Localized Immunomodulation with PD-L1 Results in Sustained Survival and Function of Allogeneic Islets without Chronic Immunosuppression.

Allogeneic islet transplantation is limited by adverse effects of chronic immunosuppression used to control rejection. The programmed cell death 1 pathway as an important immune checkpoint has the potential to obviate the need for chronic immunosuppression. We generated an oligomeric form of programmed cell death 1 ligand chimeric with core streptavidin (SA-PDL1) that inhibited the T effector cell response to alloantigens and converted T conventional cells into CD4+Foxp3+ T regulatory cells. The SA-PDL1 protein was effectively displayed on the surface of biotinylated mouse islets without a negative impact islet viability and insulin secretion. Transplantation of SA-PDL1-engineered islet grafts with a short course of rapamycin regimen resulted in sustained graft survival and function in >90% of allogeneic recipients over a 100-d observation period. Long-term survival was associated with increased levels of intragraft transcripts for innate and adaptive immune regulatory factors, including IDO-1, arginase-1, Foxp3, TGF-ß, IL-10, and decreased levels of proinflammatory T-bet, IL-1ß, TNF-α, and IFN-γ as assessed on day 3 posttransplantation. T cells of long-term graft recipients generated a proliferative response to donor Ags at a similar magnitude to T cells of naive animals, suggestive of the localized nature of tolerance. Immunohistochemical analyses showed intense peri-islet infiltration of T regulatory cells in long-term grafts and systemic depletion of this cell population resulted in prompt rejection. The transient display of SA-PDL1 protein on the surface of islets serves as a practical means of localized immunomodulation that accomplishes sustained graft survival in the absence of chronic immunosuppression with potential clinical implications.

Design and Implementation of an Open-Source SCADA System for a Community Solar-Powered Reverse Osmosis System.

Design and implementation of an open-source-based supervisory control and data acquisition (SCADA) system for a community solar-powered reverse osmosis are presented in this paper. A typical SCADA system available on the market is proprietary and has a high initial and maintenance cost. Aside from that, there is no SCADA system with an alert system available to give users updates and status information concerning the system. The objective of this study is to develop a comprehensive SCADA design that takes advantage of open-source technology to address the world's most pressing problem, access to clean water. The designed reverse Osmosis system also uses renewable energy-based power sources. In this system, all data is stored and analyzed locally, which ensures the data is secure and allows the user to make data-driven decisions based on the collected data. Among the main components of this system are the field instrument devices (FIDs), the remote terminal unit (RTU), the main terminal units (MTUs), the web-based programming software, and the data analytics software. The Node-Red programming and dashboard tool, Grafana for data analytics, and InfluxDB for database management run on the main terminal unit having Debian operating system. Data is transmitted from the FIDs to the RTU, which then redirects it to the MTU via serial communication. Node-Red displays the data processed by the MTU on its dashboard as well, as the data is stored locally on the MTU and is displayed by means of Grafana, which is also installed on the same MTU. Through the Node-Red dashboard, the system is controlled, and notifications are sent to the community.

A high level of TGF-B1 promotes endometriosis development via cell migration, adhesiveness, colonization, and invasiveness†.

Endometriosis is a prevalent gynecological disorder that eventually gives rise to painful invasive lesions. Increased levels of transforming growth factor-beta 1 (TGF-B1) have been reported in endometriosis. However, details of the effects of high TGF-B1 on downstream signaling in ectopic endometrial tissue remain obscure. We induced endometriotic lesions in mice by surgical auto-transplantation of endometrial tissues to the peritoneal regions. We then treated endometriotic (ectopic and eutopic endometrial tissues) and nonendometriotic (only eutopic endometrial tissues) animal groups with either active TGF-B1 or PBS. Our results demonstrate that externally supplemented TGF-B1 increases the growth of ectopically implanted endometrial tissues in mice, possibly via SMAD2/3 activation and PTEN suppression. Adhesion molecules integrins (beta3 and beta8) and FAK were upregulated in the ectopic endometrial tissue when TGF-B1 was administered. Phosphorylated E-cadherin, N-cadherin, and vimentin were enhanced in the ectopic endometrial tissue in the presence of TGF-B1 in the mouse model, and correlated with epithelial-mesenchymal transition (EMT) in ovarian endometriotic cells of human origin. Furthermore, in response to TGF-B1, the expression of RHOGTPases (RAC1, RHOC, and RHOG) was increased in the human endometriotic cells (ovarian cyst derived cells from endometriosis patient) and tissues from the mouse model of endometriosis (ectopic endometrial tissue). TGF-B1 enhanced the migratory, invasive, and colonizing potential of human endometriotic cells. Therefore, we conclude that TGF-B1 potentiates the adhesion of ectopic endometrial cells/tissues in the peritoneal region by enhancing the integrin and FAK signaling axis, and also migration via cadherin-mediated EMT and RHOGTPase signaling cascades.

Epidemiology of rheumatoid arthritis, clinical aspects and socio-economic determinants in Pakistani patients: A systematic review and meta-analysis.

OBJECTIVE: The study aimed to evaluate literature on rheumatoid arthritis disease in Pakistani patients, to have an understanding about its epidemiology, clinical aspects and socio-economic determinants. METHODS: The review study was conducted from December 2017, to May 2018. An online search was conducted in international and local health databases using appropriate search keywords as well as scanning reference lists of related articles. Literature published after year 2000 that reported epidemiological, demographic, clinical and socioeconomic data of Pakistani rheumatoid arthritis patients was included. Meta-analysis was performed where possible. This systematic review was registered on the international prospective register of systematic reviews PROSPERO (CRD42018090582). RESULTS: Of the 334 research articles found, 29 (8.7%) were selected. Patients were mostly females, but no study explored impact of disease on household and family role functioning of rheumatoid arthritis-affected women in Pakistan. Most patients were uneducated (55%) and unemployed; had low disease knowledge (N = 149, 74.5%) and poor adherence to disease-modifying anti-rheumatic drugs (N = 23, 23%). Point prevalence of rheumatoid arthritis reported from Karachi was high at 26.9%. Moderate disease activity, i.e., 4.5}0.7 and mild functional disability (N = 66, 51.6%) were seen in RA patients. Almost half (N = 799, 46.9%) had comorbidities. Almost a fifth proportion of RA patients had dyslipidaemia as a comorbidity (N = 134, 16.77%) and higher cardiovascular risk score as modifiable risk factor. Undiagnosed depression (N = 134, 58.3%) and low bone mineral density (N = 93, 40.6%) were reported in RA patients. Direct monthly treatment cost of disease was significantly high considering patients' socio-economic status, i.e., USD 16.47 - 100.68. Most commonly used drug was methotrexate. CONCLUSIONS: There is a paucity of data on Pakistani rheumatoid arthritis patients' demographic and socio-economic parameters, especially the gender element.

Spectral and Energy Efficient Low-Overhead Uplink and Downlink Channel Estimation for 5G Massive MIMO Systems.

Uplink and Downlink channel estimation in massive Multiple Input Multiple Output (MIMO) systems is an intricate issue because of the increasing channel matrix dimensions. The channel feedback overhead using traditional codebook schemes is very large, which consumes more bandwidth and decreases the overall system efficiency. The purpose of this paper is to decrease the channel estimation overhead by taking the advantage of sparse attributes and also to optimize the Energy Efficiency (EE) of the system. To cope with this issue, we propose a novel approach by using Compressed-Sensing (CS), Block Iterative-Support-Detection (Block-ISD), Angle-of-Departure (AoD) and Structured Compressive Sampling Matching Pursuit (S-CoSaMP) algorithms to reduce the channel estimation overhead and compare them with the traditional algorithms. The CS uses temporal-correlation of time-varying channels to produce Differential-Channel Impulse Response (DCIR) among two CIRs that are adjacent in time-slots. DCIR has greater sparsity than the conventional CIRs as it can be easily compressed. The Block-ISD uses spatial-correlation of the channels to obtain the block-sparsity which results in lower pilot-overhead. AoD quantizes the channels whose path-AoDs variation is slower than path-gains and such information is utilized for reducing the overhead. S-CoSaMP deploys structured-sparsity to obtain reliable Channel-State-Information (CSI). MATLAB simulation results show that the proposed CS based algorithms reduce the feedback and pilot-overhead by a significant percentage and also improve the system capacity as compared with the traditional algorithms. Moreover, the EE level increases with increasing Base Station (BS) density, UE density and lowering hardware impairments level.

Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study.

BACKGROUND: Friedreich's ataxia is a progressive degenerative disorder caused by deficiency of the frataxin protein. Expanded GAA repeats within intron 1 of the frataxin (FXN) gene lead to its heterochromatinisation and transcriptional silencing. Preclinical studies have shown that the histone deacetylase inhibitor nicotinamide (vitamin B3) can remodel the pathological heterochromatin and upregulate expression of FXN. We aimed to assess the epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia. METHODS: In this exploratory, open-label, dose-escalation study in the UK, male and female patients (aged 18 years or older) with Friedreich's ataxia were given single doses (phase 1) and repeated daily doses of 2-8 g oral nicotinamide for 5 days (phase 2) and 8 weeks (phase 3). Doses were gradually escalated during phases 1 and 2, with individual maximum tolerated doses used in phase 3. The primary outcome was the upregulation of frataxin expression. We also assessed the safety and tolerability of nicotinamide, used chromatin immunoprecipitation to investigate changes in chromatin structure at the FXN gene locus, and assessed the effect of nicotinamide treatment on clinical scales for ataxia. This study is registered with ClinicalTrials.gov, number NCT01589809. FINDINGS: Nicotinamide was generally well tolerated; the main adverse event was nausea, which in most cases was mild, dose-related, and resolved spontaneously or after dose reduction, use of antinausea drugs, or both. Phase 1 showed a dose-response relation for proportional change in frataxin protein concentration from baseline to 8 h post-dose, which increased with increasing dose (p=0·0004). Bayesian analysis predicted that 3·8 g would result in a 1·5-times increase and 7·5 g in a doubling of frataxin protein concentration. Phases 2 and 3 showed that daily dosing at 3·5-6 g resulted in a sustained and significant (p<0·0001) upregulation of frataxin expression, which was accompanied by a reduction in heterochromatin modifications at the FXN locus. Clinical measures showed no significant changes. INTERPRETATION: Nicotinamide was associated with a sustained improvement in frataxin concentrations towards those seen in asymptomatic carriers during 8 weeks of daily dosing. Further investigation of the long-term clinical benefits of nicotinamide and its ability to ameliorate frataxin deficiency in Friedreich's ataxia is warranted. FUNDING: Ataxia UK, Ataxia Ireland, Association Suisse de l'Ataxie de Friedreich, Associazione Italiana per le Sindromi Atassiche, UK National Institute for Health Research, European Friedreich's Ataxia Consortium for Translational Studies, and Imperial Biomedical Research Centre.

Recent developments in therapeutic protein expression technologies in plants.

Infectious diseases and cancers are some of the commonest causes of deaths throughout the world. The previous two decades have witnessed a combined endeavor across various biological sciences to address this issue in novel ways. The advent of recombinant DNA technologies has provided the tools for producing recombinant proteins that can be used as therapeutic agents. A number of expression systems have been developed for the production of pharmaceutical products. Recently, advances have been made using plants as bioreactors to produce therapeutic proteins directed against infectious diseases and cancers. This review highlights the recent progress in therapeutic protein expression in plants (stable and transient), the factors affecting heterologous protein expression, vector systems and recent developments in existing technologies and steps towards the industrial production of plant-made vaccines, antibodies, and biopharmaceuticals.

Optimization of high-Q coupled nanobeam cavity for label-free sensing.

We numerically and experimentally investigated the lateral coupling between photonic crystal (PhC) nanobeam (NB) cavities, pursuing high sensitivity and figure of merit (FOM) label-free biosensor. We numerically carried out 3D finite-difference time-domain (3D-FDTD) and the finite element method (FEM) simulations. We showed that when two PhC NB cavities separated by a small gap are evanescently coupled, the variation in the gap width significantly changes the coupling efficiency between the two coupled NB cavities and the resulting resonant frequencies split. Experimentally, we fabricated laterally-coupled PhC NB cavities using (InGaAsP) layer on the InP substrate. For sensing, we showed that the laterally coupled PhC NB cavities sensor exhibits higher sensitivity than the single PhC NB cavity. The higher sensitivity of laterally coupled PhC NB cavities is due to the strong evanescent coupling between nearby PhC NB cavities, which depends on the gap width and it is attributed to the large confinement of the electromagnetic field in the gap (air or liquid). As a result of the lateral coupling, both even (symmetric) and odd (asymmetric) modes exist. We show that even modes are more sensitive than odd modes. In addition, higher-order modes exhibit higher sensitivity. Hence, we characterized and examined the fabricated PhC NB cavity as a label-free biosensor, and it exhibits high figure of merit due to its high Q-factor. This illustrates a potentially useful method for optical sensing at nanoscale.

Impact of the Follicular Lymphoma International Prognostic Index risk categorization on survival of patients with follicular lymphoma in Pakistani population: a single centre experience.

OBJECTIVE: To determine the impact of Follicular Lymphoma International Prognostic Index risk categorisation on the survival of patients with follicular lymphoma treated in one centre. METHOD: The retrospective study comprised follicular lymphoma patients treated from 1997 to 2010 at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore. Their baseline prognostic index score, stage, bone marrow involvement and high-grade transformation were recorded. Risk categorisation was done according to the index score. SPSS 19 was used for statistical analysis. RESULTS: Median age of the 70 patients studied was 54 years (range: 23-98). There were 42 (60%) males. Overall, 58 (83%) patients presented with stage III/IV disease. Bone marrow was involved in 42 (60%) cases. High-grade transformation was reported in 12 (17.1%). According to risk categorisation, 21 (30%) were low risk, 21 (30%) intermediate and 28 (40%) were in high-risk category. Patients were treated with standard chemotherapy. Median follow-up was 3 years (range: 1-9). Median overall survival was 4.1 years (95% Cl: 4.7-6.4).The Kaplan Meier estimated overall survival at 5 years was 26 (43%). Five-year overall survival in the low, intermediate and high risk groups was 14 (66%), 10 (47%) and 7 (25%), respectively (p < 0.02). CONCLUSION: The Follicular Lymphoma International Prognostic Index showed significant prognostic value with high scores having poor overall survival compared to patients with low and intermediate scores.

FDG-PET scan in assessing lymphomas and the application of Deauville Criteria.

OBJECTIVE: To evaluate the role of Fluorine-18-fluorodexoyglucose Positron Emission Tomography (FDG-PET) scan in staging and its implications on the treatment of lymphoma, and to study the concordance between visual assessment and Deauville criteria for the interpretation of interim scans. METHODS: The prospective single-arm experimental study was conducted at the Shaukat Khanum Memorial Cancer Hospital, Lahore, from May 2011 to October 2011. It comprised 53 newly diagnosed lymphoma patients who agreed to participate in the study. All patients underwent scans with contrast-enhanced computerised tomography at baseline. Treatment plan was formulated based on the final stage. Interim scans were acquired after 2 cycles of chemotherapy and were reported using visual criteria and compared with the 5-point Deauville criteria. Score of 1-3 was taken as disease-negative, while 4-5 was taken as disease-positive. SPSS 19 was used for statistical analysis. RESULTS: Of the 53 patients, 35 (66%) had Hodgkin's Lymphoma, while 18 (34%) had Non-Hodgkin's Lymphoma. Scans resulted in disease upstaging in 4 (7.5%) patients, and detecting increased disease burden in 12 (23%). On interim scans, complete remission was achieved in 38 (71%) patients (Deauville score 1-3); 12(23%) showed partial response (Deauville score 4-5); and 3 (6%) had progression. Kappa test was statistically significant (kappa 0.856; p <0.001). CONCLUSION: The positron emission tomography helped to upstage lymphoma and reflected increased disease burden. The Deauville criteria correlated very well with visual assessment criteria and can be applied in the patient population.

Facial eccrine angiomatous hamartoma in a 52-year-old woman: A case report.

Eccrine angiomatous hamartoma is a rare, benign condition. Patients typically present with a solitary, sometimes enlarging nodule of the extremities usually appearing at birth or arising during childhood. Eccrine angiomatous hamartoma is usually sporadic, but one familial case of the multifocal variant has been reported. It is recognized histologically by increased numbers of eccrine elements as well as numerous vascular channels and proliferation of other dermal elements such as adipose tissue and hair follicles. When symptomatic, eccrine angiomatous hamartoma may be associated with hyperhidrosis or pain. We report a case of a 52-year-old woman with eccrine angiomatous hamartoma on the face and share our experience with botulinum toxins in the treatment of this condition.

One-Year Front Versus Central and Paracentral Corneal Changes After Bowman Layer Transplantation for Keratoconus.

PURPOSE: To report the front corneal versus central and paracentral corneal changes after Bowman layer transplantation for keratoconus in a tertiary hospital in the United Kingdom. METHODS: Five eyes of 5 patients receiving Bowman layer transplant for advanced keratoconus in Royal Gwent Hospital (Newport, United Kingdom) were included. Preoperative and postoperative visual acuity; Kmax; Kmean, and corneal cylinder in the front cornea, 4.5 mm central, and 6 mm central; and corneal thickness were analyzed. RESULTS: Corneal flattening and reduction in corneal astigmatism was observed, more marked in the central and paracentral zone, allowing for improvement in best-corrected visual acuity with the aid of visual correction in 4 eyes. CONCLUSIONS: These results support previous data reporting Bowman layer transplantation as a useful strategy in the treatment of advanced keratoconus and suggest greater attention may be focused on central or paracentral corneal changes.

Body Mass Index and Other Risk Factors Effects on Colon Cancer Prognosis in Pakistan.

Introduction: Asian developing countries share the burden of colorectal cancer (CRC) with rising mortality rates. This prospective study aims to apprehend the clinical relevance of age, gender, lifestyle choices (dietary habits and addiction) and body mass index (BMI) to the occurrence and progression of colon cancer (CC). Methods: A cohort of non-cancer (NC) and CC patients of South-Central Asian origin registered for screening colonoscopy or surgery at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC), Lahore, Pakistan, from 2015 to 2020 was identified. BMI (Kg/m2) was classified according to the World Health Organization criteria as underweight (<18.5 Kg/m2), normal weight (18.5-24.9 Kg/m2) and overweight (≥25 Kg/m2). Results: Among 236 participants, 99 (41.9%) belonged to the NC group, and 137 (58.1 %) participants had CC Overall, participants included 74 women and 162 men aged 20-85 years (mean ± SD; 49.9 ± 14.9). Notably, 46.0% of cancer patients had a family history of cancer. There was a direct relationship between CC with abnormal BMI (underweight and overweight), positive smoking history and positive family history of cancer. Conclusion: Being underweight or overweight is a potential risk factor for CC patients. The overall survival in patients with CC is clinically associated with lifestyle choices before CC diagnosis. A balanced diet, walking and other forms of exercise should be strongly recommended to the community and those undergoing screening colonoscopy.

AS1411-functionalized delivery nanosystems for targeted cancer therapy.

Nucleolin (NCL) is a multifunctional nucleolar phosphoprotein harboring critical roles in cells such as cell proliferation, survival, and growth. The dysregulation and overexpression of NCL are related to various pathologic and oncological indications. These characteristics of NCL make it an ideal target for the treatment of various cancers. AS1411 is a synthetic quadruplex-forming nuclease-resistant DNA oligonucleotide aptamer which shows a considerably high affinity for NCL, therefore, being capable of inducing growth inhibition in a variety of tumor cells. The high affinity and specificity of AS1411 towards NCL make it a suitable targeting tool, which can be used for the functionalization of therapeutic payloaddelivery nanosystems to selectively target tumor cells. This review explores the advances in NCL-targeting cancer therapy through AS1411-functionalized delivery nanosystems for the selective delivery of a broad spectrum of therapeutic agents.

Expression of cornulin in tongue squamous cell carcinoma.

The aim of the study is to identify cornulin (CRNN) protein expression associated with advancement of tongue squamous cell carcinoma (TSCC). A comparison of addictive (containing potential carcinogens) versus non-addiction causative agents was expected to allow detection of differences in CRNN expression associated with TSCC. Bespoke tissue microarrays (TMAs) were prepared and immunohistochemistry (IHC) performed to determine the changes in CRNN expression in epithelial cells of node-negative (pN-), node-positive (pN+) TSCC and non-cancer patients' oral tissues. TMAs were validated by performing IHC on whole diagnostic tissues. Chi-square test or Fisher's-exact tests were used to establish significant expression differences. Analogous analyses were performed for biomarkers previously associated with TSCC, namely collagen I alpha 2 (COL1A2) and decorin (DCN) to compare the significance of CRNN. Keratinisation and its level (low, extensive) were studied in relation to CRNN so that the extent of squamous differentiation could better be assessed. IHC immunoreactive score (IRS) clustered the patients based on weak/moderate (Low (IRS ≤ +3)) or strong (High (IRS ≥ +4)) expression groups. A low expression was observed in a larger number of patients in control proteins COL1A2 (77.3%), DCN (87.5%) and target protein CRNN (52.3%), respectively. Low CRNN expression was observed in TSCC where nodes were involved (pN+: mean 1.4 ± 2.1) (p = 0.248). Keratinisation (%) was low (0% ≤ 50%) in 42.2% and extensive (1% ≥ 50.0%) in 57.8% patients. In conclusion, our study suggested that Low CRNN expression was associated with grade and lymph node metastasis in TSCC. CRNN expression is independent of addiction, however potentially carcinogenic addictive substances might be aiding in the disease progression.

Complications of conventional scleral buckling occuring during and after treatment of rhegmatogenous retinal detachment.

OBJECTIVE: To identify and determine the frequency of the intra-operative and early postoperative complications of Conventional Scleral Buckling (CSB) as the primary surgical intervention in patients with Rhegmatogenous Retinal Detachment (RRD). STUDY DESIGN: A quasi-interventional study. PLACE AND DURATION OF STUDY: Khyber Institute of Ophthalmic Medical Sciences (KIOMS), Postgraduate Medical Institute (PGMI), Hayatabad Medial Complex (HMC), Peshawar, from April 2005 to June 2006. METHODOLOGY: Fifty consecutive patients who underwent CSB and fulfilled the inclusion criteria, were included in the study. Operative details and any intra-operative complications were noted. The patients underwent another detailed clinical examination and pain assessment on the first postoperative day. All the patients were followed-up minimum for 3 months. Postoperative complications were identified and recorded. The data was analyzed on SPSS 12.0 for measures of central tendency and dispersion. RESULTS: There were 36 male and 14 female subjects. Mean age was 37.18 + or - 20.045 years. Encirclement (56%) was the most frequently used CSB technique. Sixteen (32%) patients had at least one intra-operative complication. Intra-operative complications were iatrogenic scleral break (2%), accidental Sub Retinal Fluid (SRF) drainage (8%), choroidal haemorrhage (2%), subretinal haemorrhage (14%), retinal incarceration (2%), vitreous haemorrhage (6%), raised (4%) or very low (2%), intra-operative IOP and hyphema (2%). Postoperative complications included systemic complications (24%), choroidal detachment (8%), vitreous haemorrahge (16%), raised IOP (22%), angle closure (2%), conjunctivitis (4%), orbital cellulitis (2%), suspected endophthalmitis (2%), ocular movement disorders (2%) and explant exposure (6%). Mean refractive change in spherical equivalent was -1.478 + or - 0.698 D. Final re-attachment rate was (82%) and final BCVA of > 6/60 was achieved in 62% of the subjects in the treated eyes. CONCLUSION: CSB is a safe and effective option for treating uncomplicated RRD, but it is associated with certain complications. Sub-retinal bleed was the most common intra-operative complication. Raised IOP was most the common early postoperative complication followed by choroidal detachment.

Insights of Novel Coronavirus (SARS-CoV-2) disease outbreak, management and treatment.

Emerging and re-emerging viral diseases poses a threat to living organisms, and led to serious concern to humankind and public health. The last two decades, viral epidemics such as the severe acute respiratory syndrome (SARS-CoV) reported in the years 2002-2003, and H1N1 influenza (Swine flu) in 2009, middle east respiratory syndrome (MERS-CoV) from Saudi Arabia in 2012, Ebola virus in 2014-2016, and Zika virus in 2015. The recent outbreak of 2019-CoV-2 or severe acute respiratory syndrome-2 (SARS-CoV-2), novel coronavirus (2019-nCoV, or 2019 disease, COVID-19) in Dec 2019, from, Wuhan city of China, has severe implications of health concerns to the whole world, due to global spread and high health risk. More than 423349 deaths had occurred globally and is still increasing every day. The whole world is under a health emergency, and people are advised to stay at their homes to avoid the spread of person-to-person infection, and advised to maintain social distancing. The advancement in clinical diagnosis techniques like Real-Time PCR (RT-PCR), immunological, microscopy, and geographic information system (GIS) mapping technology helped in tacking the rapid diagnosis and tracking viral infection in a short period. In the same way, artificial intelligence (AI), combinatorial chemistry, and deep learning approaches help to find novel therapeutics in less time and wide applicability in biomedical research. National Institute of Allergy and Infectious Diseases (NIAID) has started the clinical trials of investigation COVID-19 vaccine. Therefore, we can expect vaccines to be available for this deadly disease in the coming few months.

Cancer Epidemiology in Lahore, Pakistan - 2010-2015.

OBJECTIVE: To study the cancer incidence rates in Lahore, which has an estimated annual population count of 10.3 million. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Data on new cancer cases diagnosed between 2010 and 2015, among the residents of Lahore district, Pakistan, was reviewed retrospectively in 2015-2017. METHODOLOGY: Nineteen collaborating centres of the population-based Punjab Cancer Registry (PCR), representing both the government and private sectors, reported their cases to the coordinating office located within the Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC). The age-standardised incidence rates (ASIR) per 100,000 population, over a six-year period, were computed. Sixteen 5-year age groups were created beginning from 0-4 to 70-74 years, followed by 75+ years. Graphs on the five-year age-specific incidence rates by gender, were also generated. RESULTS: Between 2010 and 2015, 33,028 new malignancies were recorded in Lahore, with the crude average annual incidence rate being 53.1. In adults, the highest ASIRs were noted for cancers of the breast (77.3) among females and of prostate (11.4) in men. Age-specific incidence rates for female breast cancer showed an upward trend at the age of 20 years, reaching a figure of 160 at the age of 55 years. Among males, the rates for prostate cancer started to increase at the age of 55 years and reached a peak of 93 at 75 years. CONCLUSION: These results warrant expanding cancer registration in the region and sharing statistics with policy-makers to establish hospitals accordingly to manage cancer, along with exploring various risk factors within the population.

Targeting Melanoma Hypoxia with the Food-Grade Lactic Acid Bacterium Lactococcus Lactis.

Melanoma is the most aggressive form of skin cancer. Hypoxia is a feature of the tumor microenvironment that reduces efficacy of immuno- and chemotherapies, resulting in poor clinical outcomes. Lactococcus lactis is a facultative anaerobic gram-positive lactic acid bacterium (LAB) that is Generally Recognized as Safe (GRAS). Recently, the use of LAB as a delivery vehicle has emerged as an alternative strategy to deliver therapeutic molecules; therefore, we investigated whether L. lactis can target and localize within melanoma hypoxic niches. To simulate hypoxic conditions in vitro, melanoma cells A2058, A375 and MeWo were cultured in a chamber with a gas mixture of 5% CO2, 94% N2 and 1% O2. Among the cell lines tested, MeWo cells displayed greater survival rates when compared to A2058 and A375 cells. Co-cultures of L. lactis expressing GFP or mCherry and MeWo cells revealed that L. lactis efficiently express the transgenes under hypoxic conditions. Moreover, multispectral optoacoustic tomography (MSOT), and near infrared (NIR) imaging of tumor-bearing BALB/c mice revealed that the intravenous injection of either L. lactis expressing ß-galactosidase (ß-gal) or infrared fluorescent protein (IRFP713) results in the establishment of the recombinant bacteria within tumor hypoxic niches. Overall, our data suggest that L. lactis represents an alternative strategy to target and deliver therapeutic molecules into the tumor hypoxic microenvironment.