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Digital polymerase chain reaction (dPCR) technology has provided a new technique for molecular diagnostics, with superior advantages, such as higher sensitivity, precision, and specificity over quantitative real-time PCRs (qPCR). Eight companies have offered commercial dPCR instruments: Fluidigm Corporation, Bio-Rad, RainDance Technologies, Life Technologies, Qiagen, JN MedSys Clarity, Optolane, and Stilla Technologies Naica. This paper discusses the working principle of each offered dPCR device and compares the associated: technical aspects, usability, costs, and current applications of each dPCR device. Lastly, up-and-coming dPCR technologies are also presented, as anticipation of how the dPCR device landscape may likely morph in the next few years.

Learning objectives Cancer and cardiovascular disease are the leading causes of mortality in the UK and the USA.1 2 These two diseases share multiple risk factors such as increasing age, smoking and obesity, and their coexistence imparts an adverse prognosis on the other.3 Optimisation of cardiovascular risk factors is often neglected in patients with cancer because cancer is frequently perceived to have a poor prognosis. Treatments that improve cancer prognosis and survival are frequently associated with cardiovascular toxicity, which can ameliorate the benefits of cancer treatment. In this article, we review the cardiovascular complications of anthracycline chemotherapy, HER2-targeted cancer therapies including trastuzumab (Herceptin), inhibitors of the vascular endothelial growth factor (VEGF) signalling pathway, radiotherapy, immune checkpoint inhibitors and proteasome inhibitors, and discuss their associated pathophysiology, risk factors and management strategies. ### Anthracycline chemotherapy #### Anthracycline cardiotoxicity ##### Overview Anthracycline chemotherapy (AC) is frequently used to treat breast cancer, lymphomas, leukaemias and sarcomas. Examples of AC are doxorubicin, epirubicin, daunorubicin and idarubicin, and the related anthracenedione mitoxantrone. The onset of AC cardiotoxicity is generally perceived to be either acute, early-onset chronic or late-onset chronic.4 Acute AC cardiotoxicity is rare affecting

Alginate encapsulation is amongst the most studied probiotic encapsulation formulations in the literature, preferred for its low toxicity, low cost and ability to protect entrapped probiotics against acidic pH. Despite extensive academic studies, there has been little commercial translation of alginate-encapsulated probiotic formulations. In this study, we hypothesized that factors affecting freeze-drying survivability of alginate-encapsulated probiotics could have limited its translation potential. Factors including: 1) encapsulant material, 2) cryoprotectant, 3) cross-linker, 4) Concentration of crosslinker, and 5) other Group II divalent cations cross-linkers were investigated, using two model probiotics – Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle 1917 (ECN). Divalent cations, which are used to cross-link alginates, were found to have antagonistic effects on the freeze-drying survivability of LGG and ECN. To mitigate the deleterious effects of divalent cations, the addition of sucrose was found to be useful, possibly due to its membrane stabilization mechanism. Agri-Food and Veterinary Authority of Singapore (AVA) Ministry of Education (MOE) Accepted version The first author is a recipient of the Nanyang President Graduate Scholarship from Nanyang Technological University, Singapore. This work was also supported by the Singapore Centre for Environmental Life Sciences Engineering (SCELSE) (MOE/RCE: M4330019.C70), Ministry of Education AcRF grant (RG19/18 & RT08/19), Agri-Food & Veterinary Authority of Singapore (APF LCK102), Biomedical Research Council (BMRC) – Therapeutics Development Review (TDR-G-004-001), NTU-HSPH grant (NTU-HSPH 17002), and the Bill and Melinda Gates Foundation (OPP1199116).

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.

Background: Patients with cancer are at increased risk of acute myocardial infarction (AMI). It is unclear if the Atherosclerotic Cardiovascular Disease (ASCVD) risk score at incident AMI is reflective of this higher risk in patients with prior cancer than those without. Methods: We linked nationwide AMI and cancer registries from 2008 to 2019. A total of 18,200 eligible patients with ASCVD risk score calculated at incident AMI were identified (1086 prior cancer; 17,114 no cancer). Results: At incident AMI, age-standardized mean ASCVD risk was lower in the prior cancer group (18.6%) than no cancer group (20.9%) (p < 0.001). Prior to incident AMI, smoking, hypertension, hyperlipidemia and diabetes mellitus were better controlled in the prior cancer group. However post-AMI, prior cancer was associated with lower guideline-directed medical therapy usage and higher all-cause mortality (adjusted hazard ratio 1.85, 95% confidence interval 1.66–2.07). Conclusions: AMI occurred despite better control of cardiovascular risk factors and lower age-standardized estimated mean 10-year ASCVD risk among patients with prior cancer than no cancer. Prior cancer was associated with lower guideline-directed medical therapy post-AMI and higher mortality.

Background Connexin 43 (Cx43) plays a central role in the inflammatory response and wound healing. Targeting Cx43 expression reduces inflammation in a variety of injuries. The expression pattern of Cx43 has not been described for many inflammatory skin diseases. Objectives To describe the expression patterns of Cx43 in eczema, psoriasis, Steven‐Johnson syndrome/toxic epidermal necrolysis. Methods Archival skin biopsies from patients with eczema, psoriasis, and Steven‐Johnson syndrome/toxic epidermal necrosis were identified and examined, with sister sections stained for Cx43 and imaged by confocal microscopy. All samples were compared to age and site‐matched normal skin controls. Results Epidermal Cx43 is reduced in acute eczema, absent in regions of spongiosis, and is highly elevated in subacute and chronic eczema. In plaque psoriasis, Cx43 is overexpressed in areas with psoriasiform hyperplasia with a fish‐scale‐like appearance but is lost in regions surrounding neutrophil microabscesses. Cx43 staining is strong in the neutrophils within these microabscesses. In SJS/TEN, Cx43 expression is elevated in areas bordering normal tissue but is rapidly lost in areas of keratinocyte necrosis. Conclusions Dynamic changes in Cx43 levels are seen in inflammatory skin diseases and may represent future potential therapeutic targets., Connexin 43 (Cx43) plays a central role in the inflammatory response and wound healing. Targeting Cx43 expression reduces inflammation in a variety of injuries. Here we examine the changes in Cx43 protein levels in the epidermis in eczema, psoriasis, Steven‐Johnson Syndrome/Toxic Epidermal necrolysis.

Aims Cardio-oncology clinics optimise the cardiovascular status of cancer patients but there is a limited description of their structure, case mix, activity and results. The purpose of this paper is to describe the activity and outcomes of a cardio-oncology service, particularly with respect to supporting optimal cancer treatment and survival. Methods and results We prospectively studied patients referred to our service from February 2011 to February 2016. New York Heart Association (NYHA) class and parameters of cardiac function were measured at baseline and after optimisation by our service. Up-titration of cardiac treatment, continuation of cancer therapy and mortality were used as outcome measures. Of the 535 patients (55.8% females) referred, rates of cardiotoxicity for anthracyclines, anti-HER2 agents and tyrosine kinase inhibitors were 75.8%, 69.8% and 62.1%, respectively. Patients with left ventricular systolic dysfunction (LVSD) (n=128) were younger, had higher rates of hypertension and previous exposure to chemotherapy/radiotherapy (P < 0.001). At a median follow-up of 360 days, 93.8% of the patients with LVSD showed improvement in left ventricular ejection fraction (45% pre vs. 53% post; P < 0.001) and NYHA class (NYHA III-IV in 22% pre vs. 10% post; P = 0.01). All patients with normal left ventricular ejection fraction and biochemical or functional myocardial toxicity and 88% of patients with LVSD were deemed fit for continuation of cancer therapy after cardiovascular optimisation. Conclusions Through the establishment of a cardio-oncology service, it is feasible to achieve high rates of cardiac optimisation and cancer treatment continuation.

BACKGROUND Watch-PAT 200, a novel portable sleep device worn on the wrist, has been validated against polysomnography. Although sleep disordered breathing (SDB) screening is recommended in patients with cardiovascular disease, no study has reported a comparison of results from Watch-PAT 200 and level III portable devices. METHODS Patients (n = 140) admitted with a first ST-segment elevation myocardial infarction (STEMI) participated in a hospital-based sleep study using the Watch-PAT 200 and a level III portable device (Embletta Gold) simultaneously within five days of admission. SDB was defined as an apnea-hypopnea index (AHI) of >15 events/h. RESULTS The left ventricular ejection fraction was normal (≥50%), impaired (30%-49%) and poor (

Aims The performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in diagnosing acute decompensated heart failure (ADHF) among patients presenting with breathlessness is markedly impaired in the presence of atrial fibrillation (AF). We evaluated the diagnostic performance of mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin T as possible alternative markers for discrimination of ADHF in this setting. Methods and results Breathless patients (n = 1107) were prospectively and contemporaneously recruited in emergency departments in Singapore and New Zealand. The diagnoses of ADHF and presence of AF were adjudicated by two clinician specialists, blinded to MR-proADM, NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) results. MR-proADM exhibited strong discrimination of ADHF with little change in performance irrespective of the presence of AF (area under the curve 0.83 in non-AF vs. 0.76 in AF) compared to NT-proBNP (0.91 vs. 0.71) and hs-cTnT (0.83 vs. 0.62), respectively. The accuracy of MR-proADM (73.3%) for diagnosing ADHF among patients with AF was superior to both NT-proBNP (61.6%) and hs-cTnT (64.6%). The superior performance of MR-proADM remained apparent when data from Singapore and New Zealand were analysed separately. Conclusion In the presence of AF, MR-proADM showed greater discrimination and accuracy, and less impairment in performance compared to that in non-AF cases, for the diagnosis of ADHF, compared to the guideline-endorsed NT-proBNP.

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR &lt, 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.

Purpose of review As cancer survivor rates improve with early screening and modern treatment options, cardiotoxicity is becoming an increasing problem. It is imperative for physicians to recognize adverse events early so that appropriate measures can be taken before advanced and permanent cardiac dysfunction ensues. In this review, we will evaluate the literature surrounding current cardiac biomarkers in the detection of cardiotoxicity during cancer treatment as well as discuss the role of emerging novel biomarkers. Recent findings Troponin and brain natriuretic peptides show promise in the detection of subclinical cardiotoxicity during cancer treatment. In addition to identifying late complications among cancer survivors, they have the potential to predict patients who are at risk of developing cardiotoxicity prior to the initiation of cancer therapy. However, there are also conflicting data due to varying study design. Summary Although biomarkers are an attractive option in the detection of cardiotoxicity among cancer patients, current recommendations surrounding its role are based on expert consensus opinion. Further research with appropriately designed prospective trials is required to guide optimal clinical practice.

STUDY OBJECTIVES: Sleep apnea is often newly diagnosed in patients presenting with ST-segment elevation myocardial infarction (STEMI). We assessed longitudinal changes in apnea-hypopnea index (AHI) and sleep apnea phenotype after STEMI and determined its association with changes in the left ventricular ejection fraction (LVEF). METHODS: A total of 101 eligible patients with STEMI underwent consecutive sleep studies and echocardiographic studies within 5 days of admission and at 6-month follow-up. Sleep apnea (AHI ≥ 15 events/h) was further divided into obstructive sleep apnea (OSA) or central sleep apnea (CSA). RESULTS: Both AHI (mean difference −6.4 events/h, 95% confidence interval [CI] −9.6 to 3.3, P < .001) and LVEF (mean difference 2.6%, 95% CI 1.3 to 4.0, P < .001) improved from baseline to 6 months. The improvement in AHI was associated with an increase in LVEF (β = −.47, 95% CI −.86 to −.07, P = .023) and a decrease in left ventricular end-systolic volume (LVESV) (β = .25, 95% CI .07 to .43, P = .007). Of the patients with OSA at baseline (46%), resolution of OSA was seen in 48% at 6 months. Of those with CSA at baseline (12%), conversion to OSA was seen in 83%. In contrast, among those with no sleep apnea (42%) at baseline, the diagnosis remained the same in 93% at 6 months. CONCLUSIONS: Concurrent changes in AHI, LVEF, and LVESV were seen after STEMI. Sleep studies performed on admission are reliable in excluding sleep apnea. However, patients with OSA or CSA on admission warrant re-evaluation due to evolution of the sleep apnea phenotype. CITATION: Tan LL, Ting J, Balakrishnan I, Seneviratna A, Gong L, Chan MY, Tai ES, Richards AM, Tai BC, Ling LH, Lee CH. Sleep apnea evolution and left ventricular recovery after percutaneous coronary intervention for myocardial infarction. J Clin Sleep Med. 2018;14(10):1773–1781.

Biological membranes with cubic symmetry are a hallmark of virus-infected or diseased cells. The mechanisms of formation and specific cellular functions of cubic membranes, however, are unclear. The best-documented cubic membrane formation occurs in the free-living giant amoeba Chaos carolinense. In that system, mitochondrial inner membranes undergo a reversible structural change from tubular to cubic membrane organization upon starvation of the organism. As a prerequisite to further analyze the structural and functional features of cubic membranes, we adapted protocols for the isolation of mitochondria from starved amoeba and have identified buffer conditions that preserve cubic membrane morphology in vitro. The requirement for high concentration of ion-chelating agents in the isolation media supports the importance of a balanced ion milieu in establishing and maintaining cubic membranes in vivo.

To investigate the expression patterns of long non-coding RNAs (lncRNAs) in clear cell renal cell carcinoma (ccRCC) and in metastatic renal cell carcinoma (RCC), the present study downloaded three human exon arrays available from the public Gene Expression Omnibus. The probes of the human exon arrays were re-annotated and the probes uniquely mapping to lncRNAs were retained at the gene level. Following the analysis of GSE53757 and GSE46699, which contained paired ccRCC cancer and normal adjacent tissue samples, 32 differentially expressed lncRNAs (adjusted P

AIMS This study was conducted to test the diagnostic performance of NT-proBNP for discrimination of acute decompensated heart failure (ADHF) among breathless patients presenting in an Asian compared with a Western centre. METHODS AND RESULTS Patients with breathlessness were prospectively and contemporaneously recruited in Emergency Departments in Singapore and New Zealand (NZ). The diagnosis of ADHF was adjudicated by two clinician specialists. A total of 606 patients were recruited in Singapore and 500 in NZ. The discriminative power of NT-proBNP for ADHF was superior in Singapore compared with NZ [area under the curve (AUC) 0.926 vs. 0.866; P = 0.012] both overall and among selected subgroups stratified according to age, renal function, body mass index, and presence or absence of AF or diabetes. Previously established cut-off point values of plasma NT-proBNP yielded comparable sensitivity and negative predictive values, but superior specificity and accuracy in Singapore compared with NZ. The difference in test performance was driven by the younger age (median age 56 years vs. 73 years; P < 0.001), associated with better renal function (estimated glomerular filtration rate 89 vs. 62 mL/min/1.73 m2 ; P < 0.001), and lower prevalence of AF (9.7% vs. 25.7%; P < 0.001) in acutely breathless patients in Singapore. CONCLUSION Considering emerging evidence of a lower average age of presentation with ADHF over most of Asia compared with Western countries, NT-proBNP is likely to be more accurate when applied in Asian centres than in the West.

Several new microorganisms have been isolated from soil samples with high epoxide hydrolase activity toward ethyl 3,4-epoxybutyrate. Screening was performed by enrichment culture on alkenes as sole carbon source, followed by chiral gas chromatography. Eight strains were discovered with enantioselectivity from moderate to high level and identified as bacterial and yeast species. Cells were cultivated under aerobic condition at 30 degrees C using glucose as carbon source and resting cells were used as biocatalysts for kinetic resolution of ethyl 3,4-epoxybutyrate. Among isolated microorganisms, Acinetobacter baumannii showed highest enantioselectivity for (S)-enantiomer, resulting in (R)-ethyl-3,4-epoxybutyrates (99%ee, 46% yield). It is the first report on the fact that epoxide hydrolases originating from bacterial species of A. baumannii was applied to kinetic resolution of ethyl 3,4-epoxybutyrate in order to obtain enantiopure high-value-added (R)-ethyl-3,4-epoxybutyrate.

P wave abnormalities are commonly found on ECG. However, they are seldom discussed and may also be neglected during ECG interpretion. In this article, we discuss two common types of P wave abnormalities, 'P mitrale' and 'P pulmonale'. The former was found in a patient with mitral valve stenosis, while the latter was from a patient with pulmonary hypertension. Echocardiography is important in evaluating the causes of P wave abnormalities.

Stem cells are views from the perspectives of their function, evolution, development, and cause. Counterintuitively, most stem cells may arise late in development, to act principally in tissue renewal, thus ensuring an organisms long-term survival. Surprisingly, recent reports suggest that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues. Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. The spotlight on stem cells has revealed gaps in our knowledge that must be filled if we are to take advantage of their full potential for treating devastating degenerative diseases such as Parkinsons's disease and muscular dystrophy. We need to know more about the intrinsic controls that keep stem cells as stem cells or direct them along particular differentiation pathways. Such intrinsic regulators are, in turn, sensitive to the influences of the microenvironment, or niche, where stem cells normally reside. Both intrinsic and extrinsic signals regular stem cell fate and some of these signals have now been identified. Vacek et al and Wang et al have studied the effect of low intensity laser on the haemopoietic stem cells in vitro. There experiments show there is indeed the effect of low intensity laser on the haemopoietic stem cells in vitro, and the present effect is the promotion of haemopoietic stem cells proliferation. In other words, low intensity laser irradiation can act as an extrinsic signal regulating stem cell fate. In this paper, we study how low intensity laser can be used to regulate stem cell fate from the viewpoint of collective phototransduction.