Publications by authors named "Gaurav Gupta"

542 Publications

Recurrent Papillary Tumor of Pineal Region Misdiagnosed as Pineocytoma 9-Years Ago.

Asian J Neurosurg 2021 Apr-Jun;16(2):398-401. Epub 2021 May 28.

Department of Neurosurgery, Bombay Hospital Institute of Medical Sciences, Mumbai, Maharashtra, India.

Primary tumors of the pineal gland occur infrequently with a preponderance of either parenchymal tumors or germ cells tumors. Papillary tumor of the pineal region is a rare neuroepithelial lesion that arises exclusively in the pineal region. They have been designated as either Grade II or Grade III lesions as per the 2016 WHO classification of central nervous system tumors. Clinically, they usually present with obstructive hydrocephalus and visual disturbance. On imaging, these tumors are solid-cystic, heterogeneously enhancing, and show T2 hyperintensity. Pathologically, they can closely resemble a Grade I pineocytoma and immunohistochemistry is essential to differentiate the two. No definite guidelines exist to confirm the ideal protocol of treatment. Evidence regarding the role of radiation after surgery is limited to case reports and series. Adjuvant therapy is usually recommended for tumors with subtotal excision, high proliferative/mitotic index, or proven metastasis. We describe a case of a 29-year-old male with a recurrent papillary tumor of the pineal region, 9 years after primary surgery where it was misdiagnosed as a pineocytoma. The tumor was effectively controlled with surgical excision, cerebrospinal fluid diversion, and adjuvant radiation for 8 years before showing two recurrences within a span of 6 months with a rising proliferation index.
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http://dx.doi.org/10.4103/ajns.AJNS_439_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244718PMC
May 2021

Spinal Nerve Root Extradural Melanocytoma Progressing to Malignant Melanoma: A Case Report with Review of Literature.

Asian J Neurosurg 2021 Apr-Jun;16(2):394-397. Epub 2021 May 28.

Department of Neurosurgery, Bombay Hospital Institute of Medical Sciences, Mumbai, Maharashtra, India.

Melanocytomas are rare benign pigmented tumors arising from the leptomeninges with a very remote chance of progressing to malignant melanoma. They have a predilection for occurring in the posterior fossa or in the intradural extramedullary region of the cervical spine. We report the first case of malignant transformation of a nerve root (extradural) melanocytoma wherein immunotherapy has been added for its treatment. Only four such cases of malignant transformation of central nervous system melanocytoma have been reported in the literature. Definite diagnosis in such cases is based on immunohistochemistry evaluation. Surgical resection with adjuvant radiotherapy and immunotherapy is the recommended treatment.
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http://dx.doi.org/10.4103/ajns.AJNS_416_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244717PMC
May 2021

Recent update on barbiturate in relation to brain disorder.

EXCLI J 2021 7;20:1028-1032. Epub 2021 Jun 7.

School of Pharmacy, Suresh Gyan Vihar University, Mahal Road-302017, Jagatpura, Jaipur, India.

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http://dx.doi.org/10.17179/excli2021-3687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278211PMC
June 2021

Targeting LIN28: a new hope in prostate cancer theranostics.

Future Oncol 2021 07 15. Epub 2021 Jul 15.

School of Pharmacy & Pharmaceutical Sciences, Ulster University, Coleraine, County Londonderry, Northern Ireland BT52 1SA, UK.

The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.
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http://dx.doi.org/10.2217/fon-2021-0247DOI Listing
July 2021

Donor-Specific Antibody is Associated with Increased Expression of Rejection Transcripts in Renal Transplant Biopsies Classified As No Rejection.

J Am Soc Nephrol 2021 Jul 12. Epub 2021 Jul 12.

P Halloran, Alberta Transplant Applied Genomics Centre, Edmonton, Canada

Donor-specific HLA antibody (DSA) is present in many kidney transplant patients whose biopsies are classified as no-rejection (NR). We explored whether in some NR kidneys DSA has subtle effects that are not currently being recognized. We used microarrays to examine the relationship between standard-of-care DSA and rejection-related transcript increases in 1679 kidney transplant indication biopsies in the INTERCOMEX study (ClinicalTrials.gov NCT01299168), focusing on biopsies classified as NR by automatically assigned archetypal clustering. DSA testing results were available for 835 NR biopsies and were positive in 271 (32%). DSA-positivity in NR biopsies was associated with mildly increased expression of ABMR-related transcripts, particularly IFNG-inducible and NK cell transcripts. We developed a machine learning DSA probability (DSA) classifier based on transcript expression in biopsies from DSA-positive vs. DSA-negative patients, assigning scores using 10-fold cross-validation. This DSA classifier was very similar to a previously described "ABMR probability" classifier trained on histologic ABMR in transcript associations and prediction of molecular or histologic ABMR. Plotting the biopsies using Uniform Manifold Approximation and Projection revealed a gradient of increasing molecular ABMR-like transcript expression in NR biopsies, associated with increased DSA (<2E-16). In biopsies with no molecular or histologic rejection, increased DSA or ABMR probability scores were associated with increased risk of kidney failure over three years. Many biopsies currently considered to have no molecular or histologic rejection have mild increases in expression of ABMR-related transcripts, associated with increasing frequency of DSA. Thus mild molecular ABMR-related pathology is more common than previously realized.
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http://dx.doi.org/10.1681/ASN.2021040433DOI Listing
July 2021

Role of Various Gene Expressions in Etiopathogenesis of Type 2 Diabetes Mellitus.

Adv Mind Body Med 2021 Summer;35(3):31-39

Context: Diabetes is a metabolic disease, with high mortality, and is characterized by increased glucose levels in the blood occurring due to poor pancreatic insulin secretion or development of insulin resistance in the body. Type 2 DM (T2DM) represents 90% of diabetic cases, and its pathogenesis involves a genetic correlation with insulin resistance, β-cell dysfunction, lifestyle, and environmental factors.

Objective: The current study intended to examine the pathophysiology of T2DM, including factors influencing insulin resistance and beta (β)-cell dysfunction as well as the genetic factors that indicate susceptibility to T2DM.

Design: The research team performed a narrative review by searching the Mendeley, Science Direct, Medline, PubMed, Google Scholar, and Springer databases. The search used the keywords Diabetes, insulin secretion and environmental factor.

Setting: This study was take place in School of Pharmacy, Suresh Gyan Vihar University, Jaipur, India.

Results: The paraoxonase-1 gene Q192R and the L55M, INS-VNTR, and IL-38 gene alterations can result in insulin resistance while PAM variants and miR-132 and miR-18 expression can lead to β-cell dysfunction. Palmitate-like FFA expression of mRNA MafA, and IRS-2 can lead to impairment of insulin secretion.

Conclusions: T2DM is the most common metabolic disorder of the twenty-first century, and its incidence, complications, and morbidity increase every day. The examination of T2DM's pathophysiology and the literature review have revealed that it has a strong correlation with genetic defects.
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July 2021

Finite Element Study of Bio-Convective Stefan Blowing Ag-MgO/Water Hybrid Nanofluid Induced by Stretching Cylinder Utilizing Non-Fourier and Non-Fick's Laws.

Nanomaterials (Basel) 2021 Jun 30;11(7). Epub 2021 Jun 30.

School of Mathematical Sciences, College of Science and Technology, Wenzhou-Kean University, Wenzhou 325060, China.

In the present framework, an analysis on nanofluid magneto-transport phenomena over an extending cylinder influenced by gyrotactic behavior of algal suspension, is made using the Cattaneo-Christov heat flux (non-Fourier) and mass flux (non-Fick's) concept in modified Buongiorno's model. Two dimensional incompressible MHD hybrid nanofluid which comprises chemically reactive hybrid nanomaterials (Ag-MgO NPs) and Stefan blowing effect along with multiple slips is considered. The experimental correlations with their dependency on initial nanoparticle volume fraction are used for viscosity and thermal conductivity of nanofluids. Similarity transformation is used to convert the governing PDE's into non-linear ODE's along with boundary conditions, which are solved using the Galerkin Finite Element Method (GFEM). The mesh independent test with different boundary layer thickness (ξ∞) has been conducted by taking both linear and quadratic shape functions to achieve a optimal desired value. The results are calculated for a realistic range of physical parameters. The validation of FEM results shows an excellent correlation with MATLAB subroutine. The warmth exhibitions are assessed through modified version of Buongiorno's model which effectively reflects the significant highlights of Stefan blowing, slip, curvature, free stream, thermophoresis, Brownian motion and bio-convection parameters. The present study in cylindrical domain is relevant to novel microbial fuel cell technologies utilizing hybrid nanoparticles and concept of Stefan blowing with bioconvection phenomena.
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http://dx.doi.org/10.3390/nano11071735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308164PMC
June 2021

Versatility of liquid crystalline nanoparticles in inflammatory lung diseases.

Nanomedicine (Lond) 2021 Jun 29. Epub 2021 Jun 29.

Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, 57000, Malaysia.

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http://dx.doi.org/10.2217/nnm-2021-0114DOI Listing
June 2021

Nuclear factor-kappa B and its role in inflammatory lung disease.

Chem Biol Interact 2021 Aug 25;345:109568. Epub 2021 Jun 25.

School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, 302017, Mahal Road, Jaipur, India. Electronic address:

Nuclear factor-kappa B, involved in inflammation, host immune response, cell adhesion, growth signals, cell proliferation, cell differentiation, and apoptosis defense, is a dimeric transcription factor. Inflammation is a key component of many common respiratory disorders, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and acute respiratory distress syndrome. Many basic transcription factors are found in NF-κB signaling, which is a member of the Rel protein family. Five members of this family c-REL, NF-κB2 (p100/p52), RelA (p65), NF-κB1 (p105/p50), RelB, and RelA (p65) produce 5 transcriptionally active molecules. Proinflammatory cytokines, T lymphocyte, and B lymphocyte cell mitogens, lipopolysaccharides, bacteria, viral proteins, viruses, double-stranded RNA, oxidative stress, physical exertion, various chemotherapeutics are the stimulus responsible for NF-κB activation. NF-κB act as a principal component for several common respiratory illnesses, such as asthma, lung cancer, pulmonary fibrosis, COPD as well as infectious diseases like pneumonia, tuberculosis, COVID-19. Inflammatory lung disease, especially COVID-19, can make NF-κB a key target for drug production.
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http://dx.doi.org/10.1016/j.cbi.2021.109568DOI Listing
August 2021

Changes in cytomegalovirus-specific T-cell immunity with immunomodulation in serodiscordant high-risk transplant recipients.

Transpl Infect Dis 2021 Jun 28:e13678. Epub 2021 Jun 28.

Division of Nephrology, Virginia Commonwealth University Health System, Richmond, VA, USA.

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http://dx.doi.org/10.1111/tid.13678DOI Listing
June 2021

Revolutionizing polymer-based nanoparticle-linked vaccines for targeting respiratory viruses: A perspective.

Life Sci 2021 Sep 24;280:119744. Epub 2021 Jun 24.

University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, AB T6G 2N8, Canada; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia. Electronic address:

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.
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http://dx.doi.org/10.1016/j.lfs.2021.119744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223024PMC
September 2021

Recent updates on animal models for understanding the etiopathogenesis of polycystic ovarian syndrome.

Life Sci 2021 Sep 23;280:119753. Epub 2021 Jun 23.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Australia.

Polycystic ovarian syndrome (PCOS) is the primary cause of female infertility affecting several women worldwide. Changes in hormonal functions such as hyperandrogenism are considered a significant factor in developing PCOS in women. In addition, many molecular pathways are involved in the pathogenesis of PCOS in women. To have better insights about PCOS, it is data from clinical studies carried on women suffering from PCOS should be collected. However, this approach has several implications, including ethical considerations, cost involved and availability of subject. Moreover, during the early drug development process, it is always advisable to use non-human models mimicking human physiology as they are less expensive, readily available, have a shorter gestation period and less risk involved. Many animal models have been reported that resemble the PCOS pathways in human subjects. However, the models developed on rats and mice are more preferred over other rodent/non-rodent models due to their closer resemblance with human PCOS development mechanism. The most extensively reported PCOS models for rats and mice include those induced by using testosterone, letrozole and estradiol valerate. As the pathophysiology of PCOS is complex, none of the explored models completely surrogates the PCOS related conditions occurring in women. Hence, there is a need to develop an animal model that can resemble the pathophysiology of PCOS in women. The review focuses on various animal models explored to understand the pathophysiology of PCOS. The article also highlights some environmental and food-related models that have been used to induce PCOS.
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http://dx.doi.org/10.1016/j.lfs.2021.119753DOI Listing
September 2021

The failing kidney allograft: A review and recommendations for the care and management of a complex group of patients.

Am J Transplant 2021 Jun 11. Epub 2021 Jun 11.

Division of Nephrology, Washington University in St. Louis, St. Louis, Michigan, USA.

The return to dialysis after allograft failure is associated with increased morbidity and mortality. This transition is made more complex by the rising numbers of patients who seek repeat transplantation and therefore may have indications for remaining on low levels of immunosuppression, despite the potential increased morbidity. Management strategies vary across providers, driven by limited data on how to transition off immunosuppression as the allograft fails and a paucity of randomized controlled trials to support one approach over another. In this review, we summarize the current data available for management and care of the failing allograft. Additionally, we discuss a suggested plan for immunosuppression weaning based upon the availability of re-transplantation and residual allograft function. We propose a shared-care model in which there is improved coordination between transplant providers and general nephrologists so that immunosuppression management and preparation for renal replacement therapy and/or repeat transplantation can be conducted with the goal of improved outcomes and decreased morbidity in this vulnerable patient group.
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http://dx.doi.org/10.1111/ajt.16717DOI Listing
June 2021

Middle East Respiratory Syndrome (MERS) Virus-Pathophysiological Axis and the Current Treatment Strategies.

AAPS PharmSciTech 2021 Jun 8;22(5):173. Epub 2021 Jun 8.

Department of Life Sciences, International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.
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http://dx.doi.org/10.1208/s12249-021-02062-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186825PMC
June 2021

Safety and Efficacy of Modified FOLFIRINOX in Unresectable or Metastatic Gallbladder Cancer: A Phase II Pilot Study.

JCO Glob Oncol 2021 Jun;7:820-826

Department of Medical Oncology, Dr Ram Manohar Lohia Institute of Medical Sciences, Gaumtinagar, Lucknow, India.

Purpose: For unresectable gallbladder cancer (GBC), gemcitabine and platinum is standard combination; however, outcome is poor. We conducted this study to find feasibility of modified flourouracil, oxaliplatin, and irinotecan in this group.

Materials And Methods: We conducted a prospective, phase II single-arm pilot study. Inclusion criteria were histologically proven GBC and Eastern Cooperative Oncology Group 0-1. Primary end points were overall response rates and overall survival. The following treatment was given: oxaliplatin 85 mg/m, leucovorin 400 mg/m, and irinotecan 150 mg/m, all once on day 1, fluorouracil 2,400 mg/m continuous intra-venous infusion over 46 hours repeated every 2 weeks, and maximum 12 doses, with primary granulocyte colony-stimulating factor prophylaxis.

Results: Between February 2019 and July 2020, 29 patients with unresectable GBC were enrolled. The median age was 52 years, and 18 were females. The Eastern Cooperative Oncology Group was 0 in 4. Five had bilirubin > normal, and 15 each had high serum alkaline phosphatase and carbohydrate antigen 19-9. Twenty-five patients had stage IV disease, and remaining unresectable locally advanced disease. A median of 8.5 cycles was given, and 11 completed treatment. Nine stopped chemotherapy because of progression, and one because of toxicity, and treatment is ongoing in three. Twenty-two required dose reduction. A treatment delay of 1-2 weeks was seen in 25 patients. Best response was complete response 1, partial response 13 (overall response rate 48.2%), and stable disease 9. Four patients with metastatic disease underwent R0 resection. As on cutoff date, nine are surviving (three without disease). Eighteen died of PD, and in two, cause was unknown. There was no toxic death. The median overall survival and progression-free survival were 309 and 252 days, respectively. Twenty-three patients experienced grade III or IV toxicity, and common were diarrhea (13), vomiting (12), and anemia (7).

Conclusion: First-line modified flourouracil, oxaliplatin, and irinotecan is feasible in unresectable GBC with encouraging responses. Toxicities are higher but manageable. Higher response rates make this an option to explore in borderline resectable cases.
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http://dx.doi.org/10.1200/GO.20.00657DOI Listing
June 2021

Multiple cerebral hemorrhages in sepsis-disseminated intravascular coagulation versus septic embolism: An image report.

Surg Neurol Int 2021 26;12:185. Epub 2021 Apr 26.

Department of Neurosurgery, Rutgers - Robert Wood Johnson University Hospital, New Brunswick, New Jersey, United States.

Background: Septic emboli are commonly attributed to infective endocarditis and can present with a variety of symptoms including altered mental status and focal neurological deficits. Here, we reviewed images of septic emboli with hemorrhagic conversion in a patient with sepsis and a psoas abscess. We aim to show the classical image findings in septic embolism to brain, which is sparsely described in literature and the report differentiates the septic embolism from disseminated intravascular coagulation which can present with almost identical image findings.

Case Description: A 53-year-old male patient who was operated on for a right inguinal hernia developed a postoperative wound infection 2 weeks after surgery and was started on IV antibiotics. Despite medical management, his infection did not improve, prompting a computed tomography (CT) scan which revealed a psoas abscess. The abscess was drained, and antibiotics continued. A few days later, he developed altered sensorium prompting a head CT which revealed septic emboli and hemorrhage at the gray-white junction. Cultures grew multidrug-resistant ; the patient was treated with IV tigecycline and improved over the following 4 weeks.

Conclusion: In patients with a known ongoing infectious process with hemodynamic stability who develop altered mental status in the setting of a normal coagulation profile, D-dimer, positive blood cultures, and absent signs of multiorgan failure, a diagnosis of septic emboli should be entertained. Although CT can reveal macrobleeds, MRI is more sensitive in confirming cerebral microbleeds. Thus, patients in sepsis with unexplained altered sensorium should undergo an MRI of the brain to rule out septic emboli and microbleeds.
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http://dx.doi.org/10.25259/SNI_810_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168679PMC
April 2021

Compliance With Preferred Reporting Items for Systematic Review and Meta-Analysis Individual Participant Data Statement for Meta-Analyses Published for Stroke Studies.

Stroke 2021 Jun 4:STROKEAHA120033288. Epub 2021 Jun 4.

Department of Neurosurgery, Rutgers- Robert Wood Johnson Medical School & University Hospital, New Brunswick, NJ (F.J., O.A., M.S.R., B.R., A.G., H.S., V.N., G.G., A.N.).

Background And Purpose: Individual-participant data meta-analyses (IPD-MA) are powerful evidence synthesis studies which are considered the gold-standard of MA. The quality of reporting in these studies is guided by the 2015 Preferred Reporting Items for Systematic Review and Meta-Analysis of Individual Participant Data (PRISMA-IPD) guidelines. The growing number of IPD-MA published for stroke studies calls for an assessment of the compliance of these studies with the PRISMA-IPD statement.

Methods: PubMed and EMBASE were searched for MA in stroke published between January 1, 2016, and March 30, 2020, in journals with impact factor >2. Literature reviews, scoping reviews, and aggregate MA were excluded. The final articles were scored using the 31-item PRISMA-IPD checklist. Results were depicted using descriptive statistics. Compliance with each item in PRISM-IPD guideline was recorded. The study was defined as compliant to IPD analyses if it satisfied all IPD specific items.

Results: From an initial set of 321 articles, 31 met the final eligibility for data extraction. Only 4 (13%) described the use of PRISMA-IPD guidelines in their methodology, while 8/31 (26%) used the old PRISMA guidelines and 19/31 (61%) followed none. Regardless of mention of using IPD specific guidelines, 42% (n=13) of studies were compliant with all 4 IPD specific domains. The poorest areas of compliance were bias assessment within (32%) and across (39%) studies, reporting protocol and registration (42%), and reporting of IPD integrity (48%). The median journal impact factor was similar between the compliant (median, 8.1 [interquartile range, 5.4-39.9]) and noncompliant (median, 6 [interquartile range, 4.5-16.2]) groups (=0.24). Similarly, the journal, country of correspondence, number of authors, number of studies included in MA, study sample size, and funding source were statistically similar between the groups.

Conclusions: For the published IPD-MA stroke studies, the compliance with PRISMA-IPD statement and compliance with 4 IPD specific items was suboptimal. The journal, author, and study-related factors were not associated with compliance. Additional scrutiny measures to ensure adherence to mandated guidelines might increase the compliance. Several avenues to improve compliance and ensure optimal adherence are discussed.
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http://dx.doi.org/10.1161/STROKEAHA.120.033288DOI Listing
June 2021

Correlation of Donor-Derived Cell-free DNA with Histology and Molecular Diagnoses of Kidney Transplant Biopsies.

Transplantation 2021 May 28. Epub 2021 May 28.

Division of Nephrology, Virginia Commonwealth University, Richmond, VA, United States Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA, United States Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, United States Department of Pathology, Virginia Commonwealth University, Richmond, VA, United States Alberta Transplant Applied Genomics Center, Edmonton, Canada.

Background: Circulating donor-derived cell free DNA (cfDNA), a minimally invasive diagnostic tool for kidney transplant rejection, was validated using traditional histology. The Molecular Microscope (MMDx) tissue gene expression platform may provide increased precision to traditional histology.

Methods: In this single-center prospective study of 208 biopsies (median=5.8 months) post-transplant, we report on the calibration of cfDNA with simultaneous biopsy assessments using MMDx and histology by Area under the curve (AUC) analyses for optimal criterion, as well as for, previously published cfDNA cut-offs ≤0.21% to 'rule-out' rejection and ≥1% to 'rule-in' rejection.

Results: There were significant discrepancies between histology and MMDx, with MMDx identifying more antibody-mediated rejection (65; 31%) than histology (43; 21%); the opposite was true for T-cell mediated rejection [TCMR; histology: 27 (13%) vs MMDx: 13 (6%)]. Most of the TCMR discrepancies were seen for histologic borderline/1A TCMR. AUC Curves for cfDNA and prediction of rejection were slightly better with MMDx (AUC=0.80; 95%CI: 0.74-0.86) vs. histology (AUC=0.75; 95%CI: 0.69-0.81). A cfDNA≤0.21% had similar sensitivity (~91%) to 'rule-out' rejection by histology and MMDx. Specificity was slightly higher with MMDx (92%) compared with histology (85%) to 'rule-in' rejection using cfDNA criterion≥1%. Strong positive quantitative correlations were observed between cfDNA scores and molecular acute kidney injury (AKI) for both 'rejection' and 'nonrejection' biopsies.

Conclusions: Molecular diagnostics using tissue gene expression and blood-based donor-derived cell-free DNA may add precision to some cases of traditional histology. The positive correlation of cfDNA with molecular AKI suggests a dose-dependent association with tissue injury irrespective of rejection characteristics.
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http://dx.doi.org/10.1097/TP.0000000000003838DOI Listing
May 2021

Authors' reply to the published comment regarding our article: Application of the new SMS system of cochleovestibular anomalies: our experience with nine cases of type III anomaly.

Eur Arch Otorhinolaryngol 2021 Aug 27;278(8):3131. Epub 2021 May 27.

Department of ENT and Head-Neck Surgery, SMS Medical College and Hospital, Jaipur, Rajasthan, India.

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http://dx.doi.org/10.1007/s00405-021-06869-4DOI Listing
August 2021

CT based Acute Appendicitis Severity Index for acute appendicitis and validate its effectiveness in predicting complicated appendicitis.

Emerg Radiol 2021 May 25. Epub 2021 May 25.

Diagnostic Radiology Department, Mansoura Faculty of Medicine, Mansoura University, Elgomheryia Street, Mansoura, 3512, Egypt.

Aim: To propose a CT-based scoring system called Acute Appendicitis Severity Index (AASI) for diagnosis of acute appendicitis and validates its effectiveness in predicting complicated appendicitis.

Subjects And Methods: Retrospective analyses of CT images of 120 adult patients with pathologically proven uncomplicated (n = 64) and complicated (n = 56) acute appendicitis were performed. All patients had undergone a CT scan of the abdomen and pelvis using 320 multi-detectors computed tomography with Adaptive Iterative Dose Reduction 3D (AIDR 3D). CT image parameters were identified and used to develop a CT-based scoring system (AASI) to predict the severity of acute appendicitis and its outcome. All image analysis was performed by 2 radiologists and the total score was assigned to each patient based on the proposed CT scoring system. Validation of the effectiveness of the proposed scoring system (AASI) was done using statistical models.

Results: The mean and standard deviation of AASI was found to be significantly higher (P value = 0.001) in the complicated appendicitis group (observer 1 = 10.2 ± 1.6 and observer 2 = 9.63 ± 2.3) as compared to that in uncomplicated acute appendicitis group (observer 1 = 7.09 ± 2.2 and observer 2 = 6.38 ± 1.9). There was an excellent interobserver agreement of the Acute Appendicitis Severity Index for both the uncomplicated and complicated appendicitis groups (K = 0.89, 95% CI = 0.87-0.92, P = 0.001). The cutoff value for AASI used to predict complicated appendicitis was taken as 9.5 and 8.5. This resulted in an AUC of 0.877 and 0.848, accuracy of 83% and 81%, the sensitivity of 75% and 80%, the specificity of 90% and 81%, the positive predictive value of 87% and 78%, and a negative predictive value of 81% and 83% by both reviewers respectively.

Conclusion: The proposed CT-based AASI is a reliable parameter for the prediction of complicated appendicitis.
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http://dx.doi.org/10.1007/s10140-021-01950-1DOI Listing
May 2021

Overview of key molecular and pharmacological targets for diabetes and associated diseases.

Life Sci 2021 Aug 18;278:119632. Epub 2021 May 18.

School of Pharmacy & Pharmaceutical Sciences, Ulster University, Coleraine, County Londonderry, BT52 1SA, Northern Ireland, United Kingdom. Electronic address:

Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways.
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http://dx.doi.org/10.1016/j.lfs.2021.119632DOI Listing
August 2021

Exploring role of polysaccharides present in Ganoderma lucidium extract powder and probiotics as solid carriers in development of liquisolid formulation loaded with quercetin: A novel study.

Int J Biol Macromol 2021 Jul 17;183:1630-1639. Epub 2021 May 17.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.

Ganoderma lucidium extract powder (GLEP) contains various polysaccharides which are well known for their antioxidant and anti-inflammatory actions. Probiotics (PB) are well-established for providing a plethora of health benefits. Hence, use of mushroom polysaccharides and probiotics as carriers to solidify liquisolid formulation is anticipated to function as functional excipients i.e. as adsorbent that may provide therapeutic benefits. Quercetin (QUR) has been used as model lipophilic drug in this study. QUR loaded liquisolid compacts (LSCs) were formulated using Tween 80 as solvent. These were further solidified using a combination of PB and GLEP as carriers. Aerosil-200 (A-200) was used as coating agent. The formulation exhibited very good flow characteristics. Dissolution rate of raw QUR was found to be less than 10% in 60 min while in case of QUR loaded LSCs, more than 90% drug release was observed within 5 min. Absence of crystalline peaks of QUR in the DSC and PXRD reports of LSCs and their porous appearance in SEM micrographs indicate that QUR was successfully incorporated in the LSCs. The developed formulation was found to be stable on storage under accelerated stability conditions.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.064DOI Listing
July 2021

Advances in nanotechnology-based drug delivery in targeting PI3K signaling in respiratory diseases.

Nanomedicine (Lond) 2021 Jul 17;16(16):1351-1355. Epub 2021 May 17.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia.

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http://dx.doi.org/10.2217/nnm-2021-0087DOI Listing
July 2021

A novel nano therapeutic using convalescent plasma derived exosomal (CP) for COVID-19: A combined hyperactive immune modulation and diagnostics.

Chem Biol Interact 2021 Aug 13;344:109497. Epub 2021 May 13.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia.

Extracellular vesicles like exosomes are important therapeutic tactics for treating COVID -19. By utilizing convalescent plasma derived exosomes (CP) from COVID-19 recovered persistence could accelerate the treatment strategies in the current state of affairs. Adequate literature has shown that administering the exosome to the in vivo system could be beneficial and could target the pathogens in an effective and precise manner. In this hypothesis we highlight the CP instead of convalescent plasma (CP), perhaps to dispense of exosomes are gratified and it's more effectively acquired immune response conferral through antibodies. COVID-19 convalescent plasma has billions of exosomes and it has aptitudes to carry molecular constituents like proteins, lipids, RNA and DNA, etc. Moreover, exosomes are capable of recognizing antigens with adequate sensitivity and specificity. Many of these derivatives could trigger an immune modulation into the cells and act as an epigenetic inheritor response to target pathogens through RNAs. COIVID-19 resistance activated plasma-derived exosomes are either responsible for the effects of plasma beyond the contained immune antibodies or could be inhibitory. The proposed hypothesis suggests that preselecting the plasma-derived antibodies and RNAs merged exosomes would be an optimized therapeutic tactic for COVID-19 patients. We suggest that, the CP has a multi-potential effect for treatment efficacy by acting as immunotherapeutic, drug carrier, and diagnostic target with noncoding genetic materials as a biomarker.
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http://dx.doi.org/10.1016/j.cbi.2021.109497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116126PMC
August 2021

Out of the shadows: Chronic pain in Canadian Armed Forces veterans - Proceedings of a workshop at the 2019 Forum of the Canadian Institute for Military and Veteran Health Research.

Can J Pain 2020 Sep 10;4(1):199-204. Epub 2020 Sep 10.

Chronic Pain Network, McMaster University, Hamilton, Ontario, Canada.

This commentary summarizes proceedings of a workshop on chronic pain in military personnel and veterans (released personnel) at the Annual Forum of the Canadian Institute for Military and Veteran Health Research in Gatineau and Ottawa on October 22, 2019. The extent and impact of chronic pain among Canadian Armed Forces (CAF) veterans and their families is significant and has been underappreciated, largely due to limited disclosure by serving and veteran military personnel, stemming from a fear of stigmatization. Living with pain is seen as a fact of life in military cultures, something to be endured and not discussed. Though progress is being made in reducing the stigma of mental illness, the discourse on chronic pain remains censored. This workshop's goal was to bring the discussion of chronic pain out of the shadows in the search for ways to help veterans and active service personnel living with chronic pain. Many points of view were brought forward at this first national Canadian multidisciplinary gathering of researchers, veterans with lived experience, clinicians, and policymakers. A CAF member described his lived experience with constant chronic pain. Clinicians described aspects of chronic pain in military personnel and veterans whom they treat in their clinics. Dr. Ramesh Zacharias described the new Chronic Pain Center of Excellence for Canadian Veterans that will be established with funding from Veterans Affairs Canada. Dr. Norman Buckley highlighted collaboration with the existing Chronic Pain Network funded by the Canadian Institute for Health Research. Audience members identified a diverse variety of issues.
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http://dx.doi.org/10.1080/24740527.2020.1796479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951166PMC
September 2020