Human cytomegalovirus : from novel strain, miRNAs to interplay with breast cancer

The prevalence of human cytomegalovirus (HCMV) ranges from 40% to 100% worldwide. A primary HCMV infection results in a lifelong latent or persistent infection. In healthy people, HCMV infection is often asymptomatic, but in immunosuppressed individuals it can cause life- threatening disease, and HCMV congenital infection may result in fetal malformation. Increasing evidence implies that HCMV infection is associated with different malignancies. Several studies have suggested different mechanisms by which HCMV can modulate the tumour and the tumour environment, which could be of relevance in tumour development and progression. However, the role of HCMV in cancer has remained highly controversial. The studies in this thesis investigated the possible role of HCMV in cancer, with a special focus on HCMV encoded-miRNAs. HCMV encodes at least 26 miRNAs, and are expressed during the lytic as well as latent phase of infection. Viral miRNAs are identified to target both host and viral mRNA transcripts and thereby regulate protein expression. They modulate various biological functions of the host cell and the virus life cycle by mediating latency, viral replication, cell cycle control, vesicle trafficking, virus assembly and immune evasion strategies. In study I (Manuscript), we discovered a novel genetic variant of HCMV lacking intron 2 of the major immediate early (MIE) gene in 48% tumour samples obtained from breast, colon, neuroblastoma, medulloblastoma and glioblastoma patients. In contrast, this variant was less frequently detected in healthy donors, and in patients with HCMV viremia or myocardial infarction. We found, three clinical isolate that contained both the wild type HCMV and the variant HCMV strains; the variant was successfully plaque purified from endothelial cells (HUVEC). Electron microscopy analysis found dense body like particles but no HCMV particles in variant positive HUVEC cells. The variant expressed cytoplasmic IE proteins, which were of multiple sizes. Our results demonstrate a high prevalence of a novel genetic variant of HCMV in cancer patients, which may represent a new virus strain with potential oncogenic properties that warrants further investigation. In study II (Published in PlosONE 2014), the HCMV microRNA miR-UL112-3p suggested to mediate the latency and immune evasion strategies, also highly expressed in hypertension patients and associated with increased risk of hypertension. In our study, we detected miR- UL112-3p in plasma/serum of 52% (14/27) of Diabetic Mellitus, 25% (5/20) of Glioblastoma patients, in 5% (1/20) of Rheumatoid Arthritis patients and in 10% (2/20) of Healthy Controls. Anti-HCMV IgG was detected in 85%, 65%, 75% of patients and 70% of healthy controls, respectively. Anti-HCMV IgM was found only in one Glioblastoma patient of the 87 examined patients and controls. We didn’t found significant association between serology and miR- Ul112-3p. In study III (Accepted for publication), HCMV infected cells produce mature virions and defective particles called dense bodies (DBs). In this study, we purified these particles, and found that virions and DBs incorporate viral as well as host encoded RNAs and miRNAs within the particles. Furthermore, we demonstrated that the particle associated miRNAs can be delivered to host cells, are biologically functional, which may affect cellular processes. In study IV (Published in PLOS One 2013), we found that HCMV proteins IE and LA were abundantly expressed in all breast cancer tissue specimens examined (n=73) and 94% of their paired sentinel lymph node specimens (n=32/34) with metastases. Moreover, we also found HCMV IE and LA proteins in 60% (20/35) sentinel lymph node specimens without metastases. HCMV infections were mostly confined to the neoplastic cells, while some inflammatory cells were also HCMV positive in 79% of lymph nodes with metastases and 60% in metastatic free lymph nodes. We didn’t had enough sample to perform survival analysis, as only six patients died of breast cancer in this cohort. These six patients had high grade HCMV infection. High grade HCMV IE staining are more prevalent, due to the less patients in each group no further statistical correlation analyses with clinical prognostic factors (ER-α, PR and Elston grade) are reported. We conclude that, higher prevalence of HCMV proteins found in lymph nodes with metastasis than lymph nodes with metastasis, and bigger cohort is required to perform the correlation analysis. Another project by Dr. Afsar Rahbar in our lab, using more number of patients found the high expression of HCMV IE proteins in breast cancer tumours tissues inversely correlation with ER, PR and HER2 levels (manuscript in revision). In study V (Manuscript) we further studied this phenomenon in vitro; HCMV infection resulted in significant downregulation of mRNA and protein levels of ER-α, PR and Her-2 in breast cancer cell lines. This effect was dependent on viral gene expression. We found potential viral miRNAs which can targets of ER-α (miR-UL22A-3p, miRUL36-3p and miR-US25-2- 3p) and PR (miR-UL22A-3p). Overexpression of each viral miRNAs in a breast cancer cell line resulted in downregulation of mRNA and protein levels of ER-α and PR. Thus, HCMV may promote the establishment of triple negative breast cancer, through viral miRNA induced downregulation of ER-α, PR (and Her-2 by a yet unidentified mechanism). Antiviral therapy could hence be a potential alternative treatment strategy for selected breast cancer patients

Donut-Shaped mmWave Printed Antenna Array for 5G Technology

This article presents compact and novel shape ring-slotted antenna array operating at mmwave band on central frequency of 28 GHz. The proposed structure designed at 0.256 mm thin Roggers 5880 is composed of a ring shape patch with a square slot etched at the top mid-section of partial ground plane. Through optimizing the ring and square slot parameters, a high bandwidth of 8 GHz is achieved, ranging from 26 to 32 GHz, with a simulated gain of 3.95 dBi and total efficiency of 96% for a single element. The proposed structure is further transformed in a 4-element linear array manner. With compact dimensions of 20 mm 22 mm for array, the proposed antenna delivers a high simulated gain of 10.7 dBi and is designed in such a way that it exhibits dual beam response over the entire band of interest and simulated results agree with fabricated prototype measurements

A Sustainable Indoor Air Quality Monitoring Approach through Potable Living Wall for Closed Confined Spaces: A Way Forward to Fight Covid19

The COVID-19 pandemic has greatly influenced various aspects of life, part of which has consequently paved the way toward improvements in building design criteria, especially for closed confined spaces. The closed confined spaces are directly proportional to the quantity and quality of the volatile organic compounds (VOCs) present in the atmosphere, from which human beings breathe. In managing the impact produced by VOCs, a practical, sustainable, economical and environmentally friendly concept of indoor living walls has become a prominent feature for improving the indoor air quality (IAQ) of closed confined spaces to efficiently reduce sick building syndrome (SBS) factors. In modification of common practice of ventilation systems, living wall technology leverages the natural ability of plants to purify indoor air quality by reducing air pollutants and allows the recycling of indoor air and the creation of a productive and inspiring environment. In this paper, the concept of a portable living wall through the use of a native plant species locally available in Sindh, Pakistan is introduced. Herein, the portable living concept was assessed by means of the design, construction, and data collection (testing and monitoring) of various environmental parameters carried out before and after the installation of the living wall. The study was monitored for 90 days, and analyses for various types of air pollutants were carried out in the environmental laboratory. During the monitoring period, the parameters humidity, VOCs, hazardous chemicals of concern (HCOC), CO2 and CO showed reductions in their values, with changes observed ranging from 61.5 to 58%, 0.66 to 0.01 ppm, 0.2 to 0.01 ppm, 1070 to 528 ppm and 0.2 to 0.01 ppm, respectively. The outcomes showed noticeable changes in air pollutants coupled with reductions in heating, ventilation and air conditioning (HVAC) energy consumption by up to 25%, mainly due to limited air requirements for ventilation

Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults : a systematic review and meta-analysis

BACKGROUND : Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS : We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS : In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.S1 Data. CSV-formatted analysis dataset.S1 Fig. Forest plot of individual study estimates included in meta-analysis (all adults).S1 PRISMA Checklist. PRISMA checklist.S1 Table. Literature search methodology and results, by database.S2 Table. Summary of published articles included in the analyses, with reference list.S3 Table. Median number of specimens tested and percent positive for influenza, by age group, study design, and population, among all data sources.S4 Table. Regional estimates of influenza-associated lower respiratory infection (LRI) episodes and hospitalizations, by age group.S5 Table. Sensitivity analyses.Grants from the Foundation for Influenza Epidemiology, grants from Innovative Medicines Initiative, grants from the WHO, personal fees from Bill and Melinda Gates Foundation, grants and personal fees from Sanofi, grants from National Institute of Health Research, personal fees from Janssen and personal fees from AbbVie.https://journals.plos.org/plosmedicine/am2023Medical Virolog

Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis

Background: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. Methods and findings: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996–31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle–Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20–64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%–16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000–46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000–9,432,000) LRI hospitalizations occur each year among adults. While adults &lt;65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000–5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000–44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265–612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. Conclusions: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed

Future smartphone: MIMO antenna system for 5G mobile terminals

In this article, an inverted L-shaped monopole eight elements Multiple Input Multiple Output (MIMO) antenna system is presented. The multi-antenna system is designed on a low cost 0.8 mm thick FR4 substrate having dimensions of 136 x 68 mm(2) resonating at 3.5GHz with a 6dB measured bandwidth of 450MHz, and with inter element isolation greater than 15 dB and gain of 4 dBi. The proposed design consists of eight inverted L-shaped elements and parasitic L-shaped strips extending from the ground plane. These shorted stripes acted as tuning stubs for the four inverted L-shaped monopole elements on the side of chassis. This is done to achieve the desired frequency range by increasing the electrical length of the antennas. A prototype is fabricated, and the experimental results show good impedance matching with reasonable measured isolation within the desired frequency range. The MIMO performances, such as envelope correlation coefficient (ECC) and mean effective gain (MEG) are also calculated along with the channel capacity of 38.1bps/Hz approximately 2.6 times that of 4 x 4 MIMO system. Due to its simple shape and slim design, it may be a potential chassis for future handsets. Therefore, user hand scenarios, i.e. both single and dual hand are studied. Also, the effects of hand scenarios on various MIMO parameters are discussed along with the SAR. The performance of the proposed system in different scenarios suggests that the proposed structure holds promising future within the next generation radio smart phones.Antenna and Wireless Propagation Group ; Ministerio de Ciencia, Innovacion y Universidades, Gobierno de Espana (MCIU/AEI/FEDER, UE

Nanoscale Topical Pharmacotherapy in Management of Psoriasis: Contemporary Research and Scope

Psoriasis is a typical dermal condition that has been anticipated since prehistoric times when it was mistakenly implicit in being a variant of leprosy. It is an atypical organ-specific autoimmune disorder, which is triggered by the activation of T-cells and/or B-cells. Until now, the pathophysiology of this disease is not completely explicated and still, many research investigations are ongoing. Different approaches have been investigated to treat this dreadful skin disease using various anti-psoriatic drugs of different modes of action through smart drug-delivery systems. Nevertheless, there is no ideal therapy for a complete cure of psoriasis owing to the dearth of an ideal drug-delivery system for anti-psoriatic drugs. The conventional pharmacotherapy approaches for the treatment of psoriasis demand various classes of anti-psoriatic drugs with optimum benefit/risk ratio and insignificant untoward effects. The advancement in nanoscale drug delivery had a great impact on the establishment of a nanomedicine-based therapy for better management of psoriasis in recent times. Nanodrug carriers are exploited to design and develop nanomedicine-based therapy for psoriasis. It has a promising future in the improvement of the therapeutic efficacy of conventional anti-psoriatic drugs. The present manuscript aims to discuss the pathophysiology, conventional pharmacotherapy, and contemporary research in the area of nanoscale topical drug delivery systems for better management of psoriasis including the significance of targeted pharmacotherapy in psoriasis