Miracle-dz/UniFAR-FTUs huggingface dataset:
GenCoNet – A Graph Database for the Analysis of Comorbidities by Gene Networks

Abstract The prevalence of comorbid diseases poses a major health issue for millions of people worldwide and an enormous socio-economic burden for society. The molecular mechanisms for the development of comorbidities need to be investigated. For this purpose, a workflow system was developed to aggregate data on biomedical entities from heterogeneous data sources. The process of integrating and merging all data sources of the workflow system was implemented as a semi-automatic pipeline that provides the import, fusion, and analysis of the highly connected biomedical data in a Neo4j database GenCoNet. As a starting point, data on the common comorbid diseases essential hypertension and bronchial asthma was integrated. GenCoNet (https://genconet.kalis-amts.de) is a curated database that provides a better understanding of hereditary bases of comorbidities.
The relationship between childbearing motivations with fertility preferences and actual child number in reproductive-age women in Mashhad, Iran

INTRODUCTION: Motivation is directly involved in women's childbearing decision. Considering the lack of information about reproductive-age women's childbearing motivations with preferences and actual child number in Iran, this study was conducted to determine the relationship between childbearing motivations with the fertility preferences and actual child number of reproductive-age women. MATERIALS AND METHODS: The participants in this descriptive–correlational study were 844 reproductive-age women (aged 15–49 years) who were married for the first time and came from a wide range of areas in Mashhad. Multistage and convenience samplings were applied and the data were collected using Miller's childbearing motivation and fertility preferences and actual child number questionnaire. RESULTS: The results of the study reveal that positive- and negative-childbearing motivation were correlated with preferences (P < 0.001) but were not correlated with actual child number. Furthermore, the interactional variable derived by a combination of positive and negative motivations showed a significant relationship with the ideal and actual child number (P < 0.05). CONCLUSIONS: Childbearing motivations affect the fertility preferences in reproductive-age women but do not appear to have any influence on the actual child number. Furthermore, the interactional variables affect the ideal and actual child number.
White‐Light‐Emitting Melamine‐Formaldehyde Microspheres through Polymer‐Mediated Aggregation and Encapsulation of Graphene Quantum Dots

Graphene quantum dot (GQD) encapsulated melamine‐formaldehyde (MF) polymer microspheres with uniform particle size and tunable high‐quality white‐light emissions are prepared via a polymer‐mediated GQD assembly and encapsulation strategy. In solution, GQDs are first aggregated with MF prepolymer through electrostatic interaction and further encapsulated inside the microspheres formed by polymerization of MF prepolymer under acid catalysis and heating. During this process, the aggregated GQDs are fixed in the MF polymer matrix with their emission extended from blue to full visible range, presenting bright white luminescence under ultraviolet excitation. The prepared white‐light‐emitting GQD‐MF microspheres exhibit uniform morphology with an average particle size of 2.0 ± 0.08 µm and their luminescence properties are effectively regulated by the doping concentration of GQDs in the MF polymer matrix. A series of white‐light‐emitting GQD‐MF microspheres with quantum yields from 0.83 to 0.43, Commission Internationale de L'Eclairage coordinates from (0.28, 0.28) to (0.33, 0.32), and color rendering index from 0.75 to 0.88 are obtained with excellent photostability and thermal stability. By dispersing the GQD‐MF microspheres in cross‐linked polydimethylsiloxane matrix, flexible film with dual functions of high‐quality white‐light‐emitting and light diffusion is obtained and successfully applied for white light‐emitting diode fabrication.
Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment

Multiscale systems biology and systems pharmacology are powerful methodologies that are playing increasingly important roles in understanding the fundamental mechanisms of biological phenomena and in clinical applications. In this review, we summarize the state of the art in the applications of agent-based models (ABM) and hybrid modeling to the tumor immune microenvironment and cancer immune response, including immunotherapy. Heterogeneity is a hallmark of cancer; tumor heterogeneity at the molecular, cellular, and tissue scales is a major determinant of metastasis, drug resistance, and low response rate to molecular targeted therapies and immunotherapies. Agent-based modeling is an effective methodology to obtain and understand quantitative characteristics of these processes and to propose clinical solutions aimed at overcoming the current obstacles in cancer treatment. We review models focusing on intra-tumor heterogeneity, particularly on interactions between cancer cells and stromal cells, including immune cells, the role of tumor-associated vasculature in the immune response, immune-related tumor mechanobiology, and cancer immunotherapy. We discuss the role of digital pathology in parameterizing and validating spatial computational models and potential applications to therapeutics.
Risk factors for eclampsia in pregnant women with preeclampsia and positive neurosensory signs

Objective: In Morocco, eclampsia remains the second major cause of maternal mortality. Conventionally, patients with preeclampsia and neurosensory signs (NSS) (e.g., headaches and hyperreflexia) are considered at high risk of worsening and progressing to eclampsia. However, this specific population is heterogeneous in terms of eclampsia occurrence. We aimed to identify the risk factors for the development of eclampsia in women with preeclampsia presenting with NSS at admission. Materials and Methods: We performed a single-center, retrospective case-control study of patients with preeclampsia with positive NSS from January 1st, 2012 through December 31st, 2015, to investigate predictive factors for eclamptic seizures. The case patients were pregnant women with severe preeclampsia who had NSS before developing eclampsia. Control subjects were those with positive NSS without the development of seizures during their hospital stay. One hundred-thirty eight patients with eclampsia and 272 control patients were enrolled. Results: Univariate analysis revealed that eclampsia was more likely to develop in patients with the following risk factors: maternal age ≤25 years (χ2=9.58, p=0.002), primiparity (χ2=6.38, p=0.011), inadequate prenatal care (χ2=11.62, p=0.001), systolic hypertension ≥160 mmHg (χ2=15.31, p<0.001), diastolic hypertension ≥110 mmHg (χ2=5.7, p=0.017), generalized acute edema (χ2=14.66, p<0.001), hematocrit <35% (χ2=11.16, p=0.001), serum creatinine >100 μmol/L (χ2=13.46, p<0.001), asparate aminotransferase (AST) >70 IU/L (χ2=10.15, p=0.001), and thrombocytopenia (χ2=22.73, p<0.001). Additionally, independent predictive factors for eclampsia in multivariate analysis included inadequate prenatal care [odds ratio (OR), 8.96 [95% confidence interval (CI): 3.9-20.5], p<0.001), systolic blood pressure ≥160 mmHg (OR, 3.130 [95% CI: 1.342-7.305], p=0.008), thrombocytopenia with a platelet count <50.000 (OR, 13.106 [95% CI: 1.344-127.823], p=0.027), AST ≥70 IU (OR, 3.575 [95% CI: 1.313-9.736], p=0.007), and elevated liver enzymes level, and low platelet count (ELLP) syndrome, which is an incomplete variant of HELLP syndrome (H for hemolysis) (OR, 5.83 [95% CI: 2.43- 13.9], p<0.001). Conclusion: This work highlights two major risk factors in this patient population, inadequate prenatal care and ELLP syndrome, which can help in the early identification of patients at highest risk of developing eclampsia and guide preventive measures.
Ovo-lactovegetarian diet as a possible protective factor against gallbladder polyps in Taiwan: A cross-sectional study

Objective: Gallbladder polyps (GBPs) are an increasingly common incidental finding and 3% to 8% of GBPs become malignant. A poor prognosis is expected in patients with gallbladder cancer. No studies have considered the relationship between diet and the development of GBPs in the Taiwanese population. The objective of this study was to investigate whether a vegetarian diet protects against GBP development. Materials and Methods: This cross-sectional study included 11,717 individuals who received a health checkup at Taipei Tzu Chi Hospital (New Taipei City, Taiwan) between October 2011 and October 2016. All individuals completed questionnaires that collected data about their characteristics, dietary patterns, and lifestyle. Physical examinations were conducted, and blood chemistry tests were performed. The presence of GBPs was determined using ultrasonography. We subsequently evaluated the association between diet and GBP prevalence using multivariate analysis. Results: The prevalence of GBPs for the entire group was 8.3%. GBPs were significantly less common in the vegetarian groups (vegans 9.0%, ovo-lacto vegetarians 7.5%, and semi-vegetarians 7.2%) compared with the omnivore group (9.6%) (P = 0.002). Step-wise logistic regression revealed that an ovo-lacto vegetarian diet was a possible protective factor (odds ratio = 0.83, P = 0.015). Conclusions: The study findings showed a strong negative association between an ovo-lacto vegetarian diet and GBP occurrence.
Trigeminal Nerve Transection-Induced Neuroplastic Changes in the Somatosensory and Insular Cortices in a Rat Ectopic Pain Model

Abstract The primary sensory cortex processes competitive sensory inputs. Ablation of these competitive inputs induces neuroplastic changes in local cortical circuits. However, information concerning cortical plasticity induced by a disturbance of competitive nociceptive inputs is limited. Nociceptive information from the maxillary and mandibular molar pulps converges at the border between the ventral secondary somatosensory cortex (S2) and insular oral region (IOR); therefore, S2/IOR is a suitable target for examining the cortical changes induced by a disturbance of noxious inputs, which often causes neuropathic pain and allodynia. We focused on the plastic changes in S2/IOR excitation in a model of rats subjected to inferior alveolar nerve transection (IANX). Our optical imaging using a voltage-sensitive dye (VSD) revealed that the maxillary molar pulp stimulation-induced excitatory propagation was expanded one to two weeks after IANX at the macroscopic level. At the cellular level, based on Ca2+ imaging using two-photon microscopy, the amplitude of the Ca2+ responses and the number of responding neurons in S2/IOR increased in both excitatory and inhibitory neurons. The in vitro laser scanning photostimulation (LSPS) revealed that Layer II/III pyramidal and GABAergic fast-spiking neurons in S2/IOR received larger excitatory inputs from Layer IV in the IANX models, which supports the findings obtained by the macroscopic and microscopic optical imaging. Furthermore, the inhibitory postsynaptic inputs to the pyramidal neurons were decreased in the IANX models, suggesting suppression of inhibitory synaptic transmission onto excitatory neurons. These results suggest that IANX induces plastic changes in S2/IOR by changing the local excitatory and inhibitory circuits.
Risk assessment for perioperative pressure injuries*

ABSTRACT Objectives: to evaluate and classify patients according to the Risk Assessment Scale for Perioperative Pressure Injuries; verify the association between sociodemographic and clinical variables and the risk score; and identify the occurrence of pressure injuries due to surgical positioning. Method: observational, longitudinal, prospective and quantitative study carried out in a teaching hospital with 278 patients submitted to elective surgeries. A sociodemographic and clinical characterization questionnaire and the Risk Assessment Scale for Perioperative Pressure Injuries were used. Descriptive, bivariate and logistic regression analyses were applied. Results: the majority of patients (56.5%) presented a high risk for perioperative pressure injury. Female sex, elderly group, and altered body mass index values were statistically significant (p < 0.05) for a higher risk of pressure injuries. In 77% of the patients, there were perioperative pressure injuries. Conclusion: most of the participants presented a high risk for development of perioperative decubitus ulcers. The female sex, elderly group, and altered body mass index were significant factors for increased risk. The Risk Assessment Scale for Perioperative Pressure Injuries allows the early identification of risk of injury, subsidizing the adoption of preventive strategies to ensure the quality of perioperative care.
Risk Tolerance Measured by Probability Discounting Among Individuals With Primary Mood and Psychotic Disorders

Objective: Change in risk tolerance is a feature of multiple psychiatric disorders and may contribute to adverse outcomes. We used a probability discounting (PD) task to measure risk-taking behavior among individuals with bipolar disorder (BPAD), major depressive disorder (MDD), schizoaffective disorder (SCAD), and schizophrenia (SCZ). Method: A PD task was administered to 117 patients and 88 healthy controls (HCs), along with a cognitive battery using the Cambridge Neuropsychological Test Automated Battery, and relevant symptomatology scales. We examined differences in PD rates between diagnostic groups, and compared with HCs, while controlling for potential confounding factors including measures of cognitive functioning. Results: Individuals with a diagnosis of BPAD or SCAD/SCZ prefer smaller, more guaranteed rewards rather than larger, less likely rewards as compared with healthy controls (p = .002 and p = .034, respectively). There was no effect of performance on cognitive tasks, antipsychotic treatment, or symptomatology on the rate of probability discounting. Conclusion: This study supports the transdiagnostic measurement of risk-taking behaviors, even when such behaviors are not the primary area of psychopathology. Quantifying risk-taking may enable targeted therapeutic strategies across disorders.
Organophosphate Pesticide Metabolite Concentrations in Urine during Pregnancy and Offspring Nonverbal IQ at Age 6 Years

Background: Susceptibility to organophosphate (OP) pesticide neurotoxicity may be greatest during the prenatal period; however, previous studies have produced mixed findings concerning in utero OP pesticide exposure and child cognition. Objectives: Our objective was to determine whether maternal urinary concentrations of OP pesticide metabolites are inversely associated with child nonverbal IQ at 6 y of age and to examine potential effect measure modification by the PON1 gene. Methods: Data came from 708 mother–child pairs participating in the Generation R Study. Maternal urine concentrations of six dialkylphosphates (DAPs), collected at <18, 18–25, and >25 weeks of gestation, were determined. Child nonverbal IQ was measured at 6 y of age using the Mosaics and Categories subtests from the Snijders-Oomen Nonverbal Intelligence Test–Revised. PON1 was determined in cord blood for 474 infants. Multiple linear regression models were fit to estimate the DAP–IQ associations and PON1 interactions. Results: Overall, associations between child nonverbal IQ and maternal DAP concentrations were small and imprecise, and these associations were inconsistent across urine sampling periods. However, for a 10-fold difference in total DAP concentration for the >25 weeks of gestation samples, adjusted child nonverbal IQ was 3.9 points lower (95% CI: −7.5, −0.3). Heterogeneity in the DAP–IQ association by PON1 gene allele status was not observed (n=474). Conclusions: Consistent evidence of an association between higher maternal urinary DAP concentrations and lower child IQ scores at 6 y of age was not observed. There was some evidence for an inverse relation of child nonverbal IQ and late pregnancy urinary DAPs, but the estimated association was imprecise. https://doi.org/10.1289/EHP3024
Scleroderma-related interstitial lung disease: principles of management

ABSTRACT Introduction: Interstitial lung disease (ILD) is the most common cause of mortality in systemic sclerosis; accounting for approximately 35% of deaths. Although immunosuppression is currently opted as first line therapy for scleroderma-related ILD (SSc-ILD), the benefits from it remain modest with concerns for systemic toxicity from long term use. Areas covered: We review the important facets in monitoring a patient with SSc-ILD, including recognizing various patterns of ILD, identifying those at risk for disease progression and discuss the strength of evidence for immunosuppressant drugs and lung transplantation. We also discuss the potential role of anti-fibrotic agents and the existing evidence for myeloablative stem-cell transplantation. Expert commentary: Non-specific interstitial pneumonia (NSIP) is the most common radiologic and histopathologic pattern seen, but other forms of ILD may also be appreciated. Mycophenolate mofetil and cyclophosphamide are most commonly used as first line therapy for SSc-ILD; however, the efficacy of mycophenolate is comparable to cyclophosphamide with a better tolerability profile. Selected patients with SSc-ILD may be candidates for lung transplantation, although meticulous assessment for co-morbidities is crucial. Further studies are required to deduce the role of anti-fibrotic medications, biologic agents and effects of myeloablative stem cell transplantation in SSc.
Peak performance: Simulation and the nature of expertise in emergency medicine.

are bounded only by imagination. Fast forward a few years, and research combining measurements of acute stress, gaze tracking, pupillometry, and movement analysis, all under the analytic watch of black box technology may become reality. This, in turn, may help answer some of the most persistently vexatious questions about the nature of expertise in emergency medicine in a reliable, reproducible, and quanti ﬁ able way.
Improving Early Discharge Using a Team-Based Structure for Discharge Multidisciplinary Rounds

Purpose of Study: Miscommunications during the complex process of discharging patients from acute care facilities can lead to adverse events, patient dissatisfaction, and delays in discharge. Brief multidisciplinary discharge rounds (MDRs) can increase communication between stakeholders and shorten a patient's length of stay (LOS). At our tertiary academic medical center, case managers (CMs) have historically been assigned patients by physical unit location rather than by provider teams caring for patients. As a result, medicine teams often interact with several unit-based CMs due to lack of geographically cohorted patients, leading to inefficiency and fragmentation in discharge planning communication. Our aim was to implement and evaluate the impact of multidisciplinary, team-based discharge planning rounds (MDR) for general medicine patients. Primary Practice Setting: A tertiary academic medical center. Methodology and Sample: Using the model for continuous improvement, we implemented and optimized MDR on 2 of 4 internal medicine resident ward teams that care for general internal medicine patients, including creation of a multidisciplinary team, improving physician continuity. Results: During the pilot, 1,584 patients were discharged from all medicine teams—825 from pilot teams and 759 from control teams. The proportion of patients with discharge before noon (DBN) orders was 41.2% on pilot versus 29.6% on control teams. Length of stay was 92.2 hr versus 97.2 hr, and 30-day readmission rate was 16.0% versus 18.3% for the pilot versus control teams, respectively. After the pilot concluded, we continued to have resident continuity on pilot teams but returned to the unit-based CM model. During this time, the proportion of DBN orders and LOS were similar between the pilot and control teams (29.0% vs. 24.3% and 95.8 hr vs. 96.6 hr, respectively). The 30-day readmission rate was 12.6% compared with 18.9% for the pilot versus control teams. Implications for Case Management Practice: Our team-based MDR pilot improved interdisciplinary relationships and communication and resulted in shorter LOS, earlier discharge times, and lower 30-day readmissions.
Hepatic and Intestinal Multidrug Resistance-Associated Protein 2: Transcriptional and Post-transcriptional Regulation by Xenobiotics

We are daily exposed to a large number of pharmacological drugs, environmental pollutants, and natural toxins, which represent a potential toxic insult. The organism possesses a sophisticated system of detoxification particularly expressed in the liver, intestine, and kidney. This system consists of intracellular biotransformation enzymes that convert the toxins into more hydrophilic derivatives followed by their elimination through membrane transporters. Multidrug resistance-associated protein 2 (MRP2, ABCC2) is an important member of the ATP-binding cassette (ABC) superfamily of transporters localized at the apical membrane of polarized cells, such as hepatocytes, enterocytes, and renal tubular cells. MRP2 is proposed as a major actor in the elimination of endo- and xenobiotics, mainly conjugated with glucuronic acid, glutathione, and sulfate. The small intestine and the liver constitute relevant detoxification organs expressing MRP2 and therefore preventing absorption and promoting the hepatobiliary clearance of xenobiotics. MRP2 expression and/or function can be modulated by therapeutic drugs, herbal products, dietary compounds, and environmental pollutants. Consequently, MRP2 modulation could cause changes in tissue exposure, with potential toxicological and pharmacological consequences. This chapter reviews the information available on the role of hepatic and intestinal MRP2 in detoxification processes, and their regulation by xenobiotics, considering in particular its toxicological relevance. xenobiotics such as bortezomib, BPA, and sulforaphane regulate MRP2 as a result of the interaction with Nrf2. Alternatively, regulation of MRP2 activity by xenobiotics can occur without changes in transporter expression, as it was demonstrated to GNT. Finally, it is important to note that regulation of MRP2 activity by therapeutic agents can result in changes in their therapeutic efficacy or safety, or alternative in drug–drug interactions if other drugs, substrates of MRP2, are simultaneously administered. chickenMrp2; MSDs, membrane-spanning domains; MTX, methotrexate; NAPQI, N-acetyl-p-benzoquinone imine; NBDs, nucleotide-binding domains; NO, nitric oxide; Nrf2, nuclear factor-erythroid 2- related factor-2; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; PI3K, phosphoinositide 3-kinase; PPARα, peroxisome proliferator activated receptor alpha; PXR, pregnane X receptor; RARα, retinoic acid receptor α; RES, resveratrol; RXRα, retinoid X receptor α; SF, sulforaphane; SL, spironolactone; SULT, sulphotransferase; TLR4, tool-like receptor 4; UGT, UDP-glucuro-nosyltransferase.