Abstract The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing despite a decrease in tobacco use. Almost 20–30% of patients with OPSCC do not have the traditional risk factors ...of smoking and alcohol use and in a vast majority of these patients, the human papilloma virus (HPV) appears to drive the malignant transformation. HPV induced malignant transformation is attributed to two viral oncogenes and their non-structural protein products (E6 and E7). These two proteins appear to affect carcinogenesis by their inhibitory effects on p53 and retinoblastoma proteins (Rb). Patients with HPV mediated OPSCC seem to have a better prognosis compared to their non-HPV counterparts. However, in the absence of strong evidence, standard of care at this time for OPSCC does not differ based on HPV status. Current research is focused on the role of de-escalation of treatment and elucidation of prognostic markers in this unique population. This review focuses on the pathogenesis of HPV mediated OPSCC and details the current evidence in the management of these patients.
Morbidity and mortality resulting from influenza-like disease are a threat, especially for older adults. To improve case management, next-generation broad-spectrum antiviral therapeutics that are ...efficacious against major drivers of influenza-like disease, including influenza viruses and respiratory syncytial virus (RSV), are urgently needed. Using a dual-pathogen high-throughput screening protocol for influenza A virus (IAV) and RSV inhibitors, we have identified
-hydroxycytidine (NHC) as a potent inhibitor of RSV, influenza B viruses, and IAVs of human, avian, and swine origins. Biochemical
polymerase assays and viral RNA sequencing revealed that the ribonucleotide analog is incorporated into nascent viral RNAs in place of cytidine, increasing the frequency of viral mutagenesis. Viral passaging in cell culture in the presence of an inhibitor did not induce robust resistance. Pharmacokinetic profiling demonstrated dose-dependent oral bioavailability of 36 to 56%, sustained levels of the active 5'-triphosphate anabolite in primary human airway cells and mouse lung tissue, and good tolerability after extended dosing at 800 mg/kg of body weight/day. The compound was orally efficacious against RSV and both seasonal and highly pathogenic avian IAVs in mouse models, reducing lung virus loads and alleviating disease biomarkers. Oral dosing reduced IAV burdens in a guinea pig transmission model and suppressed virus spread to uninfected contact animals through direct transmission. Based on its broad-spectrum efficacy and pharmacokinetic properties, NHC is a promising candidate for future clinical development as a treatment option for influenza-like diseases.
A honeycomb detector consisting of a matrix of 96 closely packed hexagonal cells, each working as a proportional counter with a wire readout, was fabricated and tested at the CERN PS. The cell depth ...and the radial dimensions of the cell were small, in the range 5–
10
mm
. The appropriate cell design was arrived at using GARFIELD simulations. Two geometries are described illustrating the effect of field shaping. The charged particle detection efficiency and the preshower characteristics have been studied using pion and electron beams. Average charged particle detection efficiency was found to be 98%, which is almost uniform within the cell volume and also within the array. The preshower data show that the transverse size of the shower is in close agreement with the results of simulations for a range of energies and converter thicknesses.
Our previous studies found that B16-F10 melanoma growth in the rear footpad of immunocompetent mice induces marked B cell accumulation within tumor-draining popliteal lymph nodes (TDLN). This B cell ...accumulation drives TDLN remodeling that precedes and promotes metastasis, indicating a tumor-promoting role for TDLN B cells. Here we show that phenotypic characterization of lymphocytes in mice bearing B16-F10 melanomas identifies preferential accumulation of T2-MZP B cells in the TDLN. Comparison of non-draining LNs and spleens of tumor-bearing mice with LNs and spleens from naïve mice determined that this pattern of B cell accumulation was restricted to the TDLN. B cell-deficient and immunocompetent mice reconstituted with T2-MZP B cells but not with other B cell subsets displayed accelerated tumor growth, demonstrating that T2-MZP B cells possess regulatory activity in tumor-bearing mice. Unlike splenic regulatory B cells, however, these TDLN B cells did not exhibit increased IL-10 production, nor did they promote Treg generation in the TDLN. These findings demonstrate that tumors initially signal via the lymphatic drainage to stimulate the preferential accumulation of T2-MZP regulatory B cells. This local response may be an early and critical step in generating an immunosuppressive environment to permit tumor growth and metastasis.
Bedform evolution and preserved cross strata are known to respond to floods. However, it is unclear if autogenic dynamics mask the flood signal in bedform evolution and cross strata. To address this, ...we characterize the temporal structure of autogenic noise in steady‐state bedform evolution in a physical experiment. Results reveal the existence of bedform groups—quasi‐stable collections of bedforms—that migrate at a similar speed as bedforms. We find that bedform and bedform‐group turnover timescales are the key autogenic timescales of bed evolution that set the transition time‐periods between different noise regimes in bedform evolution. Results suggest that bedform‐group turnover timescale sets the lower limit for detecting flood signals in bedform evolution, and floods with duration shorter than bedform turnover timescale can be severely degraded in bedform evolution and cross strata. Our work provides a new framework for interrogating fluvial cross strata for reconstruction of past floods.
Plain Language Summary
Bedforms are wavy features found regularly on the beds of rivers. Bedform deposits are the building blocks of the rock record on Earth and Mars. Bedforms and their deposits respond to floods; however, it is unclear if all floods are similarly represented in bedforms and their deposits. To address this, we identified the timescales over which bed elevation and sediment discharge are variable in a steady‐state experiment of bedform evolution using high‐resolution data. We investigated the time series of bed elevation to document the existence of bedform groups, which represent a collection of bedforms that have deep scours at their upstream and downstream end. We find that the turnover timescales (time required to move an entire land feature) of bedforms and bedform groups are the key controls on noise in bedform evolution. Results suggest that the signal of floods with duration less than bedform turnover timescale will not be found in bedform data and their deposits. However, floods with duration greater than the bedform‐group turnover timescale are likely to be expressed in bedform data and their deposits. These results provide a new theory for how floods are represented in river deposits.
Key Points
We show the existence of bedform groups, which are quasi‐stable collections of bedforms, previously found in aeolian dune evolution models
Bedform and bedform group turnover timescales are key autogenic timescales that describe the temporal structure of noise in bed elevation
Floods of duration shorter than bedform turnover timescale are expected to be unrecognizable in bed elevation and preserved cross strata
As the population of the United States ages, there will be increasing numbers of lung cancer patients with comorbidities at diagnosis. Comorbid conditions are important factors in both the choice of ...the lung cancer treatment and outcomes. However, the impact of individual comorbid conditions on patient survival remains unclear.
A population-based cohort study of 5,683 first-time diagnosed lung cancer patients was captured using the Nebraska Cancer Registry (NCR) linked with the Nebraska Hospital Discharge Data (NHDD) between 2005 and 2009. A Cox proportional hazards model was used to analyze the effect of comorbidities on the overall survival of patients stratified by stage and adjusting for age, race, sex, and histologic type.
Of these patients, 36.8% of them survived their first year after lung cancer diagnosis, with a median survival of 9.3 months for all stages combined. In this cohort, 26.7% of the patients did not have any comorbidity at diagnosis. The most common comorbid conditions were chronic pulmonary disease (52.5%), diabetes (15.7%), and congestive heart failure (12.9%). The adjusted overall survival of lung cancer patients was negatively associated with the existence of different comorbid conditions such as congestive heart failure, diabetes with complications, moderate or severe liver disease, dementia, renal disease, and cerebrovascular disease, depending on the stage.
The presence of comorbid conditions was associated with worse survival. Different comorbid conditions were associated with worse outcomes at different stages.
Future models for predicting lung cancer survival should take individual comorbid conditions into consideration.
Objective: We developed a wearable watch-based device to provide noninvasive, cuff-less blood pressure (BP) estimation in an at-home setting. Methods: The watch measures single-lead electrocardiogram ...(ECG), tri-axial seismocardiogram (SCG), and multi-wavelength photoplethysmogram (PPG) signals to compute the pulse transit time (PTT), allowing for BP estimation. We sent our custom watch device and an oscillometric BP cuff home with 21 healthy subjects, and captured the natural variability in BP over the course of a 24-hour period. Results: After calibration, our Pearson correlation coefficient (PCC) of 0.69 and root-mean-square-error (RMSE) of 2.72 mmHg suggest that noninvasive PTT measurements correlate with around-the-clock BP. Using a novel two-point calibration method, we achieved a RMSE of 3.86 mmHg. We further demonstrated the potential of a semi-globalized adaptive model to reduce calibration requirements. Conclusion: This is, to the best of our knowledge, the first time that BP has been comprehensively estimated noninvasively using PTT in an at-home setting. We showed a more convenient method for obtaining ambulatory BP than through the use of the standard oscillometric cuff. We presented new calibration methods for BP estimation using fewer calibration points that are more practical for a real-world scenario. Significance: A custom watch (SeismoWatch) capable of taking multiple BP measurements enables reliable remote monitoring of daily BP and paves the way towards convenient hypertension screening and management, which can potentially reduce hospitalizations and improve quality of life.
While polyamide-based reverse osmosis (RO) and nanofiltration (NF) membranes are widely used for desalination and water purification, the influence of membrane porosity and charge on water transport ...remains to be fully understood at a molecular level. Here we use molecular dynamics (MD) to build 56 distinct piperazine-based NF membranes models, which cover a membrane density range of 0.78 gcm−3 to 1.08 gcm−3. These membrane models have various charge concentrations, corresponding to a pH range of 4–11. Results indicate that membrane charge is not monotonically correlated with the membrane density or the water transport. Instead, the water transport is mostly determined by the membrane’s physical properties, specifically, the membrane density, with charged membrane end groups and counterions causing swelling of the membrane, which tends to increase flux. Additionally, the diffusion coefficient of water molecules within the membrane is strongly correlated with the membrane density. The diffusivity of water is independent of the transmembrane pressure, even under the large pressures employed in molecular simulations. Thus, the transmembrane pressure biases the direction of the random walk of water molecules through the membrane resulting in a water flux but does not alter their overall mobility within the membrane. These findings shed light on the relationship between membrane properties and water transport for charged membranes, as well as providing new insights into the structure of NF membranes at a molecular scale.
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•56 piperazine-based NF membrane models are studied using molecular dynamics.•Membrane charge can change membrane free volume, which affects flux.•Water flux and diffusivity decrease with increasing membrane density.•Membrane charge does not affect water flux or diffusivity.•This study inspires future work on ion interactions with charged membranes.
The current coronavirus disease (COVID-19) pandemic highlights the critical importance of ubiquitous respiratory health monitoring. The two fundamental elements of monitoring respiration are ...respiration rate (the frequency of breathing) and tidal volume (TV) the volume of air breathed by the lungs in each breath. Wearable sensing systems have been demonstrated to provide accurate measurement of respiration rate, but TV remains challenging to measure accurately with wearable and unobtrusive technology. In this work, we leveraged electrocardiogram (ECG) and seismocardiogram (SCG) measurements obtained with a custom wearable sensing patch to derive an estimate of TV from healthy human participants. Specifically, we fused both an ECG-derived respiratory signal (EDR) and an SCG-derived respiratory signal (SDR) and trained a machine learning model with gas rebreathing as the ground truth to estimate TV. The respiration cycle modulates ECG and SCG signals in multiple different ways that are synergistic. Thus, here, we extract EDRs and SDRs using a multitude of different demodulation techniques. The extracted features are used to train a subject-independent machine learning model to accurately estimate TV. By fusing the extracted EDRs and SDRs, we were able to estimate the TV with a root-mean-square error (RMSE) of 181.45 mL and Pearson correlation coefficient (<inline-formula> <tex-math notation="LaTeX">{r} </tex-math></inline-formula>) of 0.61, with a global subject-independent model. We further show that SDRs are better TV estimators than EDRs. Among SDRs, amplitude modulation (AM) SCG features are the most correlated with TV. We demonstrated that fusing EDRs and SDRs can result in a moderately accurate estimation of the TV using a subject-independent model. Additionally, we highlight the most informative features for estimating TV. This work presents a significant step toward achieving continuous, calibration-free, and unobtrusive TV estimation, which could advance the state of the art in wearable respiratory monitoring.
Physical Layer Design of a 5G NR Base Station S, Jeeva Keshav; Praneeth, K B S D Sai; Prasanth, K B S M D S Sai ...
2024 National Conference on Communications (NCC),
2024-Feb.-28
Conference Proceeding
The Fifth Generation (5G) systems are being used across the world to provide better connectivity and data rates. These systems are complex and involve several interactions between various components. ...Building a full 5G stack requires significant software and hardware resources and a great deal of understanding of the various layers involved. In this paper, we look at some of the high-level design aspects of the 5G physical layer that we have implemented in our 5G testbed. In particular, wehighlight the various procedures and debugging strategies including the simulation level checks, standalone transmitter and receiver testing, integrated design testing, initial attach procedures and the directions of control, data, and timing flows.
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