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Understanding language variations opens a wider perspective to language enthusiasts in boosting sociolinguistic awareness as regards to the different ways of using the language in different language contexts. It provides people from different geographical locations of Blaan to understand the language and its use. The study aimed to describe the linguistic variations of Blaan language in the four (4) sociolinguistic contexts of Blaan in Soccsksargen Region, Mindanao, Philippines such as Sarangani Blaan (SBL) of Sarangani Province, Koronadal Blaan (KBL) of South Cotabato Province, Columbio Blaan (CBL) of Sultan Kudarat Province, and Tulunan Blaan (TBL) of Cotabato Province in terms of phonological variations, morphological variations, semantic variations, and syntactic variations. Labov's (1966) variationist sociolinguistic framework was employed in describing the linguistic variations of Blaan which was qualitative in nature. The study was participated by purposively selected sixteen (16) research participants who were composed of Blaan elders and Blaan teachers. The findings of the study reveal ample linguistic variations in SBL, KBL, CBL, and TBL in terms of sound, word formation, meaning, and sentence structure. The phonological variations include the number of vowel phoneme production for/a/,/e/,/é/,/i/,/o/and/u/, the use of accent marks on vowel phonemes, the number of accented and unaccented vowel phonemes, phonetic and phonological change, and phoneme addition. The morphological variations include differences on tense markers, degrees of comparison markers, and other morphological features of the lexical categories of Blaan. The semantic variations include words that have positive meanings in one context but have offensive meanings as compared to the other context. The syntactic variations include forming of yes-no questions in Blaan and the placement of question markers. The study concludes that variations of language, in the perspective of sociolinguistics, prove that language is indeed changing, evolving, and adapting to the sociolinguistic contexts of different language communities. [ABSTRACT FROM AUTHOR]

This paper aimed to describe the use of Education Linguistic Model in teaching English as a Second Language using discourse analysis. The study focused to the four (4) ESL teachers' process in teaching English as a second language to the different groups of ESL learners in Koronadal National Comprehensive High School for the school year 2017-2018. The participants were selected based from the inclusion criteria formulated by the researcher: a) A participant must be a graduate of Bachelor in Secondary Education major in English; b) A participant must have an at least fifteen (15) years of experience in teaching English as a second language; and c) A participant must be one of the top ten (10) performing teachers as based from the Individual Performance Commitment and Review Form (IPCRF). Furthermore, classroom observation method was used to record classroom proceedings through field notes and voice recorder. Also, qualitative discourse analysis was employed to interpret and understand on how the four (4) ESL teachers utilize the seven (7) ELM categories which are building rapport, acknowledging success, modelling, addressing challenging behaviors, scaffolding the learning, responding to the individual learner and self-monitoring the teaching. The findings entail that the manifestations of ELM categories are evident in the process of teaching as a second language as reflected by the four (4) ESL teachers, but the process of exhibiting the ELM categories is unique and different compared among the ESL teachers. However, some of the categories are not consistently used in every class proceeding. Thus, modelling is not manifested by Teacher C and scaffolding the learning is not manifested by Teacher D. Moreover, both Teacher C and Teacher D do not manifest self-monitoring the teaching. Therefore, the study suggests that selfmonitoring the teaching should be observed by the ESL teachers to enhance the process of teaching English as a second language in an ESL classroom. [ABSTRACT FROM AUTHOR]

Background: Inflammation following transcatheter aortic valve implantation (TAVI) is associated with an increased risk of adverse outcomes. The aim of this study was to compare the inflammatory response between low radial force valves (Acurate neo2, Boston Scientific) and high radial force valves (Evolut R/Pro, Medtronic; SAPIEN Edwards Lifesciences; and Myval, Meril valves)., Methods: We conducted a retrospective study of patients with severe aortic stenosis treated with TAVI between 2021 and 2022. The primary endpoint was the difference in the inflammatory response between low radial force valves and high radial force valves, measured as the difference between post-procedural and pre-procedural high-sensitivity C-reactive protein levels (hsCRP delta)., Results: A total of 114 patients were included, of which 65 patients (57%) received a low radial force valve. The hsCRP delta was lower in the low radial force valve group compared to the high radial force valve group (8.7 [2.1-15.6] mg/L vs. 18.8 mg/dL [6.4-19] mg/L; P=0.003), due to a lower post-implantation hsCRP (8.9 [5.45-19.6] mg/L vs. 15.8 [9.8-27.3] mg/L; P=0.013). The incidence of new left bundle branch block (LBBB) after TAVI was lower in the low radial force valve group compared to the high radial force valve group (11 [17%] vs. 18 [37%]; P=0.020)., Conclusions: Low radial force TAVI prostheses were associated with a lower inflammatory response, and a lower incidence of new LBBB compared to the radial force valve group, suggesting that inflammation may contribute to the increased risk of conduction disturbances.

Droplet digital PCR (ddPCR) has been demonstrated in many research studies to be a sensitive method in the analysis of circulating tumour DNA (ctDNA) for identifying mutations and tracking disease. The transition of ddPCR into the diagnostic setting requires a number of critical steps including the assessment of accuracy and precision and ultimately implementation into clinical use. Here we present the clinical validation of ddPCR for the detection of BRAF mutations (V600E and V600K) from plasma. We describe the performance characteristics assessed including the limit of blank, limit of detection, ruggedness, accuracy, precision and the effect of the matrix. Overall, each assay could achieve a limit of detection of 0.5% variant allele fraction and was highly accurate, with 100% concordance of results obtained from routine diagnostic testing of formalin fixed tumour samples or reference controls (n=36 for BRAF V600E and n=30 for BRAF V600K). Inter-laboratory reproducibility across 12 plasma samples for each assay was also assessed and results were 100% concordant. Overall, we report the successful validation and translation of a ddPCR assay into clinical routine practice., (Copyright © 2022 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Background: Peripheral artery disease (PAD) is a frequent cause of morbidity and mortality. It may present with diverse clinical presentations. The aim of this study was to evaluate the prognosis of these clinical presentations., Methods: We performed a retrospective cohort study, in which symptomatic PAD patients were included from 2014 to 2020 at a university hospital in Argentina. We classified symptomatic PAD in intermittent claudication (IC), chronic limb-threatening ischemia (CLTI) and acute ischemia (AI). Our primary endpoint was to compare the composite of all-cause mortality and major amputation events between the three groups., Results: We included 309 patients, with a median follow up of 1.87 years (IQR 0.72-3.67). The primary endpoint was more prevalent in CLTI and AI patients (33% and 33.3%) compared to IC patients (8.1%), P<0.001. CLTI and AI were independently associated with the primary endpoint after adjusting for clinical variables of interest (OR 4.04 95%CI [1.86-9.07], P<0.001 and OR 5.40 95%CI [2.18-13.7], P<0.001, respectively). Mortality incidence rate (per 100 patients/year) was similar between AI and CLTI patients (14.2 95% CI [8.0-24.1] and 13.1 95%CI [8.8-19.7], respectively, P=0.67) but higher compared to IC (2.9 95%CI [1.6-5.1], P<0.01). Major amputation events were more prevalent in CLTI (16.5%) compared to AI (8.9%) and IC patients (1.2%), P<0.01., Conclusions: Those with CLTI and AI have a particular increased risk of all-cause death and major amputation events. Although mortality incidence was similar between AI and CLTI patients, the latter have an increased risk of major amputation events compared to AI and IC patients.

Background: Peripheral artery disease (PAD) frequently affects multiple segments of the limbs. Contradictory data have reported worse prognosis in aortoiliac lesions, nevertheless, diabetes and chronic limb ischemia frequently affects the infrapatellar territory. Our aim was to assess the impact of infrapatellar disease in cardiovascular outcomes., Methods: We performed a retrospective, observational cohort study at a university hospital in Argentina. Electronic health records were retrospectively reviewed including symptomatic PAD patients requiring revascularization. A multivariable regression model was performed to account for confounders. The primary endpoint was a composite of hospitalizations due to chronic limb threatening ischemia (CLTI) and major amputation events between infrapatellar and suprapatellar patients. Minor amputation events, all-cause death, myocardial infarction (MI), stroke, and major cardiovascular events (MACE) were secondary endpoints., Results: From January 2014 through July 2020, a total of 309 patients were included in the analysis. 151 patients had suprapatellar disease, and 158 had infrapatellar disease. The primary composite endpoint occurred in 35 patients (22.2%) in the infrapatellar patients and 18 patients (11.9%) in the suprapatellar patients (HR = 2.16; 95% confidence interval [CI]= [1.22-3.82]; p = 0.008). Both components of the primary outcomes occurred more frequently in infrapatellar patients.Minor amputation events were more prevalent in infrapatellar patients (HR = 5.09; 95% CI = [1.47-17.6]; p = 0.010). Death,MI, stroke, and MACE events were not different among groups (all p > 0.05)., Conclusion: Infrapatellar disease was anindependent factor for increased hospitalization of CLTI, major and minor amputations events, compared to suprapatellardisease in symptomatic revascularized PAD patients.

Background: Symptomatic but unruptured abdominal aortic aneurysm (AAA) is a potentially fatal disease since its etiopathogenesis, involving acute changes in the aortic wall, including inflammation, increasing the probability of impending rupture. The objective of the present study was to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) in patients undergoing urgent symptomatic AAA repair., Methods: This was a retrospective study including 29 patients with symptomatic AAA repaired between 2011 and 2020. Both NLR and PLR were calculated on hospital admission prior to the intervention. The primary end point was in-hospital mortality, and the secondary end point included length of hospital stay and postoperative complications., Results: In-hospital mortality rate was 10.3%. The discriminatory performance to predict the primary end point was very good both for PLR (area under the ROC curve [AUC]: 0.92 (95% confidence interval [CI]: 0.82-1.00; P=0.02) and NLR (AUC: 0.88 [95% CI: 0.75-1.00]; P=0.04). The best cutoff point to predict in-hospital mortality was 185 for PLR (100% sensitivity and 85% specificity) and 6.4 for NLR (100% sensitivity and 77% specificity). The most frequent postoperative complication was acute kidney failure (37.9%). Both elevated PLR as NLR were significantly associated with acute kidney failure and multiorgan failure in the immediate postoperative period (P<0.01). None of the two ratios was associated with length of hospital stay (P=NS)., Conclusions: Both PLR and NLR are low-cost inflammatory markers widely available in every emergency department, with excellent performance to predict in-hospital mortality in patients undergoing symptomatic AAA repair. Patients with a PLR≥185 and/or an NLR≥6.4 could benefit from a "surveyed waiting conduct" improving the preoperative clinical condition prior to the intervention, or even considering endovascular repair.

Relaxin is a pleiotropic hormone demonstrated to confer cardioprotection in animal models of myocardial infarction and ischemic heart failure by modulating inflammation, fibrosis and arrhythmogenesis. Several of these pathways in the ischemic myocardium are intricately tied with the downstream signaling of bioactive sphingolipids, which play an active role during post-infarction remodeling. In this current study, we examined the effects of relaxin on sphingosine 1-phosphate (S1P), and the potential benefits of relaxin treatment on cardiac health in a rodent model of ischemic heart failure. Acute (30 min) and sub-acute (24 h) treatment of primary cardiomyocytes with serelaxin (recombinant human relaxin-2) increased the cardiomyocyte content of S1P. In the rodent model, treatment with relaxin for 28 days following myocardial ischemia by way of permanent left coronary artery occlusion improved survival and cardiac function, reduced fibrosis and apoptosis, and mitigated the expression of several pro-inflammatory and pro-fibrotic markers. The expression of beclin-1 (autophagy marker) was also reduced. The expression of S1P was significantly higher in cardiac tissue and plasma samples extracted from serelaxin-treated mice at day 28. In conclusion, our studies show a significant protection from relaxin in ischemic heart disease, and demonstrate the association between relaxin signaling and S1P generation., (© 2022. The Author(s).)

Purpose: Common femoral artery (CFA) is a critical segment of the lower-limb arterial tree. We sought to propose an extensive classification in order to appraise a diagnostic and therapeutic approach., Methods: A retrospective cohort of CFA lesions with endovascular therapy was evaluated. We appraised the extension, the degree of stenosis and the calcium burden. A new group "IV" included lesions that started at the external iliac artery or common iliac artery extending into the CFA and affecting its bifurcation. The primary outcome was the need for a retrograde bailout access after failed anterograde access and the procedural time., Results: From 2012 to 2020, a total of 58 lower limbs in patients with CFA lesions were included. New proposed group IV compromised 36% of lesions. Additionally, procedural time was significantly longer in group IV lesions compared with the rest (76.9 ± 32.23 min vs 47.67 ± 17.93 min, p < 0.01), as was the requirement of retrograde bailout access (23.8 vs 2.6%, p = 0.03). Occlusive lesions were associated with longer procedural times and bailout retrograde access compared to stenotic lesions (74.7 ± 33.6 min vs 48.29 ± 16 min, p < 0.001 and 26.1 vs 0%, p = 0.006, respectively), as well as heavy calcification compared to mild or moderate calcification (73.18 ± 28.15 vs 51.86 ± 25.1, p = 0.06 and 29.4 vs 2.4%, p = 0.009, respectively). Secondary clinical outcomes and target lesion revascularization did not differ among groups., Conclusions: Our classification includes a new group of extensive and frequent lesions, which did not fit in previous classifications., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: Balloon aortic valvuloplasty (BAV) has been typically performed through a femoral approach thus increasing the risk of bleeding and access site-related vascular complications. The aim of this study was to describe the safety and efficacy of transradial aortic valve valvuloplasty (TRBAV)., Methods: The present research is a retrospective, single-center study including patients undergoing TRBAV (October 2019-July 2020). BAV was performed using 18-25 mm balloons through an 8-10 French (F) radial sheath. Successful BAV was defined as ≥50% reduction in peak-to-peak gradient (efficacy endpoint). Procedural complications, including radial artery occlusion (RAO) at follow-up were evaluated (safety endpoint)., Results: Twenty-four patients underwent TRBAV were included, aged 81 (73-85) years, 70% males, EuroScoreII 3.1 (2.1-5.5). Aortic valve gradient was significantly reduced (pre-50±24 vs. 18.7±13 mmHg post, P<0.001), and 91% had successful BAV. Mean gradient drop was 31.4±16.8 mmHg. One patient (4%) required cross-over to femoral access for severe vasospasm and was excluded from the analysis. Most used sheaths were 8F (46%) and 9F (37%), mostly for 20 mm (50%) and 23 mm (38%) balloons. There were neither major procedural complications (neither balloon entrapment nor compartmental syndrome) nor minor complications (any access-site bleeding). RAO was observed in 2 patients (8%), both asymptomatic., Conclusions: TRBAV was safe, feasible, and efficacious with a small rate of conversion and RAO, suggesting reproducibility of this novel technique. TRBAV may represent an alternative to femoral access in selected patients although larger studies are warranted.

Background: The human microbiome plays an important role in cancer. Accumulating evidence indicates that commensal microbiome-derived DNA may be represented in minute quantities in the cell-free DNA of human blood and could possibly be harnessed as a new cancer biomarker. However, there has been limited use of rigorous experimental controls to account for contamination, which invariably affects low-biomass microbiome studies., Results: We apply a combination of 16S-rRNA-gene sequencing and droplet digital PCR to determine if the specific detection of cell-free microbial DNA (cfmDNA) is possible in metastatic melanoma patients. Compared to matched stool and saliva samples, the absolute concentration of cfmDNA is low but significantly above the levels detected from negative controls. The microbial community of plasma is strongly influenced by laboratory and reagent contaminants introduced during the DNA extraction and sequencing processes. Through the application of an in silico decontamination strategy including the filtering of amplicon sequence variants (ASVs) with batch dependent abundances and those with a higher prevalence in negative controls, we identify known gut commensal bacteria, such as Faecalibacterium, Bacteroides and Ruminococcus, and also other uncharacterised ASVs. We analyse additional plasma samples, highlighting the potential of this framework to identify differences in cfmDNA between healthy and cancer patients., Conclusions: Together, these observations indicate that plasma can harbour a low yet detectable level of cfmDNA. The results highlight the importance of accounting for contamination and provide an analytical decontamination framework to allow the accurate detection of cfmDNA for future biomarker studies in cancer and other diseases.

Merkel cell carcinomas (MCC) are immunogenic skin cancers associated with viral infection or UV mutagenesis. To study T-cell infiltrates in MCC, we analyzed 58 MCC lesions from 39 patients using multiplex-IHC/immunofluorescence (m-IHC/IF). CD4 + or CD8 + T cells comprised the majority of infiltrating T lymphocytes in most tumors. However, almost half of the tumors harbored prominent CD4/CD8 double-negative (DN) T-cell infiltrates (>20% DN T cells), and in 12% of cases, DN T cells represented the majority of T cells. Flow cytometric analysis of single-cell suspensions from fresh tumors identified DN T cells as predominantly Vδ2 - γδ T cells. In the context of γδ T-cell inflammation, these cells expressed PD-1 and LAG3, which is consistent with a suppressed or exhausted phenotype, and CD103, which indicates tissue residency. Furthermore, single-cell RNA sequencing (scRNA-seq) identified a transcriptional profile of γδ T cells suggestive of proinflammatory potential. T-cell receptor (TCR) analysis confirmed clonal expansion of Vδ1 and Vδ3 clonotypes, and functional studies using cloned γδ TCRs demonstrated restriction of these for CD1c and MR1 antigen-presenting molecules. On the basis of a 13-gene γδ T-cell signature derived from scRNA-seq analysis, gene-set enrichment on bulk RNA-seq data showed a positive correlation between enrichment scores and DN T-cell infiltrates. An improved disease-specific survival was evident for patients with high enrichment scores, and complete responses to anti-PD-1/PD-L1 treatment were observed in three of four cases with high enrichment scores. Thus, γδ T-cell infiltration may serve as a prognostic biomarker and should be explored for therapeutic interventions. See related Spotlight on p. 600 ., (©2021 American Association for Cancer Research.)

Background: Post-mortem cardiac magnetic resonance (CMR) is a non-invasive alternative to conventional autopsy. At present, diagnostic guidelines for cardiovascular conditions such as hypertrophic cardiomyopathy have not been established. We correlated post-mortem CMR images to definite conventional autopsy findings and hypothesed that elevated T2-weighted signal intensity and RV to LV area ratios can identify myocardial infarction and pulmonary emboli respectively., Methods: For this unblinded pilot sub-study, we selected cases from the original blinded study that compared post-mortem imaging to conventional autopsy in patients referred for coronial investigation between October 2014 to November 2016. Three groups of scans were selected based on the cause of death identified by conventional autopsy: non-cardiovascular causes of death with no structural cardiac abnormality i.e., control cases, acute/subacute myocardial infarction and pulmonary emboli. Left ventricular (LV) wall thickness, LV myocardial signal intensity and ventricular cavity areas were measured., Results: Fifty-six scans were selected [39 (69.6%) males]: 37 (66.1%) controls, eight (14.3%) acute/subacute myocardial infarction and eleven (19.6%) pulmonary emboli. The median age was 61 years [Interquartile range (IQR) 50-73] and the median time from death to imaging and autopsy was 2 days (IQR 2-3) and 3 days (IQR 3-4). The septal and lateral walls were thicker {15 mm [13-17] and 15 mm [14-18]} on post-mortem CMR than published ante-mortem measurements. Areas of acute/subacute myocardial infarction had significantly higher T2-weighted signal intensity (normalised to skeletal muscle) compared to normal myocardium in those who died from other causes {2.5 [2.3-3.0.] vs. 1.9 [1.8-2.3]; P<0.001}. In cases with pulmonary emboli, there was definite RV enlargement with a larger indexed RV to LV area ratio compared to those who died from other causes {2.9 [2.5-3.0] vs. 1.8 [1.5-2.0]; P<0.001}., Conclusions: We present potential post-mortem CMR parameters to identify important cardiovascular abnormalities that may be beneficial when conventional autopsy cannot be performed. In patients without cardiovascular disease, LV wall thickness was found to be unreliable in diagnosing hypertrophic cardiomyopathy without histological and/or genetic testing. Elevated T2 signal intensity and RV to LV area ratios may be useful markers for acute/subacute myocardial infarction and pulmonary emboli. Larger studies will be necessary to define cut-offs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at: http://dx.doi.org/10.21037/cdt-20-948). The authors have no conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Although melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression.

Conventional autopsy is the gold standard for identifying unexplained death but due to declines in referrals, there is an emerging role for post-mortem imaging. We evaluated whether post-mortem magnetic resonance (PMMR) and computed tomography (PMCT) are inferior to conventional autopsy. Deceased individuals ≥ 2 years old with unexplained death referred for coronial investigation between October 2014 to December 2016 underwent PMCT and PMMR prior to conventional autopsy. Images were reported separately and then compared to the autopsy findings by independent and blinded investigators. Outcomes included the accuracy of imaging modalities to identify an organ system cause of death and other significant abnormalities. Sixty-nine individuals underwent post-mortem scanning and autopsy (50 males; 73%) with a median age of 61 years (IQR 50-73) and median time from death to imaging of 2 days (IQR 2-3). With autopsy, 48 (70%) had an organ system cause of death and were included in assessing primary outcome while the remaining 21 (30%) were only included in assessing secondary outcome; 12 (17%) had a non-structural cause and 9 (13%) had no identifiable cause. PMMR and PMCT identified the cause of death in 58% (28/48) of cases; 50% (24/48) for PMMR and 35% (17/48) for PMCT. The sensitivity and specificity were 57% and 57% for PMMR and 38% and 73% for PMCT. Both PMMR and PMCT identified 61% (57/94) of other significant abnormalities. Post-mortem imaging is inferior to autopsy but when reported by experienced clinicians, PMMR provides important information for cardiac and neurological deaths while PMCT is beneficial for neurological, traumatic and gastrointestinal deaths.