Publications by authors named "N K Jain"

2,574 Publications

  • Page 1 of 1

Cardiac Manifestations in a Case of Severe Hyperkalemia.

Cureus 2021 Mar 1;13(3):e13641. Epub 2021 Mar 1.

Internal Medicine, Louisiana State University Health Sciences Center, New Orleans, USA.

Severe hyperkalemia is a life-threatening electrolyte imbalance that may lead to fatal arrhythmias. ECG (electrocardiogram) and serum potassium levels are vital for diagnosing and stratifying the risk. Management involves shifting potassium intracellularly and eliminating it through renal and gastrointestinal routes. Failure to diagnose early and manage severe hyperkalemia requires emergent hemodialysis.
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http://dx.doi.org/10.7759/cureus.13641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012067PMC
March 2021

Exploration of structural, thermal stability and band-gap tunability of organic and inorganic mixed cation (MA)1-xCsxPbBr3 perovskite harvester via ultrasonication synthesis route.

J Phys Condens Matter 2021 Apr 6. Epub 2021 Apr 6.

Physics, Dr Hari Singh Gour University, Sagar, Sagar, Madhya Pradesh, 470003, INDIA.

Extensive investigation over the last few years has been done on Halide based perovskite light harvester due to higher power conversion efficiency (PCE) but the thermal stability with organic cation i.e. MA is challenging for the commercialization. Therefore, for improved structural and thermal stability, it is significant to develop a mixed cation base perovskite compound. To improve the thermal and structural stability of the material and easy synthesis method for industrialization of the material, we have demonstrated the compositional engineering of MA/CsPbBr3 perovskite material via ultrasonication synthesis process. The X-Ray diffraction, TEM, DRS and simultaneous thermal analyzer (STA) analysis were performed in order to understand the impact of the Cs+ into MAPbBr3 perovskite structure. Structural study reveals that up to 40% Cs+ incorporation into MAPbBr3 has pure Pm-3m cubic phase of perovskite compound with continuously increase in micro strain and lattice contraction. On the other hand, with increasing the concentration of Cs+ than MA+ , optical band gap slightly increases. The thermodynamic behavior and thermal stability of the sample was studied with STA (DSC/TG). For the new generation optoelectronics with admirable stability, we believe that pure phase MA0.60Cs0.40PbBr3 perovskite compound may be a promising candidate.
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http://dx.doi.org/10.1088/1361-648X/abf51dDOI Listing
April 2021

Outcome of patients with chronic myeloid leukemia in lymphoid blastic phase and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with hyper-CVAD and dasatinib.

Cancer 2021 Apr 6. Epub 2021 Apr 6.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Dasatinib monotherapy has demonstrated modest clinical activity in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP). The outcome of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) has dramatically improved with hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) in combination with tyrosine kinase inhibitors (TKIs).

Methods: The authors reviewed 85 patients (23 with CML-LBP and 62 with newly diagnosed Ph-positive ALL) who received hyper-CVAD plus dasatinib.

Results: In the CML-LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML-LBP. The BCR-ABL1 transcript was p210 in 22 patients (96%) and p190 in 1 patient (4%). In the Ph-positive ALL cohort, p210 and p190 transcripts were detected in 13 patients (21%) and 48 patients (77%), respectively. Patients with CML-LBP were less likely to achieve deep molecular remission than patients with Ph-positive ALL: the major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). Survival outcomes were similar for CML-LBP and Ph-positive ALL: the 5-year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML-LBP (5-year OS rate, 88% vs 57%; P = .04). In Ph-positive ALL, the outcome was driven by deeper molecular remission: the 5-year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002).

Conclusions: The outcome of CML-LBP has improved with hyper-CVAD plus dasatinib therapy with survival comparable to that of Ph-positive ALL. Further improvement may be achieved with the use of novel TKIs and targeted agents.
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http://dx.doi.org/10.1002/cncr.33539DOI Listing
April 2021

Revisiting blood agar for the isolation of .

Indian J Sex Transm Dis AIDS 2020 Jul-Dec;41(2):221-222. Epub 2020 Nov 11.

Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.4103/ijstd.IJSTD_51_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000674PMC
November 2020

Left Ventricular Strain: A Reliable Predictor of Short-Term Outcomes in Patients with Anterior Wall Myocardial Infarction without Heart Failure.

Adv Biomed Res 2020 28;9:67. Epub 2020 Nov 28.

Department of Cardiology, King George's Medical University, Lucknow, Uttar Pradesh, India.

Background: Left ventricular ejection fraction (LVEF) is a key determinant in decision-making after acute myocardial infarction (MI). Little is known of its relationship with left ventricular Strain and N-Terminal fragment of pro-B-type Natriuretic Peptide (NT-pro-BNP) following acute anterior wall MI (AWMI).

Materials And Methods: We conducted a prospective cohort study of patients with a diagnosis of acute AWMI and the absence of overt heart failure (HF). Assessment of LVEF, strain parameters on echocardiography was done, and NT-pro-BNP levels were obtained. Follow-up for adverse cardiac events was done for 30 days postdischarge. Correlation of LVEF and NT-pro-BNP with various strain parameters were ascertained.

Results: Of the total of 50 patients of AWMI enrolled, the mean LVEF in the study was 43.46 ± 3.72%.Eleven patients (22%) had adverse events at 30 days of follow-up. Patients with adverse events had significantly higher overall peak systolic longitudinal strain (PSLS), lower mid-region peak systolic longitudinal velocity (PSLV), and basal region PSLV. A significant negative correlation was observed between LVEF and mean Peak PSLS of combined apical plus mid regions of the left ventricle ( = -0.700). Log10-NT-pro BNP also showed a strong negative correlation with overall PSLV ( = -0.792) as well as regional PSLV values of combined apical plus mid ( = -0.763) and basal segments ( = -0.748).

Conclusions: In patients with AWMI without HF, PSLS and PSLV are good predictors of adverse outcomes at 30-day follow-up. Furthermore, NT-pro BNP can also be an indirect predictor of strain parameters on echocardiography.
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http://dx.doi.org/10.4103/abr.abr_213_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012861PMC
November 2020

A review of novel coronavirus disease (COVID-19): based on genomic structure, phylogeny, current shreds of evidence, candidate vaccines, and drug repurposing.

3 Biotech 2021 Apr 27;11(4):198. Epub 2021 Mar 27.

Department of Integrative Biology, School of BioSciences and Technology, Vellore Institute of Technology, Tamil Nadu, Vellore, 632 014 India.

Coronavirus disease (COVID-19) pandemic is instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of March 13, 2021, more than 118.9 million cases were infected with COVID-19 worldwide. SARS-CoV-2 is a positive-sense single-stranded RNA beta-CoV. Most COVID-19 infected individuals recover within 1-3 weeks. Nevertheless, approximately 5% of patients develop acute respiratory distress syndrome and other systemic complications, leading to death. Structural genetic analyses of SARS-CoV-2 have shown genomic resemblances but a low evolutionary correlation to SARS-CoV-1 responsible for the 2002-2004 outbreak. The S glycoprotein is critical for cell adhesion and the entrance of the virus into the host. The process of cell entry uses the cellular receptor named angiotensin-converting enzyme 2. Recent evidence proposed that the CD147 as a SARS-CoV-2's potential receptor. The viral genome is mainly held by two non-structural proteins (NSPs), ORF1a and ORF1ab, along with structural proteins. Although NSPs are conserved among the βCoVs, mutations in NSP2 and NSP3 may play critical roles in transmitting the virus and cell tropism. To date, no specific/targeted anti-viral treatments exist. Notably, more than 50 COVID-19 candidate vaccines in clinical trials, and a few being administered. Preventive precautions are the primary strategy to limit the viral load transmission and spread, emphasizing the urgent need for developing significant drug targets and vaccines against COVID-19. This review provides a cumulative overview of the genomic structure, transmission, phylogeny of SARS-CoV-2 from Indian clusters, treatment options, updated discoveries, and future standpoints for COVID-19.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-02749-0.
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http://dx.doi.org/10.1007/s13205-021-02749-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003899PMC
April 2021

EVALI - E-Cigarette or Vaping Product Use-Associated Lung Injury: A Case Report.

Cureus 2021 Feb 24;13(2):e13541. Epub 2021 Feb 24.

Critical Care Medicine, Mayo Clinic, Mankato, USA.

The use of electronic cigarettes among the young adult and adolescent population has increased over the past decade. Vaping is the process of inhaling an aerosol that is produced by heating a liquid or wax containing substances, such as nicotine, cannabinoids (e.g., tetrahydrocannabinol (THC), cannabidiol), flavoring, and additives (e.g., glycerol, propylene glycol) using an e-cigarette. A multistate epidemic associated with vaping prompted the Centers for Disease Control and Prevention (CDC) to issue an official health advisory on e-cigarette or vaping product use-associated lung injury (EVALI). EVALI is a diagnosis of exclusion with no specific diagnostic test. We present a case of EVALI before the COVID-19 pandemic time in a 23-year-old immunocompetent male student with an eight-year history of vaping. He presented to the emergency department with fever, shortness of breath, tachypnea, nausea, and diarrhea. The patient had no past medical history. The patient denied illicit drug abuse or known drug allergies. The patient was admitted with a diagnosis of sepsis and pneumonia. The patient's urine drug screen was positive for cannabinoids with a history of vaping. Community-acquired pneumonia due to Legionella, Pneumococcal, Mycoplasma bacteria was ruled out. Influenza A/B, Parainfluenza, Rhino, and Adenoviruses were negative. A computed tomographyscan of the chest showed bilateral infiltrates. He was treated with high dose steroids, empiric antibiotics, high flow oxygen and managed in ICU for seven days. The patient was discharged on tapering doses of steroid and counseled to quit vaping. EVALI outbreak is strongly linked to vitamin E acetate in vaping products. EVALI is a diagnosis of exclusion with a history of vaping and responds well to steroids.
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http://dx.doi.org/10.7759/cureus.13541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007202PMC
February 2021

Non-infectious fever in cerebral arteriovenous malformation: Central fever or paroxysmal sympathetic hyperactivity.

Indian J Anaesth 2021 Mar 20;65(Suppl 1):S55-S57. Epub 2021 Mar 20.

Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.4103/ija.IJA_590_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993038PMC
March 2021

Considerations for utilizing medullary sponge kidney allografts in pediatric patients.

Pediatr Transplant 2021 Apr 3:e13992. Epub 2021 Apr 3.

Division of Pediatric Nephrology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

Background: Medullary sponge kidney (MSK) disease predisposes patients to recurrent nephrolithiasis, which affects one in every 5000 people in the United States.

Methods: We report a rare case of a pediatric recipient of a living donor MSK transplant and discuss considerations when discussing risks and benefits of accepting MSK allografts for this population.

Results: The recipient was admitted due to concerns for nephrolithiasis, hydronephrosis, and urinary tract infection at 1-month post-transplant. The hydronephrosis was resolved by surgical removal of an encrusted ureteral stent; this was followed by supplementation with oral medications to prevent future episodes of nephrolithiasis. The recipient did not have any further episodes after this as seen at a 1-year follow-up. The donor has remained well through this period.

Conclusions: With increasing organ shortages, the use of variety of donors may need to be considered to enlarge the organ pool.
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http://dx.doi.org/10.1111/petr.13992DOI Listing
April 2021

Prognostic factors for progression in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in complete molecular response within 3 months of therapy with tyrosine kinase inhibitors.

Cancer 2021 Apr 1. Epub 2021 Apr 1.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: The achievement of a 3-month complete molecular response (CMR) is a major prognostic factor for survival in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, 25% of patients relapse during therapy with tyrosine kinase inhibitors (TKIs).

Methods: The authors reviewed 204 patients with Ph-positive ALL who were treated between January 2001 and December 2018 using the combination of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus a TKI (imatinib, 44 patients [22%]; dasatinib, 88 patients [43%]; or ponatinib, 72 patients [35%]). Progression-free survival (PFS) was defined as the time from the start date of therapy to the date of relapse, death, or last follow-up. Overall survival (OS) was defined as the time from the start date of therapy to the date of death or last follow-up.

Results: Overall, a 3-month CMR was observed in 57% of patients, including 32% of those who received imatinib, 52% of those who received dasatinib, and 74% of those who received ponatinib. The median follow-up was 74 months (imatinib, 180 months; dasatinib, 106 months; ponatinib, 43 months). Among 84 patients in 3-month CMR, 17 (20%) proceeded to undergo allogeneic stem cell transplantation (ASCT). The 5-year PFS and OS rates were 68% and 72%, respectively. By multivariate analysis, ponatinib therapy was the only significant favorable independent factor predicting for progression (P = .028; hazard ratio, 0.388; 95% CI, 0.166-0.904) and death (P = .042; hazard ratio, 0.379; 95% CI, 0.149-0.966). ASCT was not a prognostic factor for PFS and OS by univariate analysis.

Conclusions: In patients with Ph-positive ALL, ponatinib is superior to other types of TKIs in inducing and maintaining a CMR, thus preventing disease progression. ASCT does not improve outcome once a 3-month CMR is achieved.
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http://dx.doi.org/10.1002/cncr.33529DOI Listing
April 2021

Salt-and-Pepper Retinopathy in a Woman With Hearing Loss.

JAMA Ophthalmol 2021 Apr 1. Epub 2021 Apr 1.

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.

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http://dx.doi.org/10.1001/jamaophthalmol.2020.4624DOI Listing
April 2021

Prognostic value of measurable residual disease after venetoclax and decitabine in acute myeloid leukemia.

Blood Adv 2021 Apr;5(7):1876-1883

Department of Leukemia.

Assessment of measurable residual disease (MRD) provides prognostic information in acute myeloid leukemia (AML). However, the utility of MRD with venetoclax-based lower intensity regimens is unknown. We analyzed the prognostic value of achieving a negative MRD in older/"unfit" patients with AML receiving first-line therapy with 10-day decitabine and venetoclax. MRD was evaluated in bone marrow specimens using multicolor flow cytometry (sensitivity 0.1%). Ninety-seven patients achieving either a complete remission (CR) or CR with incomplete hematologic recovery (CRi) or morphologic leukemia-free state were included. Median age was 72 years (interquartile range, 68-78 years), and 64% had adverse-risk AML. Eighty-three patients achieved CR/CRi, and 52 (54%) became MRD negative. Median time to becoming MRD negative was 2.0 months (interquartile range, 0.9-3.1 months). Patients becoming MRD negative by 2 months had longer relapse-free survival (RFS) compared with those remaining MRD positive (median RFS, not reached vs 5.2 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.12-0.78; P = .004), longer event-free survival (EFS) (median EFS, not reached vs 5.8 months; HR, 0.25; 95% CI, 0.12-0.55; P < .001), as well as longer overall survival (OS) (median OS, 25.1 vs 7.1 months; HR, 0.23; 95% CI, 0.11-0.51; P < .001). Patients achieving an MRD-negative CR had longer OS compared with those with an inferior response (median OS, 25.1 vs 11.6 months; HR, 0.33; 95% CI, 0.19-0.58; P < .0005). Patients becoming MRD negative within 1 month had an improved OS compared with MRD-positive patients (median OS, 25.1 vs 3.4 months; HR, 0.15; 95% CI, 0.03-0.64; P < .0001). Differential impact of MRD status on survival outcomes persisted at a later 4-month time point of evaluation. In conclusion, MRD-negative status at 1, 2, and 4 months after starting therapy confers significantly better survival in older/unfit patients with AML receiving first-line therapy with 10-day decitabine and venetoclax. This trial was registered at www.clinicaltrials.gov as #NCT03404193.
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http://dx.doi.org/10.1182/bloodadvances.2020003717DOI Listing
April 2021

Subtype-specific and co-occurring genetic alterations in B-cell non-Hodgkin lymphoma.

Haematologica 2021 Apr 1. Epub 2021 Apr 1.

Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX.

B-cell non-Hodgkin's lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL such as diffuse large B-cell lymphoma (DLBCL) have been comprehensively interrogated at the genomic level. But rarer subtypes such as mantle cell lymphoma (MCL) remain sparsely characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth; including DLBCL, MCL, follicular lymphoma (FL), and Burkitt lymphoma (BL). We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumor from each subtype, including the frequent genetic deregulation of the ubiquitin proteasome system (UPS). In addition, we identified subtype-specific patterns of genetic alterations, including clusters of co-occurring mutations and DNA copy number alterations. The cumulative burden of mutations within a single cluster were more discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic cooperation that contribute to disease etiology. We therefore provide the first cross-sectional analysis of mutations and DNA copy number alterations across major B-NHL subtypes and a framework of co-occurring genetic alterations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis.
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http://dx.doi.org/10.3324/haematol.2020.274258DOI Listing
April 2021

Acalabrutinib in Treatment-Naïve Chronic Lymphocytic Leukemia.

Blood 2021 Mar 30. Epub 2021 Mar 30.

University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States.

Acalabrutinib has demonstrated significant efficacy and safety in relapsed chronic lymphocytic leukemia (CLL). The efficacy and safety of acalabrutinib monotherapy was evaluated in a treatment-naïve CLL cohort of a single-arm phase 1/2 clinical trial (ACE-CL-001). Adults were eligible for enrollment if chemotherapy was declined or deemed inappropriate due to comorbidities (N = 99). Patient demographics included a median age of 64 years and 47% with Rai stage III/IV disease. Acalabrutinib was administered orally either 200 mg once daily (QD) or 100 mg twice daily (BID) until progression or intolerance. A total of 99 patients were treated; 57 (62%) had unmutated immunoglobulin heavy-chain variable gene (IGHV), and 12 (18%) had TP53 aberrations. After a median follow-up of 53 months, 85 patients remain on treatment; 14 patients discontinued treatment, mostly due to adverse events (AEs) (n = 6) or disease progression (n = 3). Overall response rate was 97% (90% partial response; 7% complete response), with similar outcomes among all prognostic subgroups. Due to improved trough BTK occupancy with BID dosing, all patients were transitioned to 100 mg BID. The median duration of response (DOR) was not reached; the 48-month DOR rate was 97% (95% confidence interval [CI], 90%, 99%). Serious AEs were reported in 38 patients (38%). AEs required discontinuation in 6 patients (6%) due to second primary cancers (n = 4) and infection (n = 2). Grade ≥3 events of special interest included infection (15%), hypertension (11%), bleeding events (3%), and atrial fibrillation (2%). The durable efficacy and long-term safety of acalabrutinib in this trial provide support for its use in clinical management of symptomatic, untreated CLL patients.
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http://dx.doi.org/10.1182/blood.2020009617DOI Listing
March 2021

The accuracy of coronary CT angiography in patients with coronary calcium score above 1000 Agatston Units: Comparison with quantitative coronary angiography.

J Cardiovasc Comput Tomogr 2021 Mar 20. Epub 2021 Mar 20.

Department of Imaging, Medicine, Smidt Heart Institute, and Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA. Electronic address:

Background: High amounts of coronary artery calcium (CAC) pose challenges in interpretation of coronary CT angiography (CCTA). The accuracy of stenosis assessment by CCTA in patients with very extensive CAC is uncertain.

Methods: Retrospective study was performed including patients who underwent clinically directed CCTA with CAC score >1000 and invasive coronary angiography within 90 days. Segmental stenosis on CCTA was graded by visual inspection with two-observer consensus using categories of 0%, 1-24%, 25-49%, 50-69%, 70-99%, 100% stenosis, or uninterpretable. Blinded quantitative coronary angiography (QCA) was performed on all segments with stenosis ≥25% by CCTA. The primary outcome was vessel-based agreement between CCTA and QCA, using significant stenosis defined by diameter stenosis ≥70%. Secondary analyses on a per-patient basis and inclusive of uninterpretable segments were performed.

Results: 726 segments with stenosis ≥25% in 346 vessels within 119 patients were analyzed. Median coronary calcium score was 1616 (1221-2118). CCTA identification of QCA-based stenosis resulted in a per-vessel sensitivity of 79%, specificity of 75%, positive predictive value (PPV) of 45%, negative predictive value (NPV) of 93%, and accuracy 76% (68 false positive and 15 false negative). Per-patient analysis had sensitivity 94%, specificity 55%, PPV 63%, NPV 92%, and accuracy 72% (30 false-positive and 3 false-negative). Inclusion of uninterpretable segments had variable effect on sensitivity and specificity, depending on whether they are considered as significant or non-significant stenosis.

Conclusions: In patients with very extensive CAC (>1000 Agatston units), CCTA retained a negative predictive value ​> ​90% to identify lack of significant stenosis on a per-vessel and per-patient level, but frequently overestimated stenosis.
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http://dx.doi.org/10.1016/j.jcct.2021.03.007DOI Listing
March 2021

Nanotechnology Synergised Immunoengineering for Cancer.

Eur J Pharm Biopharm 2021 Mar 24. Epub 2021 Mar 24.

Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, Texas 78504, USA; South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, Texas 78504, USA. Electronic address:

Novel strategies modulating the immune system yielded enhanced anticancer responses and improved cancer survival. Nevertheless, the success rate of immunotherapy in cancer treatment has been below expectation(s) due to unpredictable efficacy and off-target effects from systemic dosing of immunotherapeutic. As a result, there is an unmet clinical need for improving conventional immunotherapy. Nanotechnology offers several new strategies, multimodality, and multiplex biological targeting advantage to overcome many of these challenges. These efforts enable programming the pharmacodynamics, pharmacokinetics, delivery of immunomodulatory agents/co-delivery of compounds to prime at the tumor sites for improved therapeutic benefits. This review provides an overview of the design and clinical principles of biomaterials driven nanotechnology and their potential use in personalized nanomedicines, vaccines, localized tumor modulation, and delivery strategies for cancer immunotherapy. In this review, we also summarize the latest highlights and recent advances in combinatorial therapies avail in the treatment of cold and complicated tumors. It also presents key steps and parameters implemented for clinical success. Finally, we analyse, discuss, and provide clinical perspectives on the integrated opportunities of nanotechnology and immunology to achieve synergistic and durable responses in cancer treatment.
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http://dx.doi.org/10.1016/j.ejpb.2021.03.010DOI Listing
March 2021

Effect of Early Parent Participation Program on Physiological Stability in Preterm Infants: A Randomized Controlled Trial.

Am J Perinatol 2021 Mar 23. Epub 2021 Mar 23.

Department of Neonatology, Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala, India.

Objective:  This research aimed to study the impact of early parent participation program (EPPP) for preterm infants in neonatal intensive care unit (NICU) on physiological instability, breastmilk feeding rates, and discharge timing.

Materials And Methods:  Families of 147 infants born between 28 and 33 weeks' gestation were randomized at birth to EPPP group or conventional care (CC). Families in the EPPP group were trained soon after admission by using a structured education program and encouraged to spend more time with their baby. Soon after enrolment (day of life 1 to 2), they would sequentially participate in daily NICU care processes such as orogastric tube feeding, nesting, oil massages, diaper changes, and daily weight checks. Families in the CC group would undergo the same after their infant was off parenteral nutrition and respiratory support. Proportion of infants having physiological instability (significant apnea, feeding intolerance, or needing investigation for sepsis) in two groups was compared.

Results:  There was a significant reduction in the proportion of infants with physiological instability (feeding intolerance) in the EPPP group (relative risk = 0.70 [0.52-0.94],  = 0.016). Infants in EPPP group had a trend toward higher breastmilk feeding rates at discharge (66 vs. 51%,  = 0.076).

Conclusion:  Very early parent participation was feasible in the NICU and led to decrease in physiological instability in preterm infants.

Key Points: · Family-integrated care is beneficial; however, it is often started later in the NICU course.. · This trial showed that very early involvement of family in NICU care processes is feasible and safe.. · Structured parent participation started very early improves physiological stability in preterm infants (mainly tolerance to feeds)..
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http://dx.doi.org/10.1055/s-0041-1726126DOI Listing
March 2021

Diagnostic Accuracy of Clinical Tool 'STOPS' and Serum Procalcitonin for Optimizing Antibiotic Therapy in Neonates Born at ≥ 28 Weeks of Gestation with Neonatal Sepsis.

Mediterr J Hematol Infect Dis 2021 1;13(1):e2021019. Epub 2021 Mar 1.

Department of Neonatology, Kerala Institute of Medical Sciences, Trivandrum, India.

Background: Antibiotic therapy is initiated in neonates on suspicion of sepsis. Optimizing therapy is a felt need of clinicians as prolonged injudicious use increases mortality and morbidity risk.

Objective: To evaluate the diagnostic accuracy of clinical tool 'STOPS' and serum procalcitonin (PCT) for identifying neonates with early-onset neonatal sepsis (EONS) or late-onset neonatal sepsis (LONS) and early discontinuation in those with no sepsis.

Methods: The study had a prospective analytical design conducted at a tertiary care hospital. Consecutively admitted neonates with suspected EONS or LONS were enrolled. The 'STOPS' tool comprising sensorium, temperature, oxygenation, perfusion, skin color, and blood sugar was applied at 6 and 12 hours of enrollment. Serum PCT was sent at 12 hr. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (PLR and NLR) were estimated.

Results: The study enrolled 380 neonates, of which 330 were given antibiotics for EONS and 50 for LONS. Temperature disturbance in the EONS group at 12 hr showed a PPV of 100% and a PLR of 9.1 (7.7 - 18). Perfusion assessment at 12 hr had a PPV of 77% and PLR of 8.25 (2.3 - 29). Skin color assessment at 12 hr had a PPV of 100% and PLR of 13.5 (9.7 - 27). The diagnostic accuracy of PCT in the EONS group was unremarkable. In the LONS group, skin color at 12 hr had a PPV of 100% and PLR of 11.2 (8.6 - 19.5). The diagnostic accuracy of PCT in the LONS group showed a PPV of 82% and PLR of 7 (1.7 - 29).

Conclusion: Identifying abnormal STOPS parameters was superior to PCT alone in EONS and as good as PCT in LONS. The 'STOPS' tool allows early identification of neonates with no sepsis, thereby optimizing antibiotic use.
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http://dx.doi.org/10.4084/MJHID.2021.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938925PMC
March 2021

STAT3 induces the expression of GLI1 in chronic lymphocytic leukemia cells.

Oncotarget 2021 Mar 2;12(5):401-411. Epub 2021 Mar 2.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The glioma associated oncogene-1 (GLI1), a downstream effector of the embryonic Hedgehog pathway, was detected in chronic lymphocytic leukemia (CLL), but not normal adult cells. GLI1 activating mutations were identified in 10% of patients with CLL. However, what induces GLI1 expression in GLI1-unmutated CLL cells is unknown. Because signal transducer and activator of transcription 3 (STAT3) is constitutively activated in CLL cells and sequence analysis detected putative STAT3-binding sites in the GLI1 gene promoter, we hypothesized that STAT3 induces the expression of GLI1. Western immunoblotting detected GLI1 in CLL cells from 7 of 7 patients, flow cytometry analysis confirmed that CD19+/CD5+ CLL cells co-express GLI1 and confocal microscopy showed co-localization of GLI1 and phosphorylated STAT3. Chromatin immunoprecipitation showed that STAT3 protein co-immunoprecipitated GLI1 as well as other STAT3-regulated genes. Transfection of CLL cells with STAT3-shRNA induced a mark decrease in GLI1 levels, suggesting that STAT3 binds to and induces the expression of GLI1 in CLL cells. An electromobility shift assay confirmed that STAT3 binds, and a luciferase assay showed that STAT3 activates the GLI1 gene. Transfection with GLI1-siRNA significantly increased the spontaneous apoptosis rate of CLL cells, suggesting that GLI1 inhibitors might provide therapeutic benefit to patients with CLL.
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http://dx.doi.org/10.18632/oncotarget.27884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939524PMC
March 2021

Long-term follow-up of salvage therapy using a combination of inotuzumab ozogamicin and mini-hyper-CVD with or without blinatumomab in relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia.

Cancer 2021 Mar 19. Epub 2021 Mar 19.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: The outcome of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. The combination of inotuzumab with low-intensity mini-hyper-CVD (mini-hyper-CVD; cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m × 4 doses) chemotherapy has shown encouraging results. The sequential addition of blinatumomab might improve outcome in patients with R/R ALL.

Methods: We used lower intensity chemotherapy, mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m x 4 doses) compared to conventional hyper-CVAD.

Results: Ninety-six patients with a median age of 37 years (range, 18-87 years) were treated. Overall, 77 patients (80%) responded, 55 (57%) of whom achieved complete response. The overall measurable residual disease negativity rate among responders was 83%. Forty-four (46%) patients underwent later allogeneic stem cell transplantation. Veno-occlusive disease of any grade occurred in 10 (10%) patients. The rates were 13% with the original schedule and 3% with the use of lower-dose inotuzumab and sequential blinatumomab. With a median follow-up of 36 months, the median overall survival (OS) was 13.4 months, with 3-year OS rates of 33%. The 3-year OS rate for patients with CD22 expression ≥70% and without adverse cytogenetics (KMT2A rearrangements, low hypodiploidy/near triploidy) was 55%.

Conclusion: The combination of inotuzumab and low-intensity mini-hyper-CVD chemotherapy with or without blinatumomab shows sustained efficacy in patients with R/R ALL.
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http://dx.doi.org/10.1002/cncr.33469DOI Listing
March 2021

Pentosan polysulfate maculopathy versus age-related macular degeneration: comparative assessment with multimodal imaging.

Can J Ophthalmol 2021 Mar 12. Epub 2021 Mar 12.

Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA. Electronic address:

Objective: To evaluate whether pentosan polysulfate maculopathy manifests distinctive imaging features that can be differentiated from those found in age-related macular degeneration (AMD).

Methods: Local databases were queried to identify patients with a diagnosis of interstitial cystitis who were seen at the Emory Eye Center between May 2014 and January 2019 and who had fundus imaging available for review. Ninety patients met the eligibility criteria. Masked graders categorized patients based on imaging characteristics as follows: category 1: pentosan polysulfate maculopathy; category 2: AMD or drusen; category 3: neither; and category 4: unsure. Pentosan polysulfate exposure characteristics were compared among groups.

Results: Of the 90 subjects evaluated, 79 (88%) were female and the median age was 61.5 years (range, 30-89). Seventeen patients were placed in category 1; 25 in category 2; 47 in category 3, and; 1 in category 4. Among categories 1 to 4, respectively, 17 (100%), 15 (60%), 28 (60%), and 0 patients had exposure to pentosan polysulfate (p = 0.007). Mean cumulative exposure to pentosan polysulfate across the four categories was 2.1, 0.36, 0.34, and 0 kg, respectively (p < 0.00001). Eyes with pentosan polysulfate maculopathy did not have typical drusen in the macula.

Conclusion: Although pentosan polysulfate maculopathy resembles some aspects of AMD, the two conditions can be differentiated with the use of multimodal fundus imaging.
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http://dx.doi.org/10.1016/j.jcjo.2021.02.007DOI Listing
March 2021

Characteristics of ambulatory spine care visits in the United States, 2009-2016.

J Back Musculoskelet Rehabil 2021 Mar 5. Epub 2021 Mar 5.

Department of Physical Medicine and Rehabilitation, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Back pain is a leading reason for seeking care in the United States (US), and is a major cause of morbidity.

Objective: To analyze demographic, patient, and visit characteristics of adult ambulatory spine clinic visits in the United States from 2009-2016.

Methods: Data from the National Ambulatory Medical Care Survey from 2009-2016 were used and were sample weighted.

Results: Most patients presenting for ambulatory spine care were 45-64 years (45%), were most commonly female (56.8%), and private insurance (45%) and Medicare (26%) were most common payors. The percentage of visits for spine care done at a primary care setting was 50.1% in 2009-2010 and 48.3% in 2014-2015. Approximately 15.5% were seen in orthopedic surgery clinics in 2009-2010 and 7.3% in 2015-2016. MRI was utilized in 11.7% in 2009-2010 and 11.0% in 2015-2016. Physical therapy was prescribed in 13.2% and narcotic analgesic medications were prescribed in 36.2% of patients in 2015-2016.

Conclusions: MRI was used more frequently than guidelines recommended, and physical therapy was less frequently utilized despite evidence. A relatively high use of opiates in treatment of back pain was reported and is concerning. Although back pain represents a substantial public health burden in the United States, the delivery of care is not evidence-based.
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http://dx.doi.org/10.3233/BMR-200145DOI Listing
March 2021

Airway in the Airway.

Turk J Anaesthesiol Reanim 2021 Feb 24;49(1):90-91. Epub 2020 Dec 24.

Department of Anaesthesiology and Critical Care, All India Institute of Medical Sciences (AIIMS), Jodhpur, Rajasthan, India.

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http://dx.doi.org/10.5152/TJAR.2020.210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932710PMC
February 2021

Acute lymphoblastic leukemia: A population- based study of outcome in the United States based on the surveillance, epidemiology, and end results (SEER) database, 1980-2017.

Am J Hematol 2021 Mar 11. Epub 2021 Mar 11.

Department of Leukemia, U.T. M.D. Anderson Cancer Center, Houston, Texas.

The treatment in acute lymphoblastic Leukemia (ALL) has evolved and improved dramatically over the past four decades. We assessed the outcome of ALL overall, and the two major subsets of Philadelphia chromosome (Ph)-positive and Ph-negative ALL by age, time periods, ethnicity, median household income, and geographic county area. A total of 12 788 patients diagnosed with ALL from 1980 to 2017 were included. We performed an analysis to better evaluate the outcome evolution in ALL according to time period and patient's demographic factors. The overall 5-year survival rates have improved significantly over time, from 51% before 1990 to 72% since 2010. The survival rates for children (age 0 to 14 years) and adolescents (age 15 to 19 years) have improved from 73% and 55% before 1990 to 93% and 74% since 2010, respectively. Similarly, the rates had improved from 33% to 59% for adults 20 to 29 years old, 24% to 59% for 30 to 39 years old, and 14% to 43% for 40 to 59 years old between the two time periods. The rates remained under 30% in older patients (60+ years). Since 2010, patients with Ph-negative ALL had 5-year survival rate of 73% and those with Ph-positive ALL 50%. African Americans, Hispanic ethnicity, and lower household income were associated with inferior survival. The outcome of patients with ALL showed continued improvement across all age groups in the US. The recent introduction of targeted therapies, together with optimized supportive care, will continue to improve outcomes, particularly in older patients.
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http://dx.doi.org/10.1002/ajh.26156DOI Listing
March 2021

Responses of juvenile fathead minnow (Pimephales promelas) gut microbiome to a chronic dietary exposure of benzo[a]pyrene.

Environ Pollut 2021 Feb 25;278:116821. Epub 2021 Feb 25.

Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Department of Environmental Science, Baylor University, Waco, TX, USA.

The microbiome has been described as an additional host "organ" with well-established beneficial roles. However, the effects of exposures to chemicals on both structure and function of the gut microbiome of fishes are understudied. To determine effects of benzo[a]pyrene (BaP), a model persistent organic pollutant, on structural shifts of gut microbiome in juvenile fathead minnows (Pimephales promelas), fish were exposed ad libitum in the diet to concentrations of 1, 10, 100, or 1000 μg BaP g food, in addition to a vehicle control, for two weeks. To determine the link between exposure to BaP and changes in the microbial community, concentrations of metabolites of BaP were measured in fish bile and 16S rRNA amplicon sequencing was used to evaluate the microbiome. Exposure to BaP only reduced alpha-diversity at the greatest exposure concentrations. However, it did alter community composition assessed as differential abundance of taxa and reduced network complexity of the microbial community in all exposure groups. Results presented here illustrate that environmentally-relevant concentrations of BaP can alter the diversity of the gut microbiome and community network connectivity.
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http://dx.doi.org/10.1016/j.envpol.2021.116821DOI Listing
February 2021

Patient Perceptions of SARS-CoV-2 Exposure Risk and Association With Continuity of Ophthalmic Care.

JAMA Ophthalmol 2021 Mar 11. Epub 2021 Mar 11.

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.

Importance: Patient perceptions regarding the risks of obtaining in-person ophthalmic care during the coronavirus disease 2019 (COVID-19) pandemic may affect adherence to recommended treatment plans and influence visual outcomes. A deeper understanding of patient perspectives will inform strategies to optimize adherence with vision-preserving therapies.

Objective: To evaluate perceptions of COVID-19 exposure risk and their association with appointment attendance among patients at high risk of both reversible and irreversible vision loss from lapses in care.

Design, Setting, And Participants: This survey study included a nonvalidated telephone survey designed in April and May of 2020 and a retrospective medical record review conducted in parallel with survey administration from May 22 to August 18, 2020. Participants were recruited from 2 tertiary eye care centers (Emory Eye Center in Atlanta, Georgia, and W.K. Kellogg Eye Center in Ann Arbor, Michigan). The study included a random sample of patients with diagnoses of exudative age-related macular degeneration (AMD) or diabetic retinopathy (DR) who received an intravitreal injection between January 6 and March 13, 2020, and were scheduled for a second injection between March 13 and May 6, 2020.

Main Outcomes And Measures: Association between perceptions regarding COVID-19 risks and loss to follow-up.

Results: Of 1004 eligible patients, 423 (42%) were successfully contacted, and 348 (82%) agreed to participate (participants' mean [SD] age, 75 [12] years; 195 women [56%]; 287 White [82%] patients). Respondents had a mean (SD) of 2.7 (1.1) comorbidities associated with severe COVID-19, and 77 (22%) knew someone with COVID-19. Of all respondents, 163 (47%) were very concerned or moderately concerned about vision loss from missed treatments during the pandemic. Although 208 (60%) believed the COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exposure at the eye clinic was extremely unlikely or unlikely, 49 (14%) believed it was extremely likely or likely. Seventy-eight participants (22%) were lost to follow-up. Concern regarding COVID-19 exposure during clinic visits (odds ratio [OR], 3.9; 95% CI, 1.8-8.4) and diagnosis of DR (vs AMD) (OR, 8.130; 95% CI, 3.367-20.408) were associated with an increase in likelihood of loss to follow-up.

Conclusions And Relevance: Among patients at high risk for vision loss from lapses in care, many expressed concerns regarding the effect of the pandemic on their ability to receive timely care. Survey results suggest that fear of SARS-CoV-2 exposure was associated with a roughly 4-fold increase in the odds of patient loss to follow-up. These results support the potential importance of clearly conveying infection-control measures.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.0114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953331PMC
March 2021

Long-term outcomes in patients with advanced adrenocortical carcinoma after image-guided locoregional ablation or embolization.

Cancer Med 2021 Apr 9;10(7):2259-2267. Epub 2021 Mar 9.

Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institute of Biomedical Imaging and Bioengineering and National Cancer Institute Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA.

Background: To evaluate outcomes and survival rates in patients with metastatic adrenocortical carcinoma (ACC) who were treated with image-guided locoregional treatments (IGLTs).

Purpose: To evaluate the overall survival (OS) and clinical impact of IGLT in the management of patients with advanced metastatic ACC.

Methods: Retrospective review of 39 patients treated with IGLT between 1999 and 2018 was performed. Short- and long-term efficacy of treatments were defined based upon imaging and clinical data. Subgroup survival analysis was performed on patients with metastatic disease at diagnosis (N = 17) and compared with the same stage group from the most recent National Cancer Database (NCDB) report. Statistical analysis was performed using Cox proportional hazards model.

Results: Treatments were performed at different anatomic sites including liver (N = 46), lung (N = 14), retroperitoneum (N = 5), bone (N = 4), subcutaneous (N = 2), and intracaval (N = 1). Radiofrequency, microwave, cryoablation, or a combination of two modalities (45, 18, 3, 3, respectively) were used in 69 ablation sessions. Intra-arterial procedures were performed in 12 patients in 18 treatment cycles (range 1-3 per patient). As of a 2019 analysis, 11 patients were alive with a mean follow-up of 169 months (range 63-292 months) from diagnosis. Two- and 5-year OS rates for all patients were 84.5% and 51%, respectively, and 76.5% and 59% for patients with metastatic disease at diagnosis (N = 17). This compares favorably with an NCDB report of 35% 5-year survival rate for patients with metastatic disease. Female gender and longer time from diagnosis to first IGLT were found to be predictors of prolonged survival with hazard ratios of 0.23 (p < 0.001) and 0.66 (p = 0.001), respectively.

Conclusion: IGLT may be associated with prolonged life expectancy in select patients with metastatic ACC.
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http://dx.doi.org/10.1002/cam4.3740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982621PMC
April 2021

Quality evaluation of near-isogenic line of the wheat variety HD2733 carrying the genomic region.

3 Biotech 2021 Mar 18;11(3):130. Epub 2021 Feb 18.

Division of Genetics, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India.

A near-isogenic line (NIL) of the Indian wheat variety HD2733, carrying an introgressed genomic region was used for studying the effect of this introgression on quality traits. Data on the grain yield and 21 quality traits were recorded in this NIL and its recurrent parent (RP), both of which were grown in a randomized block design for two consecutive years. The statistical analysis revealed that grain yield was on par between the NIL and the RP. The NIL and its RP were both hard grained but the NIL showed a grain hardness index reduced by 9.7%. However, quality traits such as grain weight, protein content, sedimentation value, gluten traits, and solvent retention capacity were significantly higher in the NIL. The NIL also showed an increase in dough stability a lower degree of softening and a higher farinograph quality number. These results indicated that the NIL could be utilized for hard grain, high protein and strong gluten-based products. An overall improvement in the quality of the NIL over its recurrent parent and without any yield penalty suggests that the genomic region could be gainfully utilized in wheat breeding for improving the industrial quality of wheat without jeopardising grain yield. The authors suggest that the improved quality of the NIL may be due to the genomic segment carried along with the genes.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-02679-x.
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http://dx.doi.org/10.1007/s13205-021-02679-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892657PMC
March 2021