Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic value of Platelet/lymphocyte Ratio (PLR) for predicting sentinel axillary lymph node positivity in early‐stage breast cancer compared with ultrasonography

In breast cancer, the most important prognostic factor is axillary lymph node metastasis. However, there is no method which can diagnose axillary lymph node metastasis preoperatively with high sensitivity. The aim of this study was to evaluate the relationship between platelet/lymphocyte ratio (PLR) and sentinel lymph node metastasis in early‐stage breast cancer.
Physico-thermal properties of kenaf fiber/high-density polyethylene/maleic anhydride compatibilized composites

Kenaf fiber/high-density polyethylene/maleic anhydride (MA)-compatibilized composites were melt mixed in a twin-screw extruder and molded using injection molding machine. Physicothermal properties of the composites were studied at different percentages of compatibilizer contents using various techniques. The addition of 8% compatibilizer into 8.5 and 17.5 wt% fiber content improved the adhesion and tensile strength by 14.5% and 13.6%, respectively. Compatibilized samples exhibited higher peak load and fracture energy on impact testing compared to the samples without maleic anhydride compatibilizer. The effect of the addition of maleic anhydride compatibilizer on peak load and fracture energy was observed to be at its highest at 8%. Differential scanning calorimetric measurements revealed that the melting enthalpy and degree of crystallinity of composites increased with increasing compatibilizer content up to 8% and then decreased at 12% compatibilizer content. Dynamic mechanical analysis showed that the storage modulus of composites was increased, but the loss modulus and tangent delta were decreased after the addition of compatibilizer. This indicates that compatibilized composites produced have improved toughness and reduced stiffness.
Conditioned generalisation in generalised anxiety disorder: the role of concurrent perceptual and conceptual cues

ABSTRACT Previous research in extinction indicates no difference in US expectancies for aversive and non-aversive unconditioned stimuli (USs). In this study, we bridged these topics by examining how concurrent perceptual and conceptual cues influence conditioned generalisation of generalised anxiety disorder (GAD) patients by using non-aversive USs. The study included two consecutive phases: acquisition and generalisation. In the acquisition phase, we used blue and purple images as the perceptually conditioned stimuli, images of animals and household items as the conceptually conditioned stimuli, and non-aversive images as unconditioned stimuli (US). In the generalisation phase, we used images containing both conceptual and perceptual cues (e.g. blue animals) as the generalisation stimuli. Participants rated the US expectancy for all images. We found that compared with the control group, the patients exhibited generalisation in response to stimuli that included conditional conceptual cues. These results reveal novel evidence of generalisation in GAD and may have implications for considering the concept-based information in extinction treatment.
Structural and catalytic characterization of Blastochloris viridis and Pseudomonas aeruginosa homospermidine synthases supports the essential role of cation–π interaction

The homospermidine synthases from P. aeruginosa and B. viridis, as well as their single-residue variants, are compared based on crystal structures and activity assays. A high structural similarity is demonstrated, suggesting the equivalent involvement of relevant residues in the reaction mechanism and catalytic dependence on cation–π interaction.
Pretreatment Squamous Cell Carcinoma Antigen (SCC-Ag) as a Predictive Factor for the Use of Consolidation Chemotherapy in Cervical Cancer Patients After Postoperative Extended-Field Concurrent Chemoradiotherapy

Objective: The goal of this study was to confirm the clinical value of pretreatment serum squamous cell carcinoma antigen (SCC-Ag) in the administration of consolidation chemotherapy in patients with cervical cancers undergoing postoperative extended-field radiotherapy (EFRT) and concurrent chemotherapy (CCRT). Methods: Between 2007 and 2018, a total of 113 patients were treated with postoperative extended-field intensity-modulated radiotherapy (EF-IMRT) and CCRT. There were 63 patients receiving extended-field concurrent chemoradiotherapy (EF-CCRT) and consolidation chemotherapy, while another 50 patients underwent EF-CCRT alone. For the planning target volume, the prescribed dose was 45 to 50.4Gy/25 to 28 fractions. The consolidation chemotherapy regimen contained docetaxel and cisplatin. Results: For the patients with high pretreatment SCC-Ag, the addition of consolidation chemotherapy significantly improved their treatment outcomes and they had better 5-year overall survival (OS) (81.02% vs 63.44%, P = .018) and disease-free survival (DFS) (76.95% vs 61.12%, P = .007) than those without it. Meanwhile, the patients with consolidation chemotherapy had a lower rate of distant metastasis (8.8% vs 34.8%, P = .001). For the patients with low pretreatment SCC-Ag, there was no difference in prognosis between patients receiving consolidation chemotherapy and those not receiving consolidation. In multivariate analysis, consolidation chemotherapy was found to be a factor significantly associated with DFS (P = .035, 95% confidence interval (CI): 0.304-0.977) and distant metastasis (P = .009, 95% CI: 0.125-0.841). Conclusion: The patients who received consolidation chemotherapy showed significantly better DFS. Furthermore, pretreatment serum SCC-Ag > 6.5 ng/mL may be a predictive factor for the use of consolidation chemotherapy in cervical cancer patients treated with postoperative EF-CCRT.
Trends and projections in the incidence of oesophageal cancer in the Netherlands: An age‐period‐cohort analysis from 1989 to 2041

In Western populations, the incidence of oesophageal squamous cell carcinoma (OSCC) has been declining, whereas the incidence of oesophageal adenocarcinoma (OAC) has been increasing. Our study examines temporal trends in the incidence of oesophageal cancer in the Netherlands between 1989 and 2016, in addition to predicting future trends through 2041. Data from the Netherlands Cancer Registry and Statistics Netherlands were collected to obtain incidence trends of OSCC and OAC for the period 1989 to 2016. Age‐period‐cohort (APC) modelling was used to estimate the contribution of age, calendar period and birth cohort on the observed incidence trends. To predict the future numbers of new cases of both OSCC and OAC from 2017 to 2041, log‐linear APC models were fitted to the trends of 1989 to 2016. The age‐standardised incidence rates of OSCC have decreased slightly for men and increased slightly for women. In contrast, a marked increase in the incidence of OAC was observed, ranging from 2.8 per 100 000 persons in 1989 to 10.1 in 2016. This increase in OAC incidence was more prominent in men, and it will result in an increased risk of OAC for successive generations. Future projections indicate that the incidence of OAC will further increase to 13.1 per 100 000 persons in 2037 to 2041, meaning that there will be 13 259 cases of OAC in 2037 to 2041, as compared to 9386 diagnoses in 2017 to 2021. The changing epidemiologic trends in oesophageal cancer in the Netherlands should be reflected in the development of prevention, early detection and treatment strategies.
Seed sequence polymorphism rs2168518 and allele-specific target gene regulation of hsa-miR-4513

Abstract MicroRNAs (miRNAs) are small post-transcriptional regulators that offer promising targets for treating complex diseases. To this end, hsa-miR-4513 is an excellent candidate as this gene harbors within its conserved heptametrical seed sequence a frequent polymorphism (rs2168518), which has previously been associated with several complex phenotypes. So far, little is known about the biological mechanism(s) underlying these associations. In an initial step, we now aimed to identify allele-specific target genes of hsa-miR-4513. We performed RNA sequencing in a miRNA overexpression model in human umbilical vein endothelial cells transfected with separated hsa-miR-4513 alleles at rs2168518, namely hsa-miR-4513-G and hsa-miR-4513-A. Genes specifically regulated by the rs2168518 alleles were independently verified by quantitative reverse transcription PCR (qRT-PCR), western blot analysis and allele-specific miRNA binding via a luciferase reporter assay. By a text-based search publicly available databases such as Online Mendelian Inheritance in Man and Mouse Genome Informatics were utilized to link target genes of hsa-miR-4513 to previously described phenotypes. Overall, we identified 23 allele-specific hsa-miR-4513 target genes and replicated 19 of those independently via qRT-PCR. Western blot analysis and luciferase reporter assays conducted for an exemplary subsample further confirmed the allele-specific regulation of these genes by hsa-miR-4513. Remarkably, multiple allele-specific target genes identified are linked via text retrieval to several phenotypes previously reported to be associated with hsa-miR-4513. These genes offer promising candidates for ongoing research on the functional pathobiological impact of hsa-miR-4513 and its seed polymorphism rs2168518. This could give rise to therapeutic applications targeting this miRNA.
G protein‐coupled receptor GPR37‐like 1 regulates adult oligodendrocyte generation

Oligodendrocytes (OLs) continue to be generated from OL precursors (OPs) in the adult mammalian brain. Adult‐born OLs are believed to contribute to neural plasticity, learning and memory through a process of “adaptive myelination,” but how adult OL generation and adaptive myelination are regulated remains unclear. Here, we report that the glia‐specific G protein‐coupled receptor 37‐like 1 (GPR37L1) is expressed in subsets of OPs and newly formed immature OLs in adult mouse brain. We found that OP proliferation and differentiation are inhibited in the corpus callosum of adult Gpr37l1 knockout mice, leading to a reduction in the number of adult‐born OLs. Our data raise the possibility that GPR37L1 is mechanistically involved in adult OL generation and adaptive myelination, and suggest that GPR37L1 might be a useful functional marker of OPs that are committed to OL differentiation.
In vivo hyperCEST imaging: Experimental considerations for a reliable contrast

HyperCEST contrast relies on the reduction of the solvent signal after selective saturation of the solute magnetization. The scope of this work is to outline the experimental conditions needed to obtain a reliable hyperCEST contrast in vivo, where the “solvent” signal (ie, the dissolved‐phase signal) may change over time due to the increase in xenon (Xe) accumulation into tissue.
A Cross-Sectional Survey of Risky Travel and Leisure Behaviors During the COVID-19 Pandemic

Purpose COVID-19 is largely spread through close contact with infected people in indoor spaces. Avoiding these spaces is one of the most effective ways to slow the spread. This study assessed who had engaged in risky travel and leisure behaviors before the availability of vaccines. Design National cross-sectional on-line survey collected in November and December 2020. Setting: United States; Participants: 2589 adults representative by gender and race/ethnicity to the US population; Measures: The survey assessed if people had resumed 11 risky behaviors during the pandemic, prior to vaccines. Independent variables included age, race/ethnicity, region of the country, education, income, preexisting conditions, perceived severity and susceptibility, positive COVID diagnosis, and political ideology. Analysis Univariate analysis and logistic regressions were used to assess demographic and psychological factors of those resuming these behaviors. Results: Most (60.3%) of people had resumed at least 1 behavior with eating inside of restaurants (33.2%) and visiting family and friends (37.5%) being the most prevalent. In the multivariate analyses, perceived susceptibility was significant across all behaviors. Young people, fiscal conservatives, and people with higher perceived severity were more likely to perform several of the behaviors. Preexisting conditions did not predict any of the behaviors. Conclusions Travel and leisure behaviors vary by type of risk and may need specific tailored, prevention messages to promote risk reduction during future pandemics.
Patient preferences and experiences regarding thrombopoietin-receptor agonists for immune thrombocytopenia in the United Kingdom and Ireland (TRAPeze UK & IE study)

ABSTRACT Objectives To establish the experiences with and preferences towards existing thrombopoietin-receptor agonist (TPO-RA) treatments of individuals with immune thrombocytopenia (ITP) in the UK and Ireland, based on treatment attributes. Methods Responses from UK and Ireland individuals with ITP were collected in a pan-European online survey (TRAPeze, [Thrombopoietin-Receptor Agonist Patient experience survey]) from 18 September 2020 to 18 February 2021. TRAPeze was a survey of treatment preference regarding TPO-RAs (using a discrete choice experiment design), participant demographics, disease characteristics, treatment history, overall satisfaction with therapy, direct healthcare resource utilization and wider social impact. Results The survey was completed by 32 UK respondents. Characteristics with the greatest influence on preference towards TPO-RA treatments were method of administration (odds ratio (OR) 5.6, 95% confidence interval (CI) 3.2–10.1) and drug-food interactions (OR 3.2, 95% CI 1.8–5.7). Particularly, participants were more likely to select an oral tablet over a subcutaneous injection (OR 7.4, 95% CI 3.6–15.1) and a treatment without food restrictions rather than with food restrictions (OR 3.6, 95% CI 1.8–6.8). Conclusion This is the first study to quantify the preference of individuals with ITP towards TPO-RA treatment attributes and demonstrates preference for orally administered treatments, without drug-food interactions.
In vitro and in vivo anti‐epileptic efficacy of eslicarbazepine acetate in a mouse model of KCNQ2‐related self‐limited epilepsy

The KCNQ2 gene encodes for the Kv7.2 subunit of non‐inactivating potassium channels. KCNQ2‐related diseases range from autosomal dominant neonatal self‐limited epilepsy, often caused by KCNQ2 haploinsufficiency, to severe encephalopathies caused by KCNQ2 missense variants. In vivo and in vitro effects of the sodium channel blocker eslicarbazepine acetate (ESL) and eslicarbazepine metabolite (S‐Lic) in a mouse model of self‐limited neonatal epilepsy as a first attempt to assess the utility of ESL in the KCNQ2 disease spectrum was investigated.
Tocilizumab administration for the treatment of hospitalized patients with COVID‐19: A systematic review and meta‐analysis

Tocilizumab has been repurposed against the ‘cytokine storm’ in the setting of coronavirus disease 2019 (COVID‐19). Our aim was to evaluate the efficacy of tocilizumab in the management of hospitalized COVID‐19 patients. We searched MEDLINE, CENTRAL and medRxiv for studies of tocilizumab in hospitalized COVID‐19 patients. Primary objective was the effectiveness of tocilizumab on mortality. Secondary objectives included the need for invasive mechanical ventilation (IMV), composite endpoints of mortality or IMV and intensive care unit (ICU) admission or IMV, length of hospitalization and differences in mortality in subgroups (ICU and non‐ICU patients and patients receiving or not receiving concomitant corticosteroids). We included 52 studies (nine randomized controlled trials [RCTs] and 43 observational) with a total of 27,004 patients. In both RCTs and observational studies, the use of tocilizumab was associated with a reduction in mortality; 11% in RCTs (risk ratio [RR] 0.89, 95% CI 0.82 to 0.96) and 31% in observational studies (RR 0.69, 95% CI 0.58 to 0.83). The need for IMV was reduced by 19% in RCTs (RR 0.81, 95% CI 0.71 to 0.93), while no significant reduction was observed in observational studies. Both RCTs and observational studies showed a benefit from tocilizumab on the composite endpoint of mortality or IMV. Tocilizumab improved mortality both in ICU and non‐ICU patients. Reduction in mortality was evident in observational studies regardless of the use of systemic corticosteroids, while that was not the case in the RCTs. Tocilizumab was associated with lower mortality and other clinically relevant outcomes in hospitalized patients with moderate‐to‐critical COVID‐19.
A case of etanercept (anti-TNF agent) induced granulomas on the lids

ABSTRACT Sarcoid-like granulomas are a rare adverse effect of TNF-α inhibitors that are becoming increasingly reported in the literature. A retrospective study in France estimated this adverse effect to occur in 0.04% patients. We report an important reversible cause that is more commonly being seen. A 70 year old lady presented with multiple lesions on her lids in the ophthalmology clinic. Histology confirmed that they were sarcoid-like granulomas. The patient had been started on etanercept (anti-TNF agent) a few months prior for rheumatoid arthritis. Investigations were undertaken to rule out differentials such as autoimmune conditions and infective causes like tuberculosis. After ruling out an active inflammatory disease and an autoimmune cause, etanercept induced granulomas were considered. Etanercept was stopped. This resulted in the resolution of granulomas over the course of a few months. Etanercept induced granulomas resolve when the anti-TNF agent is discontinued; however, some patients may require treatment with steroids. As this case demonstrates, ophthalmologists should be aware that anti-TNF agents can cause non-caseating granulomas, which can be cutaneous or pulmonary. This can help to result in more prompt diagnoses and appropriate treatment.
Valvuloplasty in 103 fetuses with critical aortic stenosis: outcome and new predictors for postnatal circulation

To review our experience with fetal aortic valvuloplasty (FAV) in fetuses with critical aortic stenosis (CAS) and evolving hypoplastic left heart syndrome (eHLHS), including short‐ and medium‐term postnatal outcome, and to refine selection criteria for FAV by identifying preprocedural predictors of biventricular (BV) outcome.
Utility of mutational analysis for risk stratification of indeterminate thyroid nodules in a real‐world setting

American Thyroid Association (ATAn) 2015 guidelines recommend repeat fine‐needle aspiration with molecular marker profiling (MMP) or diagnostic lobectomy in thyroid nodules yielding atypia of unknown significance/follicular lesion of unknown significance (AUS/FLUS) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cytology. Our objective is to describe the molecular profiles and histological correlates of these cytologically indeterminate nodules (CIN) to aid risk stratification.
Ethanol and opioids do not act synergistically to depress excitation in carotid body type I cells

Objective The combination of opioids and ethanol can synergistically depress breathing and the acute ventilatory response to hypoxia. Multiple studies have shown that the underlying mechanisms for this may involve calcium channel inhibition in central neurons. But we have previously identified opioid receptors in the carotid bodies and shown that their activation inhibits calcium influx into the chemosensitive cells. Given that the carotid bodies contribute to the drive to breathe and underpin the acute hypoxic ventilatory response, we hypothesized that ethanol and opioids may act synergistically in these peripheral sensory organs to further inhibit calcium influx and therefore inhibit ventilation. Methods Carotid bodies were removed from 56 Sprague–Dawley rats (1021 days old) and then enzymatically dissociated to allow calcium imaging of isolated chemosensitive type I cells. Cells were stimulated with high K+ in the presence and absence of the µ-opioid agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) (10 µM), a maximal sublethal concentration of ethanol (3 g L-1, 65.1 mM) or a combination of both. Results DAMGO alone significantly inhibited Ca2+ influx but this effect was not potentiated by the high concentration of ethanol. Conclusion These results indicate for the first time that while opioids may suppress breathing via an action at the level of the carotid bodies, ethanol is unlikely to potentiate inhibition via this pathway. Thus, the synergistic effects of ethanol and opioids on ventilatory parameters are likely mediated by central rather than peripheral actions.
Development and optimization of tibezonium iodide and lignocaine hydrochloride containing novel mucoadhesive buccal tablets: a pharmacokinetic investigation among healthy humans

Abstract Objective It is clinically important to deliver a sustained-release mucoadhesive dosage of local anesthetic and antimicrobial agents for pain control. The current study aimed to develop and evaluate chitosan (CHI) based buccal mucoadhesive delivery for the local release of tibezonium iodide (TBN) and lignocaine hydrochloride (LGN). Methods Direct compression technique was employed, aided by other mucoadhesive polymers like hydroxypropylmethylcellulose (HPMC) and sodium alginate (SA) and evaluated for physicochemical and in vivo character. Results Fourier transform infrared spectral analysis (FTIR), powdered X-ray diffraction (XRPD), and differential scanning calorimetry (DSC) absence of physical interaction between ingredients. The physical parameters complied with USP specifications for all formulations. Optimum swellability (551.9%) was offered from formulation TL15, containing 30% SA. The highest ex vivo mucoadhesive strength (24.79 g) and time (18.39 h) was found with TL8. Formulation TL8 also exhibited maximum in vivo residence time (11.37 h). Almost complete drug release at 6 h was possessed by formulation TL5 (HPMC and CHI, 20% each) for TBN (99.98%) and LGN (99.06%). The optimized formulation TL5 exhibited dosage stability up to 6 months at 75% relative humidity and retained drug contents. TL5 was well tolerated by the volunteers with no inflammation, pain or irritation found. Almost 73% of volunteers reported an increase in salivary secretion. The first-order salivary C max of TBN and LGN were found as 16.02 and 7.80 µg/mL within 4 h, respectively. Conclusion Therefore, the sustained release mucoadhesive dosage form of TBN and LGN can be an effective and alternative option to conventional delivery.