Publications by authors named "Muhammad Tariq"

455 Publications

A recessive variant in TFAM causes mtDNA depletion associated with primary ovarian insufficiency, seizures, intellectual disability and hearing loss.

Hum Genet 2021 Oct 13. Epub 2021 Oct 13.

Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.

Mitochondrial disorders are collectively common, genetically heterogeneous disorders in both pediatric and adult populations. They are caused by molecular defects in oxidative phosphorylation, failure of essential bioenergetic supply to mitochondria, and apoptosis. Here, we present three affected individuals from a consanguineous family of Pakistani origin with variable seizures and intellectual disability. Both females display primary ovarian insufficiency (POI), while the male shows abnormal sex hormone levels. We performed whole exome sequencing and identified a recessive missense variant c.694C > T, p.Arg232Cys in TFAM that segregates with disease. TFAM (mitochondrial transcription factor A) is a component of the mitochondrial replisome machinery that maintains mtDNA transcription and replication. In primary dermal fibroblasts, we show depletion of mtDNA and significantly altered mitochondrial function and morphology. Moreover, we observed reduced nucleoid numbers with significant changes in nucleoid size or shape in fibroblasts from an affected individual compared to controls. We also investigated the effect of tfam impairment in zebrafish; homozygous tfam mutants carrying an in-frame c.141_149 deletion recapitulate the mtDNA depletion and ovarian dysgenesis phenotypes observed in affected humans. Together, our genetic and functional data confirm that TFAM plays a pivotal role in gonad development and expands the repertoire of mitochondrial disease phenotypes.
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http://dx.doi.org/10.1007/s00439-021-02380-2DOI Listing
October 2021

Treatment and outcomes of soft tissue sarcoma of groin, hip and thigh: a retrospective review from a tertiary care hospital.

J Pak Med Assoc 2021 Aug;71(Suppl 5)(8):S75-S78

Aga Khan University Hospital, Karachi, Pakistan.

Objective: To study the frequency of the thigh, hip and groin soft tissue sarcomas and retrospectively analyse the management, treatment results, and outcomes of these uncommon malignant tumours, in a tertiary care hospital of the city of Karachi.

Methodology: Data of soft tissue tumours registered from 2017-2018 was retrieved during January 2019 to March 2019 from Aga Khan University Hospital, Karachi bone and soft tissue tumour registry. A retrospective review was performed and all soft tissue tumour cases treated with surgical intervention (with adjuvant /neoadjuvant therapy) or palliative intention were included.

Results: Total 119 cases of soft tissue tumours (STS) were identified out of which 85 were malignant cases (sarcomas) while 30 were benign. On presentation 84 (70.6%) were primary cases. On topographical distribution, there were 25 patients who had hip, groin and thigh sarcoma. Of these, 15 were males and 10 were females. As treatment, neo-adjuvant radiation was done in 4 (16%) patients and adjuvant chemo/radio therapy was given to 13 (52%) patients. Wide margin excision was performed in 19 (76%) patients and 4 (16%) had amputation. Reconstruction was offered to 3 (12%) patients. In post-surgical complications, 1 (4%) patient had wound infection. On final surgical histopathology, majority of the sarcomas were liposarcomas, myxofibrosarcoma, synovial sarcoma and Leiomyosarcoma. Post-surgery recurrence occurred in 7 (28%) patients. Overall survival was 76%.

Conclusions: In treatment of soft tissue sarcoma, limb salvage is an achievable option and survival results are also good.
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August 2021

Improved and Secured Electromyography in the Internet of Health Things.

IEEE J Biomed Health Inform 2021 Oct 8;PP. Epub 2021 Oct 8.

Physiological signals are of great importance for clinical analysis but are prone to diverse interferences. To enable practical applications, biosignal quality issues, especially contaminants, need to be dealt with automated processes. For example, after processing surface electromyography (sEMG), fatigue analysis can be done by looking into muscle contraction and expansion for clinical diagnosis. Contaminants can make this diagnosis difficult for the clinician. In real scenarios, there is a possibility of the presence of multiple contaminants in a biosignal. However, most of the work done until now focuses on the presence of a single contaminant at a time. This paper proposes a new method for the identification and classification of contaminants in sEMG signals where multiple contaminants are present simultaneously. We train a 1D convolutional neural network (1D-CNN) to classify different contaminant types in sEMG signals without prior feature extraction. The network is trained on simulated and real sEMG signals to identify five types of contaminants. Additionally, we train and test 1D-CNN to identify multiple contaminants when present simultaneously. Furthermore, to securely transfer the data to the clinician, we also present experimental results to secure the Internet of health things (IoHT) by using received signal strength indicators (RSSI) to generate link fingerprints (LFs). The results show higher accuracy of the classification system at low signal-to-noise ratios (SNR) and witness lightweight security of the WHMS.
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http://dx.doi.org/10.1109/JBHI.2021.3118810DOI Listing
October 2021

Inter-Subunit Dynamics Controls Tunnel Formation During the Oxygenation Process in Hemocyanin Hexamers.

Front Mol Biosci 2021 15;8:710623. Epub 2021 Sep 15.

UCL School of Pharmacy, London, United Kingdom.

Hemocyanin from horseshoe crab in its active form is a homo-hexameric protein. It exists in open and closed conformations when transitioning between deoxygenated and oxygenated states. Here, we present a detailed dynamic atomistic investigation of the oxygenated and deoxygenated states of the hexameric hemocyanin using explicit solvent molecular dynamics simulations. We focus on the variation in solvent cavities and the formation of tunnels in the two conformational states. By employing principal component analysis and CVAE-based deep learning, we are able to differentiate between the dynamics of the deoxy- and oxygenated states of hemocyanin. Finally, our results identify the deoxygenated open conformation, which adopts a stable, closed conformation after the oxygenation process.
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http://dx.doi.org/10.3389/fmolb.2021.710623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479113PMC
September 2021

Frequency and Association of Stress Levels with Modes of Commuting Among Medical Students of a Developing Country.

Malays J Med Sci 2021 Aug 26;28(4):113-122. Epub 2021 Aug 26.

Department of Community Health Sciences, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan.

Introduction: This study aimed at determining the frequency and association of stress levels with modes of transportation and was likely to reveal the contributing transportation-related factors for stress in medical students.

Methods: This was a questionnaire-based, cross-sectional study that included undergraduate medical students of a public sector medical university in Karachi, Pakistan. A total of 573 students participated voluntarily, of which 300 were provided a manual questionnaire and 273 filled it online. The reliability of the questionnaire was assessed using Cronbach's alpha at 0.791. The collected data were analysed using IBM SPSS Statistics for Windows, version 21.0.

Results: Out of 573 participants, 99.3% = 298) of students filled the questionnaire manually, whereas 100% of students filled the questionnaire online. Almost two-thirds of students used university transport; more than 90% lived more than 5 km from the university and 56% had a traveling time of more than an hour. Approximately 15.4% of students reported physical trauma and some form of harassment. Sheldon Cohen's stress scale surprisingly revealed 90% of students to be within the moderate-to-high stress category. Risk factors were associated with stress levels and significant associations were observed with noise exposure ( = 0.023) and sleep quality ( = 0.001). The most common reported stressors associated with commuting included overcrowding, long travel, and air and noise pollution. Noise pollution was the main predictor of stress among commuters.

Conclusion: Poor transportation has adverse effects on health and academic performance. Administration in their respective jurisdictions is needed to investigate this matter to make commuting a routine rather than a hassle.
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http://dx.doi.org/10.21315/mjms2021.28.4.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407788PMC
August 2021

SiO/AlO/C grafted 3-n propylpyridinium silsesquioxane chloride-based non-enzymatic electrochemical sensor for determination of carcinogenic nitrite in food products.

Food Chem 2021 Sep 1;369:130970. Epub 2021 Sep 1.

Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS University Islamabad, Lahore Campus, Defence Road, Off Raiwind Road Lahore, 54000, Pakistan. Electronic address:

The excessive uptake of nitrite is perilous and detrimental for human health that prone to cancer disease. Herein, described the synthesis of SiO/AlO/C material through the sol-gel procedure followed by grafting with 3-n propylpyridinium silsesquioxane chloride organic ligand for enhancing electrochemical activity. H-NMR, C NMR, and Si studies were performed for confirmation of surface functionalization through the grafting technique. The surface morphology was evaluated through SEM and TEM techniques. The material showed an irregular and flakes-like structure that exhibited more compactness and conglomerate structure with no segregation in phase was observed after grafting. The elemental composition was confirmed from EDX analysis. The electrochemical measurements were performed with cyclic voltammetry, electrochemical impedance spectroscopy (EIS), and chronoamperometry. The prepared hybrid inorganic-organic composite Si/C/Al/SiPyCl was applied for the modification of the glassy carbon (GC) electrode and assessed as a sensor for nitrite determination. The sensor showed the low limit of detection (0.01 μM), low limit of quantification (0.08 μM), wide linear response range (0.2-280 μM), and high sensitivity (410 μA·μM). It gave a quick response time of <1 s in the presence of 70 μM nitrite. The fabricated sensor showed high sensitivity, chemical stability, and insignificant interference from co-existing species present in sausage meat and food industry discharges. The repeatability of the sensor was evaluated as 2.5 % R.S.D.; for n = 10 at 50 μM nitrite.
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http://dx.doi.org/10.1016/j.foodchem.2021.130970DOI Listing
September 2021

Concomitant bilateral mandibular cemento-ossifying fibroma and cementoblastoma: case report of an extremely rare occurrence.

BMC Oral Health 2021 09 7;21(1):437. Epub 2021 Sep 7.

Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan.

Background: Cemento-ossifying fibroma (COF) and cementoblastoma (CB) are rare benign odontogenic tumors with a predilection for the mandible. Cemento-ossifying fibroma is a fibro-osseous lesion that originates in the tooth bearing areas of jaw and shows cementum-like tissue in a fibrotic stroma. Cementoblastoma is classically related to roots of teeth with the presence of calcified cementum-like material. To date, only a single case of concomitant unilateral COF and CB has been reported in the literature.

Case Presentation: We present an unusual case of a 37-year-old female who presented with two discrete bilateral swellings in the right and left mandible for 10 years. The larger tumor involved the left posterior mandible with extension anteriorly to the left and right anterior mandibles, and the smaller tumor was present in right posterior mandible. Radiology revealed two distinct lesions involving both sides of mandible. Histopathological examination showed characteristic features of cemento-ossifying fibroma in sections of the larger tumor and cementoblastoma in sections of smaller tumor.

Conclusion: This case shows the very unique bilateral co-existence of COF and CB, the second case reported in literature to date.
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http://dx.doi.org/10.1186/s12903-021-01794-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425131PMC
September 2021

Unveiling the catalytic ability of carbonaceous materials in Fenton-like reaction by controlled-release CaO nanoparticles for trichloroethylene degradation.

J Hazard Mater 2021 08 24;416:125935. Epub 2021 Apr 24.

State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, Shanghai 200237, China. Electronic address:

Carbonaceous materials (CMs) have been applied extensively for enhancing the catalytic performance of environmental catalysts, however, the self-catalytic mechanism of CMs for groundwater remediation is rarely investigated. Herein, we unveiled the catalytic ability of various CMs via Fe(III) reduction through polyvinyl alcohol-coated calcium peroxide nanoparticles ([email protected]) for trichloroethylene (TCE) removal. Among selected CMs (graphite (G), biochar (BC) and activated carbon (AC)), BC and AC showed enhancement of TCE removal of 89% and 98% via both adsorption and catalytic degradation. BET and SEM analyses showed a higher adsorption capacity of AC (27.8%) than others. The generation of solution-Fe(II) and surface-Fe(II) revealed the reduction of Fe(III) on CMs-surface. The role of O-containing groups was investigated by the FTIR technique and XPS quantified the 52% and 57% surface-Fe(II) in BC and AC systems, respectively. EPR and quenching tests confirmed that both solution and surface-bound species (HO•, O• and O) contributed to TCE degradation. Acidic pH condition encouraged TCE removal and the presence of HCO negatively affected TCE removal than other inorganic ions. Both schemes ([email protected]/Fe(III)/BC and [email protected]/Fe(III)/AC) exhibited promising results in the actual groundwater, surfactant-amended solution, and removal of other chlorinated-pollutants, opening a new direction towards green environmental remediation for prolonged benefits.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125935DOI Listing
August 2021

Aggrandizement of fermented cucumber through the action of autochthonous probiotic cum starter strains of and .

Ann Microbiol 2021 31;71(1):33. Epub 2021 Aug 31.

National Probiotic Laboratory, National Institute for Biotechnology and Genetic Engineering College (NIBGE-C), Faisalabad, 38000 Pakistan.

Purpose: Cucumber fermentation is traditionally done using lactic acid bacteria. The involvement of probiotic cultures in food fermentation guarantees enhanced organoleptic properties and protects food from spoilage.

Methods: Autochthonous lactic acid bacteria were isolated from spontaneously fermented cucumber and identified to species level. Only strains adjudged as safe for human consumption were examined for their technological and functional characteristics. Strain efficiency was based on maintaining high numbers of viable cells during simulated GIT conditions and fermentation, significant antioxidant activity, EPS production, nitrite degradation, and antimicrobial ability against Gram-positive and Gram-negative foodborne pathogens.

Result: Two strains, NPL 1258 and NPL 1264, showing a suite of promising functional and technological attributes, were selected as a mixed-species starter for carrying out a controlled lactic acid fermentations of a native cucumber variety. This consortium showed a faster lactic acid-based acidification with more viable cells, at 4% NaCl and 0.2% inulin (w/v) relative to its constituent strains when tested individually. Sensory evaluation rated the lactofermented cucumber acceptable based on texture, taste, aroma, and aftertaste.

Conclusion: The results suggest that the autochthonous LAB starter cultures can shorten the fermentation cycle and reduce pathogenic organism' population, thus improving the shelf life and quality of fermented cucumber. The development of these new industrial starters would increase the competitiveness of production and open the country's frontiers in the fermented vegetable market.
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http://dx.doi.org/10.1186/s13213-021-01645-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406656PMC
August 2021

Gibberellic acid and urease inhibitor optimize nitrogen uptake and yield of maize at varying nitrogen levels under changing climate.

Environ Sci Pollut Res Int 2021 Aug 28. Epub 2021 Aug 28.

Department of Agronomy, The University of Agriculture, Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan.

Worldwide, nitrogen (N) deficiency is the main yield limiting factor owing to its losses via leaching and volatilization. Urease inhibitors slow down urea hydrolysis in soil by inhibiting urease enzyme activities whereas gibberellic acid is growth regulator. That is why, we evaluated the role of urease inhibitor [N-(n-butyl)thiophosphorictriamide (NBPT)] and gibberellic acid (GA) in improving nitrogen uptake and yield of maize under different N levels (120 and 150 kg ha) along with control. Both N levels alone and in combination with GA and NBPT significantly increased yield and yield components of maize over control. In addition, 150 kg N ha + NBPT + GA produced highest biological, grain, and stover yields, 1000 grain weight, plant height, and N uptake exhibiting 33.15%, 56.46%, 27.56%, 19.56%, 23.24%, and 78% increase over 150 kg N ha, respectively. The sole use of gibberellic acid or NBPT with each level of N also improved the yield and yield components of maize compared to sole N application and control. Furthermore, application of 120 kg N ha along with NBPT and GA performed at par to 150 kg N ha + NBPT + GA but it was superior than sole applied 150 kg N ha for all the studied traits. These results imply that application of GA and/or NBPT can reduce dependence on urea and improve the yield and N uptake in maize by slowing urea hydrolysis in calcareous soils and shall be practiced.
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http://dx.doi.org/10.1007/s11356-021-16049-wDOI Listing
August 2021

CCT245718, a dual FLT3/Aurora A inhibitor overcomes D835Y-mediated resistance to FLT3 inhibitors in acute myeloid leukaemia cells.

Br J Cancer 2021 Sep 26;125(7):966-974. Epub 2021 Aug 26.

Department of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore, Pakistan.

Background: Activating mutations in the Fms-like tyrosine kinase 3 (FLT3) are among the most prevalent oncogenic mutations in acute myeloid leukaemia. Inhibitors selectively targeting FLT3 kinase have shown promising clinical activity; their success in the clinic, however, has been limited due to the emergence of acquired resistance.

Methods: CCT245718 was identified and characterised as a dual Aurora A/FLT3 inhibitor through cell-based and biochemical assays. The ability of CCT245718 to overcome TKD-mediated resistance was evaluated in a cell line-based model of drug resistance to FLT3 inhibitors.

Results: CCT245718 exhibits potent antiproliferative activity towards FLT3-ITD + AML cell lines and strongly binds to FLT3-ITD and TKD (D835Y) mutants in vitro. Activities of both FLT3-ITD and Aurora A are also inhibited in cells. Inhibition of FLT3 results in reduced phosphorylation of STAT5, downregulation of survivin and induction of apoptotic cell death. Moreover, CCT245718 overcomes TKD-mediated resistance in a MOLM-13-derived cell line containing FLT3 with both ITD and D835Y mutations. It also inhibits FLT3 signalling in both parental and resistant cell lines compared to FLT3-specific inhibitor MLN518, which is only active in the parental cell line.

Conclusions: Our results demonstrate that CCT245718 is a potent dual FLT3/Aurora A inhibitor that can overcome TKD-mediated acquired resistance.
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http://dx.doi.org/10.1038/s41416-021-01527-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476516PMC
September 2021

A Novel Missense Mutation in Causes Recessively Inherited Cardiac Conduction Disease in a Consanguineous Pakistani Family.

Genes (Basel) 2021 Aug 21;12(8). Epub 2021 Aug 21.

Institute for Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany.

Cardiac conduction disease (CCD), which causes altered electrical impulse propagation in the heart, is a life-threatening condition with high morbidity and mortality. It exhibits genetic and clinical heterogeneity with diverse pathomechanisms, but in most cases, it disrupts the synchronous activity of impulse-generating nodes and impulse-conduction underlying the normal heartbeat. In this study, we investigated a consanguineous Pakistani family comprised of four patients with CCD. We applied whole exome sequencing (WES) and co-segregation analysis, which identified a novel homozygous missense mutation (c.1531T>C;(p.Ser511Pro)) in the highly conserved kinase domain of the cardiac troponin I-interacting kinase (TNNI3K) encoding gene. The behaviors of mutant and native TNNI3K were compared by performing all-atom long-term molecular dynamics simulations, which revealed changes at the protein surface and in the hydrogen bond network. Furthermore, intra and intermolecular interaction analyses revealed that p.Ser511Pro causes structural variation in the ATP-binding pocket and the homodimer interface. These findings suggest p.Ser511Pro to be a pathogenic variant. Our study provides insights into how the variant perturbs the TNNI3K structure-function relationship, leading to a disease state. This is the first report of a recessive mutation in and the first mutation in this gene identified in the Pakistani population.
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http://dx.doi.org/10.3390/genes12081282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395014PMC
August 2021

Adenoid cystic carcinoma of external auditory canal: A rare disease.

J Pak Med Assoc 2021 Jul;71(7):1893-1896

Department of Otolaryngology, Head and Neck Surgery, Aga Khan University Hospital, Karachi, Pakistan.

External auditory canal, like other epithelialized surfaces is predisposed to malignancies such as Squamous cell carcinomas (SCC), melanomas and adenocarcinomas. In this background, malignancies like adenoid cystic carcinoma (ACC) are a rare occurrence and need to be thoroughly evaluated both locally and for distant extension. The malignancy needs to be addressed with an aggressive approach surgically with adequate marginal clearance. The role of radiation is debatable considering the outcomes in the limited data. Here we present the case of a 35-year-old female who came in with otalgia and otorrhea associated with a mass in the external auditory canal. After biopsy and imaging, a diagnosis of adenoid cystic carcinoma was made and the patient was managed accordingly.
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http://dx.doi.org/10.47391/JPMA.572DOI Listing
July 2021

Dental care of patients scheduled for cardiovascular surgery: Which protocols should be followed?

J Pak Med Assoc 2021 Jul;71(7):1875-1877

Department of Surgery, Aga Khan University, Karachi, Pakistan.

Dental extraction of abscessed or infected teeth before cardiac operation is frequently advocated to lower the risk of infections, especially infective endocarditis. The scientific evidence that supports dental procedures before cardio-valvular surgery is, however, limited. The aim of the present paper was to explore whether there are any protocols for patients needing dental treatment before cardiac surgery. Moreover, we have discussed the real life challenges encountered in the management of such patients.
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http://dx.doi.org/10.47391/JPMA.035DOI Listing
July 2021

Microbe-Assisted Nanocomposite Anodes for Aqueous Li-Ion Batteries.

ACS Appl Mater Interfaces 2021 Aug 13;13(33):39195-39204. Epub 2021 Aug 13.

Chemical and Materials Engineering Department, Charles W. Davidson College of Engineering, San José State University, One Washington Square, San José, California 95192-0080, United States.

With the rapid increase in the use of lithium-ion batteries (LIBs), the development of safe LIBs has become an important social issue. Replacing flammable organic liquid electrolytes in current LIBs with water can be an alternative route to resolve this safety concern. The water-in-salt (WIS) electrolytes received great attention as next-generation electrolytes due to their large electrochemical stability window. However, their high cathodic limit remains as a challenge, impeding the use of low-potential anodes. Here, we report the first biodirected synthesis of carbonaceous layers on anodes to use them as interlayers that prevent a direct contact of water molecules to anode particles. High-aspect ratio microbes are utilized as precursors of carbonaceous layers on TiO nanoparticles (m-TiO) to enhance the conductivity and to reduce the electrolysis of WIS electrolytes. We selected the cylindrical shape of microbes that offers geometric diversity, providing us a toolkit to investigate the effect of microbe length in forming the network in binary composites and their impacts on the battery performance with WIS electrolytes. Using microbes with varying aspect ratios, the optimal microbe size to maximize the battery performance is determined. The effects of storage time on microbe size are also studied. Compared to uncoated TiO anodes, m-TiO exhibited 49% higher capacity at the 40th cycle and enhanced the cycle life close to anodes made with a conventional carbon precursor while using an 11% less amount of carbon. We performed density functional theory calculations to unravel the underlying mechanism of the performance improvement using microbe-derived carbon layers. Computational results show that high amounts of pyridinic nitrogen present in the peptide bonds in microbes are expected to slow down the water diffusion. Our findings provide key insights into the design of an interlayer for WIS anodes and open an avenue to fabricate energy storage materials using biomaterials.
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http://dx.doi.org/10.1021/acsami.1c07309DOI Listing
August 2021

Role of Bone Biopsy during Kyphoplasty in the Setting of Known Cancer: A Case Report.

Spine (Phila Pa 1976) 2021 Aug 11. Epub 2021 Aug 11.

NYU Langone Hospital- Long Island, Department of Orthopedic Surgery, Mineola, New York 11501.

Study Design: Case Report.

Objective: The aim of this study was to emphasize the utility of routine biopsy during kyphoplasty and to report on a unique case of a patient with known history of prostate cancer found to have a new metastatic cancer.

Summary Of Background Data: Vertebral Compression Fractures (VCFs) may cause debilitating pain with nearly 1/3 of them leading to chronic pain resulting in a tremendous impact on quality of life in patients. Kyphoplasty has been established as an effective means of surgical treatment. However, routine biopsy during kyphoplasty is currently not the standard of care under the presumption that most VCFs are caused by osteoporosis. The role of biopsy in the setting of known malignancy with multiple other risk factors for VCFs is not well understood.

Methods: We report on a case of a 73 year old male with known prostate cancer presenting with persistent unremitting low back pain failing conservative management. Patient develops multiple VCFs in the course of 6 months and is treated with multiple kyphoplasties. Routine biopsy at each level is negative until the last kyphoplasty results positive for malignancy. Surprisingly, the pathology is positive for malignancy other than the patient's known prostate cancer.

Results: Pathology results prompt oncology workup on the patient which reveals multiple metastases and a new diagnosis of adenocarcinoma of possible upper gastrointestinal (GI) origin. In addition, patient's known prostate cancer is also noted to be active. Patient is subsequently started on chemotherapy.

Conclusions: We highlight the utility of routine biopsy during kyphoplasty especially in patients with known history of malignancy. We emphasize that presumptions about the etiology of a VCF are difficult to make with multiple risk factors and that routine biopsy prevents incorrect presumptions such as in this case.Level of Evidence: 5.
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http://dx.doi.org/10.1097/BRS.0000000000004194DOI Listing
August 2021

Leveraging technology and supply chain to improve family planning logistics in Pakistan.

East Mediterr Health J 2021 Jul 29;27(7):672-678. Epub 2021 Jul 29.

USAID Global Health Supply Chain Program, Procurement and Supply Management, National Science and Technology Park, Islamabad, Pakistan.

Background: Pakistan and USAID have invested in improving the contraceptive supply chain data and commodity security. In 2011, the first digital contraceptive logistics management information system (cLMIS) was launched, enabling supply chain data visibility from the federal level to health facilities. The system has built-in modules on forecasting and supply planning, inventory management, consumption reporting, business intelligence tools, automatic email and SMS alerts. Using these features, policy-makers and health managers annually forecast needs, and procure contraceptives accordingly.

Aims: The objective of this research was to understand the existing technological platforms for family planning (FP) supply chain data visibility and the potential impact on contraceptive commodity security.

Methods: The authors reviewed available published and grey literature papers on contraceptives and supplies in Pakistan. We extracted data from the cLMIS, evaluated indicators including reporting compliance, reported stock-out rates, and contraceptive performance. The analysis was validated by reviewing supply chain and FP indicators, such as average monthly consumption, months of stock, and couple years of protection.

Results: The cLMIS has resulted in improved distribution, early warning and accountability at the lowest tiers in the FP supply chain in the public sector. At the facility level, FP commodity availability increased from 40% in 2009 to 84% in 2018.

Conclusion: Contraceptive supply chain has seen significant growth over the past decade to meet expanding reproductive health evidence to inform strategic decisions; cLMIS is a prime contributor to improvements registered in FP stock availability at public sector facilities.
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http://dx.doi.org/10.26719/2021.27.7.672DOI Listing
July 2021

Carbamoyl Phosphate Synthase Subunit CgCPS1 Is Necessary for Virulence and to Regulate Stress Tolerance in Colletotrichum gloeosporioides.

Plant Pathol J 2021 Aug 1;37(4):414. Epub 2021 Aug 1.

Department of Biotechnology, Mirpur University of Science and Technology (MUST), Mirpur 10250, AJK, Pakistan.

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http://dx.doi.org/10.5423/PPJ.ER.11.2020.0208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357564PMC
August 2021

Mesenchymal Stem Cells: From Regeneration to Drug Delivery Systems.

Crit Rev Ther Drug Carrier Syst 2021 ;38(3):33-73

Department of Bioinformatics and Biotechnology, Government College University, Faisalabad (GCUF), Allama Iqbal Road, Faisalabad-38000, Pakistan.

Targeting drug delivery has been a focus of researchers in recent years for cancer and other diseases. Many approaches such as liposomes, exosomes, nanoparticles (magnetic), encapsulation etc. have been developed and investigated for their clinical applications. But disadvantages linked to these therapies limit them to be used in clinical settings. Cell based drug delivery systems has emerged as an alternative for these therapies. Among cell types, mesenchymal stem cells (MSCs) proved to a potential cell type for research due to its many characteristics including low immunogenicity, chemotaxis and homing to tumor sites which are considered mandatory for drug delivery. This chapter focuses on the challenges and opportunities in using MSCs as therapeutic carrier of drugs in different ailments.
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http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2021033916DOI Listing
January 2021

Green synthesis of [email protected] nanocomposite and its' efficient antibacterial activity.

Photodiagnosis Photodyn Ther 2021 Sep 31;35:102471. Epub 2021 Jul 31.

Beijing Advaced Innovation Centre for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China. Electronic address:

Nanotechnologyapplications in the field of biomedicine like drug delivery, cell labeling, and bacterial inhibition are growing . New nano-materials having less toxicity and excellent antibacterial activity attract research interest. In the current study, while taking advantage of green synthesis we have decorated zinc oxide on the surface of grephene oxide forming [email protected] nanocomposite. The Transmission electron microscopy (TEM) study showed successfully synthesized trigonal small sizes ZnO on the surface of GO nanosheets. The as-synthesized [email protected] was used against MDR gram-negative pathogen E-coli (BL21 DE3) and showed excellent antibacterial activity killing about 95 % toxic bacteria within 5 h due to electrostatic interaction between cell membrane of E. coli (BL21 DE3) and [email protected] complex. Hence the nano composite subsequently penetrated into the cytoplasm by damaging the cell membrane of bacteria, as a result production of ROS into the cytoplasm led to imbalance of metabolic system in the cell. Moreover, the cell membrane damage of gram-negative bacteria verified through zeta potential and propidium iodide (PI) study. Thus, our study develops a way to solve the challenge of efficient design of a drug delivery system for dissolution enhancement according to the need for required drug release.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102471DOI Listing
September 2021

A Personalized Therapeutics Approach Using an Reveals Optimal Chemo- and Targeted Therapy Combinations for Colorectal Cancer.

Front Oncol 2021 16;11:692592. Epub 2021 Jul 16.

Biomedical Informatics Research Laboratory, Department of Biology, Lahore University of Management Sciences, Lahore, Pakistan.

models of biomolecular regulation in cancer, annotated with patient-specific gene expression data, can aid in the development of novel personalized cancer therapeutic strategies. is a well-established animal model that is increasingly being employed to evaluate such preclinical personalized cancer therapies. Here, we report five Boolean network models of biomolecular regulation in cells lining the midgut epithelium and annotate them with colorectal cancer patient-specific mutation data to develop an (DPM). We employed cell-type-specific RNA-seq gene expression data from the FlyGut- database to annotate and then validate these networks. Next, we developed three literature-based colorectal cancer case studies to evaluate cell fate outcomes from the model. Results obtained from analyses of the proposed DPM help: (i) elucidate cell fate evolution in colorectal tumorigenesis, (ii) validate cytotoxicity of nine FDA-approved CRC drugs, and (iii) devise optimal personalized treatment combinations. The personalized network models helped identify synergistic combinations of paclitaxel-regorafenib, paclitaxel-bortezomib, docetaxel-bortezomib, and paclitaxel-imatinib for treating different colorectal cancer patients. Follow-on therapeutic screening of six colorectal cancer patients from cBioPortal using this drug combination demonstrated a 100% increase in apoptosis and a 100% decrease in proliferation. In conclusion, this work outlines a novel roadmap for decoding colorectal tumorigenesis along with the development of personalized combinatorial therapeutics for preclinical translational studies.
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http://dx.doi.org/10.3389/fonc.2021.692592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323493PMC
July 2021

A novel nano-sized [email protected] catalyst derived from Co-MOF template for efficient Hg removal at low temperatures with outstanding SO resistance.

Environ Sci Pollut Res Int 2021 Jul 28. Epub 2021 Jul 28.

School of Resources and Environmental Engineering, State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.

CoO is a promising Hg removal catalyst for industrial application. Operating temperature and low sulfur resistance are two of the main problems that hinder its industrial application in Hg removal. Herein, a metal-organic framework (Co-BDC) was introduced as a sacrificial template to obtain the catalyst nano-sized [email protected] by calcination. Part of the organic ligands is carbonized during the calcination. Carbon wrapped CoO and reduced metal agglomeration. The optimal Hg removal temperature of the existing cobalt oxide catalysts was always around 150 °C, but H-TPR showed that the oxygen atoms on the [email protected] were more active than those on CoO, causing the Hg removal temperature window of [email protected] to shift to lower temperatures. The Hg removal efficiency of [email protected] could reach almost 100% even at 25 °C. In the meanwhile, [email protected] also showed a strong SO resistance at ambient temperature. Experimental results and characterization proved that SO did not compete with Hg on the surface of CoO at low temperatures. On the contrary, it participated in the oxidation of Hg. This is a great improvement for CoO catalyst in Hg removal. It reduces the restrictions on the application of CoO in Hg removal. [email protected] shows considerable potential as an Hg removal catalyst.
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http://dx.doi.org/10.1007/s11356-021-15663-yDOI Listing
July 2021

Achieving Operational Excellence Through Artificial Intelligence: Driving Forces and Barriers.

Front Psychol 2021 8;12:686624. Epub 2021 Jul 8.

Abu Dhabi School of Management, Abu Dhabi, United Arab Emirates.

This paper presents an in-depth literature review on the driving forces and barriers for achieving operational excellence through artificial intelligence (AI). Artificial intelligence is a technological concept spanning operational management, philosophy, humanities, statistics, mathematics, computer sciences, and social sciences. AI refers to machines mimicking human behavior in terms of cognitive functions. The evolution of new technological procedures and advancements in producing intelligence for machines creates a positive impact on decisions, operations, strategies, and management incorporated in the production process of goods and services. Businesses develop various methods and solutions to extract meaningful information, such as big data, automatic production capabilities, and systematization for business improvement. The progress in organizational competitiveness is apparent through improvements in firm's decisions, resulting in increased operational efficiencies. Innovation with AI has enabled small businesses to reduce operating expenses and increase revenues. The focused literature review reveals the driving forces for achieving operational excellence through AI are improvement in computing abilities of machines, development of data-based AI, advancements in deep learning, cloud computing, data management, and integration of AI in operations. The barriers are mainly cultural constraints, fear of the unknown, lack of employee skills, and strategic planning for adopting AI. The current paper presents an analysis of articles focused on AI adoption in production and operations. We selected articles published between 2015 and 2020. Our study contributes to the literature reviews on operational excellence, artificial intelligence, driving forces for AI, and AI barriers in achieving operational excellence.
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http://dx.doi.org/10.3389/fpsyg.2021.686624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295597PMC
July 2021

Updates on Clinical and Genetic Heterogeneity of in 12 Autosomal Recessive Primary Microcephaly Families in Pakistani Population.

Front Pediatr 2021 6;9:695133. Epub 2021 Jul 6.

Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Microcephaly (MCPH) is a genetically heterogeneous disorder characterized by non-progressive intellectual disability, small head circumference, and small brain size compared with the age- and sex-matched population. MCPH manifests as an isolated condition or part of another clinical syndrome; so far, 25 genes have been linked with MCPH. Many of these genes are reported in Pakistani population, but due to a high rate of consanguinity, a significant proportion of MCPH cohort is yet to be explored. MCPH5 is the most frequently reported type, accounting for up to 68.75% alone in a genetically constrained population like Pakistan. In the current study, whole exome sequencing (WES) was performed on probands from 10 families sampled from South Waziristan and two families from rural areas of the Pakistani Punjab. Candidate variants were validated through Sanger sequencing in all available family members. Variant filtering and analysis identified three known mutations in , a MCPH5-associated gene. The founder mutation p.Trp1326 was segregating in 10 families, which further confirmed the evidence that it is the most prominent mutation in Pashtun ethnicity living in Pakistan and Afghanistan. Furthermore, the previously known mutations p.Arg3244 and p.Arg1019 were inherited in two families with Punjab ethnic profile. Collectively, this study added 12 more families to the mutational paradigm of and expanded the Pakistani MCPH cohort.
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http://dx.doi.org/10.3389/fped.2021.695133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290066PMC
July 2021

Human Behavior Analysis Using Intelligent Big Data Analytics.

Front Psychol 2021 6;12:686610. Epub 2021 Jul 6.

Department of Computing and Technology, Iqra University, Karachi, Pakistan.

Intelligent big data analysis is an evolving pattern in the age of big data science and artificial intelligence (AI). Analysis of organized data has been very successful, but analyzing human behavior using social media data becomes challenging. The social media data comprises a vast and unstructured format of data sources that can include likes, comments, tweets, shares, and views. Data analytics of social media data became a challenging task for companies, such as Dailymotion, that have billions of daily users and vast numbers of comments, likes, and views. Social media data is created in a significant amount and at a tremendous pace. There is a very high volume to store, sort, process, and carefully study the data for making possible decisions. This article proposes an architecture using a big data analytics mechanism to efficiently and logically process the huge social media datasets. The proposed architecture is composed of three layers. The main objective of the project is to demonstrate Apache Spark parallel processing and distributed framework technologies with other storage and processing mechanisms. The social media data generated from Dailymotion is used in this article to demonstrate the benefits of this architecture. The project utilized the application programming interface (API) of Dailymotion, allowing it to incorporate functions suitable to fetch and view information. The API key is generated to fetch information of public channel data in the form of text files. Hive storage machinist is utilized with Apache Spark for efficient data processing. The effectiveness of the proposed architecture is also highlighted.
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http://dx.doi.org/10.3389/fpsyg.2021.686610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290162PMC
July 2021

Life-Threatening Fungal Infection in Richter Transformation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Case Report and Brief Review of Literature.

Cureus 2021 Jun 25;13(6):e15924. Epub 2021 Jun 25.

Hematology and Medical Oncology, John H. Stroger, Jr. Hospital of Cook County, Chicago, USA.

Chronic lymphocytic leukemia/small lymphocytic lymphoma is an indolent B cell lymphoproliferative malignancy typically affecting the elderly. Clinical outcomes of this condition have steadily improved as a result of advances in therapy. However, an increase in survival is accompanied by increased incidence of Richter transformation into an aggressive lymphoma. We present one such case and delve into its risk factors and associated complications. Exposure to increased lines of treatment appears to be a contributing factor in transformation, such that those with fewer than two lines of treatment are considered to have a lower risk of transformation. Fever, rapid lymph node involvement and drastic increases in lactate dehydrogenase, as seen in our patient, are concerning for transformation and treatment options include chemotherapy versus novel agent therapy. However, patients receiving therapy are at risk for adverse outcomes such as invasive infections, particularly in those receiving consolidation chemotherapy. Fungal infections such as Aspergillus and Candida are gaining prominence in the setting of neutropenia which adversely impact survival, but are underreported. Efforts to improve outcomes may include consideration of growth factor therapy in neutropenic patients and continuing to be vigilant for early signs of infection.
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http://dx.doi.org/10.7759/cureus.15924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285100PMC
June 2021

A 24-generation-old founder mutation impairs splicing of RBBP8 in Pakistani families affected with Jawad syndrome.

Clin Genet 2021 10 16;100(4):486-488. Epub 2021 Jul 16.

Cologne Center for Genomics (CCG) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Jawad syndrome is a multiple congenital anomaly and intellectual disability syndrome with mutation in RBBP8 reported only in two families. Here, we report on two new families from Pakistan and identified a previously reported variant in RBBP8, NM_002894.3:c.1808-1809delTA. We could show that this mutation impairs splicing resulting in two different abnormal transcripts. Finally, we could verify a shared haplotype among all four families and estimate the founder event to have occurred some 24 generations ago.
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http://dx.doi.org/10.1111/cge.14028DOI Listing
October 2021

Field Evolved Resistance in Earias vittella (Lepidoptera: Noctuidae) From Punjab, Pakistan Against Commercial Formulations of Bacillus thuringiensis kurstaki.

J Econ Entomol 2021 Oct;114(5):2204-2213

University Institute of Biochemistry and Biotechnology (UIBB), PMAS Arid Agriculture University, Rawalpindi, Pakistan.

Transgenic commercial cotton expressing Bacillus thuringiensis (Bt) Cry endotoxins or vegetative Vip toxins provide protection to cotton against bollworm attack. Continuous exposure of these targeted pests to cry toxins and to Bt commercial spray formulations has resulted in the development of resistance through natural selection. Spotted bollworm Earias vittella (Noctuidae: Lepidoptera) is considered to be one of the most destructive pests of cotton and okra crops in South Asia including Pakistan and has developed resistance to various synthetic insecticides. In the present study, the level of resistance in field populations of the spotted bollworm E. vittella against Bt Cry toxins has been evaluated for the first time. We collected twelve populations of E. vittella from three districts of Punjab, Pakistan for testing against four commercial Bt formulations containing different strains of B. thuringiensis subspecies kurstaki (Btk) with a range of Cry toxins. Low to high levels of resistance were found in the field populations compared with a laboratory-reared susceptible population of E. vittella (resistance ratios 6 to 111-fold). These results suggest that E. vittella has developed resistance against different Cry toxins after continuous exposure to Bt cotton in field. In order to prevent field control failures, regular insecticide resistance monitoring programs are required together with the use of integrated management approaches, including the use of Bt cotton varieties expressing two or more toxins to delay the development of resistance against Bt toxins in E. vittella.
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http://dx.doi.org/10.1093/jee/toab137DOI Listing
October 2021

Heparin for Vertebral Intraluminal Thrombus Causing Retroperitoneal Hemorrhage from Occult Renal Angiomyolipoma.

Case Rep Neurol 2021 May-Aug;13(2):388-393. Epub 2021 Jun 14.

Institute for Stroke and Cerebrovascular Disease, The University of Texas Health Science Center, Houston, Texas, USA.

Stroke is a common cause of mortality and serious long-term disability worldwide. In the acute setting, current American Heart Association/American Stroke Association guidelines do not recommend routine anticoagulation for the management of acute ischemic strokes. However, short-term use of unfractionated heparin (UFH) in select subpopulations has demonstrated improved outcomes. While tools such as CHADSVASC and HASBLED scores are useful in stratifying risk of long-term anticoagulation in patients with nonvalvular atrial fibrillation and additional risk factors, the carefully selected patient populations for the design of these studies do not account for risk of hemorrhage from other preexisting conditions. Here, we present a patient with a posterior circulation intraluminal thrombus treated with UFH, who manifested with a near-fatal intra-abdominal hemorrhage from a previously undetected renal angiomyolipoma (AML).
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http://dx.doi.org/10.1159/000514090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255730PMC
June 2021

A Systematic Review of Biosynthesized Metallic Nanoparticles as a Promising Anti-Cancer-Strategy.

Cancers (Basel) 2021 Jun 5;13(11). Epub 2021 Jun 5.

Plant Cell and Tissue Culture Lab, Department of Biotechnology, Quaid-i-Azam University, Islamabad 45320, Pakistan.

Cancer is one of the foremost causes of death worldwide. Cancer develops because of mutation in genes that regulate normal cell cycle and cell division, thereby resulting in uncontrolled division and proliferation of cells. Various drugs have been used to treat cancer thus far; however, conventional chemotherapeutic drugs have lower bioavailability, rapid renal clearance, unequal delivery, and severe side effects. In the recent years, nanotechnology has flourished rapidly and has a multitude of applications in the biomedical field. Bio-mediated nanoparticles (NPs) are cost effective, safe, and biocompatible and have got substantial attention from researchers around the globe. Due to their safe profile and fewer side effects, these nanoscale materials offer a promising cure for cancer. Currently, various metallic NPs have been designed to cure or diagnose cancer; among these, silver (Ag), gold (Au), zinc (Zn) and copper (Cu) are the leading anti-cancer NPs. The anticancer potential of these NPs is attributed to the production of reactive oxygen species (ROS) in cellular compartments that eventually leads to activation of autophagic, apoptotic and necrotic death pathways. In this review, we summarized the recent advancements in the biosynthesis of Ag, Au, Zn and Cu NPs with emphasis on their mechanism of action. Moreover, nanotoxicity, as well as the future prospects and opportunities of nano-therapeutics, are also highlighted.
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http://dx.doi.org/10.3390/cancers13112818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201057PMC
June 2021
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