Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and safety results from GEICO 1205, a randomized phase II trial of neoadjuvant chemotherapy with or without bevacizumab for advanced epithelial ovarian cancer

Background Bevacizumab is an approved treatment after primary debulking surgery for ovarian cancer. However, there is limited information on bevacizumab added to neoadjuvant chemotherapy before interval debulking surgery. Objective To evaluate neoadjuvant bevacizumab in a randomized phase II trial. Methods Patients with newly diagnosed stage III/IV high-grade serous/endometrioid ovarian cancer were randomized to receive four cycles of neoadjuvant chemotherapy with or without ≥3 cycles of bevacizumab 15 mg/kg every 3 weeks. After interval debulking surgery, all patients received post-operative chemotherapy (three cycles) and bevacizumab for 15 months. The primary end point was complete macroscopic response rate at interval debulking surgery. Results Of 68 patients randomized, 64 completed four neoadjuvant cycles; 22 of 33 (67%) in the chemotherapy-alone arm and 31 of 35 (89%) in the bevacizumab arm (p=0.029) underwent surgery. The complete macroscopic response rate did not differ between treatment arms in either the intention-to-treat population of 68 patients (6.1% vs 5.7%, respectively; p=0.25) or the 55 patients who underwent surgery (8.3% vs 6.5%; p=1.00). There was no difference in complete cytoreduction rate or progression-free survival between the treatment arms. During neoadjuvant therapy, grade ≥3 adverse events were more common with chemotherapy alone than with bevacizumab (61% vs 29%, respectively; p=0.008). Intestinal (sub)occlusion, fatigue/asthenia, abdominal infection, and thrombocytopenia were less frequent with bevacizumab. The incidence of grade ≥3 adverse events was 9% in the control arm versus 16% in the experimental arm in the month after surgery. Conclusions Adding three to four pre-operative cycles of bevacizumab to neoadjuvant chemotherapy for unresectable disease did not improve the complete macroscopic response rate or surgical outcome, but improved surgical operability without increasing toxicity. These results support the early integration of bevacizumab in carefully selected high-risk patients requiring neoadjuvant chemotherapy for initially unresectable ovarian cancer.
Whole Genome Sequencing of the Blue Tilapia (Oreochromis aureus) Provides a Valuable Genetic Resource for Biomedical Research on Tilapias

Blue tilapia (Oreochromis aureus) has been an economically important fish in Asian countries. It can grow and reproduce in both freshwater and brackish water conditions, whereas it is also considered as a significant invasive species around the world. This species has been widely used as the hybridization parent(s) for tilapia breeding with a major aim to produce novel strains. However, available genomic resources are still limited for this important tilapia species. Here, we for the first time sequenced and assembled a draft genome for a seawater cultured blue tilapia (0.92 Gb), with 97.8% completeness and a scaffold N50 of 1.1 Mb, which suggests a relatively high quality of this genome assembly. We also predicted 23,117 protein-coding genes in the blue tilapia genome. Comparisons of predicted antimicrobial peptides between the blue tilapia and its close relative Nile tilapia proved that these immunological genes are highly similar with a genome-wide scattering distribution. As a valuable genetic resource, our blue tilapia genome assembly will benefit for biomedical researches and practical molecular breeding for high resistance to various diseases, which have been a critical problem in the aquaculture of tilapias.
Procedural Sedation Using a Propofol–Ketamine Combination (Ketofol) vs. Propofol Alone in the Loop Electrosurgical Excision Procedure (LEEP): A Randomized Controlled Trial

Background: Although the loop electrosurgical excision procedure (LEEP) is a brief procedure, it can cause severe pain and discomfort to patients in the absence of adequate sedation. An admixture of ketamine with propofol (ketofol), may reduce patient movement due to insufficient sedation while providing hemodynamic and respiratory stability. This study evaluated the ability of two ratios of a propofol–ketamine combination, compared with propofol alone, to reduce patient movement during procedural sedation for LEEPs. Methods: One hundred and twenty women scheduled for a LEEP were randomly assigned to three groups. Anesthesia was induced with 1 mg/kg propofol (group P), 1 mg/kg propofol and 0.33 mg/kg ketamine (group K1), or 1 mg/kg propofol and 0.66 mg/kg ketamine (group K2). The primary outcome was the incidence of adduction motion in the lower extremities during the procedure. The requirements for respiratory interventions, changes in vital signs, sedation score, additional anesthetic usage, and surgeon and patient satisfaction were also evaluated. Results: The incidence of adduction motion was significantly lower in groups K1 and K2 than in group P (overall p-value <0.001) but did not differ significantly in groups K1 and K2. Group K2 needed more jaw thrust maneuvers than group K1. Additional propofol usage was lower and surgeon satisfaction scores higher in groups K1 and K2 than in group P. Conclusion: A propofol–ketamine combination is more effective than propofol alone in reducing procedural interference during LEEPs. However, increasing the dose of ketamine showed no additional benefit.
MicroRNA-145-5p promotes asthma pathogenesis by inhibiting kinesin family member 3A expression in mouse airway epithelial cells

Background MicroRNA (miR)-145-5p is a respiratory disease biomarker, and is upregulated in asthma pathogenesis. However, its underlying mechanisms were unclear, so were investigated in the present study. Methods A mouse model of asthma was established by challenge with house dust mite (HDM) extract. An miR-145-5p antagomir was administered nasally and expression of kinesin family member 3A (KIF3A) and miR-145-5p was measured by immunohistochemistry, PCR, and western blot. Eosinophils in lavage fluid and levels of interleukin (IL)-4, IL-5, and IL-13 were quantified. Airway hyper-responsiveness was measured and KIF3A expression was tested following miR-145-5p overexpression or interference in the 16HBE14o- airway epithelial cell line. The effects of miR-145-5p and KIF3A co-transfection in 16HBE14o- cells were examined on cytokine release, epithelial barrier dysfunction, and epithelial repair in HDM-exposed cells. Results KIF3A downregulation and miR-145-5p upregulation were noted in airway epithelial cells of HDM-exposed asthmatic mice, while miR-145-5p antagonism significantly improved symptoms. MiR-145-5p promoted the HDM-induced release of chemokines and inflammatory factors and epithelial barrier dysfunction, and suppressed epithelial repair by directly targeting KIF3A. Conclusion miR-145-5p influenced HDM-induced epithelial cytokine release and epithelial barrier dysfunction via regulating KIF3 expression. It also affected epithelial repair, exacerbating the HDM-induced T helper 2-type immune response in mice.
Phytosterol enhances oral nifedipine treatment in pregnancy-induced preeclampsia: A placebo-controlled, double-blinded, randomized clinical trial

Preeclampsia is a severe complication which influences pregnant women all around the world, the symptom of which is serious maternal hypertension. Phytosterol is a type of natural compound commonly found in plant products, and has been incorporated into various food vectors and natural drugs. In the paper, the curative effect on preeclampsia by combination of oral nifedipine and phytosterol was assessed. Random grouping was carried out, with 253 preeclampsia patients being registered and taking orally nifedipine+phytosterol or nifedipine+placebo. The time for controlling the blood pressure and the time needed for the occurrence of another hypertensive crisis were defined as primary endpoints. The dosage required for controlling blood pressure, and the adverse effects from infants and mothers were defined as secondary endpoints. The nifedipine+phytosterol group required a remarkably shorter time for controlling blood pressure than the nifedipine+placebo group, an obviously delayed time for the occurrence of new hypertensive crisis, and an obvious lower dosage for controlling blood pressure. There was no difference between the two groups regarding the adverse effects from infants and mothers. Findings in the study suggest that phytosterol is an effective and safe adjuvant of the oral nifedipine and can alleviate the hypertension symptoms in preeclampsia patients. Impact statement There was no difference between the two groups regarding the adverse effects from infants and mothers. Findings in the study suggest that phytosterol is an effective and safe adjuvant of the oral nifedipine and can alleviate the hypertension symptoms in preeclampsia patients.
Attitudes of Pregnant Women and Healthcare Professionals Toward Clinical Trials and Routine Implementation of Antenatal Vaccination Against Respiratory Syncytial Virus: A Multicenter Questionnaire Study.

INTRODUCTION Respiratory syncytial virus (RSV) is a common cause of infant hospitalization and mortality. With multiple vaccines in development, we aimed to determine: (1) the awareness of RSV among pregnant women and healthcare professionals (HCPs), and (2) attitudes toward clinical trials and routine implementation of antenatal RSV vaccination. METHODS Separate questionnaires for pregnant women and HCPs were distributed within 4 hospitals in South England (July 2017-January 2018). RESULTS Responses from 314 pregnant women and 204 HCPs (18% obstetricians, 75% midwives, 7% unknown) were analyzed. Most pregnant women (88%) and midwives (66%) had no/very little awareness of RSV, unlike obstetricians (14%). Among pregnant women, 29% and 75% would likely accept RSV vaccination as part of a trial, or if routinely recommended, respectively. Younger women (16-24 years), those of 21-30 weeks' gestation, and with experience of RSV were significantly more likely to participate in trials [odds ratio (OR): 1.42 (1.72-9.86); OR: 2.29 (1.22-4.31); OR: 9.07 (1.62-50.86), respectively]. White-British women and those of 21-30 weeks' gestation were more likely to accept routinely recommended vaccination [OR: 2.16 (1.07-4.13); OR: 2.10 (1.07-4.13)]. Obstetricians were more likely than midwives to support clinical trials [92% vs. 68%, OR: 2.50 (1.01-6.16)] and routine RSV vaccination [89% vs. 79%, OR: 4.08 (1.53-9.81)], as were those with prior knowledge of RSV, and who deemed it serious. CONCLUSIONS RSV awareness is low among pregnant women and midwives. Education will be required to support successful implementation of routine antenatal vaccination. Research is needed to understand reasons for vaccine hesitancy among pregnant women and HCPs, particularly midwives.
The Push and Pull of Network Mobility: How Those High in Trait-Level Neuroticism Can Come to Occupy Peripheral Network Positions

Field research shows that people’s network positions are determined, at least in part, by their traits. For instance, over time, actors higher in trait-level neuroticism move out to the network periphery. What is unknown is how this happens. Drawing on personality and social psychological theory, we generated a model that could explain the movement of actors who are higher in neuroticism. Our aim is to add to the existing empirical literature on the interplay of actor level traits and social networks, and do so using methods that can establish possible causal pathways. In four experiments, we tested two explanatory mechanisms—aversion on the part of alters and avoidance on the part of focal actors. Results showed that potential alters indeed perceived actors higher in neuroticism as aversive, leading them to block these actors from well-connected spots. Specifically, low perceived levels of likability prevented actors from being nominated to better positions. In a test of avoidance, actors higher in neuroticism recognized the benefits of better-connected network positions, but also saw them as costly, and thus, declined opportunities to occupy them. This work shows how both alters and egos can determine egos’ place in networks, and specifies how this is done.
Identifying vulnerable older adult populations by contextualizing geriatric syndrome information in clinical notes of electronic health records

OBJECTIVE Geriatric syndromes such as functional disability and lack of social support are often not encoded in electronic health records (EHRs), thus obscuring the identification of vulnerable older adults in need of additional medical and social services. In this study, we automatically identify vulnerable older adult patients with geriatric syndrome based on clinical notes extracted from an EHR system, and demonstrate how contextual information can improve the process. MATERIALS AND METHODS We propose a novel end-to-end neural architecture to identify sentences that contain geriatric syndromes. Our model learns a representation of the sentence and augments it with contextual information: surrounding sentences, the entire clinical document, and the diagnosis codes associated with the document. We trained our system on annotated notes from 85 patients, tuned the model on another 50 patients, and evaluated its performance on the rest, 50 patients. RESULTS Contextual information improved classification, with the most effective context coming from the surrounding sentences. At sentence level, our best performing model achieved a micro-F1 of 0.605, significantly outperforming context-free baselines. At patient level, our best model achieved a micro-F1 of 0.843. DISCUSSION Our solution can be used to expand the identification of vulnerable older adults with geriatric syndromes. Since functional and social factors are often not captured by diagnosis codes in EHRs, the automatic identification of the geriatric syndrome can reduce disparities by ensuring consistent care across the older adult population. CONCLUSION EHR free-text can be used to identify vulnerable older adults with a range of geriatric syndromes.
Mutual detection of Kaposi's sarcoma‐associated herpesvirus and Epstein–Barr virus in blood and saliva of Cameroonians with and without Kaposi's sarcoma

Kaposi's sarcoma‐associated herpesvirus (KSHV) and Epstein–Barr virus (EBV) are prevalent in sub‐Saharan Africa, together with HIV; the consequent burden of disease is grave. The cofactors driving transmission of the two viruses and pathogenesis of associated malignancies are not well understood. We measured KSHV and EBV DNA in whole blood and saliva as well as serum antibodies levels in 175 Cameroonians with Kaposi's sarcoma and 1,002 age‐ and sex‐matched controls with and without HIV. KSHV seroprevalence was very high (81%) in controls, while EBV seroprevalence was 100% overall. KSHV DNA was detectable in the blood of 36–46% of cases and 6–12% of controls; EBV DNA was detected in most participants (72–89%). In saliva, more cases (50–58%) than controls (25–28%) shed KSHV, regardless of HIV infection. EBV shedding was common (75–100%); more HIV+ than HIV− controls shed EBV. Cases had higher KSHV and EBV VL in blood and saliva then controls, only among HIV+ participants. KSHV and EBV VL were also higher in HIV+ than in HIV− controls. Cases (but not controls) were more likely to have detectable KSHV in blood if they also had EBV, whereas shedding of each virus in saliva was independent. While EBV VL in saliva and blood were modestly correlated, no correlation existed for KSHV. Numerous factors, several related to parasitic coinfections, were associated with detection of either virus or with VL. These findings may help better understand the interplay between the two gammaherpesviruses and generally among copathogens contributing to cancer burden in sub‐Saharan Africa.
Tyrosine Phosphorylation as a Widespread Regulatory Mechanism in Prokaryotes

Phosphorylation events modify bacterial and archaeal proteomes, imparting cells with rapid and reversible responses to specific environmental stimuli or niches. Phosphorylated proteins are generally modified at one or more serine, threonine, or tyrosine residues. Within the last ten years, increasing numbers of global phosphoproteomic surveys of prokaryote species have revealed an abundance of tyrosine-phosphorylated proteins. ABSTRACT Phosphorylation events modify bacterial and archaeal proteomes, imparting cells with rapid and reversible responses to specific environmental stimuli or niches. Phosphorylated proteins are generally modified at one or more serine, threonine, or tyrosine residues. Within the last ten years, increasing numbers of global phosphoproteomic surveys of prokaryote species have revealed an abundance of tyrosine-phosphorylated proteins. In some cases, novel phosphorylation-dependent regulatory paradigms for cell division, gene transcription, and protein translation have been identified, suggesting that a wide scope of prokaryotic physiology remains to be characterized. Recent observations of bacterial proteins with putative phosphotyrosine binding pockets or Src homology 2 (SH2)-like domains suggest the presence of phosphotyrosine-dependent protein interaction networks. Here in this minireview, we focus on protein tyrosine phosphorylation, a posttranslational modification once thought to be rare in prokaryotes but which has emerged as an important regulatory facet in microbial biology.
The Relationship between Ferroptosis and Tumors: A Novel Landscape for Therapeutic Approach

Background Ferroptosis is a newly discovered form of iron-dependent oxidative cell death characterized by lethal accumulation of lipid-based reactive oxygen species (ROS). It is distinct from other forms of cell death including apoptosis, necrosis, and autophagy in terms of morphology, biochemistry and genetics. Discussion Ferroptosis can be induced by system xc- inhibitors or glutathione peroxidase 4 (GPx4) inhibitors, as well as drugs such as sorafenib, sulfasalazine (SAS), and artesunate (ART). Ferroptosis has been recently shown to be critical in regulating growth of tumors, such as hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), ovarian cancer, pancreatic carcinoma, and diffuse large B cell lymphoma (DLBCL). Ferroptosis is also associated with resistance to chemotherapeutic drugs and the anti-tumor efficacy of immunotherapy. Conclusion This review summarizes the mechanism of ferroptosis and its relationship with different types of tumors, to advance our understanding of cell death and to find a novel approach for clinical cancer management.
Non-syndromic occurrence of true generalized microdontia with hypodontia

Abstract Rational: Dental abnormalities can occur at any stage of tooth development. Of these abnormalities, true generalized microdontia is a rare condition in which all teeth are smaller than normal, while hypodontia is defined as the absence of 1 to 5 teeth. As far as we are aware, no article has reported a case of the non-syndromic occurrence of true generalized microdontia with hypodontia. Patient concerns: A 9-year-old girl who had no systemic diseases presented with congenital absence of maxillary lateral incisors bilaterally and small teeth involving the whole dentition. Diagnoses: Based on intraoral examinations and panoramic radiograph, the patient was diagnosed with the simultaneous occurrence of true generalized microdontia, hypodontia, and a variation of maxillary 1st molar with a single root and single canal. Also, the patient had premature loss of mandibular molars and canines, periapical periodontitis in the mandible left 1st primary molar and deep caries in mandible left secondary primary molar. Interventions: A removable appliance to hold space for early loss of mandibular molars and canines was made at the present stage. The mandible left 1st primary molar had periapical periodontitis and the affected tooth was extracted. Furthermore, the distal surface of the mandible left 2nd primary molar was filled with complex resin materials. A multi-disciplinary therapy plan was carefully designed including orthodontics, dental implants and esthetic restoration in the future. Outcomes: The patient complied well with instructions for wearing the removable space maintainer, which helps prevent mesial migration of the permanent 1st molars, at the current stage. The therapeutic efficiency on periapical periodontitis and caries lesions was also good. Lessons: The non-syndromic presence of true generalized microdontia is extremely rare. A personalized treatment plan with multi-disciplinary considerations should be given for these patients. The pathogenesis remains unclear but may be related to genetic as well as environmental factors. More studies are urgently needed to explore the pathogenesis and treatment options for the future.
Incorporation of Fibrin Matrix into Electrospun Membranes for Periodontal Wound Healing

Guided tissue regeneration (GTR) aims to regenerate the lost attachment apparatus caused by periodontal disease through the use of a membrane. The goal of this study is to create and characterize a novel hybrid membrane that contains biologically active fibrin matrix within a synthetic polycaprolactone (PCL) electrospun membrane. Three-dimensional fibrin matrices and fibrin-incorporated electrospun membrane were created from fresh frozen plasma by centrifugation in glass vials under three different conditions: 400 g for 12 min, 1450 g for 15 min and 3000 g for 60 min. Half the membranes were crosslinked with 1% genipin. Degradation against trypsin indicated biologic stability while uniaxial tensile testing characterized mechanical properties. Continuous data was analyzed by ANOVA to detect differences between groups (p = 0.05). Fibrin-incorporated electrospun membranes showed statistically significant increase in mechanical properties (elastic modulus, strain at break and energy to break) compared to fibrin matrices. While crosslinking had marginal effects on mechanical properties, it did significantly increase biologic stability against trypsin (p < 0.0001). Lastly, membranes generated at 400 g and 1450 g were superior in mechanical properties and biologic stability compared to those generated at 3000 g. Fibrin-incorporated, crosslinked electrospun PCL membranes generated at lower centrifugation forces offers a novel strategy to generate a potentially superior membrane for GTR procedures.
Concomitant pulmonary sarcoidosis and HIV infection

Abstract Rationale: Sarcoidosis is an immune-mediated systemic disease, and the increase in CD4+ T lymphocyte cells is considered as a key factor for the development of sarcoidosis. The acquired immune deficiency syndrome (AIDS) is well known as the impaired immune system and characterized by relative lack of CD4+ T lymphocytes. Thus, the coexistence of sarcoidosis and HIV infection has rarely been reported. Patient concerns: A 65-year-old female patient was admitted to our respiratory ward complained of fatigue, chest distress, and a persistent dry cough for 2 months. Diagnoses: The chest computed tomography scan showed diffuse reticulonodular infiltrates and mediastinal and hilar lymphadenopathy. Fibreoptic bronchoscopy along with transbronchial biopsy and transbronchial needle aspiration was performed. The pathological findings revealed noncaseating granulomas, and the patient was found to be HIV-seropositive through enzyme-linked immunosorbent assay and confirmed as HIV by the centers for disease control and prevention. Interventions: The patient was administered oral methylprednisolone 20 mg/day for pulmonary sarcoidosis and then referred to the hospital for infectious diseases receiving subsequent treatment for HIV. Outcomes: clinical symptoms relieved 3 months later after treatment. Lessons: The coexistence of sarcoidosis and HIV infection is rare because of paradoxical roles of CD4-positive T cells in the pathogenesis of AIDS and sarcoidosis.