DiffusionCT: Latent Diffusion Model for CT Image Standardization.

Computed tomography (CT) is one of the modalities for effective lung cancer screening, diagnosis, treatment, and prognosis. The features extracted from CT images are now used to quantify spatial and temporal variations in tumors. However, CT images obtained from various scanners with customized acquisition protocols may introduce considerable variations in texture features, even for the same patient. This presents a fundamental challenge to downstream studies that require consistent and reliable feature analysis. Existing CT image harmonization models rely on GAN-based supervised or semi-supervised learning, with limited performance. This work addresses the issue of CT image harmonization using a new diffusion-based model, named DiffusionCT, to standardize CT images acquired from different vendors and protocols. DiffusionCT operates in the latent space by mapping a latent non-standard distribution into a standard one. DiffusionCT incorporates a U-Net-based encoder-decoder, augmented by a diffusion model integrated into the bottleneck part. The model is designed in two training phases. The encoder-decoder is first trained, without embedding the diffusion model, to learn the latent representation of the input data. The latent diffusion model is then trained in the next training phase while fixing the encoder-decoder. Finally, the decoder synthesizes a standardized image with the transformed latent representation. The experimental results demonstrate a significant improvement in the performance of the standardization task using DiffusionCT.

Cross-Vendor CT Image Data Harmonization Using CVH-CT.

While remarkable advances have been made in Computed Tomography (CT), most of the existing efforts focus on imaging enhancement while reducing radiation dose. How to harmonize CT image data captured using different scanners is vital in cross-center large-scale radiomics studies but remains the boundary to explore. Furthermore, the lack of paired training image problem makes it computationally challenging to adopt existing deep learning models. We propose a novel deep learning approach called CVH-CT for harmonizing CT images captured using scanners from different vendors. The generator of CVH-CT uses a self-attention mechanism to learn the scanner-related information. We also propose a VGG feature based domain loss to effectively extract texture properties from unpaired image data to learn the scanner based texture distributions. The experimental results show that CVH-CT is clearly better than the baselines because of the use of the proposed domain loss, and CVH-CT can effectively reduce the scanner-related variability in terms of radiomic features.

STAN-CT: Standardizing CT Image using Generative Adversarial Networks.

Computed Tomography (CT) plays an important role in lung malignancy diagnostics, therapy assessment, and facilitating precision medicine delivery. However, the use of personalized imaging protocols poses a challenge in large-scale cross-center CT image radiomic studies. We present an end-to-end solution called STAN-CT for CT image standardization and normalization, which effectively reduces discrepancies in image features caused by using different imaging protocols or using different CT scanners with the same imaging protocol. STAN-CT consists oftwo components: 1)a Generative Adversarial Networks (GAN) model where a latent-feature-based loss function is adopted to learn the data distribution of standard images within a few rounds of generator training, and 2) an automatic DICOM reconstruction pipeline with systematic image quality control that ensures the generation ofhigh-quality standard DICOM images. Experimental results indicate that the training efficiency and model performance of STAN-CT have been significantly improved compared to the state-of-the-art CT image standardization and normalization algorithms.

Radiation induced DNA damage and its protection by a gadolinium(III) complex: Spectroscopic, molecular docking and gel electrophoretic studies.

The current work describes the efficacy of an artificially synthesized Gd(III) complex as a potential radioprotecting molecule. The work involves utilization of spectroscopic and electrophoretic techniques to investigate the radioprotecting behavior of the Gd(III) complex. Spectroscopic studies revealed that the complex interacted strongly with DNA while molecular docking studies suggested groove binding through H-bond formation and other non-covalent interactions. The Gd(III) complex was found to impart 94% and 91% protection to irradiatively damaged DNA at radiation doses of 20 and 25 Gy respectively. The protection is believed to occur via radical scavenging mechanism and the antioxidant behavior of the complex suggested a strong radical scavenging property.

Acetaminophen as a Renoprotective Adjunctive Treatment in Patients With Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial.

Background: Acute kidney injury independently predicts mortality in falciparum malaria. It is unknown whether acetaminophen's capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe malaria. Methods: This phase 2, open-label, randomized controlled trial conducted at two hospitals in Bangladesh assessed effects on renal function, safety, pharmacokinetic (PK) properties and pharmacodynamic (PD) effects of acetaminophen. Febrile patients (>12 years) with severe falciparum malaria were randomly assigned to receive acetaminophen (1 g 6-hourly for 72 hours) or no acetaminophen, in addition to intravenous artesunate. Primary outcome was the proportional change in creatinine after 72 hours stratified by median plasma hemoglobin. Results: Between 2012 and 2014, 62 patients were randomly assigned to receive acetaminophen (n = 31) or no acetaminophen (n = 31). Median (interquartile range) reduction in creatinine after 72 hours was 23% (37% to 18%) in patients assigned to acetaminophen, versus 14% (29% to 0%) in patients assigned to no acetaminophen (P = .043). This difference in reduction was 37% (48% to 22%) versus 14% (30% to -71%) in patients with hemoglobin ≥45000 ng/mL (P = .010). The proportion with progressing kidney injury was higher among controls (subdistribution hazard ratio, 3.0; 95% confidence interval, 1.1 to 8.5; P = .034). PK-PD analyses showed that higher exposure to acetaminophen increased the probability of creatinine improvement. No patient fulfilled Hy's law for hepatotoxicity. Conclusions: In this proof-of-principle study, acetaminophen showed renoprotection without evidence of safety concerns in patients with severe falciparum malaria, particularly in those with prominent intravascular hemolysis. Clinical Trials Registration: NCT01641289.

Groundwater arsenic contamination in Bangladesh-21 Years of research.

Department of Public Health Engineering (DPHE), Bangladesh first identified their groundwater arsenic contamination in 1993. But before the international arsenic conference in Dhaka in February 1998, the problem was not widely accepted. Even in the international arsenic conference in West-Bengal, India in February, 1995, representatives of international agencies in Bangladesh and Bangladesh government attended the conference but they denied the groundwater arsenic contamination in Bangladesh. School of Environmental Studies (SOES), Jadavpur University, Kolkata, India first identified arsenic patient in Bangladesh in 1992 and informed WHO, UNICEF of Bangladesh and Govt. of Bangladesh from April 1994 to August 1995. British Geological Survey (BGS) dug hand tube-wells in Bangladesh in 1980s and early 1990s but they did not test the water for arsenic. Again BGS came back to Bangladesh in 1992 to assess the quality of the water of the tube-wells they installed but they still did not test for arsenic when groundwater arsenic contamination and its health effects in West Bengal in Bengal delta was already published in WHO Bulletin in 1988. From December 1996, SOES in collaboration with Dhaka Community Hospital (DCH), Bangladesh started analyzing hand tube-wells for arsenic from all 64 districts in four geomorphologic regions of Bangladesh. So far over 54,000 tube-well water samples had been analyzed by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS). From SOES water analysis data at present we could assess status of arsenic groundwater contamination in four geo-morphological regions of Bangladesh and location of possible arsenic safe groundwater. SOES and DCH also made some preliminary work with their medical team to identify patients suffering from arsenic related diseases. SOES further analyzed few thousands biological samples (hair, nail, urine and skin scales) and foodstuffs for arsenic to know arsenic body burden and people sub-clinically affected. SOES and DCH made a few follow-up studies in some districts to know their overall situations after 9 to 18 years of their first exposure. The overall conclusion from these follow-up studies is (a) villagers are now more aware about the danger of drinking arsenic contaminated water (b) villagers are currently drinking less arsenic contaminated water (c) many villagers in affected village died of cancer (d) arsenic contaminated water is in use for agricultural irrigation and arsenic exposure from food chain could be future danger. Since at present more information is coming about health effects from low arsenic exposure, Bangladesh Government should immediately focus on their huge surface water management and reduce their permissible limit of arsenic in drinking water.

Synthesis and structural characterization of dioxomolybdenum and dioxotungsten hydroxamato complexes and their function in the protection of radiation induced DNA damage.

The synthesis and structural characterization of two novel dioxomolybdenum(VI) (1) and dioxotungsten(VI) (2) complexes with 2-phenylacetylhydroxamic acid (PAHH) [M(O)2(PAH)2] [M = Mo, W] have been accomplished. The dioxomolybdenum(VI) and dioxotungsten(VI) moiety is coordinated by the hydroxamate group (-CONHO(-)) of the 2-phenylacetylhydroxamate (PAH) ligand in a bi-dentate fashion. In both the complexes the PAHH ligand is coordinated through oxygen atoms forming a five membered chelate. The hydrogen atom of N-H of the hydroxamate group is engaged in intermolecular H-bonding with the carbonyl oxygen of another coordinated hydroxamate ligand, thereby forming an extended 1D chain. The ligand as well as both the complexes exhibit the ability to protect from radiation induced damage both in CTDNA as well as in pUC19 plasmid DNA. As the damage to DNA is caused by the radicals generated during radiolysis, its scavenging imparts protection from the damage to DNA. To understand the mechanism of protection, binding affinities of the ligand and the complex with DNA were determined using absorption and emission spectral studies and viscosity measurements, whereby the results indicate that both the complexes and the hydroxamate ligand interact with calf thymus DNA in the minor groove. The intrinsic binding constants, obtained from UV-vis studies, are 7.2 × 10(3) M(-1), 5.2 × 10(4) M(-1) and 1.2 × 10(4) M(-1) for the ligand and complexes 1 and 2 respectively. The Stern-Volmer quenching constants obtained from a luminescence study for both the complexes are 5.6 × 10(4) M(-1) and 1.6 × 10(4) M(-1) respectively. The dioxomolybdenum(VI) complex is found to be a more potent radioprotector compared to the dioxotungsten(VI) complex and the ligand. Radical scavenging chemical studies suggest that the complexes have a greater ability to scavenge both the hydroxyl as well as the superoxide radicals compared to the ligand. The free radical scavenging ability of the ligand and the complexes was further established by EPR spectroscopy using a stable free radical, the DPPH, as a probe. The experimental results of DNA binding are further supported by molecular docking studies.

DNA binding and nuclease activity of a one-dimensional heterometallic nitrosyl complex.

The interaction of a structurally characterized Sr-Fe nitrosyl complex with DNA has been studied by UV-vis and fluorescence spectroscopy, viscometric, and gel electrophoresis techniques. From the absorption titration studies the intrinsic binding constant of the complex with DNA was calculated to be 1.6x10(4)M(-1). Fluorimetric studies indicate that the complex compete with EB in binding to DNA. The complex shows nuclease activity on pUC19 supercoiled DNA in presence of H(2)O(2).

Effectiveness and reliability of arsenic field testing kits: are the million dollar screening projects effective or not?

The exposure of millions to arsenic contaminated water from hand tube wells is a major concern in many Asiatic countries. Field kits are currently used to classify tube wells as delivering arsenic below 50 microg/L (the recommended limit in developing countries) as safe, painted green or above 50 microg/L, unsafe and painted red. More than 1.3 million tube wells in Bangladesh alone have been tested by field kits. A few million U.S. dollars have already been spent and millions are waiting for the ongoing projects. However, the reliability of the data generated through field kits is now being questioned. Samples from 290 wells were tested by field kits and by a reliable laboratory technique to ascertain the reliability of field kits. False negatives were as high as 68% and false positives up to 35%. A statistical analysis of data from 240 and 394 other wells yielded similar rates. We then analyzed 2866 samples from previously labeled wells and found 44.9% mislabeling in the lower range (<50 microg/L) although mislabeling was considerably reduced in the higher range. Variation of analytical results due to analysts and replicates were pointed out adopting analysis of variance (ANOVA) technique. Millions of dollars are being spent without scientific validation of the field kit method. Facts and figures demand improved, environmentally friendly laboratory techniques to produce reliable data.