Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunosuppressant Use and Gout in the Prevalent Solid Organ Transplantation Population

Introduction: Gout is a common comorbidity among solid organ transplantation patients and is usually attributed to the use of cyclosporine. This study aims to evaluate the prevalence of gout among solid organ transplantation patients to determine the prevalence in the tacrolimus era. Research Questions: To what degree is cyclosporine still used among prevalent solid organ transplantation patients? How prevalent is gout in the solid organ transplantation population not being treated by cyclosporine? Methods: Immunosuppressant regimens and gout prevalence among prevalent solid organ transplantation patients were assessed using retrospective claims data for a representative sample of commercially insured patients. For comparison to the prevalent solid organ transplantation population, immunosuppressant use at time of transplantation was compiled from published reports. Results: Between 2012 and 2016, the use of cyclosporine declined while use of tacrolimus increased, with greater cyclosporine use among prevalent versus incident solid organ transplantation patients. The prevalence of gout was 18.3%, 9.3%, and 9.1% for solid organ transplantation patients on cyclosporine, tacrolimus, and neither, respectively. Among all solid organ transplantation patients with gout, 66.6% and 21.5% were on tacrolimus versus cyclosporine. The prevalence of gout among noncyclosporine solid organ transplantation patients was significantly higher than in the general population without solid organ transplantation. Discussion: Despite declining cyclosporine use, gout prevalence remains high, with the majority of patients with gout receiving tacrolimus rather than cyclosporine. In summary, gout remains a frequent comorbidity of solid organ transplantation.
Stroke Prognostic Scores and Data-Driven Prediction of Clinical Outcomes After Acute Ischemic Stroke

Supplemental Digital Content is available in the text. Background and Purpose— Several stroke prognostic scores have been developed to predict clinical outcomes after stroke. This study aimed to develop and validate novel data-driven predictive models for clinical outcomes by referring to previous prognostic scores in patients with acute ischemic stroke in a real-world setting. Methods— We used retrospective data of 4237 patients with acute ischemic stroke who were hospitalized in a single stroke center in Japan between January 2012 and August 2017. We first validated point-based stroke prognostic scores (preadmission comorbidities, level of consciousness, age, and neurological deficit [PLAN] score, ischemic stroke predictive risk score [IScore], and acute stroke registry and analysis of Lausanne [ASTRAL] score in all patients; Houston intraarterial recanalization therapy [HIAT] score, totaled health risks in vascular events [THRIVE] score, and stroke prognostication using age and National Institutes of Health Stroke Scale-100 [SPAN-100] in patients who received reperfusion therapy) in our cohort. We then developed predictive models using all available data by linear regression or decision tree ensembles (random forest and gradient boosting decision tree) and evaluated their area under the receiver operating characteristic curve for clinical outcomes after repeated random splits. Results— The mean (SD) age of the patients was 74.7 (12.9) years and 58.3% were men. Area under the receiver operating characteristic curves (95% CIs) of prognostic scores in our cohort were 0.92 PLAN score (0.90–0.93), 0.86 for IScore (0.85–0.87), 0.85 for ASTRAL score (0.83–0.86), 0.69 for HIAT score (0.62–0.75), 0.70 for THRIVE score (0.64–0.76), and 0.70 for SPAN-100 (0.63–0.76) for poor functional outcomes, and 0.87 for PLAN score (0.85–0.90), 0.88 for IScore (0.86–0.91), and 0.88 ASTRAL score (0.85–0.91) for in-hospital mortality. Internal validation of data-driven prediction models showed that their area under the receiver operating characteristic curves ranged between 0.88 and 0.94 for poor functional outcomes and between 0.84 and 0.88 for in-hospital mortality. Ensemble models of a decision tree tended to outperform linear regression models in predicting poor functional outcomes but not in predicting in-hospital mortality. Conclusions— Stroke prognostic scores perform well in predicting clinical outcomes after stroke. Data-driven models may be an alternative tool for predicting poststroke clinical outcomes in a real-world setting.
IgM-RF pada Anak Terinfeksi Virus Dengue Tidak Berkorelasi dengan Jumlah Trombosit dan Hematokrit

Banyak teori diajukan untuk menjelaskan patogenesis trombositopenia dan hemokonsentrasi pada Infeksi Virus Dengue (IVD), termasuk teori autoimun. Hal ini menimbulkan pertanyaan apakah Rheumatoid Factor (RF) yang biasa ditemukan pada pasien autoimun juga ditemukan dan berhubungan dengan perubahan jumlah trombosit dan nilai hematokrit pada pasien IVD. Tujuan penelitian adalah untuk membuktikan hubungan RF dengan jumlah trombosit dan nilai hematokrit pada anak terinfeksi virus dengue. Desain penelitian menggunakan analisis korelatif dengan pendekatan belah lintang dilakukan terhadap 40 pasien yang mengalami demam minimal 4 hari dan memenuhi kriteria diagnostik IVD menurut WHO 2009, usia di bawah 14 tahun, dan diagnosis dikonfirmasi dengan antibodi antidengue. Pasien dengan riwayat penyakit autoimun dan riwayat immunocompromised dikeluarkan dari penelitian. Sampel diambil secara konsekutif. Darah rutin diperiksa penggunakan hematology analyzer sedangkan RF diperiksa dengan metode aglutinasi lateks. Data diolah dengan uji korelasi Spearman. Hasil penelitian menunjukkan pasien dengan RF (+) sebanyak 62,5%. Hasil uji korelasi RF dan jumlah trombosit menunjukkan nilai r=0,151 dengan p=0,354 sedangkan hasil uji korelasi RF dan nilai hematokrit nilai r=0,3 dengan p=0,06. Penelitian ini menunjukkan bahwa tidak terdapat korelasi antara kadar RF serum dengan jumlah trombosit pada pasien IVD dan antara kadar RF serum dengan nilai hematokrit pada pasien IVD, walaupun ada kecenderungan peningkatan kadar RF serum diiringi dengan kenaikan nilai hematokrit.
Neonatal seizures: our experience of incidence, etiology and outcome in a tertiary care centre

Context: Neonatal seizures often evoke a sense of urgency among physician in charge of newborn as they often indicate a CNS dysfunction. Incidence of neonatal seizures remains high in our community even in this era of advanced perinatal care. Early detection of seizure and its etiology help us to provide specific therapy. Objectives: The purpose of this study was to determine the incidence, etiology and outcome of neonatal seizures. Settings and design: Prospective hospital based descriptive study conducted in the neonatal unit of tertiary care hospital. Material and methods: Consecutive newborns admitted with seizures were included in this study. Data were collected regarding relevant history and examination, thoroughly evaluated for etiology and outcome was documented. Analysed by descriptive statistics and conclusions were drawn. Results: One hundred and eight newborns with seizures were included during study period and incidence of neonatal seizure was 5.5%. Hypoxic ischemic encephalopathy (HIE) and sepsis constituted the most common etiologies. HIE was the most common etiology associated with mortality. Abnormal EEG with supressed background activity was present in majority of mortality cases. Conclusion: Most of the cases had multifactorial etiology. Measures for prevention, prompt recognition and specific management of neonatal seizure help to reduce the burden of neonatal morbidity in the community. Key words: Neonatal seizures, newborn, hypoxia-ischaemia, etiology, mortality
Surface-Specific Caries Preventive Effect of an Intervention Comprising Fissure Sealant, Povidone-Iodine and Fluoride Varnish in a Remote Indigenous Community in Australia

This study evaluates the effect of a topical intervention comprising of fissure sealant, povidone-iodine, and fluoride varnish in preventing caries on occlusal, approximal, and smooth surfaces. This three-year clinical trial was conducted in a remote Indigenous community of Australia. All schoolchildren (age range: 4–17) were invited to participate; those with parental consents to receive three-annual epidemiological examinations and interventions constituted the experimental group, while those with consents for only the epidemiological examination formed a comparison group. The intervention group received an annual application of fissure sealant, povidone–iodine and fluoride varnish for two consecutive years along with the restoration of any cavitated lesions, while the comparison group did not receive any intervention except for the usual care that included emergency treatment and restorations. Incipient and advanced caries were recorded in the permanent dentition while data on confounding variables were collected through questionnaires. Caries increment and progression were the outcome variables. A total of 408 children participated in the baseline examination, 208 finished the study. After adjusting for confounders, the prevented fraction (PF) on occlusal surfaces for advanced caries in the experimental group was 76.1% (mean difference- −0.35, 95% CI: −0.67–0.04), while the PF for progression from incipient to advanced caries was 100%(mean difference- −0.30, 95% CI: −0.52–0.09). The mean number of smooth surfaces that progressed from incipient to advanced caries in the comparison group was more than twice that of the experimental group, the mean difference was −0.25 (95% CI: −0.46–−0.03) with a PF of 61%. The intervention was only effective in preventing advanced caries on occlusal surfaces and in halting the progression of caries on occlusal and smooth surfaces but not on approximal caries.
Factors Associated with the Development of Postnatal Depression After Cesarean Delivery: A Prospective Study

Purpose Pre-operative association factors (pain and psychological vulnerability) could significantly contribute to post-Cesarean pain; however, limited information is available on the development of postnatal depression (PND). We aimed to investigate the development of PND and its association with pain vulnerability and psychological vulnerability factors. Patients and Methods Women undergoing Cesarean delivery under spinal anesthesia were given pre-operative questionnaires, psychological and pain assessments including pain on local anesthetic injection during spinal anesthesia and mechanical temporal summation. Post-operative assessments were administered at 6 to 10 weeks post-Cesarean delivery via follow-up survey to assess post-Cesarean psychological and pain outcomes. Results PND occurred in 21.1% (43 of 205) of patients who underwent elective Cesarean delivery. An increased pre-operative pain score with movement (Odds ratio (OR) 1.65, 95% CI 1.12–2.44, p = 0.0110), anxiety about upcoming surgery (OR 1.02, 95% CI 1.00–1.04, p = 0.0429), higher pre-operative Hospital Anxiety and Depression Scale (HADS) subscale on anxiety (OR 1.25, 95% CI 1.07–1.45, p = 0.0041) and higher pre-operative central sensitization inventory (CSI) scores (OR 1.05, 95% CI 1.01–1.09, p = 0.0156) were independently associated with an increased risk of PND. Anticipated pain medication needs were associated with reduced risk of PND (OR 0.48, 95% CI 0.29–0.79, p = 0.0038) (Receiver operating characteristic (ROC) = 0.8177). Conclusion Higher pre-operative anxiety, pain score, central sensitization and lower anticipated pain medication needs were associated with increased risks of PND. Further work using larger sample size will be needed to validate the model in predicting PND development after Cesarean delivery.
Prognostic Nomogram for Patients with Radical Surgery for Non-Metastatic Colorectal Cancer Incorporating Hematological Biomarkers and Clinical Characteristics

Background There is a large difference in postoperative survival in patients with non-metastatic colorectal cancer. We aimed to develop nomograms incorporating both hematological biomarkers and clinical characteristics to predict overall survival (OS) in patients with radical surgery for non-metastatic colorectal cancer. Methods A retrospective analysis was performed on date from 508 patients who underwent radical resection of colorectal cancer at the Affiliated Tumor Hospital of Guangxi Medical University from December 2011 to December 2015. Simple random sampling was performed by dividing these patients into a training set (n=355) and validation set(n=153), which yielded a 7:3 ratio in the sample sizes between these groups. Based on COX regression analysis of the results from the training cohort, a nomogram was developed to predict the three-year and five-year overall survival rate, and internal verification was also performed. The nomogram prediction accuracy and discriminating ability were evaluated by Harrell’s C-index (C-index), calibration curves and were compared with the colorectal cancer TNM staging system. Results We found that age, degree of differentiation, T stage, N stage, neurological invasion, neutrophils, monocytes, HGB, and LDH were independent risk factors for predicting OS in patients with colorectal cancer. In the training cohort, the C index was 0.796 (95% CI: 0.761–0.831). In the validation cohort, the C index was 0.671 (95% CI: 0.656–0.686). The nomogram showed a stronger predictive ability than did TNM staging. Decision curve analysis showed that the nomogram had value in terms of clinical application. Conclusion Our nomogram combined hematological biomarkers and clinical characteristics and was highly effective in predicting OS in patients with non-metastatic colorectal cancer. Hence, our nomogram may provide a reference tool for clinicians to guide individualized treatment and follow-ups for patients with colorectal cancer.
Identification of Cholangiocarcinoma Associated with Hepatolithiasis via the Combination of miRNA and Ultrasound

Background Identification of cholangiocarcinoma (CCA) associated with hepatolithiasis (HL) is difficult. There is no effective method to discriminate CCA associated with HL (HL-CCA) from HL currently. Objective To explore the value of clinical data, ultrasonic characteristics and miRNA expression level in the identification of HL-CCA. Methods Thirty-one patients with HL-CCA in Huazhong University of Science and Technology Union Shenzhen Hospital were enrolled in the observation group, while 40 patients with HL alone were included in the control group. The clinical data, ultrasonic characteristics, and miRNA expression level of the two groups were recorded and analyzed to explore the potential indicators for the identification of HL-CCA. Results The accuracy of ultrasound in the diagnosis of HL-CCA was low (54.84%). Multivariate logistic regression analysis showed that liver abscess (P=0.021), indistinct border demarcation (P=0.015), non-homogenous echotexture (P=0.019), missed portal vein around lesion (P=0.032), miRNA-21 (P=0.018) and miRNA-221 (P=0.009) were the potential indicators for the identification of HL-CCA. The combined diagnosis based on logistic regression contained liver abscess, border demarcation, echotexture, portal vein around lesion, miRNA-21 and miRNA-221. The results showed that the accuracy of combined diagnosis identifying HL-CCA was the most accurate (AUC=0.911), which was significantly greater than the AUC of miRNA-21 or miRNA-221 individually (P<0.05), with a sensitivity and specificity of 77.42% and 97.50%, respectively. Conclusion Patients with HL-CCA show high incidence of hepatic abscess and elevated miRNA-21 and miRNA-221 expression level. The ultrasonic features are more likely to show indistinct border demarcation, non-homogenous echotexture, and missed portal vein around lesion. The combined diagnosis is more accurate in the identification of HL-CCA.
RAS, wanted dead or alive: Advances in targeting RAS mutant cancers

New signaling insights level the playing field against the notoriously “undruggable” protein RAS. Oncogenic RAS proteins, which are mutated in approximately 24% of all human cancers, have earned a well-deserved reputation as being “undruggable. ” However, several studies have challenged that reputation. With the first small molecules that directly target one oncogenic RAS mutant (G12C) undergoing clinical evaluation, there have been substantial advances in finding anti-RAS therapeutic strategies. Furthermore, new insights have come from the growing appreciation that neither all RAS proteins (HRAS, NRAS, and KRAS4A/KRAS4B) nor all oncogenic RAS mutations (such as at residues Gly12, Gly13, and Gln61) have the same impact on RAS signaling and function. The role of the nonmutated, wild-type RAS proteins in the context of mutant RAS is increasingly considered to be targetable, with reports of strategies that directly disrupt either the RAS interaction with activating guanine nucleotide exchange factors (GEFs) or receptor tyrosine kinase–mediated and GEF-dependent RAS activation (such as by targeting the scaffolding phosphatase SHP2). Last, the development of agents that target downstream effectors of RAS signaling has advanced substantially. In this review, we highlight some important trends in the targeting of RAS proteins in cancer.
I NFLUENCE OF PROFESSION AL STRESS ON TEMPORA RY AND PERMANENT WORKIN G ABILITY OF EXPOSED WORKERS

Occupational stress presents a health risk and affects working ability, leaving also a significant economic impact. Our aim was to examine the effect of the level of professional stress on temporary and permanent working disability in exposed workers. The study included 3527 workers of various professions, who in the period 2011 -2016 on the territory of South East Serbia did the same job for at least last five years, and who were referred by their chosen doctor to the Disability Commission for the assessment of their permanent making disability due to a work injury or illness. The number of lost working days in relation to the level of occupational stress at their workplaces (the Occupational Stress Indexscore) was analyzed. There was an increase in the average number of lost working days in the subgroups of workers with higher levels of occupational stress. Additionally, the number of workers who were entitled to a disability pension increased in the subgroups of workers with a higher level of stress at work. The research implies that stress at the workplace significantly affects the temporary and permanent working ability of the exposed workers. Acta Medica Medianae 2017;56(3):129-136.
Bag-Valve Mask versus Endotracheal Intubation in Out-of-Hospital Cardiac Arrest on Return of Spontaneous Circulation: A National Database Study

Background Out-of-hospital cardiac arrest is the main issue for pre-hospital emergency care. There are several airway managements during the out-of-hospital cardiopulmonary resuscitation (CPR) such as endotracheal intubation (ETI) or alternative airway device: bag-valve mask (BVM). Data comparing both methods showed inconclusive results on survival and limited results on CPR outcome. This study aimed to add additional results on comparing the ETI and BVM in cardiac arrest outside hospitals; focused on the CPR outcome. Methods This study was a retrospective, analytical study. The inclusion criteria were adult patients (age of 18 years or over) with out-of-hospital cardiac arrest, who received emergency life support, and received either BVM or ETI. Data were retrieved from the Information Technology of Emergency Medical Service. The outcome was a return of spontaneous circulation (ROSC). Results During the study period, there were 1070 patients with out-of-hospital cardiac arrest who met the study criteria. Of those, 800 patients (74.77%) received BVM, while the other 270 patients (25.23%) received ETI. There were five significant factors between both groups including mean distance to scene, proportions of response time less than 8 mins, defibrillation, intravenous fluid administration, and adrenaline administration. There was no significant difference on the outcome: ROSC. The BVM group had slightly higher rate of ROSC than the ETI group (19.63% vs 15.56%; p value 0.148). Conclusion The BVM and ETI had comparable ROSC rate for out-of-hospital cardiac arrest victims. However, the study population of the BVM group had less severe conditions and received faster treatment than the ETI group.
Phylogenomics, biogeography and morphometrics reveal rapid phenotypic evolution in pythons after crossing Wallace's line.

Ecological opportunities can be provided to organisms that cross stringent biogeographic barriers towards environments with new ecological niches. Wallace's and Lyddeker's lines are arguably the most famous biogeographic barriers, separating the Asian and Australo-Papuan biotas. One of the most ecomorphologically diverse groups of reptiles, the pythons, is distributed across these lines, and are remarkably more diverse in phenotype and ecology east of Wallace's line in Australo-Papua. We used an anchored hybrid enrichment approach, with near complete taxon sampling, to extract mitochondrial genomes and 376 nuclear loci to resolve and date their phylogenetic history. Biogeographic reconstruction demonstrates that they originated in Asia around 38-45 Ma and then invaded Australo-Papua around 23 Ma. Australo-Papuan pythons display a sizeable expansion in morphological space, with shifts towards numerous new adaptive optima in head and body shape, coupled with the evolution of new micro-habitat preferences. We provide an updated taxonomy of pythons and our study also demonstrates how ecological opportunity following colonization of novel environments can promote morphological diversification in a formerly ecomorphologically conservative group.
Deterioration of hematopoietic autophagy is linked to osteoporosis

Hematopoietic disorders are known to increase the risk of complications such as osteoporosis. However, a direct link between hematopoietic cellular disorders and osteoporosis has been elusive. Here, we demonstrate that the deterioration of hematopoietic autophagy is coupled with osteoporosis in humans. With a conditional mouse model in which autophagy in the hematopoietic system is disrupted by deletion of the Atg7 gene, we show that incapacitating hematopoietic autophagy causes bone loss and perturbs osteocyte homeostasis. Induction of osteoporosis, either by ovariectomy, which blocks estrogen secretion, or by injection of ferric ammonium citrate to induce iron overload, causes dysfunction in the hematopoietic stem and progenitor cells (HSPCs) similar to that found in autophagy‐defective mice. Transcriptomic analysis of HSPCs suggests promotion of iron activity and inhibition of osteocyte differentiation and calcium metabolism by hematopoietic autophagy defect, while proteomic profiling of bone tissue proteins indicates disturbance of the extracellular matrix pathway that includes collagen family members. Finally, screening for expression of selected genes and an immunohistological assay identifies severe impairments in H vessels in the bone tissue, which results in disconnection of osteocytes from hematopoietic cells in the autophagy‐defective mice. We therefore propose that hematopoietic autophagy is required for the integrity of H vessels that bridge blood and bone cells and that its deterioration leads to osteoporosis.