Publications by authors named "Santosh Kumar"

1,199 Publications

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Efficient dual mode emission in Ce/Yb/Er doped yttrium aluminium gallium garnet for led device and optical thermometry.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Jul 26;282:121664. Epub 2022 Jul 26.

Optical Materials & Bio-imaging Research Laboratory, Department of Physics, Indian Institute of Technology (Indian School of Mines), Dhanabad 826004, India. Electronic address:

By utilizing the effective energy transfer from Ce to Yb, Er and from Yb to Er authors have achieved dual mode emission in YAlGaO activated with Ce/Yb/Er ions. Surface morphological and elemental compositions of the prepared samples have been examined using field emission scanning electron microscope (FE-SEM) and energy dispersive spectroscopy (EDS) analysis, respectively. The chemical state of the dopant ions is confirmed by the X-ray photoelectron spectroscopy (XPS). On excitation with 438 nm the prepared material has shown broad visible emission band around 511 nm due to the electronic transition of Ce ion. In addition to this sample has also shown NIR emission bands centered around 1024 nm and 1480 nm from Yb and Er ions, respectively. The emission band at 1024 nm could be due to the quantum cutting (QC) process. Furthermore, up-conversion (UC) emission against temperature and laser power variations is studied on 980 nm excitation wavelength. The prepared sample is used to fabricate visible and NIR LED devices by coating of sample on blue LED chip. Along with this demonstration, optical thermometry ability of the material is studied using emission intensity ratio of two emitting levels. Studies suggest that the prepared material could be useful as dual mode emitting phosphor and LED.
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http://dx.doi.org/10.1016/j.saa.2022.121664DOI Listing
July 2022

Tillage and crop establishment effects on weeds and productivity of a rice-wheat-mungbean rotation.

Field Crops Res 2022 Aug;284:108577

Indian Council of Agricultural Research, New Delhi, India.

Weeds are one of the key threats in sustaining the productivity of the rice-wheat cropping system in the Indo-Gangetic Plains. The development of sound integrated weed management technologies requires knowledge of mechanisms that influence weed flora composition and weed seedbank dynamics. A long-term study was initiated in 2015 at Patna, Bihar, India to evaluate the effect of seven tillage and crop establishment methods on weed density, weed seedbank composition, and crop productivity in rice-wheat-mungbean rotation. All the treatments included zero-till mungbean after wheat. Tillage and crop establishment methods had differential effects on weed and weed seedbank composition. In rice, zero-till direct-seeded rice recorded 62% lower emergence of , 82-90% of and 81-83% of total weeds compared to tilled systems, but the system of rice and wheat intensification favoured . In wheat, the system of wheat intensification favoured the and . Zero-till rice and wheat reduced the seedbank of by 95%, and total weed seedbank by 62% compared to the system of rice and wheat intensification. Nearly, 72% of seeds, 62% of grasses, and 64% of broad-leaved weeds were in 0-15 cm soil layer. Zero-till direct-seeded rice produced a 13% lower rice grain yield than conventional puddled transplanted rice. Compared to the system of wheat intensification, zero-till wheat under triple zero-till systems produced an 11.5% higher grain yield. Managing weed seedbank is a long-term endeavour. The present study revealed that tillage and crop establishment methods influence weed density and diversity. Under zero-till rice-wheat system, rice yield decreases marginally, but the system productivity maintains due to improvement in succeeding wheat yield. This system is also helpful in reducing the weed flora density and soil weed seedbank. Regular monitoring and management of emerging pests such as armyworm () are, however, required. The study suggests that the adoption of triple zero-tillage can be a viable option for reducing the weed density and weed seedbank concurrently increasing the system productivity of the rice-wheat-mungbean cropping system in eastern Indo-Gangetic Plains.
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http://dx.doi.org/10.1016/j.fcr.2022.108577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214547PMC
August 2022

Efficient optical reservoir computing for parallel data processing.

Opt Lett 2022 Aug;47(15):3784-3787

We propose and experimentally demonstrate an optical reservoir computing system in free space, using second-harmonic generation for nonlinear kernel functions and a scattering medium to enhance reservoir nodes interconnection. We test it for one-step and multi-step predication of Mackey-Glass time series with different input-mapping methods on a spatial light modulator. For one-step prediction, we achieve 1.8 × 10 normalized mean squared error (NMSE). For the multi-step prediction, we explore two different mapping methods: linear-combination and concatenation, achieving 16-step prediction with NMSE as low as 3.5 × 10. Robust and superior for multi-step prediction, our approach and design have potential for parallel data processing tasks such as video prediction, speech translation, and so on.
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http://dx.doi.org/10.1364/OL.464288DOI Listing
August 2022

Characteristics and Management of Children With Suspected COVID-19 Admitted to Hospitals in India: Implications for Future Care.

Cureus 2022 Jul 25;14(7):e27230. Epub 2022 Jul 25.

Health Policy, Centre of Medical and Bio allied Health Sciences Research, Ajman University, Ajman, ARE.

Introduction: There is a growing focus on researching the management of children with COVID-19 admitted to hospital, especially among developing countries with new variants alongside concerns with the overuse of antibiotics. Patient care can be improved with guidelines, but concerns with the continued imprudent prescribing of antimicrobials, including antibiotics, antivirals, and antimalarials.

Objective: Consequently, a need to document the current management of children with COVID-19 across India. Key outcome measures included the percentage of prescribed antimicrobials, adherence to current guidelines, and mortality.

Methodology: A point prevalence study using specially developed report forms among 30 hospitals in India.

Results: The majority of admitted children were aged between 11 and 18 years (70%) and boys (65.8%). Reasons for admission included respiratory distress, breathing difficulties, and prolonged fever. 75.3% were prescribed antibiotics typically empirically (68.3% overall), with most on the Watch list (76.7%). There were no differences in antibiotic prescribing whether hospitals followed guidelines or not. There was also appreciable prescribing of antimalarials (21.4% of children), antivirals (15.2%), and antiparasitic medicines (27.2%) despite limited evidence. The majority of children (92.2%) made a full recovery.

Conclusion: It was encouraging to see low hospitalization rates. However, concerns about high empiric use of antibiotics and high use of antimalarials, antivirals, and antiparasitic medicines exist. These can be addressed by instigating appropriate stewardship programs.
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http://dx.doi.org/10.7759/cureus.27230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311229PMC
July 2022

Bacterial diversity, physicochemical and geothermometry of South Asian hot springs.

Curr Res Microb Sci 2022 22;3:100125. Epub 2022 Mar 22.

Department of Microbiology, School of Life Sciences, Sikkim University, 6th Mile, Samdur, Gangtok, 737102 Sikkim, India.

Extreme ecosystems with enormous arrays of physicochemical or biological physiognomies serve as an important indicator of various processes occurred and/or occurring in and on the Earth. Among extreme habitats, hot springs represent geothermal features which are complex systems with a well-defined plumbing system. Besides geological tectonic based hypsography and orology annotations, the hot springs have served as hot spots for ages where there is an amalgamation of nature, religion, faith, health, and science. Thus, there remains an escalating scope to study these hot springs all over the world. The Himalayan Geothermal Belt (HGB) banquets three densely demographic countries i.e. Pakistan, India and China, that hosts numerous hot springs. Studies on the hot springs distributed over these countries reveal Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria as the predominant bacterial phyla. The bacterial diversity shows a significant positive correlation with physicochemical parameters like temperature, pH, Na, HCO , etc. Physicochemical analyses of these hot springs indicate the water mainly as Na-Cl, Na-HCO, SO-Cl, and mixed type, with temperature ranging approximately between 100-250°C as predicted by various geothermometers. Numerous studies although done, not much of a comprehensive database of the analysis are provided on the hot springs harboured by the HGB. This review aims to give a cumulative illustration on comparative facets of various characteristic features of hot springs distributed over the HGB. These are found to be of great importance with respect to the exploitation of geothermal energy and microflora in various sectors of industries and biotechnology. They are also important sources in terms of socio-economic perspective, and routes to eco-medical tourism.
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http://dx.doi.org/10.1016/j.crmicr.2022.100125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325890PMC
March 2022

The 1, 2-ethylenediamine SQ109 protects against tuberculosis by promoting M1 macrophage polarization through the p38 MAPK pathway.

Commun Biol 2022 Jul 28;5(1):759. Epub 2022 Jul 28.

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.

Directly Observed Treatment Short-course (DOTs), is an effective and widely recommended treatment for tuberculosis (TB). The antibiotics used in DOTs, are immunotoxic and impair effector T cells, increasing the risk of re-infections and reactivation. Multiple reports suggest that addition of immune-modulators along with antibiotics improves the effectiveness of TB treatment. Therefore, drugs with both antimicrobial and immunomodulatory properties are desirable. N-(Adamantan-2-yl)-N-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]ethane-1,2-diamine (SQ109) is an asymmetric diamine derivative of adamantane, that targets Mycobacterial membrane protein Large 3 (MmpL3). SQ109 dissipates the transmembrane electrochemical proton-gradient necessary for cell-wall biosynthesis and bacterial activity. Here, we examined the effects of SQ109 on host-immune responses using a murine TB model. Our results suggest the pro-inflammatory nature of SQ109, which instigates M1-macrophage polarization and induces protective pro-inflammatory cytokines through the p38-MAPK pathway. SQ109 also promotes Th1 and Th17-immune responses that inhibit the bacillary burden in a murine model of TB. These findings put forth SQ109 as a potential-adjunct to TB antibiotic therapy.
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http://dx.doi.org/10.1038/s42003-022-03693-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334294PMC
July 2022

Leveraging epigenetics to enhance the efficacy of cancer-testis antigen: a potential candidate for immunotherapy.

Epigenomics 2022 Jul 25;14(14):865-886. Epub 2022 Jul 25.

Department of Biochemistry, National Cancer Institute - India, Jhajjar Campus, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

Ovarian cancer is the most lethal gynecological malignancy in women. The phenotype is characterized by delayed diagnosis, recurrence and drug resistance. Inherent immunogenicity potential, oncogenic function and expression of cancer-testis/germline antigen (CTA) in ovarian cancer render them a potential candidate for immunotherapy. Revolutionary clinical findings indicate that tumor antigen-mediated T-cell and dendritic cell-based immunotherapeutic approaches provide an excellent strategy for targeting tumors. Currently, dendritic cell vaccination for the treatment of B-cell lymphoma and CTA-based T-cell receptor transduced T-cell therapy involving MAGE-A4 and NY-ESO-1 are well documented and shown to be effective. This review highlighted the mechanical aspects of epigenetic drugs that can elicit a CTA-based humoral and cellular immune response and implicate T-cell and dendritic cell-based immunotherapeutic approaches.
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http://dx.doi.org/10.2217/epi-2021-0479DOI Listing
July 2022

Walking the thin line-Low-grade oncocytic tumor of kidney: An emerging entity.

Med J Armed Forces India 2022 Jul 5;78(3):355-359. Epub 2021 May 5.

Professor (Urology), PGIMER, Chandigarh, India.

Low-grade oncocytic tumor (LOT) of kidney is a newly emerging provisional renal tumor entity that carries good prognosis. Here we present a case of low grade oncocytic tumor of kidney in a 68-year-old male with detailed immunohistochemical and ultrastructural description, to add to the existing knowledge about this entity. The importance of documenting low-grade oncocytoma in the literature is its indolent clinical behavior, characteristics gross and microscopic, and immunohistochemical features. The diagnosis of low-grade oncocytoma can be suspected on morphological ground but should be confirmed by immunohistochemistry.
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http://dx.doi.org/10.1016/j.mjafi.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287666PMC
July 2022

Cardiac Troponin I Detection using Gold/Cerium-Oxide Nanoparticles assisted Hetro-Core Fiber Structure.

IEEE Trans Nanobioscience 2022 Jul 19;PP. Epub 2022 Jul 19.

The article describes the development of a hetro-core optical fiber sensor structure based on localized surface plasmon resonance (LSPR) for the detection of cardiac troponin I (cTnI) solution. This was accomplished by fabricating a single-mode fiber - multimode fiber - single-mode fiber (SMS) structure. Then, fiber structure is immobilized with gold nanoparticles (AuNPs) and cerium oxide nanoparticles (CeO-NPs) to improve its sensing capabilities. An UV-Vis spectrophotometer and a high-resolution transmission electron microscope (HR-TEM) are used to determine the morphology of synthesized nanoparticles. Scanning electron microscopy (SEM) is used to examine the state of immobilized NPs on the surface of sensing region. The developed sensor probe has a linear range of 0 to 1000 ng/mL cTnI, a sensitivity of 3 pm/(ng/mL), and a limit of detection (LoD) of 108.15 ng/mL. In real time, the proposed sensor will be used in a practice to detect acute myocardial infarction (AMI).
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http://dx.doi.org/10.1109/TNB.2022.3192491DOI Listing
July 2022

Cyclodextrin Derivative Enhances the Ophthalmic Delivery of Poorly Soluble Azithromycin.

ACS Omega 2022 Jul 24;7(27):23050-23060. Epub 2022 Jun 24.

University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.

Azithromycin (AZM), a macrolide antibiotic used for the treatment of chlamydial conjunctivitis, is less effective for the treatment of this disease due to its poor bioavailability (38%). Various alternatives have been developed for improving the physicochemical properties (i.e., solubility) of the AZM without much success. To overcome the problems associated with AZM, an inclusion complex employing a modified cyclodextrin, i.e., sulfobutylether-β-cyclodextrin (SBE-β-CD), was prepared and characterized by phase solubility studies and PXRD techniques. The results portrayed the formation of an inclusion complex of AZM with SBE-β-CD in 1:2 molar stoichiometric ratios. This inclusion complex was later incorporated into a polymer matrix to prepare an gel. Various combinations of Carbopol 934P and hydroxypropyl methylcellulose (HPMC K4M) polymers were used and evaluated by rheological and drug release studies. The optimized formulation (F4) containing Carbopol 934P (0.2% w/v) and HPMC K4M (0.2% w/v) was evaluated for clarity, pH, gelling capacity, drug content, rheological properties, drug release pattern, ocular irritation test, and antimicrobial efficacy. Finally, owing to the improved antimicrobial efficacy and increased residence time, the AZM:SBE-β-CD gel was found to be a promising formulation for the efficient treatment of bacterial ocular disease.
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http://dx.doi.org/10.1021/acsomega.1c07218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280958PMC
July 2022

Editorial: New Insights Into Oxidative Stress and Inflammation in the Pathophysiology and Treatment of Cardiovascular Diseases.

Front Mol Biosci 2022 24;9:940465. Epub 2022 Jun 24.

Cardiovascular Division, Department of Medicine, and Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, United States.

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http://dx.doi.org/10.3389/fmolb.2022.940465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263691PMC
June 2022

Cancer Targeting and Diagnosis: Recent Trends with Carbon Nanotubes.

Nanomaterials (Basel) 2022 Jul 2;12(13). Epub 2022 Jul 2.

Shandong Key Laboratory of Optical Communication Science and Technology, School of Physics Science and Information Technology, Liaocheng University, Liaocheng 252059, China.

Cancer belongs to a category of disorders characterized by uncontrolled cell development with the potential to invade other bodily organs, resulting in an estimated 10 million deaths globally in 2020. With advancements in nanotechnology-based systems, biomedical applications of nanomaterials are attracting increasing interest as prospective vehicles for targeted cancer therapy and enhancing treatment results. In this context, carbon nanotubes (CNTs) have recently garnered a great deal of interest in the field of cancer diagnosis and treatment due to various factors such as biocompatibility, thermodynamic properties, and varied functionalization. In the present review, we will discuss recent advancements regarding CNT contributions to cancer diagnosis and therapy. Various sensing strategies like electrochemical, colorimetric, plasmonic, and immunosensing are discussed in detail. In the next section, therapy techniques like photothermal therapy, photodynamic therapy, drug targeting, gene therapy, and immunotherapy are also explained in-depth. The toxicological aspect of CNTs for biomedical application will also be discussed in order to ensure the safe real-life and clinical use of CNTs.
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http://dx.doi.org/10.3390/nano12132283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268713PMC
July 2022

RNA N6-methyladenosine modification in regulating cancer stem cells and tumor immune microenvironment and its implication for cancer therapy.

J Cancer Res Clin Oncol 2022 Jul 7. Epub 2022 Jul 7.

Department of Life Science, National Institute of Technology, Rourkela, India.

Therapy resistance is a well-known phenomenon in cancer treatment. It can be intrinsic or acquired, accountable for frequent tumor relapse and death worldwide. The interplay between cancer cells and their neighboring environment can activate complex signaling mechanisms influencing epigenetic changes and maintain cancer cell survival leading to the malignant phenotype. Cancer stem cells (CSCs) are tumor-initiating cells (TICs) and constitute the primary source of drug resistance and tumor recurrence. Studies have shown that cancer cells exhibit dysregulated RNA N6-methyladenosine (m6A) "writers," "erasers," and "readers" levels after acquiring drug resistance. The present review provides novel insight into the role of m6A modifiers involved in CSC generation, cancer cell proliferation, and therapy resistance. m6A RNA modifications in the cross-talk between CSC and the tumor immune microenvironment (TIME) have also been highlighted. Further, we have discussed the therapeutic potential of targeting m6A machinery for cancer diagnosis and the development of new therapies for cancer treatment.
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http://dx.doi.org/10.1007/s00432-022-04158-zDOI Listing
July 2022

Medical Students' Perception Regarding Health Policy Teaching and Their Participation in Health Policy Roles: A Survey at a Public University in Malaysia.

Healthcare (Basel) 2022 May 24;10(6). Epub 2022 May 24.

Department of Physiology, Medical College for Women and Hospital, Dhaka 1230, Bangladesh.

Background: Health policy is a set of comprehensive principles and legislations that guide how healthcare should be effectively delivered in the community. Medical schools should prepare students to undertake managerial responsibilities by incorporating health policy into the curriculum to deal with the intricacies of healthcare systems and their clinical roles in their future professional careers.

Objective: To examine medical students' perception at a Public University in Malaysia regarding teaching health policy and their participation in health policy roles.

Material And Methods: A cross-sectional study using universal sampling was carried out among the medical students using a paper-based questionnaire to collect the data.

Results: Most respondents opined their willingness to learn health policy (80.9%) and that teaching health policy (83.6%) should be compulsory for medical students. The respondents thought health policy should be introduced earlier in Year 1 or 2. The student scores on their knowledge regarding health policy and year of study were significantly associated with their involvement in the health policy roles in both the simple and multiple logistic regression. Both statistical tests reported higher participation in health policy roles with the higher year of study, though only Year 4 and 5 were significant in the simple logistic regression and only Year 5 in the multiple logistic regression compared to Year 1. On the other hand, age and type of admission show significant results only in the simple logistic regression, while the race was only significant at the multivariate level.

Conclusions: This study demonstrated that most respondents showed their willingness to learn health policy, participate in the health policy programs, and recommend that health policy be considered an essential topic in the medical curriculum, which should be taught right from the first year of medical school. We recommend encouraging students' participation in health policy activities.
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http://dx.doi.org/10.3390/healthcare10060967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223141PMC
May 2022

Dynamic Foam Characteristics during Cultivation of .

Bioengineering (Basel) 2022 Jun 16;9(6). Epub 2022 Jun 16.

State Key Laboratory of Clean Energy Utilization, Zhejiang University, Hangzhou 310027, China.

This study is aimed at understanding the serious foaming problems during microalgal cultivation in industrial raceway ponds by studying the dynamic foam properties in cultivation. was cultivated in a 4 L bowl bioreactor for 4 days, during which the foam height above the algal solution increased from 0 to 30 mm with a bubble diameter of 1.8 mm, and biomass yield reached 1.5 g/L. The algal solution surface tension decreased from 55 to 45 mN/m, which favored the adsorption of microalgae on the bubble to generate more stable foams. This resulted in increased foam stability (FS) from 1 to 10 s, foam capacity (FC) from 0.3 to 1.2, foam expansion (FE) from 15 to 43, and foam maximum density (FMD) from 0.02 to 0.07. These results show a decrease in CO flow rate and operation temperature when using the Foamscan instrument, which minimized the foaming phenomenon in algal solutions to a significantly lower and acceptable level.
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http://dx.doi.org/10.3390/bioengineering9060257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220301PMC
June 2022

The Biota orientalis, oil extract Epiitalis, is efficacious at reducing the symptoms of knee osteoarthritis: a pilot, multi-site, dose-ranging, randomized, blinded, placebo-controlled trial.

Inflammopharmacology 2022 Aug 22;30(4):1323-1334. Epub 2022 Jun 22.

Independent Consultant Biostatistician, Delhi, India.

Objective: To explore the safety, and efficacy of a proprietary hydrolyzed oil extract from seeds of Biota orientalis (hBO/Epiitalis, Interpath Pty Ltd) in patients with knee pain due to osteoarthritis (OA).

Methods: Patients aged 40-65 with X-ray diagnosed knee OA and knee pain ≥ 60 on a 100-point VAS (visual analog scale) were enrolled and randomized into four groups to receive daily hBO for 56 days as high (hBO-HD, 640 mg), mid (hBO-MD, 320 mg) or low (hBO-LD, 160 mg) doses, or a matched placebo oil. The primary outcome was change in VAS knee pain from baseline to 56 days in the mITT (modified intention to treat) population. Exploratory outcomes were the mWOMAC (modified Western Ontario and McMaster Universities Arthritis Index), and the SF-36 QoL (quality of life) questionnaire. The OMERACT-OARSI (Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International) responder index was also calculated.

Results: 223 patients were included in the mITT population. Reductions in VAS scores between baseline and day 56 [Least square mean (LS mean) and 95% confidence interval (CI) of LS mean] were 36.4 (31.7-41.0), 37.9 (33.2-42.7), 35.7 (31.2-40.1) and 9.8 (14.5-15.2) for the hBO-HD, hBO-MD, hBO-LD, and placebo groups respectively. The VAS changes in all hBO groups were significantly different (p < 0.0001) vs. changes in the placebo group. hBO treatment led to similar quantitative beneficial changes in mWOMAC, SF-36 and OMERACT-OARSI responder index. There were no SAEs and no adverse events ascribed to the intervention.

Conclusion: In a 56-day trial, hBO was safe, and was efficacious at reducing symptoms in patients with knee OA.

Registration: NCT04117490; Oct 7, 2019.
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http://dx.doi.org/10.1007/s10787-022-01013-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9216293PMC
August 2022

Phosphodiesterase 5 inhibitor sildenafil potentiates the antitumor activity of cisplatin by ROS-mediated apoptosis: a role of deregulated glucose metabolism.

Apoptosis 2022 08 20;27(7-8):606-618. Epub 2022 Jun 20.

Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.

Cyclic nucleotide phosphodiesterase 5 (PDE5) has been recently identified to play a crucial role in the progression of many cancers. PDE5 promotes tumorigenesis by dysregulating various cellular processes such as proliferation, apoptosis, angiogenesis, and invasion and migration. Interestingly, multiple studies have reported the promising chemosensitizing potential of PDE5 inhibitor sildenafil in breast, colon, prostate, glioma, and lung cancers. However, to date, the chemosensitizing action of sildenafil is not evaluated in T cell lymphoma, a rare and challenging neoplastic disorder. Hence, the present investigation was undertaken to examine the chemosensitizing potential of sildenafil against T cell lymphoma along with elucidation of possible involvement of altered apoptosis and glucose metabolism. The experimental findings of this study showed that sildenafil enhances the cytotoxic ability of cisplatin by apoptosis induction through altering the levels of apoptosis regulatory molecules: Bcl-2, Bax, cytochrome c (Cyt c), cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP). These molecular alterations were possibly driven by sildenafil through reactive oxygen species (ROS). Sildenafil deregulates glucose metabolism by markedly lowering the expression of glycolysis regulatory molecules, namely glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), hexokinase II (HKII), pyruvate kinase M2 (PKM2), and pyruvate dehydrogenase kinase 1 (PDK1) via suppressing hypoxia-inducible factor 1-alpha (HIF-1α) expression. Hence, sildenafil potentiates the tumor cell killing ability of cisplatin by augmenting ROS production through switching the glucose metabolism from glycolysis to oxidative phosphorylation (OXPHOS). Overall, our study demonstrates that sildenafil might be a promising adjunct therapeutic candidate in designing novel combinatorial chemotherapeutic regimens against T cell lymphoma.
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http://dx.doi.org/10.1007/s10495-022-01741-0DOI Listing
August 2022

SARS-CoV-2 seroprevalence in the city of Hyderabad, India in early 2021.

IJID Reg 2022 Mar 19;2:1-7. Epub 2021 Nov 19.

ICMR-National Institute of Nutrition, Tarnaka, Hyderabad.

Background: COVID-19 emerged as a global pandemic in 2020, spreading rapidly to most parts of the world. The proportion of infected individuals in a population can be reliably estimated via serosurveillance, making it a valuable tool for planning control measures. Our serosurvey study aimed to investigate SARS-CoV-2 seroprevalence in the urban population of Hyderabad at the end of the first wave of infections.

Methods: This cross-sectional survey, conducted in January 2021 and including males and females aged 10 years and above, used multi-stage random sampling. 9363 samples were collected from 30 wards distributed over six zones of Hyderabad, and tested for antibodies against SARS-CoV-2 nucleocapsid antigen.

Results: Overall seropositivity was 54.2%, ranging from 50% to 60% in most wards. Highest exposure appeared to be among those aged 30-39 and 50-59 years, with women showing greater seropositivity. Seropositivity increased with family size, with only marginal differences among people with varying levels of education. Seroprevalence was significantly lower among smokers. Only 11% of the survey subjects reported any COVID-19 symptoms, while 17% had appeared for COVID-19 testing.

Conclusion: Over half the city's population was infected within a year of onset of the pandemic. However, ∼ 46% of people remained susceptible, contributing to subsequent waves of infection.
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http://dx.doi.org/10.1016/j.ijregi.2021.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8603330PMC
March 2022

QTL Regulates Gene Expression Through Epigenetic Modification of DNA Under Phosphate Starvation Stress in Rice.

Front Plant Sci 2022 31;13:871890. Epub 2022 May 31.

Indian Council of Agricultural Research, New Delhi, India.

Cytosine methylation, epigenetic DNA modification, is well known to regulate gene expression. Among the epigenetic modifications, 5-methylcytosine (5-mC) has been one of the extensively studied epigenetic changes responsible for regulating gene expression in animals and plants. Though a dramatic change in 5-mC content is observed at the genome level, the variation in gene expression is generally less than that it is expected. Only less is understood about the significance of 5-mC in gene regulation under P-starvation stress in plants. Using whole-genome bisulfite sequencing of a pair of rice [Pusa-44 and its near-isogenic line (NIL)-23 harboring QTL] genotypes, we could decipher the role of on DNA (de)methylation-mediated regulation of gene expression under P-starvation stress. We observed 13-15% of total cytosines to be methylated in the rice genome, which increased significantly under the stress. The number of differentially methylated regions (DMRs) for hypomethylation (6,068) was higher than those (5,279) for hypermethylated DMRs under the stress, particularly in root of NIL-23. Hypomethylation in CHH context caused upregulated expression of 489 genes in shoot and 382 genes in root of NIL-23 under the stress, wherein 387 genes in shoot and 240 genes in root were upregulated exclusively in NIL-23. Many of the genes for DNA methylation, a few for DNA demethylation, and RNA-directed DNA methylation were upregulated in root of NIL-23 under the stress. Methylation or demethylation of DNA in genic regions differentially affected gene expression. Correlation analysis for the distribution of DMRs and gene expression indicated the regulation of gene mainly through (de)methylation of promoter. Many of the P-responsive genes were hypomethylated or upregulated in roots of NIL-23 under the stress. Hypermethylation of gene body in CG, CHG, and CHH contexts caused up- or downregulated expression of transcription factors (TFs), P transporters, phosphoesterases, retrotransposon proteins, and other proteins. Our integrated transcriptome and methylome analyses revealed an important role of the QTL in epigenetic regulation of the genes for transporters, TFs, phosphatases, carbohydrate metabolism, hormone-signaling, and chromatin architecture or epigenetic modifications in P-starvation tolerance. This provides insights into the molecular function of in modulating gene expression through DNA (de)methylation, which might be useful in improving P-use efficiency or productivity of rice in P-deficient soil.
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http://dx.doi.org/10.3389/fpls.2022.871890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9195100PMC
May 2022

Reactive Oxygen Species in Regulating Lymphangiogenesis and Lymphatic Function.

Cells 2022 05 26;11(11). Epub 2022 May 26.

Department of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis, TN 38017, USA.

The lymphatic system is pivotal for immunosurveillance and the maintenance of tissue homeostasis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing vessels, has both physiological and pathological roles. Recent advances in the molecular mechanisms regulating lymphangiogenesis have opened a new area of research on reparative lymphangiogenesis for the treatment of various pathological disorders comprising neurological disorders, cardiac repair, autoimmune disease, obesity, atherosclerosis, etc. Reactive oxygen species (ROS) produced by the various cell types serve as signaling molecules in several cellular mechanisms and regulate various aspects of growth-factor-mediated responses, including lymphangiogenesis. The ROS, including superoxide anion, hydrogen peroxide, and nitric oxide, play both beneficial and detrimental roles depending upon their levels and cellular microenvironment. Low ROS levels are essential for lymphangiogenesis. On the contrary, oxidative stress due to enhanced ROS generation and/or reduced levels of antioxidants suppresses lymphangiogenesis via promoting lymphatic endothelial cell apoptosis and death. In this review article, we provide an overview of types and sources of ROS, discuss the role of ROS in governing lymphangiogenesis and lymphatic function, and summarize the role of lymphatics in various diseases.
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http://dx.doi.org/10.3390/cells11111750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179518PMC
May 2022

Acute abdomen with jaundice: A clue to extrahepatic biliary tract perforation.

Int J Surg Case Rep 2022 May 1;94:107127. Epub 2022 May 1.

Department of Surgery, RIMS, Ranchi.

Introduction: Among a plethora of causes of acute abdomen, spontaneous common bile duct perforation (SCBDP) resulting in biliary peritonitis is almost never envisaged. Since the term SCBDP is often misconstrued as absence of an identifiable cause of perforation, 'nontraumatic perforation of CBD' is also in parlance to exclude relatively common causes such as trauma and iatrogenic injuries. In adults, choledochal cyst, cholangitis, infection, pancreatitis, pancreatobiliary maljunction have been identified as causes of perforation, however, choledocholithiasis remains the most common cause associated with spontaneous perforation of extra hepatic bile duct.

Case Presentation: Here we present three cases of a spontaneous common bile duct perforation that presented as acute abdomen with peritonitis. Clinical presentation, biochemical abnormalities, imaging details, treatment options, and outcome were studied. This study has been reported in line with the SCARE 2020 Guideline [1].

Discussion And Conclusion: Spontaneous perforation of the extrahepatic bile duct is a rare but important presentation of gallstones in adults and needs a high index of suspicion during day-to-day practice. Surgeons should seek out this uncommon diagnosis in the patient for early surgical intervention and appropriate drainage to ensure survival.
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http://dx.doi.org/10.1016/j.ijscr.2022.107127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092965PMC
May 2022

Quality of Life, Efficacy, and Safety of Sequential Intravesical Gemcitabine + Docetaxel versus BCG for Non-Muscle Invasive Urinary Bladder Cancer: A Pilot Study.

Urol Int 2022 2;106(8):784-790. Epub 2022 Jun 2.

Department of Urology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Purpose: Bacille Calmette-Guerin (BCG) is considered the most effective agent for non-muscle invasive bladder cancer (NMIBC). However, due to BCG-related toxicity, multiple studies have suggested the role of newer chemotherapeutic drugs. The aim of our study was to evaluate intravesical gemcitabine + docetaxel (Gem/Doce) versus BCG with respect to quality of life (QOL), safety, and efficacy in NMIBC.

Methods: A total of 60 patients with NMIBC were evaluated between July 2019 and December 2020 in a prospective manner. The sample size calculation was done, keeping in mind the incidence of intravesical BCG-related complications of up to 50-60% and 20-30% for Gem/Doce combination. The p value of 0.05 was kept as statistically significant. The enrollment ratio was kept at 1, and power of study was aimed at 80%. The study population was alternatively assigned to two groups (BCG vs. Gem/Doce) of 30 patients each. Both the groups received 6 weekly doses of induction therapy followed by 6 monthly doses of maintenance therapy if no recurrence was noted at interim follow-up. QOL scores, safety, and efficacy were assessed at beginning of intravesical therapy, end of induction, and 6 months of maintenance therapy. Cystoscopy examination and cytology were performed at the end of induction therapy and 3-monthly thereafter.

Result: The preliminary results at the end of 6 months following maintenance therapy showed that the demographic profile, histological stage, and grade were comparable between two groups. The QOL scores using QLQ-30 and QLQ-BLS-24 showed statistically significant differences with the Gem/Doce arm showing better outcomes. There were no progressions to higher stage, while one recurrence each was seen in both groups. Patient-related side effects measured by CTCAE (Common Terminology Criteria for Adverse Events)version 5 showed that the BCG group had higher toxicity profile as compared to Gem/Doce group.

Conclusion: Gem/Doce combination intravesical therapy is a promising alternative to BCG for treatment of NMIBC, showing better QOL measures and lesser side effects.
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http://dx.doi.org/10.1159/000524098DOI Listing
August 2022

Efficacy of Extended-Release Injectable Naltrexone on Alcohol Use Disorder Treatment: A Systematic Review.

J Psychoactive Drugs 2022 May 28:1-13. Epub 2022 May 28.

Sandra Atlas Bass Center for Liver Diseases & Transplantation, Department of Medicine, North Shore University Hospital/Northwell Health, Manhasset, NY, USA.

Alcohol use disorder (AUD) is a serious public health problem. Over 3.3 million people worldwide die each year due to alcohol-related causes, which is almost 5.3% of all deaths. This systematic review examines the effectiveness of injectable naltrexone treatment for people with AUD based on randomized clinical trial studies conducted between January 2004 and December 2019. Following PRISMA-P, this review searched PubMed, PsycINFO, CINAHL, Cochrane Library, and Web of Science for relevant studies. The inclusion criteria were AUD treatment, injectable naltrexone, and randomized clinical trials. Only articles written in English, involving human participants, and published in peer-reviewed journals were considered for this review. A total of 11 studies met the inclusion criteria. Ten out of the 11 studies assessed the impact of injectable naltrexone in a 3- to 6-month follow-up period, with one study having a year follow-up. This systematic review indicates that overall, injectable naltrexone therapy produced positive AUD treatment outcomes, including reduced mean time to first drinking day and/or heavy drinking day, decreased number of drinking and/or heavy drinking days, and increased abstinence, frequently at a statistically significant level in the larger studies. However, in all studies, less than half of the participants were completely abstinent after receiving injectable naltrexone. Injectable naltrexone treatment along with psychosocial therapy holds promise for addressing AUD.
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http://dx.doi.org/10.1080/02791072.2022.2073300DOI Listing
May 2022

Editorial: Non-Coding RNA Mediated Post-Transcriptional Regulation in Human Diseases.

Front Genet 2022 9;13:901664. Epub 2022 May 9.

Wadsworth Center, Center for Medical Science, New York State Department of Health, Albany, NY, United States.

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http://dx.doi.org/10.3389/fgene.2022.901664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125305PMC
May 2022

A cross-sectional study to determine the psychological distress among pulmonary tuberculosis patients during COVID-19 pandemic.

Monaldi Arch Chest Dis 2022 May 13. Epub 2022 May 13.

Department of Internal Medicine, King George's Medical University, Lucknow.

COVID-19 pandemic had adversely affected the services of the National Tuberculosis (TB) Elimination Programme, resulting in psychological distress among pulmonary tuberculosis patients (PTB). This cross-sectional, hospital-based study included 361 PTB patients. Three pre-defined questionnaires were used for the analysis, a questionnaire to evaluate anxiety related to COVID-19, a patient health questionnaire (PHQ-9) for depression, and a fear of COVID-19 scale (FCV-19S) questionnaire. Among 361 PTB patients, 13% (n=47) had COVID-19 infection. Out of the total patients, 69% (n=250) were DR-TB (drug resistance-tuberculosis) cases. Proportion of anxiety, fear and depression due to COVID-19 was found in 49% (n=177), 23% (n=83), 67% (n=247) respectively. Delay in the initiation of anti-tubercular treatment was found in 58% (n=210) of the cases, among which the majority, i.e., 69% (n=172, p=0.011), were DR-TB. This pandemic has led to a sudden step-down of PTB. Trend analysis of the psychological distress showed a peak following the COVID-19 pandemic. Most DR-TB patients had delayed initiation of the anti-tubercular treatment during the pandemic. The preponderance of the younger age group was seen in the pulmonary tuberculosis patients, and a majority of them had DR-TB. Depression was the predominant psychological distress among the study subjects during the pandemic.
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http://dx.doi.org/10.4081/monaldi.2022.2255DOI Listing
May 2022

Complete Genome Sequence of Paenibacillus polymyxa DSM 365, a Soil Bacterium of Agricultural and Industrial Importance.

Microbiol Resour Announc 2022 Jun 16;11(6):e0032922. Epub 2022 May 16.

Metabolic Engineering and Fermentation Science Group, Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA.

We report the complete genome sequence of Paenibacillus polymyxa DSM 365. The genome consists of a 5,788,318-bp chromosome, with a GC content of 45.48%. Annotation of the genome revealed a total of 5,246 genes (average length, 943 bp). Gene function analysis indicated the ability to fix nitrogen (N) and to produce value-added chemicals.
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http://dx.doi.org/10.1128/mra.00329-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202436PMC
June 2022

Cytoplasmic proteotoxicity regulates HRI-dependent phosphorylation of eIF2α via the Hsp70-Bag3 module.

iScience 2022 May 22;25(5):104282. Epub 2022 Apr 22.

Laboratory of Cancer Biology, Department of Molecular Biology, Ariel University, Ariel, 40700, Israel.

The major heat shock protein Hsp70 forms a complex with a scaffold protein Bag3 that links it to components of signaling pathways. Via these interactions, the Hsp70-Bag3 module functions as a proteotoxicity sensor that controls cell signaling. Here, to search for pathways regulated by the complex, we utilized JG-98, an allosteric inhibitor of Hsp70 that blocks its interaction with Bag3. RNAseq followed by the pathway analysis indicated that several signaling pathways including UPR were activated by JG-98. Surprisingly, only the eIF2α-associated branch of the UPR was activated, while other UPR branches were not induced, suggesting that the response was unrelated to the ER proteotoxicity and ER-associated kinase PERK1. Indeed, induction of the UPR genes under these conditions was driven by a distinct eIF2α kinase HRI. Hsp70-Bag3 directly interacted with HRI and regulated eIF2α phosphorylation upon cytoplasmic proteotoxicity. Therefore, cytosolic proteotoxicity can activate certain UPR genes via Hsp70-Bag3-HRI-eIF2α axis.
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http://dx.doi.org/10.1016/j.isci.2022.104282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097715PMC
May 2022

Smart nanomaterials for cancer diagnosis and treatment.

Nano Converg 2022 May 15;9(1):21. Epub 2022 May 15.

Amity Center for Nanobiotechnology and Nanomedicine (ACNN), Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, 303002, Rajasthan, India.

Innovations in nanomedicine has guided the improved outcomes for cancer diagnosis and therapy. However, frequent use of nanomaterials remains challenging due to specific limitations like non-targeted distribution causing low signal-to-noise ratio for diagnostics, complex fabrication, reduced-biocompatibility, decreased photostability, and systemic toxicity of nanomaterials within the body. Thus, better nanomaterial-systems with controlled physicochemical and biological properties, form the need of the hour. In this context, smart nanomaterials serve as promising solution, as they can be activated under specific exogenous or endogenous stimuli such as pH, temperature, enzymes, or a particular biological molecule. The properties of smart nanomaterials make them ideal candidates for various applications like biosensors, controlled drug release, and treatment of various diseases. Recently, smart nanomaterial-based cancer theranostic approaches have been developed, and they are displaying better selectivity and sensitivity with reduced side-effects in comparison to conventional methods. In cancer therapy, the smart nanomaterials-system only activates in response to tumor microenvironment (TME) and remains in deactivated state in normal cells, which further reduces the side-effects and systemic toxicities. Thus, the present review aims to describe the stimulus-based classification of smart nanomaterials, tumor microenvironment-responsive behaviour, and their up-to-date applications in cancer theranostics. Besides, present review addresses the development of various smart nanomaterials and their advantages for diagnosing and treating cancer. Here, we also discuss about the drug targeting and sustained drug release from nanocarriers, and different types of nanomaterials which have been engineered for this intent. Additionally, the present challenges and prospects of nanomaterials in effective cancer diagnosis and therapeutics have been discussed.
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http://dx.doi.org/10.1186/s40580-022-00313-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108129PMC
May 2022

A Two-in-One Tumor in the Adrenal: A Functional Adrenocortical Adenoma with Myelolipomatous Differentiation.

Fetal Pediatr Pathol 2022 May 10:1-6. Epub 2022 May 10.

Department of Histopathology, PGIMER, Chandigarh, India.

Background: Adrenocortical adenoma (ADA) and myelolipoma are two common benign neoplasms of the adrenal cortex that have been reported to occur together.

Case Report: A 14-year-old girl presented with the features of ACTH-independent endogenous Cushing syndrome. Abdominal CECT revealed a left adrenal 2.3 × 1.8 × 1.5 cm arterially enhancing nodular lesion with central hypodensity. Histologically, this was an ADA with oncocytic change and myelolipomatous differentiation/metaplasia.

Discussion/conclusion: ADA with myelolipomatous differentiation/metaplasia can occur in the pediatric age group.
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http://dx.doi.org/10.1080/15513815.2022.2072423DOI Listing
May 2022

MALAT1 as master regulator of biomarkers predictive of pan-cancer multi-drug resistance in the context of recalcitrant NRAS signaling pathway identified using systems-oriented approach.

Sci Rep 2022 05 9;12(1):7540. Epub 2022 May 9.

Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, 500046, India.

NRAS, a protein mutated in several cancer types, is involved in key drug resistance mechanisms and is an intractable target. The development of drug resistance is one of the major impediments in targeted therapy. Currently, gene expression data is used as the most predictive molecular profile in pan-cancer drug sensitivity and resistance studies. However, the common regulatory mechanisms that drive drug sensitivity/resistance across cancer types are as yet, not fully understood. We focused on GDSC data on NRAS-mutant pan-cancer cell lines, to pinpoint key signaling targets in direct or indirect associations with NRAS, in order to identify other druggable targets involved in drug resistance. Large-scale gene expression, comparative gene co-expression and protein-protein interaction network analyses were performed on selected drugs inducing drug sensitivity/resistance. We validated our data from cell lines with those obtained from primary tissues from TCGA. From our big data studies validated with independent datasets, protein-coding hub genes FN1, CD44, TIMP1, SNAI2, and SPARC were found significantly enriched in signal transduction, proteolysis, cell adhesion and proteoglycans pathways in cancer as well as the PI3K/Akt-signaling pathway. Further studies of the regulation of these hub/driver genes by lncRNAs revealed several lncRNAs as prominent regulators, with MALAT1 as a possible master regulator. Transcription factor EGR1 may control the transcription rate of MALAT1 transcript. Synergizing these studies, we zeroed in on a pan-cancer regulatory axis comprising EGR1-MALAT1-driver coding genes playing a role. These identified gene regulators are bound to provide new paradigms in pan-cancer targeted therapy, a foundation for precision medicine, through the targeting of these key driver genes in the improvement of multi-drug sensitivity or resistance.
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http://dx.doi.org/10.1038/s41598-022-11214-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9085754PMC
May 2022
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