DKCNN: Improving deep kernel convolutional neural network-based COVID-19 identification from CT images of the chest.

BACKGROUND: An efficient deep convolutional neural network (DeepCNN) is proposed in this article for the classification of Covid-19 disease. OBJECTIVE: A novel structure known as the Pointwise-Temporal-pointwise convolution unit is developed incorporated with the varying kernel-based depth wise temporal convolution before and after the pointwise convolution operations. METHODS: The outcome is optimized by the Slap Swarm algorithm (SSA). The proposed Deep CNN is composed of depth wise temporal convolution and end-to-end automatic detection of disease. First, the datasets SARS-COV-2 Ct-Scan Dataset and CT scan COVID Prediction dataset are preprocessed using the min-max approach and the features are extracted for further processing. RESULTS: The experimental analysis is conducted between the proposed and some state-of-art works and stated that the proposed work effectively classifies the disease than the other approaches. CONCLUSION: The proposed structural unit is used to design the deep CNN with the increasing kernel sizes. The classification process is improved by the inclusion of depth wise temporal convolutions along with the kernel variation. The computational complexity is reduced by the introduction of stride convolutions are used in the residual linkage among the adjacent structural units.

Society for Immunotherapy of Cancer (SITC) recommendations on intratumoral immunotherapy clinical trials (IICT): from premalignant to metastatic disease.

BACKGROUND: Intratumorally delivered immunotherapies have the potential to favorably alter the local tumor microenvironment and may stimulate systemic host immunity, offering an alternative or adjunct to other local and systemic treatments. Despite their potential, these therapies have had limited success in late-phase trials for advanced cancer resulting in few formal approvals. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to determine how to design clinical trials with the greatest chance of demonstrating the benefits of intratumoral immunotherapy for patients with cancers across all stages of pathogenesis. METHODS: An Intratumoral Immunotherapy Clinical Trials Expert Panel composed of international key stakeholders from academia and industry was assembled. A multiple choice/free response survey was distributed to the panel, and the results of this survey were discussed during a half-day consensus meeting. Key discussion points are summarized in the following manuscript. RESULTS: The panel determined unique clinical trial designs tailored to different stages of cancer development-from premalignant to unresectable/metastatic-that can maximize the chance of capturing the effect of intratumoral immunotherapies. Design elements discussed included study type, patient stratification and exclusion criteria, indications of randomization, study arm determination, endpoints, biological sample collection, and response assessment with biomarkers and imaging. Populations to prioritize for the study of intratumoral immunotherapy, including stage, type of cancer and line of treatment, were also discussed along with common barriers to the development of these local treatments. CONCLUSIONS: The SITC Intratumoral Immunotherapy Clinical Trials Expert Panel has identified key considerations for the design and implementation of studies that have the greatest potential to capture the effect of intratumorally delivered immunotherapies. With more effective and standardized trial designs, the potential of intratumoral immunotherapy can be realized and lead to regulatory approvals that will extend the benefit of these local treatments to the patients who need them the most.

Improvement in Pain and Quality of Life After Ultrasound-Guided Saphenous Nerve Block in Patients With Knee Osteoarthritis.

Introduction Osteoarthritis (OA) of the knee is a common complaint in the elderly population and results in considerable disability in advanced stages. Though many pharmacological, electrotherapeutic, and interventional options are available for the effective treatment of knee OA in the early stages, these modalities fail to provide effective and long-term relief in some cases where peripheral nerve blocks may prove beneficial. Hence, this study was conducted to assess the efficacy of the saphenous nerve block in knee pain due to OA. Objective To evaluate improvement in pain and quality of life after ultrasound-guided saphenous nerve block in patients with knee OA. Material and methods An interventional prospective study in patients with knee OA, with medial compartment knee pain, was conducted from March 2016 to March 2017. All patients were evaluated prior to the procedure, and then at one week, one month, three months, and six months. The pain was evaluated using the visual analog scale (VAS) and functional improvement using the Knee injury and Osteoarthritis Outcome Score (KOOS). Results Forty patients with unilateral knee OA underwent saphenous nerve block. Fifty percent of the patients reported pain relief within one week, whereas 58%, 33%, and 23% exhibited relief at subsequent follow-ups at one, three, and six months. A statistically significant difference (p < 0.0001) was observed in pain (VAS and KOOS pain) and functional scales (KOOS symptom, quality of life (QOL), and activities of daily living (ADL)) at follow-up evaluations. Conclusion Ultrasound-guided saphenous nerve block results in a significant improvement in pain and QOL in patients with knee OA.

Endoluminal Silicone-Covered Stenting in Children: Novel Applications and Lessons Learned.

BACKGROUND: Silicone-covered endoluminal stents have been applied to various hollow visceral disorders in adult patients with varying success. Efficacy of retrievable endoluminal stenting in children is less well-established. PURPOSE: The purpose of this study was to evaluate our experience with evolving applications of endoluminal silicone-covered stenting in children. RESEARCH DESIGN: Eight children 19 years and younger having silicone-covered stent placement for various indications at a single institution (2014-2021) were reviewed retrospectively. RESULTS: Eight patients received a total of 26 silicone-covered stents. Four stent placements (15.4%) were associated with a direct adverse event. To resolve the endoluminal disorder, four patients received multiple stents or further intervention. When evaluating novel applications, clinical benefit was noted for one patient with vaginal atresia, and another after ileal pouch anal anastomosis disruption. CONCLUSION: This experience highlights the broad and innovative applications for endoluminal silicone-covered natural orifice stenting in children. Acute processes respond well and rapidly to stenting, although chronic, established fistula may require additional manipulations or surgery.

Molecular and Radiological Features of Microsatellite Stable Colorectal Cancer Cases With Dramatic Responses to Immunotherapy.

BACKGROUND/AIM: The majority of colorectal cancer (CRC) cases, which are microsatellite stable (MSS) and do not harbor mismatch repair deficiency/microsatellite instability, are resistant to immunotherapy. Identification of patients with exceptional responses in MSS CRC and predictive biomarkers is an unmet need that needs to be addressed. CASE REPORT: We report three cases of MSS CRC with durable clinical benefit from immunotherapy with anti-PD-1 checkpoint inhibitors. Two cases bear a POLE P286R mutation, which has been associated with lack of immunotherapy response in MSS CRC. Two cases bear alterations in Ataxia-Telangiectasia Mutated (ATM) which may contribute to observed responses, including interaction with a co-administered intratumoral stimulator of interferon genes (STING) pathway agonist in one patient. CONCLUSION: Novel DNA damage repair alterations, including mutations in ATM, can provide insight into additional mechanisms by which genomic alterations can sensitize MSS CRC to diverse immunotherapies.

Birth preparedness and complication readiness in pregnant women attending urban tertiary care hospital.

BACKGROUND: Birth preparedness and complication readiness (BP/CR) is a strategy to promote the timely use of skilled maternal and neonatal care and is based on the theory that preparing for childbirth and being ready for complications reduce delay in obtaining care. STUDY OBJECTIVE: The objective of this study was to evaluate the incidence and predictors of birth preparedness, knowledge on danger signs, and emergency readiness among pregnant women attending outpatient clinic of a tertiary care hospital. PATIENTS AND METHODS: Six hundred pregnant women attending the outpatient department of a tertiary care hospital for the first time in an urban setting were interviewed using a tool adapted from the "Monitoring BP/CR-tools and indicators for maternal and new born health" of the "JHPIEGO." The outcomes of the study were birth preparedness, knowledge of severe illness, and emergency readiness. RESULTS: Six hundred pregnant women were in the study. Mean age of respondents was 25.2 (±4) years. The mean gestation at enrolment was 18.7 ± 8 weeks. Among the women who participated in the survey, 20% were illiterate, 70% were homemakers and nearly 70% had a monthly family income >Rs. 15,197 (n = 405). Three hundred and sixteen mothers (52%) were primigravida. As defined in the study, 71.5% were birth prepared. However, 59 women (9.8%) did not identify a place of delivery, 102 (17%) had not started saving money, and 99 mothers (16.5%) were not aware of purchasing materials needed for delivery. The predictors of birth preparedness are multiparity (odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.4-3.1), registration in the antenatal clinic in the first trimester (OR: 3.7, 95% CI: 2.2-6.1), educational status of women (OR: 1.9, 95% CI: 1.2-3.0), and pregnancy supervison by a doctor (OR: 5, 95% CI: 2.8-6.6). One hundred and sixty-four women (27%) made no arrangements in the event of an emergency, 376 women (63%) were not aware of their blood group, and 89% (n = 531) did not identify any blood donor. Only 20% (n = 120), 15.8% (n = 95), and 12% (n = 73) of the respondents had knowledge of at least 3 danger signs of pregnancy, labor, and severe illness in newborn, respectively. CONCLUSIONS: Nearly three-fourth pregnant women attending a tertiary care hospital in an urban area are birth prepared. However, emergency readiness and awareness of danger signs are very poor. Maternal education and early booking have an independent association with birth preparedness.

Tuning Lipase Reaction for Production of Fatty Acids from Oil.

Fats or oils are split partially or completely to obtain fatty acids that find wide applications in oleo-chemical industries. Lipase-mediated complete splitting (hydrolysis) of oils is a green process having great potential to replace the traditional methods of oil splitting. However, cost of lipases, mechanistic kinetic equilibrium and associated operational limitations prove to be deterrents for scale up of the enzymatic oil splitting process. In the present study, we demonstrate the use of immobilised 1,3-regioselective lipase (HyLIP) for complete hydrolysis of oil in monophasic reaction medium. Incorporation of a polar organic solvent (tert-butanol, 1:5, v/v) homogenises the oil-water mixture and contributes positively towards complete hydrolysis. The monophasic oil hydrolysis reaction with optimised water concentration (0.05 %, v/v) gave Free Fatty Acid (FFA) yield of 88 % (HyLIP and Novozym-435) and 66 % (TLIM and RMIM). Smart reaction engineering and modification of the reaction intermediates to favourable substrate lead to ∼99 % degree of hydrolysis of triglycerides with ∼90 % FFA yield using 1,3-regioselective lipase. The present work becomes basic platform for developing technologies for synthesis of fatty acids, monoglycerides, diglycerides and glycerol.

Gelatin Methacrylate Hydrogels as Biomimetic Three-Dimensional Matrixes for Modeling Breast Cancer Invasion and Chemoresponse in Vitro.

Recent studies have shown that three-dimensional (3D) culture environments allow the study of cellular responses in a setting that more closely resembles the in vivo milieu. In this context, hydrogels have become popular scaffold options for the 3D cell culture. Because the mechanical and biochemical properties of culture matrixes influence crucial cell behavior, selecting a suitable matrix for replicating in vivo cellular phenotype in vitro is essential for understanding disease progression. Gelatin methacrylate (GelMA) hydrogels have been the focus of much attention because of their inherent bioactivity, favorable hydration and diffusion properties, and ease-of-tailoring of their physicochemical characteristics. Therefore, in this study we examined the efficacy of GelMA hydrogels as a suitable platform to model specific attributes of breast cancer. We observed increased invasiveness in vitro and increased tumorigenic ability in vivo in breast cancer cells cultured on GelMA hydrogels. Further, cells cultured on GelMA matrixes were more resistant to paclitaxel treatment, as shown by the results of cell-cycle analysis and gene expression. This study, therefore, validates GelMA hydrogels as inexpensive, cell-responsive 3D platforms for modeling key characteristics associated with breast cancer metastasis, in vitro.

Purification and characterization of rat testicular glutathione S-transferases: role in the synthesis of eicosanoids.

AIM: Purification of glutathione S-transferases (GSTs) from rat testis; separation and identification of various subunits and their role in eicosanoid biosynthesis. METHODS: Purification of rat testicular GSTs by affinity chromatography, employing S-hexylglutathione-linked epoxy-activated Sepharose 6B column and separation of individual subunits by reverse phase-high pressure liquid chromatography (RP-HPLC). Characterization of affinity purified GSTs by Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. The role of testicular GSTs in eicosanoid biosynthesis was determine by incubating GSTs with 5, 6-Leukotriene A4Me (LTA4Me) and prostaglandin H2(PGH2) and analyzing the products formed on HPLC/TLC. RESULTS: The present study reveals that majority of rat testicular GSTs are of Yb size (60%) with molecular weight of 27 kDa. The most predominant subunits, however, are GST Yn2(27%), followed by GST Yc(24%) and GST Yn1(20%). These testicular GSTs showed very high Leukotriene C4 (LTC4) synthase activity with 5, 6-Leukotriene A4Me (LTA4Me) as the substrate and prostaglandin D (PGD) synthase activity with prostaglandin H2(PGH2) as the substrate. CONCLUSION: Majority of rat testicular GSTs are Yb sized and are involved in the synthesis of eicosanoids like LTC4 and PGD2.

Sarcomatoid chromophobe renal cell carcinoma: Cytohistopathological correlation of a case.

Sarcomatoid renal cell carcinomas of the kidney are rare neoplasms constituting about 1-5% of all renal malignant neoplasms. These are aggressive tumors and are commonly associated with conventional (clear cell) renal cell carcinomas, but cases associated with chromophobe renal cell carcinomas are sparse. Cytological features of such lesions have rarely been reported. Here, we report a unique case of a 48-year-old male patient who presented with right flank lump and pain. A fine needle aspiration was performed from the lesion under ultrasound guidance and a cytological diagnosis of pleomorphic sarcoma was made. A right-sided radical nephrectomy was carried out and subsequent histopathology revealed a sarcomatoid renal cell carcinoma with wide areas of necrosis coexisting with chromophobe renal cell carcinoma with calcification. Differentiation of pleomorphic sarcoma from a sarcomatoid renal cell carcinoma is, thus, challenging from cytopathology smears and the differential diagnoses should always be borne in mind while giving a cytopathological opinion.

Anaerobic bacteraemia: a review of 17 cases.

Of 93 blood cultures received with a suspicion of anaerobic bacteraemia over a period of two years, only 17 (18.3%) showed anaerobic growth. Twelve grew anaerobes alone while five had a polymicrobial flora. Seven of these patients (4.3%) had pre-existing heart disease while others had history of prior surgery, diabetes mellitus or urinary tract infection. Oropharynx was the commonest portal of entry, followed by gastrointestinal tract. The anaerobes isolated were anaerobic streptococci, Bacteroides fragilis group and Bilophila and Eubacterium species. Fifteen patients developed major complications such as congestive cardiac failure, systemic embolisation, and perforative peritonitis. The mortality rate among the cases with anaerobic bacteraemia was 23.5% in this study.

Induction of Ya1 subunit of rat hepatic glutathione S-transferases by exercise-induced oxidative stress.

Adult female rats subjected to exercise training in the form of swimming daily (for 20 min initially with gradual increase up to 90 min within a week) for 130 days showed a significant elevation of liver glutathione S-transferase (GST) activity when compared to controls. Electrophoresis and Western blot analysis of cytosolic as well as affinity-purified hepatic glutathione S-transferases revealed the induction of Ya-sized subunit in exercise-trained animals. Reverse-phase HPLC analysis of affinity-purified GSTs further revealed that Ya-sized subunits in control animals consisted of predominantly Ya2, whereas the trained animals displayed a dramatic 4.3-fold increase in Ya1. The GSTs of exercise-trained animals showed increased peroxidase activity when compared to corresponding controls, which is consistent with the changes in sub-unit composition. This could be a response to the physiological oxidative stress induced by physical exercise.

Enhanced production of LTB4 and free radicals in rat lung by exhaustive physical exercise.

Leukotrienes formed by the action of 5-lipoxygenase on arachidonic acid are a group of endogenous compounds active in hypersensitivity reactions and inflammation. In this report the formation of LTB4 from LTA4 was measured by incubating lung microsomes from normal and exercised rats to determine whether LTB4 may have a role in the mediation of exercise-induced oxidant stress. Exhaustive exercise in the form of swimming results in the enhanced production of LTB4 in lung microsomes. Further, free radicals measured by ESR spectroscopy were also significantly increased in lung tissue from exercised rats. These results suggest a role for LTB4 in the mediation of lung tissue damage during exercise-induced oxidative stress.

Sequence-function analysis of the K+-selective family of ion channels using a comprehensive alignment and the KcsA channel structure.

Sequence-function analysis of K(+)-selective channels was carried out in the context of the 3.2 A crystal structure of a K(+) channel (KcsA) from Streptomyces lividans (Doyle et al., 1998). The first step was the construction of an alignment of a comprehensive set of K(+)-selective channel sequences forming the putative permeation path. This pathway consists of two transmembrane segments plus an extracellular linker. Included in the alignment are channels from the eight major classes of K(+)-selective channels from a wide variety of species, displaying varied rectification, gating, and activation properties. Segments of the alignment were assigned to structural motifs based on the KcsA structure. The alignment's accuracy was verified by two observations on these motifs: 1), the most variability is shown in the turret region, which functionally is strongly implicated in susceptibility to toxin binding; and 2), the selectivity filter and pore helix are the most highly conserved regions. This alignment combined with the KcsA structure was used to assess whether clusters of contiguous residues linked by hydrophobic or electrostatic interactions in KcsA are conserved in the K(+)-selective channel family. Analysis of sequence conservation patterns in the alignment suggests that a cluster of conserved residues is critical for determining the degree of K(+) selectivity. The alignment also supports the near-universality of the "glycine hinge" mechanism at the center of the inner helix for opening K channels. This mechanism has been suggested by the recent crystallization of a K channel in the open state. Further, the alignment reveals a second highly conserved glycine near the extracellular end of the inner helix, which may be important in minimizing deformation of the extracellular vestibule as the channel opens. These and other sequence-function relationships found in this analysis suggest that much of the permeation path architecture in KcsA is present in most K(+)-selective channels. Because of this finding, the alignment provides a robust starting point for homology modeling of the permeation paths of other K(+)-selective channel classes and elucidation of sequence-function relationships therein. To assay these applications, a homology model of the Shaker A channel permeation path was constructed using the alignment and KcsA as the template, and its structure evaluated in light of established structural criteria.