed in the human caudate nucleus, putamen, or cortical regions of methamphetamine, cocaine or heroin users in comparison to matched controls. However, D l immunoreactivity was significantly elevated in the nucleus accumbens of human, chronic methamphetamine users (+44%), but not in the cocaine or heroin users. No changes were observed in cortical or striatal D l levels of rats exposed to methamphetamine. Conclusions: These findings suggest an up-regulated D l receptor pathway in the nucleus accumbens of human, chronic methamphetamine users, which rnight be involved in some of the long-term behavioural effects of the psychostimulant, such as drug craving .
Surfing motility is a complex adaptation dependent on the stringent stress response in Pseudomonas aeruginosa LESB58

Cystic fibrosis (CF) is a genetic disease that affects mucin-producing body organs such as the lungs. Characteristic of CF is the production of thick, viscous mucus, containing the glycoprotein mucin, that can lead to progressive airway obstruction. Recently, we demonstrated that the presence of mucin induced a rapid surface adaptation in motile bacteria termed surfing motility, which data presented here indicates is very different from swarming motility. Pseudomonas aeruginosa, the main colonizing pathogen in CF, employs several stress coping mechanisms to survive the highly viscous environment of the CF lung. We used motility-based assays and RNA-Seq to study the stringent stress response in the hypervirulent CF isolate LESB58 (Liverpool Epidemic Strain). Motility experiments revealed that an LESB58 stringent response mutant (ΔrelAΔspoT) was unable to surf. Transcriptional profiling of ΔrelAΔspoT mutant cells from surfing agar plates, when compared to wild-type cells from the surfing edge, revealed 2,584 dysregulated genes. Gene Ontology and KEGG enrichment analysis revealed effects of the stringent response on amino acid, nucleic acid and fatty acid metabolism, TCA cycle and glycolysis, type VI secretion, as well as chemotaxis, cell communication, iron transport, nitrogen metabolic processes and cyclic-di-GMP signalling. Screening of the ordered PA14 transposon library revealed 224 mutants unable to surf and very limited overlap with genes required for swarming. Mutants affecting surfing included two downstream effector genes of the stringent stress response, the copper regulator cueR and the quinolone synthase pqsH. Both the cueR and pqsH cloned genes complemented the surfing deficiency of ΔrelAΔspoT. Our study revealed insights into stringent stress dependency in LESB58 and showed that surfing motility is stringently-controlled via the expression of cueR and pqsH. Downstream factors of the stringent stress response are important to investigate in order to fully understand its ability to colonize and persist in the CF lung.
Tools to map target genes of bacterial two‐component system response regulators

Summary Studies on bacterial physiology are incomplete without knowledge of the signalling and regulatory systems that a bacterium uses to sense and respond to its environment. Two‐component systems (TCSs) are among the most prevalent bacterial signalling systems, and they control essential and secondary physiological processes; however, even in model organisms, we lack a complete understanding of the signals sensed, the phosphotransfer partners and the functions regulated by these systems. In this review, we discuss several tools to map the genes targeted by transcriptionally acting TCSs. Many of these tools have been used for studying individual TCSs across diverse species, but systematic approaches to delineate entire signalling networks have been very few. Since genome sequences and high‐throughput technologies are now readily available, the methods presented here can be applied to characterize the entire DNA‐binding TCS signalling network in any bacterial species and are especially useful for non‐model environmental bacteria.
Pretreatment Factors Influencing Radiation Pneumonitis after Stereotactic Body Radiation Therapy in the Treatment of Lung Cancer

Objective Radiation pneumonitis (RP) is a dose-limiting toxicity that affects the treatment of lung cancer. Data on factors predictive of developing symptomatic RP after stereotactic body radiation therapy (SBRT) are limited. We reviewed data to identify pretreatment factors predictive of the development of symptomatic RP in patients’ lung cancer treated with SBRT. Methods Data were collected on 296 patients treated with SBRT for lung cancer. Factors available at time of consultation were analyzed for the development of symptomatic RP, defined as CTCAE v. 4.0 ≥ Grade 2. The factors analyzed included patient demographic, tumor-specific, and pretreatment pulmonary function data. Univariate and multivariate analyses were performed to assess for predictive factors. Results Median follow-up was 22 months. The rate of symptomatic RP was 16%. Univariate analysis showed an increased rate of symptomatic RP with treatments to the right lung (22% vs. 9%, p = 0.007), driven primarily by an increased rate of symptomatic RP when treating the right lower lobe (RLL) vs. other lobes (31 vs. 13%, p = 0.03). Patients with a history of prior lung directed therapy were also more likely to develop symptomatic RP (12% vs. 24%, p = 0.008). These statistical differences were retained on multivariate analysis. Conclusion SBRT to the right lung, especially the RLL, and to patients with a history of prior lung-directed therapy increases the risk of developing symptomatic RP after SBRT. Further studies on ways to predict and prevent symptomatic RP are needed.