Prevalence of high-risk human papillomavirus in oral squamous cell carcinoma with or without chewing habits.

Oral cancer (OC) is the most common cancer in Pakistani males and the second most common in females. Major risk factors include peculiar chewing habits, human papillomavirus (HPV) infection and molecular pathways. However, less data is available for this avertible cancer regarding its association with high-risk HPV (HR-HPV) and chewing habits in this region. Therefore, this study was done to determine the prevalence of HR-HPV in oral squamous cell carcinoma (OSCC) and its correlation with p16 and chewing habits. Formalin-fixed paraffin-embedded (FFPE) biopsy specimens of 186 samples were tested for HR-HPV type 16/18 by PCR, followed by p16 immunostaining (IHC) in a subset of cases (n = 50). Appropriate statistical tests were applied to find the association between HR-HPV/p16 and peculiar chewing habits with significance criteria of p<0.05 with 95% CI. HR-HPV (type 16 &18) was present in seven out of 186 cases (3.8%). Of these seven cases, five were positive for HPV16, whereas two were positive for HPV16/18. The overall expression of p16 protein in 50 samples was 38% (n = 19), and among these 19-IHC positive samples, 26% were positive for HR-HPV DNA. No significant association was found between HR-HPV positivity and p16 and chewing habits (p>0.05). It was concluded that HR-HPV prevalence in OSCC was very low in our population, with no statistically significant correlation with p16 and chewing habits. These results suggest the role of HR-HPV as an independent risk factor in OSCC in the local setting.

Recent Advances in Cerium Oxide-Based Memristors for Neuromorphic Computing.

This review article attempts to provide a comprehensive review of the recent progress in cerium oxide (CeO2)-based resistive random-access memories (RRAMs). CeO2 is considered the most promising candidate because of its multiple oxidation states (Ce3+ and Ce4+), remarkable resistive-switching (RS) uniformity in DC mode, gradual resistance transition, cycling endurance, long data-retention period, and utilization of the RS mechanism as a dielectric layer, thereby exhibiting potential for neuromorphic computing. In this context, a detailed study of the filamentary mechanisms and their types is required. Accordingly, extensive studies on unipolar, bipolar, and threshold memristive behaviors are reviewed in this work. Furthermore, electrode-based (both symmetric and asymmetric) engineering is focused for the memristor's structures such as single-layer, bilayer (as an oxygen barrier layer), and doped switching-layer-based memristors have been proved to be unique CeO2-based synaptic devices. Hence, neuromorphic applications comprising spike-based learning processes, potentiation and depression characteristics, potentiation motion and synaptic weight decay process, short-term plasticity, and long-term plasticity are intensively studied. More recently, because learning based on Pavlov's dog experiment has been adopted as an advanced synoptic study, it is one of the primary topics of this review. Finally, CeO2-based memristors are considered promising compared to previously reported memristors for advanced synaptic study in the future, particularly by utilizing high-dielectric-constant oxide memristors.

Mimicking biological synapses with a-HfSiOx-based memristor: implications for artificial intelligence and memory applications.

Memristors, owing to their uncomplicated structure and resemblance to biological synapses, are predicted to see increased usage in the domain of artificial intelligence. Additionally, to augment the capacity for multilayer data storage in high-density memory applications, meticulous regulation of quantized conduction with an extremely low transition energy is required. In this work, an a-HfSiOx-based memristor was grown through atomic layer deposition (ALD) and investigated for its electrical and biological properties for use in multilevel switching memory and neuromorphic computing systems. The crystal structure and chemical distribution of the HfSiOx/TaN layers were analyzed using X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), respectively. The Pt/a-HfSiOx/TaN memristor was confirmed by transmission electron microscopy (TEM) and showed analog bipolar switching behavior with high endurance stability (1000 cycles), long data retention performance (104 s), and uniform voltage distribution. Its multilevel capability was demonstrated by restricting current compliance (CC) and stopping the reset voltage. The memristor exhibited synaptic properties, such as short-term plasticity, excitatory postsynaptic current (EPSC), spiking-rate-dependent plasticity (SRDP), post-tetanic potentiation (PTP), and paired-pulse facilitation (PPF). Furthermore, it demonstrated 94.6% pattern accuracy in neural network simulations. Thus, a-HfSiOx-based memristors have great potential for use in multilevel memory and neuromorphic computing systems.

Barriers and facilitators of childhood COVID-19 vaccination among parents: A systematic review.

Background: The acceptance of vaccination against COVID-19 among parents of young children plays a significant role in controlling the current pandemic. A wide range of factors that influence vaccine hesitancy in adults has been reported worldwide, but less attention has been given to COVID-19 vaccination among children. Vaccine hesitancy is considered a major challenge in achieving herd immunity, and it is more challenging among parents as they remain deeply concerned about their child's health. In this context, a systematic review of the current literature is inevitable to assess vaccine hesitancy among parents of young children to ensure a successful ongoing vaccination program. Method: A systematic search of peer-reviewed English literature indexed in Google Scholar, PubMed, Embase, and Web of science was performed using developed keywords between 1 January 2020 and August 2022. This systematic review included only those studies that focused on parental concerns about COVID-19 vaccines in children up to 12 years without a diagnosis of COVID-19. Following PRISMA guidelines, a total of 108 studies were included. The quality appraisal of the study was performed by Newcastle-Ottawa Scale (NOS). Results: The results of 108 studies depict that vaccine hesitancy rates differed globally with a considerably large number of factors associated with it. The highest vaccine hesitancy rates among parents were reported in a study from the USA (86.1%) and two studies from Saudi Arabia (>85%) and Turkey (89.6%). Conversely, the lowest vaccine hesitancy rates ranging from 0.69 and 2% were found in two studies from South Africa and Switzerland, respectively. The largest study (n = 227,740) was conducted in Switzerland while the smallest sample size (n = 12) was represented by a study conducted in the USA. The most commonly reported barriers to childhood vaccination were mothers' lower education level (N = 46/108, 43%), followed by financial instability (N = 19/108, 18%), low confidence in new vaccines (N = 13/108, 12%), and unmonitored social media platforms (N = 5/108, 4.6%). These factors were significantly associated with vaccine refusal among parents. However, the potential facilitators for vaccine uptake among respondents who intended to have their children vaccinated include higher education level (N = 12/108, 11%), followed by information obtained through healthcare professionals (N = 9/108, 8.3%) and strong confidence in preventive measures taken by the government (N = 5/81, 4.6%). Conclusion: This review underscores that parents around the globe are hesitant to vaccinate their kids against COVID-19. The spectrum of factors associated with vaccine hesitancy and uptake varies across the globe. There is a dire need to address vaccine hesitancy concerns regarding the efficacy and safety of approved vaccines. Local context is inevitable to take into account while developing programs to reduce vaccine hesitancy. There is a dire need to devise strategies to address vaccine hesitancy among parents through the identification of attributing factors.

Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex.

The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic (PL) cortex respond to both threat- and reward-associated cues. However, it remains unknown whether PL regulates threat-avoidance vs. reward-approaching responses when an animals' decision depends on previously associated memories. Using a conflict model in which male Long-Evans rats retrieve memories of shock- and food-paired cues, we observed two distinct phenotypes during conflict: (1) rats that continued to press a lever for food (Pressers) and (2) rats that exhibited a complete suppression in food seeking (Non-pressers). Single-unit recordings revealed that increased risk-taking behavior in Pressers is associated with persistent food-cue responses in PL, and reduced spontaneous activity in PL glutamatergic (PLGLUT) neurons during conflict. Activating PLGLUT neurons in Pressers attenuated food-seeking responses in a neutral context, whereas inhibiting PLGLUT neurons in Non-pressers reduced defensive responses and increased food approaching during conflict. Our results establish a causal role for PLGLUT neurons in mediating individual variability in memory-based risky decision-making by regulating threat-avoidance vs. reward-approach behaviors.

Germline and somatic mutations in the pathology of pineal cyst: A whole-exome sequencing study of 93 individuals.

BACKGROUND: Pineal cyst is a benign lesion commonly occurring in people of any age. Until now, the underlying molecular alterations have not been explored. METHODS: We performed whole exome sequencing of 93 germline samples and 21 pineal cyst tissue samples to illustrate its genetic architecture and somatic mutations. The dominant and recessive inheritance modes were considered, and a probability was calculated to evaluate the significance of variant overrepresentation. RESULTS: By analyzing pineal cyst as a Mendelian disease with a dominant inheritance pattern, we identified 42,325 rare germline variants, and NM_001004711.1:c.476A>G was highly enriched (FDR<0.2). By analyzing it as a recessive disorder, we identified 753 homozygous rare variants detected in at least one pineal cyst sample each. One STIM2 rare variant, NM_001169117.1:c.1652C>T, was overrepresented (FDR<0.05). Analyzing at a gene-based level, we identified a list of the most commonlymutated germline genes, including POP4, GNGT2 and TMEM254. A somatic mutation analysis of 21 samples identified 16 variants in 15 genes, which mainly participated in the biological processes of gene expression and epigenetic regulation, immune response modulation, and transferase activity. CONCLUSION: These molecular profiles are novel for this condition and provide data for investigators interested in pineal cysts.

Evaluation of risk factors associated with the development of MDR- and XDR-TB in a tertiary care hospital: a retrospective cohort study.

BACKGROUND: Drug resistant tuberculosis (DR-TB) infringes substantial burden in terms of longer treatment duration, morbidity and mortality. Timely identification of patients at risks of DR-TB will aid individualized treatment. Current study was aimed to ascertain several factors associated with DR-TB among patients attending a tertiary care hospital. METHODS: This retrospective study was conducted among patients with confirmed diagnosis of DR-TB and drug susceptible TB (DS-TB) seeking medical care from a tertiary care hospital during 2014-2019. The types of DR-TB included were rifampicin resistant tuberculosis (RR-TB), Multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Appropriate statistical methods were implied to evaluate the factors associated with DR-TB. RESULTS: Out of 580 patients, DS-TB was diagnosed in 198 (34.1%) patients while DR-TB was present in 382 patients. Of resistance cases, RR-TB, MDR-TB and XDR-TB were diagnosed in 176 (30.3%), 195 (33.6%) and 11 (1.9%) patients, respectively. Significant differences (P < 0.05) in demographics and clinico-laboratory characteristics were observed between patients with DS-TB and DR-TB. Logistic regression analysis revealed age ≤38 years (OR: 2.5), single marital status (OR: 11.1), tobacco use (OR: 2.9), previous treatment (OR: 19.2), treatment failure (OR: 9.2) and cavity on chest X-ray (OR: 30.1) as independent risk factors for MDR-TB. However, XDR-TB was independently associated with age group of ≤38 years (OR: 13.6), students (OR: 13.0), previous treatment (OR: 12.5), cavity on chest X-ray (OR: 59.6). The independent risk factors associated with RR-TB are age ≤38 years (OR: 2.8), females (OR: 5.7), unemployed (OR: 41.5), treatment failure (OR: 4.9), previous treatment (OR: 38.2) and cavity on chest X-ray (OR: 4.3). ROC curve analysis accentuate the excellent predictive accuracy of all logistic regression models as shown by AUC (0.968, P < 0.001) for MDR-TB, AUC (0.941, P < 0.001) for XDR-TB and AUC (0.962, P < 0.001) for RR-TB. CONCLUSIONS: Current study demonstrates a sizeable extent of resistant cases among pulmonary TB patients. This study presaged significant risk of DR-TB among females, young adults, unemployed, smokers, patients with previous treatment failure and cavitation on chest X-ray. Timely identification of high risk patients will give pronounced advantages regarding appropriate choices of prevention, treatment and disease control.

Pharmacological interventions for COVID-19: a systematic review of observational studies and clinical trials.

Introduction: Currently, there is no approved therapeutic entity for coronavirus disease 2019 (COVID-19) and clinicians are primarily relying on drug repurposing. However, findings across studies are widely disparate, making it difficult to draw firm conclusions. Since clinicians need accurate evidence to treat COVID-19, this manuscript systematically analyzed the published and ongoing studies evaluating the pharmacological interventions for COVID-19.Areas Covered: A systematic search of observational studies and Clinical Trials on the treatment and prevention of COVID-19 was performed by using various databases from inception to 2 December 2020.Expert Opinion: A total of 460 studies met the inclusion criteria. Of these, 37 were research studies, 386 were ongoing trials, and 37 were completed trials. Anti-virals, steroids, anti-malarial, plasma exchange, and monoclonal antibodies were the most common treatment modalities used alone or in combination in these studies. However, tocilizumab, plasma exchange, and steroids have shown significant improvements in patient's clinical and radiological status. Tocilizumab reported minimum hospital stay of 2 days along with maximum recovery and patient's stability rate. Existing literature demonstrate promising results of tocilizumab, plasma exchange, and steroids among COVID-19 patients. Nevertheless, these studies are accompanied by several methodological disparities which should be considered while interpreting the results.

Potential Role of Phytochemicals Against Matrix Metalloproteinase Induced Breast Cancer; An Explanatory Review.

World Health Organization (WHO) estimated breast cancer as one of the most prevailed malignancy around the globe. Its incident cases are gradually increasing every year, resulting in considerable healthcare burden. The heterogeneity of breast cancer accounts for its differential molecular subtyping, interaction between pathways, DNA damaging, and chronic inflammation. Matrix metalloproteinases (MMPs) are a group of zinc-containing, calcium dependent endopeptidases which play a substantial role in breast carcinogenesis through several mechanisms. These mechanisms include remodeling of extracellular matrix (ECM), cell proliferation, and angiogenesis which promote metastasis and result in tumor progression. In this context, compounds bearing MMP inhibitory potential can serve as potent therapeutic agents in combating MMPs provoked breast cancer. Current systematic review aimed to encompass the details of potent natural lead molecules that can deter MMPs-provoked breast cancer. Following the critical appraisal of literature, a total of n = 44 studies that explored inhibitory effect of phytochemicals on MMPs were included in this review. These phytoconstituents include alkaloids (n = 11), flavonoids (n = 23), terpenoids (n = 7), and lignans (n = 2). The most common inhibitory methods used to evaluate efficacy of these phytoconstituents included Gelatin Zymography, Western Blotting, and real time polymerase chain reaction (RT-PCR) analysis. Moreover, current limitations, challenges, and future directions of using such compounds have been critically discussed. This review underscores the potential implications of phytochemicals in the management of breast cancer which could lessen the growing encumbrance of disease.

Assessment of clinical features and determinants of mortality among cancer patients with septic shock of pulmonary origin: a prospective analysis.

BACKGROUND: Pneumonia-associated septic shock (PASS) in patients with cancer inflicts healthcare burden attributed to high morbidity and mortality. Current study was aimed to evaluate the clinical outcomes, microbiological characteristics, risk factors and impact of life-support interventions on 28-day mortality among cancer patients with PASS. METHODS: A prospective observational study was conducted among cancer patients with PASS admitted to intensive care unit (ICU) of 'Shaukat Khanum Memorial Cancer Hospital'. Data were analysed using appropriate statistical methods. RESULTS: Out of 100 patients who sought medical care during the study period, 59 (59%) were male and majority had solid tumour than haematological malignancies (68% vs 32%). Nosocomial pneumonia was most frequent (90%) followed by healthcare-associated pneumonia (HCAP) (9%) and community-acquired pneumonia (CAP) (1%). The most common causative pathogen was Pseudomonas aeruginosa, 21 (32%). Overall mortality rate was 76% including 15% hospital and 61% ICU mortality. Sequential Organ Failure Assessment (SOFA) score at first day (HR 3.8; 95% CI 1.7 to 8.9; p=0.002), SOFA score at seventh day (HR 8.9; 95% CI 3.6 to 22.7; p=<0.001), invasive mechanical ventilation (HR 8.0; 95% CI 3.2 to 20; p<0.001) and performance status (HR 5.4; 95% CI 2.5 to 11.3; p<0.001) were found to be independently associated with 28-day mortality. Receiver operating characteristic curve analysis accentuates the excellent predictive accuracy of Cox regression model for mortality indicated by area under the curve of 0.892 (95% CI 0.801 to 0.983, p<0.001). CONCLUSION: Our analysis demonstrates substantial mortality associated with PASS among patients with cancer. Timely recognition of patients with high predilection of increased mortality could be of value in improving the disease burden.

True Aneurysm of the Uterine Artery in a Young Nulliparous Female: An Extremely Rare Vascular Entity.

We present the first case of a large true uterine artery aneurysm, with a 5-cm diameter, in a 35-year-old nulliparous woman who presented with lower abdominal pain and dyspareunia. She underwent successful ligation and excision of the aneurysm using the Pfannenstiel approach. The diagnostic modalities and treatment option for such a case is discussed herein.