Publications by authors named "Abhishek Kumar"

622 Publications

Institutional end-of-life care policy for inpatients at a tertiary care centre in India: A way forward to provide a system for a dignified death.

Indian J Med Res 2022 Feb;155(2):232-242

Department of Onco-Anaesthesia & Palliative Medicine, Dr. B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.

India has a high share in the global burden of chronic terminal illnesses. However, there is a lack of a uniform system in providing better end-of-life care (EOLC) for large patients in their terminal stage of life. Institutional policies can be a good alternative as there is no national level policy for EOLC. This article describes the important aspects of the EOLC policy at one of the tertiary care institutes of India. A 15 member institutional committee including representatives from various departments was formed to develop this institutional policy. This policy document is aimed at helping to recognize the potentially non-beneficial or harmful treatments and provide transparency and accountability of the process of limitation of treatment through proper documentation that closely reflects the Indian legal viewpoint on this matter. Four steps are proposed in this direction: (i) recognition of a potentially non-beneficial or harmful treatment by the physicians, (ii) consensus among all the caregivers on a potentially non-beneficial or harmful treatment and initiation of the best supportive care pathway, (iii) initiation of EOLC pathways, and (iv) symptom management and ongoing supportive care till death. The article also focuses on the step-by-step process of formulation of this institutional policy, so that it can work as a blueprint for other institutions of our country to identify the infrastructural needs and resources and to formulate their own policies.
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http://dx.doi.org/10.4103/ijmr.IJMR_902_21DOI Listing
February 2022

TIE-2 Signaling Activation by Angiopoietin 2 On Myeloid-Derived Suppressor Cells Promotes Melanoma-Specific T-cell Inhibition.

Front Immunol 2022 22;13:932298. Epub 2022 Jul 22.

Univ. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte Tumeur/Ingénierie Cellulaire et Génique, Besançon, France.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune suppressive cells detected in several human cancers. In this study, we investigated the features and immune suppressive function of a novel subset of monocytic MDSC overexpressing TIE-2 (TIE-2 M-MDSC), the receptor for the pro-angiogenic factor angiopoietin 2 (ANGPT2). We showed that patients with melanoma exhibited a higher circulating rate of TIE-2 M-MDSCs, especially in advanced stages, as compared to healthy donors. The distribution of the TIE-2 M-MDSC rate toward the melanoma stage correlated with the serum level of ANGPT2. TIE-2 M-MDSC from melanoma patients overexpressed immune suppressive molecules such as PD-L1, CD73, TGF-β, and IL-10, suggesting a highly immunosuppressive phenotype. The exposition of these cells to ANGPT2 increased the expression of most of these molecules, mainly Arginase 1. Hence, we observed a profound impairment of melanoma-specific T-cell responses in patients harboring high levels of TIE-2 M-MDSC along with ANGPT2. This was confirmed by experiments indicating that the addition of ANGPT2 increased the ability of TIE-2 M-MDSC to suppress antitumor T-cell function. Furthermore, by using TIE-2 kinase-specific inhibitors such as regorafenib or rebastinib, we demonstrated that an active TIE-2 signaling was required for optimal suppressive activity of these cells after ANGPT2 exposition. Collectively, these results support that TIE-2 M-MDSC/ANGPT2 axis represents a potential immune escape mechanism in melanoma.
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http://dx.doi.org/10.3389/fimmu.2022.932298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353943PMC
August 2022

Appraising the Phytochemical and Therapeutic Perspectives of Bryonia laciniosa: A Literature Metasynthesis.

Comb Chem High Throughput Screen 2022 Aug 4. Epub 2022 Aug 4.

Department of Pharmacology, KIET School of Pharmacy, KIET Group of Institutions, Ghaziabad, Uttar Pradesh, India.

Background: Nature has bestowed mother Earth with an array of herbals utilized as therapeutics for various human ailments since the origin of life. Bryonia laciniosa (family: Cucurbitaceae) is one such herb which finds its mention in various traditional systems of medicine and has attracted the current researchers due to its significant therapeutic value.

Objective: The current article aims to present a literature metasynthesis on Bryonia laciniosa.

Method: The authors performed the scholarly searches for peer-reviewed findings on Bryonia laciniosa and incorporated all the data related to the phytochemical and therapeutic profile of the drug.

Results: This compilation comprises of Phytochemical and Pharmacological profile of Bryonia laciniosa elaborating its traditional significance and recent researches related to its biological activities. The plant exhibits its potential as antimicrobial, anti-inflammatory, analgesic, antipyretic, anticonvulsant, anti-asthamatic, anticancer, antioxidant, antidiabetic and aphrodiasiac agent. Also displays its benefits in wound healing and ulcerative colitis.

Conclusion: The presence of flavonoids, saponins, terpenoids, anthocyanins, coumarins, alkaloids, polyphenols, tannins and emodins in this plant is responsible for its various pharmacological activities. The retrospective study provides direction for existing research as well as future studies to support the domain of pharmaceutical and medical sciences.
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http://dx.doi.org/10.2174/1386207325666220804113744DOI Listing
August 2022

Balancing the Extent of Resection and Ischemic Complications in Insular Glioma Surgery: Technical Nuances and Proposal of a Novel Composite Postoperative Outcome Index.

Neurol India 2022 May-Jun;70(3):983-991

Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Background: Maximal safe resection remains the most desired goal of insular glioma surgery. Intraoperative surgical adjuncts provide better tumor visualization and real-time "safety" data but remain limited due to a high cost and limited availability.

Objective: To highlight the importance of anatomical landmarks in insular glioma resection and avoidance of vascular complications. We also propose to objectify the onco-functional balance in insular glioma surgery.

Methods: Forty-six insular gliomas operated upon by a single surgeon between January 2015 and February 2020 were reviewed, focusing on the operative technique and clinical outcomes. A novel composite postoperative outcome index (CPOI) was designed, comprising the extent of resection and permanent postoperative deficits, and utilized to assess the surgical outcomes.

Results: Gross-total, near-total, and subtotal resections were achieved in 10.9%, 52.1% (n = 24), and 36.9% (n = 17) patients, respectively. The median overall survival (OS) was 20 months (95% CI = 9.56-30.43). CPOI was optimal in 38 patients (82.6%). A well-defined tumor margin (P = 0.01) and surgeon's experience (P = 0.04) were significantly associated with an optimal CPOI. Out of seven (15.2%) patients who developed permanent neurological deficits, three (6.5%) patients had severe disability. Favorable prognostic factors of survival included younger age (<40 years) (P = 0.002), tumors with only frontal lobe extension (P = 0.011), tumors with caudate head involvement (P = 0.04), and non-glioblastoma histology (P = 0.006).

Conclusion: Tumor margin and increasing surgeon experience are critical to an optimal postoperative outcome. Respecting the basi-sulcal plane is key to lenticulostriate artery preservation. Caudate head involvement is a new favorable prognostic factor in insular gliomas.
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http://dx.doi.org/10.4103/0028-3886.349642DOI Listing
July 2022

Correction for Kumar et al., "Ascorbate Peroxidase, a Key Molecule Regulating Amphotericin B Resistance in Clinical Isolates of Leishmania donovani".

Antimicrob Agents Chemother 2022 Jul 21:e0082922. Epub 2022 Jul 21.

Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciencesgrid.203448.9, Agamkuan, Patna, Bihar, India.

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http://dx.doi.org/10.1128/aac.00829-22DOI Listing
July 2022

Institutional end-of-life care policy for inpatients at a tertiary care centre in India: A way forward to provide a system for a dignified death.

Indian J Med Res 2022 Jul 21. Epub 2022 Jul 21.

Department of Onco-Anaesthesia & Palliative Medicine, Dr. B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.

India has a high share in the global burden of chronic terminal illnesses. However, there is a lack of a uniform system in providing better end-of-life care (EOLC) for large patients in their terminal stage of life. Institutional policies can be a good alternative as there is no national level policy for EOLC. This article describes the important aspects of the EOLC policy at one of the tertiary care institutes of India. A 15 member institutional committee including representatives from various departments was formed to develop this institutional policy. This policy document is aimed at helping to recognize the potentially non-beneficial or harmful treatments and provide transparency and accountability of the process of limitation of treatment through proper documentation that closely reflects the Indian legal viewpoint on this matter. Four steps are proposed in this direction: (i) recognition of a potentially non-beneficial or harmful treatment by the physicians, (ii) consensus among all the caregivers on a potentially non-beneficial or harmful treatment and initiation of the best supportive care pathway, (iii) initiation of EOLC pathways, and (iv) symptom management and ongoing supportive care till death. The article also focuses on the step-by-step process of formulation of this institutional policy, so that it can work as a blueprint for other institutions of our country to identify the infrastructural needs and resources and to formulate their own policies.
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http://dx.doi.org/10.4103/ijmr.IJMR_902_21DOI Listing
July 2022

Chewing and its influence on swallowing, gastrointestinal and nutrition-related factors: a systematic review.

Crit Rev Food Sci Nutr 2022 Jul 14:1-31. Epub 2022 Jul 14.

Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.

The study aimed to evaluate the hypothesis that chewing is a mechanical and physiological contributor to swallowing, physiologic/pathologic processes of the gastrointestinal tract (GIT), and nutrition-related factors. A search strategy was applied to three different databases to investigate if chewing function in adults affects the swallowing, physiologic/pathologic processes of the GIT, and nutrition-related factors compared to controls with no exposure. The included studies were evaluated for methodological quality and risk of bias and certainty of evidence. The results showed 71 eligible studies. Overall, the results showed that 46 studies supported the hypothesis while 25 refuted it. However, the GRADE analysis showed low to very low certainty of the evidence to support the hypothesis that chewing is an important contributor in the swallowing process, and physiologic/pathologic processes in the GIT. The GRADE analysis also showed a moderate to very low certainty of the evidence to suggest that chewing function contributes to nutrition-related parameters. The overall results of the current study showed that a majority (64.7%) of the studies (46 out of 71) supported the hypothesis. However, robust studies with proper design, adequate sample size, and well-defined outcome parameters are needed to establish conclusive evidence.
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http://dx.doi.org/10.1080/10408398.2022.2098245DOI Listing
July 2022

High-Entropy Alloys for Solid Hydrogen Storage: Potentials and Prospects.

Trans Indian Natl Acad Eng 2022 9;7(1):147-156. Epub 2022 Jan 9.

Department of Metallurgical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005 India.

Hydrogen storage is one of the most significant research areas for exploiting hydrogen energy economy. To store hydrogen with a high gravimetric/volumetric density, gaseous hydrogen storage systems require a very high-pressure compressed gas cylinder which is quite unsafe and the storage in the liquid form needs cryogenic containers to be maintained at roughly 20 K under ambient pressure because hydrogen has a very low critical temperature of 33 K. However, hydrogen can be stored in solid materials with higher concentration of hydrogen compared to the gaseous and liquid hydrogen storage systems. It is therefore, worthwhile to look into the experimental and theoretical research on prospective hydrogen storage materials. The hydride-forming alloys and intermetallic compounds are found to be the most important families of hydrogen storage materials. Multicomponent alloys consisting of five or more principal elements, also known as high-entropy alloys appear to have potential for the development as hydrogen storage materials. Hydride-forming elements like Ti, Zr, V, Nb, Hf, Ta, La, Ce, Ni, and others have been shown to have hydrogen storage properties and the ability to produce single-phase high-entropy intermetallics. Here, attempts will be made to present a short review on utilization of multicomponent high-entropy alloys as solid hydrogen storage materials. Furthermore, we will also present some of our work on the synthesis, structural-microstructural characterization and hydrogen storage properties of Ti-Zr-V-Cr-Ni equi-atomic hydride-forming high-entropy alloys. From the preliminary investigation, the maximum storage capacity in this system was observed to be 1.78 wt%, which is comparable to other hydrogen storage materials. The prospects of high-entropy-based alloys for hydrogen storage will be discussed.
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http://dx.doi.org/10.1007/s41403-021-00316-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742883PMC
January 2022

Digital Inequalities in Cancer Care Delivery in India: An Overview of the Current Landscape and Recommendations for Large-Scale Adoption.

Front Digit Health 2022 27;4:916342. Epub 2022 Jun 27.

Institute of Digital Healthcare, WMG, University of Warwick, Coventry, United Kingdom.

Introduction: COVID-19 pandemic has caused major disruptions to delivery of various cancer care services as efforts were put to control the outbreak of the pandemic. Although the pandemic has highlighted the inadequacies of the system but has also led to emergence of a new cancer care delivery model which relies heavily on digital mediums. Digital health is not only restricted to virtual dissemination of information and consultation but has provided additional benefits ranging from support to cancer screening, early and more accurate diagnosis to increasing access to specialized care. This paper evaluates the challenges in the adoption of digital technologies to deliver cancer care services and provides recommendation for large-scale adoption in the Indian healthcare context.

Methods: We performed a search of PubMed and Google Scholar for numerous terms related to adoption of digital health technologies for cancer care during pandemic. We also analyze various socio-ecological challenges-from individual to community, provider and systematic level-for digital adoption of cancer care service which have existed prior to pandemic and lead to digital inequalities.

Results: Despite encouraging benefits accruing from the adoption of digital health key challenges remain for large scale adoption. With respect to user the socio-economic characteristics such as age, literacy and socio-cultural norms are the major barriers. The key challenges faced by providers include regulatory issues, data security and the inconvenience associated with transition to a new system.

Policy Summary: For equitable digital healthcare, the need is to have a participatory approach of all stakeholders and urgently addressing the digital divide adequately. Sharing of health data of public and private hospitals, within the framework of the Indian regulations and Data Protection Act, is critical to the development of digital health in India and it can go a long way in better forecasting and managing cancer burden.
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http://dx.doi.org/10.3389/fdgth.2022.916342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272889PMC
June 2022

Perioperative Radiographic Predictors of Non-Union in Infra-Isthmal Femoral Shaft Fractures after Antegrade Intramedullary Nailing: A Case-Control Study.

J Clin Med 2022 Jun 24;11(13). Epub 2022 Jun 24.

Department of Orthopedics, China Medical University Hospital, Taichung 404327, Taiwan.

Antegrade intramedullary (IM) nailing is the gold standard treatment for femoral shaft fractures; however, the non-union rate of infra-isthmal femoral shaft fractures is still high after antegrade IM nailing. This retrospective case-control study aimed to determine the association between perioperative radiographic factors and the non-union of infra-isthmal femoral shaft fractures after antegrade IM nailing. Univariate and multivariate analyses were used to evaluate the radiographic risk factors of non-union. Ninety-three patients were included, with thirty-one non-unions and sixty-two matched controls between 2007 and 2017. All were regularly followed up for 2 years. Receiver operating characteristic analysis revealed that a ratio of the unfixed distal segment > 32.5% was strongly predictive of postoperative non-union. The risk factors for non-union were AO/OTA type B and C (odds ratio [OR]: 2.20), a smaller ratio of the distal fragment (OR: 4.05), a greater ratio of the unfixed distal segment (OR: 7.16), a higher ratio of IM canal diameter to nail size at the level of fracture (OR: 6.23), and fewer distal locking screws (OR: 2.31). The radiographic risk factors for non-union after antegrade IM nailing for infra-isthmal femoral shaft fractures were unstable fractures, shorter distal fragments, longer unfixed distal fragments, wider IM canal, and fewer distal locking screws. Surgeons must strive to avoid non-union with longer and larger nails and apply more distal locking screws, especially for unstable, wider IM canal, and shorter distal fragment fractures.
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http://dx.doi.org/10.3390/jcm11133664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267532PMC
June 2022

Understanding of the Photodetachment Spectrum of Anionic Mixed Carbon-Boron Cluster CB Following Adiabatic and Nonadiabatic Quantum Chemistry Approaches.

J Phys Chem A 2022 Jul 7;126(28):4563-4576. Epub 2022 Jul 7.

Department of Chemistry, Indian Institute of Technology Patna, Patna 801106, India.

The presence of nonadiabaticity in the photodetachment bands of the anionic mixed carbon-boron cluster CB has been realized through electronic structure calculations and detailed analyses of quantum dynamics study on top of those electronic structures. In the course of our study, we traverse extensive first principles electronic structure calculations to compute potential energy curves and to trace the energetic locations for the conical intersections in the multidimensional surfaces. All the calculations are performed on the four low-lying electronic states of the CB cluster, while quantum nuclear dynamics are pursued on those electronic states by applying both time-dependent and time-independent quantum chemistry frameworks. In particular, we rely on the diabatic electronic representation to construct the molecular Hamiltonian. Altogether, the simulated theoretical spectra offer exceptional agreement with the experimental attainments.
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http://dx.doi.org/10.1021/acs.jpca.2c01683DOI Listing
July 2022

The U-shaped association of post-lung transplant mortality with pretransplant eGFR underscores possible limitations of creatinine-based estimation equations for risk stratification.

J Heart Lung Transplant 2022 Jun 4. Epub 2022 Jun 4.

Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Veterans Affairs Medical Center, Iowa City, Iowa.

Background: Pre-existing chronic kidney disease (CKD) may have an impact on post-lung transplant survival and the development of end stage kidney disease (ESKD).

Methods: We analyzed the US transplant database from 2006 to 2020. Adult patients who received their first lung transplant and were not on dialysis were included. Multivariable Cox regression was used to assess the effect of pretransplant eGFR on mortality and cumulative incidence competing risk was used to explore the effect on ESKD.

Results: The adjusted hazard ratio (aHR) for mortality showed a "U" shaped association with eGFR with a rising mortality at <60 and >100 ml/min/1.73m. The increase in mortality with higher eGFR was only seen in those <30 year and were primarily in whites with a lower body mass index and in patients with cystic fibrosis (CF). The aHR for ESKD increased below an eGFR of 100 rising to 1.74 at an eGFR of 60. Any decrease in eGFR between listing and transplant >10% was associated with higher risk of ESKD.

Conclusions: The U-shaped association of pretransplant eGFR with post-transplant mortality correlated with younger age, lower BMI and a diagnosis of CF. The aHR for ESKD following lung transplantation increased exponentially with worsening eGFR pretransplant.
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http://dx.doi.org/10.1016/j.healun.2022.05.018DOI Listing
June 2022

Characterization of aerosol plumes from singing and playing wind instruments associated with the risk of airborne virus transmission.

Indoor Air 2022 Jun;32(6):e13064

Department of Mechanical Engineering, University of Maryland, College Park, Maryland, USA.

The exhalation of aerosols during musical performances or rehearsals posed a risk of airborne virus transmission in the COVID-19 pandemic. Previous research studied aerosol plumes by only focusing on one risk factor, either the source strength or convective transport capability. Furthermore, the source strength was characterized by the aerosol concentration and ignored the airflow rate needed for risk analysis in actual musical performances. This study characterizes aerosol plumes that account for both the source strength and convective transport capability by conducting experiments with 18 human subjects. The source strength was characterized by the source aerosol emission rate, defined as the source aerosol concentration multiplied by the source airflow rate (brass 383 particle/s, singing 408 particle/s, and woodwind 480 particle/s). The convective transport capability was characterized by the plume influence distance, defined as the sum of the horizontal jet length and horizontal instrument length (brass 0.6 m, singing 0.6 m and woodwind 0.8 m). Results indicate that woodwind instruments produced the highest risk with approximately 20% higher source aerosol emission rates and 30% higher plume influence distances compared with the average of the same risk indicators for singing and brass instruments. Interestingly, the clarinet performance produced moderate source aerosol concentrations at the instrument's bell, but had the highest source aerosol emission rates due to high source airflow rates. Flute performance generated plumes with the lowest source aerosol emission rates but the highest plume influence distances due to the highest source airflow rate. Notably, these comprehensive results show that the source airflow is a critical component of the risk of airborne disease transmission. The effectiveness of masking and bell covering in reducing aerosol transmission is due to the mitigation of both source aerosol concentrations and plume influence distances. This study also found a musician who generated approximately five times more source aerosol concentrations than those of the other musicians who played the same instrument. Despite voice and brass instruments producing measurably lower average risk, it is possible to have an individual musician produce aerosol plumes with high source strength, resulting in enhanced transmission risk; however, our sample size was too small to make generalizable conclusions regarding the broad musician population.
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http://dx.doi.org/10.1111/ina.13064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328346PMC
June 2022

The evolution of performing a kidney biopsy: a single center experience comparing native and transplant kidney biopsies performed by interventional radiologists and nephrologists.

BMC Nephrol 2022 06 25;23(1):226. Epub 2022 Jun 25.

Yale School of Medicine, Section of Nephrology, New Haven, CT, USA.

Background: Kidney biopsy is the most vital tool guiding a nephrologist in diagnosis and treatment of kidney disease. Over the last few years, we have seen an increasing number of kidney biopsies being performed by interventional radiologists. The goal of our study was to compare the adequacy and complication rates between kidney biopsies performed by interventional radiology versus nephrology.  METHODS : We performed a single center retrospective analysis of a total of all kidney biopsies performed at our Institution between 2015 and 2021. All biopsies were performed using real-time ultrasound. Patients were monitored for four hours post biopsy and repeat ultrasound or hemoglobin checks were done if clinically indicated. The entire cohort was divided into two groups (Interventional radiology (IR) vs nephrology) based on who performed the biopsy. Baseline characteristics, comorbidities, blood counts, blood pressure, adequacy of the biopsy specimen and complication rates were recorded. Multivariable logistic regression was used to compare complication rates (microscopic hematuria, gross hematuria and need for blood transfusion combined) between these two groups, controlling for covariates of interest. ANCOVA (analysis of variance, controlling for covariates) was used to compare differences in biopsy adequacy (number of glomeruli per biopsy procedure) between the groups.

Results: 446 kidney biopsies were performed in the study period (229 native and 147 transplant kidney biopsies) of which 324 were performed by IR and 122 by nephrologist. There was a significantly greater number of core samples obtained by IR (mean = 3.59, std.dev. = 1.49) compared to nephrology (mean = 2.47, std.dev = 0.79), p < 0.0001. IR used 18-gauge biopsy needles while nephrologist exclusively used 16-gauge needles. IR used moderate sedation (95.99%) or general anesthesia (1.85%) for the procedures more often than nephrology, which used them only in 0.82% and 0.82% of cases respectively (p < 0.0001). Trainees (residents or fellows) participated in the biopsy procedures more often in nephrology compared to IR (97.4% versus 69.04%, p < 0.0001). The most frequent complication identified was microscopic hematuria which occurred in 6.8% of biopsies. For native biopsies only, there was no significant difference in likelihood of complication between groups, after adjustment for covariates of interest (OR = 1.01, C.I. = (0.42, 2.41), p = 0.99). For native biopsies only, there was no significant difference in mean number of glomeruli obtained per biopsy procedure between groups, after adjustment for covariates of interest (F(1,251) = 0.40, p = 0.53).

Conclusion: Our results suggest that there is no significant difference in the adequacy or complication rates between kidney biopsies performed by IR or nephrology. This conclusion may indicate that kidney biopsies can be performed safely with adequate results either by IR or nephrologists depending on each institution's resources and expertise.
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http://dx.doi.org/10.1186/s12882-022-02860-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233823PMC
June 2022

Valorization of fruit waste-based biochar for arsenic removal in soils.

Environ Res 2022 Oct 18;213:113710. Epub 2022 Jun 18.

Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.

Fruit waste disposal is a serious global problem with only 20% of such waste being routinely treated prior to discharge. Two of the most polluting fruit wastes are orange peel and walnut shell and new methods are urgently required to valorize such waste. In the present study, they where valorized via conversion into biochars at 500 °C (OPB500 for orange peel-based biochar produced at 500 °C and WaSB500 for walnut shell-based biochar produced at 500 °C), and evaluated for arsenic adsorption. A pore-rich surface morphology was observed with a low H/C ratio indicating high stability. Spectroscopic studies revealed the presence of minerals and surface functional groups (amide, carbonyl, carboxyl, and hydroxyl) suggesting high potential for arsenic immobilization. Adsorption studies revealed an arsenic removal efficiency of 88.8 ± 0.04% for WaSB500 exposed to initial arsenic concentration of 8 ppm for 5% biochar dose at 25 °C and 30 min contact time. In comparison, OPB500 showed slightly lower removal efficiency of 80.7 ± 0.1% (10 ppm initial concentration, 5% dose, 25 °C, 90 min contact time). Peak shifts in XRD and FTIR spectra together with isotherm, kinetic, and thermodynamic studies suggested arsenic sequestration was achieved via a combination of chemisorption, physisorption, ion exchange, and diffusion. The present investigation suggests valorization of fruit waste into thermo-stable biochars for sustainable arsenic remediation in dynamic soil/water systems and establishes biochar's importance for waste biomass minimization and metal (loid) removal from fertile soils.
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http://dx.doi.org/10.1016/j.envres.2022.113710DOI Listing
October 2022

A 34-Year-Old Man With Lightheadedness and Dyspnea.

Chest 2022 06;161(6):e371-e376

Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Arkansas for Medical Sciences, Little Rock, AR. Electronic address:

Case Presentation: A 34-year-old man presented to our institution with lightheadedness and dyspnea on exertion. His medical history included chronic pancreatitis, juvenile rheumatoid arthritis (JRA), gastroesophageal reflux disease, hypertension, lumbar degenerative disc disease, seizure disorder, anterior uveitis, and multiple vertebral fractures. In addition, he was a cigarette smoker with a 10-pack-year smoking history.
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http://dx.doi.org/10.1016/j.chest.2022.01.005DOI Listing
June 2022

Silver-catalyzed decarboxylative cyclization for the synthesis of substituted pyrazoles from 1,2-diaza-1,3-dienes and α-keto acids.

Chem Commun (Camb) 2022 Jun 28;58(52):7297-7300. Epub 2022 Jun 28.

Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, UP, India.

A silver-catalyzed decarboxylative cyclization process has been developed for the synthesis of substituted pyrazoles from the readily available 1,2-diaza-1,3-dienes and α-keto acids. Under the optimized conditions, a series of multisubstituted pyrazoles were well prepared in moderate to good yields. In addition, the synthetic utility of this protocol has been demonstrated by synthesizing analogs of FDA approved drugs such as anti-inflammatory drug, lonazolac and antiobesity drug, rimonabant.
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http://dx.doi.org/10.1039/d2cc01793hDOI Listing
June 2022

Signaling Pathway Reporter Screen with SARS-CoV-2 Proteins Identifies nsp5 as a Repressor of p53 Activity.

Viruses 2022 05 13;14(5). Epub 2022 May 13.

Department of Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL 32610, USA.

The dysregulation of host signaling pathways plays a critical role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and viral pathogenesis. While a number of viral proteins that can block type I IFN signaling have been identified, a comprehensive analysis of SARS-CoV-2 proteins in the regulation of other signaling pathways that can be critical for viral infection and its pathophysiology is still lacking. Here, we screened the effect of 21 SARS-CoV-2 proteins on 10 different host signaling pathways, namely, Wnt, p53, TGFβ, c-Myc, Hypoxia, Hippo, AP-1, Notch, Oct4/Sox2, and NF-κB, using a luciferase reporter assay. As a result, we identified several SARS-CoV-2 proteins that could act as activators or inhibitors for distinct signaling pathways in the context of overexpression in HEK293T cells. We also provided evidence for p53 being an intrinsic host restriction factor of SARS-CoV-2. We found that the overexpression of p53 is capable of reducing virus production, while the main viral protease nsp5 can repress the transcriptional activity of p53, which depends on the protease function of nsp5. Taken together, our results provide a foundation for future studies, which can explore how the dysregulation of specific signaling pathways by SARS-CoV-2 proteins can control viral infection and pathogenesis.
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http://dx.doi.org/10.3390/v14051039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145535PMC
May 2022

Ratio of Hydrophobic-Hydrophilic and Positive-Negative Residues at Lipid-Water-Interface Influences Surface Expression and Channel Gating of TRPV1.

J Membr Biol 2022 06 24;255(2-3):319-339. Epub 2022 May 24.

School of Biological Sciences, National Institute of Science Education and Research, Jatni Campus, Bhubaneswar, Orissa, 752050, India.

During evolution, TRPV1 has lost, retained or selected certain residues at Lipid-Water-Interface (LWI) and formed specific patterns there. The ratio of "hydrophobic-hydrophilic" and "positive-negative-charged" residues at the inner LWI remains conserved throughout vertebrate evolution and plays important role in regulating TRPV1 trafficking and localization. Arg575 is an important residue as Arg575Asp mutant has reduced surface expression, co-localization with lipid raft markers, cell area and increased cell lethality. This lethality is most likely due to the disruption of the ratio between positive-negative charges caused by the mutation. Such lethality can be rescued by either using TRPV1-specfic inhibitor 5'-IRTX or by restoring the positive-negative charge ratio at that position, i.e. by introducing Asp576Arg mutation in Arg575Asp backbone. We propose that Arg575Asp mutation confers TRPV1 in a "constitutive-open-like" condition. These findings have broader implication in understanding the molecular evolution of thermo-sensitive ion channels and the micro-environments involved in processes that goes erratic in different diseases. The segment of TRPV1 that is present at the inner lipid-water-interface (LWI) has a specific pattern of amino acid combinations. The overall ratio of +ve charge /-ve charge and the ratio of hydrophobicity/hydrophilicity remain constant throughout the vertebrate evolution (ca 450 million years). This specific pattern is not observed in the outer LWI region of TRPV1.
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http://dx.doi.org/10.1007/s00232-022-00243-zDOI Listing
June 2022

Structure, dynamics, and molecular inhibition of the Staphylococcus aureus mA22-tRNA methyltransferase TrmK.

J Biol Chem 2022 06 17;298(6):102040. Epub 2022 May 17.

School of Biology, Biomedical Sciences Research Complex, University of St Andrews, St Andrews, United Kingdom. Electronic address:

The enzyme mA22-tRNA methyltransferase (TrmK) catalyzes the transfer of a methyl group to the N1 of adenine 22 in bacterial tRNAs. TrmK is essential for Staphylococcus aureus survival during infection but has no homolog in mammals, making it a promising target for antibiotic development. Here, we characterize the structure and function of S. aureus TrmK (SaTrmK) using X-ray crystallography, binding assays, and molecular dynamics simulations. We report crystal structures for the SaTrmK apoenzyme as well as in complexes with methyl donor SAM and co-product product SAH. Isothermal titration calorimetry showed that SAM binds to the enzyme with favorable but modest enthalpic and entropic contributions, whereas SAH binding leads to an entropic penalty compensated for by a large favorable enthalpic contribution. Molecular dynamics simulations point to specific motions of the C-terminal domain being altered by SAM binding, which might have implications for tRNA recruitment. In addition, activity assays for SaTrmK-catalyzed methylation of A22 mutants of tRNA demonstrate that the adenine at position 22 is absolutely essential. In silico screening of compounds suggested the multifunctional organic toxin plumbagin as a potential inhibitor of TrmK, which was confirmed by activity measurements. Furthermore, LC-MS data indicated the protein was covalently modified by one equivalent of the inhibitor, and proteolytic digestion coupled with LC-MS identified Cys92 in the vicinity of the SAM-binding site as the sole residue modified. These results identify a cryptic binding pocket of SaTrmK, laying a foundation for future structure-based drug discovery.
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http://dx.doi.org/10.1016/j.jbc.2022.102040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190014PMC
June 2022

Long-term ecological research and the COVID-19 anthropause: A window to understanding social-ecological disturbance.

Ecosphere 2022 Apr 8;13(4):e4019. Epub 2022 Apr 8.

Warnell School of Forestry and Natural Resources University of Georgia Athens Georgia USA.

The period of disrupted human activity caused by the COVID-19 pandemic, coined the "anthropause," altered the nature of interactions between humans and ecosystems. It is uncertain how the anthropause has changed ecosystem states, functions, and feedback to human systems through shifts in ecosystem services. Here, we used an existing disturbance framework to propose new investigation pathways for coordinated studies of distributed, long-term social-ecological research to capture effects of the anthropause. Although it is still too early to comprehensively evaluate effects due to pandemic-related delays in data availability and ecological response lags, we detail three case studies that show how long-term data can be used to document and interpret changes in air and water quality and wildlife populations and behavior coinciding with the anthropause. These early findings may guide interpretations of effects of the anthropause as it interacts with other ongoing environmental changes in the future, particularly highlighting the importance of long-term data in separating disturbance impacts from natural variation and long-term trends. Effects of this global disturbance have local to global effects on ecosystems with feedback to social systems that may be detectable at spatial scales captured by nationally to globally distributed research networks.
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http://dx.doi.org/10.1002/ecs2.4019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087370PMC
April 2022

Whole exome sequencing identifies novel germline variants of SLC15A4 gene as potentially cancer predisposing in familial colorectal cancer.

Mol Genet Genomics 2022 Jul 13;297(4):965-979. Epub 2022 May 13.

Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

About 15% of colorectal cancer (CRC) patients have first-degree relatives affected by the same malignancy. However, for most families the cause of familial aggregation of CRC is unknown. To identify novel high-to-moderate-penetrance germline variants underlying CRC susceptibility, we performed whole exome sequencing (WES) on four CRC cases and two unaffected members of a Polish family without any mutation in known CRC predisposition genes. After WES, we used our in-house developed Familial Cancer Variant Prioritization Pipeline and identified two novel variants in the solute carrier family 15 member 4 (SLC15A4) gene. The heterozygous missense variant, p. Y444C, was predicted to affect the phylogenetically conserved PTR2/POT domain and to have a deleterious effect on the function of the encoded peptide/histidine transporter. The other variant was located in the upstream region of the same gene (GRCh37.p13, 12_129308531_C_T; 43 bp upstream of transcription start site, ENST00000266771.5) and it was annotated to affect the promoter region of SLC15A4 as well as binding sites of 17 different transcription factors. Our findings of two distinct variants in the same gene may indicate a synergistic up-regulation of SLC15A4 as the underlying genetic cause and implicate this gene for the first time in genetic inheritance of familial CRC.
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http://dx.doi.org/10.1007/s00438-022-01896-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250485PMC
July 2022

We need to do better: Readability analysis of online patient information on cancer survivorship and fertility preservation.

J Cancer Policy 2021 06 9;28:100276. Epub 2021 Feb 9.

Department of Hematology and Oncology, Jacobi Medical Center, Bronx, NY, United States; Albert Einstein College of Medicine, Bronx, NY, United States. Electronic address:

Objective: National Institute of Health recommends that patient education material should be written at no greater than 6-grade level. Cancer survivorship and fertility preservation discussion with patients is recommended by many national societies and being done more frequently. We sought to analyze online patient information on cancer survivorship and fertility preservation to see if they meet the criteria set by national guidelines.

Methods: Online patient information on cancer survivorship and fertility preservation was collected and analyzed by six of the most common readability tests. Only websites in English and free to access were used.

Results: A total of 15 separate websites for cancer survivorship and fertility preservation was used. All websites failed to meet national guidelines. Cancer survivorship information was written at a high school senior and a 12-grade level. Fertility preservation information was written at a high school-senior and junior college level.

Conclusion: Online patient information on cancer survivorship and fertility preservation did not meet national guidelines. Testing across six of the most used readability indexes showed that information is challenging to understand for the general patient population.

Policy Statement: This article shares an insight into the complex and growing fields of cancer survivorship and fertility preservation. Educating patients about their condition is critical and improves outcomes and participation in shared decision making. Healthcare policy should focus on implementing a system that will provide culturally and linguistically appropriate information in the community for patients about their disease.
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http://dx.doi.org/10.1016/j.jcpo.2021.100276DOI Listing
June 2021

Biochemical Characterization of Different Chemical Components of and Their Therapeutic Potential against HIV-1 RT and Microbial Growth.

Biomed Res Int 2022 28;2022:3892352. Epub 2022 Apr 28.

Department of Biochemistry, Faculty of Science, University of Allahabad, Prayagraj 211002, India.

possesses certain allelochemicals responsible for their medicinal effects. The presence of oils, polyphenols, alkaloids, terpenes, pseudoguaianolides, and histamines in has been shown to exhibit medicinal properties. However, the systematic biomedical properties of this plant are still unexplored. The extracts of leaves, stem, and flower of both at low and high temperatures (equivalent to boiling points of different solvents) were prepared. The extracts prepared in hexane, ethylacetate, methanol, and water were analyzed spectrophotometrically and colorimetrically and resolved on TLC for the presence of phytochemicals. The analyses of the free radical quenching potential of plant extracts were done by DPPH assay. The total antioxidant capacity was determined by phosphomolybdate assay and the ferric reducing antioxidant power (FRAP) assay was used to determine the reduction potential of the extracts. The spectrophotometric and qualitative analysis of plant extracts demonstrated the presence of alkaloids, terpenoids, carbohydrates, and cardiac glycosides. The occurrence of more than one Rf values for extracts determined by TLC indicated the presence of more than one phytochemical compound. The extracts contained strong antioxidant activity. These extracts exhibited strong antimicrobial activity against , , or , , and The evaluation of the antimicrobial potential of extracts was done by the disc diffusion method. These extracts also showed significant inhibition against HIV-1 RT activity. The anti-HIV-1 RT activity was done using Roche Kit. The extracts displayed the presence of many phytochemicals with strong antioxidant, antimicrobial, and anti-HIV-1 RT properties.
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http://dx.doi.org/10.1155/2022/3892352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071890PMC
May 2022

Silent Hypoxia in Coronavirus disease-2019: Is it more dangerous? -A retrospective cohort study.

Lung India 2022 May-Jun;39(3):247-253

Department of Onco-anesthesia and Palliative Medicine, All India Institute of Medical Sciences, New Delhi, India.

Background: Hypoxia in patients with COVID-19 is one of the strongest predictors of mortality. Silent hypoxia is characterised by the presence of hypoxia without dyspnoea. Silent hypoxia has been shown to affect the outcome in previous studies.

Methods: This was a retrospective study of a cohort of patients with SARS-CoV-2 infection who were hypoxic at presentation. Clinical, laboratory and treatment parameters in patients with silent hypoxia and dyspnoeic hypoxia were compared. Multivariate logistic regression models were fitted to identify the factors predicting mortality.

Results: Among 2080 patients with COVID-19 admitted to our hospital, 811 patients were hypoxic with SpO <94% at the time of presentation. Among them, 174 (21.45%) did not have dyspnoea since the onset of COVID-19 symptoms. Further, 5.2% of patients were completely asymptomatic for COVID-19 and were found to be hypoxic only on pulse oximetry. The case fatality rate in patients with silent hypoxia was 45.4% as compared to 40.03% in dyspnoeic hypoxic patients (P = 0.202). The odds ratio of death was 1.1 (95% CI: 0.41-2.97) in the patients with silent hypoxia after adjusting for baseline characteristics, laboratory parameters, treatment and in-hospital complications, which did not reach statistical significance (P = 0.851).

Conclusion: Silent hypoxia may be the only presenting feature of COVID-19. As the case fatality rate is comparable between silent and dyspnoeic hypoxia, it should be recognised early and treated as aggressively. Because home isolation is recommended in patients with COVID-19, it is essential to use pulse oximetry in the home setting to identify these patients.
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http://dx.doi.org/10.4103/lungindia.lungindia_601_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200195PMC
April 2022

Quality and Reliability of YouTube Videos on Uterine Fibroid Embolization.

J Am Coll Radiol 2022 Jul 27;19(7):905-912. Epub 2022 Apr 27.

Radiology Site Director, Director of IR Quality Assurance, and Assistant Professor, Department of Radiology, Division of Vascular and Interventional Radiology, Rutgers-New Jersey Medical School, Newark, New Jersey. Electronic address:

Purpose: To evaluate the quality of information available in YouTube videos on the treatment of uterine fibroids.

Materials And Methods: The DISCERN Scale Criterion was used to quantify the quality of YouTube videos on uterine fibroid embolization. The Video Power Index was used to quantify the popularity of videos on uterine fibroid embolization.

Results: Among the 31 videos identified in the study, the average total DISCERN score was 48.82 ± 14.48, indicative of average to poor quality. There was no correlation between a video's popularity and its quality. Popularity, as measured by Video Power Index, was not significantly different between videos containing a board-certified physician and those that did not. Videos with a board-certified interventional radiologist had a significantly lower Video Power Index than those without a board-certified physician.

Conclusion: YouTube is not currently a high-quality source of information for uterine fibroid treatment options. Physicians should be aware of highly viewed material on YouTube to have informed discussions with patients about their treatment options and address misperceptions.
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http://dx.doi.org/10.1016/j.jacr.2022.03.014DOI Listing
July 2022

Effect of apical microsurgery on force regulation of incisor teeth during unpredictable force control task.

J Oral Rehabil 2022 Aug 16;49(8):788-795. Epub 2022 May 16.

Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.

Background: Apical microsurgery (AMS) involves removal of the root-end which can affect the force regulation of teeth.

Objective: To investigate the force regulation of incisor teeth treated with AMS during the unpredictable force control task in comparison with their contralateral teeth with complete root apices, in humans.

Methods: Fifteen eligible participants (8 women and 7 men; mean age 52.9 ± SD 4.4 years) performed a standardised unpredictable force control task, which involved pulling and holding a force transducer with AMS-treated incisors and their contralateral control teeth (n = 30 teeth). A series of four load masses: 100, 200, 50 and 300 gm were attached to the force transducer through a string in an unpredictable manner. The obtained force profile was divided into initial and later time-segments. The peak force and peak force rate during the initial time-segment, and the holding force and coefficient of variability during the later time-segments were calculated and compared by the repeated measures analysis of variance.

Results: During the initial time-segment, the peak force and peak force rate were significantly lower in the AMS-treated teeth than in the controls (p = .001, p = .013, respectively). However, during the later time-segment, no significant differences in the holding force nor the coefficient of variability were observed between the AMS-treated teeth and their controls (p = .755, p = .213, respectively).

Conclusion: In contrast to incisors with complete normal root apices, AMS-treated incisors do not show robust changes in force regulation.
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http://dx.doi.org/10.1111/joor.13334DOI Listing
August 2022

Comparative analysis of contraceptive use in Punjab and Manipur: exploring beyond women's education and empowerment.

BMC Public Health 2022 04 18;22(1):781. Epub 2022 Apr 18.

Population Council, New Delhi, India.

Background: Women's education and empowerment are important predictors of contraceptive use across countries. However, two of the Indian states, namely, Punjab and Manipur, showed large variations in contraceptive use, despite the similar level of women's educational attainment and empowerment. Therefore, this paper attempts to understand variation in contraceptive use between these states, despite having similar level of educational attainment and empowerment among the married women.

Methods: This study primarily used cross-sectional data of the National Family Health Survey (NFHS) 2015-16 and to some extent the District Level Household Survey (DLHS) 2012-13 data. The analytical sample includes 13,730 currently married women in Punjab and 8,872 in Manipur. Modern contraceptive prevalence rate (mCPR) is the key outcome variable of this study. Bivariate, multivariate, and multilevel regression analysis are applied to understand the differences in mCPR between these states and its determinants.

Results: Mean years of schooling was about 8 years among women of both the states, and about 34% of the women in Punjab and 27% of the women in Manipur have high level of autonomy. Despite this, use of modern method was 66% in Punjab and only 13% in Manipur. Coverage of family planning program indicators were significantly lower in Manipur than Punjab - frontline workers' (FLWs) outreach for family planning was only 18% in Manipur compared to 52% in Punjab. Similarly, only 11% of the public health facilities in Manipur compared to 50% of the health facilities in Punjab were ready to provide at least one clinical method of family planning.

Conclusion: Despite the similar level of individual level characteristics across the two states, poor coverage of family planning programs - low outreach of FLWs, low level of facility readiness, as well as sociocultural norms discouraging contraceptive use - might be responsible for lower contraceptive use in Manipur than Punjab. This implies for strengthening the health system for family planning in Manipur to meet the contraception needs of women by addressing sociocultural barriers in the state.
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http://dx.doi.org/10.1186/s12889-022-13147-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016937PMC
April 2022
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