Miracle-dz/UniFAR-FTUs huggingface dataset:
Early-Onset Pancreas Cancer: Clinical Descriptors, Genomics, and Outcomes.

BACKGROUND Recent evidence suggests a rising incidence of cancer in younger individuals. Herein, we report the epidemiologic, pathologic, and molecular characteristics of a patient cohort with early-onset pancreas cancer (EOPC). METHODS Institutional databases were queried for demographics, treatment history, genomic results and outcomes. Overall survival (OS) from date of diagnosis was estimated using Kaplan-Meier method. RESULTS Four hundred and fifty patients with EOPC were identified at Memorial Sloan Kettering between 2008 and 2018. Median OS was 16.3 months (95% confidence interval [CI] = 14.6 to 17.7 months) in the entire cohort and 11.3 months (95% CI = 10.2 to 12.2 months) for patients with stage IV disease at diagnosis. One hundred and thirty-two (29.3% of the cohort) underwent somatic testing; 21 of 132 (15.9%) had RAS wild-type cancers with identification of several actionable alterations, including ETV6-NTRK3, TPR-NTRK1, SCLA5-NRG1 and ATP1B1-NRG1 fusions, IDH1 R132C mutation, and mismatch repair deficiency. One hundred and thirty-eight (30.7% of the cohort) underwent germline testing; 44 of 138 (31.9%) had a pathogenic germline variant (PGV) and 27.5% harbored alterations in cancer susceptibility genes. Of patients seen between 2015 and 2018, 30 of 193 (15.5%) had a pathogenic germline variant. Among 138 who underwent germline testing, those with a PGV had a reduced all-cause mortality compared to patients without a PGV controlling for stage and year of diagnosis (hazard ratio = 0.42, 95%CI = 0.26 to 0.69). CONCLUSIONS PGVs are present in a substantial minority of patients with EOPC. Actionable somatic alterations were identified frequently in EOPC, enriched in the RAS wild-type subgroup. These observations underpin the recent guidelines for universal germline testing and somatic profiling in pancreatic ductal adenocarcinoma.
Anthocyanin-Rich Aronia Berry Extract Mitigates High-Fat and High-Sucrose Diet-Induced Adipose Tissue Inflammation by Inhibiting Nuclear Factor-κB Activation.

Obesity-induced inflammation in adipose tissue (AT) promotes the development of metabolic dysregulations by increasing macrophage recruitment in the stromal vascular fraction (SVF). The activation of nuclear factor-κB (NF-κB) signaling in macrophages serves as a pivotal mediator of AT inflammatory responses by increasing the expression of proinflammatory genes in obesity. Given the purported anti-inflammatory effects of berry consumption in humans, we evaluated if anthocyanin-rich aronia berry extract (ARN) can prevent obesity-induced AT inflammation in vivo. We also examined whether ARN suppresses lipopolysaccharide (LPS)-induced NF-κB activation in RAW 264.7 macrophages and mouse bone marrow-derived macrophages (BMDMs). Male C57BL/6J mice were fed a low-fat diet, a high-fat (HF), and high-sucrose (HS) diet or HF/HS diet supplemented with 0.2% ARN (HF/HS + ARN) for 14 weeks. Compared to HF-/HS-fed mice, ARN supplementation tended to decrease fasting serum glucose (P = .07). Furthermore, ARN supplementation significantly inhibited the phosphorylation of NF-κB p65 in epididymal AT with a concomitant decrease in the expression of Cd11b and Tnfα mRNAs in epididymal SVF isolated, compared with those from HF-/HS-fed mice. Consistent with these in vivo findings, ARN treatment significantly decreased the phosphorylation of p65 in LPS-stimulated RAW 264.7 macrophages and BMDMs. Moreover, ARN suppressed LPS-induced mRNA expression of inflammation mediators (iNos, Cox-2, Tnfα, Mcp-1, and Il-6) and glycolysis markers (Glut1, G6pdh, and Hk1) in both cell types. Taken together, our in vivo and in vitro results suggest that ARN supplementation may attenuate obesity-induced AT inflammation by inhibiting NF-κB signaling and glycolytic pathway in macrophages.
Acute necrotizing encephalopathy of childhood: a single-center experience

Background/aim Acute necrotizing encephalopathy is a rare type of acute encephalopathy characterized by multi-ocal brain lesions and associated severe neurological findings and various organ dysfunctions may accompany it. Materials and Methods Patients with acute necrotizing encephalopathy of childhood diagnosed by pediatric neurology and pediatric intensive care at Sami Ulus Maternity, Child Health and Diseases Training and Research Hospital between 2007 and 2020 were included in this study. Results Nine patients (six females, three males) with a mean age of 4.05 ± 1.94 years (age range 1–6.5) were included in this study. The interval range between fever and encephalopathy in patients was 1–4 days. Influenza A (3H1N1, one untyped) was detected in four patients, influenza B in three patients, and no cause was found in two patients. Major clinical findings other than febrile encephalopathy in all patients were a hemodynamic shock in seven patients, seizures in six patients, vomiting in five patients, dystonia in three patients, and flaccid paralysis in the upper extremity in one patient. Despite all our treatment approaches, including plasmapheresis, moderate to severe neurological sequelae was observed in all of our patients, who survived even with significant radiological improvement. Three patients for whom we could not perform plasmapheresis died. Conclusion Our study revealed that thalamic involvement increased as the interval shortened, and brainstem involvement increased in patients over four years of age. The presence of persistent vomiting accompanying encephalopathy during the parainfectious period and plasmapheresis treatment being a treatment option that could prevent mortality were cautionary for our study.
An examination by year of cases applied with caesarean hysterectomy because of placenta percreta in a tertiary centre: a retrospective cohort study.

OBJECTIVES To examine cases applied with caesarean hysterectomy because of placenta percreta by comparing changes in treatment strategies and complications according to year. MATERIAL AND METHODS A retrospective examination was made of 93 patients applied with caesarean hysterectomy with a diagnosis of placenta percreta in 5-year periods of 2005-2009, 2010-2014, and 2015-2019. Demographic characteristics were recorded, and previous caesareans, history of myomectomy and curettage, gestational weeks, and infant birthweight. Intraoperative and postoperative findings were recorded as operating time, length of stay in hospital and Intensive Care Unit (ICU), transfusion requirement, the amount of erythrocyte suspension (ES) and fresh frozen plasma (FFP) transfused, and requirement for massive transfusion. Anaesthesia type, complications, and the preferred skin-uterus incision were also recorded. RESULTS The 93 patients comprised 8 cases in the period 2005-2009, 23 in 2010-2014, and 62 in 2015-2019. The number of previous caesarean procedures was observed to increase in parallel with these case numbers. A significant increase was observed in the gestational week of birth, and infant birthweight, and a decrease in operating times. In later years there was seen to be a lower amount of ES and FFP transfused and fewer patients with massive transfusion. Preoperative diagnosis of placenta percreta, the highest preference for general anaesthesia, selection of midline vertical skin incision and uterine fundal incision were greatest in the period 2015-2019. CONCLUSIONS In cases with placenta percreta, of which there is an increasing incidence, maternal and infant outcomes can be optimised with prenatal diagnosis and planned caesarean hysterectomy by a multidisciplinary team with optimal prenatal preparation.
Associations of GNAS Mutations with Surgical Outcomes in Patients with Growth Hormone-Secreting Pituitary Adenoma

Background The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics. Methods We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor. Results GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively). Conclusion GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.
Medication strategies in first episode psychosis patients: A survey among psychiatrists

There is an ongoing debate regarding the optimal timing of discontinuation of antipsychotic drugs for patients with first episode psychosis. Although most guidelines recommend maintenance therapy for at least 1 or 2 years after reaching remission, study results indicate that early discontinuation may be beneficial for at least a subsample of patients. To date, little is known about which medication strategies are applied in patients recovering from a first psychotic episode. In this study, we examined the beliefs and practices of clinicians on medication discontinuation.
High-Altitude Adaptation: Mechanistic Insights from Integrated Genomics and Physiology

Abstract Population genomic analyses of high-altitude humans and other vertebrates have identified numerous candidate genes for hypoxia adaptation, and the physiological pathways implicated by such analyses suggest testable hypotheses about underlying mechanisms. Studies of highland natives that integrate genomic data with experimental measures of physiological performance capacities and subordinate traits are revealing associations between genotypes (e.g., hypoxia-inducible factor gene variants) and hypoxia-responsive phenotypes. The subsequent search for causal mechanisms is complicated by the fact that observed genotypic associations with hypoxia-induced phenotypes may reflect second-order consequences of selection-mediated changes in other (unmeasured) traits that are coupled with the focal trait via feedback regulation. Manipulative experiments to decipher circuits of feedback control and patterns of phenotypic integration can help identify causal relationships that underlie observed genotype–phenotype associations. Such experiments are critical for correct inferences about phenotypic targets of selection and mechanisms of adaptation.
Flexural strength of modified and unmodified acrylic denture base material after different processing techniques.

Background Conventional heat cure polymerized acrylic resin(unmodified) is most acceptable denture base material in dentistry since decades. It has been modified with reinforcement of fillers and different processing techniques were introduced to enhance its mechanical and physical properties. The objective of this research is to determine and compare the effect of different processing techniques on flexural strength of modified and unmodified denture base acrylic resin. Air circulating oven is introduced for the first time in this study and its efficacy is also compared with other conventional processing techniques. Methods In this study total number of 114 rectangular specimens were fabricated by conventional heat cured acrylic (Stellon QC 20, Dentsply) for Group A (n=57), and rubber reinforced acrylic resin (High impact, Meadway) for Group B (n=57). Three equipment including water bath, dry oven and air circulating oven were utilized for processing specimens individually. Each sub-group of processing techniques (n=19) were tested for flexural strength through a three-point bending test by a universal testing machine. The statistical analysis initiated with descriptive analysis followed by independent t test for mean comparison of flexural strength of all three processing techniques among both testing group. One-way ANOVA and 2-way ANOVA followed by Scheffe post hoc test were also applied. p-value of 0.05 or less was considered as significant. Results Statically significant p-value <0.001 was found in response of flexural strength in all processing techniques (water bath, dry oven, air circulating oven) of both testing groups. Water bath processing demonstrated highest flexural strength values in both denture base material used in this study. The unit used for flexural strength was MPa. Conclusion This study manifested highest flexural strength in conventional and rubber reinforced heat cure samples when processed through water bath. Air circulating oven also presented acceptable flexural strength in conventional heat cure acrylic resin specimens when compared with other techniques.
Evolutionary conservation of RNA sequence and structure

An RNA structure prediction from a single‐sequence RNA folding program is not evidence for an RNA whose structure is important for function. Random sequences have plausible and complex predicted structures not easily distinguishable from those of structural RNAs. How to tell when an RNA has a conserved structure is a question that requires looking at the evolutionary signature left by the conserved RNA. This question is important not just for long noncoding RNAs which usually lack an identified function, but also for RNA binding protein motifs which can be single stranded RNAs or structures. Here we review recent advances using sequence and structural analysis to determine when RNA structure is conserved or not. Although covariation measures assess structural RNA conservation, one must distinguish covariation due to RNA structure from covariation due to independent phylogenetic substitutions. We review a statistical test to measure false positives expected under the null hypothesis of phylogenetic covariation alone (specificity). We also review a complementary test that measures power, that is, expected covariation derived from sequence variation alone (sensitivity). Power in the absence of covariation signals the absence of a conserved RNA structure. We analyze artifacts that falsely identify conserved RNA structure such as the misuse of programs that do not assess significance, the use of inappropriate statistics confounded by signals other than covariation, or misalignments that induce spurious covariation. Among artifacts that obscure the signal of a conserved RNA structure, we discuss the inclusion of pseudogenes in alignments which increase power but destroy covariation.
Thermodynamics and Kinetic Studies of Iron(III) Adsorption by Olive Cake in a Batch System

The adsorption of Fe(III) ions from the aqueous solution model using olive cake as an adsorbent has been investigated. The influences of the initial pH, temperature, contact time and dosage of the adsorbent on adsorption performance have been experimentally verified by a batch method. The adsorbent used in this study exhib- ited a good adsorption potential at initial pH 4.5 for temperatures 28, 35 and 45 oC. The removal efficiency and distribution coefficient have also been determined for the adsorption system as a function of dosage of the adsorbent. The experimental results are described by Langmuir, Freundlich and Dubinin-Kaganer-Radushkevich (DKR) isotherm models. Experimental results show that the kinetic model of pseudo-second order provided a good description of the whole experi- mental data more than the kinetic of the Lagergren-first order.
A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse

Abstract The process of stopping antipsychotics may be causally related to relapse, potentially linked to neuroadaptations that persist after cessation, including dopaminergic hypersensitivity. Therefore, the risk of relapse on cessation of antipsychotics may be minimized by more gradual tapering. There is converging evidence that suggests that adaptations to antipsychotic exposure can persist for months or years after stopping the medication—from animal studies, observation of tardive dyskinesia in patients, and the clustering of relapses in this time period after the cessation of antipsychotics. Furthermore, PET imaging demonstrates a hyperbolic relationship between doses of antipsychotic and D2 receptor blockade. We, therefore, suggest that when antipsychotics are reduced, it should be done gradually (over months or years) and in a hyperbolic manner (to reduce D2 blockade “evenly”): ie, reducing by one quarter (or one half) of the most recent dose of antipsychotic, equivalent approximately to a reduction of 5 (or 10) percentage points of its D2 blockade, sequentially (so that reductions become smaller and smaller in size as total dose decreases), at intervals of 3–6 months, titrated to individual tolerance. Some patients may prefer to taper at 10% or less of their most recent dose each month. This process might allow underlying adaptations time to resolve, possibly reducing the risk of relapse on discontinuation. Final doses before complete cessation may need to be as small as 1/40th a therapeutic dose to prevent a large decrease in D2 blockade when stopped. This proposal should be tested in randomized controlled trials.
Why do young people engage in dating relationships during early adolescence? An inter-generational qualitative analysis from Blantyre, Malawi

Abstract Engagement in dating relationships plays an important role in the health trajectories of young people, particularly during the early adolescent period between ages 10–14. Yet little is known about such relationships among youth in low resource contexts. This study sought to contribute to the literature on this topic by exploring reasons why school-going young people aged 12–14 years engage in dating relationships in Blantyre, Malawi. A thematic analysis was used to code and analyse in-depth interview data from 23 young people and 19 caregivers. Against the backdrop of growing sexual desires and feelings of attraction, participants stressed harassment from boys and coercion from older men, peer pressure, social status attainment, financial deprivation and encouragement during initiation ceremonies as reasons for engaging in dating relationships. Girls were found to be subject to multiple power dynamics—including gender power relations, as well as power dynamics within same-gender peer groups—that influenced their sex and relationship involvement. These findings carry implications for the design and timing of sexual and reproductive health youth programmes in Sub-Saharan Africa and emphasise the need for multi-level interventions to address the multiple influences in young people’s dating lives.
DNA affinity purification sequencing and transcriptional profiling reveal new aspects of nitrogen regulation in a filamentous fungus

Significance Microorganisms have evolved transcriptional networks to prioritize utilization of available nutrient sources. For filamentous fungi, such as Neurospora crassa, this entails distinguishing between a variety of organic and inorganic nitrogen sources. Here, we transcriptionally profiled the response of N. crassa to a variety of nitrogen sources and used DNA affinity purification sequencing to characterize the role of regulatory genes and their direct downstream targets. We identified a transcription factor responsible for regulating genes involved in amino acid and mannose metabolism. By comparing the genes regulated by transcription factors that regulate specific nitrogen utilization pathways and transcription factors that regulate utilization of all nitrogen sources that require metabolic processing before utilization, we revealed aspects of the nitrogen regulatory network. Sensing available nutrients and efficiently utilizing them is a challenge common to all organisms. The model filamentous fungus Neurospora crassa is capable of utilizing a variety of inorganic and organic nitrogen sources. Nitrogen utilization in N. crassa is regulated by a network of pathway-specific transcription factors that activate genes necessary to utilize specific nitrogen sources in combination with nitrogen catabolite repression regulatory proteins. We identified an uncharacterized pathway-specific transcription factor, amn-1, that is required for utilization of the nonpreferred nitrogen sources proline, branched-chain amino acids, and aromatic amino acids. AMN-1 also plays a role in regulating genes involved in responding to the simple sugar mannose, suggesting an integration of nitrogen and carbon metabolism. The utilization of nonpreferred nitrogen sources, which require metabolic processing before being used as a nitrogen source, is also regulated by the nitrogen catabolite regulator NIT-2. Using RNA sequencing combined with DNA affinity purification sequencing, we performed a survey of the role of NIT-2 and the pathway-specific transcription factors NIT-4 and AMN-1 in directly regulating genes involved in nitrogen utilization. Although previous studies suggested promoter binding by both a pathway-specific transcription factor and NIT-2 may be necessary for activation of nitrogen-responsive genes, our data show that pathway-specific transcription factors regulate genes involved in the catabolism of specific nitrogen sources, while NIT-2 regulates genes involved in utilization of all nonpreferred nitrogen sources, such as nitrogen transporters. Together, these transcription factors form a nutrient sensing network that allows N. crassa cells to regulate nitrogen utilization.
Genomic Characterizations of Clade III Lineage of Candida auris, California, USA

Candida auris is an emerging multidrug-resistant yeast. We describe an ongoing C. auris outbreak that began in October 2019 in Los Angeles, California, USA. We used genomic analysis to determine that isolates from 5 of 6 patients belonged to clade III; 4 isolates were closely related.
Understanding the dehydrogenation mechanism of tetrahydrocarbazole over palladium using a combined experimental and density functional theory approach

The mechanism of the dehydrogenation of tetrahydrocarbazole to carbazole over palladium has been examined for the first time. By use of a combination of deuterium exchange experiments and density functional theory calculations, a detailed reaction profile for the aromatization of tetrahydrocarbazole has been identified and validated by experiment. As with many dehydrogenation reactions, the initial hydrogen abstraction is found to have the highest reaction barrier. Tetrahydrocarbazole has four hydrogens which can, in principle, be cleaved initially; however, the theory and experiment show that the reaction is dominated by the cleavage of the carbon hydrogens at the carbon atoms in positions 1 and 4. The two pathways originating from these two C−H bond cleavage processes are found to have similar reaction energy profiles and both contribute to the overall reaction.