Miracle-dz/UniFAR-FTUs huggingface dataset:
Chlamydia trachomatis and human herpesvirus 6 infections in ovarian cancer—Casual or causal?

Ovarian cancer is one of the most lethal gynecological malignancies in the world. In the United States, more than 20,000 cases of ovarian cancer average every year, causing more than 14,000 deaths per year (www.cancer.org). This high percentage of mortality arises predominantly due to the silent nature of the disease. Ovarian cancer is diagnosed mostly in the late stages thus earning the disease its name—"Silent killer. ” It is therefore of utmost importance to identify any markers that will allow early detection of ovarian cancer. The National Cancer Institute associates 15%–20% of all cancer with infectious agents. Studies in the past have shown the presence of several viral and bacterial markers in ovarian cancer samples [1, 2]. Understanding the molecular mechanisms of pathogenesis of these oncogenic pathogens may therefore enable early intervention in treatment and care of ovarian cancer patients. In this brief review, we endeavor to highlight the role that coinfection of human herpesvirus 6 (HHV-6) and Chlamydia trachomatis may play in initiation and progression of ovarian cancer and propose a theory that may justify their presence in ovarian cancer tissues, thus enabling a directed therapeutic approach. C. trachomatis is an obligate intracellular, gram-negative bacterium that is transmitted sexually. More than 2.8 million cases are registered in the US alone [3]. However, the actual number is believed to be much higher, owing to the asymptomatic nature of most C. trachomatis infections. C. trachomatis has a 48–72 hour life cycle in which it infects the cells, replicates, and exits by host cell lysis. During its developmental cycle, C. trachomatis cycles between 2 forms—infectious elementary bodies and replicative reticulate bodies (RB). Its presence in the cell is confined to a vacuoleinclusion. One characteristic of C. trachomatis infection is its ability to persist in an individual for months up to years. It modulates the host-cell signaling pathways, interacts with various organelles, and evades apoptosis to enable the completion of its developmental cycle [4]. In its pursuit of survival, however, C. trachomatis infection induces reactive oxygen species (ROS) production via the NADPH and NOD-like receptor family member X1 (NLRX1) pathways [5]. ROS further leads to oxidative damage of DNA, which is further repaired by base excision repair (BER) and nucleotide excision repair (NER) pathways. Recent studies have shown that C. trachomatis impairs BER of damaged DNA by down-regulating polymerase beta [6]. Deficiency in BER pathway enables the cells to acquire tumorigenic properties [7]. Inefficient BER leads to accumulation of single strand breaks which eventually lead to double strand breaks in the DNA [8]. Telomeres, the protective molecular caps on chromosomes, are damaged through induced telomere shortening during C. trachomatis infection [9]. C. trachomatis also affects the DNA damage response and associated signaling of
Economic burdens on parents of children with autism: a literature review

Abstract This review aims to summarize evidence from published articles regarding the economic burdens on parents of children diagnosed with autism to elaborate on current research status, discern key findings and provide suggestions for future studies. A total of 1024 records were identified through our systematic literature research, and 33 studies were included in the review. The 33 included studies reported findings from 10 different countries around the world. These articles (published from 2003 to 2017) used a variety of research methods, including quantitative (n = 26), qualitative (n = 4), and mixed (n = 3) study designs. In summary, parents of autistic children were susceptible to adverse employment impacts and increased financial burdens, especially mothers. More attention should be given to the development of appropriate medical resource allocation and the alleviation of economic burdens on parents of children with autism.
Bortezomib therapy in a real-world setting in patients with relapsed or refractory multiple myeloma

Bortezomib is a proteasome inhibitor, approved for treating newly diagnosed and relapsed multiple myeloma (MM). This realworld, multicenter, observational, non-interventional study of bortezomib was designed to collect and analyze prospective data in Taiwanese patients with relapsed or refractory MM. The primary endpoints included clinical effectiveness outcomes (disease response, disease progression [PD], time-to-response, time-toprogression, response duration, and overall survival [OS]). Secondary endpoints were safety and healthcare resource utilization. Total 100 patients (median [range] age 64.9 [37.0-85.5] years) were enrolled; 47 patients completed the study. Of the withdrawn patients (n=53), there were 48 deaths (PD-related death: n=35, adverse events [AEs]-related: n=12, other reason: n=1), and 5 due to loss to follow-up. Four patients in Cycle 1, 6 patients each in Cycle 2 and 5, 7 in Cycle 3, 10 patients in Cycle 4, 5 patients in Cycle 6, and 3 patients each in Cycle 7 and 8 achieved overall response during the study. Time-to-response was 4.68 months (95%CI: 3.2, NE) and response duration was 10.08 months (95%CI: 2.3, 28.6). Median OS was 9.8 months (95%CI: 3.8, 13.7), and median time-to-progression was 11.3 months (95%CI: 6.2, 20.2). Most common non-hematological AEs were diarrhea (n=32) and hypoesthesia (n=25); most common hematological AE was thrombocytopenia (n=18). Efficacy and safety profile of bortezomib in Taiwanese patients with MM was similar to global and other Asian population. Study provides a critical insight on use of bortezomib in realworld clinical practice, which can be helpful for Taiwanese healthcare providers’ decision-making processes.
Complex karyotype in myelodysplastic syndromes: Diagnostic procedure and prognostic susceptibility

Complex karyotype (CK) is a poor prognosis factor in hematological malignancies. Studies have shown that the presence of CK in myelodysplastic syndrome (MDS) can be associated with MDS progression to acute myeloid leukemia. The goal of this review was to examine the relationship between different types of CK with MDS, as well as its possible role in the deterioration and progression of MDS to leukemia. The content used in this paper has been obtained by a PubMed and Google Scholar search of English language papers (1975-2018) using the terms complex karyotype and myelodysplastic syndromes. A single independent abnormality can be associated with a good prognosis. However, the coexistence of a series of abnormalities can lead to CK, which is associated with the deterioration of MDS and its progression to leukemia. Therefore, CK may be referred to as a prognostic factor in MDS. The detection of independent cytogenetic disorders that altogether can result in CK could be used as a prognostic model for laboratory and clinical use.
Ocular complications of soft tissue filler injections: A review of literature

Soft tissue filler is commonly used for facial contouring. However, incorrect use can lead to severe ocular complications. Even though filler injections are quite different from fat grafts, they are considered similar procedures. However, to date, there are no proven preventive measures or treatments for blindness secondary to soft tissue filler injections.
CRISPR-induced RASGAP deficiencies in colorectal cancer organoids reveal that only loss of NF1 promotes resistance to EGFR inhibition

Anti-EGFR therapy is used to treat metastatic colorectal cancer (CRC) patients, for which initial response rates of 10–20% have been achieved. Although the presence of HER2 amplifications and oncogenic mutations in KRAS, NRAS, and BRAF are associated with EGFR-targeted therapy resistance, for a large population of CRC patients the underlying mechanism of RAS-MEK-ERK hyperactivation is not clear. Loss-of-function mutations in RASGAPs are often speculated in literature to promote CRC growth as being negative regulators of RAS, but direct experimental evidence is lacking. We generated a CRISPR-mediated knock out panel of all RASGAPs in patient-derived CRC organoids and found that only loss of NF1, but no other RASGAPs e.g. RASA1, results in enhanced RAS-ERK signal amplification and improved tolerance towards limited EGF stimulation. Our data suggests that NF1-deficient CRCs are likely not responsive to anti-EGFR monotherapy and can potentially function as a biomarker for CRC progression.
Preoperative Mental Health Scores and Achieving Patient Acceptable Symptom State Are Predictive of Return to Work After Arthroscopic Rotator Cuff Repair

Background: The incidence of rotator cuff repairs has risen dramatically over the past 10 years, most notably in the working-class population. Return to work (RTW) is a valuable outcome measure to set patient expectations before surgery. Purpose: To establish the rate of RTW after rotator cuff repair with respect to stratified levels of occupational demand (sedentary, light, moderate, and heavy) and to identify clinical factors significantly associated with postoperative RTW. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who received rotator cuff repair between 2014 and 2017 were queried from a prospectively maintained institutional registry. Work status was evaluated from clinical and physical therapy notes, and RTW was stratified based on duty level. The minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptom state (PASS) values were calculated for American Shoulder and Elbow Surgeons (ASES) score and subjective Constant score through use of an anchor-based approach. Patient demographic factors, preoperative ASES scores, Constant scores, and health-related quality of life scores, as well as change in postoperative scores exceeding the thresholds for MCID, SCB, and PASS, were analyzed to determine significant associations with RTW without restriction. Results: In total, 89 patients with documented pre- and postoperative work status underwent surgery. Rates of RTW for sedentary, light, moderate, and heavy duties were 100%, 84.0%, 77.4%, and 63.3%, respectively, within return at less than 7 postoperative months on average. RTW was associated with achieving PASS (P = .004) but not achieving MCID and SCB (P = .429 and .452, respectively). Injury to a patient’s dominant side had reduced odds (0.057; 95% CI, 0.004-0.763; P = .030) for RTW at full duty. Tear characteristics and type of insurance were not associated with RTW. Preoperative Veterans RAND Mental Component Score (>53.3; area under the curve, 70.4%) was predictive of returning to work. Conclusion: A vast majority of patients undergoing rotator cuff repair can expect to return to work within 8 months of surgery. Preoperative mental health scores can predict future return to work, which supports the concept that mental health status plays an important role in the outcomes after rotator cuff repair surgery.
An Association Study on the Cognitive Function and the Cerebral Grey Matter Volume of Patients with First-Episode Schizophrenia

Background The impairment of cognitive function is one of the core symptoms in schizophrenia, and the degree of recovery is closely related to whether patients are able to rejoin society successfully. Objective This study was to clarify the correlation between cognitive function and cerebral grey matter volume in schizophrenia. Methods The neuro-cognitive functions of thirty-seven patients with first-episode schizophrenia (the patient group) and thirty healthy controls (the control group) was evaluated with the Clock Drawing Test, Trail Marking Test, Digit Span Test, Auditory Verbal Learning Test, Wisconsin Card Sorting Test, Verbal Fluency Test, Semantic Similarity Test and Stroop Color-Word Test. The facial emotion cognitive task was employed to assess the facial emotion cognitive functions of thirty-two patients with first-episode schizophrenia (the patient group) and 29 healthy controls (the control group). The psychotic symptoms of patients with first episode schizophrenia were evaluated using the Positive and Negative Syndrome Scale (PANSS). The brain imaging data of the patient group and control group were collected using the magnetic resonance imagine (MRI). Results The difference between the patient group and the control group in the results of Clock Drawing Test, Trail Marking Test, Digit Span Test, Auditory Verbal Learning Test, Wisconsin Card Sorting Test, Verbal Fluency Test, Semantic Similarity Test and Stroop Color-Word Test’s reaction time were significant. These two groups’ Slopes in the facial emotion cognitive task were also significantly different from each other. According to the comparison of cerebral grey matter volume between the patient group and the control group, it was found that the grey matter volume of the patient group increased in the left superior frontal gyrus, and decreased in the left occipital gyrus, lingual gyrus and upper cerebellum. Based on the analyses of neuro-cognitive data and brain imaging data of the patient group, the scores of the number of correct responses in Stroop Color-Word Test’s Card C were negatively correlated with grey matter volumes of the left upper frontal gyrus, right upper frontal gyrus and middle frontal gyrus. The analyses on the facial emotion cognitive task and brain imaging data of the patient group showed that the slope data were positively correlated with grey matter volumes of the right superior temporal gyrus, middle temporal gyrus, left middle temporal gyrus, inferior temporal gyrus and fusiform gyrus. Conclusion There are general impairments in the neuro-cognitive functions and facial emotion cognitive functions of patients with first-episode schizophrenia, and the results suggest that brain areas with abnormal grey matter volumes are likely to be the brain structure and functional basis of the cognitive impairments.
Hepatocyte nuclear factor-1β regulates Wnt signaling through genome-wide competition with β-catenin/lymphoid enhancer binding factor

Significance Canonical Wnt signaling plays essential roles in cell proliferation, differentiation, and survival. Binding of Wnt ligands to their receptors results in translocation of β-catenin to the nucleus, where it interacts with TCF/LEF transcription factors and activates Wnt target genes. Here, we show that the transcription factor HNF-1β competes with the binding of β-catenin/LEF complexes to DNA. We identify a composite DNA element to which HNF-1β binds and thereby inhibits β-catenin-dependent transcription. Genome-wide chromatin immunoprecipitation sequencing strikingly revealed that 50% of β-catenin-occupied sites in HNF-1β mutant cells colocalized with HNF-1β-occupied sites in wild-type cells, indicating that reciprocal binding is widespread. These studies reveal a direct transcriptional mechanism for inhibition of canonical Wnt signaling. Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is essential for normal kidney development and renal tubular function. Mutations of HNF-1β produce cystic kidney disease, a phenotype associated with deregulation of canonical (β-catenin–dependent) Wnt signaling. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells produces hyperresponsiveness to Wnt ligands and increases expression of Wnt target genes, including Axin2, Ccdc80, and Rnf43. Levels of β-catenin and expression of Wnt target genes are also increased in HNF-1β mutant mouse kidneys. Genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) in wild-type and mutant cells showed that ablation of HNF-1β increases by 6-fold the number of sites on chromatin that are occupied by β-catenin. Remarkably, 50% of the sites that are occupied by β-catenin in HNF-1β mutant cells colocalize with HNF-1β–occupied sites in wild-type cells, indicating widespread reciprocal binding. We found that the Wnt target genes Ccdc80 and Rnf43 contain a composite DNA element comprising a β-catenin/lymphoid enhancer binding factor (LEF) site overlapping with an HNF-1β half-site. HNF-1β and β-catenin/LEF compete for binding to this element, and thereby HNF-1β inhibits β-catenin–dependent transcription. Collectively, these studies reveal a mechanism whereby a transcription factor constrains canonical Wnt signaling through direct inhibition of β-catenin/LEF chromatin binding.
Preferences for exercise among black individuals with multiple sclerosis

Background The promotion of exercise among black individuals with multiple sclerosis (MS) is important for managing the functional and symptomatic manifestations of MS. Objective The objective of this study was to elicit exercise program preferences among black individuals with MS. Methods Participants completed a survey delivered through Qualtrics. The survey measured exercise program component preferences, the importance of racial considerations, and barriers and facilitators to exercise participation. Results Forty black individuals with MS completed the survey and reported a preference for five days per week (range 0–7) of exercise at a moderate intensity (50% of the sample). Over 60% of participants desired an exercise program that was longer than six months, and over half wanted the aid of a behavioral coach. Participants preferred weight/resistance training exercises (52.5%) and easy walking (35%) modalities. The outcomes expected from exercise were increased muscle strength (65%) and improved overall body functioning (60%). The anticipated barriers for exercise were largely fatigue (40%) and time management (32.5%). The desired facilitators were a personal trainer (57.5%) and more exercise information (32.5%). Cultural and racial tailoring was very important or held some importance on the components of the program. Conclusion The findings of this study should be considered when developing exercise interventions for black individuals with MS.
Can Your Phone Be Your Therapist? Young People’s Ethical Perspectives on the Use of Fully Automated Conversational Agents (Chatbots) in Mental Health Support

Over the last decade, there has been an explosion of digital interventions that aim to either supplement or replace face-to-face mental health services. More recently, a number of automated conversational agents have also been made available, which respond to users in ways that mirror a real-life interaction. What are the social and ethical concerns that arise from these advances? In this article, we discuss, from a young person’s perspective, the strengths and limitations of using chatbots in mental health support. We also outline what we consider to be minimum ethical standards for these platforms, including issues surrounding privacy and confidentiality, efficacy, and safety, and review three existing platforms (Woebot, Joy, and Wysa) according to our proposed framework. It is our hope that this article will stimulate ethical debate among app developers, practitioners, young people, and other stakeholders, and inspire ethically responsible practice in digital mental health.
Diagnosis of invasive fungal disease in children: a narrative review

ABSTRACT Introduction: Invasive fungal diseases (IFD) represent important causes of morbidity and mortality in pediatrics. Early diagnosis and treatment of IFD is associated with better outcome and this entails the need to use fast and highly sensitive and specific methods that can support clinicians in the management of IFD. Areas covered: A narrative review was performed on conventional diagnostic methods such as culture, microscopy and histopathology are still gold standard but are burdened by a lack of sensitivity and specificity; on the other hand, imaging and noninvasive antigen-based such as beta-D-glucan, galactomannan and molecular biomarkers are the most convenient nonculture methods for diagnosis and monitoring effects of therapy. Aim of the present review is to summarize what is available in these fields at end of the second decade of the third millennium and look for future perspectives. Expert opinion: Promising and useful diagnostic methods have been applied in infectious disease diagnosis in clinical practice or in designing platforms. Unfortunately, most of them are not standardized or validated in pediatric population. However, clinicians should be aware of all innovative diagnostic tools to use in combination with conventional diagnostic methods for a better management of pathology and patient.
Bilateral Levofloxacin-Induced Achilles Tendon Rupture: An Uncommon Case Report and Review of the Literature

Since the introduction of Fluoroquinolones (FQ) in 1960s, these antibiotics have been used in airway and urinary tract infections, due to absorption, biodisponibility, posology and long half-life time properties. However, several reports state that FQ can cause tendinopathy and rupture. These adverse effects can occur within hours after initial treatment to up to 6 months after withdrawal. FQ-induced tendinopathy was first reported in 1983; since then more than 100 cases have been published. FQ usage can lead to complete tendon rupture and no more than 8 to 15 cases are reported worldwide. Most of rupture cases have been associated to corticoid use and rheumatic, vascular or renal disease. The purpose of this case report is to present the challenging diagnosis of a bilateral rupture of Achilles tendon in an old patient, because of the uncommon of the presentation and to review the current literature on such a debilitating condition.