Miracle-dz/UniFAR-FTUs huggingface dataset:
BRAF V600E expression in ameloblastomas-A 36-patient cohort from Helsinki University Hospital.

OBJECTIVES We aimed to investigate BRAF V600E percentage immunohistochemically in ameloblastomas of a single institute cohort. We were interested if age, location, histological properties, or tumor recurrence depend on the BRAF status. SUBJECTS, MATERIALS AND METHODS We had 36 formalin-fixed, paraffin-embedded ameloblastoma tissue samples of patients treated at the Helsinki University Hospital between the years 1983-2016. Tissue sections underwent immunohistochemistry by Ventana BenchMark XT immunostainer using Ms Anti-Braf V600E (VE1) MAB. We used R 3.4. 2 and RStudio 1.1. 383 to conduct statistical analysis for BRAF positivity and earlier onset as well as tumor location. We used chi-squared tests and 2-by-2 table functions to determine connections between BRAF positivity and recurrence, growth pattern, and type. RESULTS BRAF-positive tumors occurred in younger patients compared to BRAF-negative tumors (p = 0.015) and they located mostly to the mandible (p < 0.001). Growth patterns were limited to two in BRAF-negative tumors when BRAF-positive tumors presented with one to four growth patterns (p = 0.02). None of the maxillary tumors showed BRAF positivity and of these, 72.2% recurred. CONCLUSIONS An immunohistochemical BRAF marker could be a beneficial tool to predict the outcome of patients with this aggressive, easily recurring tumor.
Management of perinatal depression with non-drug interventions

ABSTRACT Perinatal depression is a common disorder that has been associated with serious risks to mother and child. Recently, screening for depression in pregnant and postpartum women has increased, as has the development of new psychotherapy and non-drug treatment modalities. Matching patients to treatments can be challenging, and although research into personalized treatment of major depression in the general population has increased, no published guidelines focus on personalized treatment approaches to perinatal depression. In particular, guidelines on non-drug treatments are lacking. This review summarizes the evidence on personalized non-drug treatment of perinatal depression, how to incorporate patients’ preferences, novel treatments under investigation, and the potential role of biomarkers in matching patients to treatment. The review provides recommendations for future research in personalized care of perinatal depression.
Three-year follow-up of intrastromal corneal ring segment implantation in central keratoconus with regular astigmatism: ‘Bow-tie’ shape

Purpose: To assess the outcomes of implanting Ferrara-type intrastromal corneal ring segments in central ‘bow-tie’-shaped keratoconus over 3 years of follow-up. Methods: A total of 20 eyes with central ‘bow-tie’-shaped keratoconus were evaluated before and after implanting Ferrara-type intrastromal corneal ring segments (AJL Ophthalmic, Spain). LogMAR uncorrected distance visual acuity and best corrected distance visual acuity and residual refractive errors analysed using vector analysis were recorded preoperatively, at 6 months, 1 year, and 3 years postoperatively. Results: The mean uncorrected distance visual acuity (LogMAR scale) rose from a preoperative 0.75 ± 0.28 to a 6-month postoperative 0.38 ± 0.28 (p < 0.0001). The corrected distance visual acuity, in turn, improved from 0.07 ± 0.06 to 0.05 ± 0.06 (p = 0.0008). Both the uncorrected distance visual acuity and corrected distance visual acuity were stable over the postoperative period in both groups (p > 0.05). None of the eyes lost uncorrected distance visual acuity and corrected distance visual acuity lines over the postoperative follow-up period. The spherical equivalent and the refractive cylinder declined steeply after intrastromal corneal ring segments implantation (p < 0.0001). Both the spherical equivalent and refractive cylinder were stable over the postoperative period. None of the eyes had an increase in maximum or minimum keratometry greater than 0.75D over the postoperative period. Conclusion: The planning for intrastromal corneal ring segments insertion proposed in this study reduces the spherical equivalent and refractive cylinder in this type of keratoconus, while improving post-surgery uncorrected distance visual acuity and corrected distance visual acuity. These results remain stable over 3 years of follow-up. Therefore, this procedure could be considered as an effective therapeutic alternative in patients affected by this type of keratoconus.
A Preliminary Study of Clinical Concept Detection Using Syntactic Relations

Concept detection is an integral step in natural language processing (NLP) applications in the clinical domain. Clinical concepts are detailed (e.g., "pain in left/right upper/lower arm/leg") and expressed in diverse phrase types (e.g., noun, verb, adjective, or prepositional phrase). There are rich terminological resources in the clinical domain that include many concept synonyms. Even with these resources, concept detection remains challenging due to discontinuous and/or permuted phrase occurrences. To overcome this challenge, we investigated an approach to exploiting syntactic information. Syntactic patterns of concept phrases were mined from continuous, non-permuted forms of synonyms, and these patterns were used to detect discontinuous and/or permuted concept phrases. Experiments on 790 de-identified clinical notes showed that the proposed approach can potentially boost a recall of concept detection. Meanwhile, challenges and limitations were noticed. In this paper, we report and discuss our preliminary analysis and finding.
Assessment of miR-98-5p, miR-152-3p, miR-326 and miR-4289 Expression as Biomarker for Prostate Cancer Diagnosis

Prostate cancer (PCa) is one of the most commonly diagnosed cancers worldwide, accounting for almost 1 in 5 new cancer diagnoses in the US alone. The current non-invasive biomarker prostate specific antigen (PSA) has lately been presented with many limitations, such as low specificity and often associated with over-diagnosis. The dysregulation of miRNAs in cancer has been widely reported and it has often been shown to be specific, sensitive and stable, suggesting miRNAs could be a potential specific biomarker for the disease. Previously, we identified four miRNAs that are significantly upregulated in plasma from PCa patients when compared to healthy controls: miR-98-5p, miR-152-3p, miR-326 and miR-4289. This panel showed high specificity and sensitivity in detecting PCa (area under the curve (AUC) = 0.88). To investigate the specificity of these miRNAs as biomarkers for PCa, we undertook an in depth analysis on these miRNAs in cancer from the existing literature and data. Additionally, we explored their prognostic value found in the literature when available. Most studies showed these miRNAs are downregulated in cancer and this is often associated with cancer progression and poorer overall survival rate. These results suggest our four miRNA signatures could potentially become a specific PCa diagnostic tool of which prognostic potential should also be explored.
High-performance asymmetric micro-supercapacitors based on electrodeposited MnO2 and N-doped graphene

In-plane asymmetric micro-supercapacitors using nitrogen-doped graphene (NG) film as negative electrode and MnO2 nanostructures as positive electrode are fabricated onto a plastic substrate coated with Ni/Cu film. A laser-scribing machine is employed to make interdigital finger electrodes in the plastic substrate coated with NG film via a slurry coating process. MnO2 nanosheets are electrochemically deposited onto pre-coated NG film. In LiCl-based gelled electrolyte, the NG//MnO2 cell exhibits excellent electrochemical performance and a broad voltage window up to 1.8 V. The maximum specific capacitance of a single cell is measured to be 13 mF cm−2. In addition, several cells in series can be easily fabricated by combining the laser-scribing technique and the electrodeposition of MnO2 electrodes. As a proof of concept, four cells in a compact configuration and with high voltage output up to 7.2 V are demonstrated.
Management of Pediatric Severe Traumatic Brain Injury: 2019 Consensus and Guidelines-Based Algorithm for First and Second Tier Therapies

Objectives: To produce a treatment algorithm for the ICU management of infants, children, and adolescents with severe traumatic brain injury. Data Sources: Studies included in the 2019 Guidelines for the Management of Pediatric Severe Traumatic Brain Injury (Glasgow Coma Scale score ⩽ 8), consensus when evidence was insufficient to formulate a fully evidence-based approach, and selected protocols from included studies. Data Synthesis: Baseline care germane to all pediatric patients with severe traumatic brain injury along with two tiers of therapy were formulated. An approach to emergent management of the crisis scenario of cerebral herniation was also included. The first tier of therapy focuses on three therapeutic targets, namely preventing and/or treating intracranial hypertension, optimizing cerebral perfusion pressure, and optimizing partial pressure of brain tissue oxygen (when monitored). The second tier of therapy focuses on decompressive craniectomy surgery, barbiturate infusion, late application of hypothermia, induced hyperventilation, and hyperosmolar therapies. Conclusions: This article provides an algorithm of clinical practice for the bedside practitioner based on the available evidence, treatment protocols described in the articles included in the 2019 guidelines, and consensus that reflects a logical approach to mitigate intracranial hypertension, optimize cerebral perfusion, and improve outcomes in the setting of pediatric severe traumatic brain injury.
One-step enzymatic modification of RNA 3′ termini using polymerase θ

Abstract Site-specific modification of synthetic and cellular RNA such as with specific nucleobases, fluorophores and attachment chemistries is important for a variety of basic and applied research applications. However, simple and efficient methods to modify RNA such as at the 3′ terminus with specific nucleobases or nucleotide analogs conjugated to various chemical moieties are lacking. Here, we develop and characterize a one-step enzymatic method to modify RNA 3′ termini using recombinant human polymerase theta (Polθ). We demonstrate that Polθ efficiently adds 30–50 2′-deoxyribonucleotides to the 3′ terminus of RNA molecules of various lengths and sequences, and extends RNA 3′ termini with an assortment of 2′-deoxy and 2′,3′-dideoxy ribonucleotide analogs containing functional chemistries, such as high affinity attachment moieties and fluorophores. In contrast to Polθ, terminal deoxynucleotidyl transferase (TdT) is unable to use RNA as a substrate altogether. Overall, Polθ shows a strong preference for adding deoxyribonucleotides to RNA, but can also add ribonucleotides with relatively high efficiency in particular sequence contexts. We anticipate that this unique activity of Polθ will become invaluable for applications requiring 3′ terminal modification of RNA and potentially enzymatic synthesis of RNA.
Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

Most anticancer agents induce cancer cell death; however, multidrug‐resistant cancers often lead to treatment failure. The effective use of curcumin as an anticancer agent has been demonstrated in clinical trials. Tetrahydrocurcumin, a major curcumin metabolite, exhibits pharmacological activities similar to those of curcumin. Curcumin induces cell death mainly through the apoptosis pathway, and tetrahydrocurcumin induces cell death mainly via an autophagy pathway in HL60 cells. Here, we investigated whether curcumin and tetrahydrocurcumin can induce apoptosis‐ and autophagy‐mediated cell deaths in Ara‐C‐resistant cancer cells, respectively. The results demonstrated that curcumin and tetrahydrocurcumin induced cell death by apoptosis and autophagy, respectively, in Ara‐C‐resistant HL60 cells. Thus, curcumin and tetrahydrocurcumin have potential applications in the treatment of acute myeloid leukemia with Ara‐C resistance.
Isolation of Rickettsia, Rickettsiella, and Spiroplasma from Questing Ticks in Japan Using Arthropod Cells.

Ticks are blood-sucking ectoparasites that transmit zoonotic pathogens to humans and animals. Ticks harbor not only pathogenic microorganisms but also endosymbionts. Although some tick endosymbionts are known to be essential for the survival of ticks, their roles in ticks remain poorly understood. The main aim of this study was to isolate and characterize tick-borne microorganisms from field-collected ticks using two arthropod cell lines derived from Ixodes scapularis embryos (ISE6) and Aedes albopictus larvae (C6/36). A total of 170 tick homogenates originating from 15 different tick species collected in Japan were inoculated into each cell line. Bacterial growth was confirmed by PCR amplification of 16S ribosomal DNA (rDNA) of eubacteria. During the 8-week observation period, bacterial isolation was confirmed in 14 and 4 samples using ISE6 and C6/36 cells, respectively. The sequencing analysis of the 16S rDNA PCR products indicated that they were previously known tick-borne pathogens/endosymbionts in three different genera: Rickettsia, Rickettsiella, and Spiroplasma. These included four previously validated rickettsial species namely Rickettsia asiatica (n = 2), Rickettsia helvetica (n = 3), Rickettsia monacensis (n = 2), and Rickettsia tamurae (n = 3) and one uncharacterized genotype Rickettsia sp. LON (n = 2). Four isolates of Spiroplasma had the highest similarity with previously reported Spiroplasma isolates: Spiroplasma ixodetis obtained from ticks in North America and Spiroplasma sp. Bratislava 1 obtained from Ixodes ricinus in Europe, while two isolates of Rickettsiella showed 100% identity with Rickettsiella sp. detected from Ixodes uriae at Grimsey Island in Iceland. To the best of our knowledge, this is the first report on successful isolation of Rickettsiella from ticks. The isolates obtained in this study can be further analyzed to evaluate their pathogenic potential in animals and their roles as symbionts in ticks.
Genetic Variant in the CRH-binding Protein Gene (CRHBP) is Associated With Cessation of Cocaine Use in Methadone Maintenance Patients With Opioid Addiction.

OBJECTIVES We have previously shown associations between 4 genetic variants in opioid and stress-related genes (OPRM1, NPYR1/NPYR5, NR3C1, and CRHBP) and prolonged abstinence from heroin without methadone maintenance treatment (MMT). We currently assessed the associations between these variants and MMT patients' characteristics. METHODS A non-selective group of 351 patients who stayed at least 1 year in their first admission to MMT were genotyped and their characteristics and substance in urine on admission and after 1 year were studied. RESULTS The proportions of patients with both cocaine and benzodiazepine abuse were reduced significantly after 1 year in MMT; however, cocaine abuse cessation was significantly associated with the non-carriers of the CRHBP (corticotrophin releasing hormone binding protein) SNP rs1500 minor C allele (GG genotype) (P = 0.0009, PBonferroni = 0.0221). More carriers of the 2 C alleles (CC genotype) than carriers of the GC and GG genotypes abused cocaine on admission (32.3% vs 19.7%, respectively, P = 0.0414, recessive model), and more of the C allele carriers (GC and CC genotypes) than non-carriers (GG genotype) abused cocaine after 1 year in MMT (25.7% vs 15.8%, respectively, P = 0.0334, dominant model). Abusers of benzodiazepine were more prevalent among carriers of the C allele compared with non-carriers on admission (60.6% vs 45.9%, respectively, P = 0.0080, dominant model), as well as after 1 year in MMT (50.9% vs 39.1%, respectively, P = 0.0362). CONCLUSIONS Reduction in cocaine abuse among MMT patients may be mediated by a genetic effect in a stress-related gene (CRHBP SNP rs1500 minor C allele). Evaluations of larger samples, additional SNPs, and different populations are needed to support these findings.
Musculoskeletal Pain in Individuals With Inflammatory Bowel Disease Reflects Three Distinct Profiles

Objectives: Pain affects over 70% of individuals with inflammatory bowel disease (IBD), with abdominal and musculoskeletal pain representing the most common symptoms. Musculoskeletal pain in IBD is reported to be associated with multiple clinical features, however the scope and nature of pain is not well understood. Primary aims were to identify subgroups of musculoskeletal pain in individuals with IBD based on clinical features of pain and assess how these subgroups differ in aspects of demographics, comorbidity, and IBD characteristics. Methods: Cross-sectional online survey was performed on adults with IBD. Domains included: demographics, comorbidity, and clinical IBD and pain features. Latent class analysis was used to identify subgroups with similar attributes of: pain (severity, location, interference, and quality), IBD (activity, quality of life, and abdominal pain), and symptoms related to central sensitization. Correlation and regression analyses were used to profile identified subgroups. Results: Of 305 included participants, 208 indicated the presence of musculoskeletal pain. Three identified subgroups were characterized as “mixed mechanism,” “central mechanism,” and “regional and remission. ” Between subgroup differences included: total comorbidity score (P=0.005), osteoarthritis (P=0.027), osteoporosis (P=0.045), depression (P=0.001), anxiety (P=0.025), and chronic fatigue syndrome (P=0.020). Sex and age were identified as confounders for depression and anxiety. Conclusions: Study results suggest multiple mechanisms contributing to pain experiences in IBD, to include central mechanisms. Features related to demographics, extraintestinal manifestations, IBD subtype, and clinical IBD features were not predictors of subgroup membership. However, total comorbidity demonstrated association with pain subgroups in this population.
Anatomic Origin of Osteochondrogenic Progenitors Impacts Sensitivity to EWS-FLI1-Induced Transformation

Ewing sarcomas predominantly arise in pelvic and stylopod bones (i.e., femur and humerus), likely as a consequence of EWS-FLI1 oncogene-induced transformation of mesenchymal stem/progenitor cells (MSCs). MSCs located in the embryonic superficial zone cells (eSZ) of limbs express anatomically distinct posterior Hox genes. Significantly, high expression of posterior HOXD genes, especially HOXD13, is a hallmark of Ewing sarcoma. These data drove our hypothesis that Hox genes in posterior skeleton MSCs contribute to Ewing sarcoma tumorigenesis. We isolated eSZ cells from stylopod and zeugopod (i.e., tibia/fibula, radius/ulna) bones, from wild-type and Hoxd13 mutant embryos, and tested the impact of EWS-FLI1 transduction on cell proliferation, gene expression, and tumorigenicity. Our data demonstrate that both stylopod and zeugopod eSZ cells tolerate EWS-FLI1 but that stylopod eSZ cells are relatively more susceptible, demonstrating changes in proliferation and gene expression consistent with initiation of malignant transformation. Significantly, loss of Hoxd13 had no impact, showing that it is dispensable for the initiation of EWS-FLI1-induced transformation in mouse MSCs. These findings show that MSCs from anatomically distinct sites are differentially susceptible to EWS-FLI1-induced transformation, supporting the premise that the dominant presentation of Ewing sarcoma in pelvic and stylopod bones is attributable to anatomically-defined differences in MSCs.
Retrograde Intramedullary Nail Arthrodesis for Avascular Necrosis of the Talus

Background: Avascular necrosis (AVN) of the talus from any etiology is a devastating pathology. There are few salvage options available and controversy exists as to the surgical management for patients with talar AVN. The authors present their results of tibiotalocalcaneal arthrodesis with a retrograde nail. Materials and Methods: A comprehensive chart and radiographic review was pulled from our database for patients with AVN of the talus, who were treated by tibiotalocalcaneal fusion with retrograde intramedullary nail. Primary outcome was union, with time to clinical union as a secondary endpoint. Results: Fourteen patients were included. The average age at surgery was 47.4 ± 12.8 years, there were nine female patients, and the average Body Mass Index was 33.5 ± 6.0. Surgical risk factors included two patients who smoked, one was diabetic, and one had a preoperative ulceration. The average time to partial weightbearing was 70.6 ± 25.4 days, and the average time to full weightbearing was 100.6 ± 35.5 days. Four patients had postoperative complications, while no patients required major revision surgery. Twelve patients went on to solid fusion, while two went on to a stable, braceable pseudoarthrosis. Eight patients were able to return to shoes, and eight were able to walk unaided at final followup. Conclusion: Salvage of talar AVN is possible by tibiotalocalcaneal arthrodesis with an intramedullary nail. Physicians may offer this as a salvage option to patients with a high likelihood of successful fusion. Level of Evidence: IV, Retrospective Case Series
Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD and Corticosteroids: A Multi-Center Randomized Controlled Trial in RA Patients with an Inadequate Response to Conventional Synthetic DMARDs, and New Therapy with Certolizumab Pegol

Background: Treatment of rheumatoid arthritis (RA) includes the use of conventional (cs), biologic (b) disease-modifying anti-rheumatic drugs (DMARDs) and oral, intramuscularly, intravenous, or intraarticular (IA) glucocorticoids (GCs). In this paper, we analysed whether a treat-to-target (T2T) strategy optimizing csDMARD, oral, and IA-GC treatment as an adjunct new therapy to a new certolizumab pegol (CZP) therapy improves the effectivity in RA patients. Methods: 43 patients with active RA (≥6 tender, ≥6 swollen joints, ESR ≥ 20 mm/h or CRP ≥ 7mg/L) despite csDMARD treatment for ≥ 3 months and naïve to bDMARDs were randomized to CZP (200 mg/2 weeks after loading with 400 mg at weeks 0–2–4) plus a treat-to-target strategy (T2T, n = 21), or to CZP added to the established csDMARD therapy (fixed regimen, n = 22). The T2T strategy consisted of changing the baseline csDMARD therapy (1) SC-methotrexate (dose: 15 ≥ 20 ≥ 25 mg/week, depending on the initial dose) ≥ leflunomide (20 mg/d) ≥ sulphasalazine (2 × 1000 mg/d) plus (2) oral GCs (prednisolone 20–15–12.5–10–7.5–5–2.5–0 mg/d tapered every five days) and (3) injections of ≤5 affected joints with triamcinolone. DMARD modification and an addition of oral GCs were initiated, depending on the achievement of low disease activity (DAS 28 < 3.2). The primary objective was defined as the ACR 50 response at week 24. Results: ACR 50 was achieved in 76.2% of the T2T, as compared to 36.4% of the fixed regimen patients (p = 0.020). ACR 20 and 70 responses were achieved in 90.5% and 71.4% of the T2T patients and 59.1% and 27.3% of the fixed regimen patients, respectively (p = 0.045 and p = 0.010, respectively). The adverse event rate was similar for both groups (T2T n = 51; fixed regimen n = 55). Conclusion: Treat-to-target management with the optimization of csDMARDs, oral, and IA-GCs of RA patients in parallel to a newly established CZP treatment was safe and efficacious in comparison to a fixed regimen of csDMARDs background therapy.