Miracle-dz/UniFAR-FTUs huggingface dataset:
The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks

Abstract Coronavirus disease 2019, abbreviated to COVID-19 and sustained by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the latest biological hazard to assume the relevance of insidious worldwide threat. One obvious question that is now engaging the minds of many scientists and healthcare professionals is whether and eventually how laboratory medicine could efficiently contribute to counteract this and other (future) viral outbreaks. Despite there being evidence that laboratory tests are vital throughout many clinical pathways, there are at least three major areas where in vitro diagnostics can also provide essential contributions to diagnostic reasoning and managed care of patients with suspected or confirmed SARS-CoV-2 infection. These include etiological diagnosis, patient monitoring, as well as epidemiologic surveillance. Nonetheless, some structural and practical aspects may generate substantial hurdles in providing timely and efficient response to this infectious emergency, which basically include inadequate (insufficient) environment and shortage of technical and human resources for facing enhanced volume of tests on many infected patients, some of whom are with severe disease. Some proactive and reactive strategies may hence be identified to confront this serious healthcare challenge, which entail major investments on conventional laboratory resources, reinforcement of regional networks of clinical laboratories, installation of mobile laboratories, as well as being proactive in establishing laboratory emergency plans.
The impact of breast cancer resistant protein (BCRP/ABCG2) on drug transport across Caco-2 cell monolayers.

Breast cancer resistant protein (BCRP) is expressed on the apical membrane of small intestinal epithelial cells and functions as an efflux pump with broad substrate recognition. Therefore, quantitative evaluation of the contribution of BCRP to the intestinal permeability of new chemical entities is very important in drug research and development. In this study, we assessed the BCRP-mediated efflux of several model drugs in Caco-2 cells using WK-X-34 as a dual inhibitor of P-glycoprotein (P-gp) and BCRP and LY335979 as a selective inhibitor of P-gp. The permeability of daidzein was high with an apparent permeability coefficient (P AB) for apical-to-basal transport of 20.3 × 10-6 cm/sec. In addition, its efflux ratio (ER) was 1.55, indicating that the contribution of BCRP to its transport is minimal. Estrone-3-sulfate and ciprofloxacin showed relatively higher ER values (>2.0), whereas their BCRP-related absorptive quotient (AQ BCRP) was 0.21 and 0.3, respectively. These results indicate that BCRP does not play a major role in regulating the permeability of estrone-3-sulfate and ciprofloxacin in Caco-2 cells. Nitrofurantoin showed a P AB of 1.8 × 10-6 cm/sec, and its ER was 7.6. However, the AQ BCRP was 0.37, suggesting minimal contribution of BCRP to nitrofurantoin transport in Caco-2 cells. In contrast, topotecan, SN-38, and sulfasalazine had low P AB values (0.81, 1.13, and 0.19 × 10-6 cm/sec, respectively), and each AQ BCRP was above 0.6, indicating that BCRP significantly contributes to the transport of these compounds in Caco-2 cells. In conclusion, Caco-2 cells are useful to accurately estimate the contribution of BCRP to intestinal drug absorption. SIGNIFICANCE STATEMENT: We performed an in vitro assessment of the contribution of BCRP to the transport of BCRP and/or P-gp substrates across Caco-2 cell monolayers using absorptive quotient (AQ), which has been proposed to represent the contribution of drug efflux transporters to the net efflux. The present study demonstrates that the combined use of a BCRP/P-gp dual inhibitor and a P-gp selective inhibitor is useful to estimate the impact of BCRP and P-gp on the permeability of tested compounds in Caco-2 cells.
Cortical Tonotopic Map Changes in Humans Are Larger in Hearing Loss Than in Additional Tinnitus

Neural plasticity due to hearing loss results in tonotopic map changes. Several studies have suggested a relation between hearing loss-induced tonotopic reorganization and tinnitus. This large fMRI study on humans was intended to clarify the relations between hearing loss, tinnitus, and tonotopic reorganization. To determine the differential effect of hearing loss and tinnitus, both male and female participants with bilateral high-frequency hearing loss, with and without tinnitus, and a control group were included. In a total of 90 participants, bilateral cortical responses to sound stimulation were measured with loudness-matched pure-tone stimuli (0.25-8 kHz). In the bilateral auditory cortices, the high-frequency sound-evoked activation level was higher in both hearing-impaired participant groups, compared with the control group. This was most prominent in the hearing loss group without tinnitus. Similarly, the tonotopic maps for the hearing loss without tinnitus group were significantly different from the controls, whereas the maps of those with tinnitus were not. These results show that higher response amplitudes and map reorganization are a characteristic of hearing loss, not of tinnitus. Both tonotopic maps and response amplitudes of tinnitus participants appear intermediate to the controls and hearing loss without tinnitus group. This observation suggests a connection between tinnitus and an incomplete form of central compensation to hearing loss, rather than excessive adaptation. One implication of this may be that treatments for tinnitus shift their focus toward enhancing the cortical plasticity, instead of reversing it. SIGNIFICANCE STATEMENT Tinnitus, a common and potentially devastating condition, is the presence of a “phantom” sound that often accompanies hearing loss. Hearing loss is known to induce plastic changes in cortical and subcortical areas. Although plasticity is a valuable trait that allows the human brain to rewire and recover from injury and sensory deprivation, it can lead to tinnitus as an unwanted side effect. In this large fMRI study, we provide evidence that tinnitus is related to a more conservative form of reorganization than in hearing loss without tinnitus. This result contrasts with the previous notion that tinnitus is related to excessive reorganization. As a consequence, treatments for tinnitus may need to enhance the cortical plasticity, rather than reverse it.
Research Insights on Neural Effects of Auditory Deprivation and Restoration in Unilateral Hearing Loss: A Systematic Review

Neuroplasticity following bilateral deafness and auditory restoration has been repeatedly investigated. In clinical practice, however, a significant number of patients present a severe-to-profound unilateral hearing loss (UHL). To date, less is known about the neuroplasticity following monaural hearing deprivation and auditory input restoration. This article provides an overview of the current research insights on the impact of UHL on the brain and the effect of auditory input restoration with a cochlear implant (CI). An exhaustive systematic review of the literature was performed selecting 38 studies that apply different neural analyses techniques. The main results show that the hearing ear becomes functionally dominant after monaural deprivation, reshaping the lateralization of the neural network for auditory processing, a process that can be considered to influence auditory restoration. Furthermore, animal models predict that the onset time of UHL impacts auditory restoration. Hence, the results seem to advocate for early restoration of UHL, although further research is required to disambiguate the effects of duration and onset of UHL on auditory restoration and on structural neuroplasticity following UHL deprivation and restoration. Ongoing developments on CI devices compatible with Magnetic Resonance Imaging (MRI) examinations will provide a unique opportunity to investigate structural and functional neuroplasticity following CI restoration more directly.
Effects of oxytocin administration and conditioned oxytocin on brain activity: An fMRI study

It has been demonstrated that secretion of several hormones can be classically conditioned, however, the underlying brain responses of such conditioning have never been investigated before. In this study we aimed to investigate how oxytocin administration and classically conditioned oxytocin influence brain responses. In total, 88 females were allocated to one of three groups: oxytocin administration, conditioned oxytocin, or placebo, and underwent an experiment consisting of three acquisition and three evocation days. Participants in the conditioned group received 24 IU of oxytocin together with a conditioned stimulus (CS) during three acquisition days and placebo with the CS on three evocation days. The oxytocin administration group received 24 IU of oxytocin and the placebo group received placebo during all days. On the last evocation day, fMRI scanning was performed for all participants during three tasks previously shown to be affected by oxytocin: presentation of emotional faces, crying baby sounds and heat pain. Region of interest analysis revealed that there was significantly lower activation in the right amygdala and in two clusters in the left superior temporal gyrus in the oxytocin administration group compared to the placebo group in response to observing fearful faces. The activation in the conditioned oxytocin group was in between the other two groups for these clusters but did not significantly differ from either group. No group differences were found in the other tasks. Preliminary evidence was found for brain activation of a conditioned oxytocin response; however, despite this trend in the expected direction, the conditioned group did not significantly differ from other groups. Future research should, therefore, investigate the optimal timing of conditioned endocrine responses and study whether the findings generalize to other hormones as well.
Influence of Anion Structure on Thermal, Mechanical and CO2 Solubility Properties of UV-Cross-Linked Poly(ethylene glycol) Diacrylate Iongels

Iongel-based CO2 separation membranes were prepared by fast (< 1 min) UV-initiated polymerization of poly(ethylene glycol) diacrylate (PEGDA) in the presence of different ionic liquids (ILs) with the [C2mim]+ cation and anions such as [TFSI]−, [FSI]−, [C(CN)3]− and [B(CN)4]−. The four ILs were completely miscible with the non-ionic PEGDA network. Transparent and free-standing iongels containing between 60 and 90 %wt of IL were obtained and characterized by diverse techniques (FTIR, TGA, DSC, DMTA, SEM, CO2 solubility and pure gas permeability). The thermal and mechanical stability of the iongels, as well as CO2 solubility, were found to be strictly dependent on the IL content and the anion’s nature. The TGA results indicated that the iongels mostly follow the thermal profile of the respective neat ILs. The DMTA analysis revealed that the iongels based on fluorinated anions have higher storage modulus than those of cyano-functionalized anions. Conversely, the PEGDA–C(CN)3 iongels presented the highest CO2 solubility values ranging from 72 to 80 mmol/g. Single CO2 permeabilities of 583 ± 29 Barrer and ideal CO2/N2 selectivities of 66 ± 3 were obtained with the PEGDA–70 C(CN)3 iongel membrane. This work demonstrates that the combination of PEGDA with high contents of the best performing ILs is a promising and simple strategy, opening up new possibilities in the design of high-performance iongel membranes for CO2 separation.
Russian Twitter Accounts and the Partisan Polarization of Vaccine Discourse, 2015-2017.

Objectives. To understand how Twitter accounts operated by the Russian Internet Research Agency (IRA) discussed vaccines to increase the credibility of their manufactured personas.Methods. We analyzed 2.82 million tweets published by 2689 IRA accounts between 2015 and 2017. Combining unsupervised machine learning and network analysis to identify "thematic personas" (i.e., accounts that consistently share the same topics), we analyzed the ways in which each discussed vaccines.Results. We found differences in volume and valence of vaccine-related tweets among 9 thematic personas. Pro-Trump personas were more likely to express antivaccine sentiment. Anti-Trump personas expressed support for vaccination. Others offered a balanced valence, talked about vaccines neutrally, or did not tweet about vaccines.Conclusions. IRA-operated accounts discussed vaccines in manners consistent with fabricated US identities.Public Health Implications. IRA accounts discussed vaccines online in ways that evoked political identities. This could exacerbate recently emerging partisan gaps relating to vaccine misinformation, as differently valenced messages were targeted at different segments of the US public. These sophisticated targeting efforts, if repeated and increased in reach, could reduce vaccination rates and magnify health disparities. (Am J Public Health. Published online ahead of print March 19, 2020: e1-e7. doi:10.2105/AJPH.2019.305564).
Canine Mast Cell Tumours: Characterization of Subcutaneous Tumours and Receptor Tyrosine Kinase Profiling

Canine Mast Cell Tumours: Characterization of Subcutaneous Tumours and Receptor Tyrosine Kinase Profiling Jennifer Jane Thompson Co-advisor: University of Guelph, 2012 Dr. Robert A. Foster Co-advisor: Dr. Brenda L Coomber This work explored features of canine mast cell tumours (MCT) to improve prognosis and to discover potential therapeutic targets. Subcutaneous MCT a subset of these tumours arising in the subcutis are usually grouped with cutaneous MCT, but there is evidence that they may be clinically different. The first objective was to develop a grading scheme for subcutaneous MCT. Over 300 canine subcutaneous MCT were evaluated retrospectively and parameters were correlated with clinical outcomes, making this the largest retrospective survival study of these tumours to date. The results of the study showed that the majority of subcutaneous MCT had excellent outcomes and key prognostic markers were identified (mitotic index, surgical margins and degree of infiltration). A subset of the subcutaneous MCT from the retrospective study was further evaluated to assess the cellular localization of KIT a receptor tyrosine kinase (RTK) which is dysregulated and constitutively activated in some cutaneous MCT as well as Ki67, a proliferation marker. In addition, evaluation of mutations of c-KIT, the gene for KIT, was determined for each MCT. Cytoplasmic KIT localization and high Ki67 values were predictive of decreased survival time and time to local reoccurrence, but no c-KIT mutations were detected. The majority of canine MCT do not appear to depend solely upon KIT for tumour progression and few other RTK targets have been studied in canine MCT. Based on evidence that vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptors (PDGFR) may play a role in the progression of canine MCT; the expression and distribution of these RTK were evaluated. The results showed that canine MCT have unique expression profiles and activity of KIT, VEGFR2 and PDGFR. Two novel mast cell tumour cell lines were generated and used to assess signalling of KIT and VEGFR2 in vitro. Stimulatory and inhibitory responses were assessed and found to be different in both cell lines. Both had autophosphorylated VEGFR2 and an autocrine VEGF/VEGFR2 signalling pathway existed for both cell lines. These findings are unique and the first that identify autocrine VEGF signalling as a possible survival mechanism for canine MCT.
Comparison of the prognostic difference between ypTNM and equivalent pTNM stages in esophageal squamous cell carcinoma based on the 8th edition of AJCC classification

Objective: With the separate ypTNM stage groupings established in the 8th edition of AJCC staging system for esophageal squamous cell cancer (ESCC), we aimed to evaluate the prognostic difference between ypTNM stage and equivalent pTNM stage. Methods: ESCC patients with surgery alone (cohort 1) and patients with neoadjuvant therapy plus surgery (cohort 2) were enrolled in the study. Results: In p0, pIb, pIIa, pIIb, pIIIa, pIIIb and pIVa stages of cohort 1, the 5-year DFS and OS rates were 100/100%, 80.5/86.2%, 58.9/57.8%, 51.1/52.7%, 36.3/35.8%, 21.5/22.6% and 11.9/18.0%. In ypI, ypII, ypIII and ypIVa stages of cohort 2, the 5-year DFS and OS rates were 60.9/67.0%, 44.3/52.1%, 48.4/43.2% and 0. Patients in ypI stage had a tendency of poorer survival compared with those in pI stage (P=0.024 for DFS, P=0.067 for OS). There was no significant difference in terms of DFS (P=0.335) or OS (P=0.903) between ypII and pII. Patients in ypIII stage had a tendency of better survival compared with those in pIII stage (P=0.015 for DFS, P=0.059 for OS). Patients in ypIVa stage exhibited a significantly poorer OS compared with those in pIVa stage (P=0.038). Conclusions: With down-staged tumor after neoadjuvant therapy, survival of ypI was closed but not reached to the prognosis of equivalent pI, prognosis of ypII was similar to equivalent pII, and survival of ypIII tended to be better compared with equivalent pIII. However, without down-staged ypIVa tumor, the prognosis was worse compared with equivalent pIVa, indicating those patients were primary resistant to prescribed neoadjuvant therapy.
Bed nuclei of the stria terminalis modulate memory consolidation via glucocorticoid-dependent and -independent circuits

Significance Memory consolidation following emotionally significant events is enhanced by glucocorticoid hormones. Our report identifies the anteroventral bed nuclei of the stria terminalis (avBST) as capable of bidirectionally modulating memory consolidation in rats following inhibitory avoidance learning. Follow-up experiments revealed that divergent pathways from avBST are responsible for the mnemonic effects of avBST inhibition and stimulation and that they occur via glucocorticoid-dependent and -independent mechanisms, respectively. There is extensive evidence that glucocorticoid hormones enhance memory consolidation, helping to ensure that emotionally significant events are well remembered. Prior findings suggest that the anteroventral region of bed nuclei of the stria terminalis (avBST) regulates glucocorticoid release, suggesting the potential for avBST activity to influence memory consolidation following an emotionally arousing learning event. To investigate this issue, male Sprague-Dawley rats underwent inhibitory avoidance training and repeated measurement of stress hormones, immediately followed by optogenetic manipulations of either the avBST or its projections to downstream regions, and 48 h later were tested for retention. The results indicate that avBST inhibition augmented posttraining pituitary–adrenal output and enhanced the memory for inhibitory avoidance training. Pretreatment with a glucocorticoid synthesis inhibitor blocked the memory enhancement as well as the potentiated corticosterone response, indicating the dependence of the memory enhancement on glucocorticoid release during the immediate posttraining period. In contrast, posttraining avBST stimulation decreased retention yet had no effect on stress hormonal output. Subsequent experiments revealed that inhibition of avBST input to the paraventricular hypothalamus enhanced stress hormonal output and subsequent retention, whereas stimulation did not affect either. Conversely, stimulation—but not inhibition—of avBST input to the ventrolateral periaqueductal gray impaired consolidation, whereas neither manipulation affected glucocorticoid secretion. These findings indicate that divergent pathways from the avBST are responsible for the mnemonic effects of avBST inhibition versus stimulation and do so via glucocorticoid-dependent and -independent mechanisms, respectively.
Development and Validation of a Novel Recurrence Risk Stratification for Initial Non-Muscle Invasive Bladder Cancer in the Han Chinese Population

Background: Some classification models for determining the risk of recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer (NMIBC) had some shortcomings in clinical applications. This study aimed to investigate whether the European Organization for Research and Treatment of Cancer (EORTC) risk stratification was useful to predict the recurrence of NMIBC in the Han Chinese population. In addition, we developed and validated a novel risk stratification method for recurrence prediction of NMIBC. Methods: Excluding cases who do not meet the inclusion criteria, 606 patients with NMIBC from the First Affiliated Hospital of Zhengzhou University were included in the testing and validation groups. The recurrence-free survival (RFS) curve according to the EORTC risk classifications was calculated by the Kaplan-Meier and the log-rank test methods. Receiver operating characteristic (ROC) curve analysis was used to estimate the diagnosis value for recurrence. We built a logistic regression model for recurrence in NMIBC patients combining the independent recurrence prognostic factors. One external validation group including 166 patients with NMIBC from the Zhongnan Hospital of Wuhan University was also used to assess the logistic regression model. Results: There was no significant difference in RFS rates between the groups grouped according to EORTC. We constructed a novel risk model to predict recurrence by classifying patients into two groups using ten independent prognostic factors [bladder cancer-specific nuclear matrix protein 4 (BLCA-4), bladder tumour antigen (BTA), nuclear matrix protein 22 (NMP22), carcinoembryonic antigen (CEA), body mass index, smoking, family history of bladder cancer, occupational exposure to aromatic amine chemicals, number of tumours, bladder instillation of chemotherapeutic agents] to predict tumour recurrence based on logistic regression analyses (testing group). According to the novel recurrence risk classification, there was a significant difference in 5-year RFS rates between the low-risk group and the high-risk group (Validation group and the external validation group). Conclusions: Our novel classification model can be a useful tool to predict recurrence risk in the Han Chinese population with NMIBC.
Diagnostic Yield of Computed Tomography–Guided Percutaneous Lung Biopsy in Patients With Prior Nondiagnostic Transbronchial Biopsy

Purpose The purpose of this study was to assess the diagnostic yield of computed tomography (CT)–guided core needle biopsy (CNB) for initial transbronchial biopsy (TBB)–based nondiagnostic lung lesions. Methods From January 2014 to December 2017, 101 consecutive patients with initial TBB-based nondiagnostic lung lesions underwent CT-guided CNB. All procedures were performed with an 18G core needle by a chest radiologist with more than 5 years of experience. The CT-guided CNB was performed within 30 days after the initial TBB. In total, 90 and 11 central and peripheral lung lesions were observed, respectively. The mean ± SD diameter of these lesions was 58.8 ± 21.8 mm. The diagnostic yield of CT-guided CNB was assessed. Results Computed tomography–guided CNB provided a definite diagnosis for 63 (62.4%) of the 101 lesions. The 63 CNB-based lesion diagnoses included malignant (n = 57) and specific benign (n = 6) lesions. The remaining 38 CNB-based nondiagnostic lesions included nonspecific benign (n = 35) and suspected malignant (n = 3) lesions. The 38 CNB-based nondiagnostic lesions were confirmed by surgery (n = 5), repeat CNB (n = 5), or CT follow-up (n = 28). The mean ± SD follow-up was 9.9 ± 7.3 months. Based on the final diagnosis, 67 lesions were malignant and 34 lesions were benign. The sensitivity, specificity, and accuracy of CT-guided CNB were 89.6% (60/67), 100% (34/34), and 93.1% (94/101), respectively. Conclusions Computed tomography–guided CNB is a useful diagnostic modality for accurate diagnosis of lung lesions with inconclusive pathologic results after initial TBB.