An In Vitro Selection Platform to Identify Multiple Aptamers against Multiple Cell-Surface Markers Using Ligand-Guided Selection.

Aptamer ligand discovery against multiple molecules expressed on whole cells is an essential component in molecular tool development. However, owing to their intrinsic structural characteristics, cell-surface receptors have proven to be challenging targets in ligand discovery. Several variants to systematic evolution of ligands by exponential enrichment (SELEX) have been introduced to address the ″target problem″ for aptamer screening. To this end, we introduced a variant of SELEX, termed ligand-guided selection (LIGS), to identify highly specific aptamers against complex cell-surface markers in their native state. So far, the application of LIGS has been aimed at identifying aptamers against the most dominant receptors on the cell surface. Here, we report that LIGS can be expanded to identify two receptors on the same cell surface, paving the way to generate a multiplexed ligand discovery platform based on SELEX-targeting membrane receptors in their native functional state. Using CD19 and CD20 expressed on Toledo cells as a model system, multiple aptamer families were evolved against Toledo cells. We then utilized two monoclonal antibodies (mAbs) against CD20 and CD19 to selectively partition specific aptamers against CD19 and CD20. Following biochemical characterization, we introduce two specific aptamers against CD19 and two specific aptamers against CD20 with high affinity. Multi-target LIGS, as reported here, demonstrates a successful combinatorial approach for nucleic acid library screening to generate multiple artificial nucleic acid ligands against multiple receptors expressed on a single cell.

Effects of visual scanning exercises in addition to task specific approach on balance and activities of daily livings in post stroke patients with eye movement disorders: a randomized controlled trial.

BACKGROUND: Impaired vision is one of the commonest and most disabling consequence following stroke. Among all visual impairments, eye movement disorders are found in 70% of stroke patients which include nystagmus, strabismus, gaze palsies, disconjugate eye movements and cranial nerve palsies. They have a wide ranging impact on balance and activities of daily livings by creating difficulties in maintaining normal alignment and appropriate movement of eyes. The purpose of this study was to examine the effects of visual scanning exercises in addition to task specific approach on balance and activities of daily livings in post stroke patients with eye movement disorders. METHODS: This study is a randomized controlled trial and was conducted in the University of Lahore Teaching Hospital from May 2019 to October 2020. A sample of 64 patients was recruited and randomly allocated into experimental and control group. 32 patients in experimental group were treated with visual scanning exercises along with task specific approach and 32 patients in control group were treated with task specific approach alone. Pre and post assessment of balance and activities of daily livings was assessed on BERG BALANCE SCALE and BARTHEL INDEX SCALE at baseline and at 4th week. RESULTS: Intra-group analysis of BERG BALANCE SCALE in experimental group showed statistically significant result (p < 0.05) in all items except in items 4, 13 and 14 respectively. Intra-group analysis of BERG BALANCE SCALE in control group showed statistically significant result (p < 0.05) in items 3, 5, 8 and 12 respectively, whereas remaining all items showed statistically insignificant result. Intra-group analysis of BARTHEL INDEX SCALE in experimental group showed statistically significant result in all items (p < 0.05) except in items 9 and 10 respectively. Intra-group analysis of BARTHEL INDEX in control group showed statistically significant result (p < 0.05) in items 1, 3, 4 and 8 respectively whereas remaining all items showed statistically insignificant result. Inter-group analysis showed statistically significant result in total scores of BERG BALANCE SCALE (p = 0.000) and BARTHEL INEX SCALE (p = 0.033). CONCLUSION: Visual scanning exercises along with task specific approach were found to be more effective in comparison to task specific approach alone. TRIAL REGISTRATION: Trial registration number: [IRCT20190717044237N1], trial registration date: 10/11/2019.

Dual Z-scheme core-shell PANI-CeO2-Fe2O3-NiO heterostructured nanocomposite for dyes remediation under sunlight and bacterial disinfection.

Nowadays, environmental pollution due to discharge of organic pollutants from food, textile, and pharmaceutical industries into clean water and development of contagious diseases due to pathogenic organisms provide impetus to material researcher to fabricate novel design for efficient photocatalyst and antimicrobial agents. In this regard, designing a core-shell heterojunction catalyst based on metal oxides is considered an auspicious approach. In present study, combating the problems of singular oxides, core-shell PANI-CeO2-Fe2O3-NiO nanocomposite (PCFN) and CeO2-Fe2O3-NiO nanocomposite (CFN) was synthesized through sol-gel and oxidative polymerization route with cetyletrimethylammonium bromide (CTAB) as surfactant. The XRD, FTIR, and Raman confirmed the formation of nanocomposites with core-shell morphology composed of PANI (shell) and oxides (Core) in PCFN with a particle size of 52 nm (TEM). Surprisingly, PCFN has lower band gap, e-/h+ recombination, and larger charge transfer character than CFN. The decomposition test using MB and MO dyes showed that PCFN degraded 99%, 98%, while CFN degraded only 73% and 54%, respectively, under 50 min sunlight illumination. The reusability was assessed up to 7th cycle for PCFN. The influence of operational parameters (catalyst dose, dye concentration, pH) was tested for PCFN. Further, the antimicrobial action against S. aureus (gram + ve), E. coli (gram -ve) were also tested. The supreme performance of PCFN has been credited to heterostructure dual Z-scheme formation and core-shell morphology supported with PANI, which suppresses the e-/h+ recombination process by promoting their separation. The present finding indicated that the PCFN is a promising modifier for bacterial disinfection and acts as a superb photocatalyst through core-shell formation with PANI support.

Spectrum of hollow visceral injury due to isolated blunt trauma abdomen presented to a tertiary care trauma hospital of Pakistan.

OBJECTIVE: To evaluate the spectrum of isolated hollow visceral perforations in patients presenting with abdominal blunt trauma. METHODS: The observational, analytical, cross-sectional study was conducted at the surgical ward of Mayo Hospital, Lahore, Pakistan from July 1, 2020, to June 31, 2021, and comprised patients who presented in the emergency department after blunt trauma to abdomen without any open wound. Findings of hollow visceral injury were confirmed on exploration laparotomy. Data was analysed using SPSS 26. RESULTS: Of the 216 patients, 173(80.9%) were male and 43(19.9%) were female. The overall mean age was 42±9.7 years. Most of the blunt trauma abdomen cases were caused by motor vehicle accidents 59(27.3%). The most common hollow viscus affected was jejunum 42(19.4%), followed by transverse colon 29(13.4%). The most common type of injury observed was single complete disruption of hollow viscus 74(34.2%). CONCLUSIONS: The most common hollow organ affected by blunt trauma to the abdomen was jejunum, followed by transverse colon, and motor vehicle accidents were the major cause of these injuries.

Prediction of putative epitope-based vaccine against all corona virus strains for the Chinese population: Approach toward development of vaccine.

Currently, the whole world is facing the coronavirus disease-19 pandemic. As of now, approximately 0.15 million people around the globe are infected with the novel coronavirus. In the last decade, two strains of the coronavirus family, severe acute respiratory syndrome-related coronavirus and Middle East respiratory syndrome coronavirus, also resulted in epidemics in south Asian and the Middle Eastern countries with high mortality rate. This scenario demands the development of a putative vaccine which may provide immunity against all current and new evolving coronavirus strains. In this study, we designed an epitope-based vaccine using an immunoinformatic approach. This vaccine may protect against all coronavirus strains. The vaccine is developed by considering the geographical distribution of coronavirus strains and host genetics (Chinese population). Nine experimentally validated epitopes sequences from coronavirus strains were used to derive the variants considering the conservancy in all strains. Further, the binding affinities of all derived variants were checked with most abundant human leukocyte antigen alleles in the Chinese population. Three major histocompatibility complex (MHC) Class I epitopes from spike glycoprotein and nucleoprotein showed sufficient binding while one MHC Class II epitope from spike glycoprotein was found to be an effective binder. A cocktail of these epitopes gave more than 95% population coverage in the Chinese population. Moreover, molecular dynamics simulation supported the aforementioned predictions. Further, in vivo studies are needed to confirm the immunogenic potential of these vaccines.

Ligand-Guided Selection with Artificially Expanded Genetic Information Systems against TCR-CD3ε.

Here we are reporting, for the first time, a ligand-guided selection (LIGS) experiment using an artificially expanded genetic information system (AEGIS) to successfully identify an AEGIS-DNA aptamer against T cell receptor-CD3ε expressed on Jurkat.E6 cells. Thus, we have effectively combined the enhanced diversity of an AEGIS DNA library with LIGS to develop a superior screening platform to discover superior aptamers. Libraries of DNA molecules from highly diversified building blocks will provide better ligands due to more functional diversity and better-controlled folding. Thus, a DNA library with AEGIS components (dZ and dP) was used in LIGS experiments against TCR-CD3ε in its native state using two clinically relevant monoclonal antibodies to identify an aptamer termed JZPO-10, with nanomolar affinity. Multiple specificity assays using knockout cells, and competition experiments using monoclonal antibodies utilized in LIGS, show unprecedented specificity of JZPO-10, suggesting that the combination of LIGS with AEGIS-DNA libraries will provide a superior screening platform to discover artificial ligands against critical cellular targets.

Prediction of epitopes of Neisseria Gonorrhoeae against USA human leukocyte antigen background: An immunoinformatic approach towards development of future vaccines for USA population.

Gonorrheal infections are the second most prevalent sexually transmitted diseases STDs in the USA populations after Chlamydia. These infections have now become an urgent problem to address because Neisseria gonorrhoeae is capable of developing resistance to multiple antibiotic classes. Infection with these antibiotic-resistant strains has become the major public health concern. Although extensive researches are ongoing to control its transmission and to develop the productive treatments against this pathogen, no effective vaccine could develop till now. The present study will effectively contribute to the future designing of USA specific epitope-based vaccines. Through computational approaches, this study has highlighted putative epitopes from Neisseria gonorrhoeae which restrict maximally to the frequent HLA alleles in the USA populations. Antigenic and non-allergenic nature of predicted epitopes was verified using vexijen and AllerTOP tools respectively. Total seven epitopes, four from class-I and three from class-II were antigenic as well as non-allergenic. These epitopes showed USA population coverage of 99.3% with no allergenic response. Still, additional studies are needed to validate the immunogenic properties of the predicted epitopes which are likely vaccine target for gonorrhoea in the USA populations.

Structural optimization of an aptamer generated from Ligand-Guided Selection (LIGS) resulted in high affinity variant toward mIgM expressed on Burkitt's lymphoma cell lines.

Aptamers are synthetic, short nucleic acid molecules capable of specific target recognition. Aptamers are selected using a screening method termed Systematic Evolution of Ligands by Exponential enrichment (SELEX). We recently have introduced a variant of SELEX called "Ligand-Guided-Selection" (LIGS) that allows the identification of specific aptamers against known cell-surface proteins. Utilizing LIGS, we introduced three specific aptamers against membrane-bound IgM (mIgM), which is the hallmark of B cells. Out of the three aptamers selected against mIgM, an aptamer termed R1, in particular, was found to be interesting due to its ability to recognize mIgM on target cells and then block anti-IgM antibodies binding their antigen. We systematically truncated parent aptamer R1 to design shorter variants with enhanced affinity. Importantly, herein we show that the specificity of the most optimized variant of R1 aptamer is similar to that of anti-IgM antibody, indicating that the specificity of the ligand utilized in selective elution of the aptamer determines the specificity of the LIGS-generated aptamer. Furthermore, we report that truncated variants of R1 are able to recognize mIgM-positive human B lymphoma BJAB cells at physiological temperature, demonstrating that LIGS-generated aptamers could be re-optimized into higher affinity variants. Collectively, these findings show the significance of LIGS in generating highly specific aptamers with potential applications in biomedicine.

Ligand-guided selection of aptamers against T-cell Receptor-cluster of differentiation 3 (TCR-CD3) expressed on Jurkat.E6 cells.

We recently introduced a screening technology termed ligand-guided selection, (LIGS), to selectively identify target-specific aptamers from an evolved cell-SELEX library. Cell-SELEX utilizes a large combinatorial single-stranded oligonucleotide library and progressively selects DNA ligands against whole cells with variable DNA-binding affinities and specificities by repeated rounds of partition and amplification. LIGS exploits the partition step and introduces a secondary, pre-existing high-affinity monoclonal antibody (mAb) ligand to outcompete and elute specific aptamers towards the binding target of the antibody, not the cell. Here, using anti-CD3ε mAb against the cluster of differentiation 3 (CD3ε), as the guiding ligand against one of the domains of the T-cell Receptor (TCR) complex expressed on Jurkat.E6 cells, we discovered three specific aptamers against TCR complex expressed on an immortalized line of human T lymphocyte cells. In sum, we demonstrate that specific aptamers can be identified utilizing an antibody against a single domain of a multidomain protein complex in their endogenous state with neither post- nor pre-SELEX protein manipulation.

To compare the effectiveness of constraint induced movement therapy versus motor relearning programme to improve motor function of hemiplegic upper extremity after stroke.

OBJECTIVE: To compare the effectiveness of constraint induced movement therapy versus motor relearning programme to improve motor function of hemiplegic upper extremity after stroke. METHOD: A sample of 42 patients was recruited from the Physiotherapy Department of IPM&R and Neurology OPD of Civil Hospital Karachi through non probability purposive sampling technique. Twenty one patients were placed to each experimental and control groups. Experimental group was treated with Constraint Induced Movement Therapy (CIMT) and control group was treated with motor relearning programme (MRP) for three consecutive weeks. Pre and post treatment measurements were determined by upper arm section of Motor Assessment Scale (MAS) and Self Care item of Functional Independence Measure (FIM) Scale. RESULTS: Intra group analysis showed statistically significant results (p-value<0.05) in all items of MAS in both groups. However, advanced hand activities item of MAS in MRP group showed insignificant result (p-value=0.059). Self-care items of FIM Scale also showed significant result (p-value< 0.05) in both groups except dressing upper body item (p-value=0.059) in CIMT group and grooming and dressing upper body items (p-value=0.059 & 0.063) in MRP group showed insignificant p-values. CONCLUSION: CIMT group showed more significant improvement in motor function and self-care performance of hemiplegic upper extremity as compared to MRP group in patients with sub-acute stroke assessed by the MAS and FIM scales. Thus CIMT is proved to be more statistically significant and clinically effective intervention in comparison to motor relearning programme among the patients aged between 35-60 years. Further studies are needed to evaluate CIMT effects in acute and chronic post stroke population.

A comparative study on green synthesis and characterization of Mn doped ZnO nanocomposite for antibacterial and photocatalytic applications.

Biological and green synthesis of nanomaterial is a superior choice over chemical and physical methods due to nanoscale attributes implanted in a green chemistry matrix, have sparked a lot of interest for their potential uses in a variety of sectors. This research investigates the growing relevance of nanocomposites manufactured using ecologically friendly, green technologies. The transition to green synthesis correlates with the worldwide drive for environmentally sound procedures, limiting the use of traditional harsh synthetic techniques. Herein, manganese was decorated on ZnO NPs via reducing agent of Withania-extract and confirmed by UV-spectrophotometry with highest peak at 1:2 ratio precursors, and having lower bandgap energy (3.3 eV). XRD showed the sharp peaks and confirms the formation of nanoparticles, having particle size in range of 11-14 nm. SEM confirmed amorphous tetragonal structure while EDX spectroscopy showed the presence of Zn and Mn in all composition. Green synthesized Mn-decorated ZnO-NPs screened against bacterial strains and exhibited excellent antimicrobial activities against gram-negative and gram-positive bacteria. To check further, applicability of synthesized Mn-decorated Zn nanocomposites, their photocatalytic activity against toxic water pollutants (methylene blue (MB) dye) were also investigated and results showed that 53.8% degradation of MB was done successfully. Furthermore, the installation of green chemistry in synthesizing nanocomposites by using plant extract matrix optimizes antibacterial characteristics, antioxidant and biodegradability, helping to build sustainable green Mn decorated ZnO nanomaterial. This work, explains how biologically friendly Mn-doped ZnO nanocomposites can help reduce the environmental impact of traditional packaging materials. Based on these findings, it was determined that nanocomposites derived from biological resources should be produced on a wide scale to eradicate environmental and water contaminants through degradation.

The role of reduced graphene oxide on mitigation of lead phytotoxicity in Triticum aestivum L.plants at morphological and physiological levels.

Rapid global industrialization and an increase in population have enhanced the risk of heavy metals accumulation in plant bodies to disrupt the morphological, biochemical, and physiological processes of plants. To cope with this situation, reduced graphene oxide (rGO) NPs were used first time to mitigate abiotic stresses caused in plant. In this study, rGO NPs were synthesized and reduced with Tecoma stans plant leave extract through modified Hummer's methods. The well prepared rGO NPs were characterized by ultra-violet visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Zeta potential, and scanning electron microscopy (SEM). However, pot experiment was conducted with four different concentrations (15, 30, 60, 120 mg/L) of rGO NPs and three different concentrations (300, 500,700 mg/L) of lead (Pb) stress were applied. To observe the mitigative effects of rGO NPs, 30 mg/L of rGO NPs and 700 mg/L of Pb were used in combination. Changes in morphological and biochemical characteristics of wheat plants were observed for both Pb stress and rGO NPs treatments. Pb was found to inhibit the morphological and biochemical characteristics of plants. rGO NPs alone as well as in combination with Pb was found to increase the chlorophyll content of wheat plants. Under Pb stress conditions and rGO NPs treatments, antioxidant enzyme activities like ascorbate peroxidases (APX), superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were observed. Current findings revealed that greenly reduced graphene oxide NPs can effectively promote growth in wheat plants under Pb stress by elevating chlorophyll content of leaves, reducing the Pb uptake, and suppressing ROS produced due to Pb toxicity.

Personal Social Networks and Care-Seeking for Head and Neck Cancer: A Qualitative Study.

OBJECTIVES: To investigate the role of patients' personal social networks (SNs) in accessing head and neck cancer (HNC) care through patients' and health care workers' (HCWs) perspectives. STUDY DESIGN: Qualitative study. SETTING: Tertiary HNC centers at 2 academic medical centers, including 1 safety net hospital. METHODS: Patients with newly diagnosed HNC, and HCWs caring for HNC patients, aged ≥18 years were recruited between June 2022 and July 2023. Semistructured interviews were conducted with both patients and HCWs. Inductive and deductive thematic analysis was performed with 2 coders (κ = 0.82) to analyze the data. RESULTS: The study included 72 participants: 42 patients (mean age 57 years, 64% female, 81% white), and 30 HCWs (mean age 42 years, 77% female, 83% white). Four themes emerged: (1) Patients' SNs facilitate care through various forms of support, (2) patients may hesitate to seek help from their networks, (3) obligations toward SNs may act as barriers to seeking care, and (4) the SN composition and dedication influence care-seeking. CONCLUSION: Personal SNs play a vital role in prompting early care-seeking among HNC patients. SN-based interventions could enhance care and improve outcomes for HNC patients.

Perspectives on Referral Pathways for Timely Head and Neck Cancer Care.

Importance: Timely diagnosis and treatment are of paramount importance for patients with head and neck cancer (HNC) because delays are associated with reduced survival rates and increased recurrence risk. Prompt referral to HNC specialists is crucial for the timeliness of care, yet the factors that affect the referral and triage pathway remain relatively unexplored. Therefore, to identify barriers and facilitators of timely care, it is important to understand the complex journey that patients undertake from the onset of HNC symptoms to referral for diagnosis and treatment. Objective: To investigate the referral and triage process for patients with HNC and identify barriers to and facilitators of care from the perspectives of patients and health care workers. Design, Participants, and Setting: This was a qualitative study using semistructured interviews of patients with HNC and health care workers who care for them. Participants were recruited from June 2022 to July 2023 from HNC clinics at 2 tertiary care academic medical centers in Boston, Massachusetts. Data were analyzed from July 2022 to December 2023. Main Outcomes and Measures: Themes identified from the perspectives of both patients and health care workers on factors that hinder or facilitate the HNC referral and triage process. Results: In total, 72 participants were interviewed including 42 patients with HNC (median [range] age, 60.5 [19.0-81.0] years; 27 [64%] females) and 30 health care workers (median [range] age, 38.5 [20.0-68.0] years; 23 [77%] females). Using thematic analysis, 4 major themes were identified: the HNC referral and triage pathway is fragmented; primary and dental care are critical for timely referrals; efficient interclinician coordination expedites care; and consistent patient-practitioner engagement alleviates patient fear. Conclusions and Relevance: These findings describe the complex HNC referral and triage pathway, emphasizing the critical role of initial symptom recognition, primary and dental care, patient information flow, and interclinician and patient-practitioner communication, all of which facilitate prompt HNC referrals.

Healthcare Disparities in Otolaryngology.

Purpose of Review: The purpose of this review is to summarize some of the recent research studies on healthcare disparities across various subspecialties within otolaryngology. This review also highlights the impact of COVID-19 pandemic on disparities and proposes potential interventions to mitigate disparities. Recent Findings: Significant healthcare disparities in care and treatment outcomes have been reported across all areas of otolaryngology. Notable differences in survival, disease recurrence, and overall mortality have been noted based on race, ethnicity, socioeconomic status (SES), insurance status, etc. This is most well-researched in head and neck cancer (HNC) within otolaryngology. Summary: Healthcare disparities have been identified by numerous research studies within otolaryngology for many vulnerable groups that include racial and ethnic minority groups, low-income populations, and individuals from rural areas among many others. These populations continue to experience suboptimal access to timely, quality otolaryngologic care that exacerbate disparities in health outcomes.

Intrarater and interrater reliability of the dynamic gait index in post stroke patients with eye movement disorders.

BACKGROUND: The Dynamic Gait Index (DGI) is a useful tool that has been evaluated for its reliability in patients with vestibular disorders, elderly people and, in chronic stroke population. Present study was aimed to evaluate the intrarater and interrater reliability of the DGI to measure dynamic balance and gait performance in stroke patients with eye movement disorders. METHODS: A sample of 30 stroke patients suffering from eye movement disorders were recruited. Two Physical therapists assessed the intrarater and interrater reliability of the DGI in two testing sessions three days apart. In the later session, two raters assessed the patients' performance simultaneously on the DGI. The reliability was calculated using the intra-class correlation coefficient (ICC2, 1). Standard error of measurement (SEM) and minimal detectable change (MDC95) at 95% confidence interval were also calculated. A significance level was set at p-value <0.05. RESULTS: The (ICC2, 1) for intrarater and interrater reliability of total DGI scores was 0.86 and 0.91 respectively. While (ICC2, 1) for intrarater and interrater reliability of individual items ranged from 0.73 to 0.91 to 0.73-0.93, respectively. The (SEM) and (MDC95) for intrarater reliability of total DGI scores were 0.76 and 2.10, respectively. Corresponding values for interrater reliability were 0.62 and 1.71, respectively. CONCLUSIONS: The DGI is a reliable tool for evaluating the dynamic balance and gait performance in stroke patients with eye movement disorders. This tool showed good to excellent intrarater and interrater reliability of total DGI scores and moderate to good intrarater and interrater reliability of individual items of the DGI.

Improved catalytic efficiency of chimeric xylanase 10B from Thermotoga petrophila RKU1 and its synergy with cellulases.

TpXyl10B is a glycoside hydrolase family 10 xylanase of hyperthermophile Thermotoga petrophila RKU-1. This enzyme is of considerable importance due to its thermostability. However, in its native state, this enzyme does not possess any carbohydrate-binding module (CBM) for efficient binding to plant biomass. In this study CBM6 from Clostridium thermocellum was attached to the N- and C-termini of TpXyl10B, thereby producing the variants TpXyl10B-B6C and TpXyl10B-CB6, respectively. TpXyl10B-B6C showed 5-7 folds increased activity on Beechwood xylan and the different types of plant biomass as compared to that from the catalytic domain only. However, the activity of TpXyl10B-CB6 decreased 0.6-0.8 folds on Beechwood xylan and plant biomass compared to the catalytic domain. We explained these results through molecular modeling, which showed that binding residues of CBM6's cleft B, which were previously reported to show no contribution towards binding due to steric hindrance from a loop region, were exposed in a favorable position in TpXyl10B-B6C such that they efficiently bound the substrate. In contrast, these binding residues of CBM6 in TpXyl10B-CB6 were exposed opposite to the catalytic residues; thus, binding to the substrate resulted in decreased exposure of catalytic residues to the substrate. CD spectroscopy and thermostability assays showed that TpXyl10B-B6C was highly thermostable, having a melting point > 90 °C, which is relatively higher than that of the other variant, TpXyl10B-CB6. In addition, this xylanase variant showed synergism with cellulases for the hydrolysis of plant biomass. Therefore, TpXyl10B-B6C, an engineered xylanase in this study, can be a valuable candidate for industrial applications.

Circulating tumor-tissue modified HPV DNA testing in the clinical evaluation of patients at risk for HPV-positive oropharynx cancer: The IDEA-HPV study.

OBJECTIVES: While survival outcomes are favorable for Human Papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs), early diagnosis may minimize treatment-related morbidity and mortality. This study evaluated circulating tumor tissue-modified viral (TTMV)-HPV DNA plasma testing to facilitate early diagnosis of HPV-positive OPSCCs. METHODS: In this prospective exploratory cohort study, patients presenting to an Otolaryngology-Head and Neck Surgery clinic with unexplained signs or symptoms considered high-risk for HPV-positive OPSCC were recruited between March 2021-October 2022. Circulating TTMV-HPV DNA testing was performed, and results were shared with subjects and treating clinicians. Clinicians were surveyed regarding the perceived clinical utility of the test. RESULTS: Thirty-nine subjects were included. Most subjects were women (N = 23, 59 %), white (N = 32, 82 %) and never-smokers (N = 20, 51 %) with median age 60 years. Circulating TTMV-HPV DNA was detected in 2/39 subjects, both subsequently diagnosed with HPV-positive OPSCC. Both were white men aged 70-80 years with a neck mass. One subject with undetectable TTMV-HPV DNA was also diagnosed with HPV-positive OPSCC through excisional neck mass biopsy. Other eventual diagnoses included 3 HPV-negative head and neck squamous cell carcinomas and 4 other malignancies. Testing was perceived as helpful in clinical decision-making for 26/38 (68 %) subjects, and useful for similar future patients for 32/37 (86 %) subjects. CONCLUSION: Circulating TTMV-HPV DNA testing is feasible and holds potential as a diagnostic aid for HPV-positive OPSCC alongside standard clinical workup. Clinicians should be cognizant of its limitations, as a negative test does not necessarily indicate the absence of disease. Further studies to evaluate its utility are warranted.

Energy-levels well-matched direct Z-scheme ZnNiNdO/CdS heterojunction for elimination of diverse pollutants from wastewater and microbial disinfection.

Energy-levels well-matched direct Z-scheme ZnNiNdO/CdS heterojunction was successfully fabricated using facile co-precipitation and ultra-sonication techniques and characterized with XRD, FTIR, Raman, PL, UV-vis, and FE-SEM. The XRD diffractograms confirmed the co-doping of Ni-Nd in ZnO and the formation of heterostructured nanocomposite. FTIR and Raman data showed the presence of metal-oxygen vibration and optical phonon modes of ZnO and CdS. FE-SEM images exhibited the network type morphology. The energy bandgap was redshifted by co-doping (3.37-2.9 eV) and was further reduced (2.6 eV) by making a composite with CdS. The ZnNiNdO/CdS catalyst degraded 99.7, 49, 96.6, 98.6, and 98.6% methylene blue (MB), p-nitroaniline (P-Nitro), methyl orange (MO), methyl red (MR), and rhodamine B (RhB) dyes under 50 min sunlight irradiation. Moreover, ZnNiNdO/CdS showed intense inhibition activity towards Staphylococcus aureus, Escherichia coli, Proteus vulgaris, and Pseudomonas aeruginosa bacterial strains with maximum inhibition zone diameters 30, 33, 27, and 31 mm, respectively. The synergistic effects arising from band alignment can lead to efficient vectorial charge separation, transportation, and lower recombination of photoinduced charge carriers, ultimately boosting photocatalytic and antibacterial performance. The ZnNiNdO/CdS photocatalyst has higher stability up to the 7th cycle towards MB dye with ~ 5% deficit in degradation efficiency. The higher generation of superoxide and hydroxyl radical was confirmed by species trapping experiments responsible for photodegradation of dyes molecules. Furthermore, the results showed that the photocatalytic and antibacterial performance of pristine ZnO can be enhanced by co-doping and tuning energy bandgap.

Transition metal-doped SnO2 and graphene oxide (GO) supported nanocomposites as efficient photocatalysts and antibacterial agents.

In the present work, pristine and transition metal (TM) (W, Ag, Zn)-doped SnO2 nanocrystals using a facile sol-gel approach were synthesized. The grown products were anchored on graphene oxide (GO) sheets via a simple ultrasonication technique to fabricate binary nanocomposites. The structural, optical, and morphological properties of as-synthesized samples were studied by XRD, FTIR, Raman, EDX, UV-Visible, PL, and FE-SEM. The charge transferability of graphene oxide-based samples was investigated by EIS. The XRD exhibited the TM doping in SnO2 and the development of GO-based nanocomposite. FTIR data evidenced the existence of the metal-oxygen bonds. Raman spectra presented the optical phonon modes of SnO2 and the existence of oxygen vacancy defects. FE-SEM images demonstrated the anchoring of particles on the GO sheet, and EDX further approved the existence of desired dopants. The integration of SnO2 with TM doping remarkably reduced optical bandgap (3.65-3.10 eV), which was further decreased (3.10-2.99 eV) by making composite with GO. The photodegradation results exhibited that GO-based nanocomposites have the higher potential to degrade synthetic dyes (methyl red (MR), and methyl orange (MO) and SnZnO2/GO have shown superb photocatalytic performance after 80-min sunlight illumination (99.9% MR and 95.0% MO dyes) with the higher rate constant and superior stability up to 6th cycle against MR dye. The grown samples were tested for bacterial disinfection, and SnZnO2/GO sample showed a higher zone of inhibition towards S. aureus and K. pneumoniae bacteria strains. The greater charge transfer rate and lower recombination of charge carriers in GO-based composites were also observed by EIS and PL analysis. Moreover, the present article ascribed that the photocatalytic and antibacterial properties of bare SnO2 could be improved by TM doping and fabricating their composite with GO.