ZEUS (ZIF-based electrochemical ultrasensitive screening) device for isopentane analytics with focus on lung cancer diagnosis

Breath analytics is currently being explored for the development of point-of-care devices in non-invasive disease detection. It is based on the measurement of volatile organic compounds (VOCs) and gases that are produced by the body because of the metabolic pathways. The levels of these metabolites vary due to alteration in the endogenous oxidative stress-related metabolic pathways and can be correlated to understand the underlying disease condition. The levels of exhaled hydrocarbons in human breath can be used to design a rapid, easy to use method for lung cancer detection. This work outlines the development of an electrochemical sensing platform that can be used for the non-invasive diagnosis of lung cancer by monitoring isopentane levels in breath. This electrochemical sensor platform involves the use of [BMIM]BF₄@ZIF-8 for sensing the target analyte. This synthesized nanocomposite offers advantages for gas sensing applications as it possesses unique properties such as an electrochemically active Room Temperature Ionic Liquid (RTIL) and a crosslinking Metal Organic Framework (MOF) that provides increased surface area for gas absorption. This is the first report of a hydrocarbon-based sensor platform developed for lung cancer diagnosis. The developed sensor platform displays sensitivity and specificity for the detection of isopentane up to 600 parts-per-billion. We performed structural and morphological characterization of the synthesized nanocomposite using various analytical techniques such as PXRD, FESEM, FTIR, and DLS. We further analyzed the electrochemical activity of the synthesized nanocomposite using a standard glassy carbon electrode. The application of the nanocomposite for isopentane sensing was done using a commercially available carbon screen printed electrode. The results so obtained helped in strengthening our hypothesis and serve as a proof-of-concept for the development of a breathomics-enabled electrochemical strategy. We illustrated the specificity of the developed nanocomposite by cross-reactivity studies. We envision that the detection platform will allow sensitive and specific sensing of isopentane levels such that it can used for point of care applications in noninvasive and early diagnosis of lung cancer, thereby leading to its early treatment and decrease in mortality rate.

A novel synthesized [BMIM]BF₄@ZIF-8 nanocomposite for electrochemical sensing of isopentane as a biomarker for lung cancer diagnosis.     

Improving response rates and evaluating nonresponse bias in surveys: AMEE Guide No. 102

Robust response rates are essential for effective survey-based strategies. Researchers can improve survey validity by addressing both response rates and nonresponse bias. In this AMEE Guide, we explain response rate calculations and discuss methods for improving response rates to surveys as a whole (unit nonresponse) and to questions within a survey (item nonresponse). Finally, we introduce the concept of nonresponse bias and provide simple methods to measure it.     

Heterozygous CTNNB1 and TBX4 variants in a patient with abnormal lung growth,pulmonary hypertension,microcephaly, and spasticity

The canonical wingless (Wnt) and fibroblast growth factor (FGF) signaling pathways involving CTNNB1 and TBX4, respectively, are crucial for the regulation of human development. Perturbations of these pathways and disruptions from biological homeostasis have been associated with abnormal morphogenesis of multiple organs, including the lung. The aim of this study was to identify the underlying genetic cause of abnormal lung growth, pulmonary hypertension (PAH), severe microcephaly, and muscle spasticity in a full-term newborn, who died at 4 months of age due to progressively worsening PAH and respiratory failure. Family trio exome sequencing showed a de novo heterozygous nonsense c.1603C>T (p.Arg535*) variant in CTNNB1 and a paternally inherited heterozygous missense c.1198G>A (p.Glu400Lys) variant in TBX4, both predicted to be likely deleterious. We expand the phenotypic spectrum associated with CTNNB1 and TBX4 variants and indicate that they could act synergistically to produce a distinct more severe phenotype. Our findings further support a recently proposed complex compound inheritance model in lethal lung developmental diseases and the contention that dual molecular diagnoses can parsimoniously explain blended phenotypes.     

A microfluidic electrochemical cell for studying the corrosion of uranium dioxide (UO2)

We have developed a specialized microfluidic electrochemical cell that enables in situ investigation of the electrochemical corrosion of microgram quantities of redox active solids. The advantage of downscaling is the reduction of hazards, waste, expense, and greatly expanding data collection for hazardous materials, including radioactive samples. Cyclic voltammetry was used to monitor the oxidation–reduction cycle of minute quantities of micron-size uraninite (UO₂) particles, from the formation of hexavalent uranium (U(vi)), U₃O₇ and reduction to UO_2+x. Reaction progress was also studied in situ with scanning electron microscopy. The electrochemical measurements matched those obtained at the bulk-scale and were consistent with ex situ characterization of the run products by X-ray photoelectron spectroscopy, scanning transmission electron microscopy, and atomic force microscopy; thus, demonstrating the utility of the microfluidic approach for studying radioactive materials.

Highlight of the multimodal characterization of corrosion behaviour of microgram quantities of UO₂, enabled by a novel particle-attached microfluidic electrochemical cell.     

Microsatellite characterization of Plasmodium falciparum from cerebral and uncomplicated malaria patients in southern Vietnam

If parasite genotype influences the clinical course of malaria, we expect that isolates from patients with similar pathology would be more closely related than would be expected by chance. To explore this prediction, we typed nine microsatellite markers in sympatric Plasmodium falciparum isolates from cerebral and uncomplicated malaria patients from Vietnam. Temporal structure and linkage disequilibrium were also examined in this data set.     

What does fetal autopsy unmask in oligohydramnios?

Objective: We aimed to determine the value of autopsy in fetuses with antenatally diagnosed oligohydramnios.

Patients and methods: We evaluated all fetal losses over a period of 6.5 years. Those with oligohydramnios on antenatal scan were critically analyzed. Oligohydramnios was defined as amniotic fluid index of less than five objectively or as an obvious lack of liquor at subjective assessment. A detailed postmortem examination was carried out in all the fetuses after obtaining an informed consent.

Results: Fetal autopsy was conducted in 255 cases. Fifty-five (21.5%) fetuses were diagnosed to have oligohydramnios on antenatal ultrasonography. On analysis of antenatal causes of oligohydramnios, maternal/placental factors were noted in 18%, ultrasound findings known to affect amniotic fluid in 27% while cause remained unidentified in 54.5% of cases. On autopsy, fetal malformations were noted in 61.8% cases, intrauterine growth retardation in 21.8% fetuses and no obvious malformations in 16.3% fetuses. Renal anomalies were noted in 40% cases and non-renal malformations in 21.8% cases.

Conclusion: The postmortem examination helped us to identify the cause of fetal loss in 46 (83.6%) fetuses with antenatal oligohydramnios. A working diagnosis could not have been established without autopsy in 19 (34.5%) cases.