Miracle-dz/UniFAR-FTUs huggingface dataset:
Urinary biomarkers for the detection of ovarian cancer: a systematic review

Abstract Currently, the only definitive method for diagnosing ovarian cancer involves histological examination of tissue obtained at time of surgery or by invasive biopsy. Blood has traditionally been the biofluid of choice in ovarian cancer biomarker discovery; however, there has been a growing interest in exploring urinary biomarkers, particularly as it is non-invasive. In this systematic review, we present the diagnostic accuracy of urinary biomarker candidates for the detection of ovarian cancer. A comprehensive literature search was performed using the MEDLINE/PubMed and EMBASE, up to 1 April 2021. All included studies reported the diagnostic accuracy using sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. Risk of bias and applicability of included studies were assessed using the QUADAS-2 tool. Twenty-seven studies were included in the narrative synthesis. Protein/peptide biomarkers were most commonly described (n = 18), with seven studies reporting composite scores of multiple protein-based targets. The most frequently described urinary protein biomarker was HE4 (n = 5), with three studies reporting a sensitivity and specificity > 80%. Epigenetic (n = 1) and metabolomic/organic compound biomarkers (n = 8) were less commonly described. Overall, six studies achieved a sensitivity and specificity of >90% and/or an AUC > 0.9. Evaluation of urinary biomarkers for the detection of ovarian cancer is a dynamic and growing field. Currently, the most promising biomarkers are those that interrogate metabolomic pathways and organic compounds, or quantify multiple proteins. Such biomarkers require external validation in large, prospective observational studies before they can be implemented into clinical practice.
Arterial stiffness throughout pregnancy: Arteriograph device-specific reference ranges based on a low-risk population

Objective: The maternal cardiovascular system undergoes significant adaptation during pregnancy. We aimed to examine the changes in arterial stiffness parameters during normal pregnancy and establish reference ranges for the general population. Methods: We performed a prospective cross-sectional observational study at the University Hospitals of Leicester. We included low-risk healthy pregnant women with singleton and viable pregnancies with no evidence of foetal abnormality or aneuploidy. Smokers, women with pre-existing or gestational hypertensive disorders and diabetes, booking BMI at least 30, on medication that could affect cardiac function and/or those who delivered before 37 completed weeks of gestation, and/or a neonate with birthweight less than 10th centile were excluded. Brachial (BrAIx) and aortic augmentation indices (AoAIx), and pulse wave velocity (PWV) were assessed using the Arteriograph. Data were analysed using a linear mixed model. Results: We analysed a total of 571 readings from 259 women across different gestational ages and present the 10th, 25th, 50th, 75th and 90th centiles for BrAIx, AoAIx and PWV from 12+0 to 42+0 weeks’ gestation. All haemodynamic variables were significantly associated with maternal heart rate. BrAIx, AoAIx and PWV demonstrated significant change with gestation, with all reaching their lowest value in the second trimester. Conclusion: The current study presents reference ranges for BrAIx, AoAIx and PWV in low-risk singleton pregnancies. Further work is required to establish if women in whom measures of arterial stiffness lie above the 90th centile could be at increased risk of adverse pregnancy outcomes and to identify the optimum time for screening.
Hallucinogenic drugs and their potential for treating fear‐related disorders: Through the lens of fear extinction

Fear‐related disorders, mainly phobias and post‐traumatic stress disorder, are highly prevalent, debilitating disorders that pose a significant public health problem. They are characterized by aberrant processing of aversive experiences and dysregulated fear extinction, leading to excessive expression of fear and diminished quality of life. The gold standard for treating fear‐related disorders is extinction‐based exposure therapy (ET), shown to be ineffective for up to 35% of subjects. Moreover, ET combined with traditional pharmacological treatments for fear‐related disorders, such as selective serotonin reuptake inhibitors, offers no further advantage to patients. This prompted the search for ways to improve ET outcomes, with current research focused on pharmacological agents that can augment ET by strengthening fear extinction learning. Hallucinogenic drugs promote reprocessing of fear‐imbued memories and induce positive mood and openness, relieving anxiety and enabling the necessary emotional engagement during psychotherapeutic interventions. Mechanistically, hallucinogens induce dynamic structural and functional neuroplastic changes across the fear extinction circuitry and temper amygdala's hyperreactivity to threat‐related stimuli, effectively mitigating one of the hallmarks of fear‐related disorders. This paper provides the first comprehensive review of hallucinogens' potential to alleviate symptoms of fear‐related disorders by focusing on their effects on fear extinction and the underlying molecular mechanisms. We overview both preclinical and clinical studies and emphasize the advantages of hallucinogenic drugs over current first‐line treatments. We highlight 3,4‐methylenedioxymethamphetamine and ketamine as the most effective therapeutics for fear‐related disorders and discuss the potential molecular mechanisms responsible for their potency with implications for improving hallucinogen‐assisted psychotherapy.
Key sequence features of CRISPR RNA for dual-guide CRISPR-Cas9 ribonucleoprotein complexes assembled with wild-type or HiFi Cas9

Abstract Specific sequence features of the protospacer and protospacer-adjacent motif (PAM) are critical for efficient cleavage by CRISPR-Cas9, but current knowledge is largely derived from single-guide RNA (sgRNA) systems assessed in cultured cells. In this study, we sought to determine gRNA sequence features of a more native CRISPR-Cas9 ribonucleoprotein (RNP) complex with dual-guide RNAs (dgRNAs) composed of crRNA and tracrRNA, which has been used increasingly in recent CRISPR-Cas9 applications, particularly in zebrafish. Using both wild-type and HiFi SpCas9, we determined on-target cleavage efficiencies of 51 crRNAs in zebrafish embryos by assessing indel occurrence. Statistical analysis of these data identified novel position-specific mononucleotide features relevant to cleavage efficiencies throughout the protospacer sequence that may be unique to CRISPR-Cas9 RNPs pre-assembled with perfectly matched gRNAs. Overall features for wild-type Cas9 resembled those for HiFi Cas9, but specific differences were also observed. Mutational analysis of mononucleotide features confirmed their relevance to cleavage efficiencies. Moreover, the mononucleotide feature-based score, CRISPR-kp, correlated well with efficiencies of gRNAs reported in previous zebrafish RNP injection experiments, as well as independently tested crRNAs only in RNP format, but not with Cas9 mRNA co-injection. These findings will facilitate design of gRNA/crRNAs in genome editing applications, especially when using pre-assembled RNPs.
Genome of the ramshorn snail Biomphalaria straminea—an obligate intermediate host of schistosomiasis

Abstract Background Schistosomiasis, or bilharzia, is a parasitic disease caused by trematode flatworms of the genus Schistosoma. Infection by Schistosoma mansoni in humans results when cercariae emerge into water from freshwater snails in the genus Biomphalaria and seek out and penetrate human skin. The snail Biomphalaria straminea is native to South America and is now also present in Central America and China, and represents a potential vector host for spreading schistosomiasis. To date, genomic information for the genus is restricted to the neotropical species Biomphalaria glabrata. This limits understanding of the biology and management of other schistosomiasis vectors, such as B. straminea. Findings Using a combination of Illumina short‐read, 10X Genomics linked‐read, and Hi‐C sequencing data, our 1.005 Gb B. straminea genome assembly is of high contiguity, with a scaffold N50 of 25.3 Mb. Transcriptomes from adults were also obtained. Developmental homeobox genes, hormonal genes, and stress-response genes were identified, and repeat content was annotated (40.68% of genomic content). Comparisons with other mollusc genomes (including Gastropoda, Bivalvia, and Cephalopoda) revealed syntenic conservation, patterns of homeobox gene linkage indicative of evolutionary changes to gene clusters, expansion of heat shock protein genes, and the presence of sesquiterpenoid and cholesterol metabolic pathway genes in Gastropoda. In addition, hormone treatment together with RT-qPCR assay reveal a sesquiterpenoid hormone responsive system in B. straminea, illustrating that this renowned insect hormonal system is also present in the lophotrochozoan lineage. Conclusion This study provides the first genome assembly for the snail B. straminea and offers an unprecedented opportunity to address a variety of phenomena related to snail vectors of schistosomiasis, as well as evolutionary and genomics questions related to molluscs more widely.
The era of Cas12 and Cas13 CRISPR-based disease diagnosis

Abstract Clustered regularly interspaced short palindromic repeats (CRISPR) and associated protein (Cas) systems, since their discovery, have found growing applications in cell imaging, transcription modulation, therapeutics and diagnostics. Discovery of Cas12 and Cas13 have brought a new dimension to the field of disease diagnosis. These endonucleases have been extensively used for diagnosis of viral diseases in humans and animals and to a lesser extent in plants. The exigency of SARS-CoV-2 pandemic has highlighted the potential of CRISPR-Cas systems and sparked the development of innovative point-of-care diagnostic technologies. Rapid adaptation of CRISPR-chemistry combined with sensitive read-outs for emerging pathogens make them ideal candidates for detection and management of diseases in future. CRISPR-based approaches have been recruited for the challenging task of cancer detection and prognosis. It stands to reason that the field of CRISPR-Cas-based diagnosis is likely to expand with Cas12 and Cas13 playing a pivotal role. Here we focus exclusively on Cas12- and Cas13-based molecular diagnosis in humans, animals and plants including the detection of SARS-coronavirus. The CRISPR-based diagnosis of plant and animal diseases have not found adequate mention in previous reviews. We discuss various advancements, the potential shortfalls and challenges in the widespread adaptation of this technology for disease diagnosis.
Motion Estimation by Deep Learning in 2D Echocardiography: Synthetic Dataset and Validation

Motion estimation in echocardiography plays an important role in the characterization of cardiac function, allowing the computation of myocardial deformation indices. However, there exist limitations in clinical practice, particularly with regard to the accuracy and robustness of measurements extracted from images. We therefore propose a novel deep learning solution for motion estimation in echocardiography. Our network corresponds to a modified version of PWC-Net which achieves high performance on ultrasound sequences. In parallel, we designed a novel simulation pipeline allowing the generation of a large amount of realistic B-mode sequences. These synthetic data, together with strategies during training and inference, were used to improve the performance of our deep learning solution, which achieved an average endpoint error of 0.07 ± 0.06 mm per frame and 1.20 ± 0.67 mm between ED and ES on our simulated dataset. The performance of our method was further investigated on 30 patients from a publicly available clinical dataset acquired from a GE system. The method showed promise by achieving a mean absolute error of the global longitudinal strain of 2.5 ± 2.1% and a correlation of 0.77 compared to GLS derived from manual segmentation, much better than one of the most efficient methods in the state-of-the-art (namely the FFT-Xcorr block-matching method). We finally evaluated our method on an auxiliary dataset including 30 patients from another center and acquired with a different system. Comparable results were achieved, illustrating the ability of our method to maintain high performance regardless of the echocardiographic data processed.
A behavioral approach to sexual function: testing a moderation mediation model with expression of feelings, sexual self-disclosure and gender

Abstract Little is known about specific intimacy dimensions’ role in sexual function. In the current study, we aimed to gain more insight into how expression of feelings and sexual self-disclosure (a mediator) might potentially affect sexual functioning testing a theoretically based moderated mediation model, that uses gender as a moderator. A total of 661 participants, of which 211 were men (31,90%) and 450 were women (68,10%) aged 18-74 years involved in a monogamous committed relationship participated in the study. We used macro PROCESS 3.2 for IBM – SPSS to test simple mediation and moderated mediation models. The data revealed a significant overall effect of expression of feelings on sexual function, supporting that sexual self-disclosure mediates this relationship. We found that gender does not moderate either the relationship between expression of feelings and sexual self-disclosure nor the trajectory between sexual self-disclosure and sexual function. Our results highlight the importance of taking an interpersonal behavioral approach to sexual function, namely one that focuses on communication behaviors. However, these results need to be explored with clinical samples to understand their full potential for clinical interventions within a behavioral paradigm to partnered people’s sexual problems.
Ethnographic study of the barriers and facilitators to implementing human papillomavirus (HPV) self-sampling as a primary screening strategy for cervical cancer among Inuit women of Nunavik, Northern Quebec

ABSTRACT The rate of cervical cancer among Canadian Inuit women is higher than the national average. To date, early detection remains the best strategy for reducing the incidence of cervical cancer and its consequences. Thus, the aim of this study was to explore the barriers and facilitators in implementing human papillomavirus (HPV) self-sampling as a primary screening strategy for cervical cancer among Inuit women of Nunavik in Northern Quebec. A focused ethnographic approach was adopted. Inuit women of Nunavik participated in individual or group interviews during which a semi-structured interview guide was used to determine their perceptions of the barriers and facilitators to implementing HPV self-sampling as a primary screening strategy for cervical cancer. The data were analysed based on Paillé’s grounded theory of qualitative analysis. Twenty-eight Inuit women participated in this study. Analysis revealed five subcategories of facilitators and four barriers. Inuit women may embrace the self-sampling method. Importantly, in order to be effective, these strategies must be culturally sensitive and adapted to women’s preferences so as to increase sustainability. The results of this study provide the means for integrating the perspectives of Inuit women in implementing HPV self-sampling as a primary screening strategy for cervical cancer in Nunavik. Consideration of these facilitators and barriers might maximise the chance of success and optimise the screening participation rate.
Enhanced localized dipole of Pt-Au single-site catalyst for solar water splitting

Significance Single-atom or single-site catalysts have received considerable research interest in photocatalysis and many other heterogeneous catalytic processes. However, the single metal sites did not obviously change the charge transportation process of the photocatalyst and thus hardly contributed to the enhancement of charge separation and transfer. Inspired by the synergy between metal species in classical catalytic reactions, this research presents a strategy of constructing a Pt-Au binary single-site catalyst. Pt-Au binary single sites not only functioned as the catalytic reactive sites but also modulated the charge distribution and enhanced the internal electric field. The concept and the strategy of this work are expected to provide a novel perspective for improving photocatalytic charge transportation dynamics. Solar water splitting is regarded as holding great potential for clean fuels production. However, the efficiency of charge separation/transfer of photocatalysts is still too low for industrial application. This paper describes the synthesis of a Pt-Au binary single-site loaded g-C3N4 nanosheet photocatalyst inspired by the concept of the dipole. The existent larger charge imbalance greatly enhanced the localized molecular dipoles over adjacent Pt-Au sites in contrast to the unary counterparts. The superposition of molecular dipoles then further strengthened the internal electric field and thus promoted the charge transportation dynamics. In the modeling photocatalytic hydrogen evolution, the optimal Pt-Au binary site photocatalysts (0.25% loading) showed 4.9- and 2.3-fold enhancement of performance compared with their Pt and Au single-site counterparts, respectively. In addition, the reaction barrier over the Pt-Au binary sites was lowered, promoting the hydrogen evolution process. This work offers a valuable strategy for improving photocatalytic charge transportation dynamics by constructing polynary single sites.
Astragalus polysaccharide (APS) exerts protective effect against acute ischemic stroke (AIS) through enhancing M2 micoglia polarization by regulating adenosine triphosphate (ATP)/ purinergic receptor (P2X7R) axis

ABSTRACT Clinically, the effective treatment for patients with acute ischemic stroke (AIS) is very limited. Therefore, this paper aims to investigate the mechanism how astragalus polysaccharide (APS) exerts protective effect against AIS and provide a new method for the treatment of AIS. Cell surface antigen flow cytometry and immunofluorescence were used to identify M1 and M2 microglia. Western blot was used to evaluate the expression of associated protein. Oxygen-glucose deprivation (OGD) was used to simulate the effect of AIS on rat microglia. The middle cerebral artery occlusion (MCAO) model was established to simulate the effect of AIS in vivo. Evans blue dye (EBD) was used to evaluate the permeability of blood–brain barrier (BBB). Western blot and cell surface antigen flow cytometry results showed that APS promoted the M2 polarization of rat microglia by inhibiting the expression of purinergic receptor (P2X7R). APS reversed the effect of OGD on the polarization of rat microglia M1/ M2 by regulating P2X7R. APS reversed the effect of MCAO on the polarization of rat microglia M1/ M2 in vivo. Furthermore, APS inhibited the expression of P2X7R by promoting the degradation of adenosine triphosphate (ATP) in the cerebral cortex of MCAO rats. In addition, APS contributed to maintain the integrity of BBB. Summarily, APS can reduce brain injury by promoting the degradation of ATP in microglia and inhibiting the expression of P2X7R after AIS.
Can bleeding in trabeculectomy be decreased? Effectiveness of brimonidine pre-treatment

Purpose To evaluate the efficacy of preoperative topical brimonidine use to maintain visibility during trabeculectomy and control intraoperative bleeding and postoperative subconjunctival hemorrhage. Methods The first group comprised 35 eyes of 34 patients administered brimonidine tartrate 0.15% (Brimogut, Bilim Ilac, Turkey) eye drops 6 and 3 min before surgery, and 33 eyes of 31 patients who received no medication for vasoconstriction formed the second group. Preoperative and postoperative photographs and operation video images were taken and vision analysis software used. Black-and-white images were obtained to identify the blood vessel and surface hemorrhage areas. The surface area of the hemorrhage was calculated by counting the black pixels with Image J software. Results There was no significant difference between two groups in terms of baseline (preoperative) eye redness (p > 0.05). In the first group, the eye redness values were 344.7 ± 19.5 pixels preoperatively and 244.1 ± 23.3 pixels at the beginning of the surgery, respectively (p < 0.001). However, no significant change was observed in the second group in eye redness (348.2 ± 17.5 pixels preoperatively and 360.7 ± 26.8 pixels at the beginning of the surgery, p > 0.05). Cautery was used for an average of 11.91 ± 1.96 s in the first group and 25.57 ± 4.66 s in the second to control intraoperative bleeding (P < 0.001). Conclusion Preoperative topical brimonidine use in trabeculectomy surgery significantly decreased intraoperative bleeding and postoperative subconjunctival hemorrhage and facilitated bleeding control.
β-Catenin signaling in hepatocellular carcinoma

Deregulated Wnt/β-catenin signaling is one of the main genetic alterations in human hepatocellular carcinoma (HCC). Comprehensive genomic analyses have revealed that gain-of-function mutation of CTNNB1, which encodes β-catenin, and loss-of-function mutation of AXIN1 occur in approximately 35% of human HCC samples. Human HCCs with activation of the Wnt/β-catenin pathway demonstrate unique gene expression patterns and pathological features. Activated Wnt/β-catenin synergizes with multiple signaling cascades to drive HCC formation, and it functions through its downstream effectors. Therefore, strategies targeting Wnt/β-catenin have been pursued as possible therapeutics against HCC. Here, we review the genetic alterations and oncogenic roles of aberrant Wnt/β-catenin signaling during hepatocarcinogenesis. In addition, we discuss the implication of this pathway in HCC diagnosis, classification, and personalized treatment.
Previous work and meaning in life post-retirement: a reminiscence perspective

Abstract Objectives To understand how different reminiscence functions and previously meaningful work predicted meaning in life in retired adults. Method We surveyed 240 retired adults recruited from ResearchMatch and had them complete questionnaires assessing their reminiscence functions, their meaning in life, and whether they perceived their previous work as meaningful. We tested a structural model that positioned meaningful work as a mediator of the relation between reminiscence functions and meaning in life and an alternative model that positioned reminiscence functions as mediators of the relation between meaningful work and meaning in life. Results After comparing fit, we retained the structural model. Findings indicated that participants who reminisced for the sake of consolidating their identities (identity) reported their previous work as more meaningful, but those that reminisced for the sake of maintaining negative emotions (bitterness revival) reported their previous work as less meaningful. In turn, participants who perceived their previous work as more meaningful reported greater meaning in life. Identity and bitterness revival reminiscence also related to meaning in life via meaningful work. Conclusion Results suggest that retired adults’ reminiscence functions and their perceptions of their previous employment are important to understanding retired adults’ ongoing construction of meaning in their lives.